PEER REVIEWED PUBLISHED LITERATURE

Ventilator-Associated Pneumonia in Patients with COVID-19: A Systematic Review and Meta-Analysis

Ippolito et al., Antibiotics.

Published: May 7th 2021.

DOI: https://doi.org/10.3390/antibiotics10050545 

Abstract

The aim of this systematic review and meta-analysis was to estimate the pooled occurrence of ventilator-associated pneumonia (VAP) among patients admitted to an intensive care unit with COVID-19 and mortality of those who developed VAP. We performed a systematic search on PubMed, EMBASE and Web of Science from inception to 2nd March 2021 for nonrandomized studies specifically addressing VAP in adult patients with COVID-19 and reporting data on at least one primary outcome of interest. Random effect single-arm meta-analysis was performed for the occurrence of VAP and mortality (at the longest follow up) and ICU length of stay. Twenty studies were included in the systematic review and meta-analysis, for a total of 2611 patients with at least one episode of VAP. The pooled estimated occurrence of VAP was of 45.4% (95% C.I. 37.8-53.2%; 2611/5593 patients; I2 = 96%). The pooled estimated occurrence of mortality was 42.7% (95% C.I. 34-51.7%; 371/946 patients; I2 = 82%). The estimated summary estimated metric mean ICU LOS was 28.58 days (95% C.I. 21.4-35.8; I2 = 98%). Sensitivity analysis showed that patients with COVID-19 may have a higher risk of developing VAP than patients without COVID-19 (OR 3.24; 95% C.I. 2.2-4.7; P = 0.015; I2 = 67.7%; five studies with a comparison group).

Use of Procalcitonin during the First Wave of COVID-19 in the Acute NHS Hospitals: A Retrospective Observational Study

Powell et al., Antibiotics.

Published: May 1st 2021.

DOI: https://doi.org/10.3390/antibiotics10050516 

Abstract

A minority of patients presenting to hospital with COVID-19 have bacterial co-infection. Procalcitonin testing may help identify patients for whom antibiotics should be prescribed or withheld. This study describes the use of procalcitonin in English and Welsh hospitals during the first wave of the COVID-19 pandemic. A web-based survey of antimicrobial leads gathered data about the use of procalcitonin testing. Responses were received from 148/151 (98%) eligible hospitals. During the first wave of the COVID-19 pandemic, there was widespread introduction and expansion of PCT use in NHS hospitals. The number of hospitals using PCT in emergency/acute admissions rose from 17 (11%) to 74/146 (50.7%) and use in Intensive Care Units (ICU) increased from 70 (47.6%) to 124/147 (84.4%). This increase happened predominantly in March and April 2020, preceding NICE guidance. Approximately half of hospitals used PCT as a single test to guide decisions to discontinue antibiotics and half used repeated measurements. There was marked variation in the thresholds used for empiric antibiotic cessation and guidance about interpretation of values. Procalcitonin testing has been widely adopted in the NHS during the COVID-19 pandemic in an unevidenced, heterogeneous way and in conflict with relevant NICE guidance. Further research is needed urgently that assesses the impact of this change on antibiotic prescribing and patient safety.

Characterization of respiratory microbial dysbiosis in hospitalized COVID-19 patients

Zhong et al., Cell Discovery.

Published: April 13th 2021.

DOI: https://doi.org/10.1038/s41421-021-00257-2 

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic of Coronavirus disease 2019 (COVID-19). However, the microbial composition of the respiratory tract and other infected tissues as well as their possible pathogenic contributions to varying degrees of disease severity in COVID-19 patients remain unclear. Between 27 January and 26 February 2020, serial clinical specimens (sputum, nasal and throat swab, anal swab and feces) were collected from a cohort of hospitalized COVID-19 patients, including 8 mildly and 15 severely ill patients in Guangdong province, China. Total RNA was extracted and ultra-deep metatranscriptomic sequencing was performed in combination with laboratory diagnostic assays. We identified distinct signatures of microbial dysbiosis among severely ill COVID-19 patients on broad spectrum antimicrobial therapy. Co-detection of other human respiratory viruses (including human alphaherpesvirus 1, rhinovirus B, and human orthopneumovirus) was demonstrated in 30.8% (4/13) of the severely ill patients, but not in any of the mildly affected patients. Notably, the predominant respiratory microbial taxa of severely ill patients were Burkholderia cepacia complex (BCC), Staphylococcus epidermidis, or Mycoplasma spp. (including M. hominis and M. orale). The presence of the former two bacterial taxa was also confirmed by clinical cultures of respiratory specimens (expectorated sputum or nasal secretions) in 23.1% (3/13) of the severe cases. Finally, a time-dependent, secondary infection of B. cenocepacia with expressions of multiple virulence genes was demonstrated in one severely ill patient, which might accelerate his disease deterioration and death occurring one month after ICU admission. Our findings point to SARS-CoV-2-related microbial dysbiosis and various antibiotic-resistant respiratory microbes/pathogens in hospitalized COVID-19 patients in relation to disease severity. Detection and tracking strategies are needed to prevent the spread of antimicrobial resistance, improve the treatment regimen and clinical outcomes of hospitalized, severely ill COVID-19 patients.

Bacterial coinfections in coronavirus disease 2019

Westblade et al., Trends in Microbiology.

Published: April 7th 2021.

DOI: https://doi.org/10.1016/j.tim.2021.03.018 

Summary

Bacterial coinfections increase the severity of respiratory viral infections and were frequent causes of mortality in influenza pandemics but have not been well characterized in patients with coronavirus disease 2019 (COVID-19). The aim of this review was to identify the frequency and microbial etiologies of bacterial coinfections that are present upon admission to the hospital and that occur during hospitalization for COVID-19. We found that bacterial coinfections were present in <4% of patients upon admission and the yield of routine diagnostic tests for pneumonia was low. When bacterial coinfections did occur, Staphylococcus aureus, Streptococcus pneumoniae, and Haemophilus influenzae were the most common pathogens and atypical bacteria were rare. Although uncommon upon admission, bacterial infections frequently occurred in patients with prolonged hospitalization, and Pseudomonas aeruginosa, Klebsiella spp., and S. aureus were common pathogens. Antibacterial therapy and diagnostic testing for bacterial infections are unnecessary upon admission in most patients hospitalized with COVID-19, but clinicians should be vigilant for nosocomial bacterial infections.

Notes

Carbapenem-resistant Gram-negative infections are being increasingly reported in patients with COVID-19 requiring intensive care.

Key considerations on the potential impacts of the COVID-19 pandemic on antimicrobial resistance research and surveillance

Rodríguez-Baño et al., Transactions of The Royal Society of Tropical Medicine and Hygiene.

Published: March 27th 2021.

DOI: https://doi.org/10.1093/trstmh/trab048 

Abstract

Antibiotic use in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) patients during the COVID-19 pandemic has exceeded the incidence of bacterial coinfections and secondary infections, suggesting inappropriate and excessive prescribing. Even in settings with established antimicrobial stewardship (AMS) programmes, there were weaknesses exposed regarding appropriate antibiotic use in the context of the pandemic. Moreover, antimicrobial resistance (AMR) surveillance and AMS have been deprioritised with diversion of health system resources to the pandemic response. This experience highlights deficiencies in AMR containment and mitigation strategies that require urgent attention from clinical and scientific communities. These include the need to implement diagnostic stewardship to assess the global incidence of coinfections and secondary infections in COVID-19 patients, including those by multidrug-resistant pathogens, to identify patients most likely to benefit from antibiotic treatment and identify when antibiotics can be safely withheld, de-escalated or discontinued. Long-term global surveillance of clinical and societal antibiotic use and resistance trends is required to prepare for subsequent changes in AMR epidemiology, while ensuring uninterrupted supply chains and preventing drug shortages and stock outs. These interventions present implementation challenges in resource-constrained settings, making a case for implementation research on AMR. Knowledge and support for these practices will come from internationally coordinated, targeted research on AMR, supporting the preparation for future challenges from emerging AMR in the context of the current COVID-19 pandemic or future pandemics.

High rates of antibiotic prescriptions in children with COVID‐19 or multisystem inflammatory syndrome: A multinational experience in 990 cases from Latin America

Yock- Corrales et al., Acta Paediatrica.

Published: March 19th 2021.

DOI: https://doi.org/10.1111/apa.15847

Abstract

This study aims to assess rates of antibiotic prescriptions and its determinants in in children with COVID‐19 or Multisystem Inflammatory Syndrome (MIS‐C).

Methods: Children <18 years‐old assessed in five Latin Americas countries with a diagnosis of COVID‐19 or MIS‐C were enrolled. Antibiotic prescriptions and factors associated with their use were assessed.

Results: A total of 990 children were included: 921 (93%) with COVID‐19, 69 (7.0%) with MIS‐C. The prevalence of antibiotic use was 24.5% (n = 243). MIS‐C with (OR = 45.48) or without (OR = 10.35) cardiac involvement, provision of intensive care (OR = 9.60), need for hospital care (OR = 6.87), pneumonia and/or ARDS detected through chest X‐rays (OR = 4.40), administration of systemic corticosteroids (OR = 4.39), oxygen support, mechanical ventilation or CPAP (OR = 2.21), pyrexia (OR = 1.84), and female sex (OR = 1.50) were independently associated with increased use of antibiotics. There was significant variation in antibiotic use across the hospitals.

Conclusion: Our study showed a high rate of antibiotic prescriptions in children with COVID‐19, in particular in those with severe disease or MIS‐C. Prospective studies are needed to provide better evidence on the recognition and management of bacterial infections in COVID‐19 children.

Bacterial pulmonary superinfections are associated with longer duration of ventilation in critically ill COVID-19 patients

Buehler et al., Cell Reports Medicine.

Published: March 14th 2021.

DOI: https://doi.org/10.1016/j.xcrm.2021.100229 

Summary

The impact of secondary bacterial infections (superinfections) in coronavirus disease 2019 (COVID-19) is not well understood. In this prospective, monocentric cohort study, we aim to investigate the impact of superinfections in COVID-19 patients with acute respiratory distress syndrome. Patients are assessed for concomitant microbial infections by longitudinal analysis of tracheobronchial secretions, bronchoalveolar lavages, and blood cultures. In 45 critically ill patients, we identify 19 patients with superinfections (42.2%). Superinfections are detected on day 10 after intensive care admission. The proportion of participants alive and off invasive mechanical ventilation at study day 28 (ventilator-free days [VFDs] at 28 days) is substantially lower in patients with superinfection (subhazard ratio 0.37; 95% confidence interval [CI] 0.15-0.90; p = 0.028). Patients with pulmonary superinfections have a higher incidence of bacteremia, virus reactivations, yeast colonization, and required intensive care treatment for a longer time. Superinfections are frequent and associated with reduced VFDs at 28 days despite a high rate of empirical antibiotic therapy.

Antimicrobial resistance research in a post-pandemic world: Insights on antimicrobial resistance research in the COVID-19 pandemic

Rodríguez-Baño et al., Journal of Global Antimicrobial Resistance.

Published: March 1st 2021.

DOI: https://doi.org/10.1016/j.jgar.2021.02.013 

Abstract

Antimicrobial resistance must be recognised as a global societal priority - even in the face of the worldwide challenge of the COVID-19 pandemic. COVID-19 has illustrated the vulnerability of our healthcare systems in co-managing multiple infectious disease threats as resources for monitoring and detecting, and conducting research on antimicrobial resistance have been compromised during the pandemic. The increased awareness of the importance of infectious diseases, clinical microbiology and infection control and lessons learnt during the COVID-19 pandemic should be exploited to ensure that emergence of future infectious disease threats, including those related to AMR, are minimised. Harnessing the public understanding of the relevance of infectious diseases towards the long-term pandemic of AMR could have major implications for promoting good practices about the control of AMR transmission.

Self-Medication with Antibiotics for Protection against COVID-19: The Role of Psychological Distress, Knowledge of, and Experiences with Antibiotics

Zhang et al., Antibiotics.

Published: February 25th 2021.

DOI: https://doi.org/10.3390/antibiotics10030232

Abstract

Self-medication with antibiotics is a major contributing factor to antimicrobial resistance. Prior research examining factors associated with antibiotic self-medication has focused on an individual's knowledge about antibiotics, antibiotic usage practices, accessibility to antibiotic medication, and demographic characteristics. The role of psychological distress associated with perceived health risks in explaining antibiotic self-medication is less understood. This study was designed to address this knowledge gap in the context of the COVID-19 pandemic in Australia. An online survey of 2217 participants was conducted at the height of the initial outbreak and revealed that 19.5% of participants took antibiotics to protect themselves from COVID-19. Multivariate logistic analysis examined the predictors of taking antibiotics for protection against COVID-19. An integrative framework developed from the results illustrates potential pathways and facilitating factors that may contribute to prophylactic self-medication with antibiotics. Specifically, COVID-19 pandemic-induced psychological distress was significantly positively related to self-medication. Preventive use of antibiotics was also facilitated by a lack of understanding about antibiotics, inappropriate antibiotics usage practices, the nature of the patient-doctor relationship, and demographic characteristics. The findings highlight that to combat antimicrobial resistance due to self-medication, interventions need to focus on interrupting entrenched behavioural responses and addressing emotional responses to perceived health risks.

SARS-CoV-2 Respiratory Co-Infections: Incidence of Viral and Bacterial Co-Pathogens

Singh et al., International Journal of Infectious Diseases

Published: February 24th 2021

DOI: https://doi.org/10.1016/j.ijid.2021.02.087

Abstract

The COVID-19 global pandemic, caused by the SARS-CoV-2 virus, has created an unprecedented challenge to our healthcare system. Secondary and concurrent bacterial and viral co-infections are well documented for other viral respiratory pathogens however our knowledge regarding co-infections in COVID-19 remains limited. The present study encompasses concurrent testing of 50,419 individual samples for the presence of SARS-CoV-2 and other bacterial and viral respiratory pathogens between March and August 2020. Overall a lower rate of viral co-infection was observed in the SARS-CoV-2 positive population when compared to the population testing negative for the virus. Significant levels of Staphylococcus aureus and Epstein-Barr virus co-infections were detected in the SARS-CoV-2 positive population. This is one of the largest surveys looking into the co-infection patterns of SARS-CoV-2 infection in the United States. Data from the present study will enhance our understanding of the current pandemic and will assist clinicians in making better patient care decisions especially with respect to anti-microbial therapy.

COVID-19 drug practices risk antimicrobial resistance evolution

Afshinnekoo et al., The Lancet Microbe.

Published: February 24th 2021.

DOI: https://doi.org/10.1016/S2666-5247(21)00039-2 

Notes

Admission and release of patients from tertiary hospitals have risen dramatically in the past year due to the COVID-19 pandemic, with many hospitals expanding beyond capacity. With hospitalisations exceeding normal capacity due to COVID-19 combined with impaired immune function in patients, risks of co-infections have substantially increased. The gap in a comprehensive understanding of coinfection and comorbidity caused by COVID-19 has led to rapidly changing protocols for patient handling, including administering multiple drugs around the world. The use of antiparasite, antiviral, antibacterial, and anti-inflammatory drugs for preventing secondary infections in patients with COVID-19 during a prolonged pandemic will inevitably invite future complications, including aggravation of antimicrobial resistance. 

Community-acquired bacteraemia in COVID-19 in comparison to influenza A and influenza B: a retrospective cohort study

Thelen et al., BMC Infectious Diseases. 

Published: February 22nd 2021

DOI: https://doi.org/10.1186/s12879-021-05902-5

Abstract

Background

During the coronavirus disease 2019 (COVID-19) pandemic in the Netherlands it was noticed that very few blood cultures from COVID-19 patients turned positive with clinically relevant bacteria. This was particularly evident in comparison to the number of positive blood cultures during previous seasonal epidemics of influenza. This observation raised questions about the occurrence and causative microorganisms of bacteraemia in COVID-19 patients, especially in the perspective of the widely reported overuse of antibiotics and the rising rate of antibiotic resistance.

Methods

We conducted a retrospective cohort study on blood culture results in influenza A, influenza B and COVID-19 patients presenting to two hospitals in the Netherlands. Our main outcome consisted of the percentage of positive blood cultures. The percentage of clinically relevant blood cultures, isolated bacteria and 30-day all-cause mortality served as our secondary outcomes.

Results

A total of 1331 viral episodes were analysed in 1324 patients. There was no statistically significant difference (p = 0.47) in overall occurrence of blood culture positivity in COVID-19 patients (9.0, 95% CI 6.8-11.1) in comparison to influenza A (11.4, 95% CI 7.9-14.8) and influenza B patients (10.4, 95% CI 7.1-13.7,). After correcting for the high rate of contamination, the occurrence of clinically relevant bacteraemia in COVID-19 patients amounted to 1.0% (95% CI 0.3-1.8), which was statistically significantly lower (p = 0.04) compared to influenza A patients (4.0, 95% CI 1.9-6.1) and influenza B patients (3.0, 95% CI 1.2-4.9). The most frequently identified bacterial isolates in COVID-19 patients were Escherichia coli (n = 2) and Streptococcus pneumoniae (n = 2). The overall 30-day all-cause mortality for COVID-19 patients was 28.3% (95% CI 24.9-31.7), which was statistically significantly higher (p = <.001) when compared to patients with influenza A (7.1, 95% CI 4.3-9.9) and patients with influenza B (6.4, 95% CI 3.8-9.1).

Conclusions

We report a very low occurrence of community-acquired bacteraemia amongst COVID-19 patients in comparison to influenza patients. These results reinforce current clinical guidelines on antibiotic management in COVID-19, which only advise utilization of antibiotics when a bacterial co-infection is suspected.

Impact of the COVID-19 Pandemic on Antibiotic Prescribing for Common Infections in The Netherlands: A Primary Care-Based Observational Cohort Study

van de Pol., Antibiotics.

Published: February 18th 2021

DOI: https://doi.org/10.3390/antibiotics10020196

Abstract

In 2020, the COVID-19 pandemic brought dramatic changes in the delivery of primary health care across the world, presumably changing the number of consultations for infectious diseases and antibiotic use. We aimed to assess the impact of the pandemic on infections and antibiotic prescribing in Dutch primary care. All patients included in the routine health care database of the Julius General Practitioners' Network were followed from March through May 2019 (n = 389,708) and March through May 2020 (n = 405,688). We extracted data on consultations for respiratory/ear, urinary tract, gastrointestinal and skin infections using the International Classification of Primary Care (ICPC) codes. These consultations were combined in disease episodes and linked to antibiotic prescriptions. The numbers of infectious disease episodes (total and those treated with antibiotics), complications, and antibiotic prescription rates (i.e., proportion of episodes treated with antibiotics) were calculated and compared between the study periods in 2019 and 2020. Fewer episodes were observed during the pandemic months than in the same months in 2019 for both the four infectious disease entities and complications such as pneumonia, mastoiditis and pyelonephritis. The largest decline was seen for gastrointestinal infections (relative risk (RR), 0.54; confidence interval (CI), 0.51 to 0.58) and skin infections (RR, 0.71; CI, 0.67 to 0.75). The number of episodes treated with antibiotics declined as well, with the largest decrease seen for respiratory/ear infections (RR, 0.54; CI, 0.52 to 0.58). The antibiotic prescription rate for respiratory/ear infections declined from 21% to 13% (difference −8.0% (CI, −8.8 to −7.2)), yet the prescription rates for other infectious disease entities remained similar or increased slightly. The decreases in primary care infectious disease episodes and antibiotic use were most pronounced in weeks 15-19, mid-COVID-19 wave, after an initial peak in respiratory/ear infection presentation in week 11, the first week of lock-down. In conclusion, our findings indicate that the COVID-19 pandemic has had profound effects on the presentation of infectious disease episodes and antibiotic use in primary care in the Netherlands. Consequently, the number of infectious disease episodes treated with antibiotics decreased. We found no evidence of an increase in complications

Antimicrobial resistance and COVID-19: Intersections and implications

Knight et al., eLife.

Published: February 16th 2021.

DOI: 10.7554/eLife.64139 

Abstract

Before the coronavirus 2019 (COVID-19) pandemic began, antimicrobial resistance (AMR) was among the top priorities for global public health. Already a complex challenge, AMR now needs to be addressed in a changing healthcare landscape. Here, we analyse how changes due to COVID-19 in terms of antimicrobial usage, infection prevention, and health systems affect the emergence, transmission, and burden of AMR. Increased hand hygiene, decreased international travel, and decreased elective hospital procedures may reduce AMR pathogen selection and spread in the short term. However, the opposite effects may be seen if antibiotics are more widely used as standard healthcare pathways break down. Over 6 months into the COVID-19 pandemic, the dynamics of AMR remain uncertain. We call for the AMR community to keep a global perspective while designing finely tuned surveillance and research to continue to improve our preparedness and response to these intersecting public health challenges.

Investigating the impact of COVID-19 on primary care antibiotic prescribing in North West London across two epidemic waves

Zhu et al., Clinical Microbiology and Infection.

Published: February 15th 2021.

DOI: https://doi.org/10.1016/j.cmi.2021.02.007 

Abstract

Objectives: We investigated the impact of COVID-19 and national pandemic response on primary care antibiotic prescribing in London.

Methods: Individual prescribing records between 2015 and 2020 for 2 million residents in North West London were analysed. Prescribing records were linked to SARS-CoV-2 test results. Prescribing volumes, in total, and stratified by patient characteristics, antibiotic class, and AWaRe classification, were investigated. Interrupted time series analysis was performed to detect measurable change in the trend of prescribing volume since the national lockdown in March 2020, immediately before the first COVID-19 peak in London.

Results: Records covering 366,059 patients, 730,001 antibiotic items, and 848,201 SARS-CoV-2 tests between January and November 2020 were analysed. Before March 2020, there was a background downward trend (decreasing by 584 items/month) in primary care antibiotic prescribing. This reduction rate accelerated to 3504 items/month from March 2020. This rate of decrease was sustained beyond the initial peak, continuing into winter and the second peak. Despite an overall reduction in prescribing volume, co-amoxiclav, a broad-spectrum "Access" antibiotic prescribing rose by 70.1% in patients aged 50 and older from February to April. Commonly prescribed antibiotics within 14 days of a positive SARS-CoV-2 test were amoxicillin (863/2474, 34.9%) and doxycycline (678/2474, 27.4%). This aligned with national guidelines on management of community pneumonia of unclear cause. The proportion of "Watch" antibiotics used decreased during the peak in COVID-19.

Conclusions: A sustained reduction in community antibiotic prescribing was observed since the first lockdown. Investigation of community-onset infectious diseases and potential unintended consequences of reduced prescribing is urgently needed.

Clinical characteristics and risk factors for the isolation of multidrug-resistant Gram-negative bacteria from critically ill patients with Coronavirus Disease 2019

Baiou et al., Journal of Hospital Infection.

Published: February 6th 2021.

DOI: https://doi.org/10.1016/j.jhin.2021.01.027

Abstract

Background: We investigated the clinical characteristics and risk factors for the isolation of multidrug resistant (MDR) Gram-negative bacteria (GNB) from critically ill COVID-19 patients.

Methods: We retrospectively matched (1:2) critical COVID-19 patients with one or more MDR GNB from any clinical specimen (cases), with those with no MDR GNB isolates (controls).

Results: Seventy-eight cases were identified (4.5 per 1,000 ICU days, 95% confidence interval [CI] 3.6-5.7). Out of 98 MDR GNB isolates, the most frequent species were Stenotrophomonas maltophilia (24, 24.5%), and Klebsiella pneumoniae (23, 23.5%). Two (8.7%) K. pneumoniae, and six (85.7%) Pseudomonas aeruginosa isolates were carbapenem resistant. A total of 24 (24.5%) isolates were not considered to be associated with active infection. Those with active infection received appropriate antimicrobial agent within a median of one day. The case group had significantly longer median central venous line days, mechanical ventilation days, and hospital length of stay (P<0.001 for each). All-cause mortality at 28 days was not significantly different between the two groups (P = 0.19). Mechanical ventilation days (adjusted odds ratio [aOR] 1.062, 95% CI 1.012 to 1.114; P 0.015), but not receipt of corticosteroids or tocilizumab, was independently associated with the isolation of MDR GNB. There was no association between MDR GNB and 28-day all-cause mortality (aOR 2.426, 95% CI 0.833 to 7.069; P = 0.104).

Conclusion: In critically ill COVID-19 patients, prevention of MDR GNB colonization and infections requires minimising the use of invasive devices, and to remove them as soon as their presence is no longer necessary.

Doctors' Perceptions, Attitudes and Practices towards the Management of Multidrug-Resistant Organism Infections after the Implementation of an Antimicrobial Stewardship Programme during the COVID-19 Pandemic

Spernovasilis et al., Tropical Medicine and Infectious Disease.

Published: February 5th 2021

DOI: https://doi.org/10.3390/tropicalmed6010020

Abstract

Background: Greece is among the European countries with the highest consumption of antibiotics, both in community and hospital settings, including last-line antibiotics, such as carbapenems. We sought to explore doctors' perceptions, attitudes and practices towards the management of patients with multidrug-resistant organism (MDRO) infections after the implementation of an antimicrobial stewardship programme (ASP) in a tertiary academic hospital during the COVID-19 pandemic. Methods: A self-administered, internet-based questionnaire survey was completed by doctors of the University Hospital of Heraklion in Crete, Greece. Results: In total, 202 (59.1%) hospital doctors fully completed the questionnaire. Most of them agreed that the prospective audit and feedback ASP strategy is more effective and educational than the preauthorization ASP strategy. ASP implementation prompted most respondents to monitor the continuously evolving microbiological data of their patients more closely and affected them towards a multidisciplinary and personalised care of patients with infections caused by MDROs and towards a more rigorous implementation of infection prevention and control measures. The vast majority of participants (98.5%) stated that ASP must be continued and further developed during the COVID-19 pandemic. Conclusion: The ASP implementation in our hospital had a beneficial impact on doctors' perceptions, attitudes and practices with regard to the management of infections due to MDROs.

Supervised machine learning to support the diagnosis of bacterial infection in the context of COVID-19

Rawson et al., JAC-Antimicrobial Resistance.

Published: February 3rd 2021.

DOI: https://doi.org/10.1093/jacamr/dlab002 

Abstract

Background: Bacterial infection has been challenging to diagnose in patients with COVID-19. We developed and evaluated supervised machine learning algorithms to support the diagnosis of secondary bacterial infection in hospitalized patients during the COVID-19 pandemic.

Methods: Inpatient data at three London hospitals for the first COVD-19 wave in March and April 2020 were extracted. Demographic, blood test and microbiology data for individuals with and without SARS-CoV-2-positive PCR were obtained. A Gaussian Naive Bayes, Support Vector Machine (SVM) and Artificial Neural Network were trained and compared using the area under the receiver operating characteristic curve (AUCROC). The best performing algorithm (SVM with 21 blood test variables) was prospectively piloted in July 2020. AUCROC was calculated for the prediction of a positive microbiological sample within 48 h of admission.

Results: A total of 15 599 daily blood profiles for 1186 individual patients were identified to train the algorithms; 771/1186 (65%) individuals were SARS-CoV-2 PCR positive. Clinically significant microbiology results were present for 166/1186 (14%) patients during admission. An SVM algorithm trained with 21 routine blood test variables and over 8000 individual profiles had the best performance. AUCROC was 0.913, sensitivity 0.801 and specificity 0.890. Prospective testing on 54 patients on admission (28/54, 52% SARS-CoV-2 PCR positive) demonstrated an AUCROC of 0.960 (95% CI: 0.90-1.00).

Conclusions: An SVM using 21 routine blood test variables had excellent performance at inferring the likelihood of positive microbiology. Further prospective evaluation of the algorithms ability to support decision making for the diagnosis of bacterial infection in COVID-19 cohorts is underway.

The interrelationships between antimicrobial resistance, COVID-19, past, and future pandemics

Ukuhor, Journal of Infection and Public Health.

Published: January 2021.

DOI: https://doi.org/10.1016/j.jiph.2020.10.018 

Abstract

The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 was first reported in Wuhan, China in December 2019 and is associated with high levels of morbidity and mortality. Various types of bacterial and fungal infections occur in patients with COVID-19 with some resistant to antimicrobials that are associated with significantly worse outcomes and deaths. Besides, antimicrobial-resistant (AMR) co-infections are responsible for clinically significant mortality in past pandemics. There is evidence to suggest that factors such as the proliferation of adulterated antimicrobials in some developing countries, international travels, issues with healthcare financing, use/misuse by humans, and in agricultural production and climate change are determinants of AMR at various levels of society. These complex interrelated determinants intersect with AMR in current and past pandemics and could amplify the potential of a future antimicrobial resistance pandemic. Therefore, global concerted interventions targeted at all levels of society to reduce the use/misuse of antimicrobials and disrupt these multifaceted, interrelated, and interdependent factors are urgently needed. This paper leverages prior research to describe complex major determinants of antimicrobial resistance and provides fresh insights into possible intervention strategies to tackle antimicrobial resistance including in the current and future pandemics.

Co-infection in patients with hypoxemic pneumonia due to COVID-19 in Reunion Island

Allou et al., Medicine.

Published: January 29th 2021.

DOI: 1097/MD.0000000000024524

Abstract

This study aimed to evaluate the incidence of co-infection with different types of pathogens in patients with hypoxemic pneumonia due to coronavirus disease 2019 (COVID-19) in Reunion Island.

This observational study using a prospectively collected database of hypoxemic pneumonia due to COVID-19 cases was conducted at Félix Guyon University Hospital in Reunion Island, France.

Between 18 March 2020 and 15 April 2020, 156 patients were admitted to our hospital for COVID-19. A total of 36 patients had hypoxemic pneumonia (23.1%) due to COVID-19. Thirty of these cases (83.3%) were imported by travelers returning mainly from metropolitan France and Spain. Patients were screened for co-infection with other pathogens at admission: 31 (86.1%) by multiplex polymerase chain reaction (PCR) and 16 (44.4%) by cytobacteriological examination of sputum culture. Five patients (13.9%) were found to have co-infection: 1 with influenza virus A H1N1 (pdm09) associated with Branhamella catarrhalis, 1 with Streptococcus pneumoniae associated with Haemophilus influenzae, 1 with Human Coronavirus 229E, 1 with Rhinovirus, and 1 with methicillin-susceptible Staphylococcus aureus. Patients with co-infection had higher D-dimer levels than those without co-infection (1.36 [1.34-2.36] μg/mL vs 0.63 [0.51-1.12] μg/mL, P = .05).

The incidence of co-infection in our cohort was higher than expected (13.9%). Three co-infections (with influenza virus A(H1N1) pdm09, Streptococcus pneumoniae, and Staphylococcus aureus) required specific treatment. Patients with hypoxemic pneumonia due to COVID-19 should be screened for co-infection using respiratory cultures or multiplex PCR. Whilst our study has a number of limitations, the results from our study suggest that in the absence of screening, patients should be commenced on treatment for co-infection in the presence of an elevated D-dimer.

Drug-Resistant Bacteria Outbreak Linked to COVID-19 Patient Surge

Kuehn., JAMA.

Published: January 26th 2021

DOI: 10.1001/jama.2020.26113

Assessing the Impact of COVID-19 on Antimicrobial Stewardship Activities/Programs in the United Kingdom

Ashiru-Oredope et al., Antibiotics.

Published: January 23rd 2021.

DOI: https://doi.org/10.3390/antibiotics10020110

Abstract

Since first identified in late 2019, the acute respiratory syndrome coronavirus (SARS-CoV2) and the resulting coronavirus disease (COVID-19) pandemic has overwhelmed healthcare systems worldwide, often diverting key resources in a bid to meet unprecedented challenges. To measure its impact on national antimicrobial stewardship (AMS) activities, a questionnaire was designed and disseminated to antimicrobial stewardship leads in the United Kingdom (UK). Most respondents reported a reduction in AMS activity with 64% (61/95) reporting that COVID-19 had a negative impact on routine AMS activities. Activities reported to have been negatively affected by the pandemic include audit, quality improvement initiatives, education, AMS meetings, and multidisciplinary working including ward rounds. However, positive outcomes were also identified, with technology being increasingly used as a tool to facilitate stewardship, e.g., virtual meetings and ward rounds and increased the acceptance of using procalcitonin tests to distinguish between viral and bacterial infections. The COVID-19 pandemic has had a significant impact on the AMS activities undertaken across the UK. The long-term impact of the reduced AMS activities on incidence of AMR are not yet known. The legacy of innovation, use of technology, and increased collaboration from the pandemic could strengthen AMS in the post-pandemic era and presents opportunities for further development of AMS.

Reduction of Multidrug-Resistant (MDR) Bacterial Infections during the COVID-19 Pandemic: A Retrospective Study

Bentivegna et al., International Journal of Environmental Research and Public Health.

Published: January 23rd 2021.

Arteaga-Livias et al., Infection Control & Hospital Epidemiology.

Published: January 5th 2021.

DOI: https://doi.org/10.1017/ice.2020.1401 

Summary

We reported an outbreak of Klebsiella pneumoniae New Delhi metallo-β-lactamase (NDM) in a Peruvian hospital where no cases of strains with this resistance had been identified previously. All patients were admitted for a diagnosis of COVID-19 and were placed in isolation and management areas for treatment.

Trends in Antibiotic Prescribing in Out-of-Hours Primary Care in England from January 2016 to June 2020 to Understand Behaviours during the First Wave of COVID-19

Zhu et al., Antibiotics.

Published: January 1st 2021

DOI: https://doi.org/10.3390/antibiotics10010032

Abstract

We describe the trend of antibiotic prescribing in out-of-hours (OOH) general practices (GP) before and during England's first wave of the COVID-19 pandemic. We analysed practice-level prescribing records between January 2016 to June 2020 to report the trends for the total prescribing volume, prescribing of broad-spectrum antibiotics and key agents included in the national Quality Premium. We performed a time-series analysis to detect measurable changes in the prescribing volume associated with COVID-19. Before COVID-19, the total prescribing volume and the percentage of broad-spectrum antibiotics continued to decrease in-hours (IH). The prescribing of broad-spectrum antibiotics was higher in OOH (OOH: 10.1%, IH: 8.7%), but a consistent decrease in the trimethoprim-to-nitrofurantoin ratio was observed OOH. The OOH antibiotic prescribing volume diverged from the historical trend in March 2020 and started to decrease by 5088 items per month. Broad-spectrum antibiotic prescribing started to increase in OOH and IH. In OOH, co-amoxiclav and doxycycline peaked in March to May in 2020, which was out of sync with seasonality peaks (Winter) in previous years. While this increase might be explained by the implementation of the national guideline to use co-amoxiclav and doxycycline to manage pneumonia in the community during COVID-19, further investigation is required to see whether the observed reduction in OOH antibiotic prescribing persists and how this reduction might influence antimicrobial resistance and patient outcomes.

Increase in Hospital-Acquired Carbapenem-Resistant Acinetobacter baumannii Infection and Colonization in an Acute Care Hospital During a Surge in COVID-19 Admissions - New Jersey, February-July 2020

Perez et al., Morbidity and Mortality Weekly Report (CDC).

Published: December 4th 2020.

DOI: https://dx.doi.org/10.15585/mmwr.mm6948e1 

Summary

A New Jersey hospital reported a cluster of 34 Carbapenem-resistant Acinetobacter baumannii (CRAB) cases that peaked during a surge in COVID-19 hospitalizations. Strategies to preserve continuity of care led to deviations in IPC practices; CRAB cases decreased when normal operations resumed.

Notes

The multidrug-resistant CRAB definition (A. baumannii with documented resistance to three or more classes of antibiotics) was applied to hospital clinical laboratory antimicrobial susceptibility data for incident cases (4); all 34 met multidrug-resistant CRAB criteria. Thirty isolates were further evaluated for carbapenemase genes through real-time polymerase chain reaction testing. Twenty-six isolates harbored the gene encoding the OXA-23 carbapenemase. Among these isolates, two from specimens collected in February and March harbored an additional carbapenemase gene, encoding New Delhi metallo-β-lactamase (a gene rarely present in CRAB isolates from patients in the United States), indicating that at least one CRAB introduction occurred before the surge of COVID-19 cases (5). Four specimens were nonviable or did not yield CRAB growth.

Antibiotic prescribing in general practice during COVID-19

Armitage and Nellums, Lancet Infectious Diseases. 

Published: December 1st 2020.

DOI: https://doi.org/10.1016/S1473-3099(20)30917-8 

Notes

The number of antibiotic prescriptions made in general practice between April 1, and Aug 31, 2020, was 10 191 805, 15·48% lower than the figure for the corresponding period in 2019 (12 058 979). However, given the decrease in absolute number of appointments over this time, this number of prescriptions is 6·71% higher than expected (9 551 238)-a statistically significant increase (p<0·0001).

The decrease in absolute number of antibiotic prescriptions reflects the trend of falling antibiotic consumption in general practice since 2014, and the aim to reduce overprescribing. However, the unexpectedly high rate of prescribing during COVID-19 might reflect additional instances of inappropriate antibiotic use in telephone consultations.

Klebsiella pneumoniae infections in COVID-19 patients: a 2-month retrospective analysis in an Italian hospital

Arcari et al., International Journal of Antimicrobial Agents. 

Published: November 27th 2020.

DOI: https://doi.org/10.1016/j.ijantimicag.2020.106245 

Notes

In the period of this study, a total of 80 COVID-19-affected patients were hospitalised in the two ICUs at PUI. Among them, 65 patients were screened for colonisation by carbapenemase-producing Enterobacterales (CPE) (BrillianceTM CRE medium plates; Oxoid Ltd., Basingstoke, UK), including 41 of 47 SARS-CoV-2 patients hospitalised in the old ICU and 24 of 33 in the new ICU. Carbapenemase-producing Klebsiella pneumoniae were detected in 14/41 patients (34%) only in the old ICU. No CPE were detected from rectal swabs tested in patients hospitalised in the new ICU. In the same period, 11 CPE were identified from 39 rectal swabs of 48 SARS-CoV-2-negative patients (28%) hospitalised in the non-COVID ICU of the same hospital. Seven COVID-19 patients developed CPE co-infection (five bronchoalveolar lavages and two blood cultures tested positive for carbapenemase-producing K. pneumoniae), whilst in the non-COVID-19 ICU seven bloodstream infections (BSIs) also occurred. Symptomatic patients were successfully treated with ceftazidime/avibactam.

Using antibiotics wisely for respiratory tract infection in the era of covid-19

Leis et al., British Medical Journal.

Published: November 13th 2020.

DOI: https://doi.org/10.1136/bmj.m4125 

Notes

Before the covid-19 pandemic, international efforts such as the Choosing Wisely campaigns had focused on advancing improved antibiotic prescribing practices for the management of respiratory tract infection (RTI). In the era of covid-19, primary care delivery has been disrupted, and many clinicians have shifted to virtual care whenever possible, especially when supplies of personal protective equipment are limited. Clinicians who provide primary care are faced with challenging questions in the management of RTI, including when a patient should be tested for SARS-CoV-2, the virus that causes covid-19, when to prescribe antibiotics, and when a patient should be assessed in person. More than ever, a standardised approach is needed that is informed by best available evidence and promotes the judicious use of antibiotics for RTI.

Rates of bacterial co-infections and antimicrobial use in COVID-19 patients: a retrospective cohort study in light of antibiotic stewardship

Rothe et al., European Journal of Clinical Microbiology and Infectious Diseases.

Published: November 2nd 2020.

DOI: https://doi.org/10.1007/s10096-020-04063-8 

Notes

The coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide. Bacterial co-infections are associated with unfavourable outcomes in respiratory viral infections; however, microbiological and antibiotic data related to COVID-19 are sparse. Adequate use of antibiotics in line with antibiotic stewardship (ABS) principles is warranted during the pandemic. We performed a retrospective study of clinical and microbiological characteristics of 140 COVID-19 patients admitted between February and April 2020 to a German University hospital, with a focus on bacterial co-infections and antimicrobial therapy. The final date of follow-up was 6 May 2020. Clinical data of 140 COVID-19 patients were recorded: The median age was 63.5 (range 17-99) years; 64% were males. According to the implemented local ABS guidelines, the most commonly used antibiotic regimen was ampicillin/sulbactam (41.5%) with a median duration of 6 (range 1-13) days. Urinary antigen tests for Legionella pneumophila and Streptococcus peumoniae were negative in all cases. In critically ill patients admitted to intensive care units (n = 50), co-infections with Enterobacterales (34.0%) and Aspergillus fumigatus (18.0%) were detected. Blood cultures collected at admission showed a diagnostic yield of 4.2%. Bacterial and fungal co-infections are rare in COVID-19 patients and are mainly prevalent in critically ill patients. Further studies are needed to assess the impact of antimicrobial therapy on therapeutic outcome in COVID-19 patients to prevent antimicrobial overuse. ABS guidelines could help in optimising the management of COVID-19. Investigation of microbial patterns of infectious complications in critically ill COVID-19 patients is also required.

Incidence of bacterial and fungal bloodstream infections in COVID-19 patients in intensive care: An alarming "collateral effect"

Cataldo et al., Journal of Global Antimicrobial Resistance.

Published: October 29th 2020.

DOI: https://doi.org/10.1016/j.jgar.2020.10.004 

Summary

In order to assess the incidence of bacterial and fungal bloodstream infections (BSIs) in COVID-19 patients in Intensive Care, we performed a retrospective cohort study including COVID-19 adult patients hospitalised in intensive care unit (ICU) from March 1st to April 15th 2020 at the National Institute for Infectious Diseases, Rome, Italy.

Our findings evidenced an exaggerated risk of acquiring bacterial and fungal BSIs among critically ill patients with COVID-19 in ICU, namely an incidence almost 20 times higher than the incidence reported in European ICUs.

Notes

Bloodstream infections occurred in 49% of patients (28/57) with an incidence rate of 373 per 10,000 patient-days. The mean time from the ICU admission to the occurrence of BSI was 13 days ± 7 (range 3-34 days). The commonest isolated agents included Enterococcus spp (11 cases) and Pseudomonas spp (8 cases); Candida spp was isolated in 5 cases; in 3 patients more than one agent was isolated from blood cultures.

Antimicrobial stewardship in ICUs during the COVID-19 pandemic: back to the 90s?

Waele et al., Intensive Care Medicine.

Published: October 17th 2020.

DOI: https://doi.org/10.1007/s00134-020-06278-x 

Summary

SARS-CoV-2 infection has arguably been one of the most significant challenges of health care systems around the world in over a century. The coronavirus disease 2019 (COVID-19) lead to a massive increase in demand for acute care beds in many countries. Here, we focus on one of the unintended side effects of the surge in COVID-19 patients in the intensive care unit (ICU).

In summary, the use of antimicrobial drugs in the COVID-19 pandemic highlights the importance of upholding the AMS principles. Although it is challenging to apply the concepts used outside of pandemics, we need to reflect on how antimicrobial agents should be used. We have summarized a number of challenges in this respect, but for each of them, potential solutions are available. Rational infection management remains the goal.

Antimicrobial stewardship: a COVID casualty?

Lynch et al., Journal of Hospital Infection.

Published: October 8th 2020.

DOI: https://doi.org/10.1016/j.jhin.2020.10.002 

Summary

Whilst infection prevention and control teams may currently be focussed on the COVID-19 pandemic we must not forget that, along with the climate crisis, AMR presents an immediate and escalating threat to humanity which requires a One Health approach. Although the impact of infection preventionists may appear to be limited to the healthcare setting, we can also contribute by raising awareness to ensure that limiting the spread of AMR remains in the international spotlight. Courtenay et al. recently noted that COVID-19 has focused attention on nurse leaders' power and potential to promote AMS. The legacy of innovative approaches to AMS like those necessitated by the COVID-19 pandemic could actually strengthen AMS in the post-pandemic era.

Confronting antimicrobial resistance beyond the COVID-19 pandemic and the 2020 US election

Strathdee et al., The Lancet.

Published: September 29th 2020.

DOI: https://doi.org/10.1016/S0140-6736(20)32063-8 

Summary

COVID-19 is exacerbating AMR. Data from five countries suggest that 6·9% of COVID-19 diagnoses are associated with bacterial infections (3·5% diagnosed concurrently and 14·3% post-COVID-19), with higher prevalence in patients who require intensive critical care. However, a US multicentre study reported that 72% of COVID-19 patients received antibiotics even when not clinically indicated, which can promote AMR. AMR might worsen under COVID-19 due to the overuse of antibiotics in humans, continuing misuse in agriculture, and the dearth of antimicrobials in the development pipeline. Competing global priorities are reducing AMR eradication activities, including measures for multidrug-resistant tuberculosis.

Survey of antibiotic and antifungal prescribing in patients with suspected and confirmed COVID-19 in Scottish hospitals

Seaton et al., Journal of Infection.

Published: September 25th 2020.

DOI: https://doi.org/10.1016/j.jinf.2020.09.024 

Abstract

Background: Concern regarding bacterial co-infection complicating SARS-CoV-2 has created a challenge for antimicrobial stewardship. Following introduction of national antibiotic recommendations for suspected bacterial respiratory tract infection complicating COVID-19, a point prevalence survey of prescribing was conducted across acute hospitals in Scotland.

Methods: Patients in designated COVID-19 units were included and demographic, clinical and antimicrobial data were collected from 15 hospitals on a single day between 20th and 30th April 2020. Comparisons were made between SARS-CoV-2 positive and negative patients and patients on non-critical care and critical care units. Factors associated with antibiotic prescribing in SARS-CoV-2 positive patients were examined using Univariable and multivariable regression analyses.

Findings: There were 820 patients included, 64.8% were SARS-CoV-2 positive and 14.9% were managed in critical care, and 22.1% of SARS-CoV-2 infections were considered probable or definite nosocomial infections. On the survey day, antibiotic prevalence was 45.0% and 73.9% were prescribed for suspected respiratory tract infection. Amoxicillin, doxycycline and co-amoxiclav accounted for over half of all antibiotics in non-critical care wards and meropenem, piperacillin-tazobactam and co-amoxiclav accounted for approximately half prescribed in critical care. Of all SARS-CoV-2 patients, 38.3% were prescribed antibiotics. In a multivariable logistic regression analysis, COPD/chronic lung disease and CRP ≥ 100 mg/l were associated with higher odds and probable or confirmed nosocomial COVID-19, diabetes and management on an elderly care ward had lower odds of an antibiotic prescription. Systemic antifungals were prescribed in 9.8% of critical care patients and commenced a median of 18 days after critical care admission.

Interpretation: A relatively low prevalence of antibiotic prescribing in SARS-CoV-2 hospitalised patients and low proportion of broad spectrum antibiotics in non-critical care settings was observed potentially reflecting national antimicrobial stewardship initiatives. Broad spectrum antibiotic and antifungal prescribing in critical care units was observed indicating the importance of infection prevention and control and stewardship initiatives in this setting.

Understanding the role of bacterial and fungal infection in COVID-19

Rawson et al., Clinical Microbiology and Infection.

Published: September 22nd 2020.

DOI: 10.1016/j.cmi.2020.09.025 

Summary

Evidence so far suggests that detection of bacterial and fungal infection in COVID-19 is relatively low. Risk factors for nosocomial infection appear to be associated with critical care, especially mechanical ventilation and line use. Current data contrasts that of other respiratory viral pandemics, such as influenza, suggesting that SARS-CoV-2 may not have a significant impact on bacterial or fungal virulence. Reports of high rates of antimicrobial prescribing in secondary care mean that antimicrobial stewardship interventions must focus on improving diagnosis of bacterial and fungal infection, reducing unnecessary antimicrobial use in low-risk areas, and support access to therapy when required. Prospective studies are urgently required to provide greater insight into the risk factors and potential outcome of bacterial and fungal infection in COVID-19 and support evidence-based recommendations. Although the true impact of COVID-19 on AMR is difficult to predict, the enhanced focus on the consequences of infectious disease on human health should be capitalised upon to support the long-term AMR agenda. 

Nosocomial methicillin-resistant Staphylococcus aureus bacteremia in incarcerated patients with severe COVID-19 infection

Randall et al., American Journal of Infection Control.

Published: September 20th 2020.

DOI: https://doi.org/10.1016/j.ajic.2020.09.005 

Summary

Patient 1 was a 60-year-old male admitted in April 2020 for several days of fever, cough, and dyspnea. The patient had a history of chronic obstructive pulmonary disease, hypothyroidism, and coronary artery disease. He tested positive for COVID-19 and was initially admitted to the medical floor. Nasopharyngeal MRSA testing was negative on admission. The patient received systemic steroids. On hospital day 3, the patient developed worsening respiratory distress, was intubated, and had a central venous catheter placed for hypotension. The patient died this day; blood cultures drawn grew MRSA.

Patient 2 was an 83-year-old male admitted in late May 2020 with hypoxia and known COVID-19 infection. His medical history included atrial fibrillation and hypertension. Nasopharyngeal MRSA testing was negative on admission. The patient was treated with Remdesivir and systemic steroids. On hospital day 13, the patient required intubation and developed hypotension. On hospital day 14, a central venous catheter was placed; blood and throat cultures obtained were both MRSA positive. The patient died the same day from septic shock.

Patient 3 was a 60-year-old male admitted in June 2020 with severe hypoxia and COVID-19 infection. His medical history included type II diabetes, hypertension, and hepatitis C cirrhosis. Nasopharyngeal MRSA testing was negative on admission. Initially, he was admitted to the intensive care unit but improved and was transferred to the medical floor. He was treated with systemic steroids but was not a candidate for Remdesivir. On hospital day 4, he had a cardiopulmonary arrest and was transferred back to the intensive care unit. On hospital day 9, blood cultures were positive for MRSA. On hospital day 10, the patient died from pneumonia after the family signed a Do-Not-Resuscitate order.

Bacterial and viral co-infections in patients with severe SARS-CoV-2 pneumonia admitted to a French ICU

Contou et al., Annals of Intensive Care.

Published: September 7th 2020.

DOI: https://doi.org/10.1186/s13613-020-00736-x 

Abstract

Background: Data on the prevalence of bacterial and viral co-infections among patients admitted to the ICU for acute respiratory failure related to SARS-CoV-2 pneumonia are lacking. We aimed to assess the rate of bacterial and viral co-infections, as well as to report the most common micro-organisms involved in patients admitted to the ICU for severe SARS-CoV-2 pneumonia.

Patients and methods: In this monocenter retrospective study, we reviewed all the respiratory microbiological investigations performed within the first 48 h of ICU admission of COVID-19 patients (RT-PCR positive for SARS-CoV-2) admitted for acute respiratory failure.

Results: From March 13th to April 16th 2020, a total of 92 adult patients (median age: 61 years, 1st-3rd quartiles [55-70]; males: n = 73/92, 79%; baseline SOFA: 4 [3-7] and SAPS II: 31 [21-40]; invasive mechanical ventilation: n = 83/92, 90%; ICU mortality: n = 45/92, 49%) were admitted to our 40-bed ICU for acute respiratory failure due to SARS-CoV-2 pneumonia. Among them, 26 (28%) were considered as co-infected with a pathogenic bacterium at ICU admission with no co-infection related to atypical bacteria or viruses. The distribution of the 32 bacteria isolated from culture and/or respiratory PCRs was as follows: methicillin-sensitive Staphylococcus aureus (n = 10/32, 31%), Haemophilus influenzae (n = 7/32, 22%), Streptococcus pneumoniae (n = 6/32, 19%), Enterobacteriaceae (n = 5/32, 16%), Pseudomonas aeruginosa (n = 2/32, 6%), Moraxella catarrhalis (n = 1/32, 3%) and Acinetobacter baumannii (n = 1/32, 3%). Among the 24 pathogenic bacteria isolated from culture, 2 (8%) and 5 (21%) were resistant to 3rd generation cephalosporin and to amoxicillin-clavulanate combination, respectively.

Conclusions: We report on a 28% rate of bacterial co-infection at ICU admission of patients with severe SARS-CoV-2 pneumonia, mostly related to Staphylococcus aureus, Haemophilus influenzae, Streptococcus pneumoniae and Enterobacteriaceae. In French patients with confirmed severe SARS-CoV-2 pneumonia requiring ICU admission, our results encourage the systematic administration of an empiric antibiotic monotherapy with a 3rd generation cephalosporin, with a prompt de-escalation as soon as possible. Further larger studies are needed to assess the real prevalence and the predictors of co-infection together with its prognostic impact on critically ill patients with severe SARS-CoV-2 pneumonia.

COVID-19 and tuberculosis co-infection: a neglected paradigm

Bandyopadhyay et al., Monaldi Archives for Chest Disease.

Published: September 4th 2020.

DOI: https://doi.org/10.4081/monaldi.2020.1437 

Abstract

COVID-19 has been affecting mankind round the globe. The incidence of this infectious disease of respiratory origin is constantly on rise. Another infectious disease widely prevalent is tuberculosis (TB). During past corona virus pandemics of Severe Acute Respiratory Syndrome and Middle East Respiratory Syndrome, coinfection with TB was seen. We present this review as the co-infection of COVID-19 with TB has not been assessed yet, imposing a greater global threat. We suggest few measures to be implemented without delay for effectively screening the suspects of co-infection and also follow up of non-suspect patients in the post-pandemic phase.

Multidrug-Resistant Candida auris Infections in Critically Ill Coronavirus Disease Patients, India, April-July 2020

Chowdhary et al., Emerging Infectious Diseases.

Published: August 27th 2020.

DOI: 10.3201/eid2611.203504

Abstract

In New Delhi, India, candidemia affected 15 critically ill coronavirus disease patients admitted to an intensive care unit during April-July 2020. Candida auris accounted for two thirds of cases; case-fatality rate was high (60%). Hospital-acquired C. auris infections in coronavirus disease patients may lead to adverse outcomes and additional strain on healthcare resources.

Antibiotic use in patients with COVID-19: a 'snapshot' Infectious Diseases International Research Initiative (ID-IRI) survey

Beović et al., Journal of Antimicrobial Chemotherapy.

Published: August 7th 2020

DOI: https://doi.org/10.1093/jac/dkaa326

Abstract

Background: Antibiotics may be indicated in patients with COVID-19 due to suspected or confirmed bacterial superinfection.

Objectives: To investigate antibiotic prescribing practices in patients with COVID-19.

Methods: We performed an international web-based survey and investigated the pattern of antibiotic use as reported by physicians involved in treatment of COVID-19. SPSS Statistics version 25 was used for data analysis.

Results: The survey was completed by 166 participants from 23 countries and 82 different hospitals. Local guidelines for antibiotic use in COVID-19 patients were reported by 61.8% (n = 102) of participants and for 82.9% (n = 136) they did not differ from local community-acquired pneumonia guidelines. Clinical presentation was recognized as the most important reason for the start of antibiotics (mean score = 4.07 and SD = 1.095 on grading scale from 1 to 5). When antibiotics were started, most respondents rated as the highest the need for coverage of atypical pathogens (mean score = 2.8 and SD = 0.99), followed by Staphylococcus aureus (mean score = 2.67 and SD = 1.05 on bi-modal scale, with values 1 and 2 for disagreement and values 3 and 4 for agreement). In the patients on the ward, 29.1% of respondents chose not to prescribe any antibiotic. Combination of β-lactams and macrolides or fluoroquinolones was reported by 52.4% (n = 87) of respondents. In patients in the ICU, piperacillin/tazobactam was the most commonly prescribed antibiotic. The mean reported duration of antibiotic treatment was 7.12 (SD = 2.44) days.

Conclusions: The study revealed widespread broad-spectrum antibiotic use in patients with COVID-19. Implementation of antimicrobial stewardship principles is warranted to mitigate the negative consequences of antibiotic therapy.

COVID-19 associated invasive candidiasis

Al-Hatmi et al., Journal of Infection.

Published: August 6th 2020.

DOI: https://doi.org/10.1016/j.jinf.2020.08.005 

Abstract

In this review, four fungal pathogens were reported from three studies, namely Candida albicans, Candida glabrata, Aspergillus flavus and Aspergillus fumigatus. In addition, Hughes et al. retrospectively analysed hospitalised patients with confirmed COVID-19 infection (n = 836) across two acute NHS hospitals. Among the confirmed COVID-19 infection, C. albicans infections were attributed to central line source. Chen and colleagues reported both bacterial and fungal co-infections. Recently, Verweij et al., reported that Aspergillus species as co-pathogens are commonly identified in COVID-19 patients and are an important cause of mortality. Fungal co-infections and their impact on COVID-19 patients are still understudied. In this regards, we retrospectively analysed nosocomial mortality related to bloodstream infection and their risk factors associated with Covid-19 patients in the intensive care unit (ICU) at a single center in Oman. Five candidemia cases were reported from adult patients. All five patients were admitted to the ICU, had a central venous catheter (CVC) in place at the onset of candidemia, and received broad-spectrum antibiotic therapy.

Notes

Four patients received antifungal therapy; two received caspofungin alone, two received combination of (caspofungin + amphotericin B) and (voriconazole + caspofungin) and one patient did not receive any antifungals. Despite antifungal therapy, 3 out of 5 patients died. Our observations suggest increased risk for critically ill COVID-19 patients to develop co-infection with Candida, which is likely to increase mortality rates.

Bacterial co-infection and secondary infection in patients with COVID-19: a living rapid review and meta-analysis

Langford et al., Clinical Microbiology and Infection

Published: July 22nd 2020

DOI: https://doi.org/10.1016/j.cmi.2020.07.016

Abstract

Background: Bacterial co-pathogens are commonly identified in viral respiratory infections and are important causes of morbidity and mortality. The prevalence of bacterial infection in patients infected with SARS-CoV-2 is not well understood.

Aims: To determine the prevalence of bacterial co-infection (at presentation) and secondary infection (after presentation) in patients with COVID-19.

Sources: We performed a systematic search of MEDLINE, OVID Epub and EMBASE databases for English language literature from 2019 to April 16, 2020. Studies were included if they (a) evaluated patients with confirmed COVID-19 and (b) reported the prevalence of acute bacterial infection.

Content: Data were extracted by a single reviewer and cross-checked by a second reviewer. The main outcome was the proportion of COVID-19 patients with an acute bacterial infection. Any bacteria detected from non-respiratory-tract or non-bloodstream sources were excluded. Of 1308 studies screened, 24 were eligible and included in the rapid review representing 3338 patients with COVID-19 evaluated for acute bacterial infection. In the meta-analysis, bacterial co-infection (estimated on presentation) was identified in 3.5% of patients (95%CI 0.4-6.7%) and secondary bacterial infection in 14.3% of patients (95%CI 9.6-18.9%). The overall proportion of COVID-19 patients with bacterial infection was 6.9% (95%CI 4.3-9.5%). Bacterial infection was more common in critically ill patients (8.1%, 95%CI 2.3-13.8%). The majority of patients with COVID-19 received antibiotics (71.9%, 95%CI 56.1 to 87.7%).

Implications: Bacterial co-infection is relatively infrequent in hospitalized patients with COVID-19. The majority of these patients may not require empirical antibacterial treatment.

Notes

Of the bacterial co-pathogens reported, the most common organisms were Mycoplasma species (n = 11 patients, n = 3 reported as M. pneumoniae), Haemophilus influenzae (n = 5 patients) and Pseudomonas aeruginosa (n = 5 patients). The antibiotic use reported in the studies included in this review were generally broad spectrum with fluoroquinolones and third-generation cephalosporins comprising 74% of the antibiotics prescribed. 

Underestimation of co-infections in COVID-19 due to non-discriminatory use of antibiotics

Chang and Chan, Journal of Infection.

Published: July 3rd 2020

DOI: https://doi.org/10.1016/j.jinf.2020.06.077

Summary

It is unclear that the reported low co-infection rate is the result of large scales of empirical antimicrobial administration or the limitation of the overwhelmed clinical examinations in health systems during the pandemic. We concern the underestimation of the co-infections in COVID-19 patients, especially those on invasive mechanical ventilation support. However, we are also aware of the long-term impact of the development of antimicrobial resistance due to unnecessary usage of antimicrobial agents. We urge to re-establish the stewardship of antimicrobial therapy by systematic surveillance on antimicrobial usage and co-infections in COVID-19 patients. Future development in fast diagnosis for infectious agents based on genomics or proteomics identification will provide timely and accurate information for disease management. It is essential to develop evidence-based guidelines for responding the potential second wave of COVID-19 or future pandemics.

Bacterial and fungal coinfection among hospitalised patients with COVID-19: A retrospective cohort study in a UK secondary care setting

Hughes et al., Clinical Microbiology and Infection.

Published: June 26th 2020.

DOI: https://doi.org/10.1016/j.cmi.2020.06.025

Abstract:

Objectives: We investigate the incidence of bacterial and fungal co-infection of hospitalised patients with confirmed SARS-CoV-2 in this retrospective observational study across two London hospitals during the first UK wave of COVID-19.

Methods: A retrospective case-series of hospitalised patients with confirmed SARS-CoV-2 by PCR was analysed across two acute NHS hospitals (February 20-April 20; each isolate reviewed independently in parallel). This was contrasted to a control group of influenza positive patients admitted during 2019/20 flu season. Patient demographics, microbiology, and clinical outcomes were analysed.

Results: 836 patients with confirmed SARS-CoV-2 were included; 27/836(3.2%) had early confirmed bacterial isolates identified (0-5 days post-admission) rising to 51/836(6.1%) throughout admission. Blood cultures, respiratory samples, pneumococcal or legionella urinary antigens, and respiratory viral PCR panels were obtained from 643(77%), 112(13%), 249(30%), 246(29%) and 250(30%) COVID-19 patients, respectively. A positive blood culture was identified in 60(7.1%) patients, of which 39/60 were classified as contaminants. Bacteraemia secondary to respiratory infection was confirmed in two cases (1 community-acquired K. pneumoniae and 1 ventilator-associated E. cloacae). Line-related bacteraemia was identified in six patients (3 candida, 2 Enterococcus spp. and 1 Pseudomonas aeruginosa). All other community acquired bacteraemias(16) were attributed to non-respiratory infection. Zero concomitant pneumococcal, legionella or influenza infection was detected. A low yield of positive respiratory cultures was identified; S. aureus the most common respiratory pathogen isolated in community-acquired coinfection (4/24;16.7%) with pseudomonas and yeast identified in late-onset infection. Invasive fungal infections (n=3) were attributed to line related infections. Comparable rates of positive co-infection were identified in the control group of confirmed influenza infection; clinically relevant bacteraemias (2/141;1.4%), respiratory cultures (10/38;26.1%) and pneumococcal-positive antigens (1/19;5.2%) were low.

Conclusion: We find a low frequency of bacterial co-infection in early COVID hospital presentation, and no evidence of concomitant fungal infection, at least in the early phase of COVID-19.

Keywords: Antimicrobial use, drug-resistant infections and COVID-19

Chowdhary and Sharma, Journal of Global Antimicrobial Resistance.

Published: June 12th 2020

DOI: https://doi.org/10.1016/j.jgar.2020.06.003

Summary

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in late 2019 has caused a pandemic of COVID-19. A particularly disturbing feature of COVID-19 patients is their tendency to develop acute respiratory distress syndrome that requires ICU admission, mechanical ventilation and/or extracorporeal membrane oxygenation [1]. Reports from several countries suggest flooding of hospital ICUs by COVID-19 patients that require respiratory support ranging from high-flow nasal cannula to invasive ventilation. This haunting facet of COVID-19 pandemic has severely challenged even the most advanced hospital settings. Yet one potential confounder, not in the immediate attention of most healthcare professionals, is the secondary transmission of multi-drug resistant organisms like the fungus Candida auris in COVID-19 ICUs. 

Antimicrobial use, drug-resistant infections and COVID-19

Rawson et al., Nature.

Published: June 2nd 2020

DOI: https://doi.org/10.1038/s41579-020-0395-y

Summary

Coronavirus disease 2019 may have a complex long-term impact on antimicrobial resistance (AMR). Coordinated strategies at the individual, health-care and policy levels are urgently required to inform necessary actions to reduce the potential longer-term impact on AMR and on access to effective antimicrobials.

Low rate of bacterial co-infection in patients with COVID-19

Adler et al., The Lancet.

Published: June 1st 2020

DOI: https://doi.org/10.1016/S2666-5247(20)30036-7

Notes

This study reviewed the microbiology results of all patients admitted with confirmed COVID-19 to Whiston hospital (Prescot,UK) between March 6th 2020 and April 7th 2020. 195 patients were identified, five(3% of 195, or 4% of 137 patients specifically tested), had pneumococcal co-infection and all survived to hospital discharge. One of 31 patients tested was positive for the Legionella antigen without lower respiratory tract samples to confirm legionellosis. 26 sputum samples were taken, only four of them grew bacteria. All the  bacteria isolated were Gram-negative bacilli more typically associated with oropharyngeal colonisation than community-acquired pneumonia.

Prescription Fill Patterns for Commonly Used Drugs During the COVID-19 Pandemic in the United States

Vaduganathan et al., JAMA.

Published: May 28th 2020

DOI: 10.1001/jama.2020.9184

Conflicting information regarding the benefits of hydroxychloroquine/chloroquine and azithromycin in coronavirus disease 2019 (COVID-19) treatment and hypothetical concerns for drugs, such as angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs), have challenged care during the pandemic.1 However, limited data are available about how prescription of these therapies has changed. The objective of this exploratory analysis was to evaluate prescription patterns of these therapies, along with other commonly used drugs for reference, in the United States during the COVID-19 pandemic. We hypothesized that the prescription of hydroxychloroquine/chloroquine and azithromycin would exceed historical estimates while ACE inhibitor/ARB use would be reduced.

Notes

By the end of the study (end of April 2020) prescription fills declined by 64.4% for amoxicillin and 62.7% for azithromycin. These declines were noted to be out of proportion to expected seasonal declines.

Co-infections in people with COVID-19: a systematic review and meta-analysis

Lansbury et al., Journal of Infection.

Published: May 27th 2020

DOI: https://doi.org/10.1016/j.jinf.2020.05.046

Abstract

Objectives: In previous influenza pandemics, bacterial co-infections have been a major cause of mortality. We aimed to evaluate the burden of co-infections in patients with COVID-19.
Methods: We systematically searched Embase, Medline, Cochrane Library, LILACS and CINAHL for eligible studies published from 1 January 2020 to 17 April 2020. We included patients of all ages, in all settings. The main outcome was the proportion of patients with a bacterial, fungal or viral co-infection. .
Results: Thirty studies including 3834 patients were included. Overall, 7% of hospitalised COVID-19 patients had a bacterial co-infection (95% CI 3-12%, n=2183, I2=92∙2%). A higher proportion of ICU patients had bacterial co-infections than patients in mixed ward/ICU settings (14%, 95% CI 5-26, I2=74∙7% versus 4%, 95% CI 1-9, I2= 91∙7%). The commonest bacteria were Mycoplasma pneumonia, Pseudomonas aeruginosa and Haemophilus influenzae. The pooled proportion with a viral co-infection was 3% (95% CI 1-6, n=1014, I2=62∙3%), with Respiratory Syncytial Virus and influenza A the commonest. Three studies reported fungal co-infections.
Conclusions: A low proportion of COVID-19 patients have a bacterial co-infection; less than in previous influenza pandemics. These findings do not support the routine use of antibiotics in the management of confirmed COVID-19 infection.

SARS‐CoV‐2, bacterial co‐infections, and AMR: the deadly trio in COVID‐19?

Bengeochea et al., EMBO Molecular Medicine.

Published: May 26th 2020

DOI: https://doi.org/10.15252/emmm.202012560

Abstract

At the end of December 2019, Chinese public health authorities reported a cluster of pneumonia of unknown cause in central city of Wuhan in Hubei province. Shortly after, Chinese scientists identified a hitherto undescribed beta‐coronavirus as the likely causative agent. The disease is now referred to as coronavirus disease 2019 (COVID‐19), and the virus is called severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). Since 31 December 2019 and as of 25 May 2020, 5,432,512 cases of COVID‐19 (in accordance with the applied case definitions and testing strategies in the affected countries) have been reported globally, including 345,467 deaths.

Acquisition of multidrug-resistant Enterobacterales during international travel: a systematic review of clinical and microbiological characteristics and meta-analyses of risk factors

Voor in 't holt et al., Antimicrobial resistance and Infection control.

Published: May 20th 2020.

DOI: https://doi.org/10.1186/s13756-020-00733-6

Abstract

Background: International tourism increased from 25 million tourist arrivals in 1950 to over 1.3 billion in 2017. These travelers can be exposed to (multi) resistant microorganisms, may become colonized, and bring them back home. This systematic review aims to identify the carriage rates of multidrug-resistant Enterobacterales (MDR-E) among returning travelers, to identify microbiological methods used, and to identify the leading risk factors for acquiring MDR-E during international travel.

Methods: Articles related to our research question were identified through a literature search in multiple databases (until June 18, 2019) - Embase, Medline Ovid, Cochrane, Scopus, Cinahl, Web of Science, and Google Scholar.

Results: Out of 3211 potentially relevant articles, we included 22 studies in the systematic review, and 12 studies in 7 random-effects meta-analyses. Highest carriage rates of MDR-E were observed after travel to Southern Asia (median 71%), followed by travel to Northern Africa (median 42%). Carbapenemase-producing Enterobacterales (CPE) were identified in 5 out of 22 studies, from a few patients. However, in only eight out of 22 studies (36.4%) the initial laboratory method targeted detection of the presence of CPE in the original samples. The risk factor with the highest pooled odds ratio (OR) for MDR-E was travel to Southern Asia (pooled OR = 14.16, 95% confidence interval [CI] = 5.50 to 36.45), followed by antibiotic use during travel (pooled OR = 2.78, 95% CI = 1.76 to 4.39).

Conclusions: Risk of acquiring MDR-E while travelling increases depending on travel destination and if antibiotics are used during travel. This information is useful for the development of guidelines for healthcare facilities with low MDR-E prevalence rates to prevent admission of carriers without appropriate measures. The impact of such guidelines should be assessed.

Keywords: Travel, Enterobacteriaceae, Enterobacterales, Systematic review, Meta-analysis, Antimicrobial resistance, Epidemiology, Microbiology, Beta-lactamases

COVID-19 and the potential long-term impact on antimicrobial resistance

Rawson et al., Journal of Antimicrobial Chemotherapy.

Published: May 20th 2020.

DOI: https://doi.org/10.1093/jac/dkaa194

Abstract

The emergence of the Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) has required an unprecedented response to control the spread of the infection and protect the most vulnerable within society. Whilst the pandemic has focused society on the threat of emerging infections and hand hygiene, certain infection control and antimicrobial stewardship policies may have to be relaxed. It is unclear whether the unintended consequences of these changes will have a net-positive or -negative impact on rates of antimicrobial resistance. Whilst the urgent focus must be on controlling this pandemic, sustained efforts to address the longer-term global threat of antimicrobial resistance should not be overlooked.

Reduction of coronavirus burden with mass azithromycin distribution

Doan et al., Clinical Infectious Diseases.

Published: May 19th 2020.

DOI: https://doi.org/10.1093/cid/ciaa606

Abstract

We evaluated the potential antiviral effects of azithromycin on the nasopharyngeal virome of Nigerien children who had received multiple rounds of mass drug administration. We found that the respiratory burden of non-SARS coronaviruses was decreased with azithromycin distributions.

Multidrug resistant infections in the COVID-19 era, a framework for considering the potential impact

Donà et al., Journal of Hospital Infection.

Published: May 17th 2020

DOI: https://doi.org/10.1016/j.jhin.2020.05.020

A Case of COVID-19 and Pneumocystis jirovecii Co-infection

Menon et al., American Thoracic Society Journals.

Published: May 15th 2020.

DOI: https://doi.org/10.1164/rccm.202003-0766LE

Preview

Lymphocytopenia has been identified as a common laboratory finding in patients with SARS-CoV-2 infection, particularly among those with more severe presentations (1); however, there are limited data on which specific lymphocyte populations may be affected or the clinical sequelae. In this report, we describe the case of a woman with hypoxemic respiratory failure found to have co-infection with SARS-CoV-2 and Pneumocystis jirovecii, a pathogen commonly seen in patients with defects in T cell immunity.

COVID-19 and antimicrobial stewardship: What is the interplay?

Spernovasilis and Kofteridis., Infection Control & Hospital Epidemiology.

Published: May 15th 2020.

DOI: https://doi.org/10.1017/ice.2020.246

Preview

Coronavirus disease 2019 (COVID-19) is currently in the spotlight, attracting all the attention of world's medical community. Meanwhile, other longer-term public health issues, such as antimicrobial resistance caused by misuse and/or overuse of antimicrobials, may have been placed in the shadow. At this stage of the pandemic, and under the pressure caused by the absence of specific antivirals and vaccines, antimicrobials are used as:1 repurposed drugs for the treatment of COVID-19, such as the combination of azithromycin and hydroxychloroquine;2 empirical coverage for possible co-existing community-acquired infection of the respiratory tract, especially in severe cases of COVID-19; empirical coverage for possible hospital-acquired superinfection of the respiratory tract, taking into account that a significant proportion of COVID-19 hospitalised patients will have prolonged hospitalisation or will require intensive care unit (ICU) admission; targeted treatment for community or hospital-acquired respiratory tract co/superinfections; empirical or targeted treatment for co/superinfection outside of the respiratory tract.

Bacteremia and Blood Culture Utilization During COVID-19 Surge in New York City

Sepulveda et al., Journal of Clinical Microbiology.

Published: May 13th 2020

DOI: 10.1128/JCM.00875-20

Abstract

A surge of patients with coronavirus disease 2019 (COVID-19) presenting to New York City hospitals in March 2020 led to a sharp increase blood culture utilization, which overwhelmed the capacity of automated blood culture instruments. We sought to evaluate the utilization and diagnostic yield of blood cultures during the COVID-19 pandemic to determine prevalence and common etiologies of bacteremia, and to inform a diagnostic approach to relieve blood culture overutilization. We performed a retrospective cohort analysis of 88,201 blood cultures from 28,011 patients at a multicenter network of hospitals within New York City to evaluate order volume, positivity rate, time to positivity, and etiologies of positive cultures in COVID-19. Ordering volume increased by 34.8% in the second half of March 2020 compared to the first half of the month. The rate of bacteremia was significantly lower among COVID-19 patients (3.8%) than COVID-19 negative patients (8.0%) and those not tested (7.1%), p < 0.001. COVID-19 patients had a high proportion of organisms reflective of commensal skin microbiota, reducing the bacteremia rate to 1.6% when excluded. More than 98% of all positive cultures were detected within 4 days of incubation. Bloodstream infections are very rare for COVID-19 patients, which supports the judicious use of blood cultures in the absence of compelling evidence for bacterial co-infection. Clear communication with ordering providers is necessary to prevent overutilization of blood cultures during patient surges, and laboratories should consider shortening the incubation period from 5 days to 4 days, if necessary, to free additional capacity.

Notes

Among patients with positive blood cultures, COVID-19 patients had a significantly higher proportion of cultures that likely represented contamination with normal skin microbiota than all other groups. Organisms were labeled as likely contaminants if they were isolated only once per 160 patient and belonged to groups generally defined as commensal skin microbiota. Coagulase-negative Staphylococcus species accounted for 59.7% of all positive cultures among COVID-19 patients, compared to 32.0% among patients that tested negative for SARS-CoV-2, and 29.8% among patients that were not tested for SARS-CoV-2 in 2020 (p < 0.001). Corynebacterium species, Bacillus species, and Micrococcus species were also seen more frequently among COVID-19 patients. The most common causes of true bacteremia among COVID-19 patients were Escherichia coli (16.7%), Staphylococcus aureus (13.3%), Klebsiella pneumoniae (10.0%), and Enterobacter cloacae complex (8.3%).

Diagnosing COVID-19-associated pulmonary aspergillosis

Verweij et al., The Lancet Microbe

Published: May 8th 2020

DOI: https://doi.org/10.1016/S2666-5247(20)30027-6

Comment: There is increasing concern that patients with coronavirus disease 2019 (COVID-19) might be at risk of developing invasive pulmonary aspergillosis co-infection.1 In a cohort of 221 patients with COVID-19 in China, fungal infections were diagnosed in seven individuals, all of whom were admitted to the intensive care unit (ICU).2 However, causative fungal pathogens were not identified.2 Given that in China, galactomannan testing is rarely available,3 the real burden of invasive pulmonary aspergillosis in patients with COVID-19 requiring ICU admission is probably underestimated. Indeed, nine patients with COVID-19 and invasive pulmonary aspergillosis were recently described in France (33% of 27 admitted to the ICU with COVID-19),4 and five in Germany (26% of 19 admitted);5 rates similar to those observed in association with influenza.

Bacterial and fungal co-infection in individuals with coronavirus: A rapid review to support COVID-19 antimicrobial prescribing

Rawson et al., Clinical Infectious Disease

Published:May 2nd 2020

DOI: https://doi.org/10.1093/cid/ciaa530

Abstract

Background: To explore and describe the current literature surrounding bacterial/fungal co-infection in patients with coronavirus infection.

Methods: MEDLINE, EMBASE, and Web of Science were searched using broad based search criteria relating to coronavirus and bacterial co-infection. Articles presenting clinical data for patients with coronavirus infection (defined as SARS-1, MERS, SARS-COV-2, and other coronavirus) and bacterial/fungal co-infection reported in English, Mandarin, or Italian were included. Data describing bacterial/fungal co-infections, treatments, and outcomes were extracted. Secondary analysis of studies reporting antimicrobial prescribing in SARS-COV-2 even in the absence of co-infection was performed.

Results: 1007 abstracts were identified. Eighteen full texts reported bacterial/fungal co-infection were included. Most studies did not identify or report bacterial/fungal coinfection (85/140;61%). 9/18 (50%) studies reported on COVID-19, 5/18 (28%) SARS-1, 1/18 (6%) MERS, and 3/18 (17%) other coronavirus.

For COVID-19, 62/806 (8%) patients were reported as experiencing bacterial/fungal co-infection during hospital admission. Secondary analysis demonstrated wide use of broad-spectrum antibacterials, despite a paucity of evidence for bacterial coinfection. On secondary analysis, 1450/2010 (72%) of patients reported received antimicrobial therapy. No antimicrobial stewardship interventions were described.

For non-COVID-19 cases bacterial/fungal co-infection was reported in 89/815 (11%) of patients. Broad-spectrum antibiotic use was reported.

Conclusions: Despite frequent prescription of broad-spectrum empirical antimicrobials in patients with coronavirus associated respiratory infections, there is a paucity of data to support the association with respiratory bacterial/fungal co-infection. Generation of prospective evidence to support development of antimicrobial policy and appropriate stewardship interventions specific for the COVID-19 pandemic are urgently required.

COVID-19, superinfections and antimicrobial development: What can we expect?

Clancy and Nguyen, Clinical Infectious Diseases

Published: May 1st 2020

DOI: https://doi.org/10.1093/cid/ciaa524

Abstract

Coronavirus disease 2019 (COVID-19) arose at a time of great concern about antimicrobial resistance (AMR). No studies have specifically assessed COVID-19-associated superinfections or AMR. Based on limited data from case series, it is reasonable to anticipate that an appreciable minority of patients with severe COVID-19 will develop superinfections, most commonly pneumonia due to nosocomial bacteria and Aspergillus. Microbiology and AMR patterns are likely to reflect institutional ecology. Broad-spectrum antimicrobial use is likely to be widespread among hospitalized patients, both as directed and empiric therapy. Stewardship will have a crucial role in limiting unnecessary antimicrobial use and AMR. Congressional COVID-19 relief bills are considering antimicrobial reimbursement reforms and antimicrobial subscription models, but it is unclear if these will be included in final legislation. Prospective studies on COVID-19 superinfections are needed, data from which can inform rational antimicrobial treatment and stewardship strategies, and models for market reform and sustainable drug development.

COVID‐19 Associated Pulmonary Aspergillosis

Koehler et al., Mycoses.

Published: April 27th 2020

DOI: https://doi.org/10.1111/myc.13096

Abstract

Objectives; Patients with acute respiratory distress syndrome (ARDS) due to viral infection are at risk for secondary complications like invasive aspergillosis. Our study evaluates Coronavirus disease 19 (COVID‐19) associated invasive aspergillosis at a single center in Cologne, Germany.

Methods; A retrospective chart review of all patients with COVID‐19 ARDS admitted to the medical or surgical intensive care unit at the University Hospital of Cologne, Germany.

Results; COVID‐19 associated invasive pulmonary aspergillosis was found in five of 19 consecutive critically ill patients with moderate to severe ARDS.

Conclusion; Clinicians caring for patients with ARDS due to COVID‐19 should consider invasive pulmonary aspergillosis and subject respiratory samples to comprehensive analysis to detect co‐infection.

Fatal Invasive Aspergillosis and Coronavirus Disease in an Immunocompetent Patient

Blaize et al., Emerging Infectious Diseases

Published: April 27th 2020

DOI: 10.3201/eid2607.201603

Abstract: Invasive pulmonary aspergillosis is a complication in critically ill patients with acute respiratory distress syndrome, especially those with severe influenza pneumonia. We report a fatal case of invasive pulmonary aspergillosis in an immunocompetent patient in France who had severe coronavirus disease-associated pneumonia.

Co-infections: potentially lethal and unexplored in COVID-19

Cox et al., The Lancet Microbe

Published: April 24th 2020

DOI: https://doi.org/10.1016/S2666-5247(20)30009-4

Correspondence; Respiratory viral infections predispose patients to co-infections and these lead to increased disease severity and mortality. Most fatalities in the 1918 influenza outbreak were due to subsequent bacterial infection, particularly with Streptococcus pneumoniae. Poor outcomes in the 2009 H1N1 influenza pandemic were also associated with bacterial co-infections, although few studies captured these data...

Effect of High vs Low Doses of Chloroquine Diphosphate as Adjunctive Therapy for Patients Hospitalized With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection

Borba et al., 2020. JAMA Netw Open.

Published: April 24th 2020

DOI: 10.1001/jamanetworkopen.2020.8857

Importance There is no specific antiviral therapy recommended for coronavirus disease 2019 (COVID-19). In vitro studies indicate that the antiviral effect of chloroquine diphosphate (CQ) requires a high concentration of the drug.

Objective To evaluate the safety and efficacy of 2 CQ dosages in patients with severe COVID-19.

Design, Setting, and Participants This parallel, double-masked, randomized, phase IIb clinical trial with 81 adult patients who were hospitalized with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was conducted from March 23 to April 5, 2020, at a tertiary care facility in Manaus, Brazilian Amazon.

Interventions Patients were allocated to receive high-dosage CQ (ie, 600 mg CQ twice daily for 10 days) or low-dosage CQ (ie, 450 mg twice daily on day 1 and once daily for 4 days).

Main Outcomes and Measures Primary outcome was reduction in lethality by at least 50% in the high-dosage group compared with the low-dosage group. Data presented here refer primarily to safety and lethality outcomes during treatment on day 13. Secondary end points included participant clinical status, laboratory examinations, and electrocardiogram results. Outcomes will be presented to day 28. Viral respiratory secretion RNA detection was performed on days 0 and 4.

Results Out of a predefined sample size of 440 patients, 81 were enrolled (41 [50.6%] to high-dosage group and 40 [49.4%] to low-dosage group). Enrolled patients had a mean (SD) age of 51.1 (13.9) years, and most (60 [75.3%]) were men. Older age (mean [SD] age, 54.7 [13.7] years vs 47.4 [13.3] years) and more heart disease (5 of 28 [17.9%] vs 0) were seen in the high-dose group. Viral RNA was detected in 31 of 40 (77.5%) and 31 of 41 (75.6%) patients in the low-dosage and high-dosage groups, respectively. Lethality until day 13 was 39.0% in the high-dosage group (16 of 41) and 15.0% in the low-dosage group (6 of 40). The high-dosage group presented more instance of QTc interval greater than 500 milliseconds (7 of 37 [18.9%]) compared with the low-dosage group (4 of 36 [11.1%]). Respiratory secretion at day 4 was negative in only 6 of 27 patients (22.2%).

Conclusions and Relevance The preliminary findings of this study suggest that the higher CQ dosage should not be recommended for critically ill patients with COVID-19 because of its potential safety hazards, especially when taken concurrently with azithromycin and oseltamivir. These findings cannot be extrapolated to patients with nonsevere COVID-19.

Trial Registration ClinicalTrials.gov Identifier: NCT04323527

SARS-CoV-2 infection (COVID-19) in febrile infants without respiratory distress.

Paret et al., Clinical Infectious Diseases

Published: April 17th 2020

DOI: 10.1093/cid/ciaa452

Abstract

We report two cases of SARS-CoV-2 infection (COVID-19) in infants presenting with fever in the absence of respiratory distress who required hospitalization for evaluation of possible invasive bacterial infections. The diagnoses resulted from routine isolation and real-time RT-PCR-based testing for SARS-CoV-2 for febrile infants in an outbreak setting.

Notes

Case 1: A CSF PCR panel that targets E. coli K1, Haemophilus influenzae, Listeria monocytogenes, Neisseria meningitidis, Streptococcus agalactiae, Streptococcus pneumoniae and Cryptococcus neoformans/gattii was performed and was negative. A respiratory PCR panel targeting Bordetella pertussis, Chlamydophila pneumoniae, and Mycoplasma pneumoniae was performed on a nasopharyngeal (NP) sample and was also negative. Empiric therapy with parenteral ampicillin and cefepime was started on admission and continued until the blood, urine, and CSF cultures were negative for >48 hours.

Case 2: Blood and urine cultures were done, both were negative. A BioFire respiratory PCR panel was performed on an nasopharyngeal sample and was negative. The child was treated empirically with parenteral ceftriaxone until the results of blood and urine cultures were negative for >36 hours.

Clinical Characteristics of Covid-19 in New York City.

Goyal et al., The New England Journal of Medicine

Published: April 17th 2020

DOI: 10.1056/NEJMc2010419

Notes

This retrospective case series characterised the first 393 patients consecutively admitted to two hospitals in New York City. In total, 40 (10.2%) patients have died and 260 (66.2%) patients have been discharged; the data for the remaining 93 (23.7%) patients is incomplete. 19 (5.6%) of 338 patients had bacteraemia; 15 (11.9%) of the 126 who were mechanically ventilated and 4 (1.8%) of the 222 who were not mechanically ventilated.

Case Report: The Importance of Novel Coronavirus Disease (COVID-19) and Coinfection with Other Respiratory Pathogens in the Current Pandemic

Khaddour et al., The American Journal of Tropical Medicine and Hygiene.

Published: April 17th 2020

DOI: https://doi.org/10.4269/ajtmh.20-0266

Abstract

The early shortage of novel coronavirus disease (COVID-19) tests in the United States led many hospitals to first screen for common respiratory pathogens, and only if this screen was negative to proceed with COVID-19 testing. We report a case of a 56-year-old woman with severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) coinfection with group A Streptococcus. The initial testing strategy resulted in delays in both diagnosis and implementation of appropriate precautions. Underlined is the importance of testing for both SARS-CoV-2 and other common respiratory pathogens during the current pandemic.

Panton-Valentine Leukocidin-Secreting Staphylococcus aureus Pneumonia Complicating COVID-19

Duployez et al., Emerging Infectious Disease.

Published: April 16th 2020

DOI: https://doi.org/10.3201/eid2608.201413

Abstract

Necrotizing pneumonia induced by Panton-Valentine leukocidin-secreting Staphylococcus aureus is a rare but life-threatening infection that has been described in patients after they had influenza. We report a fatal case of this superinfection in a young adult who had coronavirus disease.

Rates of Co-infection Between SARS-CoV-2 and Other Respiratory Pathogens.

Kim et al., 2020, The Journal of the American Medical Association.

Published: April 15th 2020

DOI: 10.1001/jama.2020.6266

Summary

As of April 3, 2020, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had caused 972 303 cases of coronavirus disease 2019 (COVID-19) and 50 322 deaths worldwide. Early reports from China suggested that co-infection with other respiratory pathogens was rare. If this were the case, patients positive for other pathogens might be assumed unlikely to have SARS-CoV-2. The Centers for Disease Control and Prevention endorsed testing for other respiratory pathogens, suggesting that evidence of another infection could aid the evaluation of patients with potential COVID-19 in the absence of widely available rapid testing for SARS-CoV-2. Here we report on co-infection rates between SARS-CoV-2 and other respiratory pathogens in Northern California.

Notes

This study reports on the co-infection rates between SARS-CoV-2 and other respiratory pathogens in Northern California. The lab tested specimens for SARS-CoV-2 and influenza A/B, respiratory syncytial virus, non-SARS-CoV-2 Coronaviridae, adenovirus, parainfluenza 1-4, human metapneumovirus, rhinovirus/enterovirus, Chlamydia pneumoniae, Mycoplasma pneumoniae. 1217 specimens were tested, 116 (9.5%) of them were positive for SARS-CoV-2. Of these 116 positive specimens, 24 (20.7%) were positive for 1 or more additional pathogens, compared with 294 (26.7%) of the 1101 specimens negative for SARS-CoV-2. The most common co-infections in those positive for were rhinovirus/enterovirus (6.9%), respiratory syncytial virus (5.2%), and non-SARS-CoV-2 Coronaviridae (4.3%). None of the 116 tested positive for havingChlamydia pneumoniae or Mycoplasma pneumoniae co-infections.

High prevalence of putative invasive pulmonary aspergillosis in critically ill COVID-19 patients.

Alanio et al. 2020, Social Science Research Network.

Published: April 15th 2020

DOI: https://dx.doi.org/10.2139/ssrn.3575581

Abstract

We are currently facing a frightening increase in COVID-19 patients admitted to the ICU.
Aiming at screening for fungal secondary pneumonia, we collected the data of our first 27 ICU patients, who underwent bronchoalveolar lavage or bronchial aspirates. We classified the patients based on the recently published study on invasive aspergillosis in influenza patients in your journal (Schauwvlinghe et al., 2018.) and found 33% of our COVID-19 patients with putative invasive pulmonary aspergillosis.
Observing such a high prevalence in COVID-infected patients was somehow unexpected since the 30% prevalence of invasive aspergillosis in influenza patients has been attributed to the action of oseltamivir on anti-Aspergillus immunity.
Almost all critically ill COVID-19 patients develop ARDS and are likely to receive high-dose steroids or immunomodulatory therapies to prevent worsening as suggested by reports from China. In the COVID-19 patients with putative invasive aspergillosis, antifungal prophylactic therapy may be questioned to avoid increased lung inflammation that may compromise the outcome. This issue remains to be addressed in future clinical trials.
We are strongly convinced that testing deep lung specimens for Aspergillus in severe COVID-19 patients should be recommended. This message is major, given the high mortality rate of COVID-19 patients in the ICU and should be rapidly released.

Notes

Data was collected on 27 COVID-19 ICU patients admitted with pneumonia who underwent bronchoalveolar lavage or bronchial aspirates. Putative invasive pulmonary aspergillosis (IPA) was diagnosed in 9 (33%) patients, including 6 patients validating ≥2 mycological criteria and 3 patients with only Aspergillus fumigatus identification in the respiratory specimen culture. All 9 patients with putative IPA were given specific anti-Aspergillus therapy. There was no significant increase in fatality rate observed in these patients.

First COVID-19 infections in the Philippines: a case report

Edrada et al., Tropical Medicine and Health.

Published: April 14th 2020

DOI: https://doi.org/10.1186/s41182-020-00203-0

Abstract

Background: The novel coronavirus (COVID-19) is responsible for more fatalities than the SARS coronavirus, despite being in the initial stage of a global pandemic. The first suspected case in the Philippines was investigated on January 22, 2020, and 633 suspected cases were reported as of March 1. We describe the clinical and epidemiological aspects of the first two confirmed COVID-19 cases in the Philippines, both admitted to the national infectious disease referral hospital in Manila.

Case presentation: Both patients were previously healthy Chinese nationals on vacation in the Philippines travelling as a couple during January 2020. Patient 1, a 39-year-old female, had symptoms of cough and sore throat and was admitted to San Lazaro Hospital in Manila on January 25. Physical examination was unremarkable. Influenza B, human coronavirus 229E, Staphylococcus aureus and Klebsiella pneumoniae were detected by PCR on initial nasopharyngeal/oropharyngeal (NPS/OPS) swabs. On January 30, SARS-CoV-2 viral RNA was reported to be detected by PCR on the initial swabs and she was identified as the first confirmed COVID-19 case in the Philippines. Her symptoms resolved, and she was discharged. Patient 2, a 44-year-old male, had symptoms of fever, cough, and chills. Influenza B and Streptococcus pneumoniae were detected by PCR on initial NPS/OPS swabs. He was treated for community-acquired pneumonia with intravenous antibiotics, but his condition deteriorated and he required intubation. On January 31, SARS-CoV-2 viral RNA was reported to be detected by PCR on the initial swabs, and he was identified as the 2nd confirmed COVID-19 infection in the Philippines. On February 1, the patient's condition deteriorated, and following a cardiac arrest, it was not possible to revive him. He was thus confirmed as the first COVID-19 death outside of China.

Conclusions: This case report highlights several important clinical and public health issues. Despite both patients being young adults with no significant past medical history, they had very different clinical courses, illustrating how COVID-19 can present with a wide spectrum of disease. As of March 1, there have been three confirmed COVID-19 cases in the Philippines. Continued vigilance is required to identify new cases

Nosocomial infection among patients with COVID-19: A retrospective data analysis of 918 cases from a single center in Wuhan, China

He et al., 2020. Infection Control & Hospital Epidemiology

Published: April 13th 2020

DOI: https://doi.org/10.1017/ice.2020.126

To the Editor- The emergence of coronavirus disease-2019 (COVID-19) in China at the end of 2019 has caused a global pandemic and is a major public health issue.1 The percentage of nosocomial infection among COVID-19 patients who have died was significantly higher than that of patients who were cured and discharged (P = .002).2 We investigated nosocomial infection among COVID-19 patients, and we analyzed risk factors to provide basic data for nosocomial infection prevention and control.

COVID-19 with Different Severities: A Multicenter Study of Clinical Features

Feng et al., American Journal of Respiratory and Critical Care Medicine.

Published: April 10th 2020.

DOI: https://doi.org/10.1164/rccm.202002-0445OC

Abstract

Rationale: The coronavirus disease (COVID-19) pandemic is now a global health concern.

Objectives: We compared the clinical characteristics, laboratory examinations, computed tomography images, and treatments of patients with COVID-19 from three different cities in China.

Methods: A total of 476 patients were recruited from January 1, 2020, to February 15, 2020, at three hospitals in Wuhan, Shanghai, and Anhui. The patients were divided into four groups according to age and into three groups (moderate, severe, and critical) according to the fifth edition of the Guidelines on the Diagnosis and Treatment of COVID-19 issued by the National Health Commission of China.

Measurements and Main Results: The incidence of comorbidities was higher in the severe (46.3%) and critical (67.1%) groups than in the moderate group (37.8%). More patients were taking angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers in the moderate group than in the severe and critical groups. More patients had multiple lung lobe involvement and pleural effusion in the critical group than in the moderate group. More patients received antiviral agents within the first 4 days in the moderate group than in the severe group, and more patients received antibiotics and corticosteroids in the critical and severe groups. Patients >75 years old had a significantly lower survival rate than younger patients.

Conclusions: Multiple organ dysfunction and impaired immune function were the typical characteristics of patients with severe or critical illness. There was a significant difference in the use of angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers among patients with different severities of disease. Involvement of multiple lung lobes and pleural effusion were associated with the severity of COVID-19. Advanced age (≥75 yr) was a risk factor for mortality.

Notes

Of the 476 patients included in the study, 319 (67%) were given antibacterial therapy which included moxifloxacin, ceftriaxone and azithromycin. 8 (1.7%) patients received antifungal therapy. The study found that severe and critical patients who received antibiotics (or corticosteroids) had longer hospital stays than those who didn't. Critical patients also had a higher percentage of secondary bacterial infections, of 410 patients 35(8.5%) had a bacterial confections; 19(34.5%) of 55 patients in the critical group compared to 4 (8.3%) from 48 in the severe group and 12 (3.9%)/307 patients in the moderate group.

SARS-CoV-2 in Spanish Intensive Care Units: Early experience with 15-day survival in Vitoria.

Barrasa et al., Anaesthesia, Critical Care & Pain Medicine.

Published: April 9th 2020.

DOI: 10.1016/j.accpm.2020.04.001

Abstract

PURPOSE:Community transmission of SARS-CoV-2 was detected in Spain in February 2020, with 216% intensive care unit (ICU) capacity expanded in Vitoria by March 18th, 2020.

METHODS:We identified patients from the two public hospitals in Vitoria who were admitted to ICU with confirmed infection by SARS-CoV-2. Data reported here were available in April 6th, 2020. Mortality was assessed in those who completed 15-days of ICU stay.

RESULTS:We identified 48 patients (27 males) with confirmed SARS-CoV-2. Median [interquartile range (IQR)] age of patients was 63 [51-75] years. Symptoms began a median of 7 [5-12] days before ICU admission. The most common comorbidities identified were obesity (48%), arterial hypertension (44%) and chronic lung disease (37%). All patients were admitted by hypoxemic respiratory failure and none received non-invasive mechanical ventilation. Forty-five (94%) underwent intubation, 3 (6%) high flow nasal therapy (HFNT), 1 (2%) extracorporeal membrane oxygenation (ECMO) and 22 (46%) required prone position. After 15 days, 14/45 (31%) intubated patients died (13% within one week), 10/45 (22%) were extubated, and 21/45 (47%) underwent mechanical ventilation. Six patients had documented super-infection. Procalcitonin plasma above 0.5μg/L was associated with 16% vs. 19% (p=0.78) risk of death after 7 days.

CONCLUSION:This early experience with SARS-CoV-2 in Spain suggests that a strategy of right oxygenation avoiding non-invasive mechanical ventilation was life-saving. Seven-day mortality in SARS-CoV-2 requiring intubation was lower than 15%, with 80% of patients still requiring mechanical ventilation. After 15 days of ICU admission, half of patients remained intubated, whereas one third died.

Notes

Empirical antibiotic treatment treatment was given to 42 (87%) patients, these antibiotics include levofloxacin, ceftriaxone, azithromycin, linezolid and other beta-lactams. The pathogens identified in the 6 patients with super-infections were; Pseudomonas aeruginosa in 3 patients, Enterococcus faecium, Haemophilus influenza and MRSA were identified in 1 patient each.

Therapeutic Potential for Tetracyclines in the Treatment of COVID-19

Sodhi and Etminan, 2020. American College of Clinical Pharmacy.

Published: April 8th 2020.

DOI: https://doi.org/10.1002/phar.2395

Abstract

Currently there is a race against time to identify prophylactic and therapeutic treatments against COVID‐19. Until these treatments are developed, tested and mass produced, it might be prudent to look into existing therapies that could be effective against this virus. Based on the available evidence we believe that tetracyclines may be effective agents in the treatment of COVID‐19. Tetracyclines (e.g. tetracycline, doxycycline, and minocycline) are highly lipophilic antibiotics that are known to chelate zinc compounds on matrix metalloproteinases (MMPs)1. Coronaviruses are also known to heavily rely on host MMPs for survival, cell infiltration, cell to cell adhesion, and replication, many of which have zinc as part of their MMP complex2,3. It is possible that the zinc chelating properties of tetracyclines may also aid in inhibiting COVID‐19 infection in humans limiting their ability to replicate within the host.

Hospitalization and Critical Care of 109 Decedents With COVID-19 Pneumonia in Wuhan, China

Du et al., Annals of the American Thoracic Society.

Published: April 7th 2020.

DOI: https://doi.org/10.1513/AnnalsATS.202003-225OC

Abstract

RATIONALE: The current outbreak of COVID-19 pneumonia caused by SARS-CoV-2 in Wuhan, China, spreads across national and international borders. The overall death rate of COVID-19 pneumonia in Chinese population was 4%.

OBJECTIVES: To describe process of hospitalization and critical care of decedents with COVID-19 pneumonia.
METHODS: This was a multi-center observational study of 109 decedents with COVID-19 pneumonia from three hospitals in Wuhan. Demographic, clinical, laboratory, and treatment data were collected and analyzed, and final date of follow-up was February 24, 2020.
RESULTS: The mean age of 109 decedents with COVID-19 pneumonia was 70.7 years, and 35 (32.1%) patients were female. 85 (78.0%) patients suffered from one or more underlying comorbidities. Multiple organ failure, especially respiratory failure and heart failure, appeared in all patients even at early stage of disease. Overall, from onset of symptom to death, the mean time was 22.3 days. All 109 hospitalized patients needed ICU admission, however, only 51 (46.8%) had such a chance because of limited availability. The period of hospitalization to death in ICU group and non-ICU group was 15.9 days (SD, 8.8 days) and 12.5 days (8.6 days, P = 0.044), respectively.
CONCLUSIONS: Mortality due to COVID-19 pneumonia was concentrated in old people whose age was always above 65 years, especially those with major comorbidities. Patients admitted to ICU lived longer than those who did not gain admission to ICU. Our findings should aid in the recognition and clinical management of such infections, especially ICU resource allocation.

Notes

All 109 patients were given antibiotics to either treat or prevent secondary bacterial infections, 20 (39.2%) of patients in the ICU group were given antifungal drugs, however 0 patients in the non- ICU group were. However, only 42 (38.5%) of patients were actually documented to have lung bacterial or fungal infections.

Coronavirus disease 2019 in elderly patients: Characteristics and prognostic factors based on 4-week follow-up

Wang et al., 2020, Journal of Infection.

Published: March 30th 2020.

DOI: 10.1016/j.jinf.2020.03.019

Summary

Objective: To investigate the characteristics and prognostic factors in the elderly patients with COVID-19.
Methods: Consecutive cases over 60 years old with COVID-19 in Renmin Hospital of Wuhan University from Jan 1 to Feb 6, 2020 were included. The primary outcomes were death and survival till March 5. Data of demographics, clinical features, comorbidities, laboratory tests and complications were collected and compared for different outcomes. Cox regression was performed for prognostic factors.

Results: 339 patients with COVID-19 (aged 71±8 years,173 females (51%)) were enrolled, including 80 (23.6%) critical, 159 severe (46.9%) and 100 moderate (29.5%) cases. Common comorbidities were hypertension (40.8%), diabetes (16.0%) and cardiovascular disease (15.7%). Common symptoms included fever (92.0%), cough (53.0%), dyspnea (40.8%) and fatigue (39.9%). Lymphocytopenia was a common laboratory finding (63.2%). Common complications included bacterial infection (42.8%), liver enzyme abnormalities (28.7%) and acute respiratory distress syndrome (21.0%). Till Mar 5, 2020, 91 cases were discharged (26.8%), 183 cases stayed in hospital (54.0%) and 65 cases (19.2%) were dead. Shorter length of stay was found for the dead compared with the survivors (5 (3-8) vs. 28 (26-29), P < 0.001). Symptoms of dyspnea (HR 2.35, P = 0.001), comorbidities including cardiovascular disease (HR 1.86, P = 0.031) and chronic obstructive pulmonary disease (HR 2.24, P = 0.023), and acute respiratory distress syndrome (HR 29.33, P < 0.001) were strong predictors of death. And a high level of lymphocytes was predictive of better outcome (HR 0.10, P < 0.001).

Conclusions: High proportion of severe to critical cases and high fatality rate were observed in the elderly COVID-19 patients. Rapid disease progress was noted in the dead with a median survival time of 5 days after admission. Dyspnea, lymphocytopenia, comorbidities including cardiovascular disease and chronic obstructive pulmonary disease, and acute respiratory distress syndrome were predictive of poor outcome. Close monitoring and timely treatment should be performed for the elderly patients at high risk.

Covid-19 in Critically Ill Patients in the Seattle Region- Case Series

Bhatraju et al., 2020, The New England Journal of Medicine.

Published: March 30th 2020

DOI: 10.1056/NEJMoa2004500

Abstract

Background: Community transmission of coronavirus 2019 (Covid-19) was detected in the state of Washington in February 2020.

Methods: We identified patients from nine Seattle-area hospitals who were admitted to the intensive care unit (ICU) with confirmed infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Clinical data were obtained through review of medical records. The data reported here are those available through March 23, 2020. Each patient had at least 14 days of follow-up.

Results: We identified 24 patients with confirmed Covid-19. The mean (±SD) age of the patients was 64±18 years, 63% were men, and symptoms began 7±4 days before admission. The most common symptoms were cough and shortness of breath; 50% of patients had fever on admission, and 58% had diabetes mellitus. All the patients were admitted for hypoxemic respiratory failure; 75% (18 patients) needed mechanical ventilation. Most of the patients (17) also had hypotension and needed vasopressors. No patient tested positive for influenza A, influenza B, or other respiratory viruses. Half the patients (12) died between ICU day 1 and day 18, including 4 patients who had a do-not-resuscitate order on admission. Of the 12 surviving patients, 5 were discharged home, 4 were discharged from the ICU but remained in the hospital, and 3 continued to receive mechanical ventilation in the ICU.

Conclusions: During the first 3 weeks of the Covid-19 outbreak in the Seattle area, the most common reasons for admission to the ICU were hypoxemic respiratory failure leading to mechanical ventilation, hypotension requiring vasopressor treatment, or both. Mortality among these critically ill patients was high. (Funded by the National Institutes of Health.)

Notes

24 patients with confirmed Covid-19 admitted to ICU were identified from nine Seattle- area hospitals and were included in the study. Sputum samples from 15 patients were sent for bacterial culture, all were negative for bacterial culture; blood samples were also taken for bacterial culture from 20 patients and all remained negative. Two patients had bronchoscopy performed before the diagnosis of Covid-19; bacterial results were negative. All patients had at least 14 days of hospital follow-up, of the 24 patients, 12 (50%) died, 4 (17%) had been discharged from ICU but remained in hospital and 3 (13%) were receiving mechanical ventilation in ICU and 5 (21%) had been discharged from hospital.

Severity of coronavirus respiratory tract infections in adults admitted to acute care in Toronto, Ontario.

Kozak et al., Journal of Clinical Virology

Published: March 29th 2020

DOI: 10.1016/j.jcv.2020.104338

Abstract

Background: The World Health Organization has highlighted the need for improved surveillance and understanding of the health burden imposed by non-influenza RNA respiratory viruses. Human coronaviruses (CoVs) are a major cause of respiratory and gastrointestinal tract infections with associated morbidity and mortality.

Objectives: The objective of our study was to characterize the epidemiology of CoVs in our tertiary care centre, and identify clinical correlates of disease severity.

Study design: A cross-sectional study was performed of 226 patients admitted with confirmed CoV respiratory tract infection between 2010 and 2016. Variables consistent with a severe disease burden were evaluated including symptoms, length of stay, intensive care unit (ICU) admission and mortality.

Results: CoVs represented 11.3% of all positive respiratory virus samples and OC43 was the most commonly identified CoV. The majority of infections were community-associated while 21.6% were considered nosocomial. The average length of stay was 11.8 days with 17.3% of patients requiring ICU admission and an all-cause mortality of 7%. In a multivariate model, female gender and smoking were associated with increased likelihood of admission to ICU or death.

Conclusion: This study highlights the significant burden of CoVs and justifies the need for surveillance in the acute care setting.

Notes

Bacterial infections were noted in 16 patients (7.1%) of 226. The numbers were not sufficient enough to investigate correlations with disease severity. The bacteria identified in these patients were: Capnocytophage spp. (n = 1), Coagulase-negative Staphyloccocci (n = 4), Escherchia coli (n = 2), Haemophilus influenzae (n = 2), Moraxella spp. (n = 3), Streptococcus pneumoniae (n = 3), Klebsiella pneumoniae (n = 1), Pseudomonas aeruginosa (n = 1).

Clinical and virological data of the first cases of COVID-19 in Europe: a case series.

Lescure et al., 2020, The Lancet.

Published: March 27th 2020.

DOI: https://doi.org/10.1016/S1473-3099(20)30200-0

Abstract

Background: On Dec 31, 2019, China reported a cluster of cases of pneumonia in people at Wuhan, Hubei Province. The responsible pathogen is a novel coronavirus, named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We report the relevant features of the first cases in Europe of confirmed infection, named coronavirus disease 2019 (COVID-19), with the first patient diagnosed with the disease on Jan 24, 2020.

Methods: In this case series, we followed five patients admitted to Bichat-Claude Bernard University Hospital (Paris, France) and Pellegrin University Hospital (Bordeaux, France) and diagnosed with COVID-19 by semi-quantitative RT-PCR on nasopharyngeal swabs. We assessed patterns of clinical disease and viral load from different samples (nasopharyngeal and blood, urine, and stool samples), which were obtained once daily for 3 days from hospital admission, and once every 2 or 3 days until patient discharge. All samples were refrigerated and shipped to laboratories in the National Reference Center for Respiratory Viruses (The Institut Pasteur, Paris, and Hospices Civils de Lyon, Lyon, France), where RNA extraction, real-time RT-PCR, and virus isolation and titration procedures were done. Findings: The patients were three men (aged 31 years, 48 years, and 80 years) and two women (aged 30 years and 46 years), all of Chinese origin, who had travelled to France from China around mid-January, 2020. Three different clinical evolutions are described: (1) two paucisymptomatic women diagnosed within a day of exhibiting symptoms, with high nasopharyngeal titres of SARS-CoV-2 within the first 24 h of the illness onset (5·2 and 7·4 log10 copies per 1000 cells, respectively) and viral RNA detection in stools; (2) a two-step disease progression in two young men, with a secondary worsening around 10 days after disease onset despite a decreasing viral load in nasopharyngeal samples; and (3) an 80-year-old man with a rapid evolution towards multiple organ failure and a persistent high viral load in lower and upper respiratory tract with systemic virus dissemination and virus detection in plasma. The 80-year-old patient died on day 14 of illness (Feb 14, 2020); all other patients had recovered and been discharged by Feb 19, 2020.

Interpretation: We illustrated three different clinical and biological types of evolution in five patients infected with SARS-CoV-2 with detailed and comprehensive viral sampling strategy. We believe that these findings will contribute to a better understanding of the natural history of the disease and will contribute to advances in the implementation of more efficient infection control strategies.

Funding: REACTing (Research & Action Emerging Infectious Diseases).

Notes

5 patients admitted to Bichat-Clause Bernard University Hospital (Paris, France) and Pellegrin University Hospital (Bordeaux, France) and diagnosed with COVID-19 were included in this study. Two pathogens were identified in one of these patients, a susceptible Acinetobacter baumannii and Aspergillus flavus. A. baumanni was treated with meropenem, tigecycline and colimycin followed by meropenemand levofloxacin. A. flavus was treated with voriconazole but then switched to isavuconazole. The patient died on illness day 24.

Clinical and immunologic features in severe and moderate Coronavirus Disease 2019.

Huang et al., 2020, The Journal of Clinical Investigation.

Published: March 27th 2020

DOI: https://doi.org/10.1172/JCI137244

Abstract

Background: Since December 2019, an outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, and is now becoming a global threat. We aimed to delineate and compare the immunological features of severe and moderate COVID-19.

Methods: In this retrospective study, the clinical and immunological characteristics of 21 patients (17 male and 4 female) with COVID-19 were analyzed. These patients were classified as severe (11 cases) and moderate (10 cases) according to the guidelines released by the National Health Commission of China.

Results: The median age of severe and moderate cases was 61.0 and 52.0 years, respectively. Common clinical manifestations included fever, cough, and fatigue. Compared with moderate cases, severe cases more frequently had dyspnea, lymphopenia, and hypoalbuminemia, with higher levels of alanine aminotransferase, lactate dehydrogenase, C-reactive protein, ferritin, and D-dimer as well as markedly higher levels of IL-2R, IL-6, IL-10, and TNF-α. Absolute numbers of T lymphocytes, CD4+ T cells, and CD8+ T cells decreased in nearly all the patients, and were markedly lower in severe cases (294.0, 177.5, and 89.0 × 106/L, respectively) than moderate cases (640.5, 381.5, and 254.0 × 106/L, respectively). The expression of IFN-γ by CD4+ T cells tended to be lower in severe cases (14.1%) than in moderate cases (22.8%).

Conclusion: The SARS-CoV-2 infection may affect primarily T lymphocytes, particularly CD4+ and CD8+ T cells, resulting in a decrease in numbers as well as IFN-γ production by CD4+ T cells. These potential immunological markers may be of importance because of their correlation with disease severity in COVID-19.

Notes

In this retrospective study, the clinical and immunologic characteristics of 21 patients were analysed. All of these patients were admitted to hospital with pneumonia and were identified as laboratory-confirmed SARS-CoV-2. 11 of these patients were classified as severe and 10 were moderate. 4 of the 11 severe cases died at an average of 20 days of the onset of illness. 27.3% (3 patients) of severe cases had a secondary infection. All the severe and moderate cases (100%) were given empirical antimicrobial treatment (moxifloxacin and/or cephalosporin etc.).

Clinical features and obstetric and neonatal outcomes of pregnant patients with COVID-19 in Wuhan, China: a retrospective, single-centre, descriptive study.

Yu et al., The Lancet Infectious Diseases.

Published: March 24th 2020

DOI: https://doi.org/10.1016/S1473-3099(20)30176-6

Abstract

Background: In December, 2019, coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, China. The number of affected pregnant women is increasing, but scarce information is available about the clinical features of COVID-19 in pregnancy. This study aimed to clarify the clinical features and obstetric and neonatal outcomes of pregnant patients with COVID-19.

Methods: In this retrospective, single-centre study, we included all pregnant women with COVID-19 who were admitted to Tongji Hospital in Wuhan, China. Clinical features, treatments, and maternal and fetal outcomes were assessed.

Findings: Seven patients, admitted to Tongji Hospital from Jan 1, to Feb 8, 2020, were included in our study. The mean age of the patients was 32 years (range 29-34 years) and the mean gestational age was 39 weeks plus 1 day (range 37 weeks to 41 weeks plus 2 days). Clinical manifestations were fever (six [86%] patients), cough (one [14%] patient), shortness of breath (one [14%] patient), and diarrhoea (one [14%] patient). All the patients had caesarean section within 3 days of clinical presentation with an average gestational age of 39 weeks plus 2 days. The final date of follow-up was Feb 12, 2020. The outcomes of the pregnant women and neonates were good. Three neonates were tested for SARS-CoV-2 and one neonate was infected with SARS-CoV-2 36 h after birth.

Interpretation: The maternal, fetal, and neonatal outcomes of patients who were infected in late pregnancy appeared very good, and these outcomes were achieved with intensive, active management that might be the best practice in the absence of more robust data. The clinical characteristics of these patients with COVID-19 during pregnancy were similar to those of non-pregnant adults with COVID-19 that have been reported in the literature.

Notes

All patients were given antibiotic treatment: two (29%) patients were treated with a single antibiotic and five (71%) patients were given combination therapy. The antibiotics used were cephalosporins, quinolones and macrolides. One of the patients had a Legionella pneumophila co-infection.

Clinical Characteristics of Children with Coronavirus Disease 2019 in Hubei, China

Zheng et al., Current Medical Science.

Published: March 24th 2020.

DOI: 10.1007/s11596-020-2172-6

Summary

Since December 2019, COVID-19 has occurred unexpectedly and emerged as a health problem worldwide. Despite the rapidly increasing number of cases in subsequent weeks, the clinical characteristics of pediatric cases are rarely described. A cross-sectional multicenter study was carried out in 10 hospitals across Hubei province. A total of 25 confirmed pediatric cases of COVID-19 were collected. The demographic data, epidemiological history, underlying diseases, clinical manifestations, laboratory and radiological data, treatments, and outcomes were analyzed. Of 25 hospitalized patients with COVID-19, the boy to girl ratio was 1.27:1. The median age was 3 years. COVID-19 cases in children aged <3 years, 3.6 years, and ≥6-years patients were 10 (40%), 6 (24%), and 9 (36%), respectively. The most common symptoms at onset of illness were fever (13 [52%]), and dry cough (11 [44%]). Chest CT images showed essential normal in 8 cases (33.3%), unilateral involvement of lungs in 5 cases (20.8%), and bilateral involvement in 11 cases (45.8%). Clinical diagnoses included upper respiratory tract infection (n=8), mild pneumonia (n=15), and critical cases (n=2). Two critical cases (8%) were given invasive mechanical ventilation, corticosteroids, and immunoglobulin. The symptoms in 24 (96%) of 25 patients were alleviated and one patient had been discharged. It was concluded that children were susceptible to COVID-19 like adults, while the clinical presentations and outcomes were more favorable in children. However, children less than 3 years old accounted for majority cases and critical cases lied in this age group, which demanded extra attentions during home caring and hospitalization treatment.

Notes

Mycoplasma pneumoniae was identified in 3 (12%) of 25 patients and Enterobacter aerogenes was identified in 1 (8%) patient. Antibiotics were administered to the 2 critical cases, 1 patient was given cefoperazone/sulbactam and the other was given meropenem with linezolid.

High-Dose Intravenous Immunoglobulin as a Therapeutic Option for Deteriorating Patients With Coronavirus Disease 2019.

Cao et al., 2020, Open Forum Infectious Diseases.

Published: March 21st 2020

DOI: https://doi.org/10.1093/ofid/ofaa102

Abstract

The outbreak of coronavirus disease 2019 (COVID-19) has spread rapidly in China. Until now, no definite effective treatment has been identified. We reported on 3 patients with severe COVID-19 who received high-dose intravenous immunoglobulin (IVIg) with satisfactory recovery. Based on these observations, randomised studies of high-dose IVIg should be considered in deteriorating patients infected with COVID-19.

Notes

This paper reports on 3 patients admitted to Jin Yin-tan Hospital in Wuhan, China with severe COVID-19. Patient 1 was given azithromycin (and oseltamivir) by a local clinic (prior to being admitted to hospital) to empirically cover community-acquired respiratory pathogens, without any improvement. In hospital, moxifloxacin was given to the patient (as well as supportive care). They were discharged from hospital after 2 weeks. There is no record of patient 2 and 3 being given antibiotics.

Clinical Features and Treatment of COVID-19 Patients in Northeast Chongqing

Wan et al., Journal of Medical Virology.

Published: March 21st 2020.

DOI: https://doi.org/10.1002/jmv.25783

Abstract

The outbreak of the novel coronavirus in China (SARS‐CoV‐2) that began in December 2019 presents a significant and urgent threat to global health. This study was conducted to provide the international community with a deeper understanding of this new infectious disease. Epidemiological, clinical features, laboratory findings, radiological characteristics, treatment, and clinical outcomes of 135 patients in northeast Chongqing were collected and analyzed in this study. A total of 135 hospitalized patients with COVID‐19 were enrolled. The median age was 47 years (interquartile range, 36‐55), and there was no significant gender difference (53.3% men). The majority of patients had contact with people from the Wuhan area. Forty‐three (31.9%) patients had underlying disease, primarily hypertension (13 [9.6%]), diabetes (12 [8.9%]), cardiovascular disease (7 [5.2%]), and malignancy (4 [3.0%]). Common symptoms included fever (120 [88.9%]), cough (102 [76.5%]), and fatigue (44 [32.5%]). Chest computed tomography scans showed bilateral patchy shadows or ground glass opacity in the lungs of all the patients. All patients received antiviral therapy (135 [100%]) (Kaletra and interferon were both used), antibacterial therapy (59 [43.7%]), and corticosteroids (36 [26.7%]). In addition, many patients received traditional Chinese medicine (TCM) (124 [91.8%]). It is suggested that patients should receive Kaletra early and should be treated by a combination of Western and Chinese medicines. Compared to the mild cases, the severe ones had lower lymphocyte counts and higher plasma levels of Pt, APTT, d‐dimer, lactate dehydrogenase, PCT, ALB, C‐reactive protein, and aspartate aminotransferase. This study demonstrates the clinic features and therapies of 135 COVID‐19 patients. Kaletra and TCM played an important role in the treatment of the viral pneumonia. Further studies are required to explore the role of Kaletra and TCM in the treatment of COVID‐19.

The clinical characteristics of pneumonia patients coinfected with 2019 novel coronavirus and influenza virus in Wuhan, China

Ding et al., Journal of Medical Virology.

Published: March 20th 2020

DOI: https://doi.org/10.1002/jmv.25781

Abstract

The outbreak of 2019 novel coronavirus (COVID‐19) infection emerged in Wuhan, China, in December 2019. Since then the novel coronavirus pneumonia disease has been spreading quickly and many countries and territories have been affected, with major outbreaks in China, South Korea, Italy, and Iran. Influenza virus has been known as a common pathogen in winter and it can cause pneumonia. It was found clinically that very few patients were diagnosed with both COVID‐19 and influenza virus. A total of 5 of the 115 patients confirmed with COVID‐19 were also diagnosed with influenza virus infection, with three cases being influenza A and two cases being influenza B. In this study, we describe the clinical characteristics of those patients who got infected with COVID‐19 as well as influenza virus. Common symptoms at onset of illness included fever (five [100%] patients), cough (five [100%] patients), shortness of breath (five [100%] patients), nasal tampon (three [60%] patients), pharyngalgia (three [60%] patients), myalgia (two [40%] patients), fatigue (two [40%] patients), headache (two [40%] patients), and expectoration (two [40%] patients). The laboratory results showed that compared to the normal values, the patients' lymphocytes were reduced (four [80%] patients), and liver functions alanine aminotransferase and aspartate aminotransferase (two [40%] patients and two [40%] patients) and C‐reactive protein (four [80%] patients) were increased when admitted to hospital. They stayed in the hospital for 14, 30, 17, 12, and 19 days (28.4 ± 7.02), respectively. The main complications for the patients were acute respiratory distress syndrome (one [20%] patients), acute liver injury (three [60%] patients), and diarrhea (two [40%] patients). All patients were given antiviral therapy (including oseltamivir), oxygen inhalation, and antibiotics. Three patients were treated with glucocorticoids including two treated with oral glucocorticoids. One of the five patients had transient hemostatic medication for hemoptysis. Fortunately, all patients did not need intensive care unit and were discharged from the hospital without death. In conclusion, those patients with both COVID‐19 and influenza virus infection did not appear to show a more severe condition because based on the laboratory findings, imaging studies, and patient prognosis, they showed similar clinical characteristics as those patients with COVID‐19 infection only. However, it is worth noting that the symptoms of nasal tampon and pharyngalgia may be more prone to appear for those coinfection patients.

Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open- label non-randomised clinical trial.

Gautretet al., International Journal of Antimicrobial Agents

Published: 20th March 2020

DOI: https://doi.org/10.1016/j.ijantimicag.2020.105949

Abstract

Background: Chloroquine and hydroxychloroquine have been found to be efficient on SARS-CoV-2, and reported to be efficient in Chinese COV-19 patients. We evaluate the role of hydroxychloroquine on respiratory viral loads.

Patients and methods: French Confirmed COVID-19 patients were included in a single arm protocol from early March to March 16th, to receive 600mg of hydroxychloroquine daily and their viral load in nasopharyngeal swabs was tested daily in a hospital setting. Depending on their clinical presentation, azithromycin was added to the treatment. Untreated patients from another center and cases refusing the protocol were included as negative controls. Presence and absence of virus at Day6-post inclusion was considered the end point.

Results: Six patients were asymptomatic, 22 had upper respiratory tract infection symptoms and eight had lower respiratory tract infection symptoms. Twenty cases were treated in this study and showed a significant reduction of the viral carriage at D6-post inclusion compared to controls, and much lower average carrying duration than reported of untreated patients in the literature. Azithromycin added to hydroxychloroquine was significantly more efficient for virus elimination.

Conclusion: Despite its small sample size our survey shows that hydroxychloroquine treatment is significantly associated with viral load reduction/disappearance in COVID-19 patients and its effect is reinforced by azithromycin.

Eleven faces of coronavirus disease 2019.

Donget al., Allergy

Published: March 20th 2020

DOI: https://doi.org/10.1111/all.14289

Abstract

Background and aims: The outbreak of coronavirus disease 2019 (COVID‐19) caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection has recently spread worldwide and been declared a pandemic. We aim to describe here the various clinical presentations of this disease by examining eleven cases.

Methods: Electronic medical records of 11 patients with COVID‐19 were collected, and demographics, clinical manifestations, outcomes, key laboratory results, and radiological images are discussed.

Results: The clinical course of the eleven cases demonstrated the complexity of the COVID‐19 profile with different clinical presentations. Clinical manifestations range from asymptomatic cases to patients with mild and severe symptoms, with or without pneumonia. Laboratory detection of the viral nucleic acid can yield false‐negative results, and serological testing of virus‐specific IgG and IgM antibodies should be used as an alternative for diagnosis. Patients with common allergic diseases did not develop distinct symptoms and severe courses. Cases with a pre‐existing condition of chronic obstructive pulmonary disease or complicated with a secondary bacterial pneumonia were more severe.

Conclusion: All different clinical characteristics of COVID‐19 should be taken into consideration to identify patients that need to be in strict quarantine for the efficient containment of the pandemic.

Notes

3 of the 11 patients were given antibiotics as part of their treatment. Gram-positive cocci and gram- negative bacilli were detected in the sputum culture of one of the patients, this patient was regarded as a case suffering from a severe secondary bacterial pneumonia concomitant with COVID-19 infection. Another patient also appeared to have an underlying bacterial infection.

A Trial of Lopinavir-Ritonavir in Adults Hospitalized with Severe Covid-19.

Cao et al., 2020, The New England Journal of Medicine.

Published: March 18th 2020

DOI: 10.1056/NEJMoa2001282

Abstract

Background: No therapeutics have yet been proven effective for the treatment of severe illness caused by SARS-CoV-2.

Methods: We conducted a randomized, controlled, open-label trial involving hospitalized adult patients with confirmed SARS-CoV-2 infection, which causes the respiratory illness Covid-19, and an oxygen saturation (Sao2) of 94% or less while they were breathing ambient air or a ratio of the partial pressure of oxygen (Pao2) to the fraction of inspired oxygen (Fio2) of less than 300 mm Hg. Patients were randomly assigned in a 1:1 ratio to receive either lopinavir-ritonavir (400 mg and 100 mg, respectively) twice a day for 14 days, in addition to standard care, or standard care alone. The primary end point was the time to clinical improvement, defined as the time from randomization to either an improvement of two points on a seven-category ordinal scale or discharge from the hospital, whichever came first.

Results: A total of 199 patients with laboratory-confirmed SARS-CoV-2 infection underwent randomization; 99 were assigned to the lopinavir-ritonavir group, and 100 to the standard-care group. Treatment with lopinavir-ritonavir was not associated with a difference from standard care in the time to clinical improvement (hazard ratio for clinical improvement, 1.31; 95% confidence interval [CI], 0.95 to 1.80). Mortality at 28 days was similar in the lopinavir-ritonavir group and the standard-care group (19.2% vs. 25.0%; difference, −5.8 percentage points; 95% CI, −17.3 to 5.7). The percentages of patients with detectable viral RNA at various time points were similar. In a modified intention-to-treat analysis, lopinavir-ritonavir led to a median time to clinical improvement that was shorter by 1 day than that observed with standard care (hazard ratio, 1.39; 95% CI, 1.00 to 1.91). Gastrointestinal adverse events were more common in the lopinavir-ritonavir group, but serious adverse events were more common in the standard-care group. Lopinavir-ritonavir treatment was stopped early in 13 patients (13.8%) because of adverse events.

Conclusions: In hospitalized adult patients with severe Covid-19, no benefit was observed with lopinavir-ritonavir treatment beyond standard care. Future trials in patients with severe illness may help to confirm or exclude the possibility of a treatment benefit. (Funded by Major Projects of National Science and Technology on New Drug Creation and Development and others; Chinese Clinical Trial Register number, ChiCTR2000029308. opens in new tab.)

Notes

199 patients with confirmed SARS-CoV-2 infection underwent randomisation; 99 were treated with lopinavir-ritonavir and 100 of them were assigned to the standard care group. 189 of 199 (95%) patients were treated with an antibiotic agent.

Clinical Outcomes in 55 Patients With Severe Acute Respiratory Syndrome Coronavirus 2 Who Were Asymptomatic at Hospital Admission in Shenzhen, China

Wang et al., 2020, Journal of Infectious Diseases.

Published: March 17th 2020

DOI: https://doi.org/10.1093/infdis/jiaa119

Abstract

An epidemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has spread unexpectedly in Wuhan, Hubei Province, China, since December 2019. There are few reports about asymptomatic contacts of infected patients identified as positive for SARS-CoV-2 through screening. We studied the epidemiological and clinical outcomes in 55 asymptomatic carriers who were laboratory confirmed to be positive for SARS-CoV-2 through nucleic acid testing of pharyngeal swab samples. The asymptomatic carriers seldom occurred among young people (aged 18-29 years) who had close contact with infected family members. In the majority of patients, the outcome was mild or ordinary 2019 novel coronavirus disease during hospitalization.

Notes

All patients in this study recovered and were discharged, during their hospital stay 3 of 55 patients included in the study were diagnosed with a Mycoplasma pneumoniae confection.

Clinical characteristics of 113 deceased patients with coronavirus disease 2019: retrospective study.

Chen et al., 2020, British Medical Journal.

Published: March 17th 2020

DOI: https://dx.doi.org/10.1136/bmj.m1091

Abstract

Objective: To delineate the clinical characteristics of patients with coronavirus disease 2019 (covid-19) who died.

Design: Retrospective case series.

Setting: Tongji Hospital in Wuhan, China.

Participants: Among a cohort of 799 patients, 113 who died and 161 who recovered with a diagnosis of covid-19 were analysed. Data were collected until 28 February 2020.

Main outcome measures: Clinical characteristics and laboratory findings were obtained from electronic medical records with data collection forms.

Results: The median age of deceased patients (68 years) was significantly older than recovered patients (51 years). Male sex was more predominant in deceased patients (83; 73%) than in recovered patients (88; 55%). Chronic hypertension and other cardiovascular comorbidities were more frequent among deceased patients (54 (48%) and 16 (14%)) than recovered patients (39 (24%) and 7 (4%)). Dyspnoea, chest tightness, and disorder of consciousness were more common in deceased patients (70 (62%), 55 (49%), and 25 (22%)) than in recovered patients (50 (31%), 48 (30%), and 1 (1%)). The median time from disease onset to death in deceased patients was 16 (interquartile range 12.0-20.0) days. Leukocytosis was present in 56 (50%) patients who died and 6 (4%) who recovered, and lymphopenia was present in 103 (91%) and 76 (47%) respectively. Concentrations of alanine aminotransferase, aspartate aminotransferase, creatinine, creatine kinase, lactate dehydrogenase, cardiac troponin I, N-terminal pro-brain natriuretic peptide, and D-dimer were markedly higher in deceased patients than in recovered patients. Common complications observed more frequently in deceased patients included acute respiratory distress syndrome (113; 100%), type I respiratory failure (18/35; 51%), sepsis (113; 100%), acute cardiac injury (72/94; 77%), heart failure (41/83; 49%), alkalosis (14/35; 40%), hyperkalaemia (42; 37%), acute kidney injury (28; 25%), and hypoxic encephalopathy (23; 20%). Patients with cardiovascular comorbidity were more likely to develop cardiac complications. Regardless of history of cardiovascular disease, acute cardiac injury and heart failure were more common in deceased patients.

Conclusion: Severe acute respiratory syndrome coronavirus 2 infection can cause both pulmonary and systemic inflammation, leading to multi-organ dysfunction
in patients at high risk. Acute respiratory distress syndrome and respiratory failure, sepsis, acute cardiac injury, and heart failure were the most common critical complications during exacerbation of covid-19.

Notes

799 patients with confirmed covid-19 were admitted to Tongji Hospital, China. As of 28thof February 2020, 113 of these had died, 161 patients had recovered (had confirmed viral clearance) and been discharged. The remaining 525 patients were still in hospital and receiving medical care. 105 (93%) deceased patients and 144 (89%) recovered patients received empirical antibacterial therapy (moxifloxacin, cefoperazone or azithromycin). Sepsis was observed in 113 (100%) of deceased patients and in 66 (41%) recovered patients, unknown whether the cause is bacterial or viral. Most of the deceased patients and only a few recovered patients developed leucocytosis, and one third of deceased patients and only few who recovered had procalcitonin above 0.5 ng/mL, indicating that a large proportion of deceased patients might have had secondary bacterial infection, which could be strongly associated with death. In this study, for patients without a second bacterial infection, empirical antimicrobial treatment seemed to be ineffective.

Clinical Features of 69 Cases with Coronavirus Disease 2019 in Wuhan, China

Wang et al., 2020, Clinical Infectious Diseases.

Published: March 16th 2020

DOI: https://doi.org/10.1093/cid/ciaa272

Abstract

Background: From December 2019 to February 2020, 2019 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a serious outbreak of coronavirus disease 2019 (COVID-19) in Wuhan, China. Related clinical features are needed.

Methods: We reviewed 69 patients who were hospitalized in Union hospital in Wuhan between January 16 to January 29, 2020. All patients were confirmed to be infected with SARS-CoV-2 and the final date of follow-up was February 4, 2020.

Results: The median age of 69 enrolled patients was 42.0 years (IQR 35.0-62.0), and 32 patients (46%) were men. The most common symptoms were fever (60[87%]), cough (38[55%]), and fatigue (29[42%]). Most patients received antiviral therapy (66 [98.5%] of 67 patients) and antibiotic therapy (66 [98.5%] of 67 patients). As of February 4, 2020, 18 (26.9%) of 67 patients had been discharged, and five patients had died, with a mortality rate of 7.5%. According to the lowest SpO2 during admission, cases were divided into the SpO2≥90% group (n=55) and the SpO2<90% group (n=14). All 5 deaths occurred in the SpO2<90% group. Compared with SpO2≥90% group, patients of the SpO2<90% group were older, and showed more comorbidities and higher plasma levels of IL6, IL10, lactate dehydrogenase, and c reactive protein. Arbidol treatment showed tendency to improve the discharging rate and decrease the mortality rate.

Conclusions: COVID-19 appears to show frequent fever, dry cough, and increase of inflammatory cytokines, and induced a mortality rate of 7.5%. Older patients or those with underlying comorbidities are at higher risk of death.

Notes

69 patients hospitalised in Union Hospital in Wuhan, China between the 16th-29thof January 2020 were included in the study. 66 out of 67 (98.5%) of these patients received antibiotic therapy (most of which were empiric), 39 (58%) patients received specifically moxifloxacin treatment other antibiotics unknown. 29 (43%) patients were examined for sputum culture and 5 were positive, including 2 cases of Candida albicans, 2 cases of Enterobacter cloacae and 1 case of Acinetobacter baumannii.

Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China.

Wu et al., JAMA Internal Medicine.

Published: March 13th 2020.

DOI: 10.1001/jamainternmed.2020.0994

Abstract

Importance: Coronavirus disease 2019 (COVID-19) is an emerging infectious disease that was first reported in Wuhan, China, and has subsequently spread worldwide. Risk factors for the clinical outcomes of COVID-19 pneumonia have not yet been well delineated.

Objective: To describe the clinical characteristics and outcomes in patients with COVID-19 pneumonia who developed acute respiratory distress syndrome (ARDS) or died.

Design, Setting, and Participants: Retrospective cohort study of 201 patients with confirmed COVID-19 pneumonia admitted to Wuhan Jinyintan Hospital in China between December 25, 2019, and January 26, 2020. The final date of follow-up was February 13, 2020.

Exposures: Confirmed COVID-19 pneumonia.

Main Outcomes and Measures: The development of ARDS and death. Epidemiological, demographic, clinical, laboratory, management, treatment, and outcome data were also collected and analyzed.

Results: Of 201 patients, the median age was 51 years (interquartile range, 43-60 years), and 128 (63.7%) patients were men. Eighty-four patients (41.8%) developed ARDS, and of those 84 patients, 44 (52.4%) died. In those who developed ARDS, compared with those who did not, more patients presented with dyspnea (50 of 84 [59.5%] patients and 30 of 117 [25.6%] patients, respectively [difference, 33.9%; 95% CI, 19.7%-48.1%]) and had comorbidities such as hypertension (23 of 84 [27.4%] patients and 16 of 117 [13.7%] patients, respectively [difference, 13.7%; 95% CI, 1.3%-26.1%]) and diabetes (16 of 84 [19.0%] patients and 6 of 117 [5.1%] patients, respectively [difference, 13.9%; 95% CI, 3.6%-24.2%]). In bivariate Cox regression analysis, risk factors associated with the development of ARDS and progression from ARDS to death included older age (hazard ratio [HR], 3.26; 95% CI 2.08-5.11; and HR, 6.17; 95% CI, 3.26-11.67, respectively), neutrophilia (HR, 1.14; 95% CI, 1.09-1.19; and HR, 1.08; 95% CI, 1.01-1.17, respectively), and organ and coagulation dysfunction (eg, higher lactate dehydrogenase [HR, 1.61; 95% CI, 1.44-1.79; and HR, 1.30; 95% CI, 1.11-1.52, respectively] and D-dimer [HR, 1.03; 95% CI, 1.01-1.04; and HR, 1.02; 95% CI, 1.01-1.04, respectively]). High fever (≥39 °C) was associated with higher likelihood of ARDS development (HR, 1.77; 95% CI, 1.11-2.84) and lower likelihood of death (HR, 0.41; 95% CI, 0.21-0.82). Among patients with ARDS, treatment with methylprednisolone decreased the risk of death (HR, 0.38; 95% CI, 0.20-0.72).

Conclusions and Relevance: Older age was associated with greater risk of development of ARDS and death likely owing to less rigorous immune response. Although high fever was associated with the development of ARDS, it was also associated with better outcomes among patients with ARDS. Moreover, treatment with methylprednisolone may be beneficial for patients who develop ARDS.

Notes

Of the 201 patients, 196 (97.5%) patients received empirical antibiotic treatment. Bacteria and fungi cultures were collected from 148 (73.6%) patients.

Clinical Features and Short-term Outcomes of 102 Patients with Corona Virus Disease 2019 in Wuhan, China.

Cao et al., Clinical Infectious Diseases.

Published: March 13th 2020

DOI: https://doi.org/10.1093/cid/ciaa243

Abstract

Objective: In December, 2019, a series of pneumonia cases of unknown cause emerged in Wuhan, Hubei, China. In this study, we investigate clinical and laboratory features and short-term outcomes of patients with Corona Virus Disease 2019(COVID-19).

Methods: All patients with COVID-19 admitted to Wuhan University Zhongnan Hospital in Wuhan, China, between January 3 and February 1, 2020 were included. All those patients were with laboratory-confirmed infection. Epidemiological, clinical, radiological characteristics, underlying diseases, laboratory tests treatment, complications and outcomes data were collected. Outcomes were followed up at discharge until Feb 15, 2020.

Results: The study cohort included 102 adult patients. The median (IQR) age was 54 years (37-67years) and 48.0% were female. A total of 34 patients (33.3%) were exposed to source of transmission in the hospital setting (as health care workers, patients, or visitors) and 10 patients (9.8%) had a familial cluster. Eighteen patients (17.6%) were admitted to the ICU, and 17 patients died (mortality, 16.7%; 95% confidence interval [CI], 9.4%-23.9%). Among patients who survived, they were younger, more likely were health care workers and less likely suffered from comorbidities. They were also less likely suffered from complications. There was no difference in drug treatment rates between the survival and non-survival groups. Patients who survived less likely required admission to the intensive care unit (14.1% vs. 35.3%). Chest imaging examination showed that death patients more likely had ground-glass opacity (41.2% vs. 12.9%).

Conclusions: The mortality rate was high among the COVID-19 patients described in our cohort who met our criteria for inclusion in this analysis. Patient characteristics seen more frequently in those who died were development of systemic complications following onset of the illness and the severity of disease requiring admission to the ICU. Our data support those described by others that COVID-19 infection results from human-to-human transmission, including familial clustering of cases, and nosocomial transmission. There were no differences in mortality among those who did or did not receive antimicrobial or glucocorticoid drug treatment.

Notes

Complications of patients included shock and acute infection. 10 (9.8%) of all 102 patients suffered from shock, 7 (41.1%) of 17 non-survivors and 3 (3.5%) of 85 survivors. 17 (16.7%) of all 102 patients were found to have an acute infection, 14 (82.4%) of 17 non-survivors and 3 (3.5%) of 85 survivors. Antibiotic treatment was given to 101 (99%) of patients, all 17 (100%) non-survivors and 84 (98.8%) survivors. Antibiotics included Cephalosporins (33.3%), Quinolones (85.3%), Carbapenems (24.5%) and Linezolid (4.9%).

Teicoplanin: an alternative drug for the treatment of coronavirus COVID-19?

Baron et al., 2020, International Journal of Antimicrobial Agents.

Published: March 13th 2020

DOI: https://doi.org/10.1016/j.ijantimicag.2020.105944

Abstract

In December 2019, a novel coronavirus, named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged from China causing pneumonia outbreaks, first in the Wuhan region of China and then spread worldwide because of its probable high transmission efficiency. Owing to the lack of efficient and specific treatments and the need to contain the epidemic, drug repurposing appears to be the best tool to find a therapeutic solution. Chloroquine, remdesivir, lopinavir, ribavirin and ritonavir have shown efficacy to inhibit coronavirus in vitro. Teicoplanin, an antibiotic used to treat staphylococcal infections, previously showed efficacy to inhibit the first stage of the Middle East respiratory syndrome coronavirus (MERS-CoV) viral life cycle in human cells. This activity is conserved against SARS-Cov-2, thus placing teicoplanin as a potential treatment for patients with this virus.

Notes

Teicoplanin has been found to be active in vitroagainst SARS-CoV. It has also shown efficacy against various viruses- Ebola, influenza virus, flavivirus, hepatitis C virus, HIV virus and on MERS-CoV. According to Zhang et al teicoplanin acts on the early stages of the viral life cycle by inhibiting the low pH cleavage of the viral spike protein cathepsin L in the late endosomes thereby preventing the release of genomic viral RNA and the continuation of the virus replication cycle. A more recent study by the same authors showed that this activity was conserved on COVID-19. Their study showed that the concentration required to inhibit 50% of viruses in vitro was 1.66 µM.

A Comparative Study on the Clinical Features of Coronavirus 2019 (COVID-19) Pneumonia With Other Pneumonias

Zhao et al., 2020, Clinical Infectious Diseases.

Published: March 12th 2020

DOI: https://doi.org/10.1093/cid/ciaa247

Abstract

Background

A novel coronavirus (COVID-19) has raised world concern since it emerged in Wuhan, China in December 2019. The infection may result in severe pneumonia with clusters of illness onsets. Its impacts on public health make it paramount to clarify the clinical features with other pneumonias.

Methods

Nineteen COVID-19 and 15 other patients with pneumonia (non-COVID-19) in areas outside of Hubei were involved in this study. Both COVID-19 and non-COVID-19 patients were confirmed to be infected using throat swabs and/or sputa with/without COVID-2019 by real-time RT-PCR. We analyzed the demographic, epidemiological, clinical, and radiological features from those patients, and compared the differences between COVID-19 and non-COVID-19.

Results

All patients had a history of exposure to confirmed cases of COVID-19 or travel to Hubei before illness. The median (IQR) duration was 8 (6-11) and 5 (4-11) days from exposure to onset in COVID-19 and non-COVID-19 cases, respectively. The clinical symptoms were similar between COVID-19 and non-COVID-19. The most common symptoms were fever and cough. Fifteen (78.95%) COVID-19 but 4 (26.67%) non-COVID-19 patients had bilateral involvement while 17 COVID-19 patients (89.47%) but 1 non-COVID-19 patient (6.67%) had multiple mottling and ground-glass opacity on chest CT images. Compared with non-COVID-19, COVID-19 presents remarkably more abnormal laboratory tests, including AST, ALT, γ-GT, LDH, and α-HBDH.

Conclusions

The COVID-19 infection has onsets similar to other pneumonias. CT scan may be a reliable test for screening COVID-19 cases. Liver function damage is more frequent in COVID-19 than non-COVID-19 patients. LDH and α-HBDH may be considerable markers for evaluation of COVID-19.

Notes

Between the 23rd January and 5th February 2020, 19 COVID-19 patients and 15 non-COVID patients were recruited for this study at the Second Affiliated Hospital of Anhui Medical University and Suzhou Municipal Hospital in Anhui Province, China. Bacterial/viral coinfections were reported in 2 (10.53%) COVID-19 patients and 2 (13.33%) non-COVID-19 patients.

A Locally Transmitted Case of SARS-CoV-2 Infection in Taiwan.

Liu et al., The New England Journal of Medicine.

Published: March 12th 2020.

DOI: 10.1056/NEJMc2001573

Notes

A Covid-19 case of a 52-year old woman with a history of type 2 diabetes was identified in Taiwan. Assays to detect Bordetella pertussis, Chlamydia pneumoniae, and Mycoplasma pneumoniae were all negative. Upon hospitalisation the patient was given levofloxacin as an empirical therapy. The husband was hospitalised with Covid-19 shortly after but was not given any antibiotics.

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study.

Zhou et al., 2020, The Lancet.

Published: March 11th 2020

DOI: https://doi.org/10.1016/S0140-6736(20)30566-3

Abstract

Background:Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described.

Methods:In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death.

Findings:191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03-1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61-12·23; p<0·0001), and d-dimer greater than 1 μg/mL (18·42, 2·64-128·55; p=0·0033) on admission. Median duration of viral shedding was 20·0 days (IQR 17·0-24·0) in survivors, but SARS-CoV-2 was detectable until death in non-survivors. The longest observed duration of viral shedding in survivors was 37 days.

Interpretation:The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future.

Funding:Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.

Notes

191 patients (135 form Jinyintan Hospital and 56 from Wuhan Pulmonary hospital) were included in this study, 54 died in hospital and 137 were discharged. 181 (95%) of these patients were given antibiotics, more specifically 53 of the 54 (98%) who didn't survive and 128 (93%) of those who were discharged. Sepsis was the most observed complication in these patients, all 54 (100%) non-survivors were diagnosed with sepsis and 58 (42%) of patients who were discharged also were. However, it is not clear whether the cause of sepsis in these patients was viral or bacterial. 28 (15%) patients of 191 experienced a secondary infection, 27 (50%) of them non- survivors whilst only 1 survivor (1%) did.

Genomic diversity of SARS-CoV-2 in Coronavirus Disease 2019 patients.

Shen et al., 2020, Clinical Infectious Diseases.

Published: March 9th 2020

DOI: https://doi.org/10.1093/cid/ciaa203

Abstract

Background: A novel coronavirus (SARS-CoV-2) has infected more than 75,000 individuals and spread to over 20 countries. It is still unclear how fast the virus evolved and how the virus interacts with other microorganisms in the lung.
Methods: We have conducted metatranscriptome sequencing for the bronchoalveolar lavage fluid of eight SARS-CoV-2 patients, 25 community-acquired pneumonia (CAP) patients, and 20 healthy controls.
Results: The median number of intra-host variants was 1-4 in SARS-CoV-2 infected patients, which ranged between 0 and 51 in different samples. The distribution of variants on genes was similar to those observed in the population data (110 sequences). However, very few intra-host variants were observed in the population as polymorphism, implying either a bottleneck or purifying selection involved in the transmission of the virus, or a consequence of the limited diversity represented in the current polymorphism data. Although current evidence did not support the transmission of intra-host variants in a person-to-person spread, the risk should not be overlooked. The microbiota in SARS-CoV-2 infected patients was similar to those in CAP, either dominated by the pathogens or with elevated levels of oral and upper respiratory commensal bacteria.
Conclusion: SARS-CoV-2 evolves in vivo after infection, which may affect its virulence, infectivity, and transmissibility. Although how the intra-host variant spreads in the population is still elusive, it is necessary to strengthen the surveillance of the viral evolution in the population and associated clinical changes.

Notes

In this study, metatranscriptome sequencing was conducted for the bronchoalveolar lavage fluid (BALF) of 8 SARS-CoV-2 patients, 25 community-acquired pneumonia (CAP) and 20 healthy controls. COVID-19 patients had the highest proportion of microbial reads compared to CAP and Healthy, 49% of which could be mapped to SARA-CoV-2. A substantial proportion of bacteria as observed in 2 COVID-19 patients, the presence of this bacteria may increase the risk of secondary infection to the patients.

2019 novel coronavirus (2019-nCoV) outbreak: A new challenge

Lupia et al., Journal of Global Antimicrobial Resistance

Published: March 7th 2020

DOI: https://doi.org/10.1016/j.jgar.2020.02.021

Abstract

Objectives: Following the public-health emergency of international concern (PHEIC) declared by the World Health Organization (WHO) on 30 January 2020 and the recent outbreak caused by 2019 novel coronavirus (2019-nCoV) [officially renamed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)] in China and 29 other countries, we aimed to summarise the clinical aspects of the novel Betacoronavirusdisease (COVID-19) and its possible clinical presentations together with suggested therapeutic algorithms for patients who may require antimicrobial treatment.

Methods: The currently available literature was reviewed for microbiologically confirmed infections by 2019-nCoV or COVID-19 at the time of writing (13 February 2020). A literature search was performed using the PubMed database and Cochrane Library. Search terms included 'novel coronavirus' or '2019-nCoV' or 'COVID-19'.

Results: Published cases occurred mostly in males (age range, 8-92 years). Cardiovascular, digestive and endocrine system diseases were commonly reported, except previous chronic pulmonary diseases [e.g. chronic obstructive pulmonary disease (COPD), asthma, bronchiectasis] that were surprisingly underreported. Fever was present in all of the case series available, flanked by cough, dyspnoea, myalgia and fatigue. Multiple bilateral lobular and subsegmental areas of consolidation or bilateral ground-glass opacities were the main reported radiological features of 2019-nCoV infection, at least in the early phases of the disease.

Conclusions: The new 2019-nCoV epidemic is mainly associated with respiratory disease and few extrapulmonary signs. However, there is a low rate of associated pre-existing respiratory co-morbidities.

Clinical characteristics and intrauterine vertical transmission potential of COVID-19 infection in nine pregnant women: a retrospective review of medical records

Chen et al., 2020, The Lancet.

Published: March 7th 2020

DOI: https://doi.org/10.1016/S0140-6736(20)30360-3

Summary

Background: Previous studies on the pneumonia outbreak caused by the 2019 novel coronavirus disease (COVID-19) were based on information from the general population. Limited data are available for pregnant women with COVID-19 pneumonia. This study aimed to evaluate the clinical characteristics of COVID-19 in pregnancy and the intrauterine vertical transmission potential of COVID-19 infection.

Methods: Clinical records, laboratory results, and chest CT scans were retrospectively reviewed for nine pregnant women with laboratory-confirmed COVID-19 pneumonia (ie, with maternal throat swab samples that were positive for severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) who were admitted to Zhongnan Hospital of Wuhan University, Wuhan, China, from Jan 20 to Jan 31, 2020. Evidence of intrauterine vertical transmission was assessed by testing for the presence of SARS-CoV-2 in amniotic fluid, cord blood, and neonatal throat swab samples. Breastmilk samples were also collected and tested from patients after the first lactation.
Findings: All nine patients had a caesarean section in their third trimester. Seven patients presented with a fever. Other symptoms, including cough (in four of nine patients), myalgia (in three), sore throat (in two), and malaise (in two), were also observed. Fetal distress was monitored in two cases. Five of nine patients had lymphopenia (<1·0 × 10⁹ cells per L). Three patients had increased aminotransferase concentrations. None of the patients developed severe COVID-19 pneumonia or died, as of Feb 4, 2020. Nine livebirths were recorded. No neonatal asphyxia was observed in newborn babies. All nine livebirths had a 1-min Apgar score of 8-9 and a 5-min Apgar score of 9-10. Amniotic fluid, cord blood, neonatal throat swab, and breastmilk samples from six patients were tested for SARS-CoV-2, and all samples tested negative for the virus.
Interpretation: The clinical characteristics of COVID-19 pneumonia in pregnant women were similar to those reported for non-pregnant adult patients who developed COVID-19 pneumonia. Findings from this small group of cases suggest that there is currently no evidence for intrauterine infection caused by vertical transmission in women who develop COVID-19 pneumonia in late pregnancy.
Funding: Hubei Science and Technology Plan, Wuhan University Medical Development Plan.

Notes

This study evaluated the clinical characteristics of COVID-19 in pregnancy and the intrauterine vertical transmission potential of COVID-19 infection. 9 pregnant women with COVID-19 pneumonia admitted to Zhongnan Hospital of Wuhan University, Wuhan, China were included in this study. All patients had a caesarean section in their third trimester. None of the patients or their new born babies died. All 9 patients (100%) were given empirical antibiotic treatment.

First Case of 2019 Novel Coronavirus in the United States.

Holshue et al., The New England Journal of Medicine.

Published: March 5th 2020

DOI: 10.1056/NEJMoa2001191

Summary

An outbreak of novel coronavirus (2019-nCoV) that began in Wuhan, China, has spread rapidly, with cases now confirmed in multiple countries. We report the first case of 2019-nCoV infection confirmed in the United States and describe the identification, diagnosis, clinical course, and management of the case, including the patient's initial mild symptoms at presentation with progression to pneumonia on day 9 of illness. This case highlights the importance of close coordination between clinicians and public health authorities at the local, state, and federal levels, as well as the need for rapid dissemination of clinical information related to the care of patients with this emerging infection.

Notes

As a result of the growing concern about hospital-acquired pneumonia, the patient in this case was given vancomycin. Vancomycin was discontinued on the evening of day 7 after a negative nasal PCR testing for methicillin-resistant Staphylococcus aureus.

Epidemiologic Features and Clinical Course Patients Infected With SARS-CoV-2 in Singapore.

Young et al., JAMA.

Published: March 3rd 2020

DOI: 10.1001/jama.2020.3204

Abstract

Importance: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, China, in December 2019 and has spread globally with sustained human-to-human transmission outside China.

Objective: To report the initial experience in Singapore with the epidemiologic investigation of this outbreak, clinical features, and management.

Design, Setting, and Participants: Descriptive case series of the first 18 patients diagnosed with polymerase chain reaction (PCR)-confirmed SARS-CoV-2 infection at 4 hospitals in Singapore from January 23 to February 3, 2020; final follow-up date was February 25, 2020.

Exposures: Confirmed SARS-CoV-2 infection.

Main Outcomes and Measures: Clinical, laboratory, and radiologic data were collected, including PCR cycle threshold values from nasopharyngeal swabs and viral shedding in blood, urine, and stool. Clinical course was summarized, including requirement for supplemental oxygen and intensive care and use of empirical treatment with lopinavir-ritonavir.

Results: Among the 18 hospitalized patients with PCR-confirmed SARS-CoV-2 infection (median age, 47 years; 9 [50%] women), clinical presentation was an upper respiratory tract infection in 12 (67%), and viral shedding from the nasopharynx was prolonged for 7 days or longer among 15 (83%). Six individuals (33%) required supplemental oxygen; of these, 2 required intensive care. There were no deaths. Virus was detectable in the stool (4/8 [50%]) and blood (1/12 [8%]) by PCR but not in urine. Five individuals requiring supplemental oxygen were treated with lopinavir-ritonavir. For 3 of the 5 patients, fever resolved and supplemental oxygen requirement was reduced within 3 days, whereas 2 deteriorated with progressive respiratory failure. Four of the 5 patients treated with lopinavir-ritonavir developed nausea, vomiting, and/or diarrhea, and 3 developed abnormal liver function test results.

Conclusions and Relevance: Among the first 18 patients diagnosed with SARS-CoV-2 infection in Singapore, clinical presentation was frequently a mild respiratory tract infection. Some patients required supplemental oxygen and had variable clinical outcomes following treatment with an antiretroviral agent.

Notes

Patients clinically suspected of having community-acquired pneumonia were administered empirical broad-spectrum antibiotics. As of February 25th 2020, no concomitant bacteria infections were detected and there were no deaths.

Clinical Characteristics of Coronavirus Disease 2019 in China.

Guan et al., 2020, The New England Journal of Medicine.

Published: February 28th 2020

DOI: 10.1056/NEJMoa2002032

Abstract

Background: Since December 2019, when coronavirus disease 2019 (Covid-19) emerged in Wuhan city and rapidly spread throughout China, data have been needed on the clinical characteristics of the affected patients.

Methods: We extracted data regarding 1099 patients with laboratory-confirmed Covid-19 from 552 hospitals in 30 provinces, autonomous regions, and municipalities in mainland China through January 29, 2020. The primary composite end point was admission to an intensive care unit (ICU), the use of mechanical ventilation, or death.

Results: The median age of the patients was 47 years; 41.9% of the patients were female. The primary composite end point occurred in 67 patients (6.1%), including 5.0% who were admitted to the ICU, 2.3% who underwent invasive mechanical ventilation, and 1.4% who died. Only 1.9% of the patients had a history of direct contact with wildlife. Among nonresidents of Wuhan, 72.3% had contact with residents of Wuhan, including 31.3% who had visited the city. The most common symptoms were fever (43.8% on admission and 88.7% during hospitalization) and cough (67.8%). Diarrhea was uncommon (3.8%). The median incubation period was 4 days (interquartile range, 2 to 7). On admission, ground-glass opacity was the most common radiologic finding on chest computed tomography (CT) (56.4%). No radiographic or CT abnormality was found in 157 of 877 patients (17.9%) with nonsevere disease and in 5 of 173 patients (2.9%) with severe disease. Lymphocytopenia was present in 83.2% of the patients on admission.

Conclusions: During the first 2 months of the current outbreak, Covid-19 spread rapidly throughout China and caused varying degrees of illness. Patients often presented without fever, and many did not have abnormal radiologic findings. (Funded by the National Health Commission of China and others.)

Notes

Data was extracted from 1099 patients with laboratory confirmed Covid-19 from 552 hospitals in 30 provinces, autonomous regions, and municipalities in mainland China. On admission these were characterised as non-severe (926 patients) and severe (173 patients). 637 patients (58%) received intravenous antibiotic therapy, 498 (53.8%) non-severe cases and 139 (80.3%) severe cases. Due to medical resources being overwhelmed, many patients did not undergo sputum bacteriologic of fungal assessment on admission.

Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centred, retrospective, observational study.

Yang et al., 2020, The Lancet.

Published: February 24th 2020

DOI: https://doi.org/10.1016/S2213-2600(20)30079-5

Summary

Background: An ongoing outbreak of pneumonia associated with the severe acute respiratory coronavirus 2 (SARS-CoV-2) started in December, 2019, in Wuhan, China. Information about critically ill patients with SARS-CoV-2 infection is scarce. We aimed to describe the clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia.

Methods: In this single-centered, retrospective, observational study, we enrolled 52 critically ill adult patients with SARS-CoV-2 pneumonia who were admitted to the intensive care unit (ICU) of Wuhan Jin Yin-tan hospital (Wuhan, China) between late December, 2019, and Jan 26, 2020. Demographic data, symptoms, laboratory values, comorbidities, treatments, and clinical outcomes were all collected. Data were compared between survivors and non-survivors. The primary outcome was 28-day mortality, as of Feb 9, 2020. Secondary outcomes included incidence of SARS-CoV-2-related acute respiratory distress syndrome (ARDS) and the proportion of patients requiring mechanical ventilation.

Findings: Of 710 patients with SARS-CoV-2 pneumonia, 52 critically ill adult patients were included. The mean age of the 52 patients was 59·7 (SD 13·3) years, 35 (67%) were men, 21 (40%) had chronic illness, 51 (98%) had fever. 32 (61·5%) patients had died at 28 days, and the median duration from admission to the intensive care unit (ICU) to death was 7 (IQR 3-11) days for non-survivors. Compared with survivors, non-survivors were older (64·6 years [11·2] vs 51·9 years [12·9]), more likely to develop ARDS (26 [81%] patients vs 9 [45%] patients), and more likely to receive mechanical ventilation (30 [94%] patients vs 7 [35%] patients), either invasively or non-invasively. Most patients had organ function damage, including 35 (67%) with ARDS, 15 (29%) with acute kidney injury, 12 (23%) with cardiac injury, 15 (29%) with liver dysfunction, and one (2%) with pneumothorax. 37 (71%) patients required mechanical ventilation. Hospital-acquired infection occurred in seven (13·5%) patients.

Interpretation: The mortality of critically ill patients with SARS-CoV-2 pneumonia is considerable. The survival time of the non-survivors is likely to be within 1-2 weeks after ICU admission. Older patients (>65 years) with comorbidities and ARDS are at increased risk of death. The severity of SARS-CoV-2 pneumonia poses great strain on critical care resources in hospitals, especially if they are not adequately staffed or resourced.

Funding: None.

Notes

52 critically ill adult patients admitted to ICU with SARS-CoV-2 pneumonia in Jin Yin-tan hospital in Wuhan, China were included in this study. 32 of these did not survive, whilst 20 did. One (2%) patient had a pulmonary and blood stream infection of carbapenem-resistant Klebsiella pneumoniae.Candida albicans was identified in the urine culture of one patient. (2%). Both patients were amongst those who did not survive. Other microorganisms identified from respiratory tract secretions in 5 (10%) patients included Aspergillus flavus, A fumigatus, extended-spectrum β-Lactamase (ESBL)-positive K pneumonia, ESBL-positive Pseudomonas aeruginosa, and ESBL-negative Serratia marcescens, with each microorganism found in one patient each. Antibacterial agents were given to 49 (94%) of patients, 19 (95%) survivors and 30 (94%) non-survivors.

Clinical findings in a group of patients infected with the 2019 novel coronavirus (SARS-CoV-2) outside of Wuhan, China: retrospective case series

Xu et al., 2020, British Medical Journal.

Published: February 19th 2020

DOI: https://doi.org/10.1136/bmj.m606

Abstract

Objective: To study the clinical characteristics of patients in Zhejiang province, China, infected with the 2019 severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) responsible for coronavirus disease 2019 (covid-2019).

Design:Retrospective case series.

Setting:Seven hospitals in Zhejiang province, China.

Participants:62 patients admitted to hospital with laboratory confirmed SARS-Cov-2 infection. Data were collected from 10 January 2020 to 26 Janurary 2020.

Main outcome measures: Clinical data, collected using a standardised case report form, such as temperature, history of exposure, incubation period. If information was not clear, the working group in Hangzhou contacted the doctor responsible for treating the patient for clarification.

Results: Of the 62 patients studied (median age 41 years), only one was admitted to an intensive care unit, and no patients died during the study. According to research, none of the infected patients in Zhejiang province were ever exposed to the Huanan seafood market, the original source of the virus; all studied cases were infected by human to human transmission. The most common symptoms at onset of illness were fever in 48 (77%) patients, cough in 50 (81%), expectoration in 35 (56%), headache in 21 (34%), myalgia or fatigue in 32 (52%), diarrhoea in 3 (8%), and haemoptysis in 2 (3%). Only two patients (3%) developed shortness of breath on admission. The median time from exposure to onset of illness was 4 days (interquartile range 3-5 days), and from onset of symptoms to first hospital admission was 2 (1-4) days.

Conclusion: As of early February 2020, compared with patients initially infected with SARS-Cov-2 in Wuhan, the symptoms of patients in Zhejiang province are relatively mild.

Notes

62 patients from seven hospitals in Zheijiang province, China with laboratory confirmed SARS-CoV-2 infection were included in this study. Only one of these patients was admitted to ICU and none died during the study. Quinolones and second generation beta lactams (oral and intravenous) were administered to 28 (45%) patients whose fever lasted for more than 7 days or C reactive protein levels were 30mg/L or more (normal range 0-8mg/L).

Pathological findings of COVID-19 associated with acute respiratory distress syndrome

Xu et al., 2020. The Lancet.

Published: February 18th 2020

DOI: https://doi.org/10.1016/S2213-2600(20)30076-X

Notes

This study investigated the pathological characteristics of a patient who died from severe infection with SARS-CoV-2. Upon admission to a fever clinic he was given moxifloxacin (0.4g once daily, intravenously) to prevent secondary infection. The patient showed rapid progression of pneumonia thought to be caused by SARS-CoV-2.

Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China

Huang et al., 2020. The Lancet.

Published: February 15th 2020

DOI: https://doi.org/10.1016/S0140-6736(20)30183-5

Summary

Background: A recent cluster of pneumonia cases in Wuhan, China, was caused by a novel betacoronavirus, the 2019 novel coronavirus (2019-nCoV). We report the epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of these patients.

Methods: All patients with suspected 2019-nCoV were admitted to a designated hospital in Wuhan. We prospectively collected and analysed data on patients with laboratory-confirmed 2019-nCoV infection by real-time RT-PCR and next-generation sequencing. Data were obtained with standardised data collection forms shared by WHO and the International Severe Acute Respiratory and Emerging Infection Consortium from electronic medical records. Researchers also directly communicated with patients or their families to ascertain epidemiological and symptom data. Outcomes were also compared between patients who had been admitted to the intensive care unit (ICU) and those who had not.

Findings: By Jan 2, 2020, 41 admitted hospital patients had been identified as having laboratory-confirmed 2019-nCoV infection. Most of the infected patients were men (30 [73%] of 41); less than half had underlying diseases (13 [32%]), including diabetes (eight [20%]), hypertension (six [15%]), and cardiovascular disease (six [15%]). Median age was 49·0 years (IQR 41·0-58·0). 27 (66%) of 41 patients had been exposed to Huanan seafood market. One family cluster was found. Common symptoms at onset of illness were fever (40 [98%] of 41 patients), cough (31 [76%]), and myalgia or fatigue (18 [44%]); less common symptoms were sputum production (11 [28%] of 39), headache (three [8%] of 38), haemoptysis (two [5%] of 39), and diarrhoea (one [3%] of 38). Dyspnoea developed in 22 (55%) of 40 patients (median time from illness onset to dyspnoea 8·0 days [IQR 5·0-13·0]). 26 (63%) of 41 patients had lymphopenia. All 41 patients had pneumonia with abnormal findings on chest CT. Complications included acute respiratory distress syndrome (12 [29%]), RNAaemia (six [15%]), acute cardiac injury (five [12%]) and secondary infection (four [10%]). 13 (32%) patients were admitted to an ICU and six (15%) died. Compared with non-ICU patients, ICU patients had higher plasma levels of IL2, IL7, IL10, GSCF, IP10, MCP1, MIP1A, and TNFα.

Interpretation: The 2019-nCoV infection caused clusters of severe respiratory illness similar to severe acute respiratory syndrome coronavirus and was associated with ICU admission and high mortality. Major gaps in our knowledge of the origin, epidemiology, duration of human transmission, and clinical spectrum of disease need fulfilment by future studies.

Funding: Ministry of Science and Technology, Chinese Academy of Medical Sciences, National Natural Science Foundation of China, and Beijing Municipal Science and Technology Commission.

Notes

41 patients admitted to a hospital in Wuhan were included in this study. Routine bacterial and fungal examinations were performed on these patients. Given the emergence of 2019-nCoV pneumonia cases during the influenza seasons, antibiotics were empirically administered (orally and intravenously) to all 41 (100%) patients. Secondary infection was diagnosed if the patients had clinical symptoms or signs of nosocomial pneumonia or bacteraemia, and was combined with a positive culture of a new pathogen from a lower respiratory tract specimen (including the sputum, transtracheal aspirates, or bronchoalveolar lavage fluid, or from blood samples taken ≥48 h after admission). All 41 patients had pneumonia and 4 (10%) patients had a secondary infection as a complication.

Clinical Characteristics of 138 Hospitalised Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China.

Wang et al., 2020. The Journal of the American Medical Association.

Published: February 7th 2020

DOI: 10.1001/jama.2020.1585

Abstract

Importance: In December 2019, novel coronavirus (2019-nCoV)-infected pneumonia (NCIP) occurred in Wuhan, China. The number of cases has increased rapidly but information on the clinical characteristics of affected patients is limited.

Objective: To describe the epidemiological and clinical characteristics of NCIP.

Design, Setting, and Participants: Retrospective, single-center case series of the 138 consecutive hospitalized patients with confirmed NCIP at Zhongnan Hospital of Wuhan University in Wuhan, China, from January 1 to January 28, 2020; final date of follow-up was February 3, 2020.

Exposures: Documented NCIP.

Main Outcomes and Measures: Epidemiological, demographic, clinical, laboratory, radiological, and treatment data were collected and analyzed. Outcomes of critically ill patients and noncritically ill patients were compared. Presumed hospital-related transmission was suspected if a cluster of health professionals or hospitalized patients in the same wards became infected and a possible source of infection could be tracked.

Results: Of 138 hospitalized patients with NCIP, the median age was 56 years (interquartile range, 42-68; range, 22-92 years) and 75 (54.3%) were men. Hospital-associated transmission was suspected as the presumed mechanism of infection for affected health professionals (40 [29%]) and hospitalized patients (17 [12.3%]). Common symptoms included fever (136 [98.6%]), fatigue (96 [69.6%]), and dry cough (82 [59.4%]). Lymphopenia (lymphocyte count, 0.8 × 109/L [interquartile range {IQR}, 0.6-1.1]) occurred in 97 patients (70.3%), prolonged prothrombin time (13.0 seconds [IQR, 12.3-13.7]) in 80 patients (58%), and elevated lactate dehydrogenase (261 U/L [IQR, 182-403]) in 55 patients (39.9%). Chest computed tomographic scans showed bilateral patchy shadows or ground glass opacity in the lungs of all patients. Most patients received antiviral therapy (oseltamivir, 124 [89.9%]), and many received antibacterial therapy (moxifloxacin, 89 [64.4%]; ceftriaxone, 34 [24.6%]; azithromycin, 25 [18.1%]) and glucocorticoid therapy (62 [44.9%]). Thirty-six patients (26.1%) were transferred to the intensive care unit (ICU) because of complications, including acute respiratory distress syndrome (22 [61.1%]), arrhythmia (16 [44.4%]), and shock (11 [30.6%]). The median time from first symptom to dyspnea was 5.0 days, to hospital admission was 7.0 days, and to ARDS was 8.0 days. Patients treated in the ICU (n = 36), compared with patients not treated in the ICU (n = 102), were older (median age, 66 years vs 51 years), were more likely to have underlying comorbidities (26 [72.2%] vs 38 [37.3%]), and were more likely to have dyspnea (23 [63.9%] vs 20 [19.6%]), and anorexia (24 [66.7%] vs 31 [30.4%]). Of the 36 cases in the ICU, 4 (11.1%) received high-flow oxygen therapy, 15 (41.7%) received noninvasive ventilation, and 17 (47.2%) received invasive ventilation (4 were switched to extracorporeal membrane oxygenation). As of February 3, 47 patients (34.1%) were discharged and 6 died (overall mortality, 4.3%), but the remaining patients are still hospitalized. Among those discharged alive (n = 47), the median hospital stay was 10 days (IQR, 7.0-14.0).

Conclusions and Relevance: In this single-center case series of 138 hospitalized patients with confirmed NCIP in Wuhan, China, presumed hospital-related transmission of 2019-nCoV was suspected in 41% of patients, 26% of patients received ICU care, and mortality was 4.3%.

Notes

138 patients with confirmed novel coronavirus(2019-nCoV)- infected pneumonia (NCIP) at Zhongnan Hospital of Wuhan University in Wuhan, China were included in this study. All of the patients in this study received antibacterial agents, 89 (64.4%) were given moxifloxacin, 34 (24.6%) given ceftriaxone and 25 (18.1%) were given azithromycin. A month later, 85 (61.6%) patients were still hospitalised, 47 (34.1%) had been discharged and 6 (4.3%) had died.

Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study

Chen et al., 2020. The Lancet.

Published: January 30th 2020.

DOI: https://doi.org/10.1016/S0140-6736(20)30211-7

Summary

Background: In December, 2019, a pneumonia associated with the 2019 novel coronavirus (2019-nCoV) emerged in Wuhan, China. We aimed to further clarify the epidemiological and clinical characteristics of 2019-nCoV pneumonia.

Methods: In this retrospective, single-centre study, we included all confirmed cases of 2019-nCoV in Wuhan Jinyintan Hospital from Jan 1 to Jan 20, 2020. Cases were confirmed by real-time RT-PCR and were analysed for epidemiological, demographic, clinical, and radiological features and laboratory data. Outcomes were followed up until Jan 25, 2020.

Findings: Of the 99 patients with 2019-nCoV pneumonia, 49 (49%) had a history of exposure to the Huanan seafood market. The average age of the patients was 55·5 years (SD 13·1), including 67 men and 32 women. 2019-nCoV was detected in all patients by real-time RT-PCR. 50 (51%) patients had chronic diseases. Patients had clinical manifestations of fever (82 [83%] patients), cough (81 [82%] patients), shortness of breath (31 [31%] patients), muscle ache (11 [11%] patients), confusion (nine [9%] patients), headache (eight [8%] patients), sore throat (five [5%] patients), rhinorrhoea (four [4%] patients), chest pain (two [2%] patients), diarrhoea (two [2%] patients), and nausea and vomiting (one [1%] patient). According to imaging examination, 74 (75%) patients showed bilateral pneumonia, 14 (14%) patients showed multiple mottling and ground-glass opacity, and one (1%) patient had pneumothorax. 17 (17%) patients developed acute respiratory distress syndrome and, among them, 11 (11%) patients worsened in a short period of time and died of multiple organ failure.

Interpretation: The 2019-nCoV infection was of clustering onset, is more likely to affect older males with comorbidities, and can result in severe and even fatal respiratory diseases such as acute respiratory distress syndrome. In general, characteristics of patients who died were in line with the MuLBSTA score, an early warning model for predicting mortality in viral pneumonia. Further investigation is needed to explore the applicability of the MuLBSTA score in predicting the risk of mortality in 2019-nCoV infection.

Funding: National Key R&D Program of China.

Notes

Patients were recruited between Jan 1 and Jan 20, 2020 at Jinyintan Hospital in Wuhan, China. All patients who were diagnosed with 2019-nCoV pneumonia according to WHO interim guidance were enrolled in this study (99 patients). From these 99 patients, 57 (58%) remained in hospital, 31 (31%) were discharged and 11 (11%) died. 70 (71%) of the 99 patients were treated with antibiotics, 25 (25%) were treated with a single antibiotic and 45 (45%) were given combination therapy. The antibiotics used were cephalosporins, quinolones, carbapenems, tigecycline against methicillin-resistant Staphylococcus aureus, linezolid, and antifungal drugs. The duration of antibiotic treatment was 3-17 days.

Laboratory results showed that 1 (1%) patient had a bacterial co-infection. In this patient, Acinetobacter baumanii, Klebsiella pneumoniae and Aspergillus flavus were all cultured. A baumannii turned out to be highly resistant to antibiotics.

Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus-Infected Pneumonia

Li et al., 2020. The New England Journal of Medicine.

Published: January 29th 2020

DOI: 10.1056/NEJMoa2001316

Abstract

Background: The initial cases of novel coronavirus (2019-nCoV)-infected pneumonia (NCIP) occurred in Wuhan, Hubei Province, China, in December 2019 and January 2020. We analyzed data on the first 425 confirmed cases in Wuhan to determine the epidemiologic characteristics of NCIP.

Methods: We collected information on demographic characteristics, exposure history, and illness timelines of laboratory-confirmed cases of NCIP that had been reported by January 22, 2020. We described characteristics of the cases and estimated the key epidemiologic time-delay distributions. In the early period of exponential growth, we estimated the epidemic doubling time and the basic reproductive number.

Results: Among the first 425 patients with confirmed NCIP, the median age was 59 years and 56% were male. The majority of cases (55%) with onset before January 1, 2020, were linked to the Huanan Seafood Wholesale Market, as compared with 8.6% of the subsequent cases. The mean incubation period was 5.2 days (95% confidence interval [CI], 4.1 to 7.0), with the 95th percentile of the distribution at 12.5 days. In its early stages, the epidemic doubled in size every 7.4 days. With a mean serial interval of 7.5 days (95% CI, 5.3 to 19), the basic reproductive number was estimated to be 2.2 (95% CI, 1.4 to 3.9).

Conclusions: On the basis of this information, there is evidence that human-to-human transmission has occurred among close contacts since the middle of December 2019. Considerable efforts to reduce transmission will be required to control outbreaks if similar dynamics apply elsewhere. Measures to prevent or reduce transmission should be implemented in populations at risk. (Funded by the Ministry of Science and Technology of China and others.)

Notes

This study analyses data on the first 425 confirmed cases in Wuhan, China to determine the epidemiologic characteristics of novel coronavirus-infected pneumonia (NCIP). These early cases were identified as pneumonia of unknown etiology, after 3-5 days of antimicrobial treatment there was no symptomatic improvement.