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

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          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.

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          Most cited references11

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          Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China

          Dear Editor, The rapid emergence of COVID-19 in Wuhan city, Hubei Province, China, has resulted in thousands of deaths [1]. Many infected patients, however, presented mild flu-like symptoms and quickly recover [2]. To effectively prioritize resources for patients with the highest risk, we identified clinical predictors of mild and severe patient outcomes. Using the database of Jin Yin-tan Hospital and Tongji Hospital, we conducted a retrospective multicenter study of 68 death cases (68/150, 45%) and 82 discharged cases (82/150, 55%) with laboratory-confirmed infection of SARS-CoV-2. Patients met the discharge criteria if they had no fever for at least 3 days, significantly improved respiratory function, and had negative SARS-CoV-2 laboratory test results twice in succession. Case data included demographics, clinical characteristics, laboratory results, treatment options and outcomes. For statistical analysis, we represented continuous measurements as means (SDs) or as medians (IQRs) which compared with Student’s t test or the Mann–Whitney–Wilcoxon test. Categorical variables were expressed as numbers (%) and compared by the χ 2 test or Fisher’s exact test. The distribution of the enrolled patients’ age is shown in Fig. 1a. There was a significant difference in age between the death group and the discharge group (p < 0.001) but no difference in the sex ratio (p = 0.43). A total of 63% (43/68) of patients in the death group and 41% (34/82) in the discharge group had underlying diseases (p = 0.0069). It should be noted that patients with cardiovascular diseases have a significantly increased risk of death when they are infected with SARS-CoV-2 (p < 0.001). A total of 16% (11/68) of the patients in the death group had secondary infections, and 1% (1/82) of the patients in the discharge group had secondary infections (p = 0.0018). Laboratory results showed that there were significant differences in white blood cell counts, absolute values of lymphocytes, platelets, albumin, total bilirubin, blood urea nitrogen, blood creatinine, myoglobin, cardiac troponin, C-reactive protein (CRP) and interleukin-6 (IL-6) between the two groups (Fig. 1b and Supplementary Table 1). Fig. 1 a Age distribution of patients with confirmed COVID-19; b key laboratory parameters for the outcomes of patients with confirmed COVID-19; c interval from onset of symptom to death of patients with confirmed COVID-19; d summary of the cause of death of 68 died patients with confirmed COVID-19 The survival times of the enrolled patients in the death group were analyzed. The distribution of survival time from disease onset to death showed two peaks, with the first one at approximately 14 days (22 cases) and the second one at approximately 22 days (17 cases) (Fig. 1c). An analysis of the cause of death was performed. Among the 68 fatal cases, 36 patients (53%) died of respiratory failure, five patients (7%) with myocardial damage died of circulatory failure, 22 patients (33%) died of both, and five remaining died of an unknown cause (Fig. 1d). Based on the analysis of the clinical data, we confirmed that some patients died of fulminant myocarditis. In this study, we first reported that the infection of SARS-CoV-2 may cause fulminant myocarditis. Given that fulminant myocarditis is characterized by a rapid progress and a severe state of illness [3], our results should alert physicians to pay attention not only to the symptoms of respiratory dysfunction but also the symptoms of cardiac injury. Further, large-scale studies and the studies on autopsy are needed to confirm our analysis. In conclusion, predictors of a fatal outcome in COVID-19 cases included age, the presence of underlying diseases, the presence of secondary infection and elevated inflammatory indicators in the blood. The results obtained from this study also suggest that COVID-19 mortality might be due to virus-activated “cytokine storm syndrome” or fulminant myocarditis. Electronic supplementary material Below is the link to the electronic supplementary material. Supplementary material 1 (DOCX 38 kb)
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            Bacterial and fungal co-infection in individuals with coronavirus: A rapid review to support COVID-19 antimicrobial prescribing

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

              This study describes the prevalence of SARS-CoV-2 co-infection with noncoronavirus respiratory pathogens in a sample of symptomatic patients undergoing PCR testing in March 2020.
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                Author and article information

                Contributors
                Journal
                Clin Microbiol Infect
                Clin. Microbiol. Infect
                Clinical Microbiology and Infection
                European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd.
                1198-743X
                1469-0691
                27 June 2020
                27 June 2020
                Affiliations
                [1 ]Chelsea and Westminster NHS Foundation Trust, 369 Fulham Road, London, SW10 9NH. UK
                [2 ]North West London Pathology, Imperial College Healthcare NHS Trust, Fulham Palace Road. London. W6 8RF. UK
                [3 ]National Institute for Health Research Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance, Imperial College London, Hammersmith Campus, Du Cane Road, London. W12 0NN. UK
                Author notes
                []Corresponding author. Chelsea and Westminster NHS Foundation Trust, 369 Fulham Road, London, SW10 9NH. UK. Tel.: +2033155100. stephen.hughes2@ 123456chelwest.nhs.uk
                Article
                S1198-743X(20)30369-4
                10.1016/j.cmi.2020.06.025
                7320692
                32603803
                8ffef205-7b61-4a46-9ffd-92649854c0d4
                © 2020 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

                History
                : 13 May 2020
                : 15 June 2020
                : 24 June 2020
                Categories
                Article

                Microbiology & Virology
                coronavirus,pneumonia,sars-cov-2
                Microbiology & Virology
                coronavirus, pneumonia, sars-cov-2

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