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      Secondary Infections in Patients Hospitalized with COVID-19: Incidence and Predictive Factors

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          Abstract

          Objectives

          Aim of our study was to describe the incidence and predictive factors of secondary infections in patients with COVID-19.

          Methods

          Cohort study on patients hospitalized with COVID-19 at IRCCS San Raffaele Hospital between February 25 th and April 6th, 2020 (NCT04318366). We considered secondary bloodstream (BSIs) or possible lower respiratory tract infections (pLRTIs) occurred after 48 hours since hospital admission until death or discharge. We calculated multivariable Fine-Gray models, to assess factors associated with risk of secondary infections.

          Results

          Among 731 patients, a secondary infection was diagnosed in 68 patients (9.3%): 58/731 patients (7.9%) had at least one BSI and 22/731 patients (3.0%) at least one pLRTI. Overall 28-day cumulative incidence was 16.4% (95% CI 12.4% - 21.0%). The majority of BSIs was due to gram-positive pathogens (76/106 isolates, 71.7%), specifically coagulase-negative staphylococci (53/76, 69.7%), while among gram-negatives (23/106, 21.7%) Acinetobacter baumanii (7/23, 30.4%) and Escherichia coli (5/23, 21.7%) predominated. pLRTIs were mainly caused by gram-negative pathogens (14/26, 53.8%). Eleven patients were diagnosed with putative invasive aspergillosis. At multivariable analysis, factors associated with secondary infections were low baseline lymphocyte count ( <0.7 vs >0.7 per 10 9/L: subdistribution hazard ratios (sdHRs) 1.93 [95% CI 1.11-3.35]), baseline PaO 2/FiO 2 (per 100-points lower: sdHRs 1.56 [95% CI 1.21-2.04]), and intensive-care unit (ICU) admission in the first 48 hours (sdHR 2.51 [95% CI 1.04-6.05]).

          Conclusions

          Patients hospitalized with COVID-19 had a high incidence of secondary infections. At multivariable analysis, early need for ICU, respiratory failure, and severe lymphopenia, were identified as risk factors for secondary infections.

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          Clinical Characteristics of Coronavirus Disease 2019 in China

          Wei-jie Guan, Zheng-yi Ni, Yu Hu … (2020)
          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.)
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            Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

            Fei Zhou, Ting Yu, Ronghui Du … (2020)
            Summary 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.
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              Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study

              Xiaobo Yang, Yuan Yu, Jiqian Xu … (2020)
              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.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Clin Microbiol Infect
                Journal ID (iso-abbrev): Clin Microbiol Infect
                Title: Clinical Microbiology and Infection
                Publisher: European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd.
                ISSN (Print): 1198-743X
                ISSN (Electronic): 1469-0691
                Publication date PMC-release: 24 October 2020
                Publication date (Electronic): 24 October 2020
                Affiliations
                [1 ]Unit of Infectious and Tropical Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy
                [2 ]Vita-Salute San Raffaele University, Milan, Italy
                [3 ]Anesthesia and Intensive Care Department, IRCCS San Raffaele Scientific Institute, Milan, Italy
                [4 ]Unit of Immunology, Rheumatology, Allergy and Rare Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy
                [5 ]Microbiology and Virology Department, IRCCS San Raffaele Scientific Institute, Milan, Italy
                [6 ]Internal Medicine, Diabetes, and Endocrinology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
                [7 ]Hematology and Bone Marrow Transplant Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
                [8 ]General Medicine and Advanced Care Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
                Author notes
                [∗ ]Corresponding author. Unit of Infectious and Tropical Diseases, IRCCS San Raffaele Scientific Institute, Via Stamira d’Ancona 20, 20127, Milan, Italy, Tel.: +390226439195; fax: +390226439195.
                Article
                Publisher Item ID: S1198-743X(20)30652-2
                DOI: 10.1016/j.cmi.2020.10.021
                PMC ID: 7584496
                PubMed ID: 33223114
                SO-VID: 499eb999-299d-4e4b-bfdb-0676add53864
                Copyright © © 2020 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
                License:

                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
                Date received : 24 June 2020
                Date revision received : 8 October 2020
                Date accepted : 19 October 2020
                Categories
                Subject: Original Article

                ScienceOpen disciplines: Microbiology & Virology
                Data availability:
                ScienceOpen disciplines: Microbiology & Virology

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