Coronavirus Disease 2019 as Cause of Viral Sepsis: A Systematic Review and Meta-Analysis*

ABSTRACT Importance COVID-19 is a heterogenous disease most frequently causing respiratory tract infection but in its severe forms, respiratory failure and multiple organ dysfunction syndrome may occur, resembling sepsis. The prevalence of viral sepsis among COVID-19 patients is still unclear. Objective We aimed to describe this in a systematic review. Data sources MEDLINE(PubMed), Cochrane and Google Scholar databases were searched for studies reporting on patients hospitalized with confirmed COVID-19, diagnosed with sepsis or infection-related organ dysfunctions or receiving organ replacement therapy. Study selection Eligible were full-text English articles of randomized and non-randomized clinical trials and observational studies reporting on patients with confirmed COVID-19, who are diagnosed with sepsis or have infection-related organ dysfunctions. Systematic reviews, editorials, conference abstracts, animal studies, case reports, articles neither in English nor full-text, and studies with fewer than 30 participants were excluded. Data extraction and synthesis All eligible studies were included in a narrative synthesis of results and after reviewing all included studies a meta-analysis was conducted. Separate sensitivity analyses were conducted per adult vs pediatric populations and per Intensive Care Unit (ICU) vs non-ICU populations. Main outcomes and measures Primary endpoint was the prevalence of sepsis using Sepsis-3 criteria among patients with COVID-19 and among secondary, new onset of infection-related organ dysfunction. Outcomes were expressed as proportions with respective 95% confidence interval (CI). Results Of 1,903 articles, 104 were analyzed. The prevalence of sepsis in COVID-19 was 39.9% (95% CI, 35.9-44.1; I 2 , 99%). In sensitivity analysis, sepsis was present in 25.1% (95% CI, 21.8-28.9; I 2 99%) of adult patients hospitalized in non-Intensive-Care-Unit (ICU) wards (40 studies) and in 83.8 (95% CI, 78.1-88.2; I 2 ,91%) of adult patients hospitalized in the ICU (31 studies). Sepsis in children hospitalized with COVID-19 was as high as 7.8% (95% CI, 0.4-64.9; I 2 , 97%). Acute Respiratory Distress Syndrome was the most common organ dysfunction in adult patients in non-ICU (27.6; 95% CI, 21.6-34.5; I 2 , 99%) and ICU (88.3%; 95% CI, 79.7-93.5; I 2 , 97%) Conclusions and relevance Despite the high heterogeneity in reported results, sepsis frequently complicates COVID-19 among hospitalized patients and is significantly higher among those in the ICU. PROSPERO registration number: CRD42020202018. No funding. KEY POINTS Question What is the prevalence of viral sepsis by Sepsis-3 definition among hospitalized patients with COVID-19? Findings In this systematic review and meta-analysis, we systematically reviewed published literature for evidence of organ failure in COVID-19, to estimate the prevalence of viral sepsis in this setting, by means of SOFA score calculation. The prevalence of sepsis in COVID-19 was 39.9% (95% CI, 35.9-44.1; I 2 , 99%). Meaning This is the first study to address the burden of viral sepsis in hospitalized patients with COVID-19, a highly heterogenous infection ranging from asymptomatic cases to severe disease leading to death, as reflected in the high heterogeneity of this study.

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