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Meta-Analysis
. 2021 Dec 1;49(12):2042-2057.
doi: 10.1097/CCM.0000000000005195.

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

Affiliations
Meta-Analysis

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

Eleni Karakike et al. Crit Care Med. .

Abstract

Objective: Coronavirus disease 2019 is a heterogeneous disease most frequently causing respiratory tract infection, which can induce respiratory failure and multiple organ dysfunction syndrome in its severe forms. The prevalence of coronavirus disease 2019-related sepsis is still unclear; we aimed to describe this in a systematic review.

Data sources: MEDLINE (PubMed), Cochrane, and Google Scholar databases were searched based on a prespecified protocol (International Prospective Register for Systematic Reviews: CRD42020202018).

Study selection: Studies reporting on patients with confirmed coronavirus disease 2019 diagnosed with sepsis according to sepsis-3 or according to the presence of infection-related organ dysfunctions necessitating organ support/replacement were included in the analysis. The primary end point was prevalence of coronavirus disease 2019-related sepsis among adults hospitalized in the ICU and the general ward. Among secondary end points were the need for ICU admission among patients initially hospitalized in the general ward and the prevalence of new onset of organ dysfunction in the ICU. Outcomes were expressed as proportions with respective 95% CI.

Data extraction: Two reviewers independently screened and reviewed existing literature and assessed study quality with the Newcastle-Ottawa Scale and the Methodological index for nonrandomized studies.

Data synthesis: Of 3,825 articles, 151 were analyzed, only five of which directly reported sepsis prevalence. Noting the high heterogeneity observed, coronavirus disease 2019-related sepsis prevalence was 77.9% (95% CI, 75.9-79.8; I2 = 91%; 57 studies) in the ICU, and 33.3% (95% CI, 30.3-36.4; I2 = 99%; 86 studies) in the general ward. ICU admission was required for 17.7% (95% CI, 12.9-23.6; I2 = 100%) of ward patients. Acute respiratory distress syndrome was the most common organ dysfunction in the ICU (87.5%; 95% CI, 83.3-90.7; I2 = 98%).

Conclusions: The majority of coronavirus disease 2019 patients hospitalized in the ICU meet Sepsis-3 criteria and present infection-associated organ dysfunction. The medical and scientific community should be aware and systematically report viral sepsis for prognostic and treatment implications.

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Conflict of interest statement

Dr. Karakike received funding from the Horizon 2020 Marie Skłodowska-Curie Grant European Sepsis Academy (grant 676129). Dr. Netea’s institution received funding from Roche; he received funding form an ERC Advanced Grant (833247), a Spinoza grant of the Netherlands Organization for Scientific Research, TTxD, GSK, and ViiV HealthCare; he disclosed he is on the scientific Advisory Board at Trained Therapeutic and Discovery; received independent educational grants from AbbVie, Abbott CH, Astellas Pharma Europe, AxisShield, bioMérieux, InflaRx GmbH, the Medicines Company, and XBiotech. Dr. Reinhart disclosed that he was the President of the Global Sepsis Alliance and that he is a shareholder of InflaRx NV, a Jena/Germany-based Biotech Company that evaluates an immune-modulatory approach for the adjunctive treatment of coronavirus disease 2019. Dr. Giamarellos-Bourboulis’ institution received funding from the Framework 7 Program, HemoSpec (granted to the National and Kapodistrian University of Athens), the Horizon 2020 Marie-Curie Project European Sepsis Academy (granted to the National and Kapodistrian University of Athens), and the Horizon 2020 European Grant ImmunoSep (granted to the Hellenic Institute for the Study of Sepsis); he received funding from AbbVie, United States; Abbott CH; Angelini; Astellas Pharma; AxisShield; bioMérieux; Biotest; Brahms GmbH; InflaRx GmbH; MSD Greece; XBiotech; and The Medicines Company; independent educational grants from AbbVie, Abbott CH, Astellas Pharma Europe, AxisShield, bioMérieux, InflaRx GmbH, the Medicines Company, and XBiotech. The remaining authors have disclosed that they do not have any potential conflicts of interest.

Figures

Figure 1.
Figure 1.
Study selection. COVID = coronavirus disease.
Figure 2.
Figure 2.
Forest plot of sepsis prevalence among adult patients hospitalized in the ICU.
Figure 3.
Figure 3.
Forest plot of mortality among patients with coronavirus disease 2019 (COVID-19). A, Hospitalized in the ICU. B, Under invasive mechanical ventilation (IMV). REVA = Réseau Européen de Recherche en Ventilation Artificielle.

Comment in

  • How sepsis parallels and differs from COVID-19.
    Herminghaus A, Osuchowski MF. Herminghaus A, et al. EBioMedicine. 2022 Dec;86:104355. doi: 10.1016/j.ebiom.2022.104355. Epub 2022 Dec 2. EBioMedicine. 2022. PMID: 36470836 Free PMC article. No abstract available.

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