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Meta-Analysis
. 2021 Oct 6:12:744696.
doi: 10.3389/fimmu.2021.744696. eCollection 2021.

A Systematic Review and Meta-Analysis of Inpatient Mortality Associated With Nosocomial and Community COVID-19 Exposes the Vulnerability of Immunosuppressed Adults

Mark J Ponsford  1   2 , Tom J C Ward  3   4 , Simon M Stoneham  5   6 , Clare M Dallimore  7 , Davina Sham  8 , Khalid Osman  9 , Simon M Barry  9   10 , Stephen Jolles  1 , Ian R Humphreys  2   11 , Daniel Farewell  12
Affiliations
Meta-Analysis

A Systematic Review and Meta-Analysis of Inpatient Mortality Associated With Nosocomial and Community COVID-19 Exposes the Vulnerability of Immunosuppressed Adults

Mark J Ponsford et al. Front Immunol. .

Abstract

Background: Little is known about the mortality of hospital-acquired (nosocomial) COVID-19 infection globally. We investigated the risk of mortality and critical care admission in hospitalised adults with nosocomial COVID-19, relative to adults requiring hospitalisation due to community-acquired infection.

Methods: We systematically reviewed the peer-reviewed and pre-print literature from 1/1/2020 to 9/2/2021 without language restriction for studies reporting outcomes of nosocomial and community-acquired COVID-19. We performed a random effects meta-analysis (MA) to estimate the 1) relative risk of death and 2) critical care admission, stratifying studies by patient cohort characteristics and nosocomial case definition.

Results: 21 studies were included in the primary MA, describing 8,251 admissions across 8 countries during the first wave, comprising 1513 probable or definite nosocomial COVID-19, and 6738 community-acquired cases. Across all studies, the risk of mortality was 1.3 times greater in patients with nosocomial infection, compared to community-acquired (95% CI: 1.005 to 1.683). Rates of critical care admission were similar between groups (Relative Risk, RR=0.74, 95% CI: 0.50 to 1.08). Immunosuppressed patients diagnosed with nosocomial COVID-19 were twice as likely to die in hospital as those admitted with community-acquired infection (RR=2.14, 95% CI: 1.76 to 2.61).

Conclusions: Adults who acquire SARS-CoV-2 whilst already hospitalised are at greater risk of mortality compared to patients admitted following community-acquired infection; this finding is largely driven by a substantially increased risk of death in individuals with malignancy or who had undergone transplantation. These findings inform public health and infection control policy and argue for individualised clinical interventions to combat the threat of nosocomial COVID-19, particularly for immunosuppressed groups.

Systematic review registration: PROSPERO CRD42021249023.

Keywords: covid-19; hospital-acquired; immunodeficiency; infection control; nosocomial transmission.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
PRISMA Study Flow Diagram.
Figure 2
Figure 2
Timing of UK studies relative to national COVID-19 rates. Plot showing the timing of individual studies included within the primary meta-analysis reporting patients within the United Kingdom (UK), relative to national daily COVID-19 case diagnosis rates January 2020 and April 2021. * The study by Carter et al. is included here as 10/11 hospital sites were within the UK.
Figure 3
Figure 3
Relative risk of mortality in hospitalized adults with nosocomial and community-acquired COVID-19. Forest plot assessing the relative risk (RR) and 95% confidence interval (95% CI) of mortality in adults hospitalized with community-acquired and probable nosocomial COVID-19, according to the study definitions. The size of each box is proportional to the size of the individual hospital site (A-N), with the error bars representing the 95% CIs. The diamond represents the pooled average across studies, based on a random effects (RE) model. I2: heterogeneity variance, calculated using restricted effects maximum likelihood (REML).
Figure 4
Figure 4
Relative risk of critical care admission in hospitalized adults with nosocomial and community-acquired COVID-19. Forest plot assessing the relative risk (RR) and 95% confidence interval (95% CI) of critical care admission in adults hospitalized with community-acquired and probable nosocomial COVID-19. The size of each box is proportional to the size of the individual hospital site (A-N), with the error bars representing the 95% CIs. The diamond represents the pooled average across studies, based on a random effects (RE) model. I2: heterogeneity variance, calculated using restricted effects maximum likelihood (REML).
Figure 5
Figure 5
Funnel plot. Funnel plot with pseudo 95% confidence limits showing the distribution of relative risk of mortality across individual studies. Egger’s test, p = 0.51.
See this image and copyright information in PMC

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