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

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

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Abstract

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

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  1. Version published to 10.3389/fimmu.2021.744696
  2. ScreenIT

    SciScore for 10.1101/2021.07.10.21260306: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Ethicsnot detected.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    2.2 Search strategy to identify studies: 2.2.1 Database search strings: Ovid Medline, Embase, and the Social Policy & Practice databases and MedRvix.org were searched from 1/1/2020 to 9/2/2021.
    Embase
    suggested: (EMBASE, RRID:SCR_001650)
    We conducted the following pre-specified sensitivity analyses: Additional data visualization was performed in R using the ggplot2 package.
    ggplot2
    suggested: (ggplot2, RRID:SCR_014601)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    Our study also has limitations, including its focus on hospitalised patients during the first wave of the pandemic. This is likely to introduce both selection and reporting bias, as during this period limited capacity meant RT-PCR testing was initially restricted to symptomatic individuals in the community (40,41). Estimates of age-stratified infection fatality rates in the adult UK general population during the first wave ranged from 0.03% (20-29 years) to 7.8% (over 80 years) (58), far lower than the inpatient comparator mortality rate used in our analysis. By contrast, individuals admitted during nosocomial outbreaks were more likely to be subject to screening, resulting in sampling of individuals across the true spectrum of disease severities (34,44), including earlier in their disease course. Our risk of bias assessment therefore focused on study inclusion and adequate follow-up as essential domains, to account for unequal disease progression at study entry between groups. Taken together, this considerably strengthens evidence for the statement: “nosocomial COVID-19 was associated with a greater risk of mortality, compared to individuals with community-acquired COVID-19 in the general adult population during the first wave of the COVID-19 pandemic”. Due to limitations in the summary data available, we were unable to perform planned meta-regression for factors such as age, gender, frailty, ethnicity or deprivation. Similarly, as studies typically reported all-cause mortal...

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    Results from scite Reference Check: We found no unreliable references.

    About SciScore

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  3. Version published to 10.1101/2021.07.10.21260306v1 on medRxiv