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


Frontiers in Immunology

Contributing to research themes:

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.

Author list:


  1. Immunodeficiency Centre for Wales, University Hospital for Wales, Cardiff, United Kingdom,

  2. Henry Wellcome Building, Division of Infection & Immunity, School of Medicine, Cardiff University, Cardiff, United Kingdom,

  3. Department Respiratory Sciences, College of Life Sciences, University of Leicester, Leicester, United Kingdom,

  4. Institute for Lung Health, National Institute for Health Research (NIHR) Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, United Kingdom,

  5. Department of Global Health and Infection, Brighton and Sussex Medical School, University of Sussex, Brighton, United Kingdom,

  6. Department of Microbiology and Infection, Royal Sussex County Hospital, Brighton, United Kingdom,

  7. Department of Anaesthetics, University Hospital for Wales, Cardiff, United Kingdom, 

  8. Department of Neonatology, University Hospitals of Leicester National Health Service (NHS) Trust, Leicestershire, United Kingdom,

  9. Department of Respiratory Medicine, Cardiff and Vale University Health Board, Cardiff, United Kingdom,

  10. Respiratory Health Implementation Group, Swansea University, Swansea, United Kingdom,

  11. Systems Immunity Research Institute, School of Medicine, Cardiff University, Cardiff, United Kingdom,

  12. Division of Population Medicine, School of Medicine, Cardiff University, Cardiff, United Kingdom


Mark J. Ponsford1,2† , Tom J. C. Ward3,4† , Simon M. Stoneham5,6, Clare M. Dallimore7 , Davina Sham8 , Khalid Osman9 , Simon M. Barry 9,10, Stephen Jolles 1 , Ian R. Humphreys 2,11 and Daniel Farewell12

† Contributed equally