Increased in-hospital mortality in immunocompromised individuals hospitalized with COVID-19 during the global pandemic: a multinational cohort study in the EuCARE Project
File(s)
Published version (corrected proof)
Author(s)
Type
Journal Article
Abstract
Background
Although coronavirus disease 2019 (COVID-19) is no longer a public health emergency, it remains the most prevalent circulating infectious-like illness in Europe. Whether immunocompromising conditions (ICCs) still carry increased mortality risk during the Omicron era is unclear.
Methods
We conducted a cohort study across EuCARE sites in 8 countries among adults admitted to hospital with COVID-19 between 2020 and 2023. ICCs and COVID-19 pneumonia at hospitalization were defined using clinical information and ICD-10 codes. Logistic regression and counterfactual mediation analysis was used to compare 28-day in-hospital mortality risk associated with ICCs using COVID-19 pneumonia and vaccination at hospital entry as intermediates. Proportion of the total effect of ICCs mediated and the controlled direct effects (CDEs) were calculated. We also formally tested for interaction between SARS-CoV-2 variants and ICCs for mortality risk.
Results
A total of 42 488 individuals were included, of whom 1675 (3.9%) had an ICC. Fifty-five percent were male, and the median age was 67 (IQR, 52–79) years. Overall, 4344 (10.2%) individuals died in hospital. ICCs were associated with increased mortality (OR, 1.49 [95% CI, 1.25–1.79]), with no evidence for an attenuation during the Omicron phase (P value for interaction = .60). Mediation analyses showed that the total effect of ICCs was mediated by vaccination but only weakly by pneumonia. With Omicron, the excess mortality associated with ICC was higher under the scenario that everyone in the cohort was to develop COVID-19 pneumonia (CDE, 1.22 [95% CI, .09–1.65]).
Conclusions
ICC remains a significant risk factor for in-hospital death, even during the Omicron era, particularly if the infection led to the development of pneumonia.
Although coronavirus disease 2019 (COVID-19) is no longer a public health emergency, it remains the most prevalent circulating infectious-like illness in Europe. Whether immunocompromising conditions (ICCs) still carry increased mortality risk during the Omicron era is unclear.
Methods
We conducted a cohort study across EuCARE sites in 8 countries among adults admitted to hospital with COVID-19 between 2020 and 2023. ICCs and COVID-19 pneumonia at hospitalization were defined using clinical information and ICD-10 codes. Logistic regression and counterfactual mediation analysis was used to compare 28-day in-hospital mortality risk associated with ICCs using COVID-19 pneumonia and vaccination at hospital entry as intermediates. Proportion of the total effect of ICCs mediated and the controlled direct effects (CDEs) were calculated. We also formally tested for interaction between SARS-CoV-2 variants and ICCs for mortality risk.
Results
A total of 42 488 individuals were included, of whom 1675 (3.9%) had an ICC. Fifty-five percent were male, and the median age was 67 (IQR, 52–79) years. Overall, 4344 (10.2%) individuals died in hospital. ICCs were associated with increased mortality (OR, 1.49 [95% CI, 1.25–1.79]), with no evidence for an attenuation during the Omicron phase (P value for interaction = .60). Mediation analyses showed that the total effect of ICCs was mediated by vaccination but only weakly by pneumonia. With Omicron, the excess mortality associated with ICC was higher under the scenario that everyone in the cohort was to develop COVID-19 pneumonia (CDE, 1.22 [95% CI, .09–1.65]).
Conclusions
ICC remains a significant risk factor for in-hospital death, even during the Omicron era, particularly if the infection led to the development of pneumonia.
Date Issued
2026-05-08
Date Acceptance
2026-05-04
Citation
The Journal of Infectious Diseases, 2026
ISSN
0022-1899
Publisher
Oxford University Press (OUP)
Journal / Book Title
The Journal of Infectious Diseases
Copyright Statement
© The Author(s) 2026. Published by Oxford University Press on behalf of Infectious Diseases Society of America. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/42100898
PII: 8672816
Subjects
COVID-19
Immunocompromising conditions
SARS-CoV-2
in-hospital-mortality
Publication Status
Published online
Coverage Spatial
United States
Article Number
jiag254
Date Publish Online
2026-05-08