Increased in-hospital mortality in immunocompromised individuals hospitalized with COVID-19 during the global pandemic, a multinational cohort study in the EuCARE project

BACKGROUND: Although 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 2020-2023. 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. FINDINGS: 42,488 individuals were included, of which 1,675 (3.9%) had an ICC. 55% were male, median (IQR) age was 67 (52, 79) years. Overall, 4,344 (10.2%) individuals died in hospital. ICCs were associated with increased mortality, OR = 1.49 (1.25, 1.79) with no evidence for an attenuation during the Omicron phase (p-interaction=0.60). 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 (0.09, 1.65)]. INTERPRETATION: 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.