Risk of Severe Outcomes From COVID-19 in Immunocompromised People During the Omicron Era: A Systematic Review and Meta-Analysis

Purpose: COVID-19 imposes a high burden on people with immunocompromising/immunosuppressive (IC/IS) conditions. This is the first large-scale, comprehensive meta-analysis encompassing major IC/IS categories to assess the risks of severe outcomes from COVID-19 in people with IC/IS conditions during the Omicron era—the period dominated by the most recent major COVID-19 variant. Methods: A systematic search of Embase, MEDLINE, PubMed, Europe PMC, Latin American and Caribbean Health Sciences Literature, Cochrane COVID-19 Study Register, and WHO COVID-19 database was performed to identify studies published between January 1, 2022, and March 13, 2024. Studies included people (all ages) with at least one of the following conditions: unspecified IC/IS, transplant, malignancy, autoimmune diseases, liver diseases, chronic or end-stage kidney disease, and advanced/untreated HIV. Studies were synthesized quantitatively using random-effects models. Evaluated outcomes were risks of death, hospitalization, intensive care unit (ICU) admission, and any combination of these outcomes. Findings: Seventy-two studies were included, of which 66 were included in the meta-analysis. Minimum numbers of participants per IC/IS condition ranged from 12,634 to 3,287,816. Of all meta-analyzed IC/IS conditions, transplant recipients had the highest risk of death (pooled relative risk [RR], 6.78; 95% CI: 4.41–10.43; P < 0.001), hospitalization (RR, 6.75; 95% CI 3.41–13.37; P < 0.001), and combined outcomes (RR, 8.65; 95% CI 4.01–18.65; P < 0.001), while participants in the unspecified IC/IS group had the highest risk of ICU admission (RR, 3.38; 95% CI 2.37–4.83; P < 0.001) compared with participants without the respective IC/IS conditions or general population. Implications: In the Omicron era, people with IC/IS conditions have a substantially higher risk of death and hospitalization from COVID-19.