PURPOSE: Immunocompromised patients are at increased risk for severe outcomes from COVID-19 due to their altered immune responses, yet their inflammatory profiles and the interplay between immunosuppression remain poorly understood. We aimed to illustrate the inflammation profile and clinical outcomes of hospitalized immunocompromised patients with COVID-19. METHODS: We conducted a retrospective study using a multicenter database and included adult hospitalized patients with Corona virus disease 2019 (COVID-19) in China's late 2022 COVID-19 wave. Crude and adjusted 28- and 60-day mortality was compared between the two groups. Inflammatory phenotypes were evaluated by serum interleukin-6 (IL-6) and C-reactive protein (CRP) level. The interplay between overt inflammation and immunosuppression was analyzed. RESULTS: Among the 4078 included patients, 348 (8.5%) were immunocompromised. Immunocompromised patients had lower crude mortality but higher adjusted mortality at 28-day (hazard ratio [HR] = 1.55
95% CI 1.08 to 2.23) and 60-day (HR = 1.47
95% CI 1.05 to 2.06). Besides, immunocompromised patients had a higher risk of developing hyperinflammation (odd ratio [OR] =1.92
95% CI 1.47 to 2.50, p <
0.001). Moreover, hyperinflammation mediated a major part of the deleterious survival effect of immunosuppression on COVID-19. CONCLUSION: Immunodeficiency not only increases short-term mortality risk but also predisposes patients to hyperinflammation. The complex interplay between immunosuppression, hyperinflammation, and COVID-19 outcomes warrants more detailed profiling of inflammation and immunity in this population.