Xinxin Zhang,1,* Xiaobo Han,1,2,* Chenglong Li,3,4,* Junchang Cui,1,2 Xin Yuan,5 Jiguang Meng,6,7 Zhihai Han,8 Xinjie Han,1 Wei Chen,8 Junchen Xiong,6,7 Wuxiang Xie,9,10 Lixin Xie1,2 

1College of Pulmonary and Critical Care Medicine, The Eighth Medical Center, Chinese PLA General Hospital, Beijing, People’s Republic of China; 2Chinese PLA Medical School, Beijing, People’s Republic of China; 3National Institute of Health Data Science, Peking University, Beijing, People’s Republic of China; 4Institute of Medical Technology, Health Science Center, Peking University, Beijing, People’s Republic of China; 5Department of Pulmonary and Critical Care Medicine, The Fifth Medical Center, Chinese PLA General Hospital, Beijing, People’s Republic of China; 6Department of Pulmonary and Critical Care Medicine, The Fourth Medical Center of PLA General Hospital, Beijing, People’s Republic of China; 7Naval Clinical College, Anhui Medical University, Hefei, People’s Republic of China; 8Department of Pulmonary and Critical Care Medicine, The Sixth Medical Center of PLA General Hospital, Beijing, People’s Republic of China; 9Peking University Clinical Research Institute, Peking University First Hospital, Beijing, People’s Republic of China; 10Key Laboratory of Epidemiology of Major Diseases (Peking University), Ministry of Education, Beijing, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Wuxiang Xie, Peking University Clinical Research Institute, Peking University First Hospital, Beijing, People’s Republic of China, Email xiewuxiang@hsc.pku.edu.cn Lixin Xie, College of Pulmonary and Critical Care Medicine, The Eighth Medical Center, Chinese PLA General Hospital, Beijing, People’s Republic of China, Email xielx301@126.com

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.

Keywords: COVID-19, in-hospital mortality, immunosuppression, hyperinflammation