Comorbid illnesses are associated with altered adaptive immune responses to SARS-CoV-2.
2019-nCoV; washington; everett; PRMC
Comorbid medical illnesses, such as obesity and diabetes, are associated with more severe COVID-19, hospitalization, and death. However, the role of the immune system in mediating these clinical outcomes has not been determined. We used multi-parameter flow cytometry and systems serology to comprehensively profile the functions of T cells and antibodies targeting spike, nucleocapsid, and envelope proteins in a convalescent cohort of COVID-19 subjects who were either hospitalized (n=20) or not hospitalized (n=40). To avoid confounding, subjects were matched by age, sex, ethnicity, and date of symptom onset. Surprisingly, we found that the magnitude and functional breadth of virus-specific CD4 T cell and antibody responses were consistently higher among hospitalized subjects, particularly those with medical comorbidities. However, an integrated analysis identified more coordination between polyfunctional CD4 T-cells and antibodies targeting the S1 domain of spike among subjects that were not hospitalized. These data reveal a functionally diverse and coordinated response between T cells and antibodies targeting SARS-CoV-2, which is reduced in the presence of comorbid illnesses that are known risk factors for severe COVID-19.
Yu, Krystle Kq; Fischinger, Stephanie; Smith, Malisa T; Atyeo, Caroline; Cizmeci, Deniz; Wolf, Caitlin R; Layton, Erik D; Logue, Jennifer K; Aguilar, Melissa S; Shuey, Kiel; Loos, Carolin; Yu, Jingyou; Franko, Nicholas M; Choi, Robert Y; Wald, Anna; Barouch, Dan H; Koelle, David M; Lauffenburger, Douglas; Chu, Helen Y; Alter, Galit; and Seshadri, Chetan, "Comorbid illnesses are associated with altered adaptive immune responses to SARS-CoV-2." (2021). Articles, Abstracts, and Reports. 4398.