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Impact of host factors and COVID-19 infection on the humoral immune repertoire in treated HIV
- Schnittman, Samuel R;
- Jung, Wonyeong;
- Fitch, Kathleen V;
- Zanni, Markella V;
- McCallum, Sara;
- Lee, Jessica Shih-Lu;
- Shin, Sally;
- Davis, Brandon J;
- Fulda, Evelynne S;
- Diggs, Marissa R;
- Giguel, Francoise;
- Chinchay, Romina;
- Sheth, Anandi N;
- Fichtenbaum, Carl J;
- Malvestutto, Carlos D;
- Aberg, Judith A;
- Currier, Judith;
- Lauffenburger, Douglas A;
- Douglas, Pamela S;
- Ribaudo, Heather J;
- Alter, Galit;
- Grinspoon, Steven K
- et al.
Published Web Location
https://doi.org/10.1172/jci.insight.166848Abstract
People with HIV (PWH) appear to be at higher risk for suboptimal pathogen responses and for worse COVID-19 outcomes, but the effects of host factors and COVID-19 on the humoral repertoire remain unclear. We assessed the antibody isotype/subclass and Fc-receptor binding Luminex arrays of non-SARS-CoV-2 and SARS-CoV-2 humoral responses among antiretroviral therapy-treated (ART-treated) PWH. Among the entire cohort, COVID-19 infection was associated with higher cytomegalovirus (CMV) responses (vs. the COVID- cohort ), potentially signifying increased susceptibility or a consequence of persistent inflammation. Among the COVID+ participants, (a) higher BMI was associated with a striking amplification of SARS-CoV-2 responses, suggesting exaggerated inflammatory responses, and (b) lower nadir CD4 was associated with higher SARS-CoV-2 IgM and FcγRIIB binding capacity, indicating poorly functioning extrafollicular and inhibitory responses. Among the COVID-19- participants, female sex, older age, and lower nadir CD4 were associated with unique repertoire shifts. In this first comprehensive assessment of the humoral repertoire in a global cohort of PWH, we identify distinct SARS-CoV-2-specific humoral immune profiles among PWH with obesity or lower nadir CD4+ T cell count, underlining plausible mechanisms associated with worse COVID-19-related outcomes in this setting. Host factors associated with the humoral repertoire in the COVID-19- cohort enhance our understanding of these important shifts among PWH.
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