Effect of host factors and COVID-19 infection on the humoral immune repertoire in treated HIV
Name
166848.2-20230225123204-covered-4fa089109ce452e764bbb8648b44a723.pdf
Description
Published version
Size
2.66 MB
Format
Adobe PDF
Checksum (MD5)
78bb9ff23a41cff907c1f16cd6fe5370
Author(s) • • • • • • • • •
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
Date Issued
February 20, 2023
Journal
JCI Insight
Publisher
American Society for Clinical Investigation
Version
Final published version
Abstract
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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DOI of Published Version
https://doi.org/10.1172/jci.insight.166848