JCI Insight (Mar 2023)

Effect of host factors and COVID-19 infection on the humoral immune repertoire in treated HIV

  • Samuel R. Schnittman,
  • Wonyeong Jung,
  • Kathleen V. Fitch,
  • Markella V. Zanni,
  • Sara McCallum,
  • Jessica Shih-Lu Lee,
  • Sally Shin,
  • Brandon J. Davis,
  • Evelynne S. Fulda,
  • Marissa R. Diggs,
  • Francoise Giguel,
  • Romina Chinchay,
  • Anandi N. Sheth,
  • Carl J. Fichtenbaum,
  • Carlos Malvestutto,
  • Judith A. Aberg,
  • Judith Currier,
  • Douglas A. Lauffenburger,
  • Pamela S. Douglas,
  • Heather J. Ribaudo,
  • Galit Alter,
  • Steven K. Grinspoon

Journal volume & issue
Vol. 8, no. 5

Abstract

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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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