COVID-19 Infection Linked to Higher Cytomegalovirus Response in People With HIV Receiving ART


Body mass index and nadir CD4 count were major factors in SARS-CoV-2 humoral immune repertoire among people with HIV.

Among people living with HIV (PLWH), those with COVID-19 had higher cytomegalovirus (CMV) responses compared with those without COVID-19, according to a study published in JCI Insight.

This suggests potentially increased susceptibility or a consequence of persistent inflammation, the authors said.

To come to these findings, they used data from the REPRIEVE trial, with the final study cohort including 2464 REPRIEVE participants, of whom 283 had COVID-19 infection and 2181 did not. Antibody positivity was prespecified based on a SARS-CoV-2 receptor-binding domain (RBD) IgG and/or IgA more than 5 SD above plate-specific negative controls using the ELISA assay. Of the PLWH with COVID-19 infection, 271 had a positive RBD IgG, 21 had a positive RBD IgA, and 9 were positive for both.

The median age was 53 years, 35% of participants were women, and 68% were non-White. The median CD4 T cell count was 649 cells/mm3, but half had a nadir CD4 count less than 200 cells/mm3. All participants were receiving antiretroviral therapy (ART), with 53% being on ART for more than 10 years and 46% being on an integrase strand transfer inhibitor (INSTI)–based regimen. Almost all participants were virally suppressed with a CD4 count less than 400 copies/mL.

Among PLWH with COVID-19 infection, higher body mass index (BMI) was associated with a substantial amplification of SARS-CoV-2 response, which the authors said suggests exaggerated inflammatory responses in these individuals. Additionally, lower nadir CD4 count was associated with higher SARS-CoV-2 IgM and FcγRIIB binding capacity, which indicates poorly functioning extrafollicular and inhibitory responses.

“The observation that SARS-CoV-2–specific IgG4 and FcRIIB binding capacity were not broadly higher in those with higher BMIs and tended to reflect inhibitory or regulatory responses suggests that this BMI-associated humoral profile may contribute to a pathologic response,” the authors said.

Among PLWH without COVID-19, the authors found that female sex, older age, and lower nadir CD4 count were associated with unique SARS-CoV-2 humoral immune 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,” the authors said. “Host factors associated with the humoral repertoire in the COVID-19– cohort enhance our understanding of these important shifts among PWH.”

These findings among PLWH without COVID-19 were consistent with past observations that systemic inflammation from proinflammatory cytokines like IL-6 may stimulate higher antibody levels or types of antibody responses, but also greater decays in those responses after antigen exposure.


Schnittman SR, Jung W, Fitch KV, et al. Effect of host factors and COVID-19 infection on the humoral immune repertoire in treated HIV. JCI Insight. 2023;8(5):e166848. doi:10.1172/jci.insight.166848

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