New insights into how patient factors and COVID-19 infection affect antibody responses in people with HIV

The study, which is published in JCI Insight, involved data from the global Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE), a large ongoing cardiovascular prevention trial testing the effects of statins in people with HIV on antiretroviral therapy that has collected information related to COVID-19 diagnoses, symptoms, and adverse events every four months starting in April 2020. (Participants vaccinated against SARS-CoV-2 were excluded.) Investigators also used a novel platform to assess the various types of non-SARS-CoV-2 and SARS-CoV-2 antibodies present in 2,464 participants' blood.

"We asked whether COVID-19 infection impacted the antibody response to non-SARS-CoV-2 proteins -- in this case proteins from CMV and EBV. We also asked what is the effect of host factors on SARS-CoV-2 antibody responses among COVID-positive participants," says senior author Steven Grinspoon, MD, chief of the MGH Metabolism Unit and director of the Nutrition Obesity Research Center at Harvard.

In the overall analysis, COVID-19 infection was associated with higher CMV and EBV antibody responses. Among COVID-positive participants, higher body mass index was associated with an amplified SARS-CoV-2 response, and lower nadir CD4+ T-cell count (a person's lowest CD4+ T-cell count) was associated with an ineffective or poorly functional antibody response to SARS-CoV-2.

"The higher EBV and CMV responses in those with COVID-19 may signify increased susceptibility to or be a consequence of persistent inflammation, and the abnormal repertoire seen among those with obesity could portend an increased inflammatory response in this group," says Grinspoon. "The connection to nadir CD4 and increased immune response to COVID was interesting as nadir CD4 is a marker of immune function and suggests a key linkage between HIV-related immune function and abnormal COVID immune responses."

As the REPRIEVE trial continues and generates data related to the effects of statins on the acquisition and severity of COVID-19 and long COVID in people with HIV, Grinspoon and his colleagues anticipate that their novel antibody platform may provide new mechanistic insights into the short- and long-term complications of SARS-CoV-2 infection.

Co-authors include 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, and Galit Alter.

This study was supported by the National Institutes of Health, as well as Kowa Pharmaceuticals, Gilead Sciences, and ViiV Healthcare.