HIV coinfection significantly impacts B cell response to SARS-CoV-2

By Shanet Susan AlexJun 17 2022Reviewed by Emily Henderson, B.Sc.

In recent research posted to the bioRxiv* preprint server, investigators confirmed that human immunodeficiency virus (HIV) co-infection alters B cell reaction in coronavirus disease 2019 (COVID-19).

Study: HIV skews the SARS-CoV-2 B cell response toward an extrafollicular maturation pathway. Image Credit: Kateryna Kon / Shutterstock

This news article was a review of a preliminary scientific report that had not undergone peer-review at the time of publication. Since its initial publication, the scientific report has now been peer reviewed and accepted for publication in a Scientific Journal. Links to the preliminary and peer-reviewed reports are available in the Sources section at the bottom of this article. View Sources

Background

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to challenge global health, specifically with the emergence of novel, more infectious variants immune to vaccine-elicited neutralizing antibodies. While COVID-19 vaccination does not prevent viral transmission, it prevents severe illness by evoking neutralizing antibodies against the SARS-CoV-2 spike (S) protein. Old age, diabetes, preexisting heart/lung illness, and immune abnormalities linked with HIV infection are all risk factors for severe COVID-19, particularly in nonvaccinated individuals.

HIV infection affects memory B cell development and the antibody reaction to SARS-CoV-2 vaccination and infection by disrupting the B cell compartment. Evaluating the B cell response to COVID-19 in people living with HIV (PLWH) might explain why certain HIV-1 co-infections have higher morbidity, lower vaccination effectiveness, decreased viral clearance, and intra-host evolution of SARS-CoV-2.

About the study

In the present research, the scientists evaluated B cell reactions to SARS-CoV-2 in HIV-negative (HIV-ve) subjects and PLWH in a Durban, South Africa-based cohort. The work used comprehensive flow cytometry profiling of longitudinal samples with indicators of B cell homing, maturation, and regulatory traits from the initial COVID-19 pandemic wave during July 2020.

The team investigated the impact of HIV on the B cell reaction to COVID-19 utilizing B cell baits and an extensive B cell phenotyping technique to discover SARS-CoV-2-specific B cells. Following the COVID-19-positive diagnosis, at weekly intervals, they procured blood samples from HIV-negative subjects and PLWH.

In addition, this study comprised 70 SARS-CoV-2-positive subjects (confirmed by serology and quantitative polymerase chain reaction (qPCR)) and 10 COVID-19-negative control persons. COVID-19-positive participants were followed up weekly for five follow-up timestamps. Moreover, control subjects were enrolled at a single timestamp and were confirmed as COVID-19-negative by serology and qPCR.

Results and discussions

The study results indicated that of the COVID-19 patients, five, i.e., 18%, had measurable HIV in their plasma, and 28, i.e., 40%, were PLWH. Furthermore, the control volunteers consisted of two PLWH individuals. 

Regardless of variances in classical B cell characteristics preceding antibody-secreting cell (ASC) maturation, the authors discovered that PLWH developed a comparable ASC response to HIV-ve subjects against SARS-CoV-2 infection. In both PLWH and HIV-ve individuals, ASC response was linked to COVID-19 severity, yet the impact appears to be stronger in HIV-ve subjects.

The study data showed that the synchronized B cell reaction to SARS-CoV-2 infection varied considerably among PLWH and HIV-ve individuals. The present unbiased investigations persistently indicated that the B cell reaction to SARS-CoV-2 in PLWH was unbalanced, with a decrease in ASC subgroups, class switching, and germinal center (GC) homing markers (CD62 and CXCR5), as well as an expansion in B cell characteristics linked with EF maturation. The findings indicated that simultaneous HIV infection might lead to a decrease in GC class switching, homing, and memory development after COVID-19, aggravated in people having viremic HIV.

In detail, with enhanced PD-L1 protein expression and reduced T follicular helper (Tfh) frequency, memory B cells in PLWH showed signs of impaired homing ability, GC function, and class-switching reactions. Similarly, extrafollicular (EF) action was elevated, with dynamic alterations in the activated double negative (DN2) and stimulated naive B cells linked with anti-receptor-binding domain (RBD) concentrations in these subjects. An increased SARS-CoV-2-specific EF reaction in PLWH was verified employing viral RBD- and S-bait proteins. 

Irrespective of the identical SARS-CoV-2 infection severity, these patterns were the strongest in volunteers with uncontrolled HIV, suggesting that HIV is to blame for these alterations. Although EF B cell reactions were quick, they produce lesser affinity antibodies, have a shorter long-standing memory, and a weaker ability to adapt to novel SARS-CoV-2 variants.

Conclusions

According to the researchers, the current research proves that COVID-19 severity was connected to the distorting of B cell traits and shows for the first time that this distorting was altered by simultaneous HIV infection.

Collectively, utilizing longitudinal samples from the first SARS-CoV-2 wave in South Africa, the study demonstrated that HIV co-infection had a massive effect on the B cell reaction to SARS-CoV-2. In addition, the investigators noted that the B cell reaction to SARS-CoV-2 infection in PLWH was markedly distinct in the present group of individuals with primarily mild to moderate COVID-19 with lower GC function and a contrasted rise in EF activity. These findings indicate that the B cell reaction in PLWH was oriented toward the EF pathway rather than GC maturation.

Additionally, the team pointed out that it was necessary to evaluate the impact of HIV infection on COVID-19 immunity, especially in light of new SARS-CoV-2 variants. Besides, understanding the influence of COVID-19 vaccination on the B cell memory compartment will also be critical.

This news article was a review of a preliminary scientific report that had not undergone peer-review at the time of publication. Since its initial publication, the scientific report has now been peer reviewed and accepted for publication in a Scientific Journal. Links to the preliminary and peer-reviewed reports are available in the Sources section at the bottom of this article. View Sources