Coronavirus Disease 2019 (COVID-19) has caused high mortality and morbidity worldwide since it appeared in December 2019 (1, 2). The severity and progression of COVID-19 vary among individuals and appear to be linked to the role of the host immunity and adequate antibody (Ab) responses (3–5). While data suggests that after natural infection of SARS-CoV-2, the development of anti-spike protein immunoglobulin M (IgM) and immunoglobulin G (IgG) occurs at approximately 10 days after the onset of symptoms, (6–9) the longevity of Abs mediated by adaptive immunity to SARS-CoV-2 has not been fully determined (10–13).

Ab targeting viral surface glycoproteins mediate humoral immune responses to SARS-CoV-2 (14). The 180 kDa spike glycoprotein is considered an important antigenic determinant capable of inducing a protective immune response (15). The S1 subunit is the receptor-binding domain (RBD), which mediates a viral binding to the functional ACE2 receptors on susceptible cells and is the main target for SARS-CoV-2 neutralizing Ab (14). The Ab against the RBD region has been considered a reliable indicator of recent severe SARS-CoV-2 infection, future seroprotection, and vaccine response.

Several studies have described higher rates of COVID-19-related diagnosis, hospitalizations, and mortality in people with HIV (PWH) compared to those without HIV (HIV-) (16, 17). While root causes of poor outcomes remain uncertain, persistent state of immune activation and inflammation have been suggested as plausible reasons for worse outcomes in PWH (18–21). Furthermore, recent studies have found that SARS-CoV-2-coinfected PWH are almost 10 years younger than those who are HIV- despite having similar underlying medical conditions (21, 22). The difference may be related to the fact that HIV accentuates the biological age of those infected individuals, which could have important health implications when establishing a high-risk threshold for age for the population (21, 23).

Understanding the host immune response and duration of Ab levels after SARS-CoV-2 is crucial for planning for healthcare and public health interventions. Thus, in this study, we aimed to evaluate the Ab response to SARS-CoV-2 of PWH and those who are HIV- and its association with age.

This study compared the magnitude and longevity of SARS-CoV-2 Ab responses in a group of virologically suppressed PWH and HIV- controls after mild COVID-19. It also evaluated the relationship of SARS-CoV-2 Ab responses and age by HIV status. While it was hypothesized that an impaired immune response would result in lower and shorter term Ab responses in PWH, our results show that PWH can develop appropriate Ab responses to SARS-CoV-2.

These results support the growing literature on similar magnitude and durability of Ab titers in individuals with and without HIV after natural infections (29–31). In addition, similar early and acute Ab responses and time to peak Ab titer of anti-SARS-CoV-2 IgM and IgG have been observed between these groups, which are considered a marker of increased protection (29). Our findings, however, contrast with those of Spinelli et al. (34), as our results indicate that the level of Ab responses to SARS-CoV2 infection in PWH is comparable to those without HIV infection. These discrepancies may be related to the different characteristics of the study participants, such as the lower number of comorbidities, higher CD4+ T-cell count, and an HIV viral suppression seen in our participants. These findings could shed light on the understanding and management of HIV in the era of COVID-19 and highlight the importance of ensuring appropriate ART adherence during the pandemic.

Previous literature has found impaired immune responses occurring in the setting of HIV and aging (32–34). Immune responses affected by aging can lead to reduced or delayed Ab responses through cell-intrinsic defects, functional defects of T-cells, and antigen uptake, resulting in worse outcomes compared to those uninfected (35). While it is thought that HIV infection adds several years to the chronological age of those infected (21, 23) even with a higher median age of 19 years, PWH in this study had comparable Ab responses to the younger HIV-individuals. On the other hand, the HIV- group was younger than the HIV infected group, which could partially explain the lack of association between age and SARS-CoV-2 Ab titers. Recent data, however, showed that participants aged 19–30 years had significantly lower IgG levels than those aged 50–80 but not those aged 81 or older (36).

Among the general population, older age and comorbidities, including immunosuppression, are linked to severe outcomes and death due to SARS-CoV-2 (37). The limited data on PWH coinfected with SARS-CoV-2 suggest that PWH with adequate immune recovery and viral suppression have similar or better clinical course than those without HIV infection when developing COVID-19 (38, 39). For instance, a case-series report denoted similar clinical and immunological data on virally suppressed PWH hospitalized patients who showed high degrees of both cytokines production and immune activation (40). Despite having a mild presentation, IgG production was elicited in all patients and neutralized the Ab in all but one patient.

Because SARS–CoV-2 infection is associated with a broad spectrum of disease, heterogeneous Ab responses are expected. The SARS-CoV-2 Ab testing has an important role in providing insights about a previous infection, which is important for community surveillance and for determining short-term immunity and protection against reacquiring infection. As many PWHs are likely at high risk of becoming infected with SARS-CoV-2 and severe COVID-19 due to comorbid conditions (41, 42), the development of IgM and IgG Ab against the spike protein could likely indicate protection against reinfections and potential protection after vaccination against SARS-CoV-2. As such, larger and more diverse studies are needed to understand the host immune response and duration of Ab levels after SARS-CoV-2 in the HIV setting.

Our study is limited by the small sample size, a short longitudinal follow-up, and evaluation of patients at different time points after infection based on positive PCR results, which may have resulted in the participant recall bias when describing clinical presentation, and in differences in Ab titers. Due to a lack of data on antibody responses at the time the study was conducted, no a priori power analysis was conducted to determine our sample size. This study did not include participants who received a COVID-19 vaccine, had a history of hospitalization for severe disease or had a low CD4+ T-cell count as most PWH in our community are on an effective ART. This is a neoteric immunological study in co-infection of PWH and SARS-CoV-2, providing insights into short-term immunity and safeguarding against re-infection - critical for designing public health initiatives.

In summary, this study provides initial information about the magnitude and longevity of Ab responses to SARS-CoV-2 among PWH who developed mild COVID-19. Although extended longitudinal follow-ups are needed, results from this study are promising for PWH. Further characterization of these immunological dynamics might predict protection after SARS-CoV-2 vaccination.

The data underlying this article will be shared upon reasonable request to the corresponding author.

The study was approved by the University of Miami Institutional Review Board (IRB# 20200340) and informed consent was obtained prior to study assessments. All procedures were followed in accordance with the ethical standards of the University and with the Helsinki Declaration of 1975, as revised in 2013.

MA and DJ were responsible for the study concept and design. AS, NN, AM, and VJR contributed with the data analyses. All the authors had access to the full data and were responsible for drafting and critical revision of the manuscript for important intellectual content, they were also responsible for the accuracy and integrity of the data analysis, and for data acquisition and interpretation of results.

This study was supported by National Institutes of Health grants to the University of Miami Center for AIDS Research grant [P30A1073961 to MA] and the Center for HIV and Research in Mental Health [P30MH116867 to DJ]. VJR's work on this study was partially supported by a Ford Foundation Fellowship, administered by the National Academies of Science, a PEO Scholar Award from the PEO Sisterhood, and a grant from the NIH [R36MH127838].

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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