key: cord-0930830-wl3n1q6d authors: Martín-Vicente, María; Berenguer, Juan; Muñoz-Gómez, María José; Díez, Cristina; Micán, Rafael; Pérez-Elías, María Jesús; García-Fraile, Lucio Jesús; Peraire, Joaquin; Suárez-García, Inés; Jiménez-Sousa, María Ángeles; Fernández-Rodríguez, Amanda; Vázquez, Mónica; Ryan, Pablo; González-García, Juan; Jarrín, Inmaculada; Mas, Vicente; Martínez, Isidoro; Resino, Salvador title: Similar humoral immune responses against the SARS-CoV-2 spike protein in HIV and non-HIV individuals after COVID-19: Anti-SARS-CoV-2 S antibodies in PWH date: 2021-11-06 journal: J Infect DOI: 10.1016/j.jinf.2021.11.002 sha: 68c6ee055ef07c698922247baa0e8557bbd5840d doc_id: 930830 cord_uid: wl3n1q6d nan (3). These antibodies against the SARS-CoV-2 S protein block the virus union to its cellular receptor, the angiotensin-converting enzyme 2 (ACE2) receptor (2) . Thus, it is critical to determine whether the anti-SARS-CoV-2 neutralizing antibody response is impaired in PWH (2) . This study aimed to characterize plasma antibodies against SARS-CoV-2 S protein in PWH and CTRLs recovered from COVID-19. We performed a cross-sectional study in 91 PWH from the Cohort of the Spanish HIV Research Network (CoRIS) seropositive for SARS-CoV-2 and with plasma specimens collected from April 1, 2020, to September 30, 2020 (4). We also included HIV-uninfected CTRLs seropositive for SARS-CoV-2 with plasma specimens stored in the National Centre for The study population included 91 PWH -fully described elsewhere (4) -and 21 CTRLs, whose characteristics are shown in Table 1 . Concerning COVID-19, 92.3% PWH had asymptomatic or mild COVID-19 disease, 7.7% were hospitalized, and the median time from symptoms to plasma collection was 11 weeks. CTRLs had similar characteristics to PWH, except for gender. No significant differences were found between groups in plasma levels of different classes of immunoglobulins against SARS-CoV-2 S protein [IgG (p=0.414; Figure 1A) , IgM (p=0.862; Figure 1B) , and IgA (p=0.134; Figure 1C )], and percentages of inhibition of ACE2 binding to the S protein (p=0.237; Figure 1D ). Adjusted regression analysis also found no significant differences (Supplemental Table 1 ). Furthermore, we found solid and similar correlations between total plasma antibody titers against SARS-CoV-2 S protein and the percentage of inhibition of ACE2 binding to the S protein in CTRLs (r=0.580; p=0.005; Figure 1E ) and PWH (r=0.548; p<0.001; Figure 1F ). No differences were found between the regression slopes of the two study groups (p=0.849). Several studies have reported that PWH usually shows poor antibody response to other viruses or viral vaccines (5-7), raising concerns about whether they can mount an adequate humoral response against SARS-CoV-2. This issue is relevant since high antibody titers against the SARS-CoV-2 S protein correlate with virus neutralization and protection (3). Our study shows that PWH and CTRLs who recovered from COVID-19 display a similar antibody response against the S protein. To detect neutralizing antibodies, we used a stabilized trimeric S protein in its native pre-fusion conformation. The suitability of our assay was confirmed by the strong correlation between the antibody titers and their capacity to inhibit the interaction S protein-ACE2 receptor. Our data agree with recently published results showing comparable anti-SARS-CoV-2 neutralizing antibody levels between PWH under effective antiretroviral therapy (ART) and HIV-uninfected individuals (8, 9) . Succesful HIV suppression seems to be crucial for developing an adequate humoral immune response. In our study, almost all HIV patients analyzed were on ART, with good clinical, virological, and immunological control, which may have contributed to similar anti-SARS-CoV-2 antibody titers between PWH and CTRLs. We analyzed the antibody titers against the SARS-CoV-2 S protein and percentages of inhibition of ACE2 binding to the S protein according to CD4 + strata (<350, 350-500, >500 cells/mm 3 ), and we did not find significant differences (data not shown). In contrast, lower neutralizing antibody titers against SARS-CoV-2 were found in PWH than in HIV-uninfected individuals recovering from COVID-19 by Spinelli et al. (10) , although its sample size was three times lower than in our study. Differences in the characteristics of the study cohorts (sample size, ethnicity, age, sex, COVID-19 severity, percentage of people with unsuppressed viral loads, among others), study design, or assays for antibody characterization may explain these conflicting results. In conclusion, no differences in quantitative and qualitative SARS-CoV-2-specific immune humoral response were found between well-controlled PWH and CRTLs after recovery from COVID-19. This finding suggests that PWH are not an at-risk population for this infection and are potentially good vaccination responders. Comparison of outcomes in HIV-positive and HIV-negative patients with COVID-19 Pubmed Central PMCID: PMC8075775 consulting honoraria or research grants, or both, from Gilead Sciences Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection Prevalence and factors associated with SARS-CoV-2 seropositivity in the Spanish HIV Research Network Cohort Undetectable plasma HIV RNA load predicts success after hepatitis B vaccination in HIVinfected persons HIV infection Worsens Age-Associated Defects in Antibody Responses to Influenza Vaccine Long-term immune responses to vaccination in HIV-infected patients: a systematic review and meta-analysis Characterization of humoral and SARS-CoV-2 specific T cell responses in people living with HIV. Res Sq Similar antibody responses against SARS-CoV-2 in HIV uninfected and infected individuals on antiretroviral therapy during the first South African infection wave IgG concentration and pseudovirus neutralising antibody titres after infection, compared by HIV status: a matched case-control observational study Pubmed Central PMCID: PMC8084354 National Institutes of Health during conduct of the study. DVG reports personal fees from Gilead Sciences outside the submitted work. All other authors declare no competing interests We are indebted to all the patients who participated in this research. We want to acknowledge the patients in this study for their participation and the Spanish HIV HGM Not applicable. The datasets used and analyzed during the current study are available from the corresponding authors upon reasonable request. The authors declare that they have no competing interests. This study was supported by grants from Instituto de Salud Carlos III (ISCII; grant numbers COV20/00108 and COV20/1144). The study was also funded by the Spanish AIDS Research