Lower SARS-CoV-2-Specific Humoral Immunity in People Living With HIV-1 Recovered From Symptomatic Non-Hospitalized COVID-19

Abstract

Background: Compared to uninfected individuals, people living with HIV-1 (PLWH) may respond less well to vaccines owing to more rapid antibody decline following routine immunization and elevated baseline chronic inflammation. Conflicting reports have emerged on the ability of PLWH to maintain humoral protection against SARS-CoV-2 co-infection into the convalescent period. It is unknown if peak COVID-19 severity, in addition to HIV-1 infection status, associates with the quality of humoral immunity following recovery.

Methods: HVTN 405 is a cross-sectional observational cohort study that enrolled adults (median age <50) from the US and Peru diagnosed with SARS-CoV-2 infection 1-8 weeks post-recovery if symptomatic or 2-10 weeks post-diagnosis if asymptomatic between January to June of 2020. We analysed serum SARS-CoV-2-specific antibodies for response rate, binding magnitudes, ACE2 receptor blocking and antibody dependent cellular phagocytosis in a subset of the study population (N=373 participants including 43 PLWH).  Participants were stratified by HIV-1 infection status and peak COVID-19 symptom severity.

Findings: SARS-CoV-2 total IgG, IgG1, IgG3, and IgA magnitudes trended lower in PLWH, with 6P spike-specific IgG1 significantly lower (geometric mean ratio (GMR) 0.63, p=0.05) compared to HIV-1-uninfected people. When stratified by peak COVID-19 symptom severity, PLWH demonstrated significantly decreased response magnitudes among symptomatic outpatient cases of IgG1 to RBD (GMR 0.41, p =0.005), Nucleoprotein (GMR 0.38, p=0.004), N-terminal domain (GMR 0.23, p<0.001), and 6P spike (GMR 0.25, p<0.001), and total IgG to RBD (GMR 0.43, p=0.006) and 2P spike (GMR 0.41, p=0.012). ACE2 receptor blocking did not differ by HIV-1 serostatus or by peak COVID -19 symptom severity. ADCP response rates were decreased among PLWH recovered from COVID-19 requiring hospitalization (76 vs 95%, OR 0.23, p=0.039), and response magnitudes trended lower for PLWH recovered from symptomatic outpatient COVID-19 compared to HIV-1-uninfected participants.

Interpretation: PLWH on anti-retroviral therapy (ART) maintain a robust anti-SARS-CoV-2 humoral immune response into the convalescent period. Symptomatic outpatient PLWH had decreased SARS-CoV-2 antibody magnitudes and ADCP scores, and may require special consideration for vaccination and booster shots.

Funding Information: This work was supported by the National Institutes of Health NIAID funded HIV Vaccine Trials Network (HVTN /CoVPN) UM1 AI068618 (Lab); UM1 AI068635 (SDMC); UM1 AI068614 (LOC); UM1 AI148452 (UPenn HIV CTU) and UPenn CFAR (P30 AI045008) and the Duke Center for AIDS Research (P30 AI064518), T32 AI141342 (Advanced Immunobiology Training Program for Surgeons), and the Bill & Melinda Gates Foundation (Global Health Vaccine Accelerator Platform (GHVAP) Antibody Dynamics INV008612).

Declaration of Interests: We declare no competing interests.

Ethics Approval Statement: Institutional Review Board (IRB) approval was granted by a Central IRB and, as applicable, by individual clinical research sites’ IRBs. All participants provided written informed consent.

Keywords: HIV-1, PLWH, People Living with HIV, SARS-CoV-2, COVID-19, humoral immunity, antibody, antibody isotype, antibody subclass, ACE-2 blocking, ADCP, antibody dependent phagocytosis, Multiplex assay, Meso Scale Discovery, IgG, IgG1, IgG3, IgA, CoVPN