Characterization of SARS-CoV-2-specific responses in people living with HIV

Background: There is an urgent need to understand the nature of immune responses mounted against SARS-CoV-2, in order to better inform riskmitigation and vaccine strategies for people living with HIV (PLWH). Although not all PLWH are considered immunosuppressed, residual cellular immunodeficiency could influence COVID-19 disease severity and the evolution and durability of protective immunity. Information on the breadth, magnitude and longevity of SARS-CoV-2 specific responses in PLWH recovering from COVID-19 disease is currently lacking. In this study, we performed an integrated cross-sectional analysis of different branches of adaptive immunity to SARS-CoV-2 in PLWH and HIV negative donors in the convalescent phase of predominately mild COVID-19 disease. Methods: A total of n=47 HIV positive, controlled on ART, and n=35 HIV negative subjects were recruited at a median of 158 and 146 days post symptom onset respectively. SARS-CoV-2 antibodies against Spike (S1) and Nucleoprotein (N) were measured in serum by a Semiquantitative ELISA. A serum neutralisation assay with pseudotyped SARS-CoV-2 was performed to calculate the 50% inhibitory serum dilution (ID50). SARS-CoV-2 specific memory T cell responses were determined by IFN-γ ELISpot and intracellular cytokine production assays using peptide pools against SARS-CoV-2 structural and accessory proteins (Spike, Membrane, Nucleocapsid, Envelope, and ORF3a,6,7,8). Results: The majority of PLWH had detectable SARS-CoV-2 S-and N-specific antibodies with neutralizing activity at levels comparable to HIV negative subjects (p= 0.5753). Although, the overall magnitude of SARS-CoV-2 specific T cell responses measured by ELISpot was not significantly different between the groups (p=0.4642), this correlated with the size of the naive CD4 T cell pool (r=0.5518, p=0.0143) and the CD4:CD8 ratio in PLWH (r= 0.3820, p=0.037). In both groups, SARS-CoV-2 specific CD4 T cells were more abundant compared to CD8 T cells (HIV-p= 0.002, HIV+ p=0.0019). Both humoral and cellular responses were detected between 5-7 months post infection, providing evidence of medium-term durability of responses irrespective of HIV serostatus. Conclusion: The majority of PLWH mount a functional adaptive immune response to SARS-CoV-2. Incomplete immune reconstitution on ART and persistent alterations in the T cell compartment could, however, impact the development of protective immunity to SARS-CoV-2. These findings have implications for the risk stratification and management of PLWH.