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Background There is limited understanding of SARS-CoV-2 pathogenesis in African populations with a high burden of infectious disease comorbidities such as HIV. The kinetics, magnitude and duration of virus-specific antibodies and the underlying B cell responses in people living with HIV (PLWH) in sub-Saharan Africa have not been fully characterized. Methods We longitudinally followed SARS-CoV-2 infected individuals in Durban, KwaZulu-Natal, South Africa and characterized SARS-CoV-2 receptor binding domain-specific IgM, IgG and IgA antibodies weekly for a month, and then at 3 months post diagnosis. 7/30 (41.7%) were PLWH, 83% (25/30) of which were on ART and with full HIV suppression. Potency of convalescent plasma neutralization was determined using a live virus neutralization assay and antibody secreting cell population frequencies were determined by flow cytometry. Results Similar seroconversion rates, time to peak antibody titer, peak magnitude and durability of anti-SARS-CoV-2 IgM, IgG, IgA, were observed in HIV uninfected and PLWH with complete HIV suppression on ART. In addition, similar neutralization potency against an isolate of SARS-CoV-2, circulating at the time of sampling in the first wave of SARS-CoV-2 infections in South Africa was observed in both groups. Loss of IgA was significantly associated with age (p=0.023) and a previous diagnosis of TB (p=0.018). Conclusions Similar antibody response kinetics and neutralization potency in HIV negative and PLWH on stable ART in an African setting suggests that COVID-19 natural infections may confer comparable antibody immunity in these groups. This provides hope that COVID-19 vaccines will be effective in PLWH on stable ART.

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis that is distinctly characterized by granuloma formation within infected tissues. Granulomas are dynamic and organized immune cell aggregates that limit dissemination, but can also hinder bacterial clearance. Consequently, outcome in TB is influenced by how granuloma structure and composition shift the balance between these two functions. To date, our understanding of what factors drive granuloma function in humans is limited. With this in mind, we used Multiplexed Ion Beam Imaging by Time-of-Flight (MIBI-TOF) to profile 37 proteins in tissues from thirteen patients with active TB disease from the U.S. and South Africa. With this dataset, we constructed a comprehensive tissue atlas where the lineage, functional state, and spatial distribution of 19 unique cell subsets were mapped onto eight phenotypically-distinct granuloma microenvironments. This work revealed an immunosuppressed microenvironment specific to TB granulomas with spatially coordinated co-expression of IDO1 and PD-L1 by myeloid cells and proliferating regulatory T cells. Interestingly, this microenvironment lacked markers consistent with T-cell activation, supporting a myeloid-mediated mechanism of immune suppression. We observed similar trends in gene expression of immunoregulatory proteins in a confirmatory transcriptomic analysis of peripheral blood collected from over 1500 individuals with latent or active TB infection and healthy controls across 29 cohorts spanning 14 countries. Notably, PD-L1 gene expression was found to correlate with TB progression and treatment response, supporting its potential use as a blood-based biomarker. Taken together, this study serves as a framework for leveraging independent cohorts and complementary methodologies to understand how local and systemic immune responses are linked in human health and disease.