Africa Health Research Institute, Durban, South Africa; School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South Africa
Jumari Snyman
Africa Health Research Institute, Durban, South Africa; School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South Africa; HIV Pathogenesis Programme, The Doris Duke Medical Research Institute, University of KwaZulu Natal, Durban, South Africa
Hwa Shi-Hsia
Africa Health Research Institute, Durban, South Africa; Division of Infection and Immunity, University College London, London, United Kingdom
Daniel Muema
Africa Health Research Institute, Durban, South Africa; School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South Africa; HIV Pathogenesis Programme, The Doris Duke Medical Research Institute, University of KwaZulu Natal, Durban, South Africa
Africa Health Research Institute, Durban, South Africa; School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South Africa
Yashica Ganga
Africa Health Research Institute, Durban, South Africa
Abigail Ngoepe
Africa Health Research Institute, Durban, South Africa
Yenzekile Zungu
Africa Health Research Institute, Durban, South Africa; School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South Africa
Inbal Gazy
School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South Africa; KwaZulu-Natal Research Innovation and Sequencing Platform, Durban, South Africa
Mallory Bernstein
Africa Health Research Institute, Durban, South Africa
Africa Health Research Institute, Durban, South Africa; School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South Africa
Matilda Mazibuko
Africa Health Research Institute, Durban, South Africa
Ntombifuthi Mthabela
Africa Health Research Institute, Durban, South Africa
Dirhona Ramjit
Africa Health Research Institute, Durban, South Africa
COMMIT-KZN Team
Oliver Limbo
International AIDS Vaccine Initiative, New York, United States
Joseph Jardine
International AIDS Vaccine Initiative, New York, United States
Devin Sok
International AIDS Vaccine Initiative, New York, United States
Ian A Wilson
The Scripps Research Institute, La Jolla, United States
Willem Hanekom
Africa Health Research Institute, Durban, South Africa; Division of Infection and Immunity, University College London, London, United Kingdom
Africa Health Research Institute, Durban, South Africa; School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South Africa; Max Planck Institute for Infection Biology, Berlin, Germany; Centre for the AIDS Programme of Research in South Africa, Durban, South Africa
Henrik Kløverpris
Africa Health Research Institute, Durban, South Africa; Division of Infection and Immunity, University College London, London, United Kingdom; Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark
Africa Health Research Institute, Durban, South Africa; School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South Africa; HIV Pathogenesis Programme, The Doris Duke Medical Research Institute, University of KwaZulu Natal, Durban, South Africa; Division of Infection and Immunity, University College London, London, United Kingdom; Max Planck Institute for Infection Biology, Berlin, Germany
Alasdair Leslie
Africa Health Research Institute, Durban, South Africa; Division of Infection and Immunity, University College London, London, United Kingdom
Background: HIV infection dysregulates the B cell compartment, affecting memory B cell formation and the antibody response to infection and vaccination. Understanding the B cell response to SARS-CoV-2 in people living with HIV (PLWH) may explain the increased morbidity, reduced vaccine efficacy, reduced clearance, and intra-host evolution of SARS-CoV-2 observed in some HIV-1 coinfections. Methods: We compared B cell responses to COVID-19 in PLWH and HIV negative (HIV-ve) patients in a cohort recruited in Durban, South Africa, during the first pandemic wave in July 2020 using detailed flow cytometry phenotyping of longitudinal samples with markers of B cell maturation, homing, and regulatory features. Results: This revealed a coordinated B cell response to COVID-19 that differed significantly between HIV-ve and PLWH. Memory B cells in PLWH displayed evidence of reduced germinal centre (GC) activity, homing capacity, and class-switching responses, with increased PD-L1 expression, and decreased Tfh frequency. This was mirrored by increased extrafollicular (EF) activity, with dynamic changes in activated double negative (DN2) and activated naïve B cells, which correlated with anti-RBD-titres in these individuals. An elevated SARS-CoV-2-specific EF response in PLWH was confirmed using viral spike and RBD bait proteins. Conclusions: Despite similar disease severity, these trends were highest in participants with uncontrolled HIV, implicating HIV in driving these changes. EF B cell responses are rapid but give rise to lower affinity antibodies, less durable long-term memory, and reduced capacity to adapt to new variants. Further work is needed to determine the long-term effects of HIV on SARS-CoV-2 immunity, particularly as new variants emerge. Funding: This work was supported by a grant from the Wellcome Trust to the Africa Health Research Institute (Wellcome Trust Strategic Core Award [grant number 201433/Z/16/Z]). Additional funding was received from the South African Department of Science and Innovation through the National Research Foundation (South African Research Chairs Initiative [grant number 64809]), and the Victor Daitz Foundation.
