HIV infection alters SARS-CoV-2 responsive immune parameters but not clinical outcomes in COVID-19 disease

Karim, Farina; Gazy, Inbal; Cele, Sandile; Zungu, Yenzekile; Krause, Robert; Bernstein, Mallory; Ganga, Yashica; Rodel, Hylton; Mthabela, Ntombifuthi; Mazibuko, Matilda; Khan, Khadija; Muema, Daniel; Ramjit, Dirhona; Lustig, Gila; Ndung039, Thumbi; Hanekom, Willem; Gosnell, Bernadett I; Team, COMMIT-KZN; Wong, Emily; Oliveira, Tulio de; Moosa, Mahomed-Yunus S; Leslie, Alasdair; Kloverpris, Henrik; Sigal, Alex

HIV infection alters the immune response and can compromise protective immunity to multiple pathogens following vaccination. We investigated the impact of HIV on the immune response to SARS-CoV-2 using longitudinal samples from 124 participants from KwaZulu-Natal, South Africa, an area of extremely high HIV prevalence. 44% of participants were people living with HIV (PLWH) and commonly had other co-morbidities, including obesity, hypertension, and diabetes. The majority of PLWH but not HIV negative participants showed CD8 T cell expansion above the normal range post-SARS-CoV-2. Yet, in participants with HIV suppressed by antiretroviral therapy (ART), CD8 expansion was associated with milder COVID-19 disease. There were multiple differences in T cell, B cell, and natural killer cell correlations in PLWH compared to HIV negative participants, including lower tissue homing CXCR3+ CD8 T cells in the presence of SARS-CoV-2 RNA in PLWH but not HIV negative and a pronounced early antibody secreting cell (ASC) expansion in HIV negative but not PLWH. These changes were COVID-19 associated: low CXCR3 correlated with increased COVID-19 disease severity across groups, and high ASC correlated with increased disease severity in HIV negative participants and waned when SARS-CoV-2 was cleared. Despite the altered response of immune cell subsets, COVID-19 disease in PLWH was mostly mild and similar to HIV negative participants. This likely reflects the heterogeneity of an effective COVID-19 immune response. Whether the differences in immune cell dynamics in PLWH will lead to different long-term consequences or compromise vaccination is yet to be determined.