Reactivation of Kaposi's sarcoma-associated herpesvirus (KSHV) by SARS-CoV-2 in non-hospitalised HIV-infected patients.

EBioMedicine

International Centre for Genetic Engineering and Biotechnology (ICGEB), Cape Town, South Africa; Institute of Infectious Disease and Molecular Medicine (IDM), Faculty of Health Sciences, University of Cape Town, South Africa; Division of Medical Biochemistry, Department of Integrative Biomedical Sciences, University of Cape Town, South Africa; Wellcome Centre for Infectious Diseases Research in Africa, University of Cape Town, South Africa. Electronic address:

Published: February 2024

Background: While acute SARS-CoV-2 infection and associated inflammation resulted in substantial morbidity and mortality during the COVID-19 pandemic, particularly in unvaccinated patients, long-term effects of SARS-CoV-2 exposure for reactivation of latent oncogenic herpesviruses, such as KSHV, is unknown.

Methods: We performed a longitudinal observational cross-sectional study on 407 non-hospitalised adult HIV-infected (CD4 count <350 cells/μL) patients attending antiretroviral therapy services in Gugulethu, South Africa, from October 2020 to April 2023.

Findings: KSHV seroprevalence was 53.5%; the quarterly SARS-CoV-2 seroprevalence increased from 76.2% (before roll-out of COVID-19 vaccinations) to 94.9%, with 32.2% being self-reportedly vaccinated against COVID-19. Over the course of recruitment, the quarterly percentage of patients with detectable KSHV viral load (VL) in the peripheral blood increased from 3.3% to 69.2%. The presence of KSHV VL was significantly associated with SARS-CoV-2 RBD antibody titers in unvaccinated (median RBD IgG OD 1.24 [IQR 0.82-2.42] in non-reactivated versus 2.83 [IQR 1.08-4.72] in reactivated patients, p = 0.0030) but not in vaccinated patients (median RBD IgG OD 5.13 [IQR 4.11-6.36] in non-reactivated versus 4.53 [IQR 2.90-5.92] in reactivated patients, p = 0.086). Further logistic regression revealed significantly higher odds of KSHV reactivation in unvaccinated, previously SARS-CoV-2 exposed patients (p = 0.015, adjusted OR 1.28 [95% CI: 1.05-1.55]), but not vaccinated patients (p = 0.080, adjusted OR 0.83 [95% CI: 0.67-1.02]). Interestingly, detectable KSHV VL was not associated with increased inflammatory markers such as C-reactive protein and interleukin-6.

Interpretation: High, and most likely repeated, exposure to SARS-CoV-2 in unvaccinated individuals may have long-term consequences for reactivation of KSHV infection as shown here in the context of HIV-infected patients with impaired immune functions. Post-pandemic prevention and/or monitoring strategies of potential KSHV-associated pathologies in high-risk patients with immunodeficiencies are therefore highly recommended.

Funding: This research was funded by the EDCTP2 programme (Training and Mobility Action TMA2018SF-2446).

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10850403PMC
http://dx.doi.org/10.1016/j.ebiom.2024.104986DOI Listing

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