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Nat Commun . Clearance of persistent SARS-CoV-2 associates with increased neutralizing antibodies in advanced HIV disease post-ART initiation

tetano

Editor, Senior Moderator
Nat Commun


. 2024 Mar 15;15(1):2360.
doi: 10.1038/s41467-024-46673-2. Clearance of persistent SARS-CoV-2 associates with increased neutralizing antibodies in advanced HIV disease post-ART initiation

Farina Karim[SUP] 1 2 [/SUP], Catherine Riou[SUP] 3 4 [/SUP], Mallory Bernstein[SUP] 1 [/SUP], Zesuliwe Jule[SUP] 1 [/SUP], Gila Lustig[SUP] 5 [/SUP], Strauss van Graan[SUP] 6 7 [/SUP], Roanne S Keeton[SUP] 3 [/SUP], Janine-Lee Upton[SUP] 1 [/SUP], Yashica Ganga[SUP] 1 [/SUP], Khadija Khan[SUP] 1 2 [/SUP], Kajal Reedoy[SUP] 1 [/SUP], Matilda Mazibuko[SUP] 1 [/SUP], Katya Govender[SUP] 1 [/SUP], Kershnee Thambu[SUP] 1 [/SUP], Nokuthula Ngcobo[SUP] 1 [/SUP], Elizabeth Venter[SUP] 6 7 [/SUP], Zanele Makhado[SUP] 6 7 [/SUP], Willem Hanekom[SUP] 1 8 [/SUP], Anne von Gottberg[SUP] 9 10 [/SUP], Monjurul Hoque[SUP] 11 [/SUP], Quarraisha Abdool Karim[SUP] 5 12 [/SUP], Salim S Abdool Karim[SUP] 5 12 [/SUP], Nithendra Manickchund[SUP] 13 [/SUP], Nombulelo Magula[SUP] 14 [/SUP], Bernadett I Gosnell[SUP] 13 [/SUP], Richard J Lessells[SUP] 5 15 [/SUP], Penny L Moore[SUP] 6 7 [/SUP], Wendy A Burgers[SUP] 3 4 [/SUP], Tulio de Oliveira[SUP] 5 15 16 17 [/SUP], Mahomed-Yunus S Moosa[SUP] 13 [/SUP], Alex Sigal[SUP] 18 19 20 [/SUP]



Affiliations
Abstract

SARS-CoV-2 clearance requires adaptive immunity but the contribution of neutralizing antibodies and T cells in different immune states is unclear. Here we ask which adaptive immune responses associate with clearance of long-term SARS-CoV-2 infection in HIV-mediated immunosuppression after suppressive antiretroviral therapy (ART) initiation. We assembled a cohort of SARS-CoV-2 infected people in South Africa (n = 994) including participants with advanced HIV disease characterized by immunosuppression due to T cell depletion. Fifty-four percent of participants with advanced HIV disease had prolonged SARS-CoV-2 infection (>1 month). In the five vaccinated participants with advanced HIV disease tested, SARS-CoV-2 clearance associates with emergence of neutralizing antibodies but not SARS-CoV-2 specific CD8 T cells, while CD4 T cell responses were not determined due to low cell numbers. Further, complete HIV suppression is not required for clearance, although it is necessary for an effective vaccine response. Persistent SARS-CoV-2 infection led to SARS-CoV-2 evolution, including virus with extensive neutralization escape in a Delta variant infected participant. The results provide evidence that neutralizing antibodies are required for SARS-CoV-2 clearance in HIV-mediated immunosuppression recovery, and that suppressive ART is necessary to curtail evolution of co-infecting pathogens to reduce individual health consequences as well as public health risk linked with generation of escape mutants.


 
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