Thread by @sigallab

I want to tell you about a paper we published this month which is our most in-depth work on persistent SARS-CoV-2 infections in immunosuppressed people with advanced HIV disease. We focused on how it is eventually cleared.

nature.com/articles/s4146…

In our cohort we followed people after SARS-CoV-2 infection in Durban, South Africa, including people immunosuppressed because of advanced HIV disease who had delayed adherence to antiretroviral therapy to suppress HIV. We found this group had much longer SARS-CoV-2 infections:

Investigating five advanced HIV disease participants in depth, we observed that these persistent SARS-CoV-2 infections led to extensive SARS-CoV-2 evolution measured in terms of accumulated mutations:

Eventually, all five participants adhered to antiretroviral therapy and controlled their HIV infection. As they did this, they cleared their SARS-CoV-2 infection. The immune response which most closely associated with clearance was the appearance of neutralizing antibodies:

In the previous figure, top row showed the course of SARS-CoV-2 infection in each participants, which lasted for between 130 to 293 days. Bottom row shows the measured neutralization capacity at different timepoints per participant against virus isolated from each participant.

Through a close collaboration, Wendy Burgers and Catherine Riou at University of Cape Town checked whether clearance was associated with T cell responses. There were too few CD4 T cells to test, but enough CD8 T cells (bottom population below). These did not appear at clearance:

Bottom line, in persistent SARS-CoV-2 infections, neutralizing antibodies are likely key to clearance.
This likely applies when a pandemic and high HIV prevalence intersect. With low ART adherence, you will get evolution, and perhaps adaptation, of the pandemic virus.

I want to thank the lead author @farinakarim, @KhadijaKhan24, @LustigGil, @Zesuliwe_Jule and all the laboratory and clinical team, T cell collaborators Catherine Riou and Wendy Burgers, and @PennyMo70026063, @rjlessells, @Tuliodna, and especially our partner Yunus Moosa