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

Previous studies have linked the evolution of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) genetic variants to persistent infections in people with immunocompromising conditions, but the processes responsible for these observations are incompletely understood. Here we use high-throughput, single-genome amplification and sequencing (HT-SGS) to sequence SARS-CoV-2 spike genes from people with HIV (PWH, n = 22) and people without HIV (PWOH, n = 25). In PWOH and PWH with CD4 T cell counts (i.e., CD4 counts) ≥ 200 cells/μL, we find that most SARS-CoV-2 genomes sampled in each person share one spike sequence. By contrast, in people with advanced HIV infection (i.e., CD4 counts < 200 cells/μL), HT-SGS reveals a median of 46 distinct linked groupings of spike mutations per person. Elevated intra-host spike diversity in people with advanced HIV infection is detected immediately after COVID-19 symptom onset, and early intra-host spike diversity predicts SARS-CoV-2 shedding duration among PWH. Analysis of longitudinal timepoints reveals rapid fluctuations in spike sequence populations, replacement of founder sequences by groups of new haplotypes, and positive selection at functionally important residues. These findings demonstrate remarkable intra-host genetic diversity of SARS-CoV-2 in advanced HIV infection and suggest that adaptive intra-host SARS-CoV-2 evolution in this setting may contribute to the emergence of new variants of concern.

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Severe disease is not essential for a high neutralizing antibody response post-SARS-CoV-2 infection

Khairallah,

Jule,

Piller

et al. 2024

Preprint

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Neutralizing antibody responses correlate with protection from SARS-CoV-2 infection, yet higher neutralizing responses associate with more severe disease. Whether people without severe disease can also develop strong neutralizing responses to infection, and the pathways involved, is less clear. We performed a proteomic analysis on sera from 71 individuals infected with ancestral SARS-CoV-2, enrolled during the first South African infection wave. We determined disease severity by whether participants required supplemental oxygen and measured neutralizing antibody levels at convalescence. High neutralizing antibodies were associated with high disease severity, yet 40% of participants with lower disease severity had neutralizing antibody levels comparable to those with severe disease. We found 130 differentially expressed proteins between high and low neutralizers and 40 between people with high versus low disease severity. Five proteins overlapped, including furin, a protease which enhances SARS-CoV-2 infection. High neutralizers with non-severe disease had similar levels of differentially expressed neutralization response proteins to high neutralizers with severe disease, yet similar levels of differentially expressed disease severity proteins to participants with non-severe disease. Furthermore, we could reasonably predict who developed a strong neutralizing response based on a single protein, HSPA8, involved in clathrin pit uncoating. These results indicate that a strong antibody response does not always require severe disease and may involve different pathways.

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

Cited by 6 publications

References 91 publications

SARS-CoV-2 humoral immunity in people living with HIV-1

SARS-CoV-2 humoral immunity in people living with HIV-1

Rapid intra-host diversification and evolution of SARS-CoV-2 in advanced HIV infection

Severe disease is not essential for a high neutralizing antibody response post-SARS-CoV-2 infection

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