Unsuppressed HIV infection impairs T cell responses to SARS-CoV-2 infection and abrogates T cell cross-recognition
South Africa, 2020 - 2021
Get MicrodataIdentification
AHRI.SARS.CoV.2
Unsuppressed HIV infection impairs T cell responses to SARS-CoV-2 infection and abrogates T cell cross-recognition
| Name | Country code |
|---|---|
| South Africa | ZA |
In some instances, unsuppressed HIV has been associated with severe COVID-19 disease, but the mechanisms underpinning this susceptibility are still unclear. Here, we assessed the impact of HIV infection on the quality and epitope specificity of SARS-CoV-2 T cell responses in the first wave and second wave of the COVID-19 epidemic in South Africa. Flow cytometry was used to measure T cell responses following PBMC stimulation with SARS-CoV-2 peptide pools. Culture expansion was used to determine T cell immunodominance hierarchies and to assess potential SARS-CoV-2 escape from T cell recognition. HIV-seronegative individuals had significantly greater CD4+T cell responses against the Spike protein compared to the viremic PLWH. Absolute CD4 count correlated positively with SARS-CoV-2 specific CD4+ and CD8+ T cell responses (CD4 r= 0.5, p=0.03; CD8 r=0.5, p=0.001), whereas T cell activation was negatively correlated with CD4+ T cell responses (CD4 r= -0.7, p=0.04). There was diminished T cell cross-recognition between the two waves, which was more pronounced in individuals with unsuppressed HIV infection. Importantly, we identify four mutations in the Beta variant that resulted in abrogation of T cell recognition. Together, we show that unsuppressed HIV infection markedly impairs T cell responses to SARS-Cov-2 infection and diminishes T cell cross-recognition. These findings may partly explain the increased susceptibility of PLWH to severe COVID-19 and also highlights their vulnerability to emerging SARS-CoV-2 variants of concern.
Experimental data
The study measured differences in Immune responses to SARS-CoV-2 among three COVID-19 patient groups namely HIV negative, HIV positive but fully suppressed and HIV positive with unsuppressed infection
Version
V1.0.0
Scope
| Topic | Vocabulary | URI |
|---|---|---|
| T cell Immunology, SARS-CoV-2 Immune responses | Africa Health Research Institute | AHRI |
Coverage
KwaZulu-Natal
COVID-19 patient groups namely HIV negative, HIV positive but fully suppressed and HIV positive with unsuppressed infection. All the study participants were recruited in KwaZulu-Natal
Producers and sponsors
| Name | Affiliation |
|---|---|
| Thandeka Nkosi | AHRI |
| Caroline Charasa | AHRI |
| Andrea O Papadopoulos | AHRI |
| Tiza L Nguni | AHRI |
| Farina Karim | AHRI |
| Mohomed Yunus S Moosa | UKZN School of Medicine |
| Inbal Gazy: inbal | KRISP |
| Kondwani Jambo | Malawi-Liverpool Wellcom Trust |
| Willem Hanekom | AHRI |
| Alex Sigal: alex | AHRI |
| Zaza M Ndhlovu | AHRI |
| Name |
|---|
| Africa Health Research Institute |
| Name | Role |
|---|---|
| Howard Hughes Medical Institute | Funded the principal investigator Funded the principal investigator Funded the principal investigator Funded the principal investigator |
| The Bill and Melinda Gates Foundation | Funded the cohort |
Sampling
The studies are exploratory. The study included COVID-19 patients with and without prior HIV infection
Data collection
| Start | End |
|---|---|
| 2020-06-01 | 2021-06-30 |
Data processing
Immune responses data was generated using LSR Fortessa flowcytometer. Data was analysed on FlowJo v10.7.2 software. Differences between groups were considered to be significant at a P-value of <0.05. Statistical analyses were performed using GraphPad Prism 8.0 (GraphPad Software, Inc., San Diego, CA
Data Access
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Metadata production
DDI.AHRI.SARS.CoV.2
| Name |
|---|
| Africa Health Research Institute |