Immunological responses in SARS-CoV-2 and HIV co-infection versus SARS-CoV-2 mono-infection: case report of the interplay between SARS-CoV-2 and HIV

BackgroundThere is an urgent need to understand the interplay between SARS-CoV-2 and HIV to inform risk-mitigation approaches for HIV-infected individuals.ObjectivesWe conclude that people living with HIV (PLWH) who are antiretroviral therapy (ART) naive could be at a greater risk of morbidity or mortality once co-infected with SARS-CoV-2.MethodsHere, we performed extensive immune phenotyping using flow cytometry. Moreover, to compare the range of values observed in the co-infected case, we have included a larger number of mono-infected cases with SARS-CoV-2. We also quantified soluble co-inhibitory/co-stimulatory molecules in the plasma of our patients.ResultsWe noted a robust immune activation characterized by the expansion of CD8+ T cells expressing co-inhibitory/stimulatory molecules (e.g. PD-1, TIM-3, 2B4, TIGIT, CD39, and ICOS) and activation markers (CD38, CD71, and HLA-DR) in the co-infected case. We further found that neutrophilia was more pronounced at the expense of lymphopenia in the co-infected case. In particular, naive and central memory CD8+ T cells were scarce as a result of switching to effector and effector memory in the co-infected case. CD8+ T cell effector functions such as cytokine production (e.g. TNF-alpha and IFN-gamma) and cytolytic molecules expression (granzyme B and perforin) following anti-CD3/CD28 or the Spike peptide pool stimulation were more prominent in the co-infected case versus the mono-infected case. We also observed that SARS-CoV-2 alters T cell exhaustion commonly observed in PLWH.ConclusionThese findings imply that inadequate immune reconstitution and/or lack of access to ART could dysregulate immune response against SARS-CoV-2 infection, which can result in poor clinical outcomes in PLWH. Our study has implications for prioritizing PLWH in the vaccination program/access to ART in resource-constrained settings.

Automated summary

This study found that individuals with HIV who are not receiving antiretroviral therapy may be at a higher risk of morbidity or mortality when co-infected with SARS-CoV-2. The study also identified immune activation, neutrophilia, lymphopenia, and enhanced CD8+ T cell functions in co-infected individuals. These findings indicate that inadequate immune reconstitution and limited access to antiretroviral therapy can lead to dysregulated immune response and poor clinical outcomes in people living with HIV.