Durability of immune responses to SARS-CoV-2 infection in the context of HIV-infection, aging and cross-reactive immune responses.

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SUMMARY/ABSTRACT There is almost no information about the immune response to SARS-CoV-2, the causative agent of COVID 19. What little we know has either emerged in real time during the 2020 pandemic or has been gleaned from a handful of studies on SARS-CoV-1. The pressing question at the moment is whether individuals who have recovered from infection with SARS-CoV-2 will have durable immune responses that are protective against reinfection and recurring illness. Current efforts to address this question are largely focused on antibody responses as they are not only easier to measure than T-cell responses, but antibodies provide the first line of adaptive immune protection and can often neutralize a pathogen before widespread infection occurs. However, T-cells are also essential in providing protection against secondary infection and T-cell memory is ideally elicited by vaccination. Understanding the T-cell response, both the quality and durability to natural infection with SARS-CoV-2, will not only provide insight into the pathogenesis of SARS-CoV-2, but will be important for vaccine development. However, HIV-infected individuals, with immune system deficits, represent a highly at-risk population for morbidity and mortality from SARS-CoV-2. It is therefore critical to understand how this population responds to this virus and to vaccination against SARS-CoV-2. To investigate this, we will characterize IgG as well as CD4+ and CD8+ T-cell subsets in the MWCCS participants who have had confirmed infection with SARS-CoV-2, either through a clinical test to detect virus, or by the presence of post- infection antibodies. Responses to vaccination, when the vaccine is available, will also be studied and compared to the responses elicited by active infection. IgG and T-cell responses within the HIV-infected population in response to infection and vaccination will be compared to the responses observed in their HIV- seronegative peers within the MWCCS. The IgG titers and the frequency of SARS-CoV-2 responsive T-cells, their cytokine production, phenotype and durability will be analyzed in a longitudinal fashion until vaccination occurs or we have followed them for two years, whichever comes later. Numbers of senescent T-cells will be determined and associations investigated between the quantify of these cells and the post-infection immune response and severity of disease reported. Pre-SARS-CoV-2 time points will both serve as case controls and allow us to investigate the potential presence of cross-reactive immune responses as two new studies suggest that immune responses to other coronaviruses may be cross-reactive with SARS-CoV-2 which could theoretically impact immune responses to SARS-CoV-2 for better or worse. Our long-term goal is to inform vaccine studies and public policies designed to protect older adults, particularly those aging with HIV.