Upregulation of Activation Induced Cell Markers (AIM) among Severe COVID-19 patients in Bangladesh

ABSTRACT

COVID-19 caused by SARS-CoV-2 can develop the disease with different degree of clinical severity including fatality. In addition to antibody responses the antigen specific T cells may play a critical role in defining this protective immune response against this virus. As a part of a longitudinal cohort study in Bangladesh to investigate B and T cell specific immune responses, we sought to evaluate the activation induced cell marker (AIM) and the status of different immune cell subsets during infection. A total of 115 participants were analyzed in this study which included participants with asymptomatic, mild, moderate and severe clinical symptoms. In addition, healthy controls (19 in each group) were analysed. Specimens from participants collected during the pre-pandemic period were also analyzed (n=10). Follow-up visits were conducted on day 7, 14, and 28 for all the cases since the enrollment (day 1). In this study 10 participants among the moderate and severe cases expired during the course of follow up. We observed a decrease in mucosa associated invariant T (MAIT) cell frequency on the initial days (day 1 and day 7) in comparison to later days of the COVID-19 infection. However, natural killer (NK) cells were found to be elevated in symptomatic patients just after the onset of disease compared to both asymptomatic patients and healthy individuals. Moreover, we found AIM+ (both OX40+ CD137+ and OX40+ CD40L+) CD4+ T cells to show significant increase in moderate and severe COVID-19 patients in response to SARS-CoV-2 peptides (specially spike peptide) compared to prepandemic controls, who are unexposed to SARS-CoV-2. Notably, we did not observe any significant difference in the CD8+ AIM markers (CD137+ CD69+), which indicates the exhaustion of CD8+ T cells during COVID-19 infection. These findings suggest that the patients who recovered from moderate and severe COVID-19 were able to mount a strong CD4+ T cell response against shared viral determinants that ultimately induced the T cells to mount further immune responses to SARS-CoV-2.