Long-term T cell perturbations and waning antibody levels in individuals needing hospitalization for COVID-19

Abstract

COVID-19 is being extensively studied, and much remains unknown regarding the long-term consequences of the disease on immune cells. The different arms of the immune system are interlinked, with humoral responses and the production of high-affinity antibodies being largely dependent on T cell immunity. Here, we longitudinally explored the effect COVID-19 has on T cell populations and the virus-specific T cells, as well as neutralizing antibody responses, for 6-7 months following hospitalization. The CD8+ TEMRA and exhausted CD57+CD8+ T cells were markedly affected with elevated levels that lasted long into convalescence. Further, markers associated with T-cell activation were upregulated at the inclusion, and in the case of CD69+CD4+ T cells this lasted all through the study duration. The levels of T cells expressing negative immune checkpoint molecules were increased in COVID-19 patients and sustained for a prolonged duration following recovery. Within 2-3 weeks after symptom onset, all COVID-19 patients developed anti-nucleocapsid IgG and spike-neutralizing IgG as well as SARS-CoV-2-specific T cell responses. In addition, we found alterations in follicular T helper (TFH) cell populations, such as enhanced TFH-TH2 following recovery from COVID-19. Our study revealed significant and long-term alterations in T cell populations and key events associated with COVID-19 pathogenesis.

Lasting alterations in monocyte and dendritic cell subsets in individuals after hospitalization for COVID-19

“…The levels of MDSC have been found to correlate to impaired T cell responses 53, 54 . This sustained elevation suggests a long-lasting suppressive state, which we have found to be reflected in the suppressive T cell phenotypes defined in our COVID-19 cohort 55 .…”

“…Given the importance of DC for the initial activation of T cell responses, their depletion or tissue relocation could hamper the subsequent T cell response 63 . Additionally, the long-lasting alteration in the DC compartment could explain the sustained T cell dysfunction seen following COVID-19 55, 64 .…”

Factors Associated With the Decay of Anti-SARS-CoV-2 S1 IgG Antibodies Among Recipients of an Adenoviral Vector-Based AZD1222 and a Whole-Virion Inactivated BBV152 Vaccine

“…Several studies have investigated the dynamics and the duration of protection of neutralizing antibodies developed following the onset of natural SARS-CoV-2 infection or vaccination ( 7 – 11 ). The results thus far remain inconsistent, with some reporting rapid waning of antibodies months after virus exposure or following vaccine administration ( 7 – 13 ), whereas others report the prolonged presence of neutralizing antibodies ( 14 – 16 ). This discrepancy partly stems from numerous factors including differences in patient demography, vaccine type, and number of infections/vaccinations one has become exposed to, SARS-CoV-2 strains, intrinsic properties of immunity, underlying disease and many other miscellaneous factors.…”