On viral kinetics and immune responses following SARS-CoV-2 infection and vaccination

Abstract

This thesis consists of two parts, exploring different aspects of Coronavirus Disease 2019 (COVID-19), caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). The first part examines viral kinetics and antibody responses in individuals with severe and mild COVID-19. The second part assesses different components of the immune response following mild SARS-CoV-2 infections and mRNA COVID-19 vaccinations.

In Paper I, we examined the duration of viral RNA shedding with serial PCR tests from the upper respiratory tracts and investigated the association of viral load and disease severity in patients with mild (n=39) and severe (n=15) COVID-19. We observed no significant differences in median viral load between groups on day 7 and day 14, and the duration of viral shedding was similar between groups. Paper II assessed time to seroconversion, and levels of SARS-CoV-2 IgG against Nucleocapsid and Spike proteins in patients with mild (n=32) and severe (n=17) COVID-19. We found a significantly shorter time until seroconversion and significantly higher IgG levels in the severe group during early follow-up (< 35 days). In Paper III, we investigated the seroprevalence among a group of healthcare workers (HCWs) in Sweden during the first ten months of the pandemic. We found an increasing and significantly higher seroprevalence in the HCWs compared to matched blood donors. Moreover, we assessed the performance of different IgG assays targeting different antigens and analyzed CD4+ T cell reactivity in both infected and uninfected HCWs. In Paper IV, we profiled immune responses, including IgG and T cell cytokine (IFN-γ, IL-2, and TNF-α) responses, following up to four COVID-19 mRNA vaccine doses in HCWs (n=108). We found significantly higher IgG levels in previously infected than in uninfected HCWs up until the third vaccine dose, while differences in cytokine responses were less affected by previous infections or breakthrough infections.

Together, the results provide insights into viral kinetics, antibody responses and T-cell responses following SARS-CoV-2 infections and mRNA vaccinations, contributing to the understanding of immunity in different phases of the COVID-19 pandemic.