Severe COVID-19 patients display a back boost of seasonal coronavirus-specific antibodies (preprint)

Severe acquired respiratory syndrome coronavirus-2 (SARS-CoV-2) is the cause of coronavirus disease (COVID-19). In severe COVID-19 cases, higher antibody titers against seasonal coronaviruses have been observed than in mild cases. To investigate antibody cross-reactivity as potential explanation for severe disease, we determined the kinetics, breadth, magnitude and level of cross-reactivity of IgG against SARS-CoV-2 and seasonal CoV nucleocapsid and spike from 17 severe COVID-19 cases at the clonal level. Although patients mounted a mostly type-specific SARS-CoV-2 response, B-cell clones directed against seasonal CoV dominated and strongly increased over time. Seasonal CoV IgG responses that did not neutralize SARS-CoV-2 were boosted well beyond detectable cross-reactivity, particularly for HCoV-OC43 spike. These findings support a back-boost of poorly protective coronavirus-specific antibodies in severe COVID-19 patients that may negatively impact de novo SARS-CoV-2 immunity, reminiscent of original antigenic sin.

Phenotype of SARS-CoV-2-specific T-cells in COVID-19 patients with acute respiratory distress syndrome (preprint)

SARS-CoV-2 has been identified as the causative agent of a global outbreak of respiratory tract disease (COVID-19). In some patients the infection results in moderate to severe acute respiratory distress syndrome (ARDS), requiring invasive mechanical ventilation. High serum levels of IL-6 and an immune hyperresponsiveness referred to as a cytokine storm have been associated with poor clinical outcome. Despite the large numbers of cases and deaths, information on the phenotype of SARS-CoV-2-specific T-cells is scarce. Here, we detected SARS-CoV-2-specific CD4+ and CD8+ T cells in 100% and 80% of COVID-19 patients, respectively. We also detected low levels of SARS-CoV-2-reactive T-cells in 20% of the healthy controls, not previously exposed to SARS-CoV-2 and indicative of cross-reactivity due to infection with common cold coronaviruses. Strongest T-cell responses were directed to the surface glycoprotein (spike, S), and SARS-CoV-2-specific T-cells predominantly produced effector and Th1 cytokines, although Th2 and Th17 cytokines were also detected. Collectively, these data stimulate further studies into the role of T-cells in COVID-19, support vaccine design and facilitate the evaluation of vaccine candidate immunogenicity.