ABSTRACT
Background: The ongoing COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, represents a serious worldwide health concern. A deeper understanding of the immune response to SARS-CoV-2 will be required to refine vaccine development and efficacy as well as to evaluate long-term immunity in convalescent patients. With this in mind, we investigated the formation of SARS-CoV-2 specific BMEMORY cells from patient blood samples. Methods: A standard flow cytometry-based protocol for the detection of SARS-CoV-2 specific B cells was applied using fluorochrome-coupled SARS-CoV-2 spike (S) full-length protein. Cohorts of 26 central European convalescent mild/moderate COVID-19 patients and 14 healthy donors were assessed for the levels of SARS-CoV-2 S- specific BMEMORY cells. Results: Overall B cell composition was not affected by SARS-CoV-2 infection in convalescent patients. Our analysis of SARS-CoV-2 specific BMEMORY cells in samples collected at different time points revealed that S-protein specific B cells remain in peripheral blood at least up to 6 months after COVID-19 diagnosis. Conclusions: Detection of SARS-CoV-2 specific BMEMORY cells may improve our understanding of the long-term adaptive immunity in response to SARS-CoV-2, allowing for an improved public health response and vaccine development during the COVID-19 pandemic. Further validation of the study in larger and more diverse populations and a more extended observation period will be required.
Subject(s)
COVID-19ABSTRACT
Background: The efficacy of the humoral and cellular immunity determines the outcome of viral infections. An appropriate immune response mediates protection, whereas an overwhelming immune response has been associated with immune-mediated pathogenesis in viral infections. The current study explored the general and SARS-CoV-2 specific cellular and humoral immune status in patients with different COVID-19 severities. Methods: In this prospective study, we included 53 patients with moderate, severe, and critical COVID-19 manifestations comparing their quantitative, phenotypic, and functional characteristics of circulating immune cells, SARS-CoV-2 antigen specific T-cells, and humoral immunity. Results: Significantly diminished frequencies of CD8+T-cells, CD4+ and CD8+T-cell subsets with activated differentiated memory/effector phenotype and migratory capacity were found in circulation in patients with severe and/or critical COVID-19 as compared to patients with moderate disease. Importantly, the improvement of the clinical courses from severe to moderate was accompanied by an improvement in the T-cell subset alterations. Furthermore, we surprisingly observed a detectable SARS-CoV-2-reactive T-cell response in all three groups after stimulation with SARS-CoV-2 S-protein overlapping peptide pool already at the first visit. Of note, patients with a critical COVID-19 demonstrated a stronger response of SARS-CoV-2-reactive T-cells producing Th1 associated inflammatory cytokines. Furthermore, clear correlation between antibody titers and SARS-CoV-2-reactive CD4+ frequencies underscore the role of specific immunity in disease progression. Conclusion: Our data demonstrate that depletion of activated memory phenotype circulating T-cells and a strong SARS-CoV-2-specific cellular and humoral immunity are associated with COVID-19 disease severity. This counter-intuitive finding may have important implications for diagnostic, therapeutic and prophylactic COVID-19 management.