T cells play a fundamental role in the early control and clearance of many viral infections of the respiratory system. In SARS-CoV-2-infected individuals, lymphopenia with drastically reduced CD4+ and CD8+ T cells correlates with Coronavirus disease 2019 (COVID-19)-associated disease severity and mortality. In this study, we characterized cellular and humoral immune responses induced in patients with mild, severe and critical COVID-19. Peripheral blood mononuclear cells of 37 patients with mild, severe and critical COVID-19 and 10 healthy individuals were analyzed by IFNγ ELISpot and multi-color flow cytometry upon stimulation with peptide pools covering complete immunodominant SARS-CoV-2 matrix, nucleocapsid and spike proteins. In addition SARS-CoV-2 antibody levels, neutralization abilities and anaphylatoxin levels were evaluated by various commercially available ELISA platforms. Our data clearly demonstrates a significantly stronger induction of SARS-CoV-2 specific CD8+ T lymphocytes and higher IFNγ production in patients with mild compared to patients with severe or critical COVID-19. In all patients SARS-CoV-2-specific antibodies with similar neutralizing activity were detected, but highest titers of total IgGs were observed in critical patients. Finally, elevated anaphylatoxin C3a and C5a levels were identified in severe and critical COVID-19 patients probably caused by aberrant immune complex formation due to elevated antibody titers in these patients. Crucially, we provide a full picture of cellular and humoral immune responses of COVID-19 patients and prove that robust polyfunctional CD8+ T cell responses concomitant with low anaphylatoxin levels correlate with mild infections. In addition, our data indicates that high SARS-CoV-2 antibody titers are associated with severe disease progression.
Background Only a few studies directly compared virus-specific antibodies and their neutralizing capacity against SARS-CoV-2 wild type and circulating variants of concern, despite the reported high efficacy of mRNA- and vector-based vaccines. Objective Here we assessed SARS-CoV-2-S1-specific antibodies of BNT162b2, mRNA-1273 and ChAdOx1 vaccinated as well as convalescent COVID-19 patients and furthermore determined the neutralization ability against SARS-CoV-2 wild type and B.1.1.7 (Alpha), B1.1.7 E484K (Alpha E484K), B.1.351 (Beta) and B.1.617.2 (Delta) variants. Methods Serum samples of 107 fully vaccinated or convalescent individuals were analyzed for anti-SARS-CoV-2-S1 IgG and IgA as well as for total anti-SARS-CoV-2 RBD Ig. Furthermore, neutralization capacity as NT50 and NT90 values against SARS-CoV-2 wild type virus and circulating variants were determined. Results We observed a robust IgG response in all participants, however the highest titers were detected in mRNA-based vaccine recipients. In case of serum IgA responses, the difference between mRNA- and vector-based vaccines or convalescent patients was even more pronounced. Interestingly, all three vaccines could neutralize all tested VOCs in addition to wild type virus, but in some individuals only low or no neutralization especially against Alpha-E484K and Delta variant was detected. Conclusion Critically, we here studied the efficacy of various COVID-19 vaccines and found that mRNA-1273 had the highest neutralization abilities compared to BNT162b2- and ChAdOx1 vaccinees. COVID-19 convalescent patients demonstrated the most heterogeneous range of antibody titers and neutralization ability, rendering assessment of protection difficult. Furthermore a significant, positive relation between antibodies and NT50 values for immunized and convalescent individuals was determined.
Summary Background As coronavirus disease 2019 caused by severe acute respiratory syndrome coronavirus 2 evolved only recently, the persistency of the anti-viral antibody response remains to be determined. Methods We prospectively followed 29 coronavirus disease 2019 cases, mean age 44 ± 13.2 years. Except for one participant with a pre-existing diagnosis of rheumatoid arthritis, all other participants were previously healthy. We determined anti-viral binding antibodies at 2–10 weeks, 3 months, and 6 months after disease onset as well as neutralizing antibodies at 6 months. Two binding antibody assays were used, targeting the S1 subunit of the spike protein, and the receptor binding domain. Results All participants fully recovered spontaneously except for one who had persisting hyposmia. Antibodies to the receptor binding domain persisted for 6 months in all cases with a slight increase of titers, whereas antibodies to S1 dropped below the cut-off point in 2 participants and showed a minimal decrease on average, mainly at month 3 of follow-up in males; however, neutralizing antibodies were detected in all samples at 6 months of follow-up. Conclusion There is a stable and persisting antibody response against acute respiratory syndrome coronavirus 2 at 6 months after infection. Neutralizing antibodies confirm virus specificity. As the number of coronavirus disease 2019 convalescent cases is increasing sharply, antibody testing should be implemented to identify immunized individuals. This information can be helpful in various settings of professional and private life.
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