Abstract
Evaluating long-term protection against SARS-CoV-2 variants of concern in convalescing individuals is of high clinical relevance. In this prospective study of a cohort of 46 SARS-CoV-2 patients infected with the Wuhan strain of SARS-CoV-2 we longitudinally analyzed changes in humoral and cellular immunity upon early and late convalescence. Antibody neutralization capacity was measured by surrogate virus neutralization test and cellular responses were investigated with 31-colour spectral flow cytometry. Spike-specific, isotype-switched B cells developed already during the disease phase, showed a memory phenotype and did not decrease in numbers even during late convalescence. Otherwise, no long-lasting perturbations of the immune compartment following COVID-19 clearance were observed. During convalescence anti-Spike (S1) IgG antibodies strongly decreased in all patients. We detected neutralizing antibodies against the Wuhan strain as well as the Alpha and Delta but not against the Beta, Gamma or Omicron variants for up to 7 months post COVID-19. Furthermore, correlation analysis revealed a strong association between sera anti-S1 IgG titers and their neutralization capacity against the Wuhan strain as well as Alpha and Delta. Overall, our data suggest that even 7 month after the clearance of COVID-19 many patients possess a protective layer of immunity, indicated by the persistence of Spike-specific memory B cells and by the presence of neutralizing antibodies against the Alpha and Delta variants. However, lack of neutralizing antibodies against the Beta, Gamma and Omicron variants even during the peak response is of major concern as this indicates viral evasion of the humoral immune response.
Highlights
MATERIAL AND METHODSSince the emergence of the new coronavirus SARS-CoV-2 in December 2019, a growing body of literature has been published elucidating the immune responses in COVID-19 patients [1–3].The longevity of the immunological memory post SARS-CoV-2 infection is a matter of public health concern
We found all three subsets to be significantly elevated in the blood of both early and late convalescing patients compared to disease patients (Figure 1C), likely due to general lymphopenia of severe COVID-19 patients [16]
We provide evidence that all these patients developed Spike-specific memory B cells that, on average, did not drop in frequency during the 7 months observation period
Summary
Since the emergence of the new coronavirus SARS-CoV-2 in December 2019, a growing body of literature has been published elucidating the immune responses in COVID-19 patients [1–3]. Possible viral escape through mutation has become a subject of increasing interest This concern grew with recent evidence of antigen divergence of the B.1.351 (Beta) and the P.1 (Gamma, formerly named B.1.28.1) VoC [2, 6]. It is likely that the current range of mutation of SARS-CoV-2 is underestimated and further VoCs are already on the rise In this context, assessing the level of protection conferred by convalescence to (re)infection by VoCs is of great importance. Our data imply diverging rates of affinity maturation as well as decay of neutralizing antibodies against SARS-CoV-2 VoCs in COVID-19 patients and convalescent individuals, while Spikespecific B cells are shown to persist in circulation for up to seven month post clearance of COVID-19– the maximum observation period of the present study. Regardless of the disease kinetics and severity, all 120 sera sample tested revealed complete absence of neutralizing antibodies directed against the Omicron variant
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