Longitudinal Tracking of Immune Responses in COVID-19 Convalescents Reveals Absence of Neutralization Activity Against Omicron and Staggered Impairment to Other SARS-CoV-2 Variants of Concern

Ivan Odak, Christian R. Schultze-Florey, Swantje I. Hammerschmidt, Christiane Ritter, Stefanie Willenzon, Michaela Friedrichsen, Inga Ravens, Ruth Sikora, Lâle M. Bayir, Rodrigo Gutierrez Jauregui, Günter Bernhardt, Metodi V. Stankov, Anne Cossmann, Guido Hansen, Thomas Krey, Markus Cornberg, Christian Koenecke, Georg M.N. Behrens, Berislav Bošnjak, Reinhold Förster*

*Corresponding author for this work
9 Citations (Scopus)

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.

Original languageEnglish
Article number863039
JournalFrontiers in Immunology
Volume13
ISSN1664-3224
DOIs
Publication statusPublished - 14.03.2022

Funding

The study was supported by DZIF TTU 01.938 (grant 80018019238 to RF and GB), by DZL (grant 82DZL002B1 to RF), by DFG EXC 2155 “RESIST” (Project ID39087428 to RF), SFB 900/3 (Projects B1, 158989968 to RF and project B8 to CK) and FO334/7-1 to RF, by the State of Lower Saxony (14-76103-184 CORONA-11/20 to RF and TK) by the BMBF (NaFoUniMedCovid19 FKZ: 01KX2021; Project B-FAST to RF), and by the European Regional Development Fund (Defeat Corona, ZW7-8515131 and ZW7-85151373 to GB). The funding sources of this study did not play any role in the study design, the collection, analysis and interpretation of the data, in the writing of the manuscript and in the decision to submit the paper for publication. The authors have not been paid by a pharmaceutical company or other agency to write this article. The corresponding author confirms that he had full access to all data in the study and had final responsibility for the decision to submit for publication.

Research Areas and Centers

  • Academic Focus: Center for Infection and Inflammation Research (ZIEL)
  • Centers: Center for Structural and Cell Biology (CSCM/ZMSZ)

DFG Research Classification Scheme

  • 2.21-04 Virology

Coronavirus related work

  • Research on SARS-CoV-2 / COVID-19

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