Background: Marked progress is achieved in understanding the physiopathology of COVID-19 that caused global pandemics. However, CD4 + T cell population that is critical for antibody response in COVID-19 is poorly understood. Methods: In this study, we provided a comprehensive analysis of peripheral CD4 + T cells of 13 COVID-19 convalescent patients, as defined as confirmed free of SARS-CoV-2 for 2-4 weeks, using flow cytometry, magnetic chemiluminescence enzyme antibody immunoassay and correlated the data with clinical characteristics. Results: We observed that relative to healthy individuals, convalescent patients displayed an altered peripheral CD4 + T cell spectrum. Specifically, consistent with other viral infections, cTFH1 cell associated with SARS-CoV-2 targeting antibodies, which was found to skew with disease severity as more severe individuals showed higher frequency of TEM and TFH-EM cells but a lower frequency of TCM, TFH-CM and TNaive cells, relative to mild and moderate patients. Interestingly, higher frequency of cTFH-EM cells correlated with lower number of recorded admission blood oxygen level in convalescent patients. These observations might constitute residual effects by which COVID-19 can impact the homeostasis of CD4 + T cells in the long-term and explain the highest ratio of classswitched virus-specific antibody producing individuals found in our severe COVID-19 cohort. Conclusion: Together, our study demonstrated close connection between CD4 + T cells and antibody production in COVID-19 convalescents.
, the Karolinska Institutet Center for Innovative Medicine (Y.T.B.), the Swedish Childhood Cancer Foundation (J.-I.H., Y.T.B., M.M.), as well as the Stockholm County Council, the Swedish Cancer Foundation, and the Swedish Research Council (J.-I.H., Y.T.B.), the Cancer and Allergy Foundation of Sweden (J.-I.H.), the German Ministry of Education and Research (grant no. BMBF 01EO1303), and the German Research Foundation (grant no. SFB1160, TP1; S.E.). B.T. is also supported by a doctoral student scholarship from the Board of Postgraduate Studies at Karolinska Institutet. Computations were performed on resources provided by the Swedish National Infrastructure for Computing (SNIC) through the Uppsala Multidisciplinary Center for Advanced Computational Science under Project SNIC b2012204 and b2015280. Disclosure of potential conflict of interest: S. Ehl reports a grant from Deutsche Forschungsgemeinschaft (grant no. SFB1160 TP4) and a grant from BMBF (grant no. BMBF 01EO1303) during the conduct of the study and grants from Union Chimique Belge outside the submitted work. J.-I. Henter reports grants from the Swedish Childhood Cancer Foundation, the Swedish Cancer Foundation, the Swedish Research Council, the Stockholm County Council, and the Cancer and Allergy Foundation of Sweden during the conduct of the study. M. Meeths reports grants from the Swedish Childhood Cancer Foundation during the conduct of the study. The rest of the authors declare that they have no relevant conflicts of interest.
Individuals who receive a third mRNA vaccine dose show enhanced protection against severe COVID-19, but little is known about the impact of breakthrough infections on memory responses. Here, we examine the memory antibodies that develop after a third or fourth antigenic exposure by Delta or Omicron BA.1 infection, respectively. A third exposure to antigen by Delta breakthrough increases the number of memory B cells that produce antibodies with comparable potency and breadth to a third mRNA vaccine dose. A fourth antigenic exposure with Omicron BA.1 infection increased variant-specific plasma antibody and memory B cell responses. However, the fourth exposure did not increase the overall frequency of memory B cells or their general potency or breadth compared to a third mRNA vaccine dose. In conclusion, a third antigenic exposure by Delta infection elicits strain-specific memory responses and increases in the overall potency and breadth of the memory B cells. In contrast, the effects of a fourth antigenic exposure with Omicron BA.1 are limited to increased strain-specific memory with little effect on the potency or breadth of memory B cell antibodies. The results suggest that the effect of strain-specific boosting on memory B cell compartment may be limited.
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