Regulatory CD4 <sup>+</sup> and CD8 <sup>+</sup> T Cells Correlated Oppositely with CD4 <sup>+</sup>/CD8 <sup>+</sup> T Cell Ratios in Patients Acutely Infected with SARS-CoV-2

Abstract

Background: Regulatory T cell can protect against severe forms of coronaviral infections attributable to host inflammatory responses. But its role in the pathogenesis of COVID-19 is still unclear. Methods: Frequencies of total and multiple subsets of lymphocytes in peripheral blood of COVID-19 patients and recovered individuals were analyzed using multicolor flow cytometry assay. Plasma concentration of IL-10 was measured using a microsphere-based immunoassay kit. Results: Comparing to healthy controls, the frequencies of total lymphocytes and T cells decreased significantly in both acutely infected COVID-19 patients and recovered individuals. The frequencies of total lymphocytes correlated negatively with the frequencies of CD3-CD56+ NK cells. The frequencies of regulatory CD8+ CD25+ T cells correlated with CD4+/CD8+ T cell ratios positively, while the frequencies of regulatory CD4+CD25+CD127- T cells correlated negatively with CD4+ /CD8+T cell ratios. Ratios of CD4+/CD8+ T cells increased significantly in patients beyond age of 45. And accordingly, the frequencies of regulatory CD8+CD25+T cells were also found significantly increased in these patients. Interpretation: Frequencies of regulatory CD4+ and CD8+ T cells correlated oppositely with CD4+/CD8+ T cell ratios, suggesting that they may play distinct roles in the pathogenesis of COVID-19. Moreover, our data indicate that NK cells might contribute to the COVID-19 associated lymphopenia. Funding: This work was supported by the emergency project of Shanghai Science and Technology Commission [grant number 20411950502, 20431900403], the Major special projects of the Ministry of Science and technology [grant number 2018ZX10714002-001-005] and the National Natural Science Foundation of China [grant numbers 81671636, 81971559, 82041010]. Declaration of Interests: The author declared no conflicted interest. Ethics Approval Statement: Informed consents were obtained from all patients. The study was approved by the Research Ethics Review Committee (Ethics Approval Number: 2020-Y025-01) of the Shanghai Public Health Clinical Center Affiliated to Fudan University.