Dynamic changes in lymphocyte subsets and parallel cytokine levels in patients with severe and critical COVID-19

Abstract

Background: The lack of knowledge regarding the pathogenesis and host immune response during SARS-CoV-2 infection has limited the development of effective treatments. Thus, we longitudinally investigated the dynamic changes in peripheral blood lymphocyte subsets and parallel changes in cytokine levels in COVID-19 patients with different disease severities to further address disease pathogenesis.

Methods: A total of 67 patients (10 moderate, 38 severe and 19 critical cases) with COVID-19 admitted to a tertiary care hospital in Wuhan from February 8th to April 6th, 2020 were retrospectively studied. Dynamic data of lymphocyte subsets and inflammatory cytokines were collected.

Results: On admission, compared with moderate cases, severe and critical cases showed significantly decreased levels of total lymphocytes, T lymphocytes, CD4⁺ T cells, CD8⁺ T cells, B cells and NK cells. IL-6 and IL-10 were significantly higher in the critical group. During the following hospitalization period, most of the lymphocyte subsets in the critical group began to recover to levels comparable to those in the severe group from the fourth week after illness onset, except for NK cells, which recovered after the sixth week. A sustained decrease in the lymphocyte subsets and an increase in IL-6 and IL-10 were observed in the nonsurvivors until death. There was a strong negative correlation between IL-6 and IL-10 and total lymphocytes, T lymphocytes, CD4⁺ T cells, CD8⁺ T cells and NK cells.

Conclusions: A sustained decrease in lymphocyte subsets, especially CD4⁺ T cells and NK cells, interacting with proinflammatory cytokine storms was associated with severe disease and poor prognosis in COVID-19.

Keywords: COVID-19; Cytokine storm; Dynamic changes; Lymphocyte subsets; SARS-CoV-2.

Fig. 1

Dynamic changes of lymphocyte subsets in severe and critical COVID-19. Absolute numbers of total lymphocytes (a), T lymphocytes (b), CD4⁺ T-cells (c) and CD8⁺ T-cells (d), B cells (e), NK cells (f) were analyzed at different time points after hospital admission. Data were reported as median and interquartile range (IQR). The dotted line shows the lower limit of normal value of each parameter. *:p < 0.05

Fig. 2

Dynamic changes of inflammatory cytokines in severe and critical COVID-19. Serum levels of IL-2 (a), IL-4 (b), Ln(IL-6) (c), IL-10 (d), TNF-α(e) and IFN-γ (f) were analyzed at different time points after hospital admission. Data were reported as median and interquartile range (IQR). The dotted line shows the upper limit of normal value of each parameter. *:p < 0.05

Fig. 3

Correlation analysis between IL-6 and lymphocyte subsets. Correlation between Ln (IL-6) and total lymphocytes (a), T lymphocytes (b), CD4⁺ T-cells (c) and CD8⁺ T-cells (d), B cells (e), NK cells (f) were shown

Fig. 4

Correlation analysis between IL-10 and lymphocyte subsets. Correlation between IL-10 and total lymphocytes (a), T lymphocytes (b), CD4⁺ T-cells (c) and CD8⁺ T-cells (d), B cells (e), NK cells (f) were shown