The dynamic changes of lymphocyte subsets, neutrophils and cytokines profiles of patients with novel coronavirus disease (COVID-19) and their correlation with the disease severity has been studied in a paper recently published on EBioMedicine https://doi.org/10.1016/j.ebiom.2020.102763.
Of the 40 COVID-19 patients enrolled, 13 severe cases showed significant and sustained decreases in lymphocyte counts, but increases in neutrophil counts than 27 mild cases.
Further analysis demonstrated significant decreases in the counts of T cells, especially CD8+ T cells, as well as increases in IL-6, IL-10, IL-2 and IFN-g levels in the peripheral blood in the severe cases compared to those in the mild cases.
T cell counts and cytokine levels in severe COVID-19 patients who survived the disease gradually recovered at later time points to levels that were comparable to those of the mild cases.
Moreover, the neutrophil-to-lymphocyte ratio (NLR) and neutrophil-toCD8+ T cell ratio (N8R) were identified as powerful prognostic factors affecting the prognosis for severe COVID-19.
This study confirmed higher rates of developing lymphopenia in
severe patients than in mild patients (84,6% vs. 44,4%) and that the development of lymphopenia in severe patients was mainly related to the significantly decreased absolute counts of T cells, especially CD8+ T cells, but not to the absolute counts of B cells and NK cells. The decrease of T cells in the severe patient group reached its peak within the first week during the disease course, and then T cell numbers gradually increased during the second week and recovered to a comparable level to that of the mild patient group in the third week. All the severe patients included in the study survived the disease, and thus it’s speculated this course is associated with a favorable outcome in severe COVID-19 patients.
The results also demonstrate that severe COVID19 patients have higher concentrations of IL6, IL10, IL2 and IFN-g in the serum than mild cases, suggesting that the magnitude of cytokine storm is associated with the disease severity. Additionally, T cells are important for dampening overactive innate immune responses during viral infection and thus, a loss of T cells during SARS-CoV-2 infection may result in aggravated inflammatory responses, while a restoration of T cell numbers may alleviate them.
In line with this hypothesis, the authors observed that the kinetic changes of T cell counts were reversely correlated with the kinetic changes of most examined cytokine levels in the peripheral blood in severe COVID-19 patients. While T cell counts dropped to their lowest levels at 4-6 days after disease onset, serum IL-10, IL-2, IL-4, TNF-a and IFN-g levels reached their peaks. The courses of restoring T cell numbers are associated with decreases of serum IL-6, IL-10, IL-2, IL-4, TNF-a and IFN-g levels