Longitudinal characteristics of lymphocyte responses and cytokine profiles in the peripheral blood of SARS-CoV-2 infected patients

Abstract

Longitudinal characteristics of lymphocyte responses and cytokine profiles in the peripheral blood of SARS-CoV-2 infected patients, EBioMedicine (2020), doi: https://doi.Abstract Background: The dynamic changes of lymphocyte subsets and cytokines profiles of patients with novel coronavirus disease (COVID-19) and their correlation with the disease severity remain unclear. Methods: Peripheral blood samples were longitudinally collected from 40 confirmed COVID-19 patients and examined for lymphocyte subsets by flow cytometry and cytokine profiles by specific immunoassays. Findings: Of the 40 COVID-19 patients enrolled, 13 severe cases showed significant and sustained decreases in lymphocyte counts [0·6 (0·6-0·8)] but increases in neutrophil counts [4·7 (3·6-5·8)] than 27 mild cases [1.1 (0·8-1·4); 2·0 (1·5-2·9)].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-γ 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) (AUC=0·93) and neutrophil-to-CD8 + T cell ratio (N8R) (AUC =0·94) were identified as powerful prognostic factors affecting the prognosis for severe COVID-19.Interpretation: The degree of lymphopenia and a proinflammatory cytokine storm is higher in severe COVID-19 patients than in mild cases, and is associated with the disease severity. N8R and NLR may serve as a useful prognostic factor for early 4 identification of severe COVID-19 cases.

Whole blood immunophenotyping uncovers immature neutrophil-to-VD2 T-cell ratio as an early prognostic marker for severe COVID-19

“…This allowed estimation of cell counts in those groups and identification of markers that potentially depict disease severity. Consistent with previous studies on CD4 and CD8 lymphopenia 6,22,23 , CD8 + , CD4 + , MAIT, VD1 and VD2 T-cells showed a gradual reduction in the peripheral blood with increasing disease severity (Figure 3B). The effect was more pronounced for CD8 + and VD2 T-cells (Figure 3B), suggesting a strong activation and infiltration of these cells in the lungs.…”

“…Neutrophil-to-Lymphocyte Ratio (NLR) or Neutrophil-to-CD8 T-cell Ratio (N8R) were proposed to be good diagnostic and prognostic markers for severe COVID-19 respiratory disease 23,24 . However, these studies observed increased neutrophils in severe cases which was not consistent with our observations and in another study 25 (Figure 1F and 3E).…”

Nrf2 Activator PB125®as a Potential Therapeutic Agent Against COVID-19

“…It is worth noting that the longitudinal study of COVID-19 patients [47] reported a remarkably higher concentration of serum ferritin in the severe cases (averaging 835.5 g/l, with a range of 635.4 to 1538.8) versus the milder cases (averaging 367.8 g/l, with a range of 174.7 to 522.0). Ferritin has long been recognized as a source of iron released under inflammatory conditions by the superoxide radical [48][49][50][51].…”

“…We speculate that the well-documented age-related loss of Nrf2 expression [4,5] is a potential contributor to the occurrence of a cytokine storm. A longitudinal study of 40 confirmed COVID-19 patients [47] showed that the 13 severe cases, compared to the 27 milder cases, were older (mean age 59.7 vs 43.2), had significantly elevated C-reactive protein (mean 62.9 vs 7.6 mg/l), and showed consistently higher neutrophil counts and lower lymphocyte counts throughout the two week observation period. These observations [46,47] document a clear predilection for severity of COVID-19 infection directly associated with age and intensity of inflammatory response, and presumably inversely associated with Nrf2 expression.…”

“…A longitudinal study of 40 confirmed COVID-19 patients [47] showed that the 13 severe cases, compared to the 27 milder cases, were older (mean age 59.7 vs 43.2), had significantly elevated C-reactive protein (mean 62.9 vs 7.6 mg/l), and showed consistently higher neutrophil counts and lower lymphocyte counts throughout the two week observation period. These observations [46,47] document a clear predilection for severity of COVID-19 infection directly associated with age and intensity of inflammatory response, and presumably inversely associated with Nrf2 expression. The production and self-amplifying nature of an acute inflammatory response demands a prompt subsequent "survival response" from the host tissue to break the self-sustaining attraction of neutrophils to inflamed tissues.…”