A Deep Look Into COVID-19 Severity Through Dynamic Changes in Blood Cytokine Levels.

An excessive inflammatory response to SARS-CoV-2 is thought to be a major cause of disease severity and mortality in patients with COVID-19. Longitudinal analysis of cytokine release can expand our understanding of the initial stages of disease development and help to identify early markers serving as predictors of disease severity. In this study, we performed a comprehensive analysis of 46 cytokines (including chemokines and growth factors) in the peripheral blood of a large cohort of COVID-19 patients (n=444). The patients were classified into five severity groups. Longitudinal analysis of all patients revealed two groups of cytokines, characterizing the "early" and "late" stages of the disease course and the switch between type 1 and type 2 immunity. We found significantly increased levels of cytokines associated with different severities of COVID-19, and levels of some cytokines were significantly higher during the first three days from symptom onset (DfSO) in patients who eventually required intensive care unit (ICU) therapy. Additionally, we identified nine cytokines, TNF-α, IL-10, MIG, IL-6, IP-10, M-CSF, G-CSF, GM-CSF, and IFN-α2, that can be used as good predictors of ICU requirement at 4-6 DfSO.

Neutralizing Activity of Sera from Sputnik V-Vaccinated People against Variants of Concern (VOC: B.1.1.7, B.1.351, P.1, B.1.617.2, B.1.617.3) and Moscow Endemic SARS-CoV-2 Variants.

Since the beginning of the 2021 year, all the main six vaccines against COVID-19 have been used in mass vaccination companies around the world. Virus neutralization and epidemiological efficacy drop obtained for several vaccines against the B.1.1.7, B.1.351 P.1, and B.1.617 genotypes are of concern. There is a growing number of reports on mutations in receptor-binding domain (RBD) increasing the transmissibility of the virus and escaping the neutralizing effect of antibodies. The Sputnik V vaccine is currently approved for use in more than 66 countries but its activity against variants of concern (VOC) is not extensively studied yet. Virus-neutralizing activity (VNA) of sera obtained from people vaccinated with Sputnik V in relation to internationally relevant genetic lineages B.1.1.7, B.1.351, P.1, B.1.617.2, B.1.617.3 and Moscow endemic variants B.1.1.141 (T385I) and B.1.1.317 (S477N, A522S) with mutations in the RBD domain has been assessed. The data obtained indicate no significant differences in VNA against B.1.1.7, B.1.617.3 and local genetic lineages B.1.1.141 (T385I), B.1.1.317 (S477N, A522S) with RBD mutations. For the B.1.351, P.1, and B.1.617.2 statistically significant 3.1-, 2.8-, and 2.5-fold, respectively, VNA reduction was observed. Notably, this decrease is lower than that reported in publications for other vaccines. However, a direct comparative study is necessary for a conclusion. Thus, sera from "Sputnik V"-vaccinated retain neutralizing activity against VOC B.1.1.7, B.1.351, P.1, B.1.617.2, B.1.617.3 as well as local genetic lineages B.1.1.141 and B.1.1.317 circulating in Moscow.