RESUMO
Background: A better understanding of COVID-19 immunopathology is needed to identify the most vulnerable patients and improve treatment options. Objective: We aimed to identify immune system cell populations, cytokines, and inflammatory markers related to severity in COVID-19. Methods: 139 hospitalized patients with COVID-19-58 mild/moderate and 81 severe/critical-and 74 recovered patients were included in a prospective longitudinal study. Clinical data and blood samples were obtained on admission for laboratory markers, cytokines, and lymphocyte subsets study. In the recovered patients, lymphocyte subsets were analyzed 8-12 weeks after discharge. Results: A National Early Warning Score 2 >2 (OR:41.4; CI:10.38-167.0), ferritin >583 pg/mL (OR:16.3; CI: 3.88-69.9), neutrophil/lymphocyte ratio >3 (OR: 3.5; CI: 1.08-12.0), sIL-2rα (sCD25) >512 pg/mL (OR: 3.3; CI: 1.48-7.9), IL-1Ra >94 pg/mL (OR: 3.2; IC: 1.4-7.3), and IL-18 >125 pg/mL (OR: 2.4; CI: 1.1-5.0) were associated with severe/critical COVID-19 in the multivariate models used. Lower absolute values of CD3, CD4, CD8, and CD19 lymphocytes together with higher frequencies of NK cells, a CD4 and CD8 activated (CD38+HLA-DR+) memory T cell and effector memory CD45RA+ (EMRA) phenotype, and lower T regulatory cell frequencies were found in severe/critical patients relative to mild/moderate and recovered COVID-19 patients. A significant reduction in Th1, Tfh1, and Tc1 with higher Th2, Tfh2, Tc2, and plasma cell frequencies was found in the most severe cases. Conclusion: A characteristic hyperinflammatory state with significantly elevated neutrophil/lymphocyte ratio and ferritin, IL-1Ra, sIL-2rα, and IL-18 levels together with a "low T1 lymphocyte signature" was found in severe/critical COVID-19 patients.
RESUMO
Mechanisms involved in thyroid dysfunction in critically ill coronavirus disease 2019 (COVID-19) patients are not clear. Our objective was to correlate the thyroid response with the pro- and anti-inflammatory cytokines profile in critically ill COVID-19 patients. This was a prospective single-center study. We studied the relationship between continuous variables by using Pearson correlation and simple linear regression. Multiple logistic regression analysis was performed to analyze the factors independently associated with mortality. Seventy-eight patients were included in the study at intensive care unit (ICU) admission and 72 had a measurement of the thyroid and inflammatory profile at day 5. No significant correlations were found between thyroid stimulating hormone (TSH), free triiodothyronine (fT3) and free thyroxine (fT4) and inflammatory cytokines at ICU admission. At day 5, fT4, was inversely correlated with IL-10 (p = 0.035). IL-10 was associated with maximum lactate (p < 0.001) and SOFA score values (p = 0.012). The multiple logistic regression analysis showed that there was a significant relationship between IL-10 (day 5) and in-hospital mortality after adjusting by age and severity of illness. In conclusion, we found that the thyroid hormone profile and inflammatory cytokines had a weak correlation at ICU admission. Associations of interest between fT4 and IL-10 were found at day 5. IL-10 at day 5 was found to be correlated with low fT4 and markers of organ failure and death.