AUTHOR=Pons Maria J. , Ymaña Barbara , Mayanga-Herrera Ana , Sáenz Yolanda , Alvarez-Erviti Lydia , Tapia-Rojas Salyoc , Gamarra Roxana , Blanco Amanda B. , Moncunill Gemma , Ugarte-Gil Manuel F. TITLE=Cytokine Profiles Associated With Worse Prognosis in a Hospitalized Peruvian COVID-19 Cohort JOURNAL=Frontiers in Immunology VOLUME=12 YEAR=2021 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.700921 DOI=10.3389/fimmu.2021.700921 ISSN=1664-3224 ABSTRACT=

Cytokines, chemokines and growth factors present different expression profiles related to the prognosis of COVID-19. We analyzed clinical parameters and assessed the expression of these biomarkers in patients with different disease severity in a hospitalized Peruvian cohort to determine those associated with worse prognosis. We measured anti-spike IgG antibodies by ELISA and 30 cytokines by quantitative suspension array technology in 123 sera samples. We analyzed differences between patients with moderate, severe and fatal COVID-19 by logistic regression at baseline and in longitudinal samples. Significant differences were found among the clinical parameters: hemoglobin, neutrophils, lymphocytes and C-reactive protein (CRP), creatinine and D-dimer levels. Higher anti-spike IgG antibody concentrations were associated to fatal patient outcomes. At hospitalization, IL-10, IL-6, MIP-1α, GM-CSF, MCP-1, IL-15, IL-5, IL1RA, TNFα and IL-8 levels were already increased in fatal patients´ group. Meanwhile, multivariable analysis revealed that increased GM-CSF, MCP-1, IL-15, and IL-8 values were associated with fatal outcomes. Moreover, longitudinal analysis identified IL-6 and MCP-1 as the main risk factors related to mortality in hospitalized COVID-19 patients. In this Peruvian cohort we identified and validated biomarkers related to COVID-19 outcomes. Further studies are needed to identify novel criteria for stratification of SARS-CoV-2 infected patients at hospital entry.

Background

In the most severe forms of SARS-CoV-2 infection, large numbers of innate and adaptive immune cells become activated and begin to produce pro-inflammatory cytokines, establishing an exacerbated feedback loop of inflammation.

Methods

A total of 55 patients with laboratory-confirmed COVID-19 admitted to the Hospital Nacional Guillermo Almenara Irigoyen in Lima, Peru were enrolled during August-October 2020. Of these, 21 had moderate disease, 24 severe diseases and 10 died. We measured 30 cytokines and chemokines by quantitative suspension array technology and anti-spike IgG antibodies using a commercial ELISA. We evaluated these parameters in peripheral blood every 2-5 days until patient discharge or death. Patient information and clinical parameters related were obtained from the respective clinical histories.

Results

The frequency of obesity differed among the 3 groups, being most frequent in patients who died. There were also significant differences in clinical parameters: hemoglobin, segmented neutrophils, lymphocytes,C-reactive protein, creatinine and D-dimer levels. Greater anti-spike IgG antibody concentrations were associated to fatal outcomes. In univariate analyses, higher baseline concentrations of IL-6, MIP-1α, GM-CSF, MCP-1, IL-15, IL-5, IL1RA, TNFα, IL-8 and IL-12p70 correlated with severity, while multivariable analysis showed that increased concentrations in 4 biomarkers (GM-CSF, MCP-1, IL-15, IL-8) were associated with fatal outcomes. Longitudinal analysis showed IL-6 (hazard ratio [HR] 6.81, 95% confidence interval [CI] 1.6-28.7) and MCP-1 (HR 4.61, 95%CI 1.1-19.1) to be related to mortality in hospitalized COVID-19 patients.

Conclusions

Cytokine, chemokine and growth factor profiles were identified and validated related to severity and outcomes of COVID-19. Our findings may be useful to identify novel criteria for COVID-19 patient stratification at hospital entry.