DataSheet_1_Effect of antiviral and immunomodulatory treatment on a cytokine profile in patients with COVID-19.docx

BackgroundThe severity of COVID-19 is associated with an elevated level of a variety of inflammatory mediators. Increasing evidence suggests that the Th17 response contributes to the severity of COVID-19 pneumonia, whereas Th22 response plays a regulatory role in SARS-CoV-2 infection. Two main types of available COVID-19 treatments are antivirals and immunomodulatory drugs; however, their effect on a cytokine profile is yet to be determined.MethodsThis study aim to analyse a cytokine profile in peripheral blood from patients with COVID-19 (n=44) undergoing antiviral or/and immunomodulatory treatment and healthy controls (n=20). Circulating CD4+ and CD8+ T cells and their intracellular expression of IL-17A and IL-22 were assessed by flow cytometry.ResultsInitial results showed an overexpression of IL-17F, IL-17A, CCL5/RANTES, GM-CSF, IL-4, IL-10, CXCL-10/IP-10 and IL-6 in COVID-19 patients compared to healthy controls. Treatment with remdesivir resulted in a significant decline in concentrations of IL-6, IL-10, IFN-alpha and CXCL10/IP-10. Immunomodulatory treatment contributed to a significant downregulation of IL-10, IFN-alpha, CXCL10/IP-10 and B7-H3 as well as upregulation of IL-22 and IL-1 beta. A combination of an antiviral and immunomodulatory treatment resulted in a significant decrease in IL-17F, IL-10, IFN-alpha, CXCL10/IP-10 and B7-H3 levels as well as an increase in IL-17A and IL-1 beta. We found significantly higher percentage of both CD4+ and CD8+ T cells producing IL-17A and CD4+ T cells producing IL-22 in patients with COVID-19.ConclusionAdministration of antiviral or/and immunomodulatory treatment resulted in a significant downregulation of pro-inflammatory cytokine expression and an upregulation of T cell absolute counts in most cases, thus showing effectiveness of treatment in COVID-19. SARS-CoV-2 infection induced cytokine overexpression in hospitalized patients with COVID-19 as well as lymphopenia, particularly a decrease in CD4+ and CD8+ T cell counts. Moreover, despite the reduced counts of CD4+ and CD8+ T cells, both subsets showed overactivation and increased expression of IL-17A and IL-22, thus targeting Th17 response might alleviate inflammatory response in severe disease.</p

Boceprevir Plus Peginterferon Alfa-2a/Ribavirin in Treatment-Naïve Hepatitis C Virus Genotype 1 Patients: International Phase IIIb/IV TriCo Trial

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Multivariate logistic regression analysis.

ALT = alanine aminotransferase; ALT ratio = ALT divided by ULN for the local laboratory; ULN = upper limit of normal. aWald chi-square test for each regression coefficient; b Wald chi-square test for each variable</p

Patient selection for the development cohort.

Patient selection for the development cohort.</p

Relationship between alanine aminotransferase (ALT)/upper limit of normal (ULN) and sustained virologic response (SVR).

<p>Short vertical lines indicate the number of patients with SVR (black lines) and no SVR (grey lines). Open circles represent probability of SVR according to the GAM analysis. Closed circles represent empirical probability for midpoints of deciles. ALT/ULN = patients' ALT divided by the ULN for the local laboratory</p

Scoring system for predictive baseline characteristics.

<p>Scoring system for predictive baseline characteristics.</p

Patient selection for the validation cohort.

<p>Patient selection for the validation cohort.</p

Baseline demographic and disease characteristics.

<p>HCV, hepatitis C virus; <i>IL28B</i>, interleukin 28B; RBV, ribavirin; TVR, telaprevir.</p

Subgroup analysis for SVR12.

<p>CI, confidence interval; HCV, hepatitis C virus; <i>IL28B</i>, interleukin 28B; RBV, ribavirin; SVR12, sustained virologic response at week 12 post-treatment follow-up; TVR, telaprevir.</p

Relationship between age and sustained virologic response (SVR).

<p>Short vertical lines indicate the number of patients with SVR (black lines) and no SVR (grey lines). Open circles represent probability of SVR according to the GAM analysis. Closed circles represent empirical probability for midpoints of deciles.</p