Tnf-Alpha But Not Il-6 At Admission Is Associated With Duration Of Stay And Oxygen Requirement In A Diverse Cohort Of Patients With Covid-19

Introduction: SARS-COv-2, the novel coronavirus responsible for COVID19 causes a wide range of pathology. While some patients may experience mild or asymptomatic infection, others will progress to respiratory failure and death. Although some clinical parameters have been shown to predict patient outcomes, the role of cytokine measurements is controversial. The aim of the study was to determine whether admission cytokine levels can predict the clinical course of patients with COVID19. Methods: Blood was collected at admission from 41 patients with COVID19 at Virginia Commonwealth University from April-July 2020. A panel of 27 pro-inflammatory cytokines was measured in serum by multiplex assay. 20 patients were selected for analysis;10 with moderate disease (hospital admission, <4L O2 need) and 10 severe COVID patients (ICU admission);patients with active malignancy were excluded. Multivariate principal component and correlation analysis (PCA) was performed. Patient severity (ICU admission, max O2 requirement, duration of hospital stay), patient demographics (gender, race, BMI), and serum cytokine levels were analyzed. Results: The only significant correlation with disease severity was duration of stay with TNF-α (0.5772,p=0.0097, Fig. 1A). IL-6 was not correlated with severity. PCA clustered severe patients together, with more variability being observed in the moderate cases (Fig.1B). Disease severity parameters cluster together with limited association with the cytokine and demographics parameters (Fig.1C). PCA identified 2 main clusters of cytokines, but neither was associated with severity. TNF-α and IL-8 were separate from the other cytokines (Fig.1C). Discussion: In this small series of COVID19 patients from an urban academic medical center, PCA revealed correlation between admission TNF-α levels and the development of severe COVID19. No correlation was noted between admission IL-6 levels and disease severity. An association between TNF-α and outcomes has recently been described in a large cohort from the United States, but we were not able to determine other predictors of outcomes despite an extensive cytokine panel. The discrepancy with prior studies may be attributed to the high percentage of African-American subjects and high rates of comorbidities in our cohort. Our findings show low levels of key cytokines when compared to previous studies in non-COVID ARDS suggesting a difference in the pathophysiology of severe COVID19. The lack of IL-6 association with severe COVID19 is consistent with recent negative trials of IL-6 blockade in COVID19. Larger studies are needed to explore the role of TNF-α in the development of severe COVID19 and its potential as a therapeutic target.