Cytokine prediction of mortality in COVID19 patients

Abstract

Coronavirus disease 2019 (COVID19) is a life-threatening infection with uncertain progression and outcome. Assessing the severity of the disease for worsening patients is of importance in making decisions related to supportive mechanical ventilation and aggressive treatments. This was a prospective, non-randomized study that included hospitalized patients diagnosed with COVID19. Pro-inflammatory cytokines were assessed during hospitalization, and we calculated a prediction paradigm for 30-day mortality based on the serum levels of interleukin1β (IL1β), interleukin6 (IL6), interleukin8 (IL8), and tumor necrosis factor alpha (TNFα) measured by next-generation ELISA. Data of 71 COVID19 patients, mean age 62 years, SD13.8, 50 males, 21 females, were analyzed. Twelve (16.9%) patients died within 7-39 days of their first COVID19 positive nasopharyngeal test. Levels of IL6 and TNFα were significantly higher in patients that did not survive. IL6 predicted mortality at the cutoff value of 163.4 pg/ml, with a sensitivity of 91.7% and specificity of 57.6%. Our findings demonstrate that IL6 expression is significant for the prediction of 30-day mortality in hospitalized COVID19 patients and, therefore, may assist in treatment decisions.

Role of interleukin 6 as a predictive factor for a severe course of Covid-19: retrospective data analysis of patients from a Long-term Care Facility during Covid-19 Outbreak

“…There is a substantial body of evidence linking the IL-6 concentration to the severity of disease and unfavorable outcome of Covid-19 [11,12,13,14,15,16,18,19,20]. However, to our knowledge, this study is the rst study which evaluated the ability of IL-6 to predict the need for supplementary oxygen administration as a surrogate marker of severe Covid-19 requiring hospital admission in the population of high risk elderly patients.…”

“…The theory that IL-1β have an important role in the pathogenesis of Covid-19 is widely accepted [30]. However, recent study by Mandel et al found that baseline concentration of IL-1β is not signi cantly higher in nonsurvivors [20]. Giamarellos-Bourboulis et al concluded that immune dysregulation in severe Covid-19 is directly driven by IL-6, not IL-1β upregulation [19].…”

“…According to known evidence, IL-6 is superior to CRP and other markers of in ammation in predicting respiratory failure in Covid-19 [16,17]. IL-6 appears to be the most important driver of immune dysregulation and ARDS in Covid-19 [18,19,20,21]. The role of systematic measurement of IL-6, CRP, and other markers of in ammation at the initial assessment during Covid-19 outbreak in LTCF and its ability to predict the severe course of disease is yet to be determined.…”

Reply

“…Another explanation for extravascular fluid leakage into the lungs in COVID-19 is secretion of proinflammatory cytokines such as TNF and IL-6 during the cytokine storm (Fig 1, A). 7 We favor a third hypothesis, where excessive and prolonged secretion of type I and type III IFNs in the airways contributes to loss of lung epithelial barrier function during COVID-19 and other RNA virus infections (Fig 1, A). 8,9 To test whether entry of SARS-CoV-2 through ACE-2 is sufficient to induce type III IFNs without need for viral replication, we engineered a replication-deficient SARS-CoV-2 spike-HIV-luc pseudotype virus.…”

Preparing for the Storm: Mitigating the Effect of SARS-CoV-2 Induced Hypercytokinemia

“…The normal range for IL-1beta is 0.10pg/mL, and it could exceed 0.67pg/ml during disease [103].The normal range for TNF alpha is 0.0-8.1 pg/mL, and it could exceed 35pg/mL during disease [99,104]. Cytokine cut-offs are difficult to establish and may vary depending on several factors such as population genetics, pleiotropic nature, and health status of patient.…”