Interleukin-6 Is a Biomarker for the Development of Fatal Severe Acute Respiratory Syndrome Coronavirus 2 Pneumonia

Abstract

Hyper-inflammatory responses induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are a major cause of disease severity and death. Predictive prognosis biomarkers to guide therapeutics are critically lacking. Several studies have indicated a “cytokine storm” with the release of interleukin-1 (IL-1), IL-6, and IL-8, along with tumor necrosis factor alpha (TNFα) and other inflammatory mediators. Here, we proposed to assess the relationship between IL-6 and outcomes of patients with coronavirus disease 2019 (COVID-19). Our cohort consisted of 46 adult patients with PCR-proven SARS-CoV-2 infection admitted in a COVID-19 ward of the Hospital de Braga (HB) from April 7 to May 7, 2020, whose IL-6 levels were followed over time. We found that IL-6 levels were significantly different between the disease stages. Also, we found a significant negative correlation between IL-6 levels during stages IIb and III, peripheral oxygen saturation (SpO2), and partial pressure of oxygen in arterial blood (PaO2), showing that IL-6 correlates with respiratory failure. Compared to the inflammatory markers available in the clinic routine, we found a positive correlation between IL-6 and C-reactive protein (CRP). However, when we assessed the predictive value of these two markers, IL-6 behaves as a better predictor of disease progression. In a binary logistic regression, IL-6 level was the most significant predictor of the non-survivors group, when compared to age and CRP. Herein, we present IL-6 as a relevant tool for prognostic evaluation, mainly as a predictor of outcome.

Cell Population Data and Serum Polyclonal Immunoglobulin Free Light Chains in the Assessment of COVID-19 Severity

“…However, the study performed on our patients indicates significantly higher concentrations of ferritin and IL-6 in patients with COVID-19 requiring intensive care comparing with those hospitalized in non-ICU departments. With our results, we confirm observations made by other groups showing that IL-6 allows distinguishing between severe and nonsevere COVID-19 [ 38 , 39 , 40 , 41 , 42 ].…”

Proteomic and metabolomic investigation of serum lactate dehydrogenase elevation in COVID‐19 patients

“…Thirteen of the differentiated proteins were mapped into a network wherein key regulators were focused (Figure 2C). Within them, pro‐inflammatory cytokine IL‐6 has been widely recognized as a risk factor for COVID‐19 [18–22] and clinically observed to be positively correlated with serum LDH levels [23]. IL‐6 can activate TP53, which facilitates cell apoptosis and could enhance LDHA expression in blood.…”

COVID-19: Compreendendo a “tempestade de citocinas”

“…Porém, a IL-6 se comportou como um melhor preditor de progressão da doença no grupo de pacientes não sobreviventes, quando comparado à idade e a proteína C reativa. Assim, mais uma vez a dosagem sérica de IL-6 foi considerada como uma ferramenta relevante para avaliação prognóstica, principalmente como um preditor de resultado (Cruz et al, 2021;Hagab et al, 2020).…”

“…Como elevados níveis séricos de IL-6 foram fortemente associados à baixa sobrevida do paciente com COVID-19 grave teve início o tratamento de pacientes com o anticorpo monoclonal anti-IL-6, conhecido como Tocilizumabe®, que reduziu os casos de morte de pacientes hospitalizados com COVID-19 grave em 14%. Esses resultados reforçaram o papel patológico do excesso de citocinas pró-inflamatórias que culminam na tempestade de citocinas, e estimularam a busca por outros anti-inflamatórios com o mesmo objetivo de reduzir os níveis de citocinas no tecido inflamado (Cortegiani et al, 2020;Cruz et al, 2021;Han et al, 2020;Hermine et al, 2020;.…”