The Covid-19 pandemic as a challenging health issue during the recent years has about 2.3% crude mortality rate. This infection has unpredictable heterogeneous disease course. Although the most confirmed cases are mild, with cold-like symptoms to mild pneumonia, near to 14% of patients experience the severe conditions including serious pneumonia and breath shortness. It should be noted that in about 5% of cases (critically ill patients) disease can lead to developed respiratory failure, septic shock or/and multi-organ failure which is potentially life-threatening. [12] According to the results of any previous studies, IL-6 as a potent proinflammatory cytokine can stimulate c-reactive protein (CRP) and has been introduced as a trigger of the cytokine storm in COVID-19. [13–17] In this study we evaluate the relationship between serum level of IL-6 in the time of admission and disease severity among Covid-19 patients. Our results indicated that elevated IL-6 are associated with longer hospital stay and higher mortality that consistent with the results of previous studies. Keddie et al, showed that IL-6,CRP and interleukin 10 (IL-10) are strongly correlated with the illness severity. [18] Zulvikar Syambani Ulhaq et al also indicated that IL-6 has major importance because of its pleiotropic effects and circulating IL-6 serum levels can be closely linked to the severity of infection in Covid-19. [19] Association between IL-6 increasing and respiratory dysfunction has been addressed previously which imply a possible shared mechanism of cytokine-mediated lung damage resulted from SARS-CoV-2 infection. [20] Additionally, highly pathogenic SARS-CoV-2 can be associated with rapid replication of virus and a tendency to involve the lower respiratory system, resulting in an elevated response of IL-6-induced severe respiratory distress. Thus, these evidences suggest that immediately initial evaluation after hospitalization and serial measurement of IL-6 may be has an important role in assessing worsening clinical features and disease progression among Covid-19 patients. It should be noted that in addition to the association between IL-6 and Covid-19, increasing in IL-6 level has been proven to be a good biomarker for disease severity in other viral infections such as hepatitis B virus (HBV). [21]
In general, inflammation is closely associated with the covid-19 severity. Jing Gong et al in a retrospective study have shown that some inflammation-related parameters such as tumor necrosis factor α (TNFα), IL-6, interleukin-2 receptor (IL2R), interleukin-8 (IL-8), interleukin-10 (IL-10), CRP, ferroprotein, procalcitonin, white cell counts (WBC), lymphocyte counts (LC), neutrophil count (NC) and eosinophil counts (EC) are correlated to severity of COVID-19. [22]
In addition to the association between the increased IL-6 level and disease severity, the other factor which was related to the outcome in our data modeling was age so that the frequency of death and length of hospital stay increased with age. This finding is consistent with the studies of Jing Gong [22], Huang [23], Zhou [24], Wang [25] and Chen[26].
In this study we investigated the association between disease severity and some demographic and clinical variables such as diabetes mellitus, hypertension, BMI, age and gender. According to a review study, elderly age, male gender, preexisting hypertension, diabetes, obesity, COPD, tumor, immunodeficiencies, pregnancy, thromboembolism, coagulation disorders, leukocytosis, lymphopenia, eosinopenia, elevated serum levels of D-dimer, LDH, AST and ALT, BUN and creatine, cTnI, CRP, PCT, IL-6, IL-1β, KL-6, ferritin, higher CT pneumonia score, high number of affected pulmonary lobes, and smoking are major risk factors of severe clinical course and outcomes in patients with COVID-19.[27] Indeed, assessment of all potential related factors require further studies with higher sample size and multicenter design.
Our study has some limitations. First, the number of two study groups was small due to the single center design of the study. Second, clinical data and some inflammatory response markers such as C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and plasma viscosity (PV) were limited. Based on the review of the literature, most of the previous studies that investigated the role of IL-6 in the severity of covid-19 infection were done retrospectively, and the longitudinal and being straightforward design of the present study is considered to be its most important strength.