Severe COVID-19 can easily cause ARDS, multiple organ dysfunction, acute heart injury, acute kidney injury and even death . Identifying the death risk associated with critically ill patients early and giving these patients priority treatment in a timely manner are particularly important in global health emergencies. Studies have shown that a total of 60 predictors can assess the severity of COVID-19, of which 7 factors are considered to be highly correlated and consistent, including SOFA score, age, D-dimer, hs-CRP, body temperature, albumin and diabetes . The results of this study revealed that SOFA score, age, CKD, CLD1, CLD2, cystatin C, hs-CRP, CK, CK-MB and other factors were independent risk factors for in-hospital death, which was similar to the results of the above study.
Zhou et al. showed that older age, higher D-dimer levels and higher SOFA scores in COVID-19 patients at admission were associated with high in-hospital mortality. In addition, increased levels of cTnI, lactate dehydrogenase and lymphocytopenia were more common in patients with severe COVID-19 . Also, studies have shown that SARS-CoV-2 can participate in and induce the activation of complement and coagulation system, which is related to the severity of COVID-19 patients . Myocardial injury was another an independent risk factor for deterioration and death in patients with COVID-19. The risk of death of hospitalized patients with myocardial injury was 6.6–26.9 times higher than that of patients without myocardial injury .
In this study, the median age of seriously ill patients was 56.00 years, which was significantly higher than that of mild patients (38 years). Hypertension was the most common complication of COVID-19, especially in severe patients. A review of the literature showed that COVID-19 patients with hypertension, especially elderly patients, had a 2.5-fold increased risk of serious or even fatal events . Another large cohort study showed that in addition to some factors, such as advanced age, male, asthma, diabetes, increased the risk of death in COVID-19 patients, poverty and ethnicity (Blacks and South Asians) were also associated with death of COVID-19 patients .
At present, published studies have not systematically evaluated the accuracy of the SOFA score in the diagnosis of COVID-19 severity and its predictive value. The SOFA score was originally used to assess the severity of organ dysfunction in patients with severe sepsis and has been validated in ICU patients in multiple regions . As critically ill patients usually have multiple organ dysfunction, the SOFA score has been widely used to predict the clinical outcomes of critically ill patients, such as predicting mortality in patients with chronic liver failure and hematological malignancies [20, 21]. Gupta et al. summarized the clinical characteristics of SARS-CoV-2 infection, which could not only cause severe lung injury, but also damaged the heart, liver, kidney, nervous system, endocrine system, blood system and skin, resulting in arrhythmia, acute coronary syndrome, thrombosis, gastrointestinal symptoms, hyperglycemia and skin rash . Thus, the SOFA score can comprehensively assess multiple organ dysfunction caused by SARS-CoV-2.
In our study, the SOFA score was also recognized as a valuable prognostic tool for the outcome of patients with COVID-19. Univariate regression analysis showed that the increase in SOFA score and IL-6 and the decrease in lymphocyte count were related to the aggravation of the patient's condition. Multivariable regression analysis demonstrated that SOFA score, advanced age, and hypertension were independently associated with the risk of severe COVID-19. At present, it is believed that COVID-19 leads to organ failure, which is mainly related to cytokine storm and immunosuppression; the clinical manifestations are persistent fever, hemocytopenia and organ involvement . The laboratory results were characterized by increased levels of inflammatory factors such as granulocyte colony-stimulating factor (G-CSF), interleukin-2 (IL-2), IL-6, interleukin-7 (IL-7), interferon-γ–inducible protein-10 (IP-10), tumor necrosis factor α (TNF-α), macrophage inflammatory protein-1 α (MIP-1 α) and monocyte chemoattractant protein 1 (MCP-1) [24, 25]. The analysis of the immune system of patients with severe COVID-19 showed that the number of innate immune cells increased, while T cells decreased. In COVID-19 patients, the early increase of cytokines was positively correlated with poor prognosis . This may well explain why only dexamethasone has been found to reduce mortality in many clinical trials for COIVD-19 . Therefore, the SOFA score can reflect not only multiple organ failure but also the degree of inflammation and can accurately predict the severity of the patient’s disease.
Sepsis is a life-threatening organ dysfunction, caused by dysregulated host response to infection. Rapid change in SOFA score ≥ 2 points after infection is regarded as the clinical criterion of sepsis-associated organ dysfunction. The SOFA score ≥ 2 reflects approximately 10% of the overall risk of death of suspected infected patients in general hospitals, and even patients with moderate organ dysfunction may further deteriorate. Therefore, it emphasizes the seriousness of this situation and reminds clinicians to intervene in a timely and appropriate manner . In this study, the area under the ROC curve (AUC) of the SOFA score was 0.908 (95% CI: 0.857–0.960) with a diagnostic cut-off value of 2 and a sensitivity and specificity of 85.20% and 80.40%, respectively. This result suggests that a SOFA score ≥ 2 can predict the severity of COVID-19 patients. Another study also showed that among 184,875 patients admitted to the ICU, an increase of 2 or more in the SOFA score had greater prognostic accuracy for in-hospital mortality than quick SOFA (qSOFA) score or the systemic inflammatory response syndrome standard . When the cut-off value of the optimal SOFA score is 5 (AUC: 0.995, 95% CI: 0.985-1.000, sensitivity: 100.00%, specificity: 95.40%), the risk of mortality in patients with COVID-19 can be predicted. Regarding the 60-day mortality rate of patients in the high and low SOFA score groups, patients in the high SOFA score group (SOFA score ≥ 5) had a significantly higher risk of death than those in the low SOFA score group (SOFA score < 5). Wang et al. used the SOFA score to assess the predictive value of early sepsis and 30-day mortality after liver transplantation, indicating that the survival rate of patients with SOFA score > 5 within 1–7 days after liver transplantation was significantly lower than that of patients with SOFA score ≤ 5 . Therefore, SOFA score ≥ 5 can be used as a good predictor of hospital mortality in COVID-19 patients. In addition, univariate and multivariate Cox proportional hazards regression analyses demonstrated that there was a high correlation between the SOFA score and hospital mortality, and the SOFA score was a risk factor for death in COVID-19 patients. These results provide strong evidence for priority in treatment and early special care for patients.
Nevertheless, some limitations should be considered when interpreting the results of this study. First, this is a single center retrospective study involving a relatively small number of patients. Second, our study was limited by its retroactive design, which resulted in some data unavailable in the electronic medical records. In some cases, if the patient’s condition was stable during hospitalization without dyspnea and hypoxia, blood gas analysis was not performed, so the SOFA score could not be calculated accurately and had to be estimated by the EM algorithm. However, in our study, the data loss rate of this variable was less than 25%. Finally, the retrospective nature of our study may lead to selection bias, and the findings need to be verified and refined by future prospective studies.