In the present study, 262 patients with COVID-19, who were admitted in two designated hospitals, and either survived or died during the hospitalization, were analyzed. The multivariate logistic regression analysis identified age, CHD, and the five laboratory variables, which included Lym%, PLT, CRP, LDH and D-dimer, as independent factors for the survival of COVID-19 patients. Based on this, a nomogram for predicting in-hospital survival was established, with excellent performance.
Advanced age has been reported as an important independent predictor of SARS and MERS mortality [10]. Several studies have reveal that elderly patients and patients with underlying comorbidities tend to have poor outcomes [11–14]. The patients infected with SARS-CoV-2 were analyzed, and it was found that there was a significant difference in age between the survival and non-survival groups. Furthermore, the multivariate analysis also revealed that age was an independent factor that affected the prognosis of COVID-19 patients. In the nomogram established by our team, it was found that the survival rate of COVID-19 patients decreased with the increase in age. According to the present analysis of the clinical data, the proportions of hypertension and CHD were significantly higher in the non-survival group, when compared to the survival group, and CHD was an independent risk factor for the prognosis of COVID-19 patients. This suggests that patients with hypertension and CHD are susceptible to SARS-CoV-2 infection, and have a high mortality rate. Although the underlying mechanism remains unclear, this may have been contributed by the following causes. First, angiotensin converting enzyme 2 (ACE2) receptor is widely expressed in the cardiovascular system, and SARS-CoV-2, which possesses ACE2, can directly attack cardiac muscle cells through this pathway [15, 16]. Second, there may be an imbalance between Th1 and Th2 responses in COVID-19 patients, and the cytokine storm triggered by this imbalance may be another mechanism of myocardial injury [17–19].
Interestingly, it was found PLT and D-dimer were independent risk factors for predicting the outcome of COVID-19 patients. Thrombocytopenia has been reported to be present in up to 55% of patients with SARS, and has been identified as an important risk factor for mortality [20]. In a study conducted by Zou et al., merely two variables (i.e. platelet count and hypoxemia) were used to establish a SARS prognostic model, and this was used to predict the survival rate, with an accuracy of 96.2% [5]. It has been demonstrated that the pathological features of COVID-19 are similar to those of SARS and MERS [21]. In the early stage of infection, patients present with inflammation, edema, protein exudation, focal hyperplasia of alveolar epithelial cells and patchy inflammatory infiltration, as well as multi-nucleated giant cells in the lung. In the late stage, in addition to hemorrhage and some areas of interstitial fibrosis, diffuse alveolar damage was also observed [22]. Furthermore, fibrous clots and gelatinous mucus in the small airway and diffuse intravascular coagulation were observed [23]. In a previous study, it was found that lung injury was the main cause, followed by heart, liver and kidney injuries, and coagulation system abnormality [24]. In the present study, there were abnormal coagulation functions in both the survival and non-survival groups, which mainly manifested with the increase in D-dimer. At the same time, it was found that there was a significant increase in fibrin degradation products and thrombocytopenia, which was consistent with the presence of hyper-fibrinolysis, in patients with severe COVID-19 [25]. Therefore, it is not difficult to understand that platelets and D-dimers are independent risk factors that affect the outcome of patients.
The present study revealed that Lym% and CRP were also independent risk factors that affected the prognosis of patients. The decrease in Lym% indicates that the immune system of a patient with SARS-CoV-2 is more likely to be suppressed, and that the host loses the immune function to fight against the pathogen, leading to the persistence of the infection and deterioration of COVID-19. In addition, the elevated levels of CRP observed in the present study, as well as in previous studies [24, 26], also suggest that there is a persistent inflammatory response in COVID-19 patients. Finally, it was found that LDH was another independent risk factor to predict the outcome of COVID-19 patients. It has been shown that COVID-19 patients first present with lung injury, which subsequently leads to hypoxemia and multiple organ damage [27]. Consequently, LDH in cells is released, resulting in increased LDH levels. Indeed, LDH was used to predict the severity of tissue damage in the early stage of diseases as an auxiliary marker, and for the early identification of cases at high risk of progression to severe COVID-19 [28].
The nomogram, as a visual form of predictive models, has been used in the diagnosis, treatment and prognosis of various diseases [29–32]. It is visual and intuitive, and does not need to substitute the numbers into the equation calculation. Furthermore, the user only needs to draw one or more lines to quickly and reliably obtain the prediction. In the present study, a nomogram was established, which can be used to accurately predict the prognosis of COVID-19 patients. The calibration curve revealed the accuracy of the nomogramic model for predicting the prognosis of COVID-19 patients ("dominant state") and the bootstrap model ("bias correction state"), which can explain the relationship between the prediction probability and actual observation probability in the original data set.
There were a few limitations in the present study. First, this was a retrospective study with relatively a small sample size. Second, the nomogram in the present study was not externally verified through another cohort of COVID-19 patients. Thus, the predictive performance remains to be further confirmed. Third, patients included in the present study were all over 18 years old. Thus, the nomogram is not suitable for children and pregnant women.