For patients who have been diagnosed with serious COVID-19 on admission, the rapid progression of the disease, the extremely difficult process of treatment, and coupled with the risk of criticality or even death at any time, have important significance for closely monitoring the progression of the disease and taking appropriate treatment measures in a timely manner. To uncover key factors for evaluating the risk of critical progression and mortality outcomes in serious patients, we comprehensively compared the differences across various indicators of admission between severe and critical cases and between survivors and non-survivors among critical patients. In this study, by multivariable logistic regression analysis, we found that advanced age, a high level of respiratory rate, LDH and hs-cTnI, and lymphopenia and thrombocytopenia at admission were strongly associated with the incidence of poor prognosis in patients with severe COVID-19. In addition, our results also reveal that hs-cTnI levels are substantially associated with mortality outcomes in critical patients, as a high hs-cTnI level acts as a crucial risk factor for death in critical patients, both in models that included and excluded age, gender, and disease history. Moreover, it was observed that LDH and hs-cTnI were sound diagnostic markers when distinguishing between severe and critical cases, whereas PCT and D-dimer levels, along with the above two markers, were also of value when predicting mortality outcome among all patients with serious COVID-19.
In the research cohort, males accounted for a large proportion of patients admitted for severe COVID-19, and the proportion of males in the critical group was significantly higher than that in the severe group, suggesting that males appear to be more susceptible to COVID-19 and are more likely to develop into clinically severe COVID-19. Previous analysis of epidemiological characteristics also showed that the prevalence and mortality among males with COVID-19 were obviously higher than those among females [10, 11]. Possible explanations are the effects of different hormones and the fact that smoking, which is much more prevalent in the male population than in the female population, leads to an upregulation expression of angiotensin-converting enzyme 2 (ACE2), which may serve as a potential invasion receptor for SARS-CoV-2 [12–14]. The results showed that patients in severe conditions were overwhelmingly older than 50 years and that critical patients were notably older than those with severe conditions, indicating that older patients are at a higher risk of requiring critical care, which is consistent with the current study's findings . Critical patients were more likely to feel chest distress than severe patients, which means they are prone to breathlessness and require additional respiratory assistance support . The higher incidence of COLD and other diseases in critical patients can be explained by the fact that patients with comorbidities are comparatively more immunocompromised and less resistant to viruses, as previous studies have indicated that a history of underlying disease acts as an influential factor in the death of critical patients with COVID-19 . In this study, we did not identify a clear distinction between the severe and critical groups within regard to carcinoma and coronary heart disease, presumably owing to the relatively limited number of patients with the corresponding diseases. Thus, this needs to be examined further in a larger relevant population.
Among a range of indicators that differed sharply from severe to critical cases, we identified that in addition to advanced age, elevated RR, LDH, and hs-cTnI, as well as decreased lymphocyte and platelet counts, constitute important risk factors for poor prognosis in severe patients, while the ROC curve also demonstrated that LDH and hs-cTnI are valuable predictors of critical progression in severe cases. Critical patients are more likely than severe patients to suffer from shortness of breath and dyspnea, leading to acute respiratory distress syndrome (ARDS) and even respiratory failure, as rapid breathing often indicates ventilatory dysfunction . Therefore, intensely and promptly monitoring changes in respiratory rate could satisfy the auxiliary ventilation needs in severe patients and, reduce the perilous risk. lymphocyte and platelet counts are often indicative of viral infection in patients. Likewise, studies have shown that lymphopenia exists in the majority of patients with severe COVID-19 [19, 20], and sustained low levels may further exacerbate the risk of poor prognosis and death in severe cases. LDH and hs-cTnI, as sensitizing markers of myocardial injury, provide an early indicator of to the extent of cardiac damage in patients . However, the differences between the severe and critical groups suggest that patients with severe COVID-19 may have sustained varying degrees of cardiac damage as the disease progresses. Recent studies have also indicated that multiple serious sequelae persisted in patients who recovered from severe COVID-19 disease, including massive heart impairment [22, 23]. Furthermore, some other parameters with distinct differences in elevated levels such as D-dimer, cytokines (IL-2R, IL-6, IL-8, IL-10) and of inflammatory factors (CRP, PCT) also imply, to some extent, that the probability of adverse prognosis progression in severe patients, as other scholars elucidated in early research [24, 25].
Surprisingly, hs-cTnI also play a pivotal role among the risk factors affecting mortality outcomes in critically ill patients, since patients with higher hs-cTnI levels tend to experience greater severity and mortality rates among all serious cases, they are also more likely to necessitate aggressive therapeutic measures such as invasive and noninvasive mechanical ventilation and corticosteroids therapy. Hs-cTnI, compared to LDH, displays superior sensitivity and specificity in diagnosing the myocardial injury. In most clinical situations, elevated hs-cTnI is suggestive of myocardial injury with necrosis and associated with adverse clinical outcomes . Given that only 10.8% of serious patients in this study had a heart-related disease, and elevated hs-cTnI levels as shown in patients with severe and critical COVID-19 are more likely to be attributed to the primary myocardial injury caused by SARS-CoV-2. A newly research has also shown that SARS-CoV-2 can infect heart cells in petri dishes of laboratory, suggesting that the heart cells in COVID-19 patients may be directly infected by the virus, resulting in heart muscle damage and heart-related complications . Previous studies have reported an increased risk of death in COVID-19 patients with elevated hs-cTnI levels [28–29], moreover, our findings suggest that even when adjusted for influences such as sex, age and disease history, hs-cTnI levels continued to work in predicting the progression of prognosis and the outcome of death in serious cases. As a result, early monitoring of cardiac injury-related markers, including hs-cTnI, can play a significant role in reducing the risk of death in serious condition.
Unavoidably, several limitations in our study are worth noting. First, as this study was retrospective, and the outbreak of the disease imposed a tight time frame for patient resuscitation, which resulted in inadequate data for some items, thus, further validation of the specific findings is required in a prospective cohort study. In addition, the classification of indicators was based more on the healthy individuals, and more specific and detailed classification references should be established for COVID-19 patients. Finally, most of the data from this study were derived from the patient's examination results at admission, which is more applicable to the future assessment of the diagnosis and treatment of COVID-19 patients on admission, for long-term monitoring during hospitalization, subsequent follow-up data are required foe support. At present, research on patients with severe COVID-19 remains sparse and is mostly derived from single-source cases, in particular, there is a lack of appropriate pharmaceuticals and methodological support for minimizing or reducing the risk of poor prognosis and death in severe as well as critical patients. Therefore, larger, and wider case-source cohorts are called for in future studies to further explore effective treatment measures for patients with serious COVID-19.