It has been reported that the mortality of hospitalized COVID-19 patients ranged from 4.3–28.3% [3, 20, 21]. And group of severe and critical patients had highest mortality rate up to 61.5% . The mortality of included patients in our study was 17.9% which was comparable with previous studies. Increased age and comorbidities have been acknowledged as independent risk factors of mortality in COVID-19 patients [23, 24]. Our results showed that the incidence of complicated underlying diseases including hypertension, chronic lung disease and cardiovascular disease was higher in non-survivor group. In this study, the most common symptoms sequentially were fever, cough, dyspnea and fatigue, which was consistent with other studies. Compared with survivors, non-survivors were more likely to suffer organ dysfunction such as respiratory failure, AKI and liver dysfunction. These serious complications could result in the progression to unfavorable outcome.
The CONUT score, composed of lymphocyte count, albumin and cholesterol level, was generally considered as a reflection of inflammation and immune status. The reduction of lymphocyte, albumin and cholesterol could lead to the increase of CONUT score., which was commonly associated with detrimental inflammatory status and unfavorable outcomes. The immune dysfunction and cytokine storm play an important role in the progression of COVID-19 patients [25, 26]. In addition, CONUT has been confirmed valuable in assessing nutritional status and hence associated with outcome in various patients [27–29]. Malnutrition is actually a potent predictor of mortality in some viral infection such as influenza A (H1N1) virus infection [30, 31]. Consequently, we designed this study to explore the predictive value of CONUT in COVID-19 patients. Our results showed that CONUT of non-survivors was significantly higher than that of survivors in COVID-19 patients. Moreover, the CONUT was a prognostic risk factor after adjusting cofounders by multivariate logistic regression analysis. Low count of lymphocyte, which is an important component of high CONUT score, is often observed in patients with viral infection including severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) . Both recent researches of COVID-19 and this study confirmed the universal existence of lymphopenia in COVID-19 patients. Some studies have illustrated that lymphopenia is associated with disease severity and prognosis in COVID-19 patients . Higher level of neutrophil-to-lymphocyte ratio (NLR), indicating lower lymphocyte, combined with older age could be utilized as an efficient tool to recognize potential severe to critical patients who requires intensive monitoring and supportive care . The decrease of peripheral lymphocyte is mainly attributable to the decreased T cells, especially CD3+, CD4+, and CD8+T cells . Decreased CD4+ and CD8+ T cells with excessive activation of themselves could cause the immunocompromise and disease progression in COVID-19 patients . It has been testified the SARS-CoV could induce the reduction of T cell by antigen presenting cells (APC) dysfunction and excessive inflammation mediated apoptosis [36, 37]. However, it remains unclear that whether direct invasion of T cells or indirect pathway above mentioned is responsible for the lymphopenia in patients infected with SARS-CoV-2. It deserves further investigation to explore the underlying mechanism of lymphopenia in COVID-19 patients. Serum albumin level is another significant part of CONUT. Decreased albumin level, which correlates with higher CONUT score, is usually considered as a marker of malnutrition. In fact, hypoalbuminemia is a valuable marker of detrimental inflammation status and poor prognosis in various clinical settings including cancer, cardiovascular diseases and pneumonia [38–41]. Recent studies also confirmed albumin level was an independent risk factor of outcome in COVID-19 patients . Our study showed that albumin level was lower in non-survivors than survivors. Previous study demonstrated that synthetization of albumin by hepatocytes could be inhibited through the release of inflammatory cytokines such as interkulin-6 (IL-6) and tumor necrosis factor-α (TNF-α) . It is the cytokine storm, which means a great release of cytokines such as intekulin-1 (IL-1), intekulin-6 (IL-6), tumor necrosis factor-α(TNF-α), granulocyte colony stimulating factor (G-CSF), Interferon-γ (IFN-γ), inducible protein-10 (IP-10), and monocyte chemotactic protein 1 (MCP-1), lead to the severe immune damage to organs in COVID − 19 patients [26, 44]. Therefore, the correlation between albumin and prognosis may be mediated by the liver dysfunction caused by cytokine storm. As an essential part of CONUT score, serum cholesterol level is another valuable indicator of malnutrition during the acute inflammatory response . The relationship between hypocholesterolemia and mortality of critically ill surgical patients has been confirmed . And constantly decreased cholesterol levels may indicate the aggravation of infection or progression of organ dysfunction in trauma patients . Results of our study showed non-survivors had lower level of cholesterol than survivors. Actually, the metabolism of cholesterol could be disturbed by inflammatory cytokines such as IL-1 and TNF-α, which in turn lead to hypocholesterolemia . Therefore, reduced cholesterol level, the same as reduced albumin level, reflects the severe extent of cytokine storm in COVID-19 patients.
Combined effects of lymphocyte, albumin and cholesterol, the CONUT score could indicate nutritional and immune status in COVID-19 patients more synthetically. Higher level of CONUT, which means more poor nutritional status, was associated with unfavorable outcome in COVID-19 patients. The cause of malnutrition in COVID-19 patients is multifactorial. Firstly, accompanied vomiting and diarrhea could decrease food intake and absorption efficiency . Secondly, fever and respiratory distress could increase heat loss and mechanical work which means increased energy expenditure. Thirdly, prolonged bed rest and decreased physical activities lead to the reduction of muscle volume. It has been verified that low levels of micronutrients including vitamins A, B6, E, and Zn correlated with unfavorable outcomes in patients with viral infections . Although no research has illustrated optimal nutritional management and effects of nutritional support in COVID-19 patients, suitable and diversified nutrition supplement including vitamin and microelement may be essential for COVID-19 patients to enhance immunity and promote recovery.
In the multivariate logistic regression analysis, only CONUT, CRP and LDH were still statistically significant. And we found CONUT was moderately associated with CRP and LDH. CRP, an indicator of inflammatory response, has been documented correlated with prognosis of influenza pneumonia, MERS, and community acquired pneumonia patients [50–52]. In this study, the obviously higher level of CRP in non-survivors demonstrated that excessive cytokine storm played an important role in the pathogenesis of COVID-19. In fact, CRP also takes part in the innate host defense by binding to pathogens and promoting their elimination by phagocytes . Existed in all body cells, especially the myocardial and liver cells, LDH is beneficial to evaluate severity of tissue damage in early stage . Increased LDH is also associated with immunosuppression by promoting the production of lactate which in turn strengthen the immunosuppressive cells and weaken the cytolytic cells . Our prognostic model comprised of CONUT, CRP, LDH may comprehensively reflect the nutritional, inflammatory and immune status, and is a valuable tool to predict outcome of COVID-19 patients.