This study finally identified several risk factors from variables about demographic data, comorbidities and biochemical analysis of organ functions and metabolic status.
From the researches mentioned above, male patients were more susceptible to COVID-19[6,7]. In our study, there was no obviously susceptibility enhancement in male group of the whole patients, but there was an upward trend of male patients in nonwurvivors’ group. Patients with more severity would be prior to be admitted, so male patients might be in the majority in some early studies while the medical sourses were limited.
Age was proved to be an important risk factor, that was also confirmed in our study. In our data collected, mortality increased rapidly while the patients were over 60 years old. (Table S1). Elderly individuals are physically frail and are likely to have several comorbidities, which not only increase the pneumonia susceptibility, but also affect their prognosis. It had been proved in SARS and MERS[11,12]. In COVID-19, lymphopenia was common in blood test. And the function of lymphocyte would decrease accompanied by aging process, that would exacerbated losing control of viral replication and increasing the proinflammatory responses , potentially aggravating the disease progression and in-hospital death. And in out study, in-hospital death was rare in the group of people younger than 40 years old, that reminded us a large group of asymptomatic carriers of young people might exist.
Diabetes had been reported to be closed related to regression and mortality of COVID-19[6,7], it was also proved in our univariate regression analysis(Table 2). But fasting blood glucose was not explained in the studies mentioned above. In our study, fasting blood glucose was confirmed to be higher in nonsurvivors’ group. One possibility causing hyperglycemia was diabetes, another one was a stress related hyperglycemia which caused by emergencies. Glycated hemoglobin might help us identifying the different mechenism, but we didn’t take it as a routine test on admission, so no result about glycated hemoglobin could be presented. In some other respiratory epidemic diseases, such as influenza, diabetes was an important risk factor closely related to mortality[14,15]. It is partially because 90% type2 diabetes accompanied with obesity, which was a risk factors to respiratory disease, and also because of damaged immunological functions caused by chronic hyperglycemia[17,18]. In our study, we ensured the fasting blood glucose was a risk factor to in-hospital death, and mortality increased obviously while the fasting blood glucose was beyond the upper level of normal range(6mmol/L)(Table S2). We emphasized an acute stress hyperglycemia also contributed to mortality besides the chronic glucose metabolic disorder. Stress hyperglycemia was a physically reaction to diseases, rather than psychological, and usually caused by catecholamines, hypothalamic pituitary adrenal(HPA) axis activation, inflammatory cytokines and lipotoxicity. In virus infection, the rate of glucose uptake by infected cells increased continually, and the subsequently enhanced glycolysis results in higher glucose consumption and extracellular concentration of lactate[20,21]. In fact, hyperglycemia is a common finding in patients in hospital and indicates poor clinical outcome and mortality. Hyperglycemia without diagnosed diabetes would be inclined to happened to the patients who got pancreatic reserve deficiency and insulin resistance, especially those who unaware of their status. Patients with newly diagnosed hyperglycemia had a significantly higher mortality rate and a lower functional outcome than patients with a known history of diabetes or normoglycemia. In ICU ward, patients who needed treatment for hyperglycaemia those without diabetes had higher SOFA scores, greater hospital length of stay, and higher mortality rates than the patients with known diabetes, despite lower median glucose and adjustment for severity of illness and other covariates.
BUN and Cre could elevated for acute kindney injury(AKI) in patients without chronic kidney failure. In our research, means of BUN and Cre rose up in nonsurvivors’ group. Means of the two indicators in both survivors’ and nonsurvivors’ group were both in a relatively normal range of BUN and Cre, but there was still almost 50% percent increasement in nonsurvivors’ group in average. According to Acute Kidney Injury Network( AKIN) and Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease(RIFLE) criterions for AKI, 50% rise of Cre can predict risk factors of acut kidney failure[25,26]. From the researches mentioned above, acute kidney injury would appear in about 50% patients in nonsurvivors’ group compared to 1% in survivors’, but that pathological course ususlly happened 16 days after the disease was onset, or 4 days after ICU admission. So the baseline elevation of BUN and Cre should be hints for early stage of kidney damage and contributed to bad mortality.
In COVID-19, the elevation of fasting blood sugar and BUN maybe indicated more information. Lymphopenia was normal and distinct clincal character of cov-19 infected disease. In virus infected model, T cells would upregulate the uptake and utilization rates of glucose and amino acids promoting anabolic growth while stumulated by infection, so anabolism decrease caused by lymphopenia might aggravate the rise of BUN and blood sugar under a exacerbation of catabolism. We can speculated high level of BUN and blood-glucose might reflect quantitative or functional damage of T cell that would increase the glucogensis and amino acid anabolic.
Results about and lipid metabolism seemed change little during early stage of this disease. So disorders about purine and lipid metabolism might need more researches.
AST was removed in the last step of multivariable regression analysis, but it still aroused out interest. AST showed a obvious differece(p<0.001) between two groups, while the ALT didn’t(p=0.07). Abnormalities of liver function was still under discussion in the clinical course of COVID-19[28,29]. And besides liver function, AST was also used to evaluate myocaridium damage. Some reports indicated that higher visit-to-visit variability of liver enzymes was an independent predictor of all-cause mortality and cardiovascular events[30,31]. From the analysis mentioned above, acute cardiac injury would appear in about 59% patients in nonsurvivors’ group compared to 1% in survivors’, and usually happened 15 days after admission with acute elevation of hsTnI. So elevation of AST might be a hint of myocardium damage at the early stage besides liver dysfunction in COVID.
Since the incubation period and most patients would have to spent several days waiting the confirmative diagnosis for admission, the biochemical test on admission reflected the body reaction to COVID-19. Lots of supplements were needed in our study. Glycated hemoglobin would be good for classifying the reason of hyperglycemia besides history of diabetes. Dynamic changes of renal and cardiac function should be observed to assess the efficiency of alarms from biochemical test on admission.