Clinical Characteristics Of Liver And Kidney Injuries And Correlation With Severity And Mortality in Patients With COVID-19 Ⅱ

2. 2 Distribution characteristics of ALT, AST, Cr detection values in COVID-19 patients
Among the 3 548 COVID-19 patients, the detection values of ALT, AST, and Cr showed non-normal distribution (P<0. 01). The specific distribution is shown in Table 1.

Table 1 Distribution of AST, ALT, and Cr in COVID-19 patients

2. 3 Elevated ALT, AST, Cr and severe illness and death in COVID-19 patients
Compared with COVID-19 patients with normal ALT, the risk of severe disease and death in patients with elevated ALT was not significantly increased; compared with COVID-19 patients with normal AST, patients with elevated AST developed severe disease[ OR (95%CI): 2． 88 (1. 57-3. 32)] and death [OR (95%CI): 4. 76 (2. 52-8. 99) ] all had significantly increased risk; compared with COVID-19 patients with normal Cr, patients with elevated Cr developed severe disease [OR (95%CI): 2. 87 (1. 93-4. 27)] and death [OR (95%CI): 5. 75 (3. 02-1 093)] the risk was also significantly increased. The risk of severe disease in patients with hepatic or renal impairment and in patients with both hepatic and renal impairments is that of those with normal liver and renal functions respectively. 2. 32 times (95% CI: 1. 73-3. 10) and 11. 40 times (95%CI: 2. 36－54. 98), occurred

 

 

 

Click Here to Get more knowledge about How Cistanche prevent kidney function lose for Covid patients

Ask more:

wallence.suen@wecistanche.com 0015292862950

 

The risk of death is that of those with normal liver and kidney function respectively. 21 times (95%CI: 3. 10-8. 75) and 13. 53 times (95%CI: 2. 76-66. 32), see Table 2.

Table 2 The relationship between elevated AST, ALT and Cr and the risk of severe illness and death in COVID-19 patients

 

 

2. 6 Correlation between liver and kidney damage and death in COVID-19 patients
Among 3548 COVID-19 patients, 91 died during hospitalization (2. 6%). Taking death during hospitalization as the dependent variable, single-factor Logistic regression was used to screen out independent factors related to death (including age, lung disease, dyspnea, loss of appetite, and absolute value of neutrophils).

Normal, abnormal absolute value of lymphocytes, abnormal bilirubin, elevated CRP, etc.) were used as correction factors, and the correction was carried out step by step to analyze the correlation between liver or/and kidney injury and death.
As shown in Table 5, after gradually correcting age, underlying diseases, clinical manifestations and laboratory monitoring indicators (Model 3), the risk of death during hospitalization in people with liver or kidney damage is 2. 907 times (95%CI: 1. 612-5. 242), but no significant increase in the risk of death during hospitalization was found in patients with liver and kidney damage [P = 0. 555, OR (95% CI): 0. 552 ( 0. 077- 3. 967) ], estimated to be related to the small sample size of this group.

 

Table 4 Liver or kidney injury is an independent factor associated with severe disease (n = 3 548)

Table 5 Liver or kidney injury is an independent factor associated with death (n = 3 548)

 

3 Discussion
This study is a large sample size, systematically reviewing the clinical characteristics of liver and kidney dysfunction (ALT, AST, Cr) in patients with COVID-19, and analyzing the correlation between the characteristics of related indicators and the severity and death of COVID-19 patients risk research. The results showed that the risk of severe illness and death in COVID-19 patients with elevated ALT was not significantly higher than that in patients with normal ALT; while the risk of severe disease and death in COVID-19 patients with elevated AST and Cr was higher than that in patients with normal AST and Cr The risks of severe illness and death were significantly increased (P < 0.05); among COVID-19 patients with liver or kidney damage, males, aged >60 years, complicated with hypertension, lung disease, elevated CRP and elevated CKMB, etc. The proportion of patients with normal liver and kidney function was also significantly higher than that of patients with normal liver and kidney function (P<0.05), indicating that COVID-19 patients with liver or kidney damage are more prone to multiple organ dysfunction. However, multiple organ dysfunction will increase the risk of severe disease and mortality in COVID-19 patients. Early intervention can prevent the severe disease of COVID-19 patients, reduce their fatality rate, and improve the cure rate of such patients. Among the 3548 COVID-19 patients, 875 cases (24.7%) were severely ill and above, and 91 cases (2.6%) died during hospitalization. In this study, severe illness and death were used as dependent variables respectively. The single factor Logistic regression model screened independent factors related to severe illness and death as correction factors. It was found that the risk of severe illness and death during hospitalization in the population with liver or renal impairment was higher than that in the population with normal liver and kidney function (P< 0. 05), which indicates that the risk of severe disease and death in patients with liver or kidney function increases in patients with COVID-19.

According to the latest limited autopsy and local biopsy results of COVID-19 patients, SARS-CoV-2 can affect multiple organs such as lung, heart, liver, kidney, and brain tissue [13-16]. In addition, in patients with COVID-19, there will be abnormal increases in ALT and AST, and the increase in ALT and AST is more obvious in critically ill patients [7]. The pathological study results of a liver lesion specimen from a patient who died of COVID-19 showed: moderate microvesicular steatosis, mild lobular and portal vein inflammation, suggesting that SARS-CoV-2 can cause liver damage and cause elevated transaminases[ 17]. In addition, there are drug reasons. Various drugs used in the treatment of patients can potentially damage the liver [18-19]; one of the important clinical manifestations of COVID-19 patients is hypoxic state, which will affect the oxygenation of liver cells. Hepatic hypoxic injury can also cause elevated transaminases [20]; in addition, some COVID-19 patients have underlying liver diseases [21], and the combination of COVID-19 will also aggravate liver tissue damage.

Related studies have shown that angiotensin-converting enzyme 2 (ACE2) is the main functional receptor of SARS-CoV-2 [3], so organs rich in ACE2 become the main place for SARS-CoV-2 to attack human cells. The mechanism of multiple organ damage secondary to SARS-CoV-2 infection includes direct toxicity of the virus, endothelial cell injury and thrombotic inflammation, immune response dysregulation, and renin-angiotensin-aldosterone system (renin-angiolensin-aldosterone, RAAS) dysregulation22 ]. Although the relative importance of these mechanisms in the pathophysiology of COVID-19 is not fully understood, among them ACE2-mediated viral invasion and tissue damage, as well as RAAS dysregulation, may be unique to COVID-19. ACE2 is expressed in alveolar epithelial type II cells, nasal goblet secretory cells, cholangiocytes, colon cells, esophageal keratinocytes, gastrointestinal epithelial cells, pancreatic β cells, renal proximal tubules, and podocytes [23-25]. Studies have found that SARS-CoV-2 can bind to ACE2 on cholangiocytes, leading to cholangiocyte dysfunction, triggering systemic inflammatory responses, leading to liver damage and elevated transaminases [26].

 

Since ACE2 is the main functional receptor of SARS-CoV-2, and ACE2 is highly expressed in kidney tissue, it suggests that the kidney is also an important target organ for virus invasion [27]. WRAPP et al. [28] analyzed the Spike (S) glycoprotein structure of SARS CoV-2, which provided biophysical and structural evidence of a higher affinity between SARS-CoV-2 and ACE2. SARS-CoV-2 uses the highly glycosylated homotrimeric S glycoprotein to enter host cells, and the affinity between ACE2 and the S glycoprotein of SARS CoV-2 is 10 to 20 times that of SARS coronavirus, suggesting that SARS -CoV-2 is more contagious and prone to kidney disease damage [29]. In addition, blood in the body needs to be filtered through the kidneys, and SARS-CoV-2 in the blood can infect the kidneys through ACE2. In addition to increasing the SARS-CoV-2 load in the kidneys, ACE2 in endothelial cells and renal tubular epithelial cells binds to the virus. , so that the endothelial cells are marked by pathogens, making them a target for recognition and attack by the host immune system, which eventually also leads to kidney damage.

Although the exact pathogenesis of SARS-CoV-2 infection involving the kidney is unclear, SARS-CoV-2-induced acute kidney injury (AKI) associated complications such as sepsis, multiple organ failure, and shock Syndrome is still an important reason for the poor prognosis of COVID-19 patients [30].
In order to prevent the severity of COVID-19 patients and reduce the fatality rate, we need to identify the risk factors associated with the disease severity and poor prognosis of COVID-19 patients early, because the risk of severe illness and death of COVID-19 patients with organ damage Therefore, according to the WHO screening and triage guidelines, accurate assessment of risk factors for poor prognosis of COVID-19 patients is the key to early intervention and improvement of patient prognosis. At the same time, identifying patients with a tendency to become severe can help medical workers classify patients in a timely manner and transfer them to units (ICU) with treatment equipment and capabilities.
From the results of this study, the AST and Cr abnormalities of COVID-19 patients are significantly correlated with the severity and mortality of patients, and are important factors for predicting the prognosis of COVID-19 patients; the subjects of this study are from multiple centers, All meet the inclusion and exclusion criteria and have good representation
sex. Studies have shown that compared with COVID-19 patients with normal liver and kidney function tests, patients with abnormal AST and Cr have a significantly higher risk of severe illness and death, and multiple organ dysfunction will increase the mortality of patients, and in COVID-19 patients It is especially obvious in the treatment of such high-risk patients. During the treatment process, we should pay close attention to the dynamic evolution of AST and Cr indicators, and closely observe the condition, vital signs, and changes in the function of each target organ. Early intervention can prevent COVID-19 patients from becoming seriously ill. To reduce the fatality rate and improve the success rate of treatment of such patients.
However, there are still some limitations in this study. Individual cases do not have sufficient medical history, and COVID-19 patients will have different incubation periods when clinical symptoms appear. The data we use is the data at the time of admission. Little is known about functional changes. In earlier studies, procalcitonin and platelet count were potential predictors of disease severity [31-32], however, this study showed that patients with COVID-19