COVID-19 is an emerging respiratory disease caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) and has become a worldwide pandemic. This article mainly summarized the life cycle of SARS-CoV-2 in host cell and biochemical clinical features of different populations.
Figure 1. Structure of SARS-CoV-2 
The following sections will be discussed in this article:
Angiotensin converting enzyme 2(ACE2) is one of the major receptors for SARS-CoV  and SARS-CoV-2. ACE2 are widely expressed in respiratory tract, heart, kidney, intestine, brain neurons, vascular endothelium, immune cells, renal tubules and pancreas [3,4].
Figure 2. SARS-CoV-2 and SARS-CoV have the same activation of cell attachment factor (ACE2) and cell protease TMPRSS2. 
Life cycle of SARS-CoV-2 in host cells begins with the binding of S proteins to cell receptor ACE2. After binding, the conformation of S protein changed promotes viral envelope fusion with cell membrane through endocytosis pathway. Then SARS-CoV-2 release the genome RNA to enter the host cell. The genomic RNA was translated into viral replicase polyprotein pp1a and 1 ab, which was then cleaved into small products by viral proteases. This polymerase produces a series of subgenomes mRNA by discontinuous transcription, and eventually translates into related viral proteins. The viral proteins and genomes RNA of SARS-CoV-2 were subsequently assembled into viral particles in the endoplasmic reticulum and Golgi apparatus and then transported through vesicles and released out of the cells .
Figure 3. Life cycle of SARS-CoV-2 in host cells
SARS-CoV-2 enter the target cells by binding to the Angiotensin Converting Enzyme 2 (ACE2) receptor , infecting THE upper respiratory tract and lung tissue cells after replication, and then the patients begin to develop clinical symptoms and signs.
Most patients with COVID-19 may have symptoms of fever or cough and 1/3 develop shortness of breath. Other symptoms include muscle soreness, headache, disturbance of consciousness, chest pain and diarrhea. Organ function impairment in some patients, including ARDS,acute respiratory failure, acute kidney injury, septic shock .
Figure 4. General and respiratory diseases caused by COVID-19 infections 
Laboratory examination indicators showed that most patients with severe COVID-19 showed a significant increase in serum proinflammatory cytokine levels, including cytokine storms characterized by IL-6,IL-1β,IL2,IL-8,IL-7,CSF,GM-CSF,IP10,MCP1,CCL3 and TNF [9–12]. High levels of proinflammatory cytokines may lead to shock and tissue damage in the heart, liver and kidney, as well as respiratory failure or multiple organ failure . The white blood cell count was lower than normal in 9% of patients, and neutrophil count increased in 38% of patients. Lymphocytes and hemoglobin in many patients were below the normal range. Many patients also developed abnormal myocardial enzyme profiles with increased creatine kinase (CK) and increased lactate dehydrogenase (LDH). Some patients showed abnormal liver function in varying degrees, showing increased alanine aminotransferase (ALT) or aspartate aminotransferase (AST). Some patients also developed varying degrees of renal impairment, showing increased blood urea nitrogen (BUN) or serum creatinine (Cr) .
Most COVID-19 patients showed mild to moderate symptoms, but about 15% may develop into severe pneumonia, and about 5% eventually develop into acute respiratory distress syndrome (ARDS), septic shock, and multiple organ failure . Some patients have cardiovascular and cerebrovascular diseases, endocrine system diseases, digestive system diseases, respiratory diseases, malignant tumors and nervous system diseases and other chronic basic diseases .
It is reported that the characteristic symptom of COVID-19is viral pneumonia, such as fever, fatigue, dry cough and lymphocytopenia. However, many elderly patients with severe illness are accompanied by basic diseases, such as heart disease, liver disease, kidney disease, malignant tumor and so on [14-16]. As these critically ill elderly patients often end up dying from underlying diseases, accurate assessment of COVID-19 patients with underlying diseases is required.
Besides causing pneumonia, COVID-19 can also damage multiple organs, such as the heart, liver, kidney, as well as multiple systems, as well as multiple systems, such as the blood system, immune system [14–16], eventually leading patients to die of multiple organ failure, shock, acute respiratory distress syndrome, heart failure, arrhythmia, and renal failure [16,17]. As a result, in the treatment of COVID-19, attention should always be paid to potential multiple organ damage, and protection and prevention should be taken .
Classification of COVID-19 critical patients is helpful for individualized assessment of different patients according to their condition and provides more effective individualized treatment.
Literatures showed that 12% of COVID-19 patients had existing liver diseases, and 14%~53% of patients with advanced COVID-19 had elevated alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. The alkaline phosphatase (ALP) level increased in 1.8% of COVID-19 patients during hospitalization. There is a higher incidence of liver dysfunction in severe COVID-19 patients .
A direct cause of liver injury in COVID-19 infected patients may be that the virus infects liver cells. Approximately 2%~10% of COVID-19 patients developed diarrhea symptoms and SARS-CoV-2 nucleic acids were detected in their feces and blood samples , which suggests that the virus may invade the liver through digestive tract or blood circulation.
Glutamyl transpeptidase (GGT) is a biomarker for the diagnosis of cholangiocyte injury. Some COVID-19 patients have GGT elevated during hospitalization. There are literatures suggests that ACE2 is highly expressed on cholangiocytes , suggesting that SARS-CoV-2 may bind directly to ACE2 positive cholangiocytes, which leading to liver dysfunction.
People with advanced liver disease, especially older patients with other complications, have a lower immune function. Patients with these existing physical illnesses needed to be intensively monitored of clinical indicators after infection COVID-19, or the personalized treatment protocols for patient conditions should be made. Follow-up studies need to pay more attention to the causes of liver injury caused by COVID-19 infection and the effect of liver-related complications on the therapeutic effect and prognosis of COVID-19.
The specific mechanism of diarrhea pathogenesis in COVID-19 infected patients is not completely clear at present, while viral infection may cause changes in intestinal permeability and lead to poor intestinal cell absorption . Intestinal ACE2 is involved in dietary amino acid uptake, regulating the expression of antimicrobial peptides and promoting the homeostasis of intestinal flora . Experiments with mouse models showed that changes in ACE2 were associated with colitis, suggesting that viral activity may lead to altered enzymes that increase susceptibility to intestinal inflammation and diarrhea . Further studies are needed to elucidate the underlying diarrhea mechanisms in these viral infections and to determine the correlation between respiratory and gastrointestinal symptoms.
Animal models showed that Angiotensin-converting enzyme (ACE) and Angiotensin receptor inhibition were associated with increased ACE2 levels in circulation . The use of ACE or angiotensin receptor blockers (AR) should be investigated based on the pathogenesis of diarrhea and the key role of ACE2, especially in elderly or cardiovascular patients, as it may lead to a higher risk of developing COVID-19 diarrhea . Importantly, this hypothesis has not been confirmed and further studies are needed to demonstrate whether the use of ACE/AR inhibitors is a COVID-19 risk factor .
In conclusion, the presence of diarrhea should cause suspicion of possible SARS-CoV-2 infection and should be investigated in order to make an early diagnosis of COVID-19.
Data on glucose metabolism and complicated acute diabetic complications (such as ketoacidosis) in COVID-19 patients are scarce. Infection SARS-CoV-2 in diabetic patients may trigger higher stress states and release more hyperglycemia hormones, such as glucocorticoids and catecholamines, leading to elevated blood glucose levels and abnormal blood glucose variability . On the other hand, a retrospective study in Wuhan reported that approximately 10% of elderly patients with type 2 diabetes (T2DM) and COVID-19 had at least once hypoglycemia (< 3.9mmol/L) . Hypoglycemia has been shown to have be able to mobilize proinflammatory monocytes and increase platelet-responsive activity, leading to higher cardiovascular disease mortality in diabetic patients . However, how exactly inflammation and immune responses occur in these patients, and whether hyperglycemia or hypoglycemia alters SARS-CoV-2 toxicity, or whether the virus itself interferes with insulin secretion or glycemic control, remains unknown. Furthermore, the effect of conventional diabetic drug therapy on COVID-19 and the treatment of glycemic regulation in COVID-19 patients are still unclear.
The most severe and fatal COVID-19 cases occur in elderly or potentially comorbid patients, especially cardiovascular disease, diabetes, chronic liver and kidney disease, hypertension, and cancer [30-33]. Among COVID-19 patients, the most common cardiovascular metabolic comorbidity is hypertension and cardiovascular disease, followed by diabetes . Diabetes is a chronic inflammation caused by multiple metabolic and vascular abnormalities caused by pathogen response . In addition to stimulating the production of adhesion molecules that mediate tissue inflammation, hyperglycemia and insulin resistance promote the synthesis of glycation end products (AGEs) and proinflammatory cytokines, oxidative stress [35, 36]. This inflammatory process may constitute a potential mechanism leading to a higher propensity to infect, whereas the prognosis of diabetic patients is worse .
Diabetes and other complications are important predictors of morbidity and mortality in COVID-19 patients. Further studies are urgently needed to better understand the potential differences in genetic predisposition among populations, the underlying pathophysiological mechanisms of association between COVID-19 and diabetes, and their clinical management.
It is reported that among 9 SARS-CoV-2 patients at the end of pregnancy, 7 of whom developed fever symptoms, cough (4 out of 9), myalgia (3), sore throat (2), and discomfort (2). Complications of pregnancy following SARS-CoV-2 infection include fetal distress and premature rupture of membranes. Of the 9 patients, 5 had lymphopenia (< 1.0×109/ L) and 3 had elevated ALT and AST, of which 1 had an ALT level of 2093 and a level of 1263 U/L .
All 9 patients underwent caesarean sections in the late pregnancy. As of February 4, 2020, all patients had no severe COVID-19 pneumonia or death and no neonatal asphyxia. The amniotic fluid, umbilical cord blood, neonatal throat swabs and breast milk samples of 6 patient were tested, and results of virus detection in all samples were negative .
Clinical characteristics of COVID-19 patients with late pregnancy are similar to those of non-pregnant adults. From these limited cases, there is no evidence that SARS-CoV-2 infection at late pregnancy can lead to vertical transmission leading to intrauterine infection.
The common complications of death patients are: acute respiratory distress syndrome, sepsis, acute heart injury, heart failure, alkalosis, hyperkalemia, acute kidney injury, hypoxic encephalopathy. Among them, acute heart injury, heart failure is more common. Acute respiratory distress syndrome and respiratory failure, septicemia, acute cardiac injury, and heart failure are the most common key complications of COVID-19 exacerbation .
Initial clinical laboratory investigations included complete blood cell counts, serum biochemical tests (including liver and kidney function, creatine kinase, lactate dehydrogenase, and electrolytes), coagulation function, and cytokine tests.
The concentrations of glutamate aminotransferase (ALT), aspartate aminotransferase (AST), creatinine (Cr), total cholesterol (TBil), alkaline phosphatase (ALP), glutamyl transpeptidase (γ-GT), blood urea nitrogen (BUN), potassium (K), triglyceride (TG), creatine kinase (CK), and lactate dehydrogenase (LDH) in the dead patients were significantly higher than those in the rehabilitated patients. Albumin concentration in the dead patients was significantly lower than in the rehabilitation patients .
Some COVID-19 patients, especially those with advanced age and high blood pressure, are in critical condition at the time of admission, and they may rapidly deteriorate to death within 2~3 weeks. SARS-CoV-2 infection can cause lung and systemic inflammation, leading to multiple organ dysfunction in high-risk populations. Besides acute respiratory distress syndrome and type I respiratory failure, acute cardiac injury and heart failure may also lead to critical states associated with high mortality, which highlights the importance of early cardiac monitoring and supportive care for such patients.
It was found that there are differences in the abundance of 373 and 204 metabolites in COVID-19 patients, and changes in metabolites were found to be associated with disease severity in metabolomics data .82 metabolites were involved in the biological processes of complement system activation, macrophage function, and platelet damage .
Nicotinamide adenine dinucleotides (NAD) are cofactors in many cellular redox reactions that can be synthesized by tryptophan via the canine urisine pathway and act as a response switch for macrophage effects . The increasing of glucose (Glu), glucuronide, bilirubin degradation products, and four bile acid derivatives suggest inhibition of liver detoxification . Vascular cell adhesion protein 1 (VCAM-1) helps regulate leukocyte transendothelial migration by stimulating the production of reactive oxygen species (ROS). As antioxidants and inhibitors of VCAM-1 dependent cell activity , bilirubin concentrations decreased in metabolic data. Glycerophospholipids, sphingolipids, and fatty acids have been reported to play important roles in the early development of envelope viruses .
Figure 5. Molecules change in serum may provide important diagnostic markers or therapeutic targets for patients with severe COVID-19
Molecular changes in the serum of COVID-19 patients make it possible for us to propose new therapeutic strategies for severe patients .
We hope that the above introduction can help researchers to understand the COVID-19.
|Target||Cat. No.||Product Name|
|Fatty Acids||E-BC-K013-M||Non-esterified Free Fatty Acids (NEFA) Colorimetric Assay Kit|
|Lactate Dehydrogenase (LDH)||E-BC-K046-M||Lactate Dehydrogenase (LDH) Activity Assay Kit|
|Albumin (ALB)||E-BC-K057-M||Albumin (ALB) Colorimetric Assay Kit (Bromocresol Green Method)|
|Reactive Oxygen Species (ROS)||E-BC-K138-F||Reactive Oxygen Species (ROS) Fluorometric Assay Kit|
|Glucose (Glu)||E-BC-K234-M||Glucose (Glu) Colorimetric Assay Kit (GOD-POD Method)|
|Alanine Aminotransferase (ALT/GPT)||E-BC-K235-M||Alanine Aminotransferase (ALT/GPT) Activity Assay Kit (Reitman-Frankel Method)|
|Aspartate Aminotransferase (AST/GOT)||E-BC-K236-M||Aspartate Aminotransferase (AST/GOT) Activity Assay Kit (Reitman-Frankel Method)|
|Potassium (K)||E-BC-K279-M||Potassium (K) Turbidimetric Assay Kit|
|Creatine kinase (CK)||E-BC-K558-S||Creatine kinase (CK) Activity Assay Kit|
|Alkaline Phosphatase (ALP)||E-BC-K091-M||Alkaline Phosphatase (ALP) Activity Assay Kit|
|Urea (BUN)||E-BC-K183-M||Urea (BUN) Colorimetric Assay Kit (Urease Method)|
|Creatinine (Cr)||E-BC-K188-M||Creatinine (Cr) Colorimetric Assay Kit (Sarcosine Oxidase Method)|