The team screened 20 protein markers from the urine and built a model, which successfully achieved the classification and prediction of patients with mild and severe new coronary pneumonia.

This study shows that protein molecules obtained from the urine of patients with new coronary pneumonia can sensitively reflect the pathological state of the body.

  ◎Hong Hengfei reporter Jiang Yun

  Recently, Guo Tiannan's laboratory and cooperative team from the School of Life Sciences of West Lake University published the latest research results in "Cell Reports", a sub-journal of "Cell": the joint team screened 20 protein markers from urine and established a model, which successfully realized the detection of light , Severe new coronary pneumonia patients were classified and predicted, and the evidence of potential kidney damage in patients with new coronary pneumonia was pointedly put forward.

  This study shows that protein molecules obtained from the urine of patients with new coronary pneumonia can sensitively reflect the pathological state of the body.

  Normal urine contains thousands of trace proteins, which are closely related to the body's immunity and metabolism.

Compared with serum, tissue, etc., the acquisition of urine does not require professional collection methods, which can meet the needs of daily real-time monitoring of health.

  Urine information is huge

  Algorithmic models refine predictions

  Identifying the mild and severe severity of COVID-19 patients is particularly important for treatment.

  It is understood that the joint team conducted quantitative research and analysis of 1494 serum proteins, 3854 urine proteins, 903 serum metabolites and 1033 urine metabolites, and found that the molecular weight distribution of proteins in urine is similar to that of the whole human proteome. The protein molecular weight distribution is consistent, that is, the urine sample will not miss a certain type of protein and cause information loss.

Moreover, the ability of urine protein to distinguish between mild and severe new coronary pneumonia is basically the same as that of serum protein.

  "Using the analysis methods of proteomics and metabolomics, we conducted a systematic study and comparison of the urine and serum samples of the new coronary pneumonia patient group and the healthy control group." Guo Tiannan introduced that from the protein level analysis, mild and severe new coronary pneumonia The urine protein content per unit volume of patients in the patient group was significantly higher than that in the healthy group, which suggests that urine may be more sensitive to changes in the body's disease level.

  Medicine tends to judge health status by specific values, such as measuring body temperature, blood pressure, etc.

There is a lot of information in urine, but the values ​​of different types of proteins are obviously not intuitive.

To this end, the joint team established a machine learning model based on 20 urine proteins for computational transformation.

  "This algorithm model can be understood as a function, input values ​​such as 'X', Y', Z', etc., and a predicted value can be obtained for evaluation." Guo Tiannan introduced that the predicted value has a numerical range, from low to low High corresponds to the situation of patients with mild and severe new coronary pneumonia.

During the recovery process of patients with severe new coronary pneumonia, the predicted value of the model gradually decreased with time; while in the recovery of patients with mild new coronary pneumonia, the predicted value tended to be flat and did not change significantly.

The results of this study further confirmed that these 20 urine proteins have the potential to classify and predict the severity of new coronary pneumonia.

"The team has developed a special kit for urine sample collection and efficient inspection." Guo Tiannan said.

  Protein dysregulation damages kidneys

  Immune disorders trigger a series of problems

  Cytokines are a class of proteins that are mainly synthesized and secreted by immune cells.

Among them, the cytokine CXCL14 is involved in the regulation of many biological processes in vivo, such as inflammatory immune response, tumor-related angiogenesis, etc.

  Cytokine storm caused by uncontrolled innate inflammatory response is the main cause of high mortality in patients with new coronary pneumonia.

Therefore, the joint team focused on the changes of cytokines in serum and urine, and conducted quantitative studies on 124 serum cytokines and 197 urinary cytokines.

  Lymphopenia is common in patients with new coronary pneumonia and is closely related to the severity of the patient's condition.

The study found that in urine, the level of cytokine CXCL14 was significantly correlated with lymphocyte counts in patients with new coronary pneumonia, or it could be used as a biomarker to indicate the severity of new coronary pneumonia.

  It is worth noting that this study obtained many proteins that frequently appeared in differentially expressed pathways through differential pathway analysis.

Among them, CDC42, RAC1/RAC2 and RHOA of the Rho GTPase family frequently appeared.

  "In addition, the dynamic regulation of renal podocyte actin requires a large amount of adenosine triphosphate (ATP)." Guo Tiannan introduced that metabolomics data showed that the content of adenosine, a product of ATP metabolism, was significantly reduced in the urine of patients with severe new coronary pneumonia. , which further suggests that there may be podocyte motility disorders and potential kidney damage in patients.

  The joint team found that, like other viral infections, the new coronavirus can trigger oxidative stress by disrupting the balance between the body's oxidative and antioxidant systems.

Based on multiple clues, the study speculates that the inflammatory response, coagulation response, and cellular fibrosis triggered by the immune disorder caused by the new coronavirus in the patient eventually damaged kidney tissue.

  "Clinical data show that although the indicators of various types of kidney damage in patients with severe new coronary pneumonia are still within the normal range, they have changed significantly compared with the healthy control group." Guo Tiannan said that research shows that the new coronavirus may cause kidney damage in patients , it is necessary to pay close attention to the clinical indications of renal injury in patients with new coronary pneumonia, and maintain follow-up observation of their renal function after recovery from new coronary pneumonia.