Biomarker for diagnosing asthma caused by SARS-cov-2 infection and uses thereof

Abstract

The present invention relates to a biomarker composition for diagnosing asthma caused by SARS-CoV-2 infection, and uses thereof. Through a change in the expression of CDHR3, SCGB3A2, PLAU, or NPY, which are biomarkers according to an embodiment of the present invention, it was confirmed that patients infected with SARS-CoV-2 have a higher incidence of asthma compared with healthy individuals, and thus the biomarker can be widely applied in the fields of diagnosis of SARS-CoV-2-induced asthma and drug screening.

Description

Biomarkers for the Diagnosis of Asthma Caused by SARS-COV-2 Infection and Their Uses

[0001] The present invention relates to a biomarker for diagnosing asthma caused by SARS-CoV-2 infection and the use thereof.

[0002] Asthma is a lung disease characterized by chronic inflammation of the bronchi, which causes the airways to narrow and become hypersensitive. It is triggered by air pollutants, yellow dust, and allergens. Asthma is a disease characterized by major symptoms such as wheezing, chest tightness, shortness of breath, and persistent coughing. It occurs due to a combination of genetic predisposition and environmental factors, and symptoms can be triggered or exacerbated by irritants, particularly allergens, air pollution, and cigarette smoke.

[0003] The treatment of asthma focuses on symptom management and the prevention of attacks, primarily using steroids, bronchodilators, and anti-inflammatory drugs. During an acute attack, bronchodilators are used to rapidly open the airways, while inhaled steroids are used for continuous management to suppress inflammation. Although inhaled corticosteroids, currently the most widely used medications, demonstrate excellent therapeutic effects, long-term use is known to cause adrenal suppression, decreased bone density, growth disorders, complications affecting the eyes and skin, and increased collagen synthesis, in proportion to the dose and duration of use.

[0004] Meanwhile, COVID-19 is a respiratory infection caused by the SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus-2) virus. It is a highly contagious disease that has spread globally since its initial discovery in China in 2019. Symptoms vary widely, ranging from mild cold-like symptoms to severe shortness of breath; typical symptoms include fever, cough, sore throat, muscle pain, fatigue, and loss of taste and smell. The aftereffects of COVID-19, known as "long COVID," refer to various symptoms that persist for weeks to months even after recovery from the viral infection. Common aftereffects include chronic fatigue, shortness of breath, cough, muscle pain, headache, and loss of taste and smell. A decline in cognitive function, such as memory loss or difficulty concentrating, may also occur. In severe cases, it can lead to pulmonary fibrosis or damage to heart and kidney function, and the risk of developing aftereffects is particularly high in severely infected patients and those with underlying medical conditions.

[0005] Various studies are being conducted on the correlation between COVID-19 and the onset of asthma. Asthma patients may be more vulnerable to respiratory infections due to the characteristics of their airways becoming hypersensitive and persistent inflammation, which implies the possibility of increased severity if they contract COVID-19. Recent studies have shown a higher incidence of new asthma cases during the outbreak of COVID-19 (Kim, Bo-Guen et al., 2024). Therefore, the importance of the risk of asthma following the onset of COVID-19 and the technology to diagnose it is increasing; however, to date, there are no biomarkers available to accurately diagnose asthma following the onset of COVID-19.

[0006] To solve the aforementioned problems, the inventors identified genes with significant expression changes in a severe COVID-19 model through gene expression analysis using Next-Gene Sequencing (NGS), selected genes by comparing them with asthma-related genes, and confirmed the expression of the corresponding genes in a dataset of severe COVID-19 patients, thereby discovering a biomarker capable of precisely diagnosing asthma after the onset of COVID-19 and completing the present invention.

[0007] Accordingly, the objective of the present invention is to provide a biomarker composition for diagnosing asthma caused by SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus-2) infection comprising one or more selected from the group consisting of CDHR3 (Cadherin related family member 3) or SCGB3A2 (secretoglobin family 3A member 2), PLAU (plasminogen activator, urokinase) and NPY (neuropeptide Y).

[0008] Another object of the present invention is to provide a composition for diagnosing asthma caused by SARS-CoV-2 infection, comprising a preparation for measuring the expression of one or more genes selected from the group consisting of CDHR3, SCGB3A2, PLAU, and NPY or genes encoding therefrom.

[0009] Another objective of the present invention is to provide a kit for diagnosing asthma caused by SARS-CoV-2 infection comprising the above-mentioned asthma diagnostic composition.

[0010] Another objective of the present invention is to provide a method for providing information on the diagnosis of asthma caused by SARS-CoV-2 infection.

[0011] Another objective of the present invention is to provide a screening method for asthma treatments caused by SARS-CoV-2 infection.

[0012] The terms used herein are for descriptive purposes only and should not be interpreted as being limiting. Singular expressions include plural expressions unless the context clearly indicates otherwise. In this specification, terms such as "comprising" or "having" are intended to indicate the existence of the features, numbers, steps, actions, components, parts, or combinations thereof described in the specification, and should be understood as not precluding the existence or addition of one or more other features, numbers, steps, actions, components, parts, or combinations thereof.

[0013] Furthermore, unless otherwise defined, all terms used herein, including technical or scientific terms, have the same meaning as generally understood by those skilled in the art to which the embodiments pertain. Terms such as those defined in commonly used dictionaries should be interpreted as having a meaning consistent with their meaning in the context of the relevant technology, and should not be interpreted in an ideal or overly formal sense unless explicitly defined in this application.

[0014] In the case of duplicate content or terms in this invention, their description has been omitted to avoid excessive complexity in this specification.

[0015]

[0016] To achieve the above objective, one aspect of the present invention provides a biomarker composition for diagnosing asthma caused by SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus-2) infection, comprising one or more selected from the group consisting of CDHR3 (Cadherin related family member 3), SCGB3A2 (secretoglobin family 3A member 2), PLAU (plasminogen activator, urokinase), and NPY (neuropeptide Y).

[0017] In the present invention, CDHR3 (Cadherin related family member 3) is a membrane protein involved in intercellular adhesion and signal transduction, also known as CDH28, and consists of an extracellular domain capable of calcium binding, a transmembrane domain, and a short cytoplasmic tail inside the cell.

[0018] In the present invention, SCGB3A2 (secretoglobin family 3A member 2) is a small secretory protein, also known as LU103, PNSP1, UGRP1, and pnSP-1, and exists as a monomer or dimer, and is known to be effective in anti-inflammatory action and immune modulation due to its structural characteristics.

[0019] In the present invention, PLAU (plasminogen activator, urokinase) is also known as ATF, QPD, UPA, URK, u-PA, and BDPLT5, exists as an active and inactive protein, and is composed of a prodomain, an active center, a binding domain, etc.

[0020] In the present invention, NPY (neuropeptide Y) is a neuropeptide composed of 36 amino acids, also known as PYY4, and has an alpha-helical structure so that it can bind to various receptors.

[0021] The term “asthma” used in this invention is a comprehensive disease name that collectively refers to various diseases characterized by inflammatory reactions in the airways extending from the trachea, bronchi, bronchioles, and alveoli, as well as damage and changes in airway tissues resulting therefrom. Specifically, asthma is a condition in which the bronchi within the lungs become highly sensitive, and symptoms such as shortness of breath, wheezing, and severe coughing occur as the bronchi occasionally narrow. It is an allergic disease caused by an allergic inflammatory reaction in the bronchi. Typical symptoms of asthma include shortness of breath, coughing, and wheezing (a rough, whistling sound). Representative treatments used include symptom relievers (bronchodilators) that alleviate narrowed bronchi within a short period of time, or disease controllers (anti-inflammatory agents, leukotriene modifiers) that suppress allergic inflammation in the bronchi to prevent asthma attacks.

[0022] In one embodiment of the present invention, the asthma may be asthma caused by SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus-2) infection.

[0023] The above-mentioned SARS-CoV-2 is a type of coronavirus that causes COVID-19, a respiratory infectious disease. SARS-CoV-2 is primarily transmitted through droplets or airborne aerosols, and infection can result in a wide range of symptoms, from mild cold symptoms to severe respiratory distress. Structurally, it possesses spike proteins on its exterior, which bind to the ACE2 receptor of host cells to penetrate into the cell. This not only affects respiratory cells, particularly those in the lungs, but in severe cases, can lead to pneumonia and multiple organ damage. Furthermore, active mutations occur, which can alter transmissibility and severity. In the present invention, SARS-CoV-2 may be used interchangeably with “SARS-CoV-2 virus,” and “SARS-CoV-2 infection” may be used interchangeably with COVID-19.

[0024] The term "diagnosis" as used in the present invention refers to confirming the existence or characteristics of a pathological condition. Such diagnosis can provide objective basic information necessary for monitoring not only the onset of the disease but also the prognosis, course of asthma, and stage, and excludes the clinical judgment or opinion of a physician. For the purposes of the present invention, diagnosis refers to confirming the onset, prognosis, course, stage, or characteristics of asthma.

[0025] The term “biomarker” as used in the present invention refers to a substance that specifically responds to diagnosing a particular disease or determining a treatment method. In the present invention, a biomarker is a substance obtained by comparing asthma-related gene expression with a severe COVID-19 model infected with the SARS-COV-2 virus, and includes nucleic acids, genes, or proteins that show an increasing or decreasing pattern in the tissues or cells of asthma patients compared to normal specimens (control group).

[0026] In one embodiment of the present invention, the biomarker may be selected through database analysis such as Gene Ontology (GO), Disease Ontology (DO), and CTD (Comparative Toxicogenomics Database).

[0027] The aforementioned gene ontology (GO) refers to a database that defines gene and protein functions using standardized vocabulary, dividing them into three main categories: biological processes, molecular functions, and cellular locations. GO enables a clear understanding and analysis of gene functions and can be widely utilized, particularly in large-scale genomic data analysis, protein network research, and gene-disease association studies. It can be used to identify the role that a specific gene or protein plays in biological processes or to predict the corresponding gene or biological function.

[0028] The aforementioned Disease Ontology (DO) refers to a database that integrates various bioinformatics data by standardizing the names and definitions of diseases. DO can provide structured information on various diseases to enable the systematic analysis of relationships between genes, proteins, and environmental factors in disease-related research. Furthermore, DO is widely used in gene-disease association studies and biomedical research, and can be utilized to identify and predict which diseases specific gene variants affect.

[0029] The aforementioned Comparative Toxicogenomics Database (CTD) refers to a public database that studies the impact of environmental exposure on diseases through the interactions between genes, chemicals, and diseases. CTD analysis is performed based on data regarding chemical-gene interactions, gene-disease associations, and chemical-disease relationships. Furthermore, CTD analysis can be used to predict biological responses to specific genes, toxicity mechanisms, and potential associations with diseases.

[0030] In one embodiment of the present invention, it was confirmed that the expression of CDHR3 and SCGB3A2 is decreased in the lung tissue of a COVID-19 model and an asthma patient, while the expression of PLAU and NPY is increased, so they can be utilized as biomarkers for diagnosing asthma caused by SARS-CoV-2 infection.

[0031]

[0032] According to another aspect of the present invention, the present invention provides a composition for diagnosing asthma caused by SARS-CoV-2 infection, comprising a preparation for measuring the expression of one or more selected from the group consisting of CDHR3, SCGB3A2, PLAU, and NPY; or a gene encoding therefrom.

[0033] In the present invention, a preparation for measuring the expression of any one or more selected from the group consisting of CDHR3, SCGB3A2, PLAU, and NPY; or a gene encoding therefrom; refers to a molecule that can be used for the detection of a marker by specifically binding to CDHR3 and SCGB3A2 proteins or mRNA encoding therefrom, which are markers whose expression decreases in biological samples isolated from asthma patients as described above, or by specifically binding to PLAU and NPY proteins or mRNA encoding therefrom, which are markers whose expression increases in biological samples isolated from asthma patients, thereby confirming the expression level thereof.

[0034] The agent for measuring the expression of one or more selected from the group consisting of CDHR3, SCGB3A2, PLAU, and NPY may be an oligopeptide, monoclonal antibody, polyclonal antibody, chimeric antibody, ligand, PNA (Peptide nucleic acid), or aptamer that specifically binds to one or more selected from the group consisting of CDHR3, SCGB3A2, PLAU, and NPY.

[0035] The term "antibody" as used in the present invention refers to a specific protein molecule indicated for an antigenic site, as is a term known in the art. For the purposes of the present invention, an antibody refers to an antibody that specifically binds to one or more selected from the group consisting of CDHR3, SCGB3A2, PLAU, and NPY, which are the markers of the present invention. Such antibodies can be prepared by conventional methods by cloning each gene into an expression vector according to conventional methods to obtain a protein encoded by said marker gene, and from the obtained protein. This includes partial peptides that can be produced from said protein. The form of the antibody of the present invention is not particularly limited, and polyclonal antibodies, monoclonal antibodies, or parts thereof having antigen-binding ability are included in the antibody of the present invention, and all immunoglobulin antibodies are included. Furthermore, the antibody of the present invention includes special antibodies such as humanized antibodies.

[0036] The antibody used for detecting the asthma diagnostic biomarker of the present invention comprises not only a complete form having two full-length light chains and two full-length heavy chains, but also functional fragments of the antibody molecule. A functional fragment of the antibody molecule refers to a fragment that possesses at least an antigen-binding function, and includes Fab, F(ab'), F(ab') 2, and Fv.

[0037] The agent for measuring the expression of one or more genes coding for selected from the group consisting of CDHR3, SCGB3A2, PLAU, and NPY may be an antisense oligonucleotide, a primer pair, or a probe.

[0038] In the present invention, "primer" refers to a short nucleic acid sequence having a short free 3' hydroxyl group, capable of forming base pairs with a complementary template, and functioning as a starting point for template strand replication. DNA synthesis can be initiated by the primer in the presence of a reagent for a polymerization reaction (i.e., DNA polymerase or reverse transcriptase) and four different nucleoside triphosphates at an appropriate buffer solution and temperature. Specifically, asthma can be diagnosed by determining whether a desired product is produced by performing PCR amplification using sense and antisense primers of one or more polynucleotides selected from the group consisting of CDHR3, SCGB3A2, PLAU, and NPY. The PCR conditions and the lengths of the sense and antisense primers can be modified based on those known in the art.

[0039] In the present invention, "probe" refers to a nucleic acid fragment, such as RNA or DNA, ranging from a few bases to several hundred bases in length, capable of forming a specific binding with mRNA, and is labeled to confirm the presence or absence of a specific mRNA. The probe may be constructed in the form of an oligonucleotide probe, a single-stranded DNA probe, a double-stranded DNA probe, an RNA probe, etc. The selection of a suitable probe and hybridization conditions may be modified based on those known in the art.

[0040] The primers or probes of the present invention may be chemically synthesized using the phosphoramidite solid support method or other widely known methods. These nucleic acid sequences may also be modified using many means known in the art. Non-limiting examples of such modifications include methylation, "capping," substitution with one or more homologues of the natural nucleotide, and modification between nucleotides, for example, modification to an uncharged linkage (e.g., methyl phosphonate, phosphotriester, phosphoroamidate, carbamate, etc.) or a charged linkage (e.g., phosphorothioate, phosphorodithioate, etc.).

[0041]

[0042] According to another aspect of the present invention, the present invention provides a kit for diagnosing asthma caused by SARS-CoV-2 infection comprising the above-mentioned composition for diagnosing asthma caused by SARS-CoV-2 infection.

[0043] The above kit may be an RT-PCR kit, a DNA chip kit, a Western blotting kit, or a protein chip kit, but is not limited thereto.

[0044] The above kit may include not only a preparation for measuring the expression of one or more selected from the group consisting of CDHR3, SCGB3A2, PLAU, and NPY; or a gene encoding therefrom; but also tools, reagents, etc. commonly used in the field for immunological analysis.

[0045] Examples of the above tools or reagents include, but are not limited to, a suitable carrier, a labeling substance capable of generating a detectable signal, chromophores, a solvent, a cleaning agent, a buffer, a stabilizer, etc. If the labeling substance is an enzyme, it may include a substrate capable of measuring enzyme activity and a reaction stopping agent. The carrier may be a soluble carrier or an insoluble carrier. An example of a soluble carrier is a physiologically acceptable buffer known in the art, e.g., PBS. An example of an insoluble carrier may be a polymer such as polystyrene, polyethylene, polypropylene, polyester, polyacrylonitrile, fluoropolymer, cross-linked dextran, polysaccharide, or latex plated with metal, other paper, glass, metal, agarose, and combinations thereof.

[0046] Since the kit of the present invention comprises the aforementioned biomarker composition and diagnostic composition, redundant details are omitted to avoid excessive complexity in this specification.

[0047]

[0048] According to another aspect of the present invention, the present invention provides a method for providing information on the diagnosis of asthma caused by SARS-CoV-2 infection, comprising the step of measuring the expression of one or more selected from the group consisting of CDHR3, SCGB3A2, PLAU, and NPY; or a gene encoding therefrom in a biological sample.

[0049] The information regarding the above diagnosis is measurement information regarding the expression of one or more selected from a group consisting of CDHR3, SCGB3A2, PLAU, and NPY in patients with asthma caused by SARS-CoV-2 infection. For the purposes of the present invention, it is suggested that the incidence of asthma after SARS-CoV-2 infection increases when the expression of CDHR3 and SCGB3A2 is measured to be decreased or the expression of PLAU and NPY is measured to be increased. Based on this, the present invention provides information on whether an individual develops asthma caused by SARS-CoV-2 infection.

[0050] In the present invention, "measuring the expression of one or more selected from the group consisting of CDHR3, SCGB3A2, PLAU, and NPY" is a process of confirming the presence and degree of expression of a protein expressed in a biological sample for the diagnosis of asthma, and confirming the amount of protein using a molecule that specifically binds to said protein.

[0051] Analysis methods for this include, but are not limited to, Western blotting, ELISA (enzyme-linked immunosorbent assay), radioimmunoassay (RIA), radioimmunodiffusion, Ouchterlony immunodiffusion, rocket immunoelectrophoresis, tissue immunostaining, immunoprecipitation assay, complement fixation assay, FACS, and protein chip.

[0052] In the present invention, "measuring the expression of one or more genes coding for selected from the group consisting of CDHR3, SCGB3A2, PLAU, and NPY" is a process of confirming the presence and level of expression of mRNA of an asthma diagnostic biomarker gene in a biological sample to diagnose asthma, which can be determined by measuring the amount of mRNA.

[0053] Analysis methods for this include RT-PCR, Competitive RT-PCR, Real-time RT-PCR, RNase protection assay (RPA), Northern blotting, or DNA chips, but are not limited to these.

[0054] The biological sample mentioned above may be blood, plasma, serum, urine, saliva, or tissue, but is not limited thereto.

[0055]

[0056] According to another aspect of the present invention, the present invention comprises the steps of: (a) treating a target substance to be screened on isolated cells, isolated tissues, or animals other than humans as an experimental group; and

[0057] (b) a step of measuring and comparing the expression of one or more selected from the group consisting of CDHR3, SCGB3A2, PLAU, and NPY; or genes encoding therefrom; in the experimental group of step (a) above and a control group not treated with the target substance; thereby providing a screening method for an asthma treatment agent for SARS-CoV-2 infection.

[0058] The above screening method may further include a step of selecting a target substance that inhibits the expression of CDHR3 and SCGB3A2; or the gene encoding them; in the experimental group compared to the control group, based on the comparison result of step (b) above.

[0059] Additionally, the screening method may further include a step of selecting a target substance that promotes the expression of PLAU and NPY; or the gene encoding them; in the experimental group compared to the control group based on the comparison result of step (b).

[0060] As it was confirmed through changes in the expression of biomarkers CDHR3, SCGB3A2, PLAU, or NPY according to one embodiment of the present invention that the incidence of asthma is higher in patients infected with SARS-CoV-2 compared to normal individuals, this can be utilized in various ways in the fields of diagnosis of SARS-CoV-2-induced asthma and drug screening.

[0061] Figure 1a is a list of 145 genes with the largest changes in gene expression compared to the lung injury-only group or the SARS-CoV-2 virus-infected-mice group, using RNA sequencing (RNA-seq).

[0062] Figure 1b is a figure analyzing the association between inflammation and immune-related responses and lung disease in a group of lung-damaged mice infected with SARS-CoV-2 virus (hereinafter referred to as severe SARS-CoV-2 infected mice) through Gene ontology (GO) and Disease ontology (DO) analysis on a list of 145 genes.

[0063] Figure 2 shows the results of a CTD (Comparative Toxicogenomics Database) analysis of the list of genes with the greatest changes (a total of 145) in a mouse model of severe SARS-CoV-2 infection, visualized as a Venn diagram.

[0064] Figure 3a shows the expression patterns of CDHR3, SCGB3A2, PLAU, and NPY among the eight secondary selected genes, compared with the gene expression GSE data set of patients with severe SARS-CoV-2 infection.

[0065] Figure 3b shows the expression patterns of adcyap1r1, alox5, hmox1, and ccl2 among the eight secondary selected genes, compared with the gene expression GSE data set of patients with severe SARS-CoV-2 infection.

[0066] Figure 4 shows the results of confirming the expression of the four biomarkers in a mouse model of severe SARS-CoV-2 infection using real-time RT-PCR for the four finally selected biomarkers.

[0067] The present invention will be explained in more detail below through specific embodiments. The details described in the following embodiments describe a preferred embodiment of the present invention, and the scope of the present invention is not limited by the details described in the following embodiments.

[0068]

[0069] Example 1. Primary gene screening via NGS in a severe COVID-19 mouse model

[0070] Histopathological analysis and cytokine expression analysis confirmed that infecting mice with lung injury with the SARS-CoV-2 virus exacerbated COVID-19 and pulmonary fibrosis. In addition, to investigate the induced molecular changes, a list of genes with the greatest changes in expression was derived in the group of lung injury mice infected with the SARS-CoV-2 virus compared to the group with lung injury alone or the group infected with the SARS-CoV-2 virus alone, and this is shown in Figure 1.

[0071] As shown in Figure 1, a total of 145 genes were significantly regulated compared to other groups, of which 46 genes increased and 99 genes decreased (Figure 1a). In addition, Gene ontology (GO) and Disease ontology (DO) analyses were performed on this gene list, confirming increased inflammation and immune-related responses and increased associations related to lung disease, thereby confirming once again through genetic changes that this group represents a severe COVID-19 mouse model (Figure 1b).

[0072]

[0073] Example 2. Secondary gene screening through comparison with asthma-related genes

[0074] As asthma was induced in the histopathological analysis of mice infected with severe SARS-CoV-2, CTD (Comparative Toxicogenomics Database) analysis was performed on the list of genes with the greatest changes (a total of 145) in the severe SARS-CoV-2 infected mouse model according to Example 1 to identify common genes by plotting the association between asthma and SARS-CoV-2 using a Venn diagram, and this is shown in Figure 2.

[0075] As shown in Figure 2, out of 145 genes, a total of 8 genes related to asthma were identified as ADCYAP1R1, ALOX5, CDHR3, HMOX1, NPY, PLAU, SCGB3A2, and CCL2.

[0076]

[0077] Example 3. Final gene screening through confirmation of expression in a dataset of patients with severe SARS-CoV-2 infection

[0078] To discover clinically applicable biomarkers, patient gene expression data was obtained using the GSE dataset provided by NCBI, a bioinformatics site under the U.S. NIH. Among the GSE datasets, the gene expression datasets of patients with severe SARS-CoV-2 infection (GSE172114, GSE211979) were utilized. For the eight previously selected genes, it was confirmed whether the expression pattern of each gene showed a common expression pattern with the gene expression of patients in the GSE dataset, and the results are shown in Figures 3a and 3b.

[0079] As shown in Figures 3a and 3b, it was confirmed that CDHR3, SCGB3A2, PLAU, and NPY exhibited expression patterns similar to those of patients with severe SARS-CoV-2 infection (Figure 3a). However, it was confirmed that ADCYDP1R1, ALOX5, HMOX1, and CCL2 showed no difference from the existing patterns or exhibited patterns opposite to those of patients with severe SARS-CoV-2 infection (Figure 3b). Based on these results, four genes—CDHR3, SCGB3A2, PLAU, and NPY—were finally selected as biomarkers for diagnosing asthma caused by SARS-CoV-2 infection.

[0080]

[0081] Example 4. Verification of the usefulness of the finally selected biomarker

[0082] To verify the utility of the four finally selected biomarkers, the expression of the four biomarkers was confirmed in a mouse model of severe SARS-CoV-2 infection using real-time RT-PCR, and the results are shown in Figure 4.

[0083] As shown in Figure 4, it was confirmed that the expression of CDHR3 and SCGB3A2 was significantly reduced compared to the control group, the lung injury-only group, and the SARS-CoV-2 virus infection-only group, while the expression of PLAU and NPY was significantly increased compared to the control group, the lung injury-only group, and the SARS-CoV-2 virus infection-only group.

[0084]

[0085] Based on the above results, the four biomarkers of the present invention show changes in expression in both SARS-CoV-2 infected patients and asthma patients, so it is expected that they can be usefully used as biomarkers for diagnosing asthma caused by SARS-CoV-2 infection.

[0086]

[0087] Although the present invention has been described as a preferred embodiment mentioned above, various modifications and variations are possible without departing from the essence and scope of the invention. Furthermore, the appended claims include such modifications and variations that fall within the essence of the invention.

[0088] As it was confirmed through changes in the expression of biomarkers CDHR3, SCGB3A2, PLAU, or NPY according to one embodiment of the present invention that the incidence of asthma is higher in patients infected with SARS-CoV-2 compared to normal individuals, there is industrial applicability as it can be utilized in various fields of diagnosis of SARS-CoV-2-induced asthma and drug screening.

Claims

1. A biomarker composition for diagnosing asthma caused by SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus-2) infection comprising one or more selected from the group consisting of CDHR3 (Cadherin-related family member 3) or SCGB3A2 (secretoglobin family 3A member 2), PLAU (plasminogen activator, urokinase), and NPY (neuropeptide Y).

2. In Paragraph 1, A biomarker composition in which the above CDHR3 or SCGB3A2 is reduced in expression in the lung tissue of asthma patients.

3. In Paragraph 1, The above-mentioned PLAU or NPY is a biomarker composition in which expression increases in the lung tissue of asthma patients.

4. A composition for diagnosing asthma caused by SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus-2) infection, comprising a preparation for measuring the expression of any one or more selected from the group consisting of CDHR3, SCGB3A2, PLAU, and NPY; or a gene encoding therefrom.

5. In Paragraph 4, A composition for diagnosing asthma, wherein the agent for measuring the above expression is an oligopeptide, monoclonal antibody, polyclonal antibody, chimeric antibody, ligand, PNA (Peptide nucleic acid), or aptamer that specifically binds to CDHR3, SCGB3A2, PLAU, or NPY.

6. A kit for diagnosing asthma caused by SARS-CoV-2 infection comprising the composition of claim 4 or 5.

7. In Paragraph 6, The above kit is an asthma diagnostic kit, which is an RT-PCR kit, a DNA chip kit, a Western blotting kit, or a protein chip kit.

8. A method for providing information on the diagnosis of asthma caused by SARS-CoV-2 infection, comprising the step of measuring the expression of one or more selected from the group consisting of CDHR3, SCGB3A2, PLAU, and NPY; or a gene encoding therefrom in a biological sample.

9. (a) a step of treating isolated cells, isolated tissues, or animals other than humans as an experimental group with a target substance to be screened; and (b) a step of measuring and comparing the expression of one or more selected from the group consisting of CDHR3, SCGB3A2, PLAU, and NPY; or genes encoding therefrom; in the experimental group of step (a) above and the control group not treated with the target substance; a screening method for an asthma treatment agent for SARS-CoV-2 infection comprising: (b) a step of measuring and comparing the expression of CDHR3, SCGB3A2, PLAU, and NPY; or genes encoding therefrom.

10. In Paragraph 10, The above screening method (c) a step of selecting a target substance that inhibits the expression of CDHR3 and SCGB3A2; or genes encoding them; in the experimental group compared to the control group based on the comparison result of step (b) above; a screening method for asthma treatments further comprising 11. In Paragraph 10, The above screening method (c) a step of selecting a target substance that promotes the expression of PLAU and NPY; or the gene encoding them; in the experimental group compared to the control group based on the comparison result of step (b) above; a screening method for asthma treatments further comprising: (c) a step of selecting a target substance that promotes the expression of PLAU and NPY; or the gene encoding them; in the experimental group compared to the control group.

12. A method for diagnosing asthma caused by SARS-CoV-2 infection, comprising the step of measuring the expression of one or more selected from the group consisting of CDHR3, SCGB3A2, PLAU, and NPY; or a gene encoding therefrom in a biological sample.

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