Risk Stratification of COVID-19 Using Urine Biomarkers

Study Overview
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Brief Summary
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Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and in infected patients, it produces symptoms which range from completely asymptomatic to those expressing severe illness. Early recognition of those developing severe manifestations allows for rapid and appropriate intervention, including admission to intensive care unit and intensive care therapy, such as mechanical ventilation. A current problem is that only limited data exist predicting the clinical course of COVID-19. This study will determine whether non-invasive urinalysis is useful in assessing and predicting the severity or clinical course of patients with COVID-19.

Detailed Description
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This study will conduct to elucidate the following clinical question; if the single urinary biomarker or the combination of urinary biomarkers will clarify the risk of COVID-19 confirmed mild cases. These biomarkers must be warranted to clinical use based on the evaluation by either CE or PMDA or FDA. Examination should be done within 72 h after the start of COVID-19. if above addressed biomarker can classify the effectiveness of therapy directed to COVID-19.

Official Title
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Monitoring of COVID-19 Using Urine POC Kit

Conditions
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Covid19, Urine, Biomarker, Acute Respiratory Failure With Hypoxia

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: COVID-19 confirmed cases by qPCR exam or equivalent. Those who agreed to join this study Those who received treatment at NCGM, affiliated hospital and institute including accommodation facilities for observational purposes. Exclusion Criteria: Age less than 20 Those who do not have smart phone (no personal contract) eGFR less than 30 Any pre-existing illness with fever, weakness, or respiratory difficulties, Pregnancy or breastfeeding. Doctors' judgements to inappropriate for inclusion

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| UrBMC19 Group (International Cooperative Group)<br>The examination of urine for mild pre-diagnosed COVID-19 cases are conducted to evaluate the risk classification and detect the effectiveness of early intervention by COVID-19 treatment such as dexamethasone, chloroquine, remdesivir, ivermectin, actemra, and so forth within the period of 14 days after starting the intervention. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Risk Stratification of COVID-19 Participants Using Urine Biomarkers | Urine L-FABP will be measured to detect the risk in COVID-19 confirmed cases focusing to no symptom, mild case, and moderate case. Urine beta2 microglobulin will be measured to detect the risk in COVID-19 confirmed cases. Urine L-FABP and beta2 microgloburin will be combined to examine the improvement on risk classification. The risk to develop hypoxic condition, adopted from NEJM 382:1787, 2020 (PMID: 32187464), will be pre-determined by single or dual urine biomarkers using definite cut-off values. | 10 days after starting the initial examination. | 
| Prediction of COVID-19 Treatment by Urine L-FABP | The treatment efficacy of a certain specific treatment (ex. dexamethasone, tocilizumab, remdesivir, ivermectin, favipiravir, Hydroxychloroquine, etc) to COVID-19 will be predicted through the initial urine L-FABP level in mild to moderate cases. | 14 days after starting the initial intervention. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Increase of O2 support, hospital days, worsening of chest X-ray and CT, and survival rate, at 14 and/or 30 days. | Applicability of urine L-FABP and beta2 microgloburin will be measured. Single urine biomarker (L-FABP or beta2 microgloburin) or those combination will be evaluated for predictions such as; i) increase of O2 & respiratory supports, ii) increase of hospital days, iii) worsening level of chest X-ray & CT, and iv) survival rate and SOFA in ICU. At 14 and/or 30 days after the inclusion these clinical parameters will be evaluated based on the cut off value of single urine biomarker (L-FABP or beta2 microgloburin) and those aggregates. | 30 days after starting the initial examination. | 
| Comparison of Risk Stratification with Other Biomarkers | Urine L-FABP and beta2 microgloburin will be measured. Single urine biomarker (L-FABP or beta2 microgloburin) or those combination will be compared with d-Dimer and IL-6 for the risk evaluation of COVID-19 in te scope of Outcome 3. | 7 days and 10 days after starting the initial examination. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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L-type Fatty Acid-binding Protein, beta 2 microglobulin