Predict Adverse Events by Covid-19 Nephritis

Study Overview
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Brief Summary
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This non-interventional, observational study retrospectively (and in parts prospectively) investigates, if a Covid-19 associated Nephritis, diagnosed by Urine-dipstick and further Urine-analyses on addmission, can help to predict later complications, adverse outcomes and later need for ICU-capacity in Covid-19 patients as well as can guide preventive strategies.

Detailed Description
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Parameters predicting risks for Covid-19 patients are urgently sought. The current study investigates, if Covid-19 associated nephritis indicating systemic cappillary leak syndrome/severe nephrotic syndrome could be the major driver for complications, predictor for respiratory failure and later need for ICU, and death. This study intends to generate an algorithm for University hospitals, which allows early detection of Covid-19 associated nephritis and to classify the risk for respiratory decompensation by quantification of severity of nephrotic syndrome. The rationale of the observational study can be explained by the hypothesis that Covid-19 causes Nephritis: Podocytes express high levels of ACE2, which makes the glomerulus to a target for Covid-19. Other zoonoses, such as Hanta-virus, are a well described cause of nephrotic syndrome inducing cardiopulmonary syndrome. Life-threatening complications of severe nephrotic syndrome are well known as are preventive therapies. Covid-19 ICU patients with nephritis have pulmonary interstitial edema, possibly also due to capillary leak/ nephrotic syndrome; immune-incompetence, due to renal loss of immunoglobulins; circulatory insufficiency, due to hypalbuminemia (which might explain sudden deaths in the geriatric population); less response to some medications caused by impaired plasma protein binding of drugs due to hypalbuminemia and renal loss; thromboembolic events, due to antithrombin-deficiency (which might explain lethality in oligo-symptomatic young patients). In conclusion, ACE2 in the respiratory tract is the gateway for Covid-19 for infection, however, the study postulates that Covid-19 associated nephritis and severe cappillary leak/nephrotic syndrome is a major driver of adverse outcome. If confirmed by others, these findings and algorithm would allow early prediction of later need for ICU-capacity, better allocation of patients for clinical trials, and preventive strategies focused on the nephrotic syndrome including treatment, which can save lives. Same might apply for risk-evaluation of outpatients.

Official Title
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Covid-19 Associated Nephritis as Early Predictor for Complicated Course of Disease

Conditions
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Covid-19

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: approved Covid-19 diagnosis (by PCR or CT-scan); urine status during hospital stay Patient expressed willingness to participate in observational studies during hospital admission. Exclusion Criteria: 1) Patient expressed unwillingness to participate in observational studies during hospital admission.
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| low risk<br>This group has a normal urine status on admission to hospital. Abnormal urine status is defined anuric OR as 2* or more of the following findings: urine osmolarity below normal values leukozyturia hematuria albuminuria/ proteinuria * if urine is positive for nitrite or bacteria, abnormal urine status is defined as 3 or more of the findings. | |
| intermediate risk<br>This group has an abnormal urine status on admission to hospital WITHOUT serum-albumin below 2.0 g/dl AND WITHOUT antithrombin III level below 70%. | |
| high risk<br>This group has an abnormal urine status on admission to hospital PLUS serum-albumin below 2.0 g/dl OR antithrombin III level below 70%. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Disease-Aggravation | Time (in days) from hospital admission to transferral to ICU (ICU level high) OR time (in days) from Hospital Admission to Death | during first 10 days after admission to hospital | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complications | Number of Complications are defined as Need of transferral to ICU low (ICU level 1)* Need of transferral to ICU high (ICU level 3)* Need of mechanical ventilation* OR Need for renal replacement therapy* OR Need of extracorporeal membrane oxygenation* OR Death * in the first 10 days after admission to hospital | during first 10 days after admission to hospital | 
| Resources | Time on ICU low (in days), Time on ICU high (in days), Time on invasive mechanical ventilation (in days) Time on extracorporeal membrane oxygenation (in days) Time on renal replacement therapy (in days) | during hospital stay, up to 2 months | 
| Blood-test | lowest serum-albumin lowest antithrombin III | during hospital stay, up to 2 months |