Clinical trial NCT04347824: Predict Adverse Events by Covid-19 Nephritis
Official title: Covid-19 Associated Nephritis as Early Predictor for Complicated Course of Disease
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Covid-19
Lead sponsor: University Hospital Goettingen
Sponsor class: OTHER
Collaborators: name: Universitätsklinikum Hamburg-Eppendorf
name: University Hospital, Aachen
name: Transplantationszentrum Köln-Merheim
First posted: 2020-04-15
Enrollment: 223
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_ONLY
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: This observational study investigates the outcome of patients with approved Covid-19 diagnosis.

Brief summary: 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: 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

1. pulmonary interstitial edema, possibly also due to capillary leak/ nephrotic syndrome;
2. immune-incompetence, due to renal loss of immunoglobulins;
3. circulatory insufficiency, due to hypalbuminemia (which might explain sudden deaths in the geriatric population);
4. less response to some medications caused by impaired plasma protein binding of drugs due to hypalbuminemia and renal loss;
5. 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.

Eligibility criteria: Inclusion Criteria:

1. approved Covid-19 diagnosis (by PCR or CT-scan);
2. urine status during hospital stay
3. 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.

Primary outcomes:
measure: Time to Disease-Aggravation
timeFrame: during first 10 days after admission to hospital
Secondary outcomes:
measure: Complications
timeFrame: during first 10 days after admission to hospital
measure: Resources
timeFrame: during hospital stay, up to 2 months
measure: Blood-test
timeFrame: during hospital stay, up to 2 months
Other outcomes:
Locations:
city: Göttingen
country: Germany
facility: University Medical Center Goettingen
Study officials:
References:
citation: Gross O, Moerer O, Weber M, Huber TB, Scheithauer S. COVID-19-associated nephritis: early warning for disease severity and complications? Lancet. 2020 May 16;395(10236):e87-e88. doi: 10.1016/S0140-6736(20)31041-2. Epub 2020 May 6. No abstract available.
citation: Puelles VG, Lutgehetmann M, Lindenmeyer MT, Sperhake JP, Wong MN, Allweiss L, Chilla S, Heinemann A, Wanner N, Liu S, Braun F, Lu S, Pfefferle S, Schroder AS, Edler C, Gross O, Glatzel M, Wichmann D, Wiech T, Kluge S, Pueschel K, Aepfelbacher M, Huber TB. Multiorgan and Renal Tropism of SARS-CoV-2. N Engl J Med. 2020 Aug 6;383(6):590-592. doi: 10.1056/NEJMc2011400. Epub 2020 May 13. No abstract available.
citation: Gross O, Moerer O, Rauen T, Bockhaus J, Hoxha E, Jorres A, Kamm M, Elfanish A, Windisch W, Dreher M, Floege J, Kluge S, Schmidt-Lauber C, Turner JE, Huber S, Addo MM, Scheithauer S, Friede T, Braun GS, Huber TB, Blaschke S. Validation of a Prospective Urinalysis-Based Prediction Model for ICU Resources and Outcome of COVID-19 Disease: A Multicenter Cohort Study. J Clin Med. 2021 Jul 9;10(14):3049. doi: 10.3390/jcm10143049.