Urinary Levels of SARS-CoV-2 Nucleocapsid Protein Associate With Risk of AKI and COVID-19 Severity: A Single-Center Observational Study

Désirée Tampe; Samy Hakroush; Mark-Sebastian Bösherz; Jonas Franz; Heike Hofmann-Winkler; Stefan Pöhlmann; Stefan Kluge; Onnen Moerer; Christine Stadelmann; Philipp Ströbel; Martin Sebastian Winkler; Björn Tampe

doi:10.3389/fmed.2021.644715

Urinary Levels of SARS-CoV-2 Nucleocapsid Protein Associate With Risk of AKI and COVID-19 Severity: A Single-Center Observational Study

Front Med (Lausanne). 2021 May 25:8:644715. doi: 10.3389/fmed.2021.644715. eCollection 2021.

Authors

Affiliations

¹ Department of Nephrology and Rheumatology, University Medical Center Göttingen, Göttingen, Germany.
² Institute of Pathology, University Medical Center Göttingen, Göttingen, Germany.
³ Institute of Neuropathology, University Medical Center Göttingen, Göttingen, Germany.
⁴ Max Planck Institute for Experimental Medicine, Göttingen, Germany.
⁵ Campus Institute for Dynamics of Biological Networks, University of Göttingen, Göttingen, Germany.
⁶ Infection Biology Unit, German Primate Center, Leibniz Institute for Primate Research Göttingen, Göttingen, Germany.
⁷ Faculty of Biology and Psychology, University Göttingen, Göttingen, Germany.
⁸ Department of Intensive Care Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
⁹ Department of Anesthesiology, Emergency and Intensive Care Medicine, University Medical Center Göttingen, Göttingen, Germany.

Abstract

Background: Acute kidney injury (AKI) is very common in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) disease 2019 (COVID-19) and considered as a risk factor for COVID-19 severity. SARS-CoV-2 renal tropism has been observed in COVID-19 patients, suggesting that direct viral injury of the kidneys may contribute to AKI. We examined 20 adult cases with confirmed SARS-CoV-2 infection requiring ICU supportive care in a single-center prospective observational study and investigated whether urinary markers for viral infection (SARS-CoV-2 N) and shedded cellular membrane proteins (ACE2, TMPRSS2) allow identification of patients at risk for AKI and outcome of COVID-19. Objectives: The objective of the study was to evaluate whether urinary markers for viral infection (SARS-CoV-2 N) and shedded cellular membrane proteins (ACE2, TMPRSS2) allow identification of patients at risk for AKI and outcome of COVID-19. Results: Urinary SARS-CoV-2 N measured at ICU admission identified patients at risk for AKI in COVID-19 (HR 5.9, 95% CI 1.4-26, p = 0.0095). In addition, the combination of urinary SARS-CoV-2 N and plasma albumin measurements further improved the association with AKI (HR 11.4, 95% CI 2.7-48, p = 0.0016). Finally, combining urinary SARS-CoV-2 N and plasma albumin measurements associated with the length of ICU supportive care (HR 3.3, 95% CI 1.1-9.9, p = 0.0273) and premature death (HR 7.6, 95% CI 1.3-44, p = 0.0240). In contrast, urinary ACE2 and TMPRSS2 did not correlate with AKI in COVID-19. Conclusions: In conclusion, urinary SARS-CoV-2 N levels associate with risk for AKI and correlate with COVID-19 severity.

Keywords: SARS-CoV-2 disease 2019; acute kidney injury; intensive care; risk prediction; severe acute respiratory syndrome coronavirus-2.