Paulo S Caceres1,2, Gina Savickas1,2,3, Shannon L Murray3, Kausik Umanath4,5, Junior Uduman4, Jerry Yee4,5, Tang-Dong Liao1, Steven Bolin6, Albert M Levin7,8, Moomal N Khan3, Sarah Sarkar3, Jamie Fitzgerald9, Dipak Maskey1, Adrian H Ormsby10, Yuvraj Sharma4, Pablo A Ortiz11,2,3. 1. Hypertension and Vascular Research Division, Department of Internal Medicine, Henry Ford Hospital, Detroit, Michigan. 2. Department of Physiology, Wayne State University, Detroit, Michigan. 3. Translational and Clinical Research Center, Henry Ford Hospital, Detroit, Michigan. 4. Division of Nephrology and Hypertension, Department of Internal Medicine, Henry Ford Hospital, Detroit, Michigan. 5. Division of Nephrology and Hypertension, Wayne State University, Detroit, Michigan. 6. Veterinary Diagnostic Laboratory, Michigan State University, Lansing, Michigan. 7. Division of Biostatistics, Department of Public Health Sciences, Henry Ford Hospital, Detroit, Michigan. 8. Center for Bioinformatics, Henry Ford Hospital, Detroit, Michigan. 9. Department of Orthopedic Surgery, Bone and Joint Center, Henry Ford Hospital, Detroit, Michigan. 10. Department of Pathology and Laboratory Medicine, Henry Ford Hospital, Detroit, Michigan. 11. Hypertension and Vascular Research Division, Department of Internal Medicine, Henry Ford Hospital, Detroit, Michigan portiz1@hfhs.org.
Abstract
BACKGROUND: AKI is a complication of coronavirus disease 2019 (COVID-19) that is associated with high mortality. Despite documented kidney tropism of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), there are no consistent reports of viral detection in urine or correlation with AKI or COVID-19 severity. Here, we hypothesize that quantification of the viral load of SARS-CoV-2 in urine sediment from patients with COVID-19 correlates with occurrence of AKI and mortality. METHODS: The viral load of SARS-CoV-2 in urine sediments (U-viral load) was quantified by qRT-PCR in 52 patients with PCR-confirmed COVID-19 diagnosis, who were hospitalized between March 15 and June 8, 2020. Immunolabeling of SARS-CoV-2 proteins Spike and Nucleocapsid was performed in two COVID-19 kidney biopsy specimens and urine sediments. Viral infectivity assays were performed from 32 urine sediments. RESULTS: A total of 20 patients with COVID-19 (39%) had detectable SARS-CoV-2 U-viral load, of which 17 (85%) developed AKI with an average U-viral load four-times higher than patients with COVID-19 who did not have AKI. U-viral load was highest (7.7-fold) within 2 weeks after AKI diagnosis. A higher U-viral load correlated with mortality but not with albuminuria or AKI stage. SARS-CoV-2 proteins partially colocalized with the viral receptor ACE2 in kidney biopsy specimens in tubules and parietal cells, and in urine sediment cells. Infective SARS-CoV-2 was not detected in urine sediments. CONCLUSION: Our results further support SARS-CoV-2 kidney tropism. A higher SARS-CoV-2 viral load in urine sediments from patients with COVID-19 correlated with increased incidence of AKI and mortality. Urinary viral detection could inform the medical care of patients with COVID-19 and kidney injury to improve prognosis.
BACKGROUND: AKI is a complication of coronavirus disease 2019 (COVID-19) that is associated with high mortality. Despite documented kidney tropism of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), there are no consistent reports of viral detection in urine or correlation with AKI or COVID-19 severity. Here, we hypothesize that quantification of the viral load of SARS-CoV-2 in urine sediment from patients with COVID-19 correlates with occurrence of AKI and mortality. METHODS: The viral load of SARS-CoV-2 in urine sediments (U-viral load) was quantified by qRT-PCR in 52 patients with PCR-confirmed COVID-19 diagnosis, who were hospitalized between March 15 and June 8, 2020. Immunolabeling of SARS-CoV-2 proteins Spike and Nucleocapsid was performed in two COVID-19 kidney biopsy specimens and urine sediments. Viral infectivity assays were performed from 32 urine sediments. RESULTS: A total of 20 patients with COVID-19 (39%) had detectable SARS-CoV-2 U-viral load, of which 17 (85%) developed AKI with an average U-viral load four-times higher than patients with COVID-19 who did not have AKI. U-viral load was highest (7.7-fold) within 2 weeks after AKI diagnosis. A higher U-viral load correlated with mortality but not with albuminuria or AKI stage. SARS-CoV-2 proteins partially colocalized with the viral receptor ACE2 in kidney biopsy specimens in tubules and parietal cells, and in urine sediment cells. Infective SARS-CoV-2 was not detected in urine sediments. CONCLUSION: Our results further support SARS-CoV-2 kidney tropism. A higher SARS-CoV-2 viral load in urine sediments from patients with COVID-19 correlated with increased incidence of AKI and mortality. Urinary viral detection could inform the medical care of patients with COVID-19 and kidney injury to improve prognosis.
Authors: Matt Arentz; Eric Yim; Lindy Klaff; Sharukh Lokhandwala; Francis X Riedo; Maria Chong; Melissa Lee Journal: JAMA Date: 2020-04-28 Impact factor: 56.272
Authors: M Donoghue; F Hsieh; E Baronas; K Godbout; M Gosselin; N Stagliano; M Donovan; B Woolf; K Robison; R Jeyaseelan; R E Breitbart; S Acton Journal: Circ Res Date: 2000-09-01 Impact factor: 17.367
Authors: Roman Wölfel; Victor M Corman; Wolfgang Guggemos; Michael Seilmaier; Sabine Zange; Marcel A Müller; Daniela Niemeyer; Terry C Jones; Patrick Vollmar; Camilla Rothe; Michael Hoelscher; Tobias Bleicker; Sebastian Brünink; Julia Schneider; Rosina Ehmann; Katrin Zwirglmaier; Christian Drosten; Clemens Wendtner Journal: Nature Date: 2020-04-01 Impact factor: 49.962