High SARS-CoV-2 Viral Load in Urine Sediment Correlates with Acute Kidney Injury and Poor COVID-19 Outcome
Paulo S. Caceres, Gina Savickas, Shannon L. Murray, Kausik Umanath, Junior Uduman, Jerry Yee, Tang‐Dong Liao, Steven R. Bolin, Albert M. Levin, Moomal N. Khan, Sarah Sarkar, Jamie M. Fitzgerald, Dipak Maskey, Adrian Ormsby, Yuvraj Sharma, Pablo A. Ortiz
Abstract
Significance statement AKI has been recognized as a common complication of coronavirus disease 2019 (COVID-19) and is associated with disease severity and mortality. The mechanisms behind these associations remain obscure, due, in part, to unsuccessful attempts to consistently detect the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in urine, despite evidence of kidney tropism. This study consistently quantifies the SARS-CoV-2 genome via quantitative RT-PCR in cells of urine sediments from patients with COVID-19. It was found that viral load in urine sediment was higher within 2 weeks of the AKI event among patients with COVID-19, and it correlated with increased risk of death. Quantification of viral load in urine sediment offers a noninvasive approach that could help identify and care for those patients with COVID-19 who are at higher risk of kidney injury and poor outcome. 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.