High SARS-CoV-2 Viral Load in Urine Sediment Correlates with Acute Kidney Injury and Poor COVID-19 Outcome.

Caceres, Paulo; Savickas, Gina; Murray, Shannon; Umanath, Kausik; Uduman, Junior; Yee, Jerry; Liao, Tang-Dong; Bolin, Steven; Levin, Albert; Khan, Moomal; Sarkar, Sarah; Fitzgerald, Jamie; Maskey, Dipak; Ormsby, Adrian; Sharma, Yuvraj; Ortiz, Pablo

Background Acute kidney injury (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 SARS-CoV-2 viral load in urine sediment from COVID-19 patients correlates with occurrence of AKI and mortality. Methods SARS-CoV-2 viral load in urine sediments (U-viral load) was quantified by qRT-PCR in 52 patients with PCR-confirmed COVID-19 diagnosis, hospitalized between March 15th and June 8th, 2020. Immunolabeling of SARS-CoV-2 proteins Spike and Nucleocapsid was performed in two COVID-19 kidney biopsies and urine sediments. Viral infectivity assays were performed from 32 urine sediments. Results Twenty COVID-19 patients (39%) had detectable SARS-CoV-2 U-viral load, of which 17 (85%) developed AKI with an average U-viral load 4-times higher than non-AKI COVID-19 patients. U-viral load was highest (7.7-fold) within two 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 biopsies 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 COVID-19 patients correlated with increased incidence of AKI and mortality. Urinary viral detection could inform medical care of COVID-19 patients with kidney injury to improve prognosis.