SARS-CoV-2 renal tropism associates with acute kidney injury.

Acute kidney injury is a commonly described complication of COVID-19 that has been linked to increased morbidity and mortality. Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been found in the kidney, the clinical effect remains unclear. Here, we present data from a post-mortem series of 63 patients who had SARS-CoV-2 respiratory infection (appendix pp 2–3), linking SARS-CoV-2 renal tropism to clinical outcome and acute kidney injury.

In this cohort, SARS-CoV-2 RNA was found in 38 (60%) of 63 patients. Presence of SARS-CoV-2 RNA in the kidney was associated with older age and an increased number of coexisting conditions (figure ). Furthermore, SARS-CoV-2 RNA was associated with a reduction in patients' survival time, obtained by calculating the time interval between COVID-19 diagnosis and date of death (figure). These findings support a potential correlation between extra-respiratory viral tropism, disease severity, and increased risk of premature death within the first 3 weeks of disease.

Figure

Association between SARS-CoV-2 renal tropism, disease severity, and acute kidney injury

SARS-CoV-2 tropism was associated with older age and a number of coexisting conditions (A). Survival graph comparing patients with (n=19) and without (n=13) SARS-CoV-2 renal tropism (B). High frequency of SARS-CoV-2 renal tropism in patients with acute kidney injury (C). Successful isolation of infectious SARS-CoV-2 from a post-mortem kidney tissue sample (D). SARS-CoV-2=severe acute respiratory syndrome coronavirus 2. CEC=coexisting conditions. HR=hazard ratio.

Previous studies have identified an increased risk of acute kidney injury in patients with COVID-19. Within our cohort, clinical kidney status was defined in 39 (62%) patients during the course of their disease progression (appendix pp 4–5). SARS-CoV-2 RNA was detected in the kidneys of 23 (72%) of 32 patients with acute kidney injury. By contrast, patients without acute kidney injury showed a lower frequency of SARS-CoV-2 renal tropism, with viral RNA only found in three (43%) of seven patients (figure).

SARS-CoV-2-mediated acute kidney injury might be explained by indirect factors (eg, cytokine-mediated injury) and by direct viral infection and replication in kidney epithelial cells. We isolated SARS-CoV-2 from an autopsied kidney, which produced a 1000-times increase in viral RNA after 48 h of cell infection in vitro (figure; appendix p 1), thus confirming the presence of infective virus in the kidney, even under post-mortem conditions. Furthermore, we found that patient-derived SARS-CoV-2 replicates in non-human primate kidney tubular epithelial cells (the main cellular target of acute kidney injury) using indirect immunofluorescence imaging of SARS-CoV-2 non-structural protein 3, one of the SARS-CoV replicase cleaving products (appendix p 5).

Our findings indicate that SARS-CoV-2 renal tropism is associated with disease severity (ie, premature death) and development of acute kidney injury. This suggests that SARS-CoV-2 is able to target the kidney, pointing towards the importance of early urinary testing and eventual therapeutic prevention of kidney infection.