It is well established that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) — the cause of the pandemic of coronavirus disease 2019 (COVID-19) — primarily targets cells in the respiratory tract and results in an increased respiratory failure. However, there is mounting evidence that SARS-CoV-2 pathogenicity extends beyond the respiratory tract, affecting multiple organs, including the kidneys, heart, brain and liver. This multi-organ tropism may underlie the high pathogenicity of SARS-CoV-2 and progression to severe COVID-19.

Emerging reports from the review of health records revealed that acute kidney injury frequently occurs in patients hospitalized with COVID-19 and associates with respiratory failure and poor prognosis (see for example Hirsch et al. 2020). Still, it has been unclear whether SARS-CoV-2 can directly infect human kidney cells and if so, whether it employs similar mechanisms for entry and processing (for example, binding to angiotensin-converting enzyme 2 (ACE2)) as during respiratory cell infection.

These questions have not been fully addressed, but a recent publication by Puelles et al. (2020) has helped shed some light on this topic. By analysing viral load in autopsy tissues obtained from patients who had died from COVID-19, the authors showed that the kidneys are among the most common targets of SARS-CoV-2, even in patients without prior history of chronic kidney disease. Intriguingly, SARS-CoV-2 was detectable in multiple kidney compartments (glomeruli, cortex and medulla) of randomized samples from patients with COVID-19, with preferential targeting of glomerular cells. Additional analyses of publicly available data sets from single-cell RNA sequencing revealed that multiple kidney cell types (including podocytes, glomerular endothelium, proximal tubule epithelial cells and collecting duct) express host factor genes such as ACE2, TMPRSS2 and CTSL, which are implicated in SARS-CoV-2 infectivity and pathogenicity, which could underlie SARS-CoV-2 affinity with kidney cells. Based on these findings, the authors speculated that SARS-CoV-2 multi-organ tropism might affect the severity of COVID-19 disease and related health outcomes.

the kidneys are among the most common targets of SARS-CoV-2

Recent advances in human stem cell differentiation into specialized kidney cells and the engineering of in vitro renal tissue models, such as organoids and organ-on-chip cultures, will now be instrumental in experimental investigation of SARS-CoV-2 infections in human kidney cells and in uncovering the mechanism of multi-organ tropism and associated tissue injury in patients with COVID-19 disease.