Evidence For and Against Direct Kidney Infection by SARS-CoV-2 in Patients with COVID-19

Abstract

Despite evidence of multiorgan tropism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in patients with coronavirus disease 2019 (COVID-19), direct viral kidney invasion has been difficult to demonstrate. The question of whether SARS-CoV2 can directly infect the kidney is relevant to the understanding of pathogenesis of AKI and collapsing glomerulopathy in patients with COVID-19. Methodologies to document SARS-CoV-2 infection that have been used include immunohistochemistry, immunofluorescence, RT-PCR, in situ hybridization, and electron microscopy. In our review of studies to date, we found that SARS-CoV-2 in the kidneys of patients with COVID-19 was detected in 18 of 94 (19%) by immunohistochemistry, 71 of 144 (49%) by RT-PCR, and 11 of 84 (13%) by in situ hybridization. In a smaller number of patients with COVID-19 examined by immunofluorescence, SARS-CoV-2 was detected in 10 of 13 (77%). In total, in kidneys from 102 of 235 patients (43%), the presence of SARS-CoV-2 was suggested by at least one of the methods used. Despite these positive findings, caution is needed because many other studies have been negative for SARS-CoV-2 and it should be noted that when detected, it was only in kidneys obtained at autopsy. There is a clear need for studies from kidney biopsies, including those performed at early stages of the COVID-19-associated kidney disease. Development of tests to detect kidney viral infection in urine samples would be more practical as a noninvasive way to evaluate SARS-CoV-2 infection during the evolution of COVID-19-associated kidney disease.

Keywords: COVID-19; interstitial nephritis; podocyte; proximal tubule; pyelonephritis.

Figure 1.

Immunofluorescence and immunogold analysis of angiotensin-converting enzyme 2 (ACE2) in the kidney. (A) Immunofluorescence staining of ACE2 (red) in proximal tubules. (B) ACE2 immunogold labeling in glomeruli. ACE2 labeled with 15 nm of gold particles is distributed in podocyte foot processes and slit diaphragm (A, arrows). The glomerular basement membrane (GBM) does not have ACE2 immunogold particles (modified from ref. with permission).

Figure 2.

Summary of data against and in favor of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in kidneys from patients with coronavirus disease 2019 (COVID-19). Number and percentage of patients in whom SARS-CoV-2 spike or nucleocapsid protein or RNA was detected (red) or not (blue). Each circle depicts immunohistochemistry, immunofluorescence, RT-PCR, or in situ hybridization. Data extracted from Tables 2 and 3.