Kidney Week

Abstract: FR-PO020

Lack of Evidence for Kidney Invasion by SARS-CoV-2 in a Lethal Mouse Model

Session Information

• COVID-19: AKI Outcomes, Biomarkers, Treatments, Case Reports
  November 04, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
  Abstract Time: 10:00 AM - 12:00 PM

Category: Coronavirus (COVID-19)

• 000 Coronavirus (COVID-19)

Authors

• Syed, Mariya, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States

Mariya Syed,

• Cianfarini, Cosimo L., Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States

Cosimo L. Cianfarini,

• Hassler, Luise, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States

Luise Hassler,

• Ye, Minghao, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States

Minghao Ye,

• Wysocki, Jan, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States

Jan Wysocki,

• Kanwar, Yashpal S., Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States

Yashpal S. Kanwar,

• Missiakas, Dominique, University of Chicago Department of Microbiology, Chicago, Illinois, United States

Dominique Missiakas,

• Randall, Glenn, University of Chicago Department of Microbiology, Chicago, Illinois, United States

Glenn Randall,

• Batlle, Daniel, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States

Daniel Batlle,

Background

There is an ongoing controversy as to whether SARS CoV-2 can infect the kidney parenchyma directly. To date, the presence of SARS CoV-2 in the kidney has been described mainly post-mortem in autopsy studies of patients who died of or with COVID-19, but this has not been examined in an experimental model where the timing of SARS-CoV-2 infection can be defined. We used transgenic mice expressing human ACE2 (k18hACE2) susceptible to lethal SARS-CoV-2 infection to study this issue directly on kidney tissue taken at defined time points and using lung tissue as positive control.

Methods

Transgenic k18hACE2 mice were inoculated with 3x10⁴ PFU SARS-CoV-2 in a BSL-3 facility. Kidneys and lungs were removed from the animals sacrificed on days 5 to 7 and used for histology (PAS-staining), immunofluorescence (IF) of the S1 spike protein of SARS-CoV-2 and measurement of viral load by plaque assay. Kidney samples were additionally evaluated by IF using kidney injury markers NGAL and KIM-1.

Results

Kidney tissue stained using an anti-S1-spike antibody showed negative results in all samples (n=15). By plaque assay, viral titers were also not detectable in any of the kidneys. By contrast, lungs from infected mice showed strong staining for the S1 spike protein in 13 of 14 cases and this was associated with positive viral titers in all lung samples. Despite severe lung disease, only mild and variable kidney damage was observed by histopathology. Positive staining for NGAL in the proximal tubules was consistently seen, while KIM-1 staining was rarely positive.

Conclusion

In a transgenic mouse model with lethal SARS-CoV-2 infection and severe lung but mild kidney disease there is no evidence of S1 spike protein in the kidney, which is consistent with lack of detection of replicating virus by plaque assay.

Funding

• Other NIH Support