SARS-CoV-2 May Exploit Injured Kidney Cells to Cause Infecti
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SARS-CoV-2 does not seem to injure the kidney directly, but may trigger acute injury or tubular damage in already injured cells, a preclinical study suggests. The human adult kidney cells the team studied "had all of the molecules required for viral entry - ACE2 and others - and indeed, they observed both infection and replication of the virus in the cells. No evidence for cell destruction and cell death was apparent.

A separate comparison of human adult kidney cells to a monkey kidney cell line deficient in interferon molecules showed that in the interferon-deficient cells, destruction and the cytopathic response was clearly evident within a short period of time, the researcher noted. The baseline levels of interferon molecules measured in the human kidney cells were relatively high. They propose that this is a protective mechanism, allowing the human kidney cells to survive invasion by the virus.

"We were also surprised that when cells were grown in 'injury mode,' they were more susceptible to infection and replication of the virus and consequent inflammatory response,' he said. "In addition, molecular markers related to kidney injury were significantly changed in these cells following viral infection, suggesting some damage caused by the virus."

The team did a series of experiments in ex vivo cell models to analyze SARSCov2 interactions with kidney tubular cells and assess the direct tubular injury. They grew primary human kidney epithelial cells derived from nephrectomies as three-dimensional spheroids that imitate the healthy kidney, and as a two-dimensional layer that mimics the cells of an acutely injured kidney.

They noted, cells that mimicked an acutely injured kidney were more prone to infection and additional injury, but not cell death, suggesting that the virus is unlikely to be a primary cause of the acute injury seen in COVID-19, and that if such injury takes place in the kidney by any cause, the virus might take the opportunity to intensify it.

The researcher said, "We suggest that if one contracts the virus and it ends up in kidney cells, this would not directly or by itself lead to profound AKI or acute tubular necrosis (ATN). Presumably, if AKI/ATN does occur for a variety of medical reasons and kidney cells turn to 'injury' mode, the virus may exploit this weakness to add some form of damage. "In hospitalized COVID-19 cases, we should try and make every effort to perfuse kidneys well and prevent the injury mode cascade," he concluded.

Source:
https://jasn.asnjournals.org/content/early/2021/06/10/ASN.2020111546/tab-article-info
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Jun 27, 2021Like1