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covid-19 has ‘strong affinity’ for damaging kidney cells
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a new study explains the connection between rising covid-19 case counts in early 2020 and the growing number of kidney injuries. getty
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a new study has shed light on how sars-cov-2, the virus that causes covid-19, can lead to acute kidney injury in previously healthy patients with no history of kidney problems.
the research, published in the journal frontiers in cell and developmental biology, helps explain the underlying mechanism behind a main complication of severe covid that has baffled physicians since the pandemic began. as case counts began to explode in early 2020, doctors could not explain the growing number of kidney injuries resulting from a virus that primarily attacks cells in the respiratory tract.
covid-19 patients suddenly need dialysis
“it was shocking to hear doctors describe how patients who were healthy suddenly developed kidney injury and needed to go on dialysis after contracting sars-cov-2,” said samira musah, an assistant professor of biomedical engineering and medicine at duke university. “it was clear that the virus was doing something to the kidneys but it was so early in the pandemic that nobody was sure what was going on.”
the mystery was of particular interest to musah, whose previous work involved guiding human induced pluripotent stem cells to develop in functional podocytes, a specific type of kidney cell responsible for removing toxins from the blood. as proof of concept, musah and her team applied a pseudovirus version of sars-cov-2 to their podocyte model. the spike protein of the this pseudovirus — which mimicked specific characteristics of sars-cov-2 but could not replicate — showed an immediate appetite for the receptors on these kidney cells.
“we found that the virus was especially adept at binding to two key receptors on the surface of the podocytes and these receptors are abundant in these kidney cells,” said titilola kalejaiye, first author of the paper a postdoctoral fellow in the lab. “there was a strong uptake of the virus initially and we also found that when you increased the dose of the virus, the uptake would increase even further. the virus seemed to have a strong affinity for these kidney cells.”
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to test their podocyte model with a live version of sars-cov-2, musah and kalejaiye joined forces with maria blasi, an assistant professor of medicine at duke, who was exploring how viruses such as hiv are capable of infecting and damaging another type of kidney cell known as renal tubular epithelial cells.
“it was a stroke of luck that we crossed paths at the faculty meeting we both attended,” blasi said. “samira was looking for someone with experience handling live viruses and i was looking for a model of the podocytes that samira can make, so we decided to kill two birds with one stone.”
virus can ‘hijack’ kidney cells
tests would soon reveal that the live virus has the same attraction to kidney cells as the pseudovirus and the same ability to infect podocytes and cause their finger-like structures, which are responsible for filtering blood, to shrivel and retract. if this damage becomes too severe, the cells can die. “beyond the structural damage, we saw that the virus could hijack the machinery of the podocytes to produce additional viral particles that could spread to infect additional cells,” blasi said.
the team intends to follow this research with a new study that will explore how the different variants of the virus affect the cells of the kidney. as sars-cov-2 has mutated, kidney damage has become less frequent, suggesting the new variants may be losing their ability to damage podocytes.
“i think it’s remarkable that we went from being home and hearing the initial reports from physicians to forming this collaboration virtually and having these results on such a short timeline,” musah said. “we had the right people and the right tools at the right time.
“it’s been one of the most successful collaborations of my relatively young lab and i’m looking forward to continuing this work.”
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dave yasvinski is a writer with healthing.ca
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