The virus that causes COVID-19 can cause a specific type of cell to die. The discovery helps explain why patients with severe COVID-19 are more likely to suffer from acute kidney injury.
The research was published in the journal on April 20.
When COVID-19 began spreading in early 2020, physicians knew it was a respiratory tract virus. As the case numbers grew, physicians were surprised to see that many patients were also developing injuries to their kidneys.
When she attended a virtual symposium in the spring of 2020, the issue came to her attention. Musah, an assistant professor of biomedical engineering and medicine at Duke, was listening to the research that showed how patients who had never experienced any issues with the kidneys were developing it after getting sick with COVID-19.
It was shocking to hear doctors describe how patients who were healthy suddenly developed kidney injury and needed to go on a transplant.
Musah and her team showed that they could guide human stem cells to become functional Podocytes, which are a specific type of kidney cell that helps control the removal of toxins and waste from the blood. Musah and Titilola wanted to see if they could use the model to figure out how and why the disease was able to damage the kidneys.
As a proof of concept, they worked with a pseudoviruses. The psuedoviruses are safe to use for broad research because they are incapable of producing replication-competent viral particles. After introducing the pseudoviruses into their cell model, it was found that the spikeProtein of the virus could bind to the surface of the cells.
The virus binding to the two key receptors on the surface of the Podocytes was found to be especially effective by the team. The virus had a strong affinity for these cells.
The Duke Human Vaccine Institute and Maria Blasi, an assistant professor of medicine at Duke, collaborated with Musah and Kalejaiye to test their model with the real SARS-CoV-2 virus. Blasi was researching how viruses, including HIV, can cause damage to a subset of kidneys called therenal tubular epithelial cells.
It was a stroke of luck that we crossed paths at the faculty meeting.
The team observed that the live version of the virus had a strong affinity for the cells. The long, finger-like structures of the Podocytes were damaged by the virus, and they help filter blood. The cells would die if the injuries were too severe.
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 other cells.
The team hopes to study how the different versions of SARS-CoV-2 behave in the body. There are less injuries to the kidneys as a result of the virus. The team is questioning how the new variant are changing and if they are less capable of causing harm to the body.
Musah said it was remarkable that they went from being home and hearing the initial reports from physicians to having these results on such a short time frame. It has been one of the most successful collaborations of my lab, and I am looking forward to continuing this work.
The work was supported by a Whitehead Scholarship in Biomedical Research, a Chair's Research Award from the Department of Medicine at Duke University, a Duke MEDx Pilot Grant on Biomechanics in Injury or Injury Repair, and a Genen. The National Institute of Diabetes and Digestive and Kidney Diseases grant number is R01DK130381. The Duke Regional Biocontainment Laboratory (RBL) received partial support for construction from the National Institute of Allergy and Infectious Diseases, which supported the work with live SARS-CoV-2 isolate.
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Duke University provided the materials. Michaela Kane wrote the original. Content can be edited for style and length.
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