Study finds SARS-CoV-2 responses varied significantly depending on cell types

PARKVILLE: Researchers employed heart and lung stem cells infected with the virus that causes COVID-19 to better understand how the illness affects various organs, paving the path for more tailored therapies.

The study, co-led by Murdoch Children's Research Institute and the Peter Doherty Institute for Infection and Immunity (Doherty Institute), discovered that SARS-CoV-2 responses varied significantly depending on cell type, allowing the researchers to identify effective anti-viral drugs to treat infection in heart and lung cells. The findings were reported in Stem Cell Reports' 10th anniversary issue.

Murdoch Children's Associate Professor David Elliott, also a principal investigator at The Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW), said discovering that COVID-19 triggered variable cellular responses in different organs would provide new insights into treatment strategies.

"To further our knowledge on the impact of SARS-CoV-2 on different organs, we engineered human stem cells in the lab into lung and heart cells and infected with them with the virus," he said.

"We found the heart and lungs exhibit distinct antiviral and toxicity profiles that could inform better COVID-19 therapies and treat its complications," he added.

"Our findings highlight the importance of using several cell types for the evaluation of antiviral drugs to determine the best drug combinations for effective treatment of a virus that affects multiple organ systems," he added.

The Royal Melbourne Hospital and University of Melbourne Professor Kanta Subbarao, Virologist and Director of the WHO Collaborating Centre for Reference and Research on Influenza at the Doherty Institute, said while SARS-CoV-2 primarily infected the respiratory tract, lung and cardiac complications occur in severe cases of Covid-19.

Cardiac complications are observed in up to 78 per cent of recovered Covid-19 patients and ongoing myocardial inflammation in 60 per cent of patients.

"Although COVID-19 vaccines are highly effective in preventing severe illness and death, antiviral compounds are required for the treatment of Covid-19, particularly with the emergence of variant viruses that evade immunity," Professor Subbarao said.

"To date, only a handful of drugs have been approved for use in hospitalised Covid-19 patients and more are needed."

The study also looked at approved drugs for treating Covid-19, including Remdesivir and Molnupiravir, with some found to be more effective than others at treating infection in lung and heart stem cells. It identified Alectinib and SPHINX31 as promising antivirals for SARS-CoV-2 in both heart and lung cells.

"We have provided valuable insights into virus-host interactions in tissues that are significantly affected in Covid-19, with implications that will further therapeutic options," Professor Subbarao said.