Covid-19 scientists flag key immune function as a turning point in life threatening cases

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When two brothers fell critically ill with Covid-19 around the same time in March, their doctors were baffled. Both were young—29 and 31 years old— and healthy. Yet within days they couldn’t breathe on their own and, tragically, one of them died.

Two weeks later, when a second pair of Covid-stricken brothers, both in their 20s, also appeared in the Netherlands, geneticists were called in to investigate. What they uncovered was a path leading from severe cases, genetic variations, and gender differences to a loss of immune function that may ultimately yield a new approach to treating thousands of coronavirus patients.

The common thread in the research is the lack of a substance called interferon that helps orchestrate the body’s defense against viral pathogens and can be infused to treat conditions such as infectious hepatitis. Now, increasing evidence suggests that a significant minority of Covid-19 patients get very ill because of an impaired interferon response. Twin landmark studies published Thursday in the journal Science showed that insufficient interferon may lurk at a dangerous turning point in SARS-CoV-2 infections.

“It looks like this virus has one big trick,” said Shane Crotty, a professor in the Center for Infectious Disease and Vaccine Research at the La Jolla Institute for Immunology in California. “That big trick is to avoid the initial innate immune response for a significant period of time and, in particular, avoid an early type-1 interferon response.”

The work highlights the potential for interferon-based therapies to enlarge a slowly accumulating range of Covid-19 treatments. These include Gilead Sciences Inc.’s remdesivir and convalescent plasma, a component of the blood of recovered patients that may contain beneficial immune factors.

These treatments provide limited benefit and are typically used in very sick, hospitalized patients. The possibility that interferon may help some people is enticing because it appears most efficacious in the early stages of infection, when life-threatening respiratory failure could still be averted. Dozens of studies of interferon treatment are now recruiting Covid-19 patients.

“We think timing may be essential because it’s only in the very early phase one can really battle the virus particles and defend against infection,” said Alexander Hoischen, head of the genomic technologies and immuno-genomics group at Radboud University Medical Center in Nijmegen that analyzed the DNA of the two sets of brothers.

Being male, elderly, and having underlying medical conditions can all raise patients’ risk of life-threatening Covid-19. But even within these groups, disease severity varies widely. Scientists have speculated other factors influence susceptibility, including pre-existing levels of inflammation and immunity, the amount of virus that starts an infection, and patients’ genetic makeup.

New Nexus

Interferon’s role represents a new nexus in Covid-19’s complex interaction with the human immune system. Many patients suffer their worst complications because of an immune overreaction sometimes called a cytokine storm, and may benefit from dexamethasone, a cheap generic that calms these storms.

“It’s …read more

Source:: Usa Today News

      

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