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 a very interesting disease because too little immunity is no good,” Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, said Sept. 10 in an on-line briefing for Massachusetts General Hospital staff. “Too much immunity is really, really bad.”

Whether sufficient interferon is available early or late in Covid-19 cases has a major bearing on disease severity, according to Yuen Kwok-Yung, chair of infectious diseases in the University of Hong Kong’s department of microbiology. Ideally, production of the antiviral substance would be triggered when immune cells encounter SARS-CoV-2 genetic material, stopping rapid viral reproduction inside the body and averting complications, he said.

“But the SARS-CoV-2 virus has anti-interferon genes which can stop or antagonize the production or effect of interferon,” said Yuen, who measured the effects in human lung tissue. If the interferon response is delayed and the amount of virus in the body peaks at a high level, other parts of the immune system will be “awakened.”

‘Really Disastrous’

That may trigger lung-injuring inflammation — collateral damage from an excessive immune reaction to the virus. “This is really disastrous,” he said.

Some people are known to have trouble fighting infections because they make antibodies that deactivate their own interferon. On Thursday, a global consortium of researchers said such immune reactions to the protein could account for life-threatening Covid-19 pneumonia in at least 2.6% of women and 12.5% of men.

Interferon-blocking antibodies appeared in 101 of 987 patients with severe disease, but none of 663 people with an asymptomatic or mild case, according to the study in Science. Patients over age 65 were also more likely than younger ones to have the autoimmune abnormality, which was “clinically silent until the patients were infected with SARS-CoV-2,” the group of more than 100 scientists said.

‘First Explanation’

“These findings provide a first explanation for the excess of men among patients with life-threatening Covid-19 and the increase in risk with age,” the researchers led by Jean-Laurent Casanova, head of Rockefeller University’s St. Giles Laboratory of Human Genetics of Infectious Diseases in New York said. “They also provide a means of identifying individuals at risk of developing life-threatening Covid-19.”

Genetic analysis of Covid-19 patients published in the same journal revealed two dozen gene mutations that had been “silent” until patients were infected by SARS-CoV-2. Researchers — many of them also involved in the antibody study — sequenced the genomes of 659 patients with life-threatening cases of the disease; 3.5% carried genetic variations that inhibit interferon production.

Those genetic flaws were similar to the ones that Hoischen and his colleagues from a dozen Dutch centers described in the Journal of the American Medical Association two months ago. The two sets of brothers had inherited a gene mutation that impaired the interferon response, keeping their immune systems from fighting the coronavirus until it had replicated for days.

In the Dutch men, the effects were cruel. The first, a young father from a town in the southern Netherlands, suffered shortness of breath, cough and fever at home for eight days before admission to intensive care. He was to spend 33 days in the hospital, 10 of them on a ventilator.

Raging Fever

His 29-year-old brother succumbed to Covid-19 in an intensive care unit in Rotterdam, after being treated for shock and a fever that soared to 44 degrees Celsius (111 degrees Fahrenheit). When doctors at Radboud learned of his younger sibling’s case, as well as a second pair — 21- and 23-year-old brothers also in respiratory failure — they went looking for a genetic cause.

They found a mutation that was carried on the X chromosome. Defects on this chromosome are more likely to affect men, who have only one copy, while women have two.

The men’s mutations are rare — occurring in 1 in 10,000 people — and an unlikely explanation for the vast majority of severe Covid-19 cases. But the studies in Science indicate that various forms of interferon dysfunction may underlie as many as 14% of critical patients, and that screening and targeted treatment might prevent severe illnesses and deaths.

“If we manage to get them into our university medical center early enough,” Hoischen said, “our clinicians may be able to treat them with interferons.”

Other ways of overcoming autoimmunity, like the removal of antibodies against interferon from the blood, called plasmapheresis, could also help patients. On the other hand, patients who produce antibodies against interferon shouldn’t donate blood products for treating other patients.

“The rare diseases and the more common forms of the same disease may converge, and we can learn from each other,” said Hoischen. “That’s the hope.”

-With assistance from Marthe Fourcade.

More coronavirus coverage from Fortune:

• Will the pandemic give us a Sputnik moment?
• Researchers find a “druggable pocket” in coronavirus that could lead to new antivirals
• When Bill Gates thinks we’ll have a COVID-19 vaccine—and why that won’t be the end of the pandemic
• The CEO of the Serum Institute of India on his company’s COVID-19 vaccine campaign
• How a company that makes COVID tests is keeping its own 50,000 employees safe

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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 some COVID-19 patients get very ill because of an impaired interferon response. 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.

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 a very interesting disease because too little immunity is no good,” Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, said Sept. 10 in an online briefing for Massachusetts General Hospital staff. “Too much immunity is really, really bad.”

Some people are known to have trouble fighting infections because they make antibodies that deactivate their own interferon. On Thursday, a global consortium of researchers said such immune reactions to the protein could account for life-threatening COVID-19 pneumonia in at least 2.6% of women and 12.5% of men.

Interferon-blocking antibodies appeared in 101 of 987 patients with severe disease, but none of 663 people with an asymptomatic or mild case, according to the study in Science. Patients over age 65 were also more likely than younger ones to have the autoimmune abnormality, which was “clinically silent until the patients were infected with SARS-CoV-2,” the group of more than 100 scientists said.

“These findings provide a first explanation for the excess of men among patients with life-threatening COVID-19 and the increase in risk with age,” the researchers led by Jean-Laurent Casanova, head of Rockefeller University’s St. Giles Laboratory of Human Genetics of Infectious Diseases in New York said. “They also provide a means of identifying individuals at risk of developing life-threatening COVID-19.”

Genetic analysis of COVID-19 patients published in the same journal revealed two dozen gene mutations that had been “silent” until patients were infected by SARS-CoV-2. Researchers—many of them also involved in the antibody study—sequenced the genomes of 659 patients with life-threatening cases of the disease; 3.5% carried genetic variations that inhibit interferon production.

Those genetic flaws were similar to the ones that Mr. Hoischen and his colleagues from a dozen Dutch centers described in the Journal of the American Medical Association two months ago. The two sets of brothers had inherited a gene mutation that impaired the interferon response, keeping their immune systems from fighting the coronavirus until it had replicated for days.

In the Dutch men, the effects were cruel. The first, a young father from a town in the southern Netherlands, suffered shortness of breath, cough, and fever at home for eight days before admission to intensive care. He was to spend 33 days in the hospital, 10 of them on a ventilator.

His 29-year-old brother succumbed to COVID-19 in an intensive care unit in Rotterdam, after being treated for shock and a fever that soared to 44 degrees Celsius. When doctors at Radboud learned of his younger sibling’s case, as well as a second pair—21- and 23-year-old brothers also in respiratory failure—they went looking for a genetic cause.

They found a mutation that was carried on the X chromosome. Defects on this chromosome are more likely to affect men, who have only one copy, while women have two.

The men’s mutations are rare—occurring in 1 in 10,000 people—and an unlikely explanation for the vast majority of severe COVID-19 cases. But the studies in Science indicate that various forms of interferon dysfunction may underlie as many as one in eight critical patients, and that screening and targeted treatment might prevent severe illnesses and deaths.

“If we manage to get them into our university medical center early enough,” Mr. Hoischen said, “our clinicians may be able to treat them with interferons.”

Other ways of overcoming autoimmunity, like the removal of antibodies against interferon from the blood, called plasmapheresis, could also help patients.

“The rare diseases and the more common forms of the same disease may converge, and we can learn from each other,” said Mr. Hoischen. “That’s the hope.” — Jason Gale/Bloomberg

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When AG Hair moved into its new, 70,000-sq.-foot, state-of-the-art manufacturing facility in Coquitlam, B.C., two years ago, it was part of a plan to supercharge expansion of its hair care product line to salons in international markets. Europe was next on its list. Then COVID-19 hit.

Not only was the European expansion put on hold, but salons in major markets across Canada and the United States were temporarily closed. Very few were purchasing hair products, so manufacturing was halted in mid-March, leaving most of the company’s 82 employees out of work.

AG Hair could have waited out the pandemic but instead decided to lean into its entrepreneurial culture and make a sharp pivot. It began providing hand-sanitizing products for front-line health-care workers, addressing a global shortage.

“We realized there was this massive need for health-care professionals, and we wanted to make a difference and be able to provide them with the products they needed,” says AG Hair CEO Graham Fraser.

AG Hair received Canadian and U.S. approvals a week after applying for the licences needed to make sanitizer, and produced samples to show local authorities within 48 hours.

“That rapid response time, and the fact that we had gone through all of the Health Canada regulatory hurdles, showed [the local health authorities] that we were a partner they could trust and someone they could look to, to deliver the products they needed,” Fraser says.

Within a month, the company started pumping out the products, first for the health-care industry, then for consumers on its own website and on Amazon. About 10 per cent of AG Hair’s hand-sanitizer production also went to people in need, as identified by organizations such as United Way.

Parallel 49 Brewing Company is also using AG Hair’s Coquitlam manufacturing facility to produce its own blend of liquid hand sanitizer for front-line health and emergency workers, in partnership with the B.C. government.

Fraser credits his team for its energy and creativity in making the hand-sanitizer production happen, and helping put AG Hair staff back to work.

“We realized we had an opportunity . . . and then it became this incredible, almost war-room mentality and collaboration with our owners, our executive team and our people to say, ‘How are we going to get through this?’ ” Fraser recalls. “I think our success speaks to the type of people we have and the entrepreneurial spirit of pursuing every avenue we have, understanding how we can produce the products and making it happen.”

AG Hair’s commitment to investing in future growth is a big part of what makes it a Best Managed company, says Nicole Coleman, a partner at Deloitte and co-lead of its Best Managed Program in B.C.

“Capability and innovation come through quite strongly with this company,” says Coleman, who is also AG Hair’s coach at Deloitte. “I don’t think they would be able to pivot as quickly if they weren’t so strategic and had the internal capabilities to do it.”

The manufacturing facility was a big investment, but one Coleman says has already paid dividends.

“They were looking forward with a strategic plan in mind about future growth and how they could expand, rather than just focusing on the day to day,” she says. “Best Managed companies are always pushing the envelope and are conscious about planning for the future.”

AG Hair was founded in Vancouver in 1989 by hairstylist John Davis and graphic artist Lotte Davis. The husband-and-wife team began bottling hair products in their basement and selling them direct to salons from the back of a station wagon.

The company eventually moved its manufacturing off-site, to a third party. One day, John went to watch the operations and was surprised to see salt being poured into the mixture. Although he was told salt is commonly used as a thickener, he didn’t like the potential side effects of dry hair and skin.

It was at that moment John decided the company would oversee its own manufacturing. “Through that experience, John also became an expert in product development,” says Fraser, who came to the company in 2000 as director of sales.

After having worked for more than two decades at PepsiCo and Kraft Foods, Fraser was eager to work at a smaller, more agile company where he felt he could help make a difference.

“It was perfect because I got to bring a lot of structure and process that I learned in those organizations, but I also learned an awful lot about being an entrepreneur from John and Lotte: that sense of urgency, the decision-making process, the need to get things done and drive things forward and pursue opportunities,” he says.

Fraser has helped drive AG Hair’s expansion into the U.S. and internationally, including Australia, Taiwan, and Central and South America. A portion of its sales go to One Girl Can, a charity founded by Lotte that provides schooling, education and mentoring for girls in sub-Saharan Africa.

Fraser also oversees the development of new, trending products, including a new deep-conditioning hair mask made with 98 per cent plant-based and natural ingredients. Hand-sanitizing spray and gel will be the latest addition to the company’s product lineup.

“We don’t see the demand [for hand-sanitizing products] going away,” he says. “As the isolation policies start to get lifted, people are going to need forms of security and protocols as they get back into regular life and work. We see there’s going to be a need for these types of products long-term.”

This article appears in print in the June 2020 issue of Maclean’s magazine with the headline, “Working out the kinks.” Subscribe to the monthly print magazine here.

The post How a hair-care company went from salon supplier to sanitizer powerhouse appeared first on Canadian Business - Your Source For Business News.

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