Beautiful Virgin Islands

Tuesday, Oct 21, 2025

"This Virus Has A Big Trick": Why COVID-19 Is Life-Threatening For Some

"This Virus Has A Big Trick": Why COVID-19 Is Life-Threatening For Some

Increasing evidence suggests that some Covid-19 patients get very ill because of an impaired interferon response.

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 on-line 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 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 (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 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," 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 Hoischen. "That's the hope."

Newsletter

Related Articles

Beautiful Virgin Islands
0:00
0:00
Close
This Is How the 'Heist of the Century' Was Carried Out at the Louvre in Seven Minutes: France Humiliated as Crown with 2,000 Diamonds Vanishes
China Warns UK of ‘Consequences’ After Delay to London Embassy Approval
France’s Wealthy Shift Billions to Luxembourg and Switzerland Amid Tax and Political Turmoil
"Sniper Position": Observation Post Targeting 'Air Force One' Found Before Trump’s Arrival in Florida
Shouting Match at the White House: 'Trump Cursed, Threw Maps, and Told Zelensky – "Putin Will Destroy You"'
Windows’ Own ‘Siri’ Has Arrived: You Can Now Talk to Your Computer
Thailand and Singapore Investigate Cambodian-Based Prince Group as U.S. and U.K. Sanctions Unfold
‘No Kings’ Protests Inflate Numbers — But History Shows Nations Collapse Without Strong Executive Power
Chinese Tech Giants Halt Stablecoin Launches After Beijing’s Regulatory Intervention
Manhattan Jury Holds BNP Paribas Liable for Enabling Sudanese Government Abuses
Trump Orders Immediate Release of Former Congressman George Santos After Commuting Prison Sentence
S&P Downgrades France’s Credit Rating, Citing Soaring Debt and Political Instability
Ofcom Rules BBC’s Gaza Documentary ‘Materially Misleading’ Over Narrator’s Hamas Ties
Diane Keaton’s Cause of Death Revealed as Pneumonia, Family Confirms
Former Lostprophets Frontman Ian Watkins Stabbed to Death in British Prison
"The Tsunami Is Coming, and It’s Massive": The World’s Richest Man Unveils a New AI Vision
Outsider, Heroine, Trailblazer: Diane Keaton Was Always a Little Strange — and Forever One of a Kind
Dramatic Development in the Death of 'Mango' Founder: Billionaire's Son Suspected of Murder
Two Years of Darkness: The Harrowing Testimonies of Israeli Hostages Emerging From Gaza Captivity
EU Moves to Use Frozen Russian Assets to Buy U.S. Weapons for Ukraine
Europe Emerges as the Biggest Casualty in U.S.-China Rare Earth Rivalry
HSBC Confronts Strategic Crossroads as NAB Seeks Only Retail Arm in Australia Exit
U.S. Chamber Sues Trump Over $100,000 H-1B Visa Fee
Shenzhen Expo Spotlights China’s Quantum Step in Semiconductor Self-Reliance
China Accelerates to the Forefront in Global Nuclear Fusion Race
Yachts, Private Jets, and a Picasso Painting: Exposed as 'One of the Largest Frauds in History'
Australia’s Wedgetail Spies Aid NATO Response as Russian MiGs Breach Estonian Airspace
McGowan Urges Chalmers to Cut Spending Over Tax Hike to Close $20 Billion Budget Gap
Victoria Orders Review of Transgender Prison Placement Amid Safety Concerns for Female Inmates
U.S. Treasury Mobilises New $20 Billion Debt Facility to Stabilise Argentina
French Business Leaders Decry Budget as Macron’s Pro-Enterprise Promise Undermined
Trump Claims Modi Pledged India Would End Russian Oil Imports Amid U.S. Tariff Pressure
Surging AI Startup Valuations Fuel Bubble Concerns Among Top Investors
Australian Punter Archie Wilson Tears Up During Nebraska Press Conference, Sparking Conversation on Male Vulnerability
Australia Confirms U.S. Access to Upgraded Submarine Shipyard Under AUKUS Deal
“Firepower” Promised for Ukraine as NATO Ministers Meet — But U.S. Tomahawks Remain Undecided
Brands Confront New Dilemma as Extremists Adopt Fashion Labels
The Sydney Sweeney and Jeans Storm: “The Outcome Surpassed Our Wildest Dreams”
Erika Kirk Delivers Moving Tribute at White House as Trump Awards Charlie Presidential Medal of Freedom
British Food Influencer ‘Big John’ Detained in Australia After Visa Dispute
ScamBodia: The Chinese Fraud Empire Shielded by Cambodia’s Ruling Elite
French PM Suspends Macron’s Pension Reform Until After 2027 in Bid to Stabilize Government
Orange, Bouygues and Free Make €17 Billion Bid for Drahi’s Altice France Telecom Assets
Dutch Government Seizes Chipmaker After U.S. Presses for Removal of Chinese CEO
Bessent Accuses China of Dragging Down Global Economy Amid New Trade Curbs
U.S. Revokes Visas of Foreign Nationals Who ‘Celebrated’ Charlie Kirk’s Assassination
AI and Cybersecurity at Forefront as GITEX Global 2025 Kicks Off in Dubai
DJI Loses Appeal to Remove Pentagon’s ‘Chinese Military Company’ Label
EU Deploys New Biometric Entry/Exit System: What Non-EU Travelers Must Know
Australian Prime Minister’s Private Number Exposed Through AI Contact Scraper
×