How the Coronavirus Short-Circuits the Immune System


At the beginning of the pandemic, the coronavirus looked to be another respiratory illness. But the virus has turned out to affect not just the lungs, but the kidneys, the heart and the circulatory system — even, somehow, our senses of smell and taste.

Now researchers have discovered yet another unpleasant surprise. In many patients hospitalized with the coronavirus, the immune system is threatened by a depletion of certain essential cells, suggesting eerie parallels with H.I.V.

The findings suggest that a popular treatment to tamp down the immune system in severely ill patients may help a few, but could harm many others. The research offers clues about why very few children get sick when they are infected, and hints that a cocktail of drugs may be needed to bring the coronavirus under control, as is the case with H.I.V.

Growing research points to “very complex immunological signatures of the virus,” said Dr. John Wherry, an immunologist at the University of Pennsylvania whose lab is taking a detailed look at the immune systems of Covid-19 patients.

In May, Dr. Wherry and his colleagues posted online a paper showing a range of immune system defects in severely ill patients, including a loss of virus-fighting T cells in parts of the body.

In a separate study, the investigators identified three patterns of immune defects, and concluded that T cells and B cells, which help orchestrate the immune response, were inactive in roughly 30 percent of the 71 Covid-19 patients they examined. None of the papers have yet been published or peer reviewed.

Researchers in China have reported a similar depletion of T cells in critically ill patients, Dr. Wherry noted. But the emerging data could be difficult to interpret, he said — “like a Rorschach test.”

Research with severely ill Covid-19 patients is fraught with difficulties, noted Dr. Carl June, an immunologist at the University of Pennsylvania who was not involved with the work.

“It is hard to separate the effects of simply being critically ill and in an I.C.U., which can cause havoc on your immune system,” he said. “What is missing is a control population infected with another severe virus, like influenza.”

One of the more detailed studies, published as a preprint and under review at Nature Medicine, was conducted by Dr. Adrian Hayday, an immunologist at King’s College London.

He and his colleagues compared 63 Covid-19 patients at St. Thomas’s Hospital in London to 55 healthy people, some of whom had recovered from coronavirus infections.

Dr. Hayday and his colleagues began with the assumption that the patients would generate a profound immune response to the coronavirus. That is why most people recover from infections with few, if any, symptoms.

But those who get very sick from the virus could have immune systems that become impaired because they overreact, as happens in sepsis patients. Alternately, the scientists hypothesized, these patients could have immune systems that struggle mightily, but fail to respond adequately to the virus.

One of the most striking aberrations in Covid-19 patients, the investigators found, was a marked increase in levels of a molecule called IP10, which sends T cells to areas of the body where they are needed.

Ordinarily, IP10 levels are only briefly elevated while T cells are dispatched. But in Covid-19 patients — as was the case in patients with SARS and MERS, also caused by coronaviruses — IP10 levels go up and stay up.

That may create chaotic signaling in the body: “It’s like Usain Bolt hearing the starting gun and starting to run,” Dr. Hayday said, referring to the Olympic sprinter. “Then someone keeps firing the starting gun over and over. What would he do? He’d stop, confused and disoriented.”

The result is that the body may be signaling T cells almost at random, confusing the immune response. Some T cells are prepared to destroy the viruses but seem undermined, behaving aberrantly. Many T cells apparently die, and so the body’s reserves are depleted — particularly in those over age 40, in whom the thymus gland, the organ that generates new T cells, has become less efficient.

  • Updated June 24, 2020

    • Is it harder to exercise while wearing a mask?

      A commentary published this month on the website of the British Journal of Sports Medicine points out that covering your face during exercise “comes with issues of potential breathing restriction and discomfort” and requires “balancing benefits versus possible adverse events.” Masks do alter exercise, says Cedric X. Bryant, the president and chief science officer of the American Council on Exercise, a nonprofit organization that funds exercise research and certifies fitness professionals. “In my personal experience,” he says, “heart rates are higher at the same relative intensity when you wear a mask.” Some people also could experience lightheadedness during familiar workouts while masked, says Len Kravitz, a professor of exercise science at the University of New Mexico.

    • I’ve heard about a treatment called dexamethasone. Does it work?

      The steroid, dexamethasone, is the first treatment shown to reduce mortality in severely ill patients, according to scientists in Britain. The drug appears to reduce inflammation caused by the immune system, protecting the tissues. In the study, dexamethasone reduced deaths of patients on ventilators by one-third, and deaths of patients on oxygen by one-fifth.

    • What is pandemic paid leave?

      The coronavirus emergency relief package gives many American workers paid leave if they need to take time off because of the virus. It gives qualified workers two weeks of paid sick leave if they are ill, quarantined or seeking diagnosis or preventive care for coronavirus, or if they are caring for sick family members. It gives 12 weeks of paid leave to people caring for children whose schools are closed or whose child care provider is unavailable because of the coronavirus. It is the first time the United States has had widespread federally mandated paid leave, and includes people who don’t typically get such benefits, like part-time and gig economy workers. But the measure excludes at least half of private-sector workers, including those at the country’s largest employers, and gives small employers significant leeway to deny leave.

    • Does asymptomatic transmission of Covid-19 happen?

      So far, the evidence seems to show it does. A widely cited paper published in April suggests that people are most infectious about two days before the onset of coronavirus symptoms and estimated that 44 percent of new infections were a result of transmission from people who were not yet showing symptoms. Recently, a top expert at the World Health Organization stated that transmission of the coronavirus by people who did not have symptoms was “very rare,” but she later walked back that statement.

    • What’s the risk of catching coronavirus from a surface?

      Touching contaminated objects and then infecting ourselves with the germs is not typically how the virus spreads. But it can happen. A number of studies of flu, rhinovirus, coronavirus and other microbes have shown that respiratory illnesses, including the new coronavirus, can spread by touching contaminated surfaces, particularly in places like day care centers, offices and hospitals. But a long chain of events has to happen for the disease to spread that way. The best way to protect yourself from coronavirus — whether it’s surface transmission or close human contact — is still social distancing, washing your hands, not touching your face and wearing masks.

    • How does blood type influence coronavirus?

      A study by European scientists is the first to document a strong statistical link between genetic variations and Covid-19, the illness caused by the coronavirus. Having Type A blood was linked to a 50 percent increase in the likelihood that a patient would need to get oxygen or to go on a ventilator, according to the new study.

    • How many people have lost their jobs due to coronavirus in the U.S.?

      The unemployment rate fell to 13.3 percent in May, the Labor Department said on June 5, an unexpected improvement in the nation’s job market as hiring rebounded faster than economists expected. Economists had forecast the unemployment rate to increase to as much as 20 percent, after it hit 14.7 percent in April, which was the highest since the government began keeping official statistics after World War II. But the unemployment rate dipped instead, with employers adding 2.5 million jobs, after more than 20 million jobs were lost in April.

    • What are the symptoms of coronavirus?

      Common symptoms include fever, a dry cough, fatigue and difficulty breathing or shortness of breath. Some of these symptoms overlap with those of the flu, making detection difficult, but runny noses and stuffy sinuses are less common. The C.D.C. has also added chills, muscle pain, sore throat, headache and a new loss of the sense of taste or smell as symptoms to look out for. Most people fall ill five to seven days after exposure, but symptoms may appear in as few as two days or as many as 14 days.

    • How can I protect myself while flying?

      If air travel is unavoidable, there are some steps you can take to protect yourself. Most important: Wash your hands often, and stop touching your face. If possible, choose a window seat. A study from Emory University found that during flu season, the safest place to sit on a plane is by a window, as people sitting in window seats had less contact with potentially sick people. Disinfect hard surfaces. When you get to your seat and your hands are clean, use disinfecting wipes to clean the hard surfaces at your seat like the head and arm rest, the seatbelt buckle, the remote, screen, seat back pocket and the tray table. If the seat is hard and nonporous or leather or pleather, you can wipe that down, too. (Using wipes on upholstered seats could lead to a wet seat and spreading of germs rather than killing them.)

    • What should I do if I feel sick?

      If you’ve been exposed to the coronavirus or think you have, and have a fever or symptoms like a cough or difficulty breathing, call a doctor. They should give you advice on whether you should be tested, how to get tested, and how to seek medical treatment without potentially infecting or exposing others.


The research also suggests that a popular idea for treatment may not help most people.

Some patients are severely affected by coronavirus infections because their immune systems respond too vigorously to the virus. The result, a so-called cytokine storm, also has been seen in cancer patients treated with drugs that supercharge T cells to attack tumors.

These overreactions can be quelled with medications that block a molecule called IL-6, another organizer of immune cells. But these drugs have not been markedly effective in most Covid-19 patients, and for good reason, Dr. Hayday said.

“There clearly are some patients where IL-6 is elevated, and so suppressing it may help,” he explained. But “the core goal should be to restore and resurrect the immune system, not suppress it.”

The new research may help answer another pressing question: Why is it so rare for a child to get sick from the coronavirus?

Children have highly active thymus glands, the source of new T cells. That may allow them to stay ahead of the virus, making new T cells faster than the virus can destroy them. In older adults, the thymus does not function as well.

The emerging picture indicates that the model for H.I.V. treatment, a cocktail of antiviral drugs, may be a good bet both for those with mild illnesses and those who are severely ill.

Some experts have wondered if antiviral treatment makes sense for severely ill Covid-19 patients, if their main affliction is an immune system overreaction.

But if the virus directly causes the immune system to malfunction, Dr. Hayday said, then an antiviral makes sense — and perhaps even more than one, since it’s important to stop the infection before it depletes T cells and harms other parts of the immune system.

“I have not lost one ounce of my optimism,” Dr. Hayday said. Even without a vaccine, he foresees Covid-19 becoming a manageable disease, controlled by drugs that act directly against the virus.

“A vaccine would be great,” he said. “But with the logistics of its global rollout being so challenging, it’s comforting to think we may not depend on one.”



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