To Fight Coronavirus, You Have to Understand How Weird It Is

The novel coronavirus is unusual. That much was obvious early in the pandemic, as the pathogen seemed to spread much faster than other coronaviruses, and kill at a higher rate than influenza viruses. 

Since then, a team of researchers—most of them at the Icahn School of Medicine at Mount Sinai in New York—has begun to explain just how weird SARS-CoV-2 is. Their study, which first appeared in the scientific journal Cell last month, could help to nudge other researchers toward more effective therapies as the novel coronavirus pandemic continues to worsen in many parts of the United States.

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The 15 researchers studied cell cultures and conducted experiments on both ferrets and dead and living human beings, focusing their attention on how cells exposed to the novel coronavirus respond to infection over time. “Taken together, the data presented here suggest that the response to SARS-CoV-2 is imbalanced with regard to controlling virus replication versus activation of the adaptive immune response,” they wrote.

In other words, it seems like we do a terrible job of suppressing the virus during the early stages of an infection. Then, once the pathogen has taken hold in our cells, our immune systems try too hard to fight back. The resulting, well-documented “cytokine storm” immune response can destroy healthy tissue and cause organ failure.

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Most other viruses don’t affect us this way. Even pathogens that are broadly similar to SARS-CoV-2, including MERS and SARS, don’t elicit such a powerfully self-destructive immune response. 

If nothing else, a growing body of scholarship is helping unpack why COVID-19 provokes such a distinct reaction. Increasingly, it seems the disease behaves like a covert enemy that slips behind normally stout defenses—a Trojan Horse that deceives the body into submission.

The human body has two basic lines of defense against infection. First, the innate immune system detects invaders such as viruses or bacteria and sends up little chemical signal flares, called interferons, that can warn cells to prepare for an attack while also mobilizing white blood cells to rally for a defensive effort. That scab and pus-buildup you get after a scrape? That’s your innate immune system in action.

The second line of defense, the adaptive immune system, is more sophisticated. It crafts special antibodies specifically for counterattacks on the invading pathogen. Immunity is basically your body’s memory of that last time it attacked a particular disease. A vaccine is essentially a crash-course in immunity.

Pathogen-killing T-cells are part of the adaptive immune response. Cytokines are the T-cells’ own signal flares. Some diseases provoke such intense T-cell activity that the cells don’t stop at killing pathogens. They ignore their own chemical warnings and destroy healthy cells, as well. 

What’s odd about the novel coronavirus is that it manages to skip right past the innate immune system before catastrophically provoking the runaway adaptive immune system, the Cell authors explained. “The overall transcriptional induction to SARS-CoV-2 is aberrant,” they wrote. “Despite virus replication, the host response to SARS-CoV-2 fails to launch a robust [interferon] response while simultaneously inducing high levels of chemokines needed to recruit effector cells.”

Scientists don’t know yet why the novel-coronavirus behaves in this way. But Niema Moshiri, a geneticist at the University of California, San Diego, told The Daily Beast that SARS-CoV-2’s unique effect on the human immune system could be a “side effect” of the virus’s original evolution in animal hosts such as bats or pangolins. 

Meanwhile, the Cell authors urged their fellow scientists and doctors to rethink their approach to fighting the novel coronavirus. Worry less about the innate immune response to SARS-CoV-2. Worry more about the adaptive response, perhaps with “immunomodulating” drugs that can calm the cytokine storm. “Future efforts should focus on U.S. Food and Drug Administration-approved drugs that can be rapidly deployed and have immunomodulating properties,” they wrote, 

Several scientists told The Daily Beast that the Cell authors were likely correct in recommending renewed focus on the cytokine storm as the country settles in for a potentially brutal summer. “I think the paper reflects a plausible hypothesis, that much of the lung damage and illness we’re seeing in COVID is from an over-exuberant immune response, even after the virus is starting to get under control,” said Keith Jerome, director of the University of Washington Virology Lab.

Others warned there could be a weak link in the chain of findings that comprises the Cell study. The ferret experiments, in particular, trouble some scientists. “Animal models can be misleading,” David Morrison, a biologist at Uppsala University in Sweden, told The Daily Beast.

The Cell authors did not respond to a request for comment before press time. But inasmuch as they underscored just how strange and dangerous the novel coronavirus is, their work is undeniably valuable. “The exaggerated response of some people [to infection] needs explaining,” Morrison told The Daily Beast.

Their explanation of the virus’s working—how it skips over the body’s innate immune system before provoking a dangerous adaptive immune reaction —is “reasonable,” Morrison added.

Still, scientists need time to crack the novel coronavirus’ code and understand exactly why it kills the way it does. The longer that takes, the more lives will be lost.