Researchers Find Different Immune Responses Between Mild and Severe COVID Cases

Scientists in the U.K. have identified differences in the immune responses between people with asymptomatic cases of COVID-19 and those who had a serious reaction to the virus.

The April study, which was published in the journal Nature Medicine, found higher levels of certain immune cells in people with COVID-19 who did not have symptoms. Researchers also found that people who had more serious forms of COVID-19 did not have elevated levels of these protective immune cells, and also gained inflammatory cells.

In people with asymptomatic cases, the researchers found increased levels of B cells, which produce antibodies that are found in mucus passages like the nose. These cells are thought to be protective against COVID-19. But those same cells were missing in people with severe cases, suggesting that this function of the immune response failed.

This, the researchers say, could help explain why people with severe forms of COVID-19 are at risk of developing lung inflammation and blood clots.

Why It’s Important to Understand Immune Responses

There are a few reasons why it’s crucial to examine the immune responses in COVID-19 patients, senior study author Muzlifah Haniffa, PhD, a professor at Newcastle University and senior clinical fellow at the Wellcome Sanger Institute, tells Verywell. “One is to know how the body fights off an infection successfully,” she says. “The other is to know how the immune response can be damaging to an individual.”

That, Haniffa says, is important in finding new ways to successfully treat COVID-19, especially in patients with severe forms of the disease.

“From the beginning of the pandemic, we’ve seen some people get very sick and die from COVID-19 while others have mild or even no symptoms,” Thomas Giordano, MD, MPH, professor of medicine and section chief of infectious diseases at Baylor College of Medicine, tells Verywell. “These differences are not completely explained by age and health conditions that put some people at higher risk of more severe disease.”

When people get severely ill from COVID-19 “it is not from an overwhelming viral infection, it is more likely a big infection coupled with a particular immune response to that infection,” Giordano says. “If we can better understand what the best immune response is—not too weak, not too strong, but just right—maybe we can assist the immune system in having that best response and avoiding harmful responses.”

What Does This Mean for Treatment?

While the findings won’t exactly predict who will have a severe reaction to COVID-19, it may help doctors determine who won’t react as well to existing treatments for COVID-19. “Those patients who have a higher proportion of a particular type of ‘B cell,’ the cells which produce antibodies to neutralize the virus, may respond less well [to certain medications],” lead study author Emily Stephenson, a PhD student at Newcastle University, tells Verywell.

David Cennimo, MD, assistant professor of medicine-pediatrics infectious disease at Rutgers New Jersey Medical School, tells Verywell that “understanding the immune response would help predict who may have a severe infection and how to best modify their responses for optimal outcome.”

He gives the example of the immunosuppressant tocilizumab. “It appears to have some benefits in those patients with very high inflammation markers,” he says. “It is like we are treating different illnesses. One is the direct viral invasion of cells; the other is the host response to the infection which may become more damaging than the infection itself.”

While doctors can’t predict right now how strongly the virus will impact any given person, Cennimo says he “could imagine a future where we can fine-tune our medications to the individual’s levels of immune activation.” 

The researchers didn’t analyze vaccinated people as part of their study, but Haniffa says their data may be useful for vaccine development in the future.

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