Why some people who haven't had COVID-19 might already have some immunity

Thursday, July 30, 2020
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Seventy-one percent of COVID outpatients reported fatigue, 61 percent reported a cough, and another 61 percent reported headaches.

The immune systems of some people who have not been exposed to the novel coronavirus could have some familiarity with the pathogen -- possibly helping to reduce the severity of illness if that person does get COVID-19, a new study suggests.

The study, published in the journal Nature on Wednesday, found that among a sample of 68 healthy adults in Germany who had not been exposed to the coronavirus, 35% had T cells in their blood that were reactive to the virus.

T cells are part of the immune system and help protect the body from infection. T cell reactivity suggests that the immune system might have had some previous experience fighting a similar infection and may use that memory to help fight a new infection.

So how could their immune system have reactive T cells if they never had Covid-19? They were "probably acquired in previous infections with endemic" coronaviruses, the researchers -- from various institutions in Germany and the United Kingdom -- wrote in the new study. Using this T cell memory from another-yet-similar infection to respond to a new infection is called "cross-reactivity."

'The big question is ... understanding what the role of those T cells might be'

The new study involved analyzing blood samples from 18 COVID-19 patients, ages 21 to 81, and healthy donors, ages 20 to 64, based in Germany. The study found that T cells reactive to the coronavirus were detected in 83% of the COVID-19 patients.

While the researchers also found pre-existing cross-reactive T cells in the healthy donors, they wrote in the study that the impact those cells might have on the outcome of a COVID-19 illness still remains unknown.

The study findings certainly call for more research, said Dr. Amesh Adalja, senior scholar at the Johns Hopkins University Center for Health Security, who was not involved in the new study.

"It does appear in this study that there is a significant proportion of individuals that have this cross-reactive T cell immunity from other coronavirus infections that may have some impact on how they fare with the novel coronavirus. I think the big question is trying to jump from the fact that they have these T cells to understanding what the role of those T cells might be," Adalja said.

"We know, for example, children and younger adults are relatively spared from the severe consequences of this disease, and I think that one hypothesis might be that the pre-existing T cells that exist may be much more numerous or more active in younger age cohorts than in older age cohorts," Adalja said.

"And if you could compare people maybe with severe and mild illness and try and look at the T cells in those individuals and say, 'Are people who have severe disease less likely to have cross reactive T cells versus people who have mild disease maybe having more cross reactive T cells?' I think that there's biological plausibility to that hypothesis," he said. "It's clear though that the T cell presence doesn't prevent people from getting infected, but does it modulate the severity of infection? That's what it appears could be the case."

So far during the coronavirus pandemic, much focus has been on COVID-19 antibodies and the role they play in building immunity against the disease.

But infectious disease expert Dr. William Schaffner, a professor of preventive medicine and infectious diseases at Vanderbilt University School of Medicine in Nashville who was not involved in the new study, said that T cells can not be overlooked.

"Here's a study that suggests actually there may be some cross-reactivity -- some priming of the pump if you will -- with the normal conventional coronaviruses that cause colds in humans and there may be some cross-reactivity with the COVID virus that's causing so much damage. That's in and of itself intriguing because we had thought from the antibody perspective that there wasn't much cross at all," Schaffner said.

"It's not entirely surprising because these are all members of a family. It's as though they're cousins in the same family," he said. "Now we have to see whether there is any impact of this in clinical practice. ... Does it make it more or less likely that the person who is infected with COVID actually will develop an illness? And does it have any implications for vaccine development?"

'Almost every person in the world has had some encounter with a coronavirus'

Adalja added that he was not surprised to see this T cell cross-reactivity in the study participants who had not been exposed to the novel coronavirus, named SARS-CoV-2.

"SARS-CoV-2 is the seventh human coronavirus that has been discovered, and four of the human coronaviruses are what we call community-acquired coronaviruses, and together those four are responsible for 25% of our common colds," Adalja said. "Almost every person in the world has had some encounter with a coronavirus, and since they are all part of the same family, there is some cross reactive immunity that develops."

The new Nature study isn't the only paper to suggest a certain level of pre-existing immunity among some people to the novel coronavirus.

Alessandro Sette and Shane Crotty, both of the University of California, San Diego, wrote in a comment paper published in the journal Nature earlier this month, that "20--50% of unexposed donors display significant reactivity to SARS-CoV-2 antigen peptide pools," based on separate research -- but they noted that the source and clinical relevance of the reactivity remains unknown.

Sette and Crotty wrote that "it is now established that SARS-CoV-2 pre-existing immune reactivity exists to some degree in the general population. It is hypothesized, but not yet proven, that this might be due to immunity to" common cold coronaviruses.