Emerging Data Support Lasting COVID-19 Immunity Via T Cells

Antibodies are just one part of the immune response, and according to a new article published in The BMJ evidence is growing that many of us already have cross-reactive cellular immunity to the “novel” coronavirus.

According to the BMJ feature, at least 6 past studies have reported T cell reactivity against SARS-CoV-2 in 20% to 50% of people with no known exposure to the virus.

“Memory T cells are known for their ability to affect the clinical severity and susceptibility to future infection,” authors write. “T cell studies documenting pre-existing reactivity to SARS-CoV-2 in 20-50% of people suggest that antibodies are not the full story.”

If coronavirus re-infection were likely to drive a massive wave of re-infection, it’s already doubtful relevant cases would be such sparse outliers tracked down 9 months into the coronavirus pandemic. However, as recent headlines suggest, the human antibody response to SARS-CoV-2 can wane. And to some, this is cause for alarm.

Luckily, antibody response is only one aspect of the total immune reaction of the body. SARS-CoV-1 reactive T cells, for example, were found in SARS patients 17 years after infection

Investigators behind the feature in BMJ pointed to several important pieces of evidence that there is an important cellular response to COVID-19.

• In a study of donor blood specimens from the US collected 2015-2018, 50% of samples showed various forms of T cell reactivity to SARS-CoV-2.

• A similar Dutch study reported T cell reactivity in 2 of 10 people who had not been exposed to the virus.

• In Singapore, investigators used samples taken from individuals with no contact or personal history of SARS-1 or SARS-CoV-2.

• In the Singapore population, 12 of the 26 specimens taken before July 2019 showed reactivity to SARS-CoV-2, as did 7 of 11 from people who were seronegative against the virus.

• In a German study, reactive T cells were found in 23 of 68 SARS-CoV-2 seronegative donors.

• “Reactivity was also discovered in the UK and Sweden,” authors write.

These are small studies are, and as the authors point out they do not yet allow for exact estimates of prior immunity to SARS-CoV-2. However, the information is hard to ignore, with several of the articles cited being published in Cell and Nature.

Alessandro Sette, an immunologist from La Jolla Institute for Immunology in California and an author of several of the studies told BMJ, “At this point there are a number of studies that are seeing this reactivity in different continents, different labs. As a scientist you know that is a hallmark of something that has a very strong footing.”

Seroprevalence surveys measuring antibodies have been the go-to means for gauging how many people in a given population have been infected by SARS-CoV-2. Estimates of where we are with respect to herd immunity thresholds typically come from these surveys.

“Whether we overcome it through naturally derived immunity or vaccination, the sense is that it won’t be over until we reach a level of herd immunity,” authors explain.

And since a minority of people display antibodies against SARS-CoV-2, health officials tend to assume the pandemic is just starting. In New York City, only just over a fifth of people surveyed had antibodies. Yet the level of social mobility in New York City has likely only increased since the peak of the pandemic.

“Maybe we were a little naive to take measurements such as serology testing to look at how many people were infected with the virus,” Karolinska Institute immunologist Marcus Buggert told BMJ. “Maybe there is more immunity out there.”

The authors use the growing body research to highlight immunology is not necessarily intuitive:

“Physiological responses may have fewer sharp distinctions than in the popular imagination: exposure does not necessarily lead to infection, infection does not necessarily lead to disease, and disease does not necessarily produce detectable antibodies. And within the body, the roles of various immune system components are complex and interconnected. B cells produce antibodies, but B cells are regulated by T cells, and while T cells and antibodies both respond to viruses in the body, T cells do so on infected cells, whereas antibodies help prevent cells from being infected.”

Antibody immunity is, approximately speaking, what we might loosely refer to as seasonal immunity in this case. Cellular immunity is likely to last much longer, based on coronaviruses related to SARS-CoV-2.

“The conventional wisdom is that lockdown occurred as the epidemic curve was rising,” Oxford University epidemiologist Sunetra Gupta has told BMJ. “So once you remove lockdown that curve should continue to rise.”

For some reason, however, many locales have not seen cases rise proportionately to the increase in mobility since lockdown compliance reduced in the summer. It’s time to take finding out why seriously.

Interview: T Cell Recognition of Cold Coronaviruses May Help in Protecting Against COVID-19 | AUG 20, 2020 | JOHN PARKINSON

A new study led by scientists at the La Jolla Institute for Immunology (LJI) shows that memory helper T cells that recognize common cold coronaviruses also recognize matching sites on SARS-CoV-2.

The research, published in Science, may explain why some people have milder COVID-19 cases than others—though the researchers emphasized that this is speculation and much more data is needed.

One of the coauthors of the new study, LJI Professor Alessandro Sette, Dr Biol, Sci, talked with Contagion® about it.

This latest paper builds upon a previous paper written by Sette, et al., on similar research that came out earlier this year.

At LJI, they had previous blood samples from years before SARS-CoV-2 existed. When Sette and his team took some of these samples and exposed them to the virus the samples had some immunity or protection against it because some of the memory T cells recognized SARS-CoV-2 as a virus.

“We detected responses against SARS-CoV-2 pieces in people who had not been exposed to SARS-CoV-2,” Sette explained.

While this was an important hypothesis, Sette and his team went to work to prove it.

“We mapped the specific amino acids recognized by T cells of non-exposed individuals. Then, we made synthesized corresponding pieces from the common cold coronaviruses and we proved that these T cells cross-recognized the common cold coronavirus and SARS-CoV-2.”

In addition, they were able to show these were memory T cells that induced an immunity response.

Sette also discusses how this preexisting reactivity might work to help fight the virus. “If you have this preexisting memory you may be able to mount a faster or stronger immune response, and this might explain in part why some people get more sick than others.”

While this might lay down a foundation for future work in the area, Sette acknowledges it still needs to be proven. In his discussion with Contagion®, he also lays out theories on how this could be done.