A big mystery: why do some people get seriously ill and even die from their disease, while other people like it show no symptoms and may not realize they have been infected?
But the reverse may also be true: might some people actually have some kind of protection?
“What we found was that people who had never been exposed to SARS Cov2 … about half the people had a certain T cell reactivity,” co-author of the article Alessandro Sette of the Center for Infectious Disease and Vaccine Research at The Jolla Institute for Immunology, he told CNN.
To understand why it is important, here is a small intensive immunology course. The human immune system, which has the job of keeping you healthy in the face of bacterial, viral, fungal, parasitic and other invaders, has two main components: the innate immune system and the adaptive immune system.
The innate immune system is the first line of defense. Some parts include physical barriers such as skin and mucous membranes, which physically prevent invaders from entering. It also includes some cells, proteins and chemicals that do things like create inflammation and destroy invading cells.
Where the innate immune system is immediate and non-specific (tries to stop anything from entering the body), the adaptive immune system is targeted against a specific and previously recognized invader. This takes a little longer to engage the gear.
The adaptive immune system includes a type of white blood cell, called a B cell, which patrols the body in search of villains. Each of the B cells has a unique antibody that is found on its surface and can bind to a unique antigen (the technical name for the foreign invader) and prevent it from entering a host cell. When it finds and binds to a bad boy, cell B activates: it copies and produces antibodies, eventually creating a mega army of neutralizers for that particular invader.
That’s where the antibodies created by the immune system of people who have had Covid-19 come from. Unfortunately, some recent studies have found that antibodies to this particular coronavirus can fade quickly enough especially in people who have had mild cases of Covid-19. This has worried many researchers: as the antibody response seems to quickly fade, the scientific community is not sure how long a person who has been infected with this virus will remain protected from a new infection. This is also worrying as we rely on vaccines to trigger an antibody response to help protect us and we want that protection to last long.
Fortunately, antibodies are not the only weapon used by our adaptive immune system to avoid an infection. Enter the T cell. T cells, which come in three varieties, are created by the body after an infection to help future infections from the same invader. One of those T cells helps the body remember that invader in case it knocks again, another hunts and destroys the infected host cells and a third helps in other ways.
It is T cells like those that reacted to the SARS-CoV-2 virus, which Sette and her co-author Shane Crotty discovered – almost by accident – in the blood of people collected several years before the start of this pandemic.
They were conducting an experiment with Covid-19 convalescent blood. Since they needed a “negative control” to deal with convalescent blood, they took blood samples from healthy people collected in San Diego between 2015 and 2018.
“It was not possible that these people had been exposed to SARS-CoV2. And when we ran those … it turns out that the negative control was not so negative: about half the people had reactivity,” explained Seven.
“Shane and I studied the data carefully; we were looking at them from the right, from the left, from the top, from the bottom – and it was really” real “; this responsiveness was real. So, this showed that people who never saw this virus have some T cell reactivity against the virus. ”
Seven and Crotty note in their current summary article that they are not the only ones who have seen it.
“This has now been confirmed in different continents, different laboratories, with different techniques, which is one of the hallmarks of when you really start to believe that something is scientifically well established because it is found independently by different studies and different laboratories,” said Seven .
They speculate that this recognition of T cells of parts of the SARS-CoV-2 virus may stem in part from past exposure to one of the four known circulating coronaviruses that cause the common cold in millions of people every year.
“The hypothesis is that it actually comes from the common cold coronaviruses that people have already seen before, and Alex’s part was working very hard to figure it out, because it’s still scientifically a big debate,” said Crotty.
Friend or foe?
But many questions remain, including whether this recognition of parts of SARS-CoV-2 by T cells helps or hurts.
“These memory T cells would be helpful in protecting you from Covid-19 disease, that’s the huge question,” said Crotty. “We don’t know if [the T cells] they are useful or not, but we think it reasonable to assume that they can be useful. It’s not that we think they would completely protect against any infection, but if you already have some cells around, they can fight the virus faster and it is therefore plausible that instead of ending up in intensive care, you don’t. And instead of ending up in the hospital, you only have a bad cold. ”
Other researchers are also intrigued by the possibilities offered by this discovery.
Dr. Arturo Casadevall told CNN that his first thought was “not surprising, important, good to know”. Casadevall chairs the molecular microbiology and immunology department of the Johns Hopkins School of Public Health.
“Since these coronaviruses are all related, as we stumble upon one of them every year, it’s no surprise that we have reactive T cells with them,” he said. But, like Seven and Crotty, he wonders if this reactivity is a positive or negative thing.
“One of the things we know about this disease is that what kills you is an exuberant immune response in the lung … So when you say” They have a T cell reactivity “, this could help in some people, it could hurt others.” he said.
Casadevall speculates that some asymptomatic people may be able to quickly eliminate the virus thanks to this T cell reactivity. “At the same time, some of the very sick people have that immunological history that instead of helping them, causes the immune system to put us all against, and the net result is that you get this exuberant response, “he said, referring to the cytokine storm that some of the sickest of the sick with the Covid-19 experience.
Seven and Crotty are looking into this possibility. But they say that the overreaction of the innate immune system, not an overreaction to T cells, seems to trigger the cytokine storm. “The data is still somewhat preliminary, but I think it is in that direction. Of course, we haven’t seen an immune response related to T cells in overdrive in very severe cases,” said Seven.
Big implications for vaccines
So assuming that a large portion of the population has some sort of T cell reactivity to the SARS-CoV-2 virus, what does this mean for vaccination efforts?
There are several implications.
For Dr. Bruce Walker, an infectious disease physician-scientist who spends most of his time researching human immunology, opens the door to a different type of vaccine, similar to those that are used against certain cancers, like melanoma.
“What we do know is that most of the vaccines that have been generated so far have been based on the generation of antibodies. Now, the antibodies should theoretically be able to prevent infection of any cell – if you have enough antibodies in circulation. and the incoming virus has the potential to infect a cell, it can be theoretically neutralized by the right type of antibody, “explained Walker, who is the founding director of the Ragon Institute of Massachusetts General Hospital, MIT and Harvard.
“On the other hand, if some viruses creep in and infect a cell; then the body relies on T cells to eliminate the virus,” he said. “And here’s the opportunity for us to rethink what we’re doing in terms of vaccination – because those T cells, at least theoretically, could be very powerful and mitigate the disease. In other words, they wouldn’t protect against infection, but they could make the infections so asymptomatic that you wouldn’t notice it yourself and, in fact, you would never have enough viruses in your body to pass it on to someone else. This is the hypothesis. “
Another implication is that the results of a small Phase 1 vaccine study could be misinterpreted in one way or another if the participants’ T cell reactivity status is not taken into account. “For example, if subjects with pre-existing reactivity were classified unevenly in different groups of vaccine doses, this could lead to erroneous conclusions,” wrote Seven and Crotty in their article.
In addition, Seven said that upcoming vaccine studies could help uncover the effect of this cross-reactivity of T cells much cheaper and easier than other experiments. “It is conceivable that if you have 10 people who have reactivity and 10 people who do not have pre-existing reactivity and vaccines with a SARS CoV-2 vaccine, those who have pre-existing immunity will respond faster or better for a vaccine. The beauty is that it is a relatively fast study with fewer numbers [of people] … So, we suggested to anyone who is doing vaccine studies to measure T cell response as well, “said Seven.
The herd (immunity) gets stronger
There are also implications for when we might get “herd immunity” – which means that part of the population is immune to SARS-CoV-2, thanks to infection or vaccination, and the virus can no longer be easily transmitted. .
“For herd immunity, if in fact we have a very large percentage of the population that is already immune in one way or another, through these cellular responses, they can count on the pool you need to establish the immunity of the herd. If you already have 50% in some sense immune, because of these existing immune responses, then you don’t need 60-80%, you need 10-30% – you’ve already covered 50%. having pre-existing immunity suggests that perhaps you need a small portion of the population to be affected before the epidemic wave dies out, “said Dr. John Ioannidis, professor of medicine, epidemiology and population health at Stanford University.
In other words, if there is a level of immunity in the herd, this changes the rate at which the virus spreads across different communities and populations.
In fact, Seven and Crotty wrote in their article, “It should be noted that if some degree of pre-existing immunity against SARS-CoV-2 exists in the general population, this could also affect epidemiological modeling …”
For example, Crotty said that when the authors added a hypothetical 30% immunity to their epidemiological model of how many cases there would be in the world in the next two years, the virus disappeared in the near future before returning in three or four. years .
More questions than answers for now
And this brings us to another question raised by the Seven and Crotty article: since common circulating coronaviruses (CCCs) appear in different places, at different times, some countries, cities or locations may be disproportionately affected (or spared ) why did the population have less exposure to these CCCs, thus creating fewer opportunities to develop cross-reactivity?
“If pre-existing T-cell immunity is related to exposure to CCCs, it will become important to better understand the patterns of exposure to CCCs in space and time. It is known that the four major CCCs are cyclical in their prevalence, after a multi-year period. cycles, which may differ between different geographic areas. This leads to the speculative hypothesis that the differences in CCC geo-distribution may be related to the severity load of COVID-19 disease, “wrote Seven and Crotty.
So, ultimately, can it be said that some people have at least partial natural protection from SARS-CoV-2, the new coronavirus, if they have cross-reactivity of T cells?
“The biggest problem is that everyone wants a simple answer,” said Johns Hopkins’ Casadevall. “What nobody wants to hear is that it’s unpredictable, because many variables play together in ways you can’t put together: your story, your diet, the way you got infected, how much [virus] you have – even the time of day you got infected. And all these variables combine in unpredictable ways. “