Dear Reader:

CNN, Do  some people have protection against the coronavirus? (Aug 3): “We know some of the big factors that put people at higher risk of having a severe, even fatal, course of the disease: being over 60, being overweight or obese, having one or more chronic diseases such as diabetes, cardiovascular disease, kidney or lung disease, and cancer.. But might the opposite also be true: could certain people actually have some type of protection?..

“A large percentage of the population appears to have immune cells that are able to recognize part of the SARS-COv-2 virus, and that may possibly be giving them a head start in fighting off an infection. In other words, some people may have some unknown degree of protection. ‘What we found is that people that had never been exposed to SARS-Cov-2.. about half of the people had some T-cell reactivity,’ co-author of the paper Alessandro Sette from the Center for Infectious Disease and Vaccine Research at La Jolla Institute for Immunology, told CNN…

“here’s a little crash course in immunology. The human immune system, which is tasked with keeping you healthy in the face of bacterial, viral, fungal, parasitical and other invaders, has two main components: the innate immune system and the adaptive immune system. The innate immune system is the very first line of defense. Parts of it include physical barriers like your skin and mucosal membranes, which physically stop invaders from getting it. It also includes certain cells, proteins and chemicals that do things like create inflammation and destroy invading cells.

“Where the innate immune system is immediate and nonspecific (it tries to stop anything from entering the body), the adaptive immune system is targeted against a specific and previously recognized invader. This takes a bit longer to kick into gear. The adaptive immune system includes a type of white blood cell, called a B cell, which patrols the body looking for bad guys. B cells each  have a unique antibody that sits on its surface and can bind to a unique antigen (the technical name for the foreign invader) and stop it from entering a host cell. When it finds and binds to a bad guy, the B cell gets activated: it copies itself and churns out antibodies, eventually creating a mega-army of neutralizers for that particular invader.

“That’s where antibodies created by the immune systems of people who’ve had Covid-19 come from. Unfortunately, a few recent studies have found that antibodies to this particular coronavirus can fade away pretty quickly especially in people who have had mild cases of Covid-19. This has worried many researchers:because the antibody response appears to fade quickly, the scientific community is not sure how long a person who has been infected with the virus will stay protected from new infection… ‘This is also worrisome since we are relying on vaccines to trigger an antibody response to help protect us, and we want a protection to last a long time.

“Fortunately, antibodies aren’t the only weapon our adaptive immune system uses to stave off an infection. Enter the T cell. T cells, which come in three varieties, are created by the body after an infection to help with future infections from the same invader. One of those T cells helps the body remember that invader in case it comes knocking again, another hunts down and destroys infected host cells and a third helps out in other ways.

“It’s T cells like those, which reacted to the SARS-COv-2 virus, that Sette and his co-author Shane Crotty discovered- quite by accident- in the blood of people collected several years before this pandemic began… people who have never seen this virus have some T-cell reactivity against the virus.. That has been now confirmed in different continents, different labs, with different techniques.. They speculate that this T cell recognition of parts of the SARS-Cov-2 virus may come 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 assumption is that’s actually coming from common cold coronaviruses that people have seen before.’ said Crotty…

“‘We don’t know if (the T cells) are helpful or not, but we think it’s reasonable to speculate that they may be helpful. It’s not that we think they would completely  protect against any infection at all, but if you already have some cells around, they can fight the virus faster and so it’s plausible that instead of ending up in the ICU, you don’t. And instead of ending up in the hospital, you just end up with a bad cold.’..

“‘Because these coronaviruses are all related, given that every year we run into one of them, it’s not surprising that we have T cells that are reactive with them..’ .. ‘One of the things we know about this disease is that what kills you is an over exuberant immune system, in the lungs.. So, when you say, ‘They have T-cell reactivity,’ well that could help in some people, it could hurt in others…

“Casadevall speculates that some of the asymptomatic people may be able to rapidly clear 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, makes the immune system throw everything at it, and the net result is that you get this over-exuberant response,’ he said, referring to the cytokine storm that some of the sickest of the sic with Covid-19 experience.

“Sette and Crotty .. say the overreaction of the innate immune system, not overreacting T cells, appears to set off the cytokine storm. ‘The data are still somewhat preliminary, but I think it’s in that direction. Certainly, we have not seen an immune response related to T cells in overdrive in the very severe cases.’ said Sette.

“So, assuming that a large portion of the population has some kind of T-cell reactivity to the SARS-Cov-2, what does that mean for vaccine efforts? There are several implications… it opens the door to a different type of vaccine, similar to the ones that are being used against certain cancers, like melanoma.

“What we know is that most vaccines that have been generated thus far have been based on generating antibodies. Now, antibodies should theoretically be able to prevent any cells from becoming infected- if you have enough antibodies around and any virus coming in, before it gets a chance to infect a cell, can be theoretically neutralized by the right kind 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 sneak through and infect a cell; then the body is dependent upon T cells to eliminate the virus,’ he said. And therein lies the opportunity for us to rethink what we’re doing in terms of vaccination- because those T cells, at least theoretically, could be highly potent and could attenuate the disease. In other words, they wouldn’t protect against infection, but they might make infections so asymptomatic that you would not notice it yourself and, in fact, you would never have enough virus in your body to transmit it to somebody else. That’s the hypothesis.’..

“Furthermore, Sette said.. ‘It is conceivable that if you have 10 people that have reactivity and 10 people that don’t have the pre-existing reactivity and you vaccinate them with a SARS-Cov-2 vaccine, the ones that have the pre-existing immunity will respond faster or better to a vaccine… So, we have been suggesting to anybody that is running vaccine trials to also measure T-cell response,’ said Sette.

“There are also implications for when we might achieve ‘herd immunity’- meaning that enough of the population is immune to SARS-Cov-2, thanks either to infection or vaccination, and the virus can no longer be easily transmitted… if some degree of pre-existing immunity against SARS-Cov-2 exists in the general population, this could also influence epidemiological modelling…

“‘The biggest problem is that everybody wants a simple answer,’ said John Hopkins’ Casadevall. ‘What nobody wants to hear is that it’s unpredictable, because many variables play together in ways that you can’t put together: your history, your nutrition, how you got infected, how much (virus) you got- even the time of the day you got infected. And all these variables combine in ways that are unpredictable.”

anita