Corona: What we know about immunity
Antibodies or innate defenses
To answer the question of how many people have had the coronavirus, they rely almost entirely on antibody testing. But this gives too limited a picture of the number of infected and immune people.
"The reality is that a large part of the Dutch population will be infected with the virus in the near future," says the TV speech by Prime Minister Rutte on March 16 [the lockdown announcement for the wholecountryand not only the Carnaval area]. At that time it is already clear that a large part of the population will develop "mild" symptoms, but for many - with the intense images from China and Italy still sharply focused - it is a terrifying scenario. Rutte's message echoes that of other authorities and leading scientists: This is a new virus. No one is immune, so it can make us all sick.
Virologist Rory de Vries of Erasmus MC in Rotterdam already suspects that this is not necessarily the case. One of his scientific interests is cross-reactivity: the phenomenon that the immune system can also switch off related pathogens more quickly after exposure to one pathogen. De Vries studied it with the measles virus and flu viruses and made a research request a few years ago to look at cross-reactivity between the MERS-COV virus, a corona virus that appeared in 2012 in the Middle East, and the four 'ordinary' , common coronaviruses that cause one in three colds. "That request was unfortunately rejected."
De Vries is not the only immunologist who played with this idea. "The statement that everyone was susceptible to the virus was more policy-based than scientific," said George Kassiotis, professor of immunology at the Francis Crick Institute in London. "Little was known about the virus and we had to prepare for the worst. Imagine if they had communicated, "Well, it's just a coronavirus, it usually doesn't cause more than a cold." That would have been a disaster.
Much is still unclear about the coronavirus SARS-CoV-2, but it has now been established that a large part of the population, especially children and young people, hardly get sick. It seems that about 45 percent of the infected persons even remain completely "asymptomatic". Immunologists see evidence that many people's immune systems render the virus harmless before it can cause symptoms. In many cases, they do not produce detectable antibodies, but, as recent studies show, they probably produce other forms of defense. That could mean that a larger group of people than previously thought is no longer susceptible to the virus. In scientific articles on the coronavirus and the immune system, the focus in recent months has been mainly on the worst case scenario: in patients with severe Covid-19, the body's immune response has the greatest difficulty in curbing the virus and often runs wild, sometimes fatal.
But the vast majority of people who get infected with the virus are very different. When the coronavirus enters the respiratory tract, it encounters the first line of the immune system: the so-called "innate" defense. White blood cells recognize the viruses as foreign, bombard them with inflammatory molecules and gobble them up, says Mihai Netea, professor of experimental internal medicine at the Raboudumc in Nijmegen. He suspects that the innate defenses in some people turn off the virus in a curse and a sigh. He knows this phenomenon from his tuberculosis research, about which he published in April together with international colleagues. "There are people who have lived in a person with open TB for weeks on end and who never got sick and did not make antibodies. We call these early clearers or resisters. They have a strong innate immune system, which is partly genetic and partly enhanced by previous infections or vaccinations with live pathogens. "
https://academic.oup.com/jid/article/221/8/1342/5431213
In tuberculosis, fifteen to forty percent of the population is resistant to the infection thanks to these innate defenses. "I would be surprised if this phenomenon doesn't exist in diseases like Covid-19," says Netea, "but to what extent we don't know yet. We are now trying to figure this out by studying the innate immune response of roommates of Covid-19 patients. " When a part of the population does not produce antibodies after exposure, they do not actually become "immune". On the other hand, says Netea, "there is a good chance that those who have been asymptomatic with a first infection will be back with a possible second infection."
Fortunately for all non-resistors, the innate immune system is not alone in the fight against the coronavirus. As soon as it comes across the virus, it enlists the help of other white blood cells, the so-called B and T cells. B cells make the specific antibodies: these are molecules that sit on the pathogen so that it can no longer properly attach to body cells to infect them. In addition, the antibodies act as a marker for other immune cells, which deactivate the pathogen. The T cells stimulate the production of antibodies (or antibodies) by the B cells and if cells become infected, they destroy them. After the immune response, the antibodies continue to circulate in the blood for a while, leaving B and T memory cells that can multiply again very quickly when reinfected with the same virus.
The website of the so-called Pienterstudie, with which RIVM tries to map the spread of the virus in the Netherlands, states: "Everyone who comes into contact with the virus makes antibodies. By measuring those antibodies in the blood, we know how many people in our population have been exposed to the virus. "
However, anyone who takes this figure as a measure of the number of people exposed to the virus is underestimated, says Hans Zaaijer, who, as professor of infectious diseases at the Sanquin blood bank, leads the antibody studies among blood donors. In early June, Sanquin reported that 5.5 percent of donors nationally have antibodies. "The patients who have been hospitalized all have antibodies," says Zaaijer. "The patients who were seriously ill at home, too. But of the patients with mild complaints, this is ninety percent. And in hospital staff without complaints that tested positive for the virus, you often only see a small amount of antibodies for a very short time. It could well be that the antibodies only remain in the lung mucous membranes and that they are therefore immune. "
Research conducted at the University of Zurich (not yet reviewed by fellow researchers) endorses this: Investigated subjects who had a mild Covid-19 infection did not build up a measurable antibody response in their blood, but in their mucous membranes.
https://www.biorxiv.org/content/biorxiv/early/2020/05/23/2020.05.21.108308.full.pdf
Antibody polls have another shortcoming, Zaaijer acknowledges, because they do not look at that other branch of the defense: T cells. Rory de Vries mapped out this T-cell response in patients who ended up on IC in Erasmus MC.
https://immunology.sciencemag.org/content/5/48/eabd2071
And patients with mild symptoms also produce virus-responsive T cells, fellow researchers at the La Jolla Institute of Immunology in San Diego showed online in Cell on May 14.
https://www.cell.com/cell/pdf/S0092-8674(20)30610-3.pdf?_returnURL=https://linkinghub.elsevier.com/retrieve/pii/S0092867420306103?showall=true
In fact, there is some evidence that the T cell response in mild and asymptomatic individuals is stronger or at least more measurable than the antibody response. On June 29, Swedish researchers published an article (not yet peer-reviewed) in which they show that the subjects they studied who had no or mild symptoms had T-cells 1.5 times more often than antibodies to the virus. French researchers published a similar article a week earlier about roommates of Covid-19 patients.
https://www.medrxiv.org/content/10.1101/2020.06.21.20132449v1
Follow-up research will have to show whether these persons are really immune.
The San Diego researchers discovered another startling finding: they found not only specific T cells in former patients,
but also in just under half of the blood samples taken from volunteers well before the outbreak. In unpublished follow-up experiments, they confirm that this pre-existing immunity is a result of contamination with common cold coronaviruses. "We don't know how much of this type of cross-reactivity occurs in the population and what the effect is on the new coronavirus," said one of the researchers, Sydney Ramirez. "But it is at least possible that these T cells help the immune response."
Rory de Vries also found in two of his ten blood samples taken before the corona outbreak on the T cells responding to the corona virus. Several other labs published similar results. Follow-up research will have to show whether the coronavirus will show the same pattern as in the 2009 Mexican flu: those who had T cells reacting to the virus before the outbreak were not completely immune, but more often contracted a milder infection than those who cells. "That is in line with what we know about T cells, namely that they only act when cells are already infected, but that they can prevent serious infections by clearing them up," says De Vries.
Antibodies usually remain in the blood for much less time after infection than T cells, so less cross-reactivity can be expected. Despite this, the George Kassiotis team in London found antibodies that reacted to the new coronavirus in a portion of non-infected individuals, and Sanquin also noted in its first report that fourteen percent of those tested positive had these antibodies a year before the outbreak. had.
https://www.researchsquare.com/article/rs-25862/v1
Kassiotis emphasizes that such antibodies are unlikely to give complete immunity, but may, like the T cells, reduce the severity of the disease.
All in all, therefore, fewer people seem to be susceptible to the virus than the antibody polls suggest. However, this does not mean that the pursuit of group immunity will become attractive again. Too little is known about the extent to which the immunity already present and built up actually stops the spread in order to protect the vulnerable. It is possible that resistant or partially immune persons can pass on the virus.
The World Health Organization was still confused about this in early June when technical head for Covid-19 Maria Van Kerkhove stated at a press conference that asymptomatic spread was "very rare," and reverted to that statement a day later because science is not yet ready.
A Chinese study published in Nature Medicine on June 18 is not very hopeful: 37 studied asymptomatic individuals excreted virus particles for two weeks - although the authors emphasize that they do not know whether those virus particles are really contagious.
https://www.nature.com/articles/s41591-020-0965-6
Furthermore, the virus rarely causes serious complications even in children and it is far from certain that a mild-symptomatic or even an asymptomatic infection cannot cause permanent damage.
A presumably significant group of mildly symptomatic patients has long-term complaints of the lungs, heart and sometimes other organs. In addition, the virus has, according to the many new outbreaks in various parts of the world, hardly ever been in many places - in the Netherlands in particular the northeast. In all these places, outbreaks can occur if insufficient measures are taken and, despite the better starting position, if the attitude is too lax, the same scenes as in Northern Italy, New York and Brabant still threaten.
Protecting vulnerable groups has hitherto only been effective where the spread among other groups has been severely limited and it remains to be seen how this can be achieved without long-term exclusion. To what extent immunity and resistance in a part of the population has contributed to damming the virus and to what extent they will be able to do so in the coming months is one of the main questions that scientists have now turned to.
https://www.groene.nl/artikel/antilichamen-of-aangeboren-afweer
