A new immunological study shows that many more people may have had contact with the coronavirus than previously thought – which means the virus is likely much less deadly.
Alexandra Broehm, Swiss Sunday Times, June 2, 2020 (German original)
Anyone who gets infected with the corona virus eventually forms antibodies, and these antibodies can be detected with a blood test. That was our current state of knowledge. But new research is now calling these certainties into question: immunologists at the University of Zurich have discovered that people with a severe course of disease have detectable antibodies in their blood, whereas mild cases hardly ever do. But more than 80 percent of Covid-19 cases are mild. What does this new finding mean for broad-based antibody tests in the population?
For the study, which has now been published as a preprint, the team led by Onur Boyman, professor at the Department of Immunology at the University Hospital in Zurich, examined two different groups. The first group consisted of patients with mild or severe disease progression; the participants in the second group were healthcare professionals that had been exposed to corona virus. In both groups, the researchers searched for antibodies not only in the blood, as the usual antibody tests do, but also in the eyes, nose and mouth.
The immunologists were able to prove for the first time for Covid-19 that infected people also have antibodies in the mucous membranes.
Our immune system defends itself against infection with various weapons. In doing so, it forms different antibodies (immunoglobulins). What before the pandemic were common abbreviations only in expert circles could be read again and again in the discussions about antibody tests in recent weeks: IgM, IgA or IgG are the names of the immunoglobulins with which the immune system fights against invaders. They have different abilities, occur at different stages of the infection and above all at different places in the body.
Only a fraction falls seriously ill
The IgM are the first line of defence. They are the largest antibodies and can therefore block more viruses at once, but because of their size they cannot penetrate the tissue easily. They also disappear again the fastest. IgA and IgG are smaller and bind more strongly, IgA is mainly found in the mucous membranes, IgG are the most agile and can reach everywhere. In the new study, IgA appeared in mild cases about eight days after the onset of symptoms, and could be detected in the blood in a small number of cases, but only temporarily.
However, the infected persons with mild cases usually had no IgG at all in their blood – actually those antibodies that are detectable for the longest time. On the other hand, the scientists found IgA in the nasal mucous membranes of mildly affected patients and, above all, of health care workers, even when the patients did not show any symptoms. The immunologists were thus able to prove for the first time for Covid-19 that infected persons also have antibodies in the mucous membranes – as is known from other diseases. However, the usual antibody tests look in the blood. There, the scientists found clearly detectable amounts of IgG only in the severely ill, which also occurred at an early stage. “The current antibody tests do not cover all cases by a long way,” says study director Boyman. Therefore, it can be assumed that five times more people than are detected in broad-based antibody tests have already had contact with the new coronavirus. This is because less than one fifth of all infected people fall seriously ill and consequently have clearly detectable antibodies in their blood. If one takes the example of Geneva, where around five percent of the population had a positive antibody test in April, the actual figures there could be 25 percent of the population.
It is known from other viral diseases that severe disease progression also leads to stronger immune responses.
According to Boyman, the number of infections might even exceed five times the known figures. This has to do with how our immune system works. Besides antibodies, there is also the cellular immune response, the so-called T-lymphocytes. The antibodies fight the virus as soon as it is in the body and before it can enter cells. Once inside the cell, it is the T-lymphocytes, specialised defence cells, which eliminate infected body cells. They also have a memory, remember illnesses that have already occurred and activate correspondingly specialised cells. If a person has only these T-lymphocytes as remnants of an infection, no antibodies are detectable. Nevertheless, at least partial immunity could exist.
How long does the protection last?
“This is a fascinating study,” says Francois Spertini, Professor of Immunology at the University Hospital of Lausanne CHUV. “It helps us to explain why so few people have antibodies in their blood and why these levels are probably misleading.” “This is an interesting study,” says Daniel Pinschewer, who heads the Department of Experimental Virology at the University of Basel’s Department of Biomedicine. “I find it plausible that with today’s blood antibody tests we cannot detect all surviving infections.”
But what do these findings – and this is the price question – mean for a possible protection against further infection with the sars-CoV-2 in the future? Are only people who are seriously ill protected? Or do they simply have even stronger protection than mild cases? And how long does a possible protection actually last?
The new corona virus is dangerous because our immune system has never had to deal with it before.
There are no conclusive answers to these questions yet, but there are nevertheless certain indications. It is known from other viral diseases that severe disease progression also produces stronger immune responses. However, there is not yet much research on this aspect, whether a stronger current immune response means longer-term protection. “But antibodies in the mucous membranes, not only in the blood, can also offer protection in principle,” says Boyman. The younger the participants in the current study were, the more likely the researchers were to find antibodies in their mucous membranes.
However, researchers from King’s College, London, wrote this week in a commentary for the “Physiological Society”: “Viruses that affect the respiratory tract are not known to cause people to develop a long immunity after they have been through illness. Experts are also warning at the moment that the results of the study should not lead to a neglect of protective measures. The study was not particularly large, with 165 participants. And there are still too many unanswered questions as to who might be immune and how, and whether people who only had a mild disease might easily become infected again in the future. And even a mild case could in turn infect someone who is then very seriously ill.
Protection through frequent infections
Nevertheless, one factor will be important, which was often formulated as a warning at the beginning of the pandemic: the new corona virus is dangerous because our immune system has never dealt with it before and its defence against this new threat has yet to learn. Now, if more people than previously thought had at least had contact with the virus, there is hope that a second infection would not be too severe for those affected.
The new study also provides some clues to another mystery that is affecting many people during this pandemic. “Because children often suffer from upper respiratory tract infections, they may have protective IgA antibodies in their mucous membranes,” the authors write. These antibodies could be caused by a fitter immune defence in the mucous membranes and therefore offer at least partial protection. “This could explain, among other things, why children rarely develop severe diseases.”