How does our immune system react to the coronavirus?

The coronavirus is — like any other virus — not much more than a shell around genetic material and a few proteins. To replicate, it needs a host in the form of a living cell. Once infected, this cell does what the virus commands it to do: copy information, assemble it, release it.

But this does not go unnoticed. Within a few minutes, the body's immune defense system intervenes with its innate response: Granulocytes, scavenger cells and killer cells from the blood and lymphatic system stream in to fight the virus. They are supported by numerous plasma proteins that either act as messengers or help to destroy the virus.

For many viruses and bacteria, this initial activity of the immune system is already sufficient to fight an intruder. It often happens very quickly and efficiently. We often notice only small signs that the system is working: We have a cold, a fever. 

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Interferons are a subgroup of signaling proteins that are normally secreted by infected cells. SARS-CoV-1, which was responsible for the SARS epidemic in 2003, appears to have suppressed the production of one of these interferons and thus at least delayed the attraction of immune cells. To what extent this is also the case with SARS-CoV-2, the name given to the coronavirus behind the current pandemic, is still unclear. However, interferons support the body's own virus defense and are now being tested as a therapy in clinical trials.

At a certain point, however, the host response is so strong that its effect can be counterproductive. For example, numerous immune cells can enter our lungs and cause the membrane through which oxygen normally passes from the air into the blood to thicken. The exchange of gases is restricted, and in the worst case, ventilation may be necessary.

Sometimes the reaction can overshoot and be directed against healthy cells as well. This could also be the case with the novel coronavirus. So drugs are also being tested that suppress an excessive immune reaction and that are already known from the treatment of autoimmune diseases. The balance between protective and overly aggressive immune processes in dealing with the coronavirus is currently a big mystery. This must now be investigated, says Achim Hörauf, Director of the Institute of Medical Microbiology, Immunology and Parasitology at the University of Bonn. 

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After a time delay, the acquired immune system finally sets itself in motion. It is different for every person and depends on what we have experienced and with which pathogens we have come into contact. While T cells help destroy infected cells, B cells form antibodies that can keep the virus in check. In the case of the coronavirus, these are neutralizing antibodies that bind to the spike protein of the virus. This is the site of attack of the virus, with which it enters the host, i.e. our human cell. Neutralizing antibodies specifically incapacitate the spike protein. Our immune system remembers the antibodies it has produced and is thus prepared for a new infection with the same intruder.

Is there an immunity? How long does it last?

The good news is that it is very likely there is an immunity. This is suggested by the proximity to other viruses, epidemiological data and animal experiments. Researchers infected four rhesus monkeys, a species close to humans, with SARS-CoV-2. The monkeys showed symptoms of COVID-19, the disease caused by the coronavirus, developed neutralizing antibodies and recovered after a few days. When the recovered animals were reinfected with the virus, they no longer developed any symptoms: They were immune. 

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The bad news: It is not (yet) known how long the immunity will last. It depends on whether a patient has successfully developed neutralizing antibodies. Achim Hörauf estimates that the immunity should last at least one year. Within this year, every new contact with the virus acts as a kind of booster vaccination, which in turn might prolong the immunity.

"The virus is so new that nobody has a reasonable immune response," says the immunologist. He believes that lifelong immunity is unlikely. This "privilege" is reserved for viruses that remain in the body for a long time and give our immune system a virtually permanent opportunity to get to know it. Since the coronavirus is an RNA (and not a DNA) virus, it cannot permanently settle in the body, says Hörauf.

The Heidelberg immunologist Stefan Meuer predicts that the novel coronavirus will also mutate like all viruses. He assumes that this could be the case in 10 to 15 years: "At some point, the acquired immunity will no longer be of any use to us because then another coronavirus will return, against which the protection that has now been formed will not help us because the virus has changed in such a way that the antibodies are no longer responsible. And then no vaccination will help either."

How can we take advantage of the antibody response of the immune system?

Researchers are already collecting plasma from people who have successfully survived an infection with SARS-CoV-2 and are using it to treat a limited number of patients suffering from COVID-19. The underlying principle: passive immunization. The studies carried out to date have shown positive results, but they have usually been carried out on only a few people. 

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At best, passive immunization is used only when the patient's own immune system has already started to work against the virus, says Achim Hörauf: "The longer you can leave the patients alone with the infection before you protect them with passive immunization, the better." Only through active immunization can one be protected in the long term. At the same time, it is difficult to recognize the right point in time.

PCR (polymerase chain reaction) tests are currently used to find out whether a person is infected with the coronavirus. With the help of PCR, it is not possible to tell whether or not there is reproducible viral RNA; it is just a proof of whether the virus is still present, dead or alive. A PCR test cannot tell us whether our immune system has already intervened, i.e. whether we have had contact with the virus in the past, have formed antibodies and are now protected. Researchers are therefore working on tests that check our blood for the presence of antibodies. They are already in use in Singapore, for example, and are nearing completion in the USA. With the help of these tests, it would finally be possible to gain an overview of the unclear case numbers. In addition, people who have developed antibodies against the virus could be used at the forefront of health care, for example. An "immunity passport" is even under discussion.

Is it possible to become infected and/or ill several times with the coronavirus?

"According to all we know, it is not possible with the same pathogen," says Achim Hörauf. It is possible to become infected with other coronaviruses or viruses from the SARS or MERS group if their spike proteins look different. "As far as the current epidemic is concerned, it can be assumed that people who have been through COVID-19 will not become ill from it for the time being and will not transmit the virus any further,"  he says.

How long before you're no longer contagious?

A study carried out on the first coronavirus patients in Germany showed that no viruses that are capable of replication can be found from day eight after the onset of symptoms, even though PCR can still detect up to 100,000 gene copies per sample. This could change the current quarantine recommendations in the future.

According to the Robert Koch Institute, patients can currently be discharged from hospital if they show two negative PCR samples from the throat within 24 hours. If they have had a severe case of the disease, they should remain in domestic isolation for another two weeks. For each discharge, whether from hospital or home isolation, they should have been symptom-free for at least 48 hours.

Why do people react differently to the virus?

While some people get off with a mild cold, others are put on ventilators or even die of SARS-Cov-2. Especially people with pre-existing conditions and older people seem to be worst-affected by the virus. Why? This is  the hottest question at the moment.

It will still take a very, very long time to understand the mechanistic, biological basis for why some people are so much more severely affected than others, virologist Angela Rasmussen told The Scientist. "The virus is important, but the host response is at least as important, if not more important," her colleague Stanley Perlman told the magazine.

Stefan Meuer sees a fundamental survival principle of nature in the different equipment and activity of our immune systems: "If we were all the same, one and the same virus could wipe out the entire human species at once. Due to the genetic range, it is quite normal that some people die from a viral disease while others do not even notice it. "

Achim Hörauf also suspects immunological variants that could be genetically determined. Since interstitial pneumonia is observed with the coronavirus, the focus is probably on an overreaction of the immune system. However, it is also possible that each person affected may have been loaded with a different dose of the virus, which in turn leads to different outcomes. And finally, it makes a difference how robust the body and lungs are: Competitive athletes simply have more lung volume than long-time smokers.