How long will immunity to the new coronavirus last?

Now some states are thinking about Coronavirus UK: health passports ‘possible in months’ on the introduction of "immune passports" based on the results of tests for antibodies to coronavirus - to allow their holders to move freely. This idea is based on the assumption that someone who has antibodies has already been ill, will not infect anyone else, and will not get sick a second time. The efforts of the immune system are really aimed at preventing infection from occurring during a second encounter with the causative agent of the disease, but not in all cases everything goes according to plan. We figure out what exactly can go wrong.

Start over from the beginning

At the end of April, Korean doctors reported to SOUTH KOREA EXPERTS SAY RECOVERED CORONAVIRUS PATIENTS RETESTED POSITIVE BECAUSE OF ‘DEAD’ VIRUS PARTS about 263 patients whose viral particle tests were again positive after people had recovered from the coronavirus infection. These people were considered to have already recovered, and the penultimate test did not find the virus in their bodies. This is not the first news of this kind: Coronavirus: Japanese woman tests positive for the second time has already received similar reports from Japan and China.

This can be explained:

reactivation of the virus,
re-infection,
testing error.

Let's start with the latter - an error is considered the most likely cause of what happened. The head of the committee of the Korean Center for Disease Control and Prevention (KCDC) Oh Myoung-don believes Tests in recovered patients found false positives, not reinfections, experts say that a positive test result is not associated with recurrent disease. His explanation is that the test did not detect full-fledged viruses, but their fragments stuck in the epithelium. The test does not capture this difference: it shows the presence of viral RNA in the sample, but which virus it belongs to - capable of multiplication or simply its “fragments” - cannot.

There are other failures of test systems: for example, false negative results - showing the absence of viral RNA where it is, and with a large volume, the poor quality of the tests will inevitably become noticeable. At the stage of recovery, there are already few viral particles in the body, and the chances of "catching" them with a test also decrease.

Judging by the accumulated data, the remains of the virus can remain in the human body for a long time after recovery. In some patients, the virus is found Prolonged presence of SARS-CoV-2 viral RNA in faecal samples in sputum and stool for a couple of months after the onset of symptoms. In the case of Korean patients, Oh Myeong-dong points out that the replacement of half of the epithelium lining our airways occurs on average in three months, and suggests that the RNA of the virus may well get into the sample a month after recovery.

Against the hypothesis of reactivation of the virus (roughly speaking, the restoration of an untreated disease), it is also said that none of the Korean patients were subsequently Recovered coronavirus patients are testing positive again. Can you get reinfected? contagious, although 44% developed mild symptoms. In addition, when Korean researchers tried to isolate and cultivate viral particles from several of these patients, they failed. This also suggests that there were no more full-fledged viral particles in their bodies. So mild symptoms could simply be a consequence of the fact that the immunity finished off pathogenic bacteria that were activated in an organism exhausted by the fight against coronavirus - or simply a hypochondriacal episode.

And it is not yet known about unequivocally confirmed cases of secondary infection with coronavirus. In addition, scientists conducted the Lack of Reinfection in Rhesus Macaques Infected with SARS-CoV-2 experiment, in which they tried to re-infect macaques with the same SARS-CoV-2 during the recovery phase after the primary infection. Nothing worked for them: the acquired immunity worked.

On this basis, it is worth proceeding from the fact that the immune response in the case of COVID-19 works as it should: once a person has recovered, then in the near future he is insured against infection with the same virus.

But how long the acquired immunity to SARS-CoV-2 will protect the body, and whether it may not work after a while, remains unknown. WHO has taken "Immunity passports" in the context of COVID-19 on this issue, an extremely accurate position and claims that people who have recovered with antibodies are not immune from re-infection.

How the immune response works

The immune response to SARS-CoV 2 or any other infection is structured as follows. Within a few hours after infection, it is activated innate immunitywhich provides general protection. In general, it independently pacifies the vast majority of infections in the background, and we will not even know that someone tried to attack us.

In parallel, the body is taken to develop a specific response, sharpened for a specific ailment. Formation of such acquired immunity takes about a week. During this time, the body selects lymphocytes that the virus can recognize, optimizes them and clones them many times.

Such an army has many ways of fighting. Lymphocytes can independently deal with infected cells, "incite" other cells to the virus, or produce antibodies that mark viral particles for the rest of the immune system and prevent the virus from entering the cell. At the same time, some of the lymphocytes are stored in reserve: they form long-lived cells of immune memory, which can work quickly in the event of a secondary infection. The speed and strength of the reaction in this case depends largely on the number and characteristics of these cells and, in particular, on how well they recognize the pathogen.

Defense test

You can find out the reaction of acquired immunity using another test that checks for the presence in the human body of antibodies produced by B-lymphocytes. This method is widely used in the case of many infections. It is these tests that are supposed to be used in the "immune passports" program.

But strictly speaking, a positive test result does not always mean that a person has been ill with COVID-19 and his body is reliably protected. There may be several reasons for this.

First, it is possible that a positive test result is caused by antibodies to other coronaviruses. In addition to SARS-CoV-2, six more coronaviruses are known that can infect humans:

the first SARS-CoV associated with the 2002-2003 epidemic in Asia;
MERS, the causative agent of Middle East respiratory syndrome;
the other four (OC43, HKU1, 229E, NL63) cause the common seasonal cold.

If a person has already met with them and developed antibodies to them, then due to the similarity of coronaviruses, they can react to SARS-CoV-2 and give a positive test result. For example, antibodies in the blood plasma of some patients who have recovered from SARS-CoV were able to neutralize SARS-CoV-2 in vitro with SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. But it is unclear how well they will be able to fight the new coronavirus in vivo.

The opposite situation, when a person has been ill with COVID-19 and developed immunity, but received a negative result when tested for antibodies, is also possible. This is due to the lack of test sensitivity, which many developers are currently working on improving. So, the Roche’s COVID-19 antibody test, which was released on the market just a few days ago, receives the FDA Emergency Use Authorization and is available in markets accepting the CE mark from Roche, which has a declared specificity of 99.8% and a sensitivity of 100%. It should be borne in mind that the last figure was obtained for patients on the 14th day after confirmation of the disease, when the level of antibodies is high. Neutralizing antibody responses to SARS-CoV-2 in a COVID-19 recovered patient cohort and their implications, and how well will it “catch” a long-standing infection is not yet clear.

What antibodies talk about

The antibodies that we check for with this test are not the only, and perhaps not even the most important, contributor to the response. The acquired immunity activates several types of "troops" at once, and the test notices only the "shells" with which one of its parts - B-lymphocytes - bombards the enemy. In addition to B-lymphocytes, T-lymphocytes are involved in the immune response. Some of them directly target the infected immune cells, while others - T-helpers - help other cells to fight pathogens. At the same time, the ratio of antibodies, B- and T-cells is important for the patient both for the current struggle and in the future.

Information is gradually accumulating that a high level of antibodies for the fight against coronavirus infection may not be very useful. So in patients The trinity of COVID-19: immunity, inflammation and intervention with MERS and Anti-spike IgG monkeys causes severe acute lung injury by skewing macrophage responses during acute SARS-CoV infection infected with SARS-CoV, the severe course of the disease correlated antibodies. Comparison of Neutralizing antibody responses to SARS-CoV-2 in a COVID-19 recovered patient cohort and their implications of 175 patients who have had COVID-19 virus. At the same time, in about 30% of patients, among whom were people of all ages, the level of antibodies was extremely low. And this does not necessarily mean that their acquired immunity responded less effectively than the immunity of other recovered people.

This does not contradict the "healing" nature of antibodies: the severe course of COVID-19 is often associated with a delayed and excessive immune response, which, along with the virus, cripples the patient's lung tissue.

At the same time, T-lymphocytes have shown themselves to be good. The study Elevated exhaustion levels and reduced functional diversity of T cells in peripheral blood may predict severe progression in COVID-19 patients of 16 patients with COVID-19 showed that the shortage and depletion of T-lymphocytes is correlated with the severe course of the disease.

And this, too, may be the reason why older people get more sick. The production of T cells ceases in adolescence, and by old age the number and variety of free T cells that are not occupied in memory of other diseases decreases. This means that when faced with a previously unknown infection in an elderly organism, there may simply not be T cells suitable for the fight, or there will be not enough of them. T cells provide targeted destruction of the pathogen and are able to correctly "build" B cells and components of innate immunity, which in their absence lose coherence.

Classical testing of the immune response is based on testing antibodies, but now - when the ambiguity of their role in pathogenesis has become apparent - ELISPOT testing - the "Wikipedia" of the T-cell immune response may become more popular.

How long will the protection last?

The duration of acquired immunity to different infections is very different. The body can remember the measles virus for the rest of its life, while the flu can get sick several times in one season - by contracting different strains.

No long-term surveillance of coronavirus immunity has yet been conducted, and it cannot be said with certainty where it is on this scale.

One of the reasons for the "forgetfulness" of influenza immunity lies in the speed of evolution and the diversity of seasonal flu: this virus is very variable, so that every year we meet a new strain. After an illness, our immunity continues to recognize those details of the virus that helped to cope with it for the first time. If in a strain that has spread after several seasons these details change or simply disappear, then the acquired immunity will work badly.

SARS-CoV 2 belongs to the variable RNA viruses, but according to the available data Real-time tracking of influenza A / H3N2 evolution using data from GISAID, the rate at which it mutates is ten times lower than that of seasonal flu.

Similar studies on other coronaviruses do not yet allow predicting the behavior of SARS-CoV-2. One of the oldest works says The time course of the immune response to experimental coronavirus infection of man that immunity to the seasonal cold-causing lung coronaviruses does not last long. This was tested on 15 volunteers who allowed themselves to be infected and then periodically donated blood to check the level of antibodies. A year later, they were again infected with the same strain, and they became infected again, although the symptoms were much milder.

More recent papers on highly pathogenic strains of coronaviruses provide examples of T-cell immunity of SARS-CoV: Implications for vaccine development against MERS-CoV patients in whom antibodies and infection-specific T cells could be found several years after illness. Unfortunately, most of such works were also carried out on small samples and there is no data on reinfection there.

Available data do not allow predicting how long the coronavirus immunity will last. If immunity persists for a long time, then, according to the results of modeling the Projecting the transmission dynamics of SARS-CoV-2 through the postpandemic period, one can hope that the virus will disappear in five years. If not, then COVID-19 will become a seasonal disease, similar to those caused by the low pathogenic relatives of SARS-CoV-2. It is not known exactly how its pathogenicity will change.