What do we know about cases of Covid-19 re-infection and why we need to study them

What do we know about cases of Covid-19 re-infection and why we need to study them

Documented cases of re-infection remain few. But studying them is crucial to understanding how the immune system responds to a second infection of the same pathogen

(illustration: Getty Images) Serological tests. Plasma therapy of convalescents. Monoclonal antibodies. The (disputed) herd immunity. Re-infections. The vaccines . All chapters of one great book, the one that tries to understand how the immune system responds to Sars-CoV-2. Research efforts in this field - as well as all fields around the coronavirus to be honest - are enormous, because the fallout is enormous. Understanding how the immune system responds to the coronavirus can allow us to carry out epidemiological investigations, but also to develop new therapies, such as monoclonal antibodies and vaccines, which aim to train the immune system by preparing it for the encounter with a new pathogen. But understanding if when and how you become immune to the coronavirus also serves to understand if it is possible to become infected again with Sars-CoV2. In reality, today we are proceeding backwards, at least on this front: by studying whether and how it is possible to reinfect with the coronavirus we can understand something more about the functioning of the immune system against the virus. And maybe even the long-awaited vaccines.

(Not) it's easy to say re-infections

But let's go in order. As far as we know today, coronavirus re-infections are possible. They are a fairly rare occurrence, but they are possible. In fact, even establishing its spread and defining a case of re-infection is quite difficult. On the one hand, in fact, we are talking about possible re-infections in the event that the appearance of the symptoms arouses a suspicion, or perhaps following screening activities: this necessarily leads to underestimating the cases of re-infection we are talking about, commented Akiko. Iwasaki of Yale University in Lancet. And among all the possible cases, those confirmed to date are only a handful: just six of which information is available (not always presented in peer-reviewed publications, but the pandemic has accustomed us to this). The case series is limited and it is not possible to identify any trends, apart from the fact that they were young subjects and without immunological pathologies: some were symptomatic patients at the first infection as well as at the second, others, most were symptomatic in both cases, in a case with more serious illness than at the first meeting.

What unites the different cases, they write from the European Center for Disease Control and Prevention (Ecdc) on the subject, is that there are reasonable evidence to consider them all second cases of re-infection. And it's evidence that has to do with the sequencing of the viral genome detected in the participants. In fact, to talk about a second re-infection it is not enough to return positive after being declared cured from a previous infection: in addition to the limits of the accuracy of the tests, molecular swabs can remain positive for a long time even in the absence of viable viral particles, such as it is known, even after the disappearance of any symptoms, and in the same way the swabs can be negative if the sample taken is little. This is why in general, to talk about re-infection, it is necessary to have the genetic sequences of the viral samples of the first and second infections available and compare them. If they are different enough - and by belonging to different lineages or by the number of considerable mutations - it is reasonable to believe that we are facing tough different infections.In reality, as explained by the ECDCs, it is more complicated: viruses can accumulate mutations when they are found in their hosts, and multiple viral strains can infect the same host. For this reason, epidemiological analysis, that of the timing of infections, outside the genetics laboratory, remain fundamental. Laboratory tests on the immune response can also be helpful.

Infections and immune response

If infections can happen again in subjects already exposed to the virus, albeit rarely as observed, this means that having contracted Sars-CoV-2 does not confer long-term immunity, intended as protection from a new infection, at least not always (even if the question is not so clear for everyone). The same happens with other seasonal coronaviruses, such as colds. But does having already been exposed to the virus in any case prevent severe cases of the disease? Or does it change affect the transmissibility of the virus? Answering is not that simple. First of all because documented cases of re-infections are few to draw conclusions and lack of complete data - such as antibody or cellular immunity data - and largely because we still know little about the adaptive immune response to the coronavirus, its role protective of, for example, antibodies and T lymphocytes.

We know that most people develop an antibody response to the virus and that in the vast majority neutralizing antibodies are observed (and this is where the search for monoclonal antibodies starts ). But even today, as mentioned in the past, we don't know how long these antibodies remain. They vanish, like those that develop against other coronaviruses, over time (from a few months to a few years), especially in cases of mild infections. And it is also not known what level of antibodies is needed to provide protection. "The extent and time period of the decrease in antibody levels as well as the impact of cellular immunity - again summarized by the ECDCs - have not been sufficiently studied on large groups and for long periods".

On the transmissibility of the virus in case of re-infections, there are currently no indications to consider these patients different from all the others. So much so that Iwasaki writes precisely on this: "The cases of reinfection say that we cannot rely on immunity acquired through natural infection to arrive at herd immunity; not only is this strategy lethal for many people, it is not effective either. Herd immunity requires safe and effective vaccines and the implementation of a solid vaccination ".

Reinfections and vaccines

Speaking of vaccines, what do reinfections mean? Do they mean that we run the risk of having vaccines that are not effective enough? To date, Iwasaki continues, we have no reason to believe that re-infections have occurred due to a process of evasion of the immune system, and better studying any cases of re-infection will help the development of effective vaccines, directing towards those better able to confer immunity. And it is not excluded that this requires repeated vaccinations in the event that immunity is lost in the short term, as an editorial in Nature also notes.

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