June 21, 2021

The first documented case of reinfection by the SARS-CoV-2 virus raises some certainties and many more unknowns

Almost eight months after the start of the COVID-19 pandemic and more than 23 million registered cases of coronavirus in the world, on August 24 it was publicly announced the first scientifically proven case of reinfection by the new coronavirus. The University of Hong Kong reported in an accepted article in the medical journal Clinical Infectious Diseases (not yet published) that it was a Hong Kong man who was infected with the SARS-CoV-2 virus last March and was infected again on his trip to Spain in August. While in the first infection he had typical symptoms of COVID-19 (fever, sore throat, headache, cough …), in the second time this person was asymptomatic. Between the two infections, about four and a half months passed.

Although there had long been suspicions of reinfections by the SARS-CoV-2 virus in particular cases, until now it had not been documented that they were true reinfections, but consisted of errors or limitations in PCR tests that indicated remains of coronavirus that were no longer infective or the same persistent infection. The current case of reinfection is real and the University of Hong Kong has been the first to prove it scientifically. And although it is, for the moment, an exceptional case, it raises a series of certainties and even more unknowns.

The certainties

Is it certain that it is a reinfection with the SARS-CoV-2 virus?

Yes, scientists from the University of Hong Kong not only performed PCRs (which tested positive) to detect the coronavirus in the first and second reinfection, but they also analyzed their complete genomes (the RNA sequences) to see if they could be the same viruses or different. Knowing the genetic sequence of an organism is like having access to its unique and unrepeatable identity card (except for identical clones and twins). These analyzes show that the genomes of the viruses in both infections come from clearly different strains, although their genetic differences are very small (only 24 different nucleotides). This proves that it is not the persistence of the same coronavirus in the body of this person over time, but a new infection with another slightly different coronavirus four and a half months after the first.

Could there be more people who have been reinfected without knowing it?

It is true that, until now, this case is something exceptional, but it is certain that there are more cases around the world that have not been identified when they are off the radar. Today, The Netherlands and Belgium have reported more cases of coronavirus reinfection. Demonstrating cases of reinfections is not an easy task, you must have the resources and knowledge to perform PCRs and genetic sequencing. PCRs are the order of the day to identify coronavirus cases, but coronavirus genetic sequencing is highly restricted. Furthermore, the “luck” factor also plays a role. If a person is reinfected a second time, without any symptoms, it is quite possible that they will not be identified, unless it is detected as a “contact” in a scan or goes through an airport control (or otherwise) and is carried out a PCR. And, in the event that the PCR is positive, it is also necessary to carry out the genetic sequencing of the virus from the second infection and to be lucky enough to previously have the genetic sequence or a sample of the virus from the first infection.

The Hong Kong researchers were fortunate, as they were able to learn the genetic sequence of the coronavirus that caused the first infection and compare it with the sequence of the virus in the second. This contrasts with the bigger picture: of the more than 23 million people officially infected by coronavirus, only a tiny percentage of them (tens of thousands) have stored genetic samples or sequences of the coronaviruses that caused their infections.

The unknowns

Could people with a second infection spread it to others?

It is impossible to know at the moment. On the one hand, the information provided by this first case of reinfection is very limited and may not reflect what a second infection would be like in other people, due to the biological variability in immune responses. We do not know if this reinfected patient has biological peculiarities that do not occur in other individuals. Therefore, it is essential to continue studying more cases of reinfections to establish solid conclusions. For now, we do not yet know if Hong Kong is contagious to others. Researchers are conducting in vitro tests to see if this person’s coronaviruses can infect cells, and it will take time for results to appear and be published.

Even today it remains unclear if all asymptomatic patients are capable of infecting other people and what capacity they have to do so. Much less is known about reinfected people. In any case, scientists hope that, if they are really capable of infecting, their ability to do so will be reduced compared to people who pass the first infection with symptoms.

What is the cause of reinfection, coronavirus mutations, a transient immunity, or both?

It is unknown. On the one hand, it was observed that, of the 24 mutations that the coronavirus from the second infection had, some of them caused changes in four amino acids that are part of protein S. Protein S is one of the proteins that are part of the spicules of the coronavirus and that intervenes in the invasion of the coronavirus in the cell. It is also one of the proteins that the immune system recognizes to identify this virus as a foreign agent and attack it. Could these protein S changes have triggered re-infection by a less effective immune response? It is not known, the Hong Kong researchers acknowledge that more studies, serological among them, are needed to clarify this issue.

On the other hand, it was also observed that this reinfected person did not have detectable IgG antibodies against SARS-CoV-2 only 10 days after showing mild symptoms in the first infection. It is possible that people with these characteristics are more susceptible to reinfection and their immunity decreases over time. In any case, we already knew from multiple studies that immunity against coronaviruses is not lifelong, but temporary (especially for cold coronaviruses). It was a matter of time before reinfections from this new coronavirus appeared, although it was hoped that years and not months would pass before detecting reinfections.

In any case, it is important to clarify that immunity is not a matter of black and white. It is not about whether someone is protected or not, but about the degree of protection they have. The good news is that the reinfected person from Hong Kong had no symptoms in the second infection, which is most likely due to the person retaining some immunity from the first time. Enough protection not to have symptoms, but not enough to prevent infection entirely.

Could reinfections also occur after receiving a coronavirus vaccine?

We do not know yet. In addition to the fact that conclusions cannot be extrapolated from a single case of reinfection or a small number of them, it must also be borne in mind that certain vaccines can offer more lasting protection than passing the infection naturally. The coronavirus mutates slowly compared to the influenza virus, so the chances that an annual revaccination will be necessary as with this virus are reduced. In any case, even in the event that reinfections could occur after vaccines, it is expected that people would have mild symptoms or were asymptomatic, so they would protect people from risk.

How likely is reinfection by coronavirus going to be as time goes by?

We will only know this with the passage of time and as more cases of reinfection appear. Whether it appears earlier or later, the magnitude of reinfections and whether they are contagious or could not make the control of the pandemic more complicated.


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