RIO DE JANEIRO, BRAZIL – On Monday, Hong Kong scientists announced the first confirmation of a case of reinfection by Covid-19, the disease caused by the novel coronavirus (Sars-CoV-2). The research with the finding was validated and published in the “Clinical Infectious Diseases” of the Oxford University publishing house in the United Kingdom.
The patient, a 33-year-old man, became infected with the virus for the second time after traveling to Spain. The first time, he had only mild symptoms. The second time, he had no symptoms at all.
In this report, readers will learn, in questions and answers, what is known about the case, what it means and its implications for a vaccine:
Is this the first confirmed case of reinfection?
Why is it difficult to confirm suspected cases of more than one infection?
How important is confirmation?
Will we achieve herd immunity?
Will everyone who has had Covid have it again?
Will having antibodies ensure immunity?
Will the vaccine work?
1. Is this the first confirmed case of reinfection?
As far as known, yes. Reinfection can be difficult to confirm, but this time researchers say they are certain because the virus that infected the patient is different from the first one. They found this with a genetic sequencing of the virus, which determined that the origin of the second virus was different from the first infection.
“Our results prove that the second infection is caused by a new virus, which he recently acquired, rather than a prolonged viral spread,” said Kelvin Kai-Wang To, a clinical microbiologist at the University of Hong Kong.
According to Hong Kong scientists, the second “version” of the virus is closer to the one in circulation in Europe between July and August (the patient had returned from a trip to Spain). The first virus was similar to those in circulation in March and April.
2. Why is it difficult to confirm suspected cases of more than one infection?
One of the challenges in determining whether or not the individual has indeed been infected with the coronavirus again is to know if the virus detected the second time is the same as the first. It can be the same and it may only be showing up again in the tests, even if it has some potential mutations.
This is because the individual may keep the virus in the body, hidden and mutating, even after its trail no longer shows in the tests, explains scientist Ester Sabino, from USP (University of São Paulo) Medical School, who was part of the team that sequenced the genome of the coronavirus in Brazil.
“It has been six months, even if it is inside the person, it may develop other mutations,” explains Sabino.
Therefore, genetic sequencing is recommended, as the scientists in Hong Kong did. With it, it is possible to assemble what is called a phylogenetic tree, which details the relationships between various species and the mutations they have undergone (see below).
“Without sequencing the first [infection] and the next, you can’t prove it,” says the USP researcher.
“When you perform the sequencing and put it in a tree, if it were [the same virus], you would have the sequencing, with the mutation, different from the first virus, but the two would be in the same tree group. And this is not what happened. So you know that the other virus is not the one there before,” explains Ester Sabino.
In their research, scientists claim to have found 24 parts of the second infection virus that are different from the first. But Sabino explains that it is a phylogenetic origin, and not the mutations themselves, that are the most important.
“It could have acquired 24 mutations, but when you analyze the tree, they would stay together anyway. And that’s not the case. So, it is clearly reinfection. Clearly, the origin of the first sample is different from the second,” adds the scientist.
Sabino says the difference is clear in this case. If it were the case of a patient who was in Brazil the whole time, for instance, it could be more difficult to determine if there was a new infection or if it is the same virus, but with minor changes.
“It is much more difficult to prove when one is in the same region, because the viruses are very similar and it is much more difficult to tell if the sample has mutated inside or outside the individual. It is much more complex to prove the infection in Brazil because the strains are all similar to each other. It’s much easier in a case like this one in Hong Kong, where the person traveled and caught it somewhere else,” she explains.
In the sequencing that her team performed in June, more than 400 genetic codes of the coronavirus were found in Brazil, with three main strains (“versions”) that gained ground and began to circulate throughout the country.
3. What is the significance of confirmation?
In the scientists’ opinion, this means that the coronavirus will possibly be circulating among humans permanently, like colds – because even those who have already had it can become infected again.
“The Covid-19 will probably continue to circulate among the human population, as is the case of other human coronaviruses. Reinfection is common for other ‘seasonal’ coronaviruses,” say Hong Kong researchers.
In May, the World Health Organization (W.H.O.) had already raised the possibility that the coronavirus would become endemic (i.e., it would be found regularly in a certain area or population), like HIV, without ever vanishing.
“This has consequence because the virus is kept circulating for a long time. That’s what endemic is. It is a problem,” says Ester Sabino.
4. Are we going to achieve herd immunity?
For Hong Kong scientists, we may never achieve the so-called “herd immunity”.
The concept is typically used when referring to the vaccination rates required for a certain disease to stop circulating among a population, even if not everyone is vaccinated (in the case of measles, for instance, the rate is 95 percent).
Expecting herd immunity ‘is absurd and unethical,’ says study leader investigating how many had Covid-19 in Brazil
“First, it is unlikely that herd immunity can eliminate Sars-CoV-2, although it is possible that subsequent infections may be milder than the first, as is the case with this patient,” the study researchers say.
5. Will everyone who has had Covid have it again?
Not necessarily – science still does not know the answer to that question. Ester Sabino recalls that the Hong Kong patient’s case may be rare, occurring once in every hundreds of thousands of people.
“The fact itself is important. It defines the possibility of reinfection. The first step is to determine what occurs. The second is to determine how frequent it is,” she recalls.
“It may be that this individual has lost [the antibodies] quickly. But if most lose them within a year, maybe every year you will have to be administered a dose of that vaccine again, along with the influenza vaccine,” she says.
6. Does having antibodies ensure immunity?
It is not yet known for certain. After a while, the antibodies tend to disappear, but there is another type of immune response, of the T cells, which also helps in the fight against the coronavirus.
There are studies that suggest that this response, the so-called cellular immune response, lasts longer than antibodies (the humoral immune response). Moreover, this type of cell has already been found even in people who did not have antibodies detected.
In the case of the Hong Kong patient, although he had the first coronavirus infection, no antibodies were detected as soon as he was infected for the second time – they only emerged five days later. This may suggest two possibilities, according to the scientists: that he did not develop the antibodies after the first infection; or that he developed the antibodies after the first infection, but they were “fading”, and when he was infected for the second time, it was no longer possible to detect them.
According to scientists, this lack of antibody response can have consequences both in terms of allowing people to be infected with the coronavirus more than once and in terms of the severity of the disease.
“Although our patient is asymptomatic during the second infection, it is possible that reinfection in other patients will result in a more severe infection,” they warn.
But they point out that it is possible that the patient developed the antibodies after the first time he became sick – this may just not have been detected by the tests.
Concurrently, researchers also point out that the T-cell immune response may play a role in improving the severity of the disease in a second infection. (Scientists in Hong Kong have not discussed this response in the reinfected patient.)
7. Will the vaccine work?
No one knows. The main doubt is how long the immune response induced by the vaccine will ensure protection, explains Ester Sabino.
For a future vaccine, mutations are not the issue, says Sabino, because apart from being few, in the case of the coronavirus, the mutations it undergoes do not change the way it is recognized by the immune system. The question is if the body is able to maintain this long-term recognition. And this matters because, when administered a vaccine, the body is induced to produce antibodies for a certain disease.
“For the vaccine, this is the issue. The person had the infection and lost the antibodies. Will the same thing happen with the vaccine? How long will the vaccine last? The problem is the protection, not the mutation”, she explains.
To clarify the difference, Sabino compares Sars-CoV-2 to HIV – which is a virus that has many mutations, so it is difficult to find a vaccine that works against it. Unlike the coronavirus, HIV “changes” so much that the immune system is no longer able to recognize it, and therefore has difficulty in fighting it.
In the Hong Kong research, scientists say that a vaccine for Covid-19 should not be able to provide lifelong protection. In addition, they recommend that even patients who have already had the disease should be immunized.