September 29, 2020

“The reinfections are going to give us many clues to all of us who try to generate vaccines”

If the month of August has traditionally been characterized by one thing in the newsroom, it is because of the drought of issues that forced journalists to search for news under the stones.

The pandemic has ended this union topic. This Monday, a local Hong Kong media announced what had not been documented until now: the first case of reinfection by SARS-CoV-2. A 33-year-old Hong Kong man was discharged after being cured of the virus in April, but tested positive again in August after returning from Spain. He had mild symptoms the first time and none the second.

The study has been accepted by the scientific journal Clinical Infectious Diseases and is pending publication. Just one day later, Dutch and Belgian researchers reported two new reinfections in their countries.

In netherlands, an elderly man with an impaired immune system would have contracted the coronavirus a second time, while in Belgium a patient who had overcome the coronavirus would have relapsed three months after the first infection. Apparently, in the absence of the findings being published in scientific journals, in all three cases the new infections would come from viruses of different strains compared to the initial infections.

To the virologist Sonia Zuniga These news have caught him spending a few days on vacation, although, according to his account to SINC, he continues to “review projects” and attend to the media, as he has not stopped doing throughout the pandemic. This researcher at the Coronavirus laboratory of the National Center for Biotechnology of the CSIC is part of one of the spanish teams what are you trying to develop a vaccine against SARS-CoV-2, so reinfections and how the immune system responds are essential to keep moving forward.

Were you surprised by these findings or was it a matter of time before any reinfections were identified?

They have surprised me, although there are still few cases, even with these two recently reported. With the millions of infections out there and the number of people who have suffered from moderate or severe illness, these few cases don’t seem like many. I would get the positive reading that, in general, in the time that has passed, it seems that people who have suffered the disease are protected.

The case that came out last week from the ship’s crew – those who had been infected and had antibodies were protected – goes along the same lines. As for the case of Hong Kong, what strikes me a lot is how this person’s immune response was after the first infection. It will give many clues to all of us who are trying to generate vaccines to know what the protective responses have to be. The immune response that this man had has not protected him from reinfection – if what the authors say is true – but it has protected him from having symptoms, because apparently he is asymptomatic. In the Dutch case, it appears that the person had immune problems.

Focusing on the case of Hong Kong, the fact that the second time was asymptomatic, would it mean that the immune system reduced the severity of the infection?

Yes, it is the most realistic possibility, although we do not have the data. We are assuming that in the first infection he had a general immune response like the one presented by other patients, that is, with antibodies neutralizers. It would be interesting to know what levels they would be at when it was reinfected again. He would also have developed a memory cell response so that, when reinfected, there would be no serious symptoms.

Another interesting point is, in the first infection, how long it took until the patient stopped having symptoms and registered a negative CRP. That might give an idea of ​​how long it took to clear the virus, if it was the pre-existing immune response that cleared it faster.

One of the researchers told us that although the patient was asymptomatic, he did have contagion capacity and was high. That would be bad news, wouldn’t it?

That means that it had a lot of virus but they themselves say, according to the press release, that they are analyzing if there is an infectious virus. The fact of detecting the RNA of the virus does not imply that it is infective. To really know how much there is, you have to isolate the virus. I suppose that the work will be published with that data because it is very important.

From what one of the authors has told us, the cultivation is still underway at the moment and the article is already accepted by the journal.

Well, it is a very important piece of information that they should include because the interesting thing about this case is that if we know all the data, it will provide a very good overview. We have been saying this for a long time, especially in those individuals in whom the immune response generated in the first infection has not been very strong and declines over time. Can the person get reinfected? If it gets infected, what will happen?

Another question that arises is how long we will be protected if we have passed the disease …

That is why it would be very interesting to know the type of immune response that this patient generated from the first infection. What is known from studies that have already been published is that, in general, patients who have had a moderate or severe disease generate more neutralizing antibodies, than they protect, than individuals who have had a mild or asymptomatic disease. These antibodies decay over time and do so faster the less the disease has been.

The question that still remains to be answered and for which we have no data, is about the other pathway of the immune response, the cellular one. Has it been generated? And if it has been generated, does it protect or not? These cases could provide clues.

If immunity were short-lived, according to the authors, this coronavirus will persist in the population like cold viruses. Do you agree?

It could be a possibility. This is important for many laboratories in the world involved in generating vaccines that have to elicit an immune response better than that of the virus. If the response of the virus does not prevent you from being reinfected, but rather prevents you from having a severe disease, either you have to vaccinate more often or you have to improve the vaccine so that it ultimately prevents infection. In other words, lengthen that response, whether it is antibody, cellular response, or both.

How do these reinfections affect herd immunity? Is it no longer possible?

It would still be possible. Antibody immunity is known to decline over time. [Que hubiera muchas reinfecciones] It would affect group immunity because to achieve it, a greater number of people who were immunized in some way would be needed. But, I insist, immunity is not achieved only by antibodies. There is also cellular immunity. At the moment we do not know how it develops or what protective role it may have. In other words, in herd immunity, it is not only the antibody response that has to intervene, it can also be immunity due to the cellular response.

On the genetic analysis that the Hong Kong authors commented that they had done, are the strains of this coronavirus that move through Europe and Asia very different?

They are not very different but they do have some changes. There are thousands of sequences already released from all over the world and from all stages of the epidemic and it is not that there are many changes, but there are some. For example, the strains that initially circulated in Asia had a series of alterations that can produce modifications in the virus protein, but these are genetic changes that can be mapped. The strains that have circulated in Europe or the United States in many cases do not have these changes. By sequencing the 30,0000 nucleotides certain genomes appear that give clues as to whether the virus comes from one place or another.

It’s the same as with the study that was done in Spain which showed that there had been 15 different introductions of the virus from different places, why? Because viruses were different and looked like those that came from one place or another. Knowing the entire sequence of the virus allows you to trace where it came from.

According to the researchers, when the vaccine is developed it is recommended that people who have been infected put it on and do not stop using a mask or the rest of the prevention elements. Should they not lower their guard?

This is something that the scientific community has been saying for a long time. Be careful with thinking that one is already protected because the disease has passed and there are antibodies. It is very likely that if someone becomes infected again, the disease will not happen again, but could transmit the virus to other people as asymptomatic. Safety measures, mask, social distance and hand washing have to continue to be maintained.

These three cases of possible reinfections show what is happening in the pandemic: researchers presenting their findings without waiting for them to be published in scientific journals. Is the health crisis transforming the way scientists show your results?

Many jobs are appearing in prepublication repositories those that have not yet passed peer review. Clearly this did not happen before and the truth is that it is making a lot of noise. There are many works in prepublication, especially from the beginning, which were later withdrawn or never published in specialized journals because they did not meet the criteria when they passed the peer review and, nevertheless, they remain.

The knowledge that is in those jobs spreads and you have to be very careful. We look at the works that are in prepublication with caution and even those that are published, we look at the data in detail. With the works that are in prepublication, even more so. In the case of this pandemic, it is true that this has been a boom. I no longer know how many publications there are per day of this virus and you have to be very selective.


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