COVID-19: should we be worried about the effects of repeated infections?

More and more patients are coming to the clinic of Dr. Ziyad Al-Aly, chief of research and development at the St. Louis Veterans Health and Care Center and clinical epidemiologist at Washington University in St. Louis in Missouri, with what he describes as looking invincible. It was March 2022, and these patients were vaccinated against COVID-19 and had recently recovered from an infection. In their minds, the immunity combined with the vaccine would protect them from any harm related to the virus.

“I started wondering if that was really the case,” says Al-Aly. Intrigued, he turned to the Veterans Health Center medical records database.

, the months that have passed have clearly shown that the shield created by natural and vaccine-induced immunity is fragile: reinfection rates increase with the emergence of more contagious variants, with some people even reporting a third or a fourth infection. Studies have also shown that Omicron subvariants are better able to evade prior immunity.

(Read: COVID-19: What We Know About Omicron’s BA.2 Sub-Variant.)

If these epidemiological data demonstrate that reinfections with COVID-19 are possible, do these present a real risk for patients?

According to him, “the answer is clearly yes”. In June, Al-Aly published a study, which has not yet undergone the peer review process, which analyzed the medical records of more than 5.6 million US military veterans and showed that each new infection increased the risk of dying from any cause. It also increased the chances of getting other health problems, such as heart, blood and brain disorders, as well as diseases like diabetes, chronic fatigue and long COVID.

However, like other experts, Al-Aly recalls that many questions remain. We still do not understand why the reinfections were associated with an accumulated risk of these health problems among veterans of the Health Center, a population that does not represent the general public because it is rather male, elderly and white. We also don’t know if newer variants of COVID-19 are more likely to cause serious illness, or how long it will take for our immunity to weaken and make us vulnerable to reinfection.

“When you take all this into account, you see that many factors remain unknown, and that’s what makes the situation so complicated,” says Michael Osterholm, director of the Center for Infectious Disease Research and Policy at the University of Minnesota.

Here’s what scientists know today, and how they’re trying to solve this complex equation.

REINFECTIONS AND IMMUNITY

The risks of reinfection vary by disease. For some of them, such as measles, yellow fever and rubella, there is no need to worry about reinfection, because a first infection or vaccination confers long-lasting immunity. In general, this allows either not to be reinfected, or to have an infection so slight that the patient does not even notice it.

For other diseases, immunity weakens over time, making the person more susceptible to reinfections. The severity of the latter depends on many factors, including the underlying conditions, changes in the person’s health that may have challenged their immune system, the timing of the vaccination, and variations in the virus. himself.

Take the example of the flu. The virus mutes so frequently that it confuses the immune system: each new infection thus has the effect of a first flu. The body therefore cannot recognize and fight it, according to Al-Aly.

However, as a rule, reinfections are less severe than first infections, says Laith J. Abu-Raddad, an infectious disease epidemiologist at the Weill Cornell Institute of Medicine in Qatar. “It makes perfect sense: the immune system is prepared for it. We may have symptoms, but the response is so rapid that it eventually controls replication. »

Dengue, or tropical flu, is the exception that confirms this rule. It causes a rare phenomenon: immunity from a previous infection can make the situation worse by allowing antibodies that inadvertently help the virus invade host cells. There is no evidence that this is the case with SARS-CoV-2, and if it were, hospitalizations would likely be skyrocketing right now. But according to the scientists, it is important to rule out the possibility that the virus could take this direction.

(Read: Even mild forms of COVID-19 can damage our brains.)

IS THE RISK NON-EXISTENT OR REDUCED?

It is now clear that natural immunity and immunity conferred by a COVID-19 vaccine both weaken over time. The severity of reinfections, meanwhile, is hotly debated.

When Al-Aly’s report was published in June, the study caused controversy on social media because it seemed to suggest that reinfections were more serious than first infections. According to Al-Aly, this controversy was the result of a misinterpretation of his conclusions: his idea is that, even if most reinfections are less serious, it is still important not to take them lightly.

The researcher points out that “the essential point here is that the risk is not zero” and compares the situation to the aftermath of a fire in a house. “You can’t say to your family, ‘Now that I know how to put out a fire, let’s put the house back on fire.’ It’s entirely possible that your immune system is able to deal with it. But you know what’s even better? Not to be infected at all”.

Abu-Raddad agrees. His own research, published in the New England Journal of Medicine at the beginning of July, showed that people who have been vaccinated and who have already been infected in the past have approximately 97% less risk of contracting a serious, critical or fatal infection. In other words, the risk is “really, really low,” but each new infection increases the cumulative risk of harm from COVID-19.

According to Osterholm, further studies like Al-Aly’s would provide insight into how reinfections can worsen the harmful effects of COVID-19. For example, it is possible that an infection causes long-term inflammation in the blood vessels, which could lead to the development of blood clots and therefore a risk of accumulating heart attacks or strokes.

“It’s a good example of a subject that we really deserve to have better understood,” says Michael Osterholm.

REINFECTIONS AND LONG COVID

Another question worries scientists: does every new infection pose a risk of developing long-lasting COVID, a mysterious disease associated with a long list of disparate symptoms that can last months or even years after the initial infection? Although its causes remain unknown, scientists hope to determine whether or not immunity stands for some protection against long-lasting COVID.

So far, the results are mixed. A study published in September 2021 in The Lancet showed that people who received two doses of the COVID-19 vaccine were half as likely to develop COVID symptoms for a long time as unvaccinated people, suggesting that vaccines confer some protection. A study carried out in May 2022 and published in natural medicinewhich Al-Aly also authored, however, assumes that vaccination only reduces the risk of developing long-lasting COVID symptoms by about 15%.

(Read: How long does COVID-19 stay in the body?)

Al-Aly’s more recent study, on the other hand, suggests that long-lasting COVID is more common among people who have had multiple infections than among those who have only been sick once. Abu-Raddad clarifies that this observation does not mean that the second infection is necessarily more serious than the first, but that each new infection is a new risk of being affected by long COVID.

However, before we can begin to ask whether reinfections play a role in long COVID, scientists need to learn the causes, argues Benjamin Krishna, a postdoctoral researcher specializing in virology and immunology at the University of Cambridge.

According to some researchers, COVID could be prolonged by virus particles lingering in the body long after the acute phase of the disease has ended. Others know that this long form is caused by pre-existing autoimmune disorders or an immune system that has not reset properly from a previous illness. Krishna admits that he would be surprised if a second infection played an amplifying role in the appearance of long COVID: for him, it would be more like a game of chance.

“Every time you roll the dice, there’s a chance you’ll have chronic fatigue disease,” he says.

PROTECT YOURSELF FROM UNCERTAINTY

Scientists need more data before they can draw conclusions about the severity of COVID-19 reinfections. Al-Aly’s next step will be to determine whether the variants that currently dominate are more likely to cause serious reinfections than others.

While the Veterans Health Center database is not perfect, its sheer size is a definite advantage in disentangling the many variables at play. Indeed, with millions of medical records, the researcher will be able to analyze reinfection in subgroups of people who have, for example, only been infected with the Delta variant, compared to those who have been supported by Omicron and its variants. Will the BA.4 and BA.5 variants really evolve vaccines? Will they cause the same COVID risk for long? “These are open questions to which we all want to know the answers. »

Abu-Raddad would also retain that more studies look at the clinical characteristics of reinfections. Such an undertaking, however, would be colossal: to determine whether reinfections cause compound damage to the body would require a comprehensive analysis of each person after each infection.

Scientists will therefore need more time. Although the pandemic may seem long after more than two years, Krishna points out that this period is still relatively short to study the reaction of antibodies to a virus. A year and a half from now, we might as well find that reinfections are much worse, or get to a point where we’re all immune for life. You will then have to be patient.

Osterholm notes that a variant or sub-variant could also appear and result in an entirely new equation. “Each time we tried to get ahead of this virus, it made us question ourselves,” he recalls. He remains optimistic and thinks that scientists will manage to better control it.

In the meantime, experts say we have many keys at our disposal to protect ourselves from this uncertainty: getting vaccinated or having a booster dose if necessary, and taking other reasonable precautions, such as wearing a mask and avoiding situations of high risk of exposure to the virus.

“Every time we expose ourselves to re-infection, we are playing a very dangerous game,” says Abu-Raddad. “This specific infection may be the one that will be severe. »

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