The question was: “Do you have covid?” Now it’s: “How often have you had it?” In recent months we have both been (re)infected with covid. Many of us know people who are currently suffering from or have recently recovered from Covid. In the week ending June 24, an estimated 1 in 30 people (some 2.3 million people) in the UK were infected with Covid, a 32% increase on the previous week. (Also Read: Mild Covid Side Effects: Common Long Term Covid Symptoms To Watch Out for)
This often reflects a changing virus. The UK’s Health Security Agency reckons Omicron’s most prevalent variants, BA.4/5, account for more than half of new infections. The Centers for Disease Control in the US came to a similar conclusion.
While people are still hospitalized with covid and there are still covid deaths (especially among the most frail or unvaccinated), the vast majority of vaccinated people recover soon, although the illness is still rough for many. “In terms of its type of lethality, now the picture is much closer to seasonal flu. [coronavirus] emerged earlier,” Jonathan Van-Tom, formerly England’s deputy chief medical officer, told the BBC recently.
That leaves the question of how to manage the virus in the coming winter. On the one hand, countries with high levels of vaccination should have greater resilience and therefore fewer restrictions. On the other hand, the ability of the virus to mutate means that high levels of infection pose risks. We discuss what lies ahead for booster shots and other strategies to contain the epidemic.
Therese Raphael: Pfizer Inc. and Moderna Inc. Both have announced that their vaccine candidates targeting the omicron will provide more potent and potentially long-lasting immune responses. The FDA’s advisory panel on Tuesday recommended that updated Covid-19 booster shots contain the Omicron component. Do you think it’s OK to proceed with the Omicron-specific booster?
Sam Fazely: There was some uncertainty among FDA panel members about whether Omicron shots would defeat the current vaccine, but most believed that a vaccine containing the Omicron sequence would have a good chance of being beneficial against Omicron while providing protection against other variants. Yet, when you look at the data presented by the companies, both fail somewhat to show statistical superiority of their new vaccines against BA.1 compared to currently available shots.
TR: So what gives the committee confidence that they will prevail?
SF: Shots still showed improved antibody responses to BA.1, the basic omicron variant. But the committee said they need the BA.4/5 omicron shot, and I think regulators are going to ask the companies to update their vaccines again. Data on shots based on Omicron BA.1 induced three times less neutralization against BA.4 and BA.5 than BA.1. My math suggests that BA.4 and BA.5 are about 50% effective against infections after three to four months.
Pfizer has already started work on a vaccine to combat BA.4 and BA.5, and they showed some promising data at the meeting looking at neutralization in mice. If those findings carry over to humans, it would make for a better vaccine than one based on BA.1.
TR: That’s good, because most of us seem to have re-infections getting subsequent episodes. Summer is hardly here, but think ahead, should we do something different this winter? Especially if the flu is more prevalent than the previous two years? Or do natural immunity levels do the job of booster shots?
SF: Vaccines or prior infection do not prevent reinfections. I was fully vaccinated two weeks ago and tested positive for delta infection last October. Vaccination may delay it for a few months, but infections will eventually occur, even if Moderna is correct that a bivalent vaccine (treating both omicron and earlier variants) can induce long-lasting antibodies.
The concept of herd immunity is really dead when it comes to infection. What we need to do is ensure that we protect the most vulnerable segments of the population from severe disease, as the FDA panel has noted several times. Whether it’s people over 65 or 60 or 50, we see what the FDA says.
TR: We were told that mRNA technology can be easily adapted to adapt to emerging virus strands, so it’s surprising that we don’t yet have a booster shot for BA.1 on the market. why not
SF: Let’s not forget that this is the first time we are updating vaccines and the virus is changing very fast. However, Pfizer noted at the meeting that it could have high-volume production of the BA.4/5 Shot in September and the Moderna in October or November. This assumes that the FDA does not require large human trials with a couple of months of safety data. Both the companies are adamant that they can get the finished product within 90 to 100 days.
TR: When most vaccinated people think about the new covid variants these days there are two things. One is the risk of serious illness and the other is long covid. Have those risks changed in light of BA.4/5?
SF: Data from South Africa and Portugal do not indicate a major change in severity with BA.4/5 compared to BA.1. But don’t forget that this is in the background where many people were infected with BA.1 in the first omicron wave, so it’s not easy to compare.
It is worth mentioning a recent study showing increased severity after reinfections involving an omicron mutation. The problem is that the study was done on patient data from the US Department of Veterans Affairs electronic health records, with most subjects being over 60 years old and having comorbidities that increase the risk of severe disease. It is noteworthy that the majority of those included in the analysis were unvaccinated.
But its biggest drawback is what we call “confirmation bias,” which arises when some members of the target population are less likely to be included than others. For example, if most people have mild symptoms due to reinfection and don’t bother to be officially tested, the data skews toward more severe disease, leading to overestimation.
As for Long Covid, a recent study showed that Omicron causes fewer cases of Long Covid than previous variants. Note, this was in the UK, where most people have the triple-vaccination.
TR: It seems many of us are dealing with re-infections this winter. Are we likely to see another significant mutation with greater ability to evade immunity? Will updated vaccines be able to protect us against new mutations?
SF: The problem is that we don’t know what the next transformation will look like. Everyone thought any new mutation would be based on the delta mutation – instead it came from a host of mutations that some expected from left field. Using a bivalent vaccine may already be the first step to a multivalent shot. But, let’s not forget that the majority of people have been vaccinated or infected, so these booster shots are based on pre-existing immunity. That leads to immune suppression, where the body is pushed to make the same antibodies.
As for new mutations, so far large mutational jumps such as Omicron have been caused not by background immunity but by chronic infections in immunocompromised people.
If there are major changes in Omicron again, or if an entirely new mutation emerges, we may need to develop a vaccine for another mutation. But, if immune imprinting is not a problem, immunization with each successive infection or updated vaccine can extend the immune response and further reduce the risk of severe illness. Alas, antibody levels drop within a few months after each infection or vaccination, making the chances of re-infection and developing mild disease returning.
Therese Raphael is a Bloomberg opinion columnist covering health care and British politics. Previously, he was editorial page editor for The Wall Street Journal Europe.
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