Vaccine Policy Should Consider the Power of ‘Hybrid Immunity’

As a physician in a Covid-19 care unit, I celebrate the vaccines as one of medicine’s greatest triumphs. They provide extraordinary protection against severe disease and death, and are the world’s best option for returning to a more normal life. As a scientist and lead investigator for a study on Covid-19 immunity, I have also come to appreciate the significance of so-called natural immunity acquired by those who have had Covid-19, and the power of “hybrid immunity” — the protection gained when such people also get vaccinated.

While the concept of natural immunity has often been misused by people opposed to vaccine mandates, public health officials and scientists should be open to the evidence. Research, including my team’s study of the immune responses of nearly 2,150 health care workers in Sweden after infection with SARS-CoV-2 — the virus that causes Covid-19 — and vaccination, suggests that the protection gained from infection is long-lasting and that it can be significantly bolstered by a single Covid-19 vaccine dose.

These insights should be factored into vaccine policies. For example, should vaccine mandates and passports make exceptions or accommodations for people who have already had Covid-19? Should children who have been infected receive two vaccine doses when they might be well protected with one? These are just some of the questions scientists and vaccine policymakers should be asking.

Infection, like vaccination, trains the immune system to fight off disease. In both cases, antibodies are produced by what’s known as memory B cells, which help prevent future infection. Memory T cells then support antibody production and control the infection by killing infected cells.

But the immunity provided by an infection versus a vaccination differs in many ways. For example, a Covid-19 vaccine teaches the immune system to target a specific part of the virus, the spike protein, over a few hours or days. When people are infected with SARS-CoV-2 their immune system is exposed to the whole virus for several days or weeks. This provides the immune system with significant time to build a comprehensive defense if the infected person survives. These distinctions result in broader immunity for people who are infected versus people who are vaccinated.

The immune cells that a person develops after infection also continue to evolve to become more potent and diverse. Once a person who was previously infected also gets vaccinated against Covid-19, these cells are awakened, and they start generating antibodies that may be able to help tackle new variants. This is what scientists call hybrid immunity.

No one should ever try to get Covid-19 to gain the protection of so-called natural immunity. Even a mild infection carries the risk of longer-term serious health problems.

But there are settings in which someone’s previous Covid-19 infection should be taken into consideration for vaccine policies, and some countries are already doing so.

As of late September, 14 European countries, including France, Germany, Italy and Spain recommend that people without underlying health conditions who have already been infected receive one dose of a vaccine (for vaccines with a two-dose schedule). Israel offers a temporary “green pass,” an immunity passport, to people who have recovered from Covid-19 within the last six months regardless of their vaccination status. The European Union allows travel between member states if citizens or residents have a positive PCR test showing they’ve recovered from Covid-19 in the past 180 days. Britain also accepts proof of a positive Covid-19 test result within 180 days for its Covid Pass.

But these are exceptions; many countries still recommend two Covid-19 vaccine doses for everyone and issue vaccine mandates that make no exception for people who have had Covid-19 previously.

The rationale behind such blanket recommendations is that not everyone mounts a strong immune response after infection. And data shows that while so-called natural immunity can last a long time — possibly up to a year — the duration varies based on factors such as a person’s age, medical conditions and disease severity.

But studies also suggest that otherwise healthy people who previously had Covid-19 do exhibit equal or higher levels of immune responses after one vaccine dose compared to people with two doses and no prior infection. People with hybrid immunity also don’t appear to gain much more immunity from a second dose, which suggests second shots may not be necessary for them (though future boosters may still be needed).

A more tailored approach may be worth considering for certain groups.

Children, for example, are far less likely than adults to become severely ill from Covid-19. And there is a risk, though it is rare, of vaccine-related myocarditis (inflammation of the heart) which is more common in younger people, in particular boys, after their second dose of an mRNA vaccine. Some countries like Norway and Britain give only one dose of the Pfizer vaccine to children age 12 to 15 to avoid potential risks like myocarditis from the second dose.

But giving a single dose to all children comes with concerns that one dose might not provide strong and long-lasting protection. Whether a child has had Covid-19 or not isn’t a part of these vaccination decisions — and should be.

If scientists and policymakers consider the power of hybrid immunity, it’s reasonable to recommend a single dose for children without serious health problems who have had Covid-19. If parents are unsure if their children have been previously infected, antibody tests could be given when they get their first vaccine dose. Although these tests may not pick up all children who have had Covid-19, they would pick up most, and only children without confirmed infection could be called back for a second dose. Such an approach could also help free up doses for the many other countries with low vaccine supply and at-risk adults who haven’t been vaccinated. The approach should at least be considered for further study.

There are other reasons for not factoring natural immunity into decisions about vaccination. Adding antibody tests to determine who has had Covid-19 to an already logistically challenging vaccine rollout may be difficult. In countries like the United States with deep political divides concerning the vaccines, a “one size fits all” strategy may be preferable over a more tailored approach that could sow confusion, rouse anti-vaccine sentiment and interfere with the issuing of vaccine passports.

But recognition of prior infection as a strong contributor to immunity must not be mistaken as an anti-vaccination stand. The effectiveness of the Covid-19 vaccines is not in question. But a full vaccine course is not the only way that people can be protected from Covid-19. Open discussions about the risks and benefits of tailored approaches for groups like children are worth having.

Charlotte Thålin is the lead investigator of a study on Covid-19 immunity at the Karolinska Institute in Stockholm, where she is also a physician at Danderyd Hospital.

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