Thu. May 19th, 2022

A masked woman makes a heart symbol with her hands.
Enlarge / Dr. Silvia Gelvez gestures after receiving a dose of the Pfizer BioNTech vaccine against COVID-19 at Colombia University Clinic in Bogota on February 18, 2021.

As long as there have been vaccines against COVID-19, there have been arguments as to why people should not get these vaccines. One of the more persistent — and hairier — arguments is that people who have already been infected with the pandemic coronavirus, SARS-CoV-2, do not need a vaccine. An infection will generate immune response similar to those generated by vaccines, mindset. So why waste coveted vaccine doses on people who already have an immune response to the virus – which can also unnecessarily put these people at risk for vaccine side effects, but rare?

That is a reasonable question and there is a legitimate scientific debate about it. There are also different approaches to the issue with regard to public health policy. In Israel, for example, people who have recovered from COVID-19 after testing positive for a PCR test can get a “Green Pass” vaccination that is valid for up to six months. The passport gives them access to various places, just as it does for people who are fully vaccinated. In the EU, some Member States offer a similar “Digital COVID Certificate” to people who have recovered from COVID-19 and received only one dose of a two-dose mRNA vaccine regimen.

In the United States, however, public health officials are unequivocal in their approach: People are categorized as either vaccinated or unvaccinated, regardless of previous infection. It is an approach with many strengths, including robust scientific data that supports vaccination for people who have recovered. These data – which we will discuss below – have consistently shown that immune responses from natural infections are extremely variable and thus unreliable. Vaccines, on the other hand, have repeatedly been shown to generate highly protective immune responses.

The vaccines are also remarkably safe, with few types of serious side effects that occur only extremely rarely. One of the most worrying side effects is myocarditis (inflammation of the heart muscle). However, even there, the incidence of myocarditis in the most vulnerable group (men aged 12 to 29) is estimated to be only 41 out of a million, and the cases are generally mild.

Comparing it to actual COVID-19 infections — which can cause serious illness even in young, healthy people and can cause persistent, months-long symptoms in up to half of those infected — there is no competition. Vaccines are safer. And they are just as safe for people who have recovered in the past. People with previous COVID-19 cases are not more likely to get serious side effects from vaccines than people who have not been infected before, although they may have more side effects.

The US approach also has logistical advantages. Simple categories of “vaccinated” and “unvaccinated” skip the messy and difficult step of finding out who has been infected and when. From the early stages of the pandemic, the United States has struggled — and still struggles — to roll out accurate, widely available tests for SARS-CoV-2. Many people who have been infected never officially tested positive. Others assumed they were infected when in fact they had actually had one of many other respiratory infections. And antibody tests that look for signs of previous infections are notoriously inaccurate.

Although opponents claim that mass vaccination is driven by “evil companies” for a huge profit at any cost, the fact is that vaccines are extremely safe and give recovered people a strong, lasting protection against a virus that has already killed more than 700,000 Americans .

Efficiency and variation

This is not to say that there are no weaknesses in the US approach. First, the approach can make vaccines look bad. In many cases, the effectiveness of the vaccine is measured by comparing cases of COVID-19 between vaccinated and non-vaccinated people. But in the United States, they include unvaccinated people who have no immunity and recovered people who have some immunity and are therefore expected to have fewer infections. This reduces the number of cases in the unvaccinated group and ends up lowering the vaccination effectiveness estimates.

Nevertheless, the estimates for the effectiveness of the vaccine are extraordinarily good. A recent study showed that the Pfizer-BioNTech mRNA vaccine persisted with 90 percent efficacy against COVID-19 hospitalization for at least six months. A separate study showed that the Moderna mRNA vaccine was 93 percent effective against hospitalizations among people without immunocompromising conditions. Johnson & Johnson’s vaccine was 71 percent effective.

And again, these would mean that you have to spend for these processes. How much lower? It’s unclear. Since the onset of the pandemic, researchers have repeatedly noted that immune responses generated by SARS-CoV-2 infections vary widely, with some of the weaker responses seen in people with mild illness and stronger response in people with severe illness.

In a study Ars reported back in June last year, researchers looking at SARS-CoV-2 antibodies in people who had recovered found that the difference between the highest and lowest levels varied by a factor of over 1,000. The researchers saw even more variation when they looked at neutralizing antibodies – those that are known to bind to the virus and prevent it from infecting cells. Neutralization of antibody levels in recovered humans varied over a range of 40,000 times, and up to 20 percent of humans had no detectable level of neutralizing antibody.


Of course, antibodies are not the entire immune response that determines whether a person becomes infected or not, and if they do, how severe their infection becomes. However, antibodies can provide a reasonable measure of how well someone is protected. A study late last year that tracked 12,500 healthcare workers found that the higher the antibody levels, the lower the risk of infection. And in May of this year, the researchers found “a remarkably strong” relationship between neutralizing antibody levels and vaccine protection.

A fundamental difference between the immune responses of vaccines and natural infection is their specificity. In a natural infection, whole SARS-CoV-2 viruses infect cells in the airways. Reactive immune cells can target any number of facets of these viruses. This creates a relatively large diversity of antibodies that bind to different bits of SARS-CoV-2. The vaccines, meanwhile, serve only up to the immune system’s key extract of SARS-CoV-2 – namely the spike protein of the virus. This is the protein that SARS-CoV-2 uses to enter human cells, and it is a key target for the neutralization of antibodies. All antibodies in the vaccinated will target the spike protein. Although vaccinated people have less antibody diversity than previously infected humans, they have high levels of highly targeted antibodies. Think of it as the difference between chasing a small virus with a shotgun and a sniper rifle.

With variable immune responses after infection comes variable real data on how well previous infection protects against re-infection, which has led to the different public policy approaches. In a study conducted at the Cleveland Clinic and posted online in June, researchers found that among 52,238 employees, there were no differences in COVID-19 case rates between employees who were unvaccinated but previously infected, vaccinated, and previously infected and vaccinated people without previous infection. “Individuals who have had SARS-CoV-2 infection are unlikely to benefit from COVID-19 vaccination,” the authors concluded.

But in another study published in August by the Centers for Disease Control and Prevention, researchers looked at the vaccination status of more than 200 Kentucky residents who had tested positive for SARS-CoV-2 by 2020 and then tested positive again during of May and June 2021. CDC researchers found that people who were previously infected but not vaccinated were 2.34 times more likely to be re-infected than people who were previously infected and fully vaccinated.

Delta difference

The time frame for the CDC study coincides with the increase in the delta coronavirus variant in the United States, which may also play a role in levels of protection against previous infection. In a French study published in July in Nature, researchers examined antibodies in 56 unvaccinated people who had recovered from a SARS-CoV-2 infection before the increase in delta. Six months after their infection and in the midst of the increase in the delta, the researchers found that their neutralizing antibody levels were 4 to 6 times lower against the delta than they were against previous variants.

The researchers then looked at another group of 42 people who had gone a year since a SARS-CoV-2 infection. Of the 42, 26 were still unvaccinated and 21 had received a dose of a vaccine. At that time, the unvaccinated had 26 extremely low levels of neutralizing antibodies to all SARS-CoV-2 variants, especially delta. Many people had no detectable levels of neutralizing antibody to delta. The vaccinated group, meanwhile, had high levels of neutralizing antibody equal to or above the levels seen in humans who were fully vaccinated.

That finding has played out in several studies. For example, a March study by researchers in Washington State found that a dose of an mRNA vaccine in humans who had recovered increased levels of neutralizing antibody to all SARS-CoV-2 variants up to a thousand-fold. And several other studies have found that post-infection vaccine doses cause soaring increases in antibody levels. Some data have also suggested that antibody levels in the recovered vaccinated are even higher than people who have only been vaccinated.

Overall, the variable immune responses to infection, lower delta neutralization and the clear boost in protection against a highly safe, highly effective vaccine are a strong argument for vaccinating the recovered.

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