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Scientists are learning about why people get COVID-19 twice. Newsday LLC/Getty Images
  • Some people who have recovered from COVID-19 can contract an infection again.
  • A new study found a man had a severe case of COVID-19 last April and a mild case 4 months later.
  • Now new SARS-CoV-2 variants have emerged that may circumvent the immune protection that people gain when they successfully fight off the virus.

Most people who recover from COVID-19 have some protection against the new coronavirus, SARS-CoV-2, that causes this disease due to antibodies and other immune responses.

Some research suggests this protection lasts for at least 8 months.

But reinfections are possible, even just a few months apart, a group of physicians from Yale University School of Medicine warned today in BMJ Case Reports.

They reported on a man in his 40s who had a severe case of COVID-19 last April and a mild case 4 months later.

In April and August he tested positive for SARS-CoV-2. In between, he had four negative tests.

This isn’t the first case of someone contracting the new coronavirus a second time.

However, it’s difficult to know how common reinfections are because scientists don’t routinely monitor for them, and symptoms may be less noticeable the second time around.

“A lot of reinfections are very mild. People don’t even realize they have gotten reinfected,” said Theodora Hatziioannou, PhD, a virologist at Rockefeller University. “So, I would guess that [reinfection] actually happens a lot.”

A study of more than 20,000 healthcare workers in the United Kingdom found that of the more than 6,600 people who had a previous SARS-CoV-2 infection, only 44 contracted it again — less than 1 percent.

In addition, people who had a previous infection were 83 percent less likely to contract an infection again during the 5 months of the study compared to those with no prior infection.

The results were published Jan. 15 on the preprint server medRxiv. The study hasn’t been peer reviewed, so the results should be viewed with some caution.

These results, though, are in line with another study carried out by Dr. Stuart C. Sealfon, a professor of neurology, neuroscience, and pharmacological sciences at the Icahn School of Medicine at Mount Sinai, and colleagues.

This group followed more than 3,000 Marine recruits attending basic training in South Carolina, including almost 190 recruits who had a previous SARS-CoV-2 infection.

During the 6 weeks of the study, around 10 percent of those with a prior infection contracted another infection. However, they were 82 percent less likely to contract an infection compared to recruits with no previous infection.

“The risk of reinfection is roughly one-fifth the risk of getting a first infection,” Sealfon said. “So, the previous infection provides considerable protection, but reinfection is far from rare.”

The study was published Jan. 29 on medRxiv. It’s also awaiting peer review.

Since these studies were carried out, new SARS-CoV-2 variants have emerged that may circumvent the immune protection that people gain when they successfully fight off the virus, at least somewhat.

“Some [SARS-CoV-2] variants may increase the risk of reinfection beyond what we have seen [in our study],” Sealfon said.

Every time this coronavirus replicates — which it does quite rapidly — there’s a chance that a mutation will occur. This is true of all viruses.

Scientists estimate that the RNA genome of SARS-CoV-2 acquires around two single-letter changes each month, which is about half as fast as the influenza virus.

Some mutations are harmful to the virus; these are eventually eliminated from the virus population or reduced to low levels. Other mutations, though, give the virus an advantage over our immune system.

Scientists are currently keeping an eye on three rapidly spreading variants first identified in the United Kingdom (B.1.1.7 variant), South Africa (B.1.351 variant), and Brazil (P.1 variant).

Both the B.1.1.7 variant and the B.1.351 variant are thought to spread more easily and quickly. B.1.1.7 may also cause more severe disease, but scientists are still investigating this.

Another concern is that certain mutations may enable a variant to evade the immune system, which could increase the chance of reinfection. Scientists are carrying out research to determine how likely this is.

In one study that hasn’t been peer reviewed, researchers collected serum samples from 44 people who had recovered from COVID-19. These samples contained antibodies produced by their immune system to fight the coronavirus.

Researchers found that serum samples from 21 of these participants weren’t capable of neutralizing the B.1.351 variant in the laboratory. The virus was also partially resistant to most of the remaining samples.

The results highlight the possibility of “reinfection with antigenically distinct variants,” the authors reported.

There have also been documented cases of reinfections with a new variant, including a man in Israel who contracted a second infection with the B.1.351 variant, and a person who contracted a second infection with the P.1 variant.

As with the man described in BMJ Case Reports, the Israeli man had mild symptoms during his reinfection. This suggests that even when reinfection occurs, there’s still enough immune protection to prevent more severe disease.

The ability of certain mutations to evade the immune system isn’t just a concern for people who’ve had COVID-19, but also for the ability of COVID-19 vaccines to protect people who have never contracted an infection.

COVID-19 vaccines protect people by priming the immune system to fight a SARS-CoV-2 infection without actually causing COVID-19.

The side effects experienced by people who have been vaccinated aren’t symptoms of the disease. Rather, they’re a sign that the immune system is learning to recognize and fight the coronavirus.

Research carried out in the laboratory by Hatziioannou and her colleagues suggest that certain SARS-CoV-2 mutations in the spike protein may allow variants to evade the protection offered by the COVID-19 vaccines.

SARS-CoV-2 uses the spike protein to infect cells in the body by binding to a receptor on the surface of human cells called ACE2.

In Hatziioannou’s study, researchers collected plasma from 20 people who had received the Moderna-NIAID or Pfizer-BioNTech vaccine. They tested this against pseudoviruses containing certain spike protein mutations found in the new SARS-CoV-2 variants.

The antibodies of people who had been vaccinated were less effective against the pseudoviruses that contained these mutations compared to pseudoviruses with the original spike protein configuration.

This study was published on the preprint server bioRxiv. Hatziioannou said the paper has been accepted for publication in the journal Nature.

Vaccine-makers have also been testing their vaccines in the laboratory to see how well they work against the new variants, with mixed results.

Preliminary data suggests that the Pfizer-BioNTech vaccine works against the B.1.1.7 variant.

Moderna also reported preliminary results from laboratory studies showing that its vaccine protects against the B.1.1.7 variant, although researchers did see decreased protection against the B.1.351 variant.

In phase 3 clinical trials, vaccine-makers Johnson & Johnson and Novavax found that their vaccines had lower efficacy in South Africa, where the B.1.351 variant has spread widely.

While the emergence of SARS-CoV-2 variants that can evade the immune system is concerning, Hatziioannou points out that the immune system has ways of dealing with the virus other than the antibodies that it is evading.

In addition, some of the phase 3 vaccine trials, such as Moderna’s, show that the vaccines stimulate the immune system to produce high levels of antibodies, often higher than those acquired through natural infection.

So, even if a variant reduced the antibody effectiveness tenfold, the vaccine would still be effective against the virus, Jesse Bloom, PhD, an evolutionary biologist at the Fred Hutchinson Cancer Research Center in Seattle, told The New York Times.

Also, if the variants reduce the overall effectiveness of the vaccines, people might still be protected against severe disease.

This seems to be the case with the Johnson & Johnson vaccine. The vaccine was 85 percent effective against severe disease, even in South Africa.

Vaccine-makers, though, are already preparing to update their vaccines to better protect against variants, should the need arise.

Reducing severe disease — even if people get mild symptoms — will still reduce hospitalizations and deaths.

Dr. Eric Topol, director and founder of the Scripps Research Translational Institute, pointed out on Twitter that with six phase 3 COVID-19 vaccine trials completed so far, no one who has received a vaccine has died from COVID-19.

“Not a single death or hospitalization in the vaccine arms due to COVID-19 in over 75,000 participants,” he said.

Hatziioannou points out that the primary goal of the vaccine trials wasn’t to prevent all infections, but to reduce more serious disease.

For Moderna-NIAID and Pfizer-BioNTech, the primary endpoint was to prevent symptomatic infections. For Johnson & Johnson, it was to prevent moderate or severe disease.

“Protection from severe disease can be achieved without stopping transmission,” Hatziioannou said, but “I think that the [COVID-19] vaccines will still protect you from disease from these new variants.”

Unless we start randomly testing people more often, we may never know how frequent coronavirus reinfections are. But Sealfon thinks that just being aware of the risk is enough.

“It is important to know there is a surprisingly high rate of reinfections,” he said, “so people previously infected [should] get vaccinated and continue to utilize masks and other infection prevention procedures to protect themselves and others.”