Is COVID-19 always protective against infection in the future?

Is COVID-19 always protective against infection in the future?
New research looks into a unique type of antibody response to the SARS-CoV-2 virus.
  • According to the findings of an unpublished investigation, one-fifth of those who have had COVID-19 may not have a specific type of antibody and hence may not be adequately protected against subsequent infections.
  • The researchers looked for core anti-N antibodies, which can only be produced by a natural infection, in volunteers who had previously been infected with SARS-CoV-2.
  • Individuals who smoked and those who had pre-existing medical issues were more likely to test negative for the antibodies.
  • The existence of this sort of antibody, according to the study’s critics, is a poor predictor of overall protection to future COVID-19 infection.
  • They also point out that surveys that rely on the core anti-N antibody may underestimate the prevalence of COVID-19 infection in the general population.

People who have been infected with COVID-19 may argue that they do not need to be vaccinated since their infection has rendered them immune to the virus.

However, according to a new study, almost a fifth of those who recover from COVID-19 may not be adequately protected against subsequent infections.

“Our data shows that the best way to protect yourself and others from COVID-19, even if you have had the virus previously, is to have two doses of vaccine and the booster when offered,” says the study’s lead scientist Dr. Tim Spector, professor of genetic epidemiology at King’s College London in the United Kingdom.

Anti-N antibodies were not produced in 19% of persons with a previously proven infection, according to the research.

The nucleocapsid protein identified inside SARS-CoV-2, the virus that causes COVID-19, is the target of these antibodies.

Anti-N antibodies can only be produced by a natural SARS-CoV-2 infection, whereas vaccinations cause antibodies to be produced against the virus’s spike protein, which is found on the outside.

The study looked at 8,193 persons who used the ZOE COVID smartphone app to report a past SARS-CoV-2 infection that was validated by a PCR test. In the following two weeks, each participant reported at least one symptom and accepted an offer to test for anti-N antibodies at home.

The response rate to their request for more testing was not disclosed by the researchers.

Between April and August 2021, the app’s creators sent out invitations. They didn’t say when the subjects were notified of their positive PCR findings.

Anti-N antibodies were found in 81 percent of the subjects, whereas 19 percent were negative.

Participants who tested negative were more likely to be smokers and to have one or more concomitant medical disorders.

Those who tested positive for COVID-19, on the other hand, tended to have more symptoms, or at least one of the classic COVID-19 symptoms of fever, persistent cough, and anosmia (a loss of taste and smell).

There was no indication of a reduction in anti-N antibodies in the subjects who tested positive for up to 9 months after infection. As a result, it appears that some participants registered their positive test as early as January or February 2021, but no information about this was included in the study’s press release or blog.

The research shows that not everyone who has received COVID-19 maintains their antibody response to the virus, according to Dr. Claire Steves, a scientist participating in the ZOE COVID studies and a senior clinical lecturer at King’s College London.

“This underlines the importance of getting vaccinated even if you have had exposure to the virus,” says Dr. Steves.

“Our data show that this is particularly important for people with other preexisting health conditions and people who smoke,” she adds.

The research’s weaknesses

Scientists speaking to the Science Media Centre in London pointed out various flaws in the work, which has yet to be published as a preprint or peer-reviewed manuscript.

Dr. Julian Tang, professor of respiratory sciences at the University of Leicester in the United Kingdom, commented, “These results are rather simplistic and incomplete.”

He pointed out that the study did not assess the reactions of participants’ T cells, which, like B cells, play an important role in the body’s adaptive immune system.

“T cell responses have previously been studied and have been shown to provide immunological protection even in the absence of an antibody (B cell) response — or symptomatic infection,” he said.

Furthermore, he stated that the study did not look at a kind of antibody known as IgA in mucous membranes. These are the body’s first line of defense against infection in the respiratory tract.

Dr. Tang also mentioned a study that indicated that people’s antibody responses (IgA and IgG to spike protein) to SARS-CoV-2 infection range from 0 to 33 days after onset of symptoms.

While the ZOE research was not particularly on anti-N antibody levels, it’s plausible that the timing of the sample influenced the results. Over a period of at least 9 months from the beginning of symptoms, they only examined a single sample from each subject.

Finally, he pointed out that the ZOE research did not look for antibodies against the virus’s other proteins.

“This is why natural infection with viruses generally provides longer lasting and broader immune protection — compared to vaccination,” said Dr. Tang.

“Vaccination after natural infection boosts the immunity to that particular vaccine target — but that background, primed level of immunity is still protective to some degree — probably for life — as we have previously seen with influenza,” he added.

The most important protein in the body

Dr. Simon Clarke, an associate professor of cellular microbiology at the University of Reading in the United Kingdom, concurred that the ZOE study’s testing for anti-N antibodies was a severe weakness.

He said that it remains possible that people had antibodies reactive to other coronavirus proteins, which conferred some protection against infection or disease, and this is an obvious research question to ask.

Dr. Clarke pointed out that, unlike surface proteins like the spike protein, which the virus employs to infect cells, the nucleocapsid protein is found in the virus’s core.

“Therefore, it’s difficult to envisage exactly how antibodies reactive to N-protein would work to block the virus interacting with our cells or to tag it for destruction by our white blood cells,” he said.

“It might be the case that someone with low anti-N-protein antibodies has a stonking amount of anti-spike protein antibodies and some killer T cells, which confers strong protection,” he added.

Is it necessary to have antibodies?

“It is well recognized that patients do not always acquire antibodies following [SARS-CoV-2] infection or vaccination,” said Dr. Paul Hunter, a professor of medicine at the University of East Anglia in the United Kingdom.

He claimed that antibodies aren’t required for COVID-19 recovery.

He noted a research that revealed that even patients with a compromised immune system, which makes it harder to manufacture antibodies, may only have moderate COVID-19 symptoms.

“Although people with lower anti-spike antibody levels tend to be more at risk of reinfection, there is still some degree of protection after infection even with no antibody response,” he said.

Because there is insufficient material in the press release and blog to evaluate degrees of bias and the influence of other kinds of immunity, it is impossible to interpret this study in terms of a future risk of infection following a natural infection. Dr. Hunter, on the other hand, sees one crucial implication from this study that is likely to hold up when it is peer-reviewed:

“One of the most important ramifications of this is that studies that used the prevalence of [antibodies] in a community to determine prior infection […] will very certainly have significantly underestimated the number of patients who have already had COVID-19 and recovered.”