Lack of context: While it’s a known fact that SARS-CoV-2 infection can protect against reinfection, the level of infection-induced immunity varies from person to person and SARS-CoV-2 infection carries an inherent risk of severe symptoms, sequelae or death. By contrast, vaccination is a safer and effective strategy to acquire immunity and can also enhance infection-induced immunity.
RECLAMACION: A study from Johns Hopkins on natural immunity to COVID-19 demonstrates that infection provides better protection than vaccination, challenging official vaccine recommendations for previously infected people; data in favor of infection-induced immunity are being ignored; vaccination isn’t the safest strategy
REVIEW
As of February 2022, more than 77 million people in the U.S. have been diagnosed with SARS-CoV-2 infection, with more than 4 million requiring hospitalization, and more than 910,000 deaths.
But many of these outcomes are preventable with vaccination. Clinical studies found that COVID-19 vaccines are safe and effective and have prevented the death of hundreds of thousands of individuals[1,2].
As both the COVID-19 pandemic and the COVID-19 vaccination campaign progressed, some questioned the need for previously infected people to get vaccinated, giving rise to debates about the relative pros and cons of infection-induced immunity versus vaccination-induced immunity.
A post published in February 2022 on the Family Research Council website suggested that novel scientific results were challenging the official recommendations in favor of vaccination. The post reported on a scientific study by Alejo et al. published on 3 February 2022[3] and extensively cited one of the authors, surgeon Marty Makary, who previously authored an opinion article for the Wall Street Journal about herd immunity that was reviewed by experts and found to be of very low scientific credibility.
The study by Alejo et al. reported that recovered COVID-19 patients possessed antibodies against SARS-CoV-2 circulating in their blood several months after the infection. The Family Research Council post claimed that “the conclusions of the [the study by Alejo et al.], are far from ‘fringe’” and that “for millions of Americans who have recovered from COVID-19, this is good news. But there couldn’t be worse news for Dr. Fauci”. Citing Makary, the post then concluded that vaccination wasn’t the safest strategy for acquiring immunity.
By its framing, the post built the narrative that the new study by Alejo et al. provided grounds for questioning the vaccination policy and reinforced the idea of infection-induced immunity as a safe and more effective alternative to vaccination.
Health Feedback reviewed the evidence and found the post’s claims and narrative to be misleading and an overstatement of the study’s conclusions.
The study by Alejo et al. doesn’t prove that infection-induced immunity alone is durable enough to exclude the need for vaccination
First, let us summarize what the study by Alejo et al. did. The authors recruited 816 people via public posts on social media and had them perform a serological test to detect the presence of antibodies against SARS-CoV-2 in their blood.
Antibodies are produced by the immune system upon infection or vaccination and are an important component of our immunity. Alejo et al. found that 99% of the volunteers who had been diagnosed with COVID-19 in the past had detectable antibodies against SARS-CoV-2. The median elapsed time since their diagnosis was eight months, and some volunteers had detectable antibodies levels even after 20 months.
However, the study also contained several limitations, which were also stated by the authors and which precludes drawing conclusions on whether past COVID-19 infections durably protect from reinfection, as we explain below.
First, it is important to distinguish two concepts: binding antibodies and neutralizing antibodies. Binding antibodies are able to bind onto parts of the virus. For example, anti-S antibodies bind to the Spike protein of SARS-CoV-2. But the fact that they bind to the virus alone doesn’t tell us whether they can stop the virus from infecting our cells. By contrast, neutralizing antibodies bind to the virus in such a way that they block its ability to infect[4]. Some binding antibodies can be neutralizing antibodies, but not all of them are. In order to determine if an antibody neutralizes a virus, specific assays must be carried out[5], but Alejo et al. didn’t perform any tests for neutralizing capacity.
While data indicate that the presence of binding antibodies is correlated with neutralizing antibodies[6], another study reported that only half of the people who had binding antibodies also exhibited neutralizing antibodies[7]. Therefore, the presence of antibodies doesn’t necessarily mean that these antibodies can neutralize the virus and protect against the disease. This is why the U.S. Food and Drug Administration warned that antibody testing cannot be used to determine whether someone is immune to SARS-CoV-2 reinfection, because these tests measure binding antibodies, not neutralizing antibodies.
Furthermore, the presence of neutralizing antibodies itself isn’t sufficient to predict that the individual won’t be vulnerable to reinfection, because it is unclear how much of those neutralizing antibodies will be necessary to offer protection. As the U.S. Centers for Diseases Control and Prevention (CDC) explained, there is currently “no specific antibody test or antibody threshold that can determine an individual’s risk of subsequent infection”.
Therefore, the results from this scientific study don’t provide conclusive evidence about whether recovered COVID-19 patients are protected against reinfection and how infection-induced immunity compares to vaccine-induced immunity.
Infection-induced immunity can provide protective immunity, but is riskier than vaccination
In its report of the study by Alejo et al., the Family Research Council post omitted important context to understand why relying on infection instead of vaccination to develop immunity in the population isn’t as safe and reliable.
It’s important to acknowledge that there is ample evidence that past infection protects from reinfection. Contrary to what the post claimed, this has been extensively studied and publicly available results demonstrate the existence of infection-induced antibody production and immunity[7,8,9,10,11] several retrospective studies showing that a first infection with SARS-CoV-2 decreased risk of subsequent infection by 80–93% for at least 6–9 months.
However, one important consideration is that SARS-CoV-2 infections come in many flavors. Some people remain asymptomatic, some develop mild symptoms on par with a cold, while others become very ill and require hospitalization. A serological survey found that the level of antibodies produced in response to SARS-CoV-2 infection varies greatly depending on disease severity[11]. The virus variant involved[12] as well as the viral load can differ between people[13]. Therefore, the potency and duration of infection-acquired immunity is unpredictable.
Grant McFadden, director of the Biodesign Center for Immunotherapy, Vaccines and Virotherapy at Arizona State University, told USA Today: “Recovery from COVID results in very variable immunity to a second infection, and this is reflected in the wide range of anti-spike antibodies in recovered patients. On the other hand, the immunity from the vaccines (especially the messenger RNA versions) is much more uniform, both in terms of protection from COVID and in anti-spike antibody levels.”
Furthermore, a major difference between infection-induced and vaccine-induced immunity is that vaccines carry fewer risks than infection. The aforementioned studies, which measure the amount of circulating antibodies in recovered COVID-19 patients or assess the risk of reinfection can only examine surviving patients, not the ones who died (survivorship bias). Therefore, the toll of SARS-CoV-2 infection isn’t taken into consideration in such studies, providing a false sense of security to infection-induced immunity.
By contrast, COVID-19 vaccines have been shown to be safe in large clinical studies[14,15,16,17]. Severe adverse events, like blood clots, may occur following vaccination in some cases but these are very rare. For example, researchers found that the risk of severe thrombosis was much higher following SARS-CoV-2 infection than after vaccination[18], undermining the article’s claim that vaccination isn’t a safer strategy.
Apart from the risks to the individual, there are risks to the community. Infected people become a vector for transmitting the virus to others. Some of these people may be more vulnerable to COVID-19 and are more likely to require hospitalization and die from COVID-19, such as those with certain medical conditions, like asthma and pregnancy.
Another group that is vulnerable to COVID-19 are people with weakened immune systems. This can include people on immunosuppressive drugs, like those who received transplants, and people whose immune systems don’t work properly because of illness, like cancer patients. This group cannot safely rely on infection-induced immunity for obvious reasons and there are many such people in the community. Although this population can be vaccinated to shore up their defenses against COVID-19, their ability to respond to the vaccine is limited due to their weakened immune system. They will therefore have to rely on the people around them getting vaccinated for protection.
Conclusion
A scientific study published in early 2022 by Alejo et al. reported that recovered COVID-19 patients could have SARS-CoV-2 antibodies in their blood during several months. However, contrary to what was suggested in a website post, the research article by Alejo et al. didn’t provide data proving that recovered COVID-19 patients are reliably protected from reinfection. While previous studies have shown that infection can induce a certain degree of immunity to COVID-19, vaccination remains the safer option when it comes to acquiring immunity. As immunity from previous infection may not persist, vaccination also offers benefits to previously infected people.
REFERENCES
- 1 – Meslé et al. (2021) Estimated number of deaths directly averted in people 60 years and older as a result of COVID-19 vaccination in the WHO European Region, December 2020 to November 2021. Eurosurveillance.
- 2 – Vilches et al. (2022) Estimating COVID-19 Infections, Hospitalizations, and Deaths Following the US Vaccination Campaigns During the Pandemic. Journal of the American Medical Association.
- 3 – Alejo et al. (2022) Prevalence and Durability of SARS-CoV-2 Antibodies Among Unvaccinated US Adults by History of COVID-19. Journal of the American Medical Association.
- 4 – Pang et al. (2021) Understanding neutralising antibodies against SARS-CoV-2 and their implications in clinical practice. Military Medical Research.
- 5 – Nie et al. (2020) Quantification of SARS-CoV-2 neutralizing antibody by a pseudotyped virus-based assay. Nature protocols.
- 6 – Gilbert et al. (2021) Immune correlates analysis of the mRNA-1273 COVID-19 vaccine efficacy clinical trial. Science.
- 7 – Nayak et al. (2021) Characterization of neutralizing versus binding antibodies and memory B cells in COVID-19 recovered individuals from India. Virology.
- 8 – Wajnberg et al. (2020) Robust neutralizing antibodies to SARS-CoV-2 infection persist for months. Science.
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- 11 – Peluso et al. (2021) SARS-CoV-2 antibody magnitude and detectability are driven by disease severity, timing, and assay. Science advances.
- 12 – Laurie et al. (2022) SARS-CoV-2 Variant Exposures Elicit Antibody Responses With Differential Cross-Neutralization of Established and Emerging Strains Including Delta and Omicron. The Journal of infectious diseases.
- 13 – Sui et al. (2021) Viral dynamics and antibody responses in people with asymptomatic SARS-CoV-2 infection. Signal transduction and targeted therapy.
- 14 – Walter et al. (2022) Evaluation of the BNT162b2 Covid-19 Vaccine in Children 5 to 11 Years of Age. The New England Journal of Medicine.
- 15 – Munro et al. (2021) Safety and immunogenicity of seven COVID-19 vaccines as a third dose (booster) following two doses of ChAdOx1 nCov-19 or BNT162b2 in the UK (COV-BOOST): a blinded, multicentre, randomised, controlled, phase 2 trial. The Lancet.
- 16 – Polack et al. (2020) Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine. The New England Journal of Medicine.
- 17 – Barda et al. (2021) Safety of the BNT162b2 mRNA Covid-19 Vaccine in a Nationwide Setting. The New England Journal of Medicine.
- 18 – Hippisley-Cox et al. (2021) Risk of thrombocytopenia and thromboembolism after covid-19 vaccination and SARS-CoV-2 positive testing: self-controlled case series study. The British Medical Journal.
