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Vaccinating people who have had covid-19: why doesn’t natural immunity count in the US?

BMJ 2021; 374 doi: (Published 13 September 2021) Cite this as: BMJ 2021;374:n2101

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We must stop ignoring natural immunity - it’s now long overdue!

Dear Editor

There is now growing body of literature supporting the conclusion that natural immunity not only confers robust, durable, and high-level protection against COVID-19, but also better than vaccine induced immunity (1-5). Yet most scientific journals, media outlets, self-proclaimed health experts and public policy messaging continue to cast doubt. That doubt has real-world consequences, particularly for resource limited countries. We would like to review available data.

Infection generates immunity. The “SIREN” study in the Lancet addressed the relationships between seropositivity in people with previous COVID-19 infection and subsequent risk of severe acute respiratory syndrome due to SARS-CoV-2 infection over the subsequent 7-12 months (2). Prior infection decreased risk of symptomatic re-infection by 93%. A large cohort study published in JAMA Internal Medicine looked at 3.2 million US patients and showed that the risk of infection was significantly lower (0.3%) in seropositive patients v/s those who are seronegative (3%) (3).

Perhaps even more important to the question of duration of immunity is a recent study that has demonstrated the presence of long-lived memory immune cells in those who have recovered from COVID-19 (4). This implies a prolonged (perhaps years) capacity to respond to new infection with new antibodies.

In contrast to this collective data demonstrating both adequate and long-lasting protection in those who have recovered from COVID-19, the duration of vaccine-induced immunity is not fully known - but breakthrough infections in Israel, Iceland and in the US suggests a few months. Before CDC decided to stop collecting data on all breakthrough infections at the end of April, 2021, it reported >10,000 breakthrough infections (2 weeks after completion of vaccination) in the US, with a mortality of ~2% (6). Booster COVID vaccine recommendations have been already announced in Israel and in the US proving vaccine failure within 6 months.

How should we use the collective data to prioritize vaccination? These new data support simple and logical concepts. The goal of vaccination is to generate memory cells that can recognize SARS-CoV-2 and rapidly generate neutralizing antibodies that either prevent or mitigate both infection and transmission. Those who have survived COVID-19 must almost by definition have mounted an effective immune response; it is not surprising that the evolving literature shows that prior infection decreases vulnerability. In our view, the data suggest that people confirmed to have been infected with SARS-CoV-2 may not need vaccination. We should not be debating the implications of prior infection; we should be debating how to confirm prior infection.

Manish Joshi, MD
Thaddeus Bartter, MD
Anita Joshi, BDS, MPH

1. Sivan Gazit, Roei Shlezinger, Galit Perez et al. Comparing SARS-CoV-2 natural immunity to vaccine-induced immunity: reinfections versus breakthrough infections
medRxiv 2021.08.24.21262415; doi:
2. Hall VJ, Foulkes S, Charlett A et al. SARS-CoV-2 infection rates of antibody-positive compared with antibody-negative health-care workers in England: large, multicentre, prospective cohort study (SIREN). Lancet. 2021
3. Harvey RA, Rassen JA, Kabelac CA, et al. Association of SARS-CoV-2 Seropositive Antibody Test With Risk of Future Infection. JAMA Intern Med.
4. Turner, J.S., Kim, W., Kalaidina, E. et al. SARS-CoV-2 infection induces long-lived bone marrow plasma cells in humans. Nature 2021
5. Wang, Z., Yang, X., Zhong, J. et al. Exposure to SARS-CoV-2 generates T-cell memory in the absence of a detectable viral infection. Nat Commun 12, 1724 (2021).
7. Kuehn BM. High-Income Countries Have Secured the Bulk of COVID-19 Vaccines. JAMA. 2021;325(7):612

Competing interests: No competing interests

13 September 2021
Thaddeus Bartter, MD; Anita Joshi, BDS, MPH