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Covid-19: Two vaccine doses are crucial for protection against delta, study finds

BMJ 2021; 374 doi: (Published 16 August 2021) Cite this as: BMJ 2021;374:n2029

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The Delta variant: not the only reason for the latest surge

Dear Editor,

“Two vaccine doses are crucial…” says Elisabeth Mahase. (BMJ 2021;374n:2029, August 16) Perhaps she understates the case. In the US we are now told that everyone will need a third dose of the Pfizer or the Moderna vaccine. It looks like vaccinations will be never-ending, and at this point we need additional perspective.

According to the CDC’s COVID Data Tracker the number of US cases peaked on January 10, 2021 and was followed by a precipitous 80% decline over the next nine weeks. The decline was the result of herd immunity from natural infections, not from vaccine rollouts as was frequently asserted in news releases. The fact is, it wasn’t until January 9 that the first American was completely vaccinated. There was a small uptick in mid-April before the number of US cases again declined and bottomed out on June 18, 95% lower than the peak in January. The subsequent surge has been ascribed to the highly transmissible Delta variant (Ro~6.0), but the problem is somewhat more complex.

There has been a marked decline in vaccine immunity. In clinical trials the Pfizer vaccine was 95% effective against infection, but the Mayo Clinic has found that the effectiveness of the Pfizer vaccine against infection had dropped to 42% in July. ( A similar decline was seen in Israel. This has been accompanied by a huge jump in infection rates, including breakthrough infections in vaccinated individuals. (Wadman,, August 16) Based on our experience with mutating influenza viruses and the well-described waning in effectiveness of seasonal influenza vaccines, this might have been predictable. (NOTE: “95% and 42% effective” refer to relative vaccine effectiveness in populations. Absolute effectiveness, the real benefit to individuals, is only a tiny fraction of 1% for the prevention of serious illness caused by Covid-19. ( )

Shifty variants notwithstanding, it appears that the broad and durable increase in herd immunity from natural infections was interrupted by massive vaccine rollouts and replaced by the limited immunity from vaccines. This fact is reinforced by the discovery that some of the first US patients to recover from Covid-19 infections have potent antibodies against a diverse range of variants, including the Delta variant. (Reported by Jennifer Abbasi in JAMA 2021;326:589, August 17)

A related factor that has to be considered is antibody-dependent enhancement of infection (ADE) by vaccines. This is best known with dengue, RSV and measles vaccines. It occurs when non-neutralizing antibodies actually facilitate attachment of wild viruses to cells, thereby producing more severe illness in vaccinated individuals than in unvaccinated individuals. Iwasaki and Yang suggested that this is a potential danger with Covid-19 vaccines. (Nat Rev Immunol 2020;20:339) It may, therefore, be of vital importance that Yahi and colleagues have shown that vaccines directed against the original Wuhan/D614G strain produce antibodies that fail to neutralize Delta variants and allow the attachment of Delta viruses to cells. (Yahi et al, Journal of Infection 2021;16:58, August 16) Some of the breakthrough illnesses caused by the Delta variant in vaccinated individuals may be the result of this interaction.

It is not too late to step back from the relentless policy of universal vaccination in the US and the UK and concentrate on individuals at truly high risk. This would allow the large majority of young and healthy individuals to safely acquire broad and lasting immunity from natural infections, without the risks of adverse vaccine effects, known and unknown. It would also free up vaccines for more equitable distribution in populations that really need them. (Hassan et al, BMJ 2021;374:n2027, August 16) There are good reasons for some individuals to be hesitant about vaccines, and good reasons not to impose mandates.

ALLAN S. CUNNINGHAM 19 August 2021

Competing interests: No competing interests

19 August 2021
Allan S. Cunningham
Retired pediatrician
Cooperstown NY 13326 USA <