Variants and Vaccines

Photograph Source: Travis Wise – CC BY 2.0

In late 2020 the British noticed that coronavirus cases were spiraling upward in the region of Kent. The culprit turned out to be a variant of the COVID-19 virus identified in September, Mutations in the genetic make-up, the RNA, lead to variants. They are still COVID-19 viruses, but they can behave differently. The variant first identified in Kent, UK (scientific name B.1.1.7, WHO name Alpha) is more infectious than the original strain which emerged from Wuhan, China.

The number of other people that each infected person infects is called the basic reproduction number, or R0 (“R naught”), in epidemiological parlance. It’s a measure of the biological characteristics of an infectious agent, but it can be affected by social and environmental conditions and human behavior (e.g. crowding vs. social distancing, ventilation, facemasks). The R0 of seasonal influenza is 1.3. The R0 of measles is around 15. As it emerged in Wuhan, the R0 of the original COVID-19 strain was 2.4—2.6. The R0 of the Alpha variant is 4 to 5.

The Beta variant (scientific name B.1.351) arose in South Africa in October 2020. It was found that the AstraZeneca vaccine was ineffective against the Beta strain – leading to a pause in its use there in February 2021. (The AstraZeneca vaccine may make a comeback in South Africa, since it is effective against the Delta strain, which is poised to become dominant there.)

The Gamma variant (scientific name P.1) arose in Brazil in December 2020. Manaus, in the Amazon, had had a severe epidemic of COVID-19 during 2020, such that it was estimated that 50% of its residents had been infected by October 2020. In December, Manaus experienced a second wave, more severe than the first, during which the Gamma strain was detected. Of note, Gamma caused infections in individuals who had been previously infected – demonstrating that an infection with one strain of COVID-19 might not lead to immunity against a different strain.

The Delta variant (scientific name B.1.617.2) was responsible for the April-June 2021 second wave in India. At its peak, India was recording nearly 400,000 cases and over 4000 deaths per day, believed to be a severe undercount. The true cases may have been over a million per day, and true deaths may have been 10 to 15,000 per day. Between January and June 2021, 3 to 4.7 million excess deaths occurred in India. The Delta variant has a R0 of 5 to 8. Each case of Delta leads to 5 to 8 more cases. An infected individual is likely to infect everybody else in the household. This gives it an evolutionary advantage over even the Alpha variant. The WHO declared Delta a “variant of concern” on May 10. By mid-July Delta was the dominant variant in the U.S.

A study involving 4272 cases of Delta from Public Health England (published July 21 in the New England Journal of Medicine) concluded that two doses of the Pfizer-BioNTech vaccine was 88% effective and  that two doses of the AstraZeneca vaccine was 67% effective in preventing symptomatic COVID-19. (One dose of Pfizer was only 35.6% effective against Delta.) In contrast, according to Israeli data from mid-June to mid-July 2021, the Pfizer vaccine was only 39% effective in preventing COVID-19 infection, but this data has not been published in the peer-reviewed literature. Of note, however, vaccination was 91.4% effective in preventing severe COVID-19. On July 22, Los Angeles County Public Health Director Barbara Ferrer announced that 20% of the COVID-19 cases in LA County over the past month were breakthrough infections in individuals who had been fully vaccinated.

Parts of the world that have vaccinated their populations with the Sinopharm and Sinovac vaccines from China are experiencing outbreaks. Indonesia, which is currently experiencing a major Delta wave, has relied on vaccines from China.

While the currently available mRNA vaccines (Pfizer and Moderna) are not quite as effective against Delta as it was against the original COVID-19 virus, they nevertheless prevent hospitalization and death. Currently, in the U.S., 97% of those hospitalized with coronavirus and 99.5% of those dying from coronavirus are unvaccinated. Clearly, we must continue to promote vaccination.

Delta has put “herd immunity” nearly out of reach, however. The percentage of the population that needs to be immune [whether from vaccine immunity or from infection with the original virus (I hesitate to say “wild type”) or a prior variant] to achieve herd immunity is derived from R0. From the estimate that the original COVID-19 strain had an R0=2.5, the

% needed to achieve herd immunity = 1 – 1/R0 = 1 – 0.4 = 60%

which is close to (though a little less than) 70%. This is the basis for government officials telling us that we need to vaccinate 70% of the population. Since the R0 of Delta is estimated to be from 5 to 8, using R0=6,

% needed to achieve herd immunity = 1 – 1/R0 = 1 – 0.17 = 83%

The next variant of concern (or the one after, or the one after that . . . twenty letters left to go in the Greek alphabet) may not only be as contagious as Delta. It may also more easily escape vaccine immunity (like Beta with AstraZeneca) or natural immunity (like Gamma). It is entirely plausible that vaccines will need to be reformulated to match future variants.

As difficult as it may be to achieve, we must continue to try to achieve herd immunity. In the U.S., FDA approval will allow employers and schools to mandate vaccines. During the current Delta wave, because of breakthrough infections, even the vaccinated should maintain social distancing and wear masks indoors. With businesses pressuring government officials not to impose lockdowns, it will be up to the informed to take measures on their own.

The current Delta wave will also pass. Many will die, but because many of the elderly and infirm have been vaccinated, not as many as in the dark days of January. Since the beginning of COVID-19, the epidemic curves of the U.S. and the U.K. have been shaped similarly. Of course, the U.S. has five times the population of the U.K. (331.4 million vs 68.2 million), so its absolute numbers of cases has generally been approximately five times that of the U.K. – except since late June, when Delta, which hit the U.K. earlier, gave the U.K. an absolute number of daily cases higher than that of the U.S. During the Delta wave, the daily cases in the U.K. approached those of its worst days in early January. The U.K.’s Delta wave appears to have peaked, however. The U.S.’s Delta wave is still in its exponential climb.

Regardless of what the future may bring, the task at hand is to deliver life-saving vaccines to the world. To stave off more India-like disasters around the world, we must support an accelerating, global Covid immunization campaign. The Biden Administration’s decision to support the suspension of intellectual property rights for vaccine manufacturing was a step in the right direction. On June 9, the US announced that it will purchase and donate 500 million doses of the Pfizer vaccine. This is clearly inadequate when fewer than 5 doses per 100 people have been administered in Africa (total population 1.34 billion). U.S. taxpayers subsidized the development of the mRNA vaccines. It is a travesty that Pharma profits so handsomely from public investment. Life-saving vaccines are public goods that belong to the people.

Seiji Yamada, a native of Hiroshima, is a family physician practicing and teaching in Hawaii.

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