Forget herd immunity. You have a binary choice: get vaccinated, or get COVID-19. It's not more complex than that. If you are fully vaccinated, you are unlikely to get COVID-19 and have almost no chance of dying. If you don't get vaccinated, COVID-19 will find you. When it does, you will have about a 1% chance of dying and about a 25% chance of long-term sequelae. You will also lend your body to the virus as a bioreactor for producing yet more infectious variants. Thanks a lot.

Introduction

With the emergence of new variants of SARS-CoV-2, another wave of COVID-19 is crossing the globe (asamonitor.pub/3ki9qb3). Driven by the Delta variant, new cases are surging in two of the most vaccinated countries in the world, Israel and the U.K. (asamonitor.pub/3hGdrnR). See Figure 1. The Delta variant has been rising rapidly in the United States and now accounts for more than half of the new cases of COVID-19 (asamonitor.pub/3BfRTq7). See Figure 2.

It has been estimated that R0 for the Delta variant, the initial reproduction number in a susceptible population, is approximately 7 (Lancet July 2021). Herd immunity occurs when a closed group of individuals has sufficient immunity that a new infection does not initiate an outbreak. The threshold can be calculated as 1-1/R0. For the Delta variant, the herd immunity threshold is 1-1/7, or 86%. No country is close to that level of immunity. However, it probably does not matter. Herd immunity requires a closed system to protect those without immunity. As long as new cases are continually introduced from outside the “herd,” nobody inside the herd is safe without immunity. Put another way, unvaccinated individuals are not protected if even 86% of their neighbors are vaccinated. Our exceptional social mobility ensures that individuals from outside will continuously expose everyone in the community to COVID-19. If you are not vaccinated, you will eventually get COVID-19. It is only a matter of time. With the Delta variant, you may not have to wait very long.

Manaus, Brazil, and Iquitos, Peru

In March of 2020, Manaus, Brazil, the capital of the Amazonas state, reported its first case of COVID-19 (Science 2021;371:288-92). Serologic surveys suggested that attack rate for SARS-CoV-2 was 66% as of June 2020 and 76% as of October 2020. The toll was horrific. By October, there were approximately 1,200 confirmed COVID-19 deaths per million inhabitants and 1,800 acute respiratory syndrome deaths per million inhabitants. These figures were generally higher than the observed mortalities in other countries: U.K. – 620 per million, France – 490 per million, or the U.S. – 625 per million. Perhaps the worst was over for Manaus, Brazil.

As can be seen in Figure 3, the residents of Manaus likely thought that by August 2020, the worst was over (Lancet 2021;397:452-5). Physical distancing was eased and, after several months, entertainment venues opened. The Gamma (“P1”) variant appeared in Manaus in December (Science 2021;372:815-21). In January 2021, all hell broke loose (Lancet 2021;397:452-5). “Herd immunity” proved meaningless. Cases and deaths surged to rates not previously seen. Figure 1 tells the same story as Figure 3 about the outcome when a population believes “the worst is over” just as a more infectious variant appears. As mentioned two months ago in this column, “it ain't over ‘til it's over” (ASA Monitor 2021;85:1-7).

The Gamma variant also caused a resurgence in Iquitos, Peru. As reported by Álvarez-Antonia and colleagues, last summer serological data suggested that 65%-85% of the Iquitos population was immune, depending on age (Lancet 2021;9:E925-31). Despite high levels of immunity, the Gamma variant caused a second surge in January 2021. As shown in Figure 4, the surge resulted in an acceleration of case and death rates throughout Peru, which now has the highest mortality in the world (asamonitor.pub/3wHRlWc). One in 150 Peruvians have died from COVID-19.

Herd immunity failed to protect Manaus, Brazil, or Iquitos, Peru, from a highly infectious variant. Because restrictions had been relaxed, both experienced surges in cases and deaths as severe as during the original wave of the pandemic. These cities are cautionary tales for the rest of the world.

In a perspective article in Science, two University of Edinburgh researchers review the implications of the surges in Manaus and Iquitos on public health strategies for SARS-CoV-2 (Science 2021;371:230-1). Drs. Sridhar and Gurdasani conclude that “Achieving herd immunity through infection will be very costly in terms of mortality and morbidity, with little guarantee of success .... Even a mitigation strategy whereby the virus is allowed to spread through the population with the objective of keeping admissions just below health care capacity, as is done for influenza virus, is clearly misguided for SARS-CoV-2.”

European spread of SARS-CoV-2

In a February 2021 Nature article, European and American researchers discussed the problems associated with managing the spread of SARS-CoV-2 during the “second wave” of COVID-19 in early 2021 (Nature June 2021). Regarding the minimization of disease burden spread, the authors comment, “We believe that travel policies may be a key consideration in this respect because similar conditions may arise as the ones we demonstrated to provide fertile ground for viral dissemination and resurgence in 2020.” The authors cite a recent study predicting dire consequences following premature or sudden cessation of containment efforts (Lancet 2021;21:P793-802). In their conclusion, the authors note, “Well-coordinated European strategies will therefore be required to manage the spread of SARS-CoV-2 and reduce future waves of infection, with hopefully a more unified implementation than hitherto observed.” Presciently, the authors voice concern that future spread in Europe may “also involve the spread of variants that evade immune responses triggered by vaccines and previous infections.”

According to the most recent technical briefing published by Public Health England (PHE) on SARS-CoV-2, the Delta variant now accounts for nearly all cases of SARS-CoV-2 (asamonitor.pub/3iiKuh3). Between February 1, 2021, and June 21, 2021, the U.K. reported a total of 123,620 cases of confirmed Delta variant COVID-19, with 71,932 being unvaccinated and 14,359 having unknown vaccination status. This is similar to the experience reported in Belgium in late May 2021 (asamonitor.pub/3kqKhea). In the Nos Tayons assisted-living facility in Nivelles, Belgium, 119 of the 121 residents were fully vaccinated against SARS-CoV-2. Despite nearly 100% vaccination, 55 still developed COVID-19, of which 12 eventually died (asamonitor.pub/3kmwKEp). There were also 16 cases of COVID that were identified among the 107 staff (76% of whom were fully vaccinated).

The events that transpired at the Nos Tayons facility were consistent with the findings of a study that compared the immune responses of elderly patients and younger health care workers who received the BNT162b22 (Pfizer/BioNTech) vaccine (Nature June 2021). After the initial dose of vaccine, reduced neutralization potency against the Alpha, Beta, and Gamma variants relative to wild-type SARS-CoV-2 was noted in participants who were older than 80 years. After the second shot, however, neutralization was noted in all age groups.

Conclusion

The current consensus is that, provided both shots of the vaccine are given (unless the manufacturer only recommends a single shot), vaccines confer significant immunity against infection and exceptionally strong protection against death from the known variants (Science 2021;371:1103-4; Nature July 2021; Cell June 2021; J Travel Med July 2021; Lancet 2021;397:2461-2).

That's excellent news. Although the variants have reduced vaccine efficacy, vaccines remain generally effective at reducing the probability of infection and hugely effective at reducing the possibility of death.

We can count on the virus evolving. As the virus increasingly seeks to infect those with pre-existing immunity, it will adopt new mutations that evade existing immunity. We can prevent this by vaccinating the world as quickly as possible. As succinctly stated by Altmann et al., “A virus that cannot transmit and infect others has no chance to mutate” (Science 2021;371:1103-4).

Get vaccinated, or get COVID-19. To paraphrase Albus Dumbledore, “It is our choices that show what we truly are” (Harry Potter and the Chamber of Secrets. 1998).

Richard Simoneaux is a freelance writer with an MS in organic chemistry from Indiana University. He has more than 15 years of experience covering the pharmaceutical industry and an additional seven years as a laboratory-based medicinal chemist.