With new COVID-19 cases in steady decline across the United States, and the pace of vaccination accelerating, Americans may feel optimistic about what feels like a turning point. Despite this encouraging news and crucial progress, the uncontrolled, global spread of COVID-19 has produced a new problem: mutant viruses or variants, several of which are proving difficult to control.

How did that happen? The answer is viral evolution — in this case, the selection of mutant viruses that transmit from one person to another more effectively and/or are more capable of defeating the human immune system. With each virus producing more than 10,000 new viruses, simultaneously occurring across millions of infected individuals, there is a near certainty that new versions of the virus will emerge.

Natural selection occurs when these new viruses are tested against millions of human immune systems from across the globe. Virtually all viruses fail that test. However, the rare survivor virus successfully replicates itself, leading to ever more infectious viruses that transmit more efficiently. These new variant viruses make it harder to end the pandemic. In fact, more infectious variants mean we will need to vaccinate a greater proportion of the population than would have been required to control the original COVID-19 virus.


These more infectious COVID-19 variants spread both more efficiently and at accelerated rates. A more transmissible virus is like a car that accelerates to a faster speed; to stop it, we must brake sooner, and brake harder. The preventive steps, or braking, that eventually achieved control during the spring wave in the United States may not be sufficient to control the next variant. New variants, such as B.1.1.7 identified in November in the United Kingdom, defeated some of the most aggressive community lockdowns, school closures and stay-at-home orders.

Elsewhere, we are now aware that new COVID-19 variants are appearing wherever we are doing high quality sequencing of the virus’s genetic code. We are blinded to the magnitude of the threat of variants, as the majority emerge outside of our current ability to sequence the virus. This blind spot has immediate ramifications for each nation. For example, our partner hospitals in Brazil reported that patients infected with COVID-19 last spring have recently been re-infected by new variants. These variants appear to escape immune protection acquired from the first infection. This is not good.

In Manaus, Brazil, after an uncontrolled first wave of COVID-19 between April and November, over 70 percent of the population developed antibodies to the virus — a level of protection we would have predicted would protect the population against re-infection. However, the emergence of another new variant, P.1., breached these immune defenses, resulting in Manaus suffering a catastrophic second wave of infection. Although scientists are still studying this event, initial evidence indicates certain mutations in the virus’s genetic code, along with waning immunity over time, result in people being susceptible to reinfection with the new variant.

This is a very serious warning to the rest of the world: Immunity is not absolute — and may have an expiration date. The bottom line: we are far from being out of the woods, even while there is reason for hope.

Will vaccines prevent a worsening of this situation? Several vaccines, particularly the mRNA vaccines produced by Moderna and Pfizer-BioNtech, appear to provide protection against most circulating variants. Yet, the recent failure of AstraZeneca’s vaccine to protect against the South African variant is a major setback. The attractiveness of the AstraZeneca vaccine is its ease of storage, very low cost, high safety and respectable effectiveness, all key attributes critical for vaccination of those living in austere, underserved regions. Separate results from two other promising vaccines, manufactured by Johnson & Johnson and Novavax, suggest additional breaches of vaccine protection by South African strains may be possible. This is particularly concerning because the J&J and Novovax vaccines, unlike the more costly and difficult-to-store Moderna and Pfizer-BioNT vaccines, are ideally suited for use in low- and middle-income countries where extreme cold-refrigeration is not possible, and where the public health impact of these variants is greatest.


Failure of any COVID vaccine, in any nation, is a problem in the United States as well. Stated plainly, the spread of a vaccine-defeating COVID variant anywhere on the planet can reboot the pandemic here in the U.S. Even when nations achieve herd immunity through vaccination, that nation is susceptible to new variants imported from areas in which transmission is uncontrolled.

The message to Americans, our businesses and our elected officials needs to be clear and unwavering. We must go to battle with the weapons we have. Our weapons are vaccines developed under extraordinary circumstances and at unprecedented speed. They are a great success. These fast, safe vaccines did not cut corners on safety but, rather, were accelerated by running multiple safety trials in series, rather than one at a time, as is routine for the vaccine industry. The current U.S. vaccines and public health measures are undeniably effective at stopping or, at the very least, slowing the spread of the current COVID-19 strains.

Our risk rises with the next steps — specifically, if we fail to prevent transmission through rapid, early vaccination rollout and continued rigorous, persistent use of public health controls, which otherwise will increase the probability of an escape variant emerging. If allowed to propagate, these vaccine-defeat and more transmissible variants will rapidly undermine the nation’s hard-earned gains to control COVID-19. We cannot wait for these variants to gain momentum: The U.S. must partner with other nations to reduce new infections, everywhere, as much as possible and as soon as possible.

The fact that the U.S is energetically re-engaging with the World Health Organization and partner nations means that we are correcting our blind spots and regaining access to data critical to protecting the U.S. against new, potentially more dangerous variants. These steps, urgently implemented and energetically enforced, could prevent the emergence of a “COVID-21.” Variants that defeat vaccines and overcome public health controls in one country threaten all nations. As such, all nations need prompt access to safe, effective vaccines and to redouble their use of proven public health measures like masks and social distancing.

Our national response must accept the global health truth that the nations of the world are deeply interconnected and interdependent, and that the current pandemic is not over for any individual nation until it is over for all nations.

Michael V. Callahan, M.D., DTM&H, MSPH, is former COVID special advisor to the Assistant Secretary for Public Health Preparedness at the Department of Health and Human Services. He is director of the Clinical Translation, Vaccine and Immunotherapy Center at Massachusetts General Hospital.

Jacob Lemieux, M.D., DPhil., is an instructor of medicine at Harvard Medical School and the Infectious Diseases Division of Massachusetts General Hospital.

Mark C. Poznansky, M.D., PhD., FIDSA, is director of the Vaccine and Immunotherapy Center, Infectious Diseases Division, of Massachusetts General Hospital and an associate professor at Harvard Medical School.

You Might Like
Learn more about RevenueStripe...