Op-Ed: A Better Way to End the Pandemic Quickly

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The FDA now has authorized vaccines from both Pfizer/BioNTech and Moderna. However, the news is not all good. We are a country of about 325 million people, yet, in the near term, there will only be enough vaccine for about 20 million people. Hopes that the majority of the population will be vaccinated by spring have given way to more pessimistic projections of summer or even fall. What are we to do?

There are two strategies that will allow us to end the epidemic in a more timely fashion. Both solutions require that, at least in the short run, we use the available supply of vaccine more efficiently. First, we should not use the limited supply of vaccine for people who do not need it.

There is convincing evidence that people who are known to have been infected already have immunity to SARS-CoV-2. As of December 21, there have been 77 million cases of COVID-19 reported worldwide. A group that tracks confirmed reinfections has documented only 30 cases. To be fair, this may be an underestimate. But even if we inflated the number of known reinfection cases 10-fold, the incidence of infection in the active vaccine arm of the Moderna trial would still be more than 200 times greater.

In Pfizer’s trial, although the published summary noted that exclusion criteria included a medical history of COVID-19, the FDA briefing document showed that 1,093 persons (526 in the vaccine group and 567 in the placebo group) were positive for SARS-CoV-2 at baseline (via a positive antibody, positive PCR test, or medical history of COVID-19). In this group, there were only two incident cases, one in each arm of the trial. Similarly, in the Moderna trial, only one person in the placebo arm with SARS-CoV-2 antibodies at baseline developed COVID. Overall, the literature suggests the efficacy of prior infection for preventing reinfection is over 99%. At a minimum, we feel that persons with COVID-19 infection in the last 90 days should not be immediately prioritized.

Finally, the number of people who have had a prior infection may be greater than realized. The CDC estimates there are currently eight undiagnosed COVID-19 cases for each diagnosed case. By December 30, it is estimated that about 20 million people in the U.S. will have been infected with the coronavirus. That means that 160,000,000 Americans, or nearly half the population, will have immunity, dramatically limiting the need for vaccine.

Frequent side effects were reported with these vaccines, though typically short term and self-limited. However, a few cases of Bell’s palsy and severe allergic reactions have been reported. Of perhaps greater concern is that these two vaccines represent a new technology and any long-term effects remain unknown. With the vaccine in short supply, what rationale is there for vaccinating someone with near-zero risk of future disease?

The second way to stretch the limited supply of vaccine is to delay the second dose. The current plan is to give two doses, 21 days apart for the Pfizer product and 30 days apart for Moderna’s. Alternatively, all available doses could be given immediately, doubling the number of people who could be reached. Both Pfizer and Moderna report that the efficacy of a single dose is only about 50%. But a closer look at their incidence curves suggests that immunity appears to be maximized about 14 days after the first dose. In the Moderna trial, for example, most of the cases in the vaccine arm occurred during the first 2 weeks following the initial dose. We recognize that the vaccine was developed and tested on the assumption that two doses are necessary. Yet, the trial data suggest that a single dose provides substantial immunity. During this severe pandemic, it seems reasonable to use the available supply to reach as many people as possible in the short term. Delaying the second dose would maximize limited resources and could reduce serious illness and death. A recent projection suggests the U.S. will receive 40 million doses of the two mRNA vaccines by early 2021. A rough calculation suggests that vaccinating 40 million persons with these 40 million doses versus 20 million persons with two doses each could prevent over 100,000 severe cases and save over 10,000 lives.

We understand that these suggestions depart from the current protocol and that the protection by a single dose of these vaccines beyond 1 month is unknown. Yet, the situation is urgent. We need to use the limited supply of vaccine to have the most benefit for the most people and to prevent as many cases of severe disease and death as possible. Once the epidemic begins to wane, we would then reexamine the need for second doses and for vaccinating those who have already been infected.

Michael H. Criqui, MD, MPH, is a Distinguished Professor at the University of California San Diego School of Medicine and past Chief of the Division of Preventive Medicine. He is an epidemiologist and preventive medicine specialist.

Robert M. Kaplan, PhD, is a faculty member at Stanford Medical School’s Clinical Excellence Research Center, a former associate director of the National Institutes of Health, and former chief science officer for the U.S. Agency for Health Care Research and Quality.

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