A Shot (Instead of Two) at Saving Lives

Waiting on the Covid booster would allow more people to be vaccinated sooner.

By Michael Segal

Recent days brought good news and bad news about coronavirus vaccines. The developments could add up to months of delay in getting most Americans inoculated. But there’s a way to make use of the good news to speed up herd immunity.

The bad news is that in July the U.S. passed up an opportunity to secure by June 2021 more than 100 million doses of the Pfizer vaccine, now expected to receive emergency-use authorization in the next few days. Instead, officials followed a balanced-portfolio strategy that reserved as many as 300 million doses of the AstraZeneca vaccine, whose prospects are unclear.

The good news is that the Pfizer and Moderna vaccines performed at the upper end of expectations, with 95% efficacy after two doses. And intriguingly, Pfizer’s submission to the Food and Drug Administration shows that the efficacy of the vaccine in preventing disease had largely kicked in by two weeks after the first dose, and there was no dramatic increase in efficacy after the booster was given three weeks later.

The protocol in Pfizer’s clinical trial was to give all participants two doses. The FDA is likely to approve this protocol, and standard procedure is to prescribe a drug according to protocol. But we are in a pandemic and supplies of vaccine are inadequate. There’s an alternative: vaccinating as many people as possible with a first dose and waiting on the booster until supplies are plentiful.

The Pfizer study wasn’t designed to put a number on first-dose efficacy, but the data in Pfizer’s “cumulative incidence curves” suggest at least 75% efficacy for two weeks after one dose. The question is whether to use the 100 million doses on 50 million people, of whom two doses would protect roughly 47.5 million, or to give one dose each to 100 million people and protect at least 75 million.

States have the authority to allocate vaccines as they choose, but they’re unlikely to deviate from the study protocol unless a federal authority—whether the Centers for Disease Control and Prevention or a coronavirus “czar”—suggests this as an option.

Even under such an approach, some essential personnel—such as doctors and nurses who work directly with coronavirus patients and health aides who work in multiple nursing homes—should get two doses as soon as possible, given their high-risk role in the pandemic response.

The U.S. will have more than these 100 million doses of the Pfizer vaccine. Some will come from Moderna, and the federal government could use the Defense Production Act to snatch some Pfizer doses that the company contracted to sell to other countries. Even so, supply will be constrained at first, and officials need to think clearly and flexibly about how to allocate the limited doses that will be available soon.

Harvard epidemiologist Michael Mina expressed his disappointment with society’s decision making during the pandemic: “I’m just astounded by the dysfunction, the willingness to just stay the course as hundreds of thousands of people die, and the unwillingness to innovate in literally any way.” Here’s a simple innovation that could save many lives.

Dr. Segal is a neurologist and neuroscientist.

Appeared in the December 11, 2020, print edition of the Wall Street Journal.

Copyright ©2020 Michael Segal

Addendum on first dose efficacy:
There has been considerable confusion about Pfizer's figure of 52.4% efficacy after the first dose.

The "After dose 1 to before dose 2" table in Figure 3 of their New England Journal of Medicine paper lists 52.4% efficacy for that period.  The number is derived from 39 symptomatic patients in the vaccine group compared to 82 symptomatic patients in the placebo group ( vaccine 39 / 21669 risk divided by placebo 82 / 21686 risk gives 47.6% relative risk, i.e., 52.4% vaccine efficacy).  The 52.4% vaccine efficacy applies to the entire 21 day period "After dose 1 to before dose 2".  As can be seen in the graph in the figure and the expansion of the initial period in the inset, there is essentially no protection for the first 10 days and then the protection afterwards is so good that there is no obvious effect of the booster at day 21.  If you average 0% efficacy for 10 days with near-perfect efficacy for the next 11 days, you get the 52.4% efficacy that Pfizer listed in the table.  One can calculate an efficacy for the period from 11 days to 21 days as ~85%, but because of the small numbers the more conservative assumption of 75% was used in the WSJ article.  Michael Mina makes the same point here.

There were similar results in the Moderna FDA submission (Figure 2 and Table 15) released on 15 December 2020.  Moderna calculated the efficacy for > 14 days after dose 1 as being 92.1%.

Addendum on testing positive after vaccination:
Many have expressed surprise that people test positive after one or even 2 doses of these vaccines. This is expected, and should not be alarming for the following reasons:

  1. Efficacy takes time: Until ~12 days after the first dose one can come down with clinical illness and also test positive, as was seen in the Pfizer and Moderna studies.  The immunity takes about a week to develop, but if you are infected at one week you will show symptoms at ~12 days.
  2. Some testing shows infection that has resolved already: After 12 days the positive RNA test in an asymptomatic person may just be from RNA remaining from dead viruses.
  3. Some infection is asymptomatic: Even if someone tests positive for virus protein or using a virus culture, that is not the same as illness.  The vaccine results in the body making immunoglobulin G (IgG), but to prevent virus in the nose, mucosal IgD is what is most needed.  Experts expect that vaccinated people will remain somewhat susceptible to a mild nose cold that won’t spread systemically but will test positive on nose swabs and could be infectious to others. What matters most is preventing clinical illness, and most importantly, preventing severe disability or death.
  4. Mild clinical infection does occur in a small percent: The efficacy numbers in the Pfizer and Moderna studies were for clinical symptoms.  Efficacy against positive virus tests must necessarily be lower because some people have positive tests for virus in the nose but are asymptomatic.  My estimate of 75% clinical efficacy in the WSJ article, before the Moderna data, was purposely conservative.  In the articles below that came out after release of the Moderna data, the epidemiologists use more likely numbers for clinical efficacy after one dose of 80% to 90% and 92%. 

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