Opinion | One Dose Now for Everyone Most Likely to Die

In the race to prevent ever more deaths from Covid-19, the United States faces two major problems: not having enough doses of vaccine on hand and struggling to deliver those that are available. According to data from the Centers for Disease Control and Prevention, as of Jan. 28 about 48.4 million doses had been distributed, but only 26.2 million administered.

The Food and Drug Administration has granted emergency-use authorization to two vaccines requiring two doses — with the first shot and the booster to be delivered three weeks apart in the case of the Pfizer-BioNTech vaccine, and four weeks apart for the Moderna vaccine.

As of Thursday, just 4.2 million people in America had received both doses, according to the C.D.C. Uncertain about vaccine supplies, some inoculation centers have canceled first-time appointments while keeping second appointments on schedule.

This is exactly backward.

The Biden administration’s Covid-19 response and pandemic preparedness plan aims to provide 100 million doses within 100 days of the president’s inauguration, especially to people over 65, all essential workers (not only those in health care services) and “the highest-risk members of the public, including racial, ethnic and rural populations and those in congregate facilities.” Both the plan’s sense of urgency and its focus on some of the most vulnerable groups are welcome. But the proposal also backs the use of second doses and supports sticking to F.D.A.-recommended timelines for administering them, and that is misguided.

We think more lives would be saved by providing as soon as possible (a) just one dose of vaccine (b) to all people who face the highest risk of dying from Covid-19, whatever the reason (advanced age, other medical conditions, severe obesity), and (c) just forgetting about any boosters for a while, maybe even a very long while. Second doses should be deferred for the time it takes to achieve this primary goal.

The two vaccines’ manufacturers and the F.D.A. have been reluctant to endorse any change to the vaccination schedules that were tested in Phase 3 clinical trials, on grounds that other options weren’t tested and so their efficacy is unknown. On the face of it, this position seems sensible; yet under current circumstances, it is dangerously overcautious.

The C.D.C. has authorized giving a second dose up to six weeks after the first one if sticking to the recommended interval is “not feasible.” But this is an arbitrary extension — it wasn’t tested any more than any other modification — and we think it’s too short to accomplish much good society-wide.

Bear in mind that the clinical trials performed for both the Pfizer-BioNTech and Moderna vaccines weren’t designed to identify the optimal number of doses for inoculation, nor the perfect schedule for administering them. The goal of those trials was only to test whether two doses of vaccine given according to the schedule chosen by the manufacturers did confer sufficient protection against Covid-19.

Note, too, that in the case of both those vaccines the intervals tested (three and four weeks) were unusually short. In standard schedules for childhood vaccines in the United States, for example, the gap between the first shot and the booster typically is no less than two months. The fact that the trials did not test whether administering a second dose much later, or not at all, might work just as well than the recommended schedule, or well enough, also means that it could work.

And there is good reason to think that it would.

With some vaccines, like those for hepatitis A or human papillomavirus (HPV), delaying the second dose by as long as several years has been shown to not decrease the protection conferred by the vaccine. In other cases, such as influenza vaccines, increasing the interval actually improves the response. (This likely is because the cells in the body that develop the immune memory necessary to repeatedly fend of infections can take weeks or months to develop.)

In trials for another Covid-19 vaccine not currently available in the United States — this one developed by Oxford-AstraZeneca — study subjects were supposed to get a booster one month after the first shot but some received it up to 12 weeks later. Results for the latecomers were outside the trials’ formal ambit, but they are available, and they suggest that the subjects who waited to get their booster beyond the recommended delay displayed better immune responses than the subjects who got it on time.

In non-pandemic situations, the usual approach is to give a vaccine to the wider public in precisely the same way that it was studied and vetted in Phase 3 trials, as well as to initiate new clinical trials or real-world studies to evaluate alternative ways of administering it. As a result of this practice, recommended doses were reduced for vaccines against, for example, HPV (from three to two) and meningococcal B in infants (from four to three) — with no significant reduction in immune responses.

Such precedents may be one reason that some doctors and social scientists are now calling for promptly conducting studies to assess the performance of single doses of Pfizer-BioNTech’s and Moderna’s Covid-19 vaccines in young, healthy subjects, the group least likely to become severely sick with Covid-19.

Yet this approach, too, misses the mark. With the pandemic raging as it is — one person is dying of Covid-19 about every 30 seconds in America — there is no time to wait for the results from additional clinical trials, which would take months to complete, before vaccine-rollout plans are modified. And studying the efficacy of single doses only among individuals who face a very low risk of dying from Covid-19 wouldn’t say much anyway about the viability of using single doses with the people most at risk of death.

We must go ahead right now, even without trials, with a one-dose- approach targeting the most vulnerable.

Would doing so be a dangerous gamble and possibly mean playing with people’s lives? A lot less so than you might think.

Even in non-pandemic times, the public health authorities of certain countries, notably Britain, have sometimes deviated from vaccine schedules tested in clinical trials without conducting additional trials.

Take the vaccine for seasonal influenza. The schedule endorsed by the American Academy of Pediatrics calls for two doses to be given four weeks apart to children between six months old and eight years old the first time they are inoculated. But the health authorities in Britain have decided — and without first formally testing this out in a trial — to forgo the booster dose for most two- to nine-year-olds, in order to get available vaccines out to more children.

The strategy has paid off. During the 2016-17 influenza season, the overall effectiveness of the vaccine programs in the United States and Britain was about the same (or 40 percent).

Similarly with the pneumococcal conjugate vaccine. In the United States, it is administered in three injections during the first year of life followed by a booster at age one; this is the so-called 3+1 schedule. Many European countries have dropped one of the first three doses (that’s the 2+1 schedule) — and with no apparent reduction in protection. The World Health Organization has endorsed administering a total of just three shots (whether 2+1 or 3+0).

There is evidence today that something similar could be true with Covid-19 vaccines. In both the Pfizer-BioNTech and Moderna Phase 3 trials, the first dose achieved at least 89 percent efficacy starting two weeks after immunization. Preliminary data from Israel’s mass inoculation campaign suggest likewise, with significant protection against infection reported in the first 430,000 individuals who received an initial shot.

As the F.D.A. points out, estimates of efficacy rates after the first dose in clinical trials are based on a short period of observation: Most participants receive their second dose just three or four weeks later. In theory, delaying the second doses could mean that whatever immunity individuals acquired after the first shot would wane in the interim. Yet typically — as with the vaccines against meningococcus, influenza or typhoid — if immunity following a single dose wanes at all, it does so over months or years, not in a matter of weeks. Just one dose can buy a lot of time.

The Biden administration’s by-the-book approach to Covid-19 vaccination — two shots and delivered, as much as is possible, according to the schedule set by manufacturers — may be the safest for policymakers, but it isn’t the safest for the public. It’s overly prudent, and at this stage of the pandemic, the excess of caution is killing people.

More lives could be saved if we simply forgot about boosters and more trials for a while and rushed right now to give just one shot to all the people who are most immediately at risk of dying.

Adam Finn (@adamhfinn) is a senior clinician in the pediatric immunology and infectious diseases clinical service at Bristol Royal Hospital for Children and a professor of pediatrics at the University of Bristol. Richard Malley (@rickmalley) is a physician specializing in infectious diseases at Boston Children’s Hospital and a professor of pediatrics at Harvard Medical School.

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