Op-Ed: Forget Second COVID Vaccine Doses for Now

— It’s far more important to get first doses to as many people as possible

https://www.medpagetoday.com/blogs/marty-makary/91029

Tragically, only 62% of COVID-19 vaccines distributed in the U.S. have been administered. One reason for the slow rollout: states and some hospitals are holding back vaccines for scheduled second doses. But to save more American lives and beat back the threat of new variants, we should use the entire current vaccine supply to offer a first dose to all seniors and high-risk people before we administer second doses.

Data are mounting to show that one dose can be highly effective in the short term. In the Pfizer vaccine trial results, there was 91% protection in the first 7 days after the second dose, a period in which the second dose has not yet kicked in. The 91% efficacy observed at 4 weeks is entirely attributable to the first dose.

We also got news on Jan. 13 from Johnson & Johnson’s phase I/IIa vaccine trial two weeks ago. It affirmed a scientific principle often seen with vaccines — that immunity naturally increases in the second month. In the New England Journal of Medicine article by Sadoff et al., neutralizing antibodies were observed in 90% of participants by day 29 to 100% by day 57 after receiving the J&J vaccine.

The second dose may actually be more effective when it’s delayed. “Generally, a longer gap between vaccine doses leads to a better immune response,” Andrew Pollard, director of the University of Oxford’s vaccine group, told The BMJ. He pointed to the HPV vaccine, where a one-year gap between doses yields stronger immunity than a one-month gap. He also pointed out that in the AstraZeneca/Oxford vaccine trials, the immune response was about three times greater when the second dose was given at 2-3 months versus 4 weeks. Similarly, a multinational study found that the first dose of the Moderna vaccine had 80% efficacy and that a delay of 9-12 weeks “could enhance the program effectiveness and prevent additional infections, hospitalizations, and deaths, compared to a 4-week interval between the doses.”

Put simply, in the midst of a horrific war with thousands of Americans dying each day, would you rather give 50 people 95% protection or 100 people 80%-90% protection?

That’s why the U.K. has already recently issued official guidance recommending that people wait closer to 12 weeks to get their second vaccine dose.

Yet the U.S. medical establishment has been oddly dismissive of the immunity attributable to the first dose and the broader strategy of maximizing first doses before administering second doses. This rigidity is consistent with the track record of U.S. scientists refusing to participate in the RECOVERY trial because it did not meet the elaborate standards the U.S. scientists insisted upon. U.K. doctors eventually completed the trial without U.S. participation and established steroids as a standard of care for COVID patients.

Finally, we must remember that the ultimate endpoint is death, not just infection. To date, there are no reports of anyone who has died of COVID-19 because they missed or delayed their second vaccine dose. Partial immunity appears to have the ability to reduce the severity of illness. People in academic ivory towers often speak with a denial that there is severe rationing of healthcare. Right now, we are rationing like crazy. The data are now clear on how we should ration the life-saving vaccine doses. As the data accumulate, we must be willing to evolve our strategy.

To be clear, people who receive an initial vaccine dose should get a second dose with the Pfizer and Moderna vaccines — but not while we are severely supply-constrained and 3,000 Americans die each day. Holding back vaccines for second dose reservations leaves more seniors as sitting ducks in this deadly war because they can’t get any vaccine.

Unfortunately, the FDA has a policy of not being fully transparent with vaccine data. They don’t release the entire vaccine application to the public as they should once they receive an application. That prevents smart people from weighing in on what they should do and it allows the FDA to function at turtle speed. Much of the efficacy data for the first dose was only made public once all the vaccine trial data was made public after the FDA authorized the vaccine.

When I first reviewed the vaccine data to look at the effectiveness of the first dose, I felt like a lone wolf going on television suggesting to hold off on second doses as long as we were severely supply-constrained. But since then, a growing chorus of leading physicians have advocated for the same approach.

On Sunday, Michael Osterholm, PhD, MPH, a member of the Biden administration’s COVID task force, said, “We still want to get two doses in everyone, but I think right now, in advance of this surge, we need to get as many one-doses in as many people over 65 as we possibly can.” This comment made waves since it was in sharp contrast to what the old guard medical establishment was saying. The new CDC director, Rochelle Walensky, MD, MPH, quickly upheld the two-dose on-time position when she said only in “rare circumstances” should one wait as long as 6 weeks after the first dose.

Ashish Jha, MD, MPH, and Bob Wachter, MD, were some of the first people to suggest that delaying the second dose may be a better strategy to vaccinate more people. They floated the idea in the Washington Post as something to consider (in classic academic discussion fashion), with a pre-emptive disclaimer that smart people will disagree and that their position is not a “no-brainer.” I replied that it is both a “no-brainer” and a “brainer.”

We just need to move fast to implement the idea into policy. On a personal level, I’m encouraging patients I see, friends, and family to hold off on the second vaccine dose for the benefit of vulnerable Americans. As I detailed in MedPage Today, as someone at a very low personal risk of COVID mortality and a very low risk of acquiring or transmitting the virus in the hospital, I will not be taking the vaccine until every high-risk American has been offered it first.

Our national vaccine strategy should also acknowledge the current disconnect between the scientific ivory tower and the real-world. In the real world, there is a massive vaccine grab, dominated by the wealthy and connected. As the Miami Herald reported this week, Fisher Island, Florida, the wealthiest zip code in the U.S., has a vaccination rate of 51% while nearby Opa-locka, where 40% of the population lives in poverty, has 2% of their population vaccinated. How can we justify denying Opa-locka residents a first dose when Fisher Island residents are getting a second? Prioritizing first doses at a time when we are supply-constrained could help reduce the racial and socioeconomic divide that vaccine greed is increasing by the minute.

We should also remember our country’s vaccine journey. This past summer, we all waited intently to see if a vaccine could meet the stated goal of being at least 50% effective. Imagine our reaction then if a company suddenly announced that a single-dose vaccine was found to be 80%-90% effective at 4 weeks. We’d say that’s a home run! If someone were to later add that giving the same vaccine a second time would increase the efficacy level by four percentage points, we’d probably say let’s just get everyone one dose and then talk about getting people a second dose.

It’s time the medical establishment and federal and state governments have the courage to take a hard look at the data and make a bold wartime decision, even if it rattles an older framework.

The race to beat new variants is on. The longer COVID-19 circulates unabated, the more opportunity it has to mutate and morph into new strains that may not be encompassed by our current vaccines. In order to save as many American lives as possible and optimize our chances of crushing the new variants, we need to ration our scarce vaccine supply more wisely. To date, the allocation has been erratic, wasteful. It’s also been oddly blind to those with natural immunity from prior COVID-19 infection. Let’s be guided by science and have the humility to change our approach to protect as many vulnerable people as we can.

Some scientist friends have told me not to talk about the high effectiveness of the first dose publicly because people might hear that information and decide not to get the second dose. But in principle, I believe we should not hide data from the public in hope of steering them with partial information. Second doses should be administered after every high-risk American, regardless of race or income, has been offered a first dose.

Filed under: General Problems