POST 124. February 5, 2021. CORONAVIRUS. Dr. Osterholm ” …it may be time to..go with a ‘first-dose only’ approach, so more people over the age of 65 can have at least some protection right away. He said that would require delaying second doses until this summer.” Dr.Fauci “warned against this practice, and cautioned people about “the danger” that could come with focusing only on the first dose.”

“Dr. Michael Osterholm, a University of Minnesota infectious disease expert, warned Minnesota lawmakers Wednesday about the possibility of another ‘major surge’ in COVID-19 cases, as new variants of the virus start to spread in the United States….

He said there is growing concern about the U.K. strain that is now circulating in the U.S….

“I think we have a real possibility of seeing a major surge of cases this fall into early winter here in Minnesota and throughout the United States with this B117 strain, which if we do, I am convinced it’ll be much more severe than anything we’ve seen to date,” Dr. Osterholm said.

Dr. Osterholm told lawmakers it may be time to rethink our vaccine strategy and go with a ‘first-dose only’ approach, so more people over the age of 65 can have at least some protection right away. He said that would require delaying second doses until this summer.

He said the idea is being looked at ‘on the national level.’ He believes the strategy would help lower the baseline of infections in the U.S.

“I can tell you, we are going to have another surge and when it happens, the lower we start from, the better we’re going to be,” Dr. Osterholm said.” (A)

“However, White House chief COVID adviser Anthony Fauci, MD, just warned against this practice, and cautioned people about “the danger” that could come with focusing only on the first dose.

On Feb. 2, Fauci warned against administering just the first dose of the COVID vaccine in an effort to immunize as many people as possible without concern for when the second dose will be available. According to Fauci, there are risks involved with using this tactic. “The danger is that the efficacy following a single dose is not as great as after the second dose,” Fauci explained during a live Twitter event with The Washington Post. “If you have sub-optimum efficacy, you could, in fact, paradoxically be selecting for more mutations. That’s the danger there. … It’s taking a chance.”

While Fauci didn’t elaborate on that last point, some experts have expressed caution that delaying second doses of the vaccine—and therefore delaying the vaccine’s maximum potential protection—could lead to an “escape mutant” that could survive and evade shots when they are finally administered, Business Insider points out.

In The Washington Post interview, Fauci reminded viewers that the science behind the clinical trials showed that the optimal approach is receiving your second Pfizer dose 21 days after your first and your second Moderna dose 28 days after your first. He cautioned against straying from this recommendation seeing as the Pfizer vaccine is 52 percent effective after the first dose and the Moderna vaccine is 80.2 percent effective after just one shot.”(B)

“A (British) government vaccine adviser has defended plans to delay the second dose of the Pfizer coronavirus vaccine from three weeks to 12 weeks after the first jab, as the United States’ top doctor said he disagreed with the approach…

Following the approval of a second vaccine developed by Oxford/AstraZeneca last week, the Department of Health and Social Care said it would prioritise giving the first jab to “as many people in at-risk groups”.

“Everyone will still receive their second dose and this will be within 12 weeks of their first,” it added in a statement. “The second dose completes this course and is important for longer term protection.”…

The British Medical Association also claimed it was “grossly unfair” that patients who have already received their fist dose of the Pfizer/BioNtech vaccine were having appointments cancelled due to the change in guidance.

But speaking to BBC Radio 4’s Today programme, professor Anthony Harnden, the deputy chairman of the Joint Committee on Vaccination and Immunisation (JCVI), stressed that delaying the second dose was the correct approach.

He said that patients he had dealt with accepted the move, adding: “When it was explained to them that the vaccine offers 90 per cent protection for one dose, and the priority was to get as many people vaccinated in the elderly and vulnerable community as possible, they understood.

“I think the country is all in this together. And I think we really, really want to pull together to try to do the best strategy possible”.

He insisted: “It’s clear from looking at the data the Pfizer/BioNtech vaccine after one dose after 14 days is 90 per cent.”

Pressed on Dr Fauci’s comments, he replied: “That’s up to the Americans what they do… we’re not saying that you shouldn’t have a second dose, you do need a second dose, but that it can be temporarily delayed so that we can get many, many more people vaccinated in this vulnerable and elderly group as well as the clinically extremely vulnerable groups so that we get on top of this virus much quicker.

“We are in a dire situation in this country at the moment. The virus is rapidly spreading and the more vaccine we can get into these priority groups that we’ve identified the more deaths and hospitalisations that we will prevent.”  (C)

“It is still recommended for people to get their second dose of Covid-19 vaccine on time, Dr. Rochelle Walensky, director of the US Centers for Disease Control and Prevention, said during a virtual White House briefing on Monday.

“Until we have further data,” Walensky said, people should continue to follow the data from trials by continuing the schedule of receiving two doses 21 days apart for the Pfizer/BioNTech vaccine and 28 days apart for the Moderna vaccine. Those are the two vaccines currently authorized for emergency use in the United States…

Delaying second doses would go against the vaccine schedules that have been authorized under the US Food and Drug Administration.

In January, the FDA made clear that it does not plan to change coronavirus vaccine dosing schedules — and for such adjustments to occur, the vaccine manufacturer would have to specifically ask the agency to adjust authorization.

CNN confirmed with the FDA in January that if a manufacturer requests a change to its emergency use authorization, the manufacturer would need to submit data to the FDA supporting the requested change…

“At this point, everything we know about vaccines suggests that actually the protection may be enhanced by giving a booster several months after the first dose,” said Osterholm, who was a coronavirus adviser to the Biden transition team.

Osterholm pointed to a letter-to-the-editor that published in the journal Clinical Infectious Diseases last week, in which Dr. Stanley Plotkin of the University of Pennsylvania and Dr. Neal Halsey of Johns Hopkins University calculated about how many people could be protected against Covid-19 if single doses are given.

The researchers hypothesized, “suppose that 1 million people are to be vaccinated but only 1 million doses are available. If two doses are given to each vaccinee and the efficacy is 95%, 475,000 people will be protected. If single doses are given and the efficacy is 80%, 800,000 people will be protected.”

Osterholm said that getting people vaccinated — even with just one dose for now — remains urgent as more coronavirus variants circulate, including the B.1.1.7 variant first identified in the United Kingdom, B.1.351 first identified in South Africa, P.1 variant first identified in Brazil and the L452R first seen in California.

“We need to have a really comprehensive review and discussion of this as quickly as possible because you know this new variant B.1.1.7 could cause a surge in our cases within weeks,” Osterholm said. He described the emergence of these variants as similar to a hurricane approaching on the horizon.

“I feel like I’m sitting here on a beautiful beach — the light breeze, perfectly blue skies and everybody — and I’m telling them to start to evacuate. People are saying, ‘Are you crazy?’ But I see that 450 miles south, there’s a category five hurricane,” Osterholm said. “That’s the challenge. How do you get people to take action?”… (D)

“What the one-shot, two-shot debate has to teach us about uncertainty and science

The pandemic has repeatedly challenged some assumptions of science communications, where journalists confidently report what is evidence-based and what has “no evidence.” That vocabulary has shaped the conversation about vaccine dosing; for example, Pfizer has said there is “no data” to demonstrate that the immunity from the first dose lasts more than 21 days.

It’s true that length of immunity from the first dose is not what their clinical trials studied. But scientific evidence isn’t all-or-nothing like that. In many cases, scientists (and historians, and researchers in every field) have deeply limited evidence about the topic of interest. Often they’re in a position of trying to make inferences from the results of other similar events, from a few unusual data points that arose due to accidents, or from measured results that were not the primary aim of the trial they were measured in.

Sources of evidence like these are being employed when researchers try to estimate the likely duration of immunity from a single vaccine dose. The UK’s Working Group that made the delayed dosing recommendation “concluded that vaccine efficacy will be maintained with dosing intervals longer than 21 days … based on clinical trial data that showed the vaccine was 90.5 percent effective against preventing Covid-19 after the first dose once the protection that starts at around 12 days kicks in, and there was no evidence to suggest that the effectiveness of the vaccine is declining toward the end of the 21-day period following the first dose,” a spokesperson said.

From one perspective, that study produced “no data” about effectiveness past 21 days. For another research team, it shows there’s “no evidence” of declining effectiveness…

“It’s been a repeated problem throughout the pandemic that we have relied on this ‘we have the evidence/we don’t have the evidence’ binary, meaning that we have moved slowly, waiting for rock-solid confirmation; but moving faster, making decisions on imperfect information, would have saved a lot of lives,” British science journalist Tom Chivers argued in an article Wednesday about the difference between the US and UK approaches to vaccination.

While randomized controlled trials (RCTs) are incredibly valuable for determining how well vaccines work, decisions about vaccination in a pandemic require many judgment calls that we unfortunately cannot assess in advance with an RCT. And to be clear, concerns like whether the change in vaccination schedules will limit public confidence in the vaccine, increase vaccine hesitancy, or prompt individuals to take risks, believing themselves fully immune when they aren’t, are very legitimate and should no doubt feature in our reasoning and planning about vaccination.

But those concerns have also not been rigorously demonstrated in an RCT. No one has conducted a controlled study on how delaying the second dose will affect vaccine hesitancy. Instead, public health officials who raise vaccine hesitancy concerns are looking at lots of factors and making their best informed prediction about what will happen — and public health officials who estimate that delayed second dosing is worth it are doing the same thing.”  (E)

“Pfizer, sounded more cautious on the prospect of shifting the schedule of the second dose of the vaccine, noting it had not been evaluated on different dosing schedules.

“There are no data to demonstrate that protection after the first dose is sustained after 21 days,” it said in a statement, adding the implementation of alternative schedules should be closely monitored.

“While decisions on alternative dosing regimens reside with health authorities, Pfizer believes it is critical… to ensure each recipient is afforded the maximum possible protection, which means immunisation with two doses of the vaccine.”

Britain has said the new strategy still means everyone will receive a second dose within 12 weeks of the vaccine.” (F)

“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…

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

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.” (G)

“There are two ways to resolve this question: We can debate it on social media or we can go get more data. I believe we should do the latter, and propose that academic nonprofit hospitals in the U.S. immediately start a study of their own employees.

The data this study would generate could clarify whether the seemingly intuitive first-shot approach has downsides when compared to the stricter set-aside strategy by focusing on two questions: How long does immunity from the first shot last? And how well does the booster work when it is delayed (no one has yet proposed just a single shot with no booster)?

Here’s how the study would work: Every employee gets a first shot, as many already have. Then, before the second-shot booster, employees — with their consent, of course — are randomized to a second shot according to the FDA authorized schedule or to a placebo shot of saline. (Because vaccines are being drawn up within hospitals, the placebo could be made in the pharmacy and all other levels of blinding can be preserved). Participants would be tested weekly for the infection and cases of clinical Covid-19 would be recorded.

The primary endpoint would be differential rates of clinical Covid-19 beginning a week after the second shot is administered. Secondary endpoints would include rates of asymptomatic carriers. Hospitals would follow a common protocol, but the data could be housed within each hospital and shared only at the time of analyses.

When rates start to diverge, which would answer the first question, all placebo recipients would receive a booster, producing data with varying time between first shot and booster that could help answer the second question to some extent…

Let me put it another way: Hospitals, for the sake of your workers and for all of us, please get your IRBs going.” (H)

(A)U of M infectious disease expert warns lawmakers of another possible ‘major surge’ in COVID-19 cases, by Alex Jokich, https://kstp.com/coronavirus/u-of-m-infectious-disease-expert-warns-lawmakers-of-another-possible-major-surge-in-covid-19-cases-new-variant-doctor-michael-osterholm/6000544/

(B)Dr. Fauci Just Warned of “The Danger” With This Kind of Vaccination, By ALLIE HOGAN, https://bestlifeonline.com/fauci-first-dose-news/

(C) UK Covid vaccine adviser defends second dose delay plan as Fauci says ‘I would not be in favour’, by Ashley Cowburn, https://www.independent.co.uk/news/uk/politics/covid-vaccine-doses-pfizer-fauci-b1781455.html

(D)Experts split on delaying Covid-19 vaccine second doses. Here’s why, By Jacqueline Howard, https://www.cnn.com/2021/02/02/health/covid-19-vaccine-second-doses-debate-explainer-wellness/index.html

(E) Should the US hold back vaccine doses? Biden says no., By Kelsey Piper, https://www.vox.com/future-perfect/2021/1/7/22213953/covid-vaccine-pfizer-moderna-dosing-science-delays

(F) Shots first, questions later: Britain’s new COVID-19 vaccine rollout approach, By Alistair Smout, https://www.reuters.com/article/us-health-coronavirus-britain-vaccine-st-idUSKBN294257

(G) One Dose Now for Everyone Most Likely to Die, By Adam Finn and Richard Malley, https://www.nytimes.com/2021/01/29/opinion/covid-vaccine-booster.html?referringSource=articleShare

(H) Instead of debating ‘first-shot’ vs. ‘set-aside’ vaccine approaches, hospitals’ study should compare them, By PETER B. BACHJANUARY, https://www.statnews.com/2021/01/04/stop-debating-first-shot-vs-set-aside-hospitals-should-compare-them/