Experts Debate Wisdom of Delaying Second COVID-19 Vaccine Dose


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A proposal to delay administration of the second dose of COVID-19 vaccines — suggested as a strategy to boost the number of people who get some degree of protection from a single immunization with the Pfizer/BioNTech or Moderna vaccines — is inciting a strong debate among clinicians and public health officials.

Proponents argue that getting some degree of protection to a greater number of Americans is worthwhile, particularly as case numbers and hospitalizations continue to rise and with the emergence of a more contagious variant.

Opponents raise concerns about diverting from the two-dose schedule evaluated in clinical trials, including a lack of data on long-term protection from a single dose. They also suggest a longer interval between dosing could increase resistance of SARS-CoV-2 virus.

It is time to consider delaying the second dose, Robert M. Wachter, MD, at the University of California San Francisco and Ashish Jha, MD, MPH, at Brown University in Providence, Rhode Island, write in an opinion piece in The Washington Post January 3. 

The two experts state that supply constraints, distribution bottlenecks, and hundreds of thousands of new infections daily prompted them to change their stance on administering COVID-19 vaccines according to the two-dose clinical trial regimen. Furthermore, they cite a study in the New England Journal of Medicine that suggests 80% to 90% efficacy for preventing SARS-CoV-2 infection following one dose of the Moderna vaccine. 

Not everyone agrees one dose is a good idea. “Clinical trials with specific schedules for vaccine dosing — that’s the whole basis of the scientific evidence,” Maria Elena Bottazzi, PhD, associate dean of the National School of Tropical Medicine at Baylor College of Medicine in Houston, Texas, told Medscape Medical News.

After one dose “the immune system is learning, but it’s not ideal. That’s why you need the second dose,” Bottazzi said. “I appreciate the urgency and the anxiety…but the data support [that] clinical efficacy requires two doses.”

Another proposed strategy to extend the current supply of COVID-19 vaccines to more Americans involves splitting the current dosage of the Moderna vaccine in half. Officials in the United States and the United Kingdom are reportedly considering this approach. In the US, the FDA would have to approve any dosing change.

Agreeing to Disagree

Wachter shared a link to his opinion piece on Twitter, stating that “We both came to this view because of the slow rollout & the new variant. But it’s a tough call and reasonable people will disagree.”

As predicted, the tweet elicited a number of strong opinions.

“There are no correct answers but there’s data deficiency, plenty of fodder and need for healthy, intellectual debate. That wouldn’t be occurring if there was an ample supply of vaccines,” Eric Topol, MD, director of the Scripps Translational Science Institute and editor-in-chief of Medscape, tweeted on January 3.

“If the problem were with the supply of the vaccine, one might make an argument for focusing on 1st dose. But the problem is in distribution of the vaccine & giving actual doses,” John Grohol, PsyD, tweeted.

“Right now we don’t have a supply issue, we have a distribution issue,” Angela Shen, ScD, MPH, a research scientist in the Vaccine Education Center at Children’s Hospital of Philadelphia, told Medscape Medical News. Emergency use authorization for the Johnson & Johnson and other COVID-19 vaccines in development could further boost available supplies, she added.

“The clinical trials studied two doses,” Shen said. “We don’t have data that one dose is going to have lasting protection.” 

Does New Variant Change Equation?

Wachter and Jha, in their editorial, cited quote from former boxing champion Mike Tyson that, “Everybody has a plan until they’ve been punched in the mouth.” ‘Punches’ such as the new variant, the high number of cases and deaths in the United States, and other problems prompted them to advocate for the delayed dosing strategy.

“Appreciate the concern for the new variant — I think it’s worth noting that we’re punching ourselves in the mouth with the slow vaccine rollout, which is the first problem to solve,” Jake Quinton, MD, an internist at UCLA Health in Los Angeles, noted on twitter.

Vaccine and Public Resistance Raised

“I agree with the problem but not with the proposed solution, which is guess work not based on data,” the Jan Grimm Lab at Memorial Sloan Kettering Cancer Center in New York City responded to Wachter and Jha on Twitter. “There ARE data though that show that 1 shot alone did not elicit sufficient T-cell nor antibody response. This might also lead to mutations resistant to the vaccines. Dangerous!”

Other physicians took to Twitter to point out that changing the recommendations at this point could further erode public confidence in COVID-19 immunization. For example, Deirdre Habermehl, MD, wrote, “We’ve spent months telling the public the best route is to follow the science and now without data think a course correction based on a guesstimate is ok? Public confidence is low enough and the real issue is logistics at this point.”

Shen and Bottazzi have disclosed no relevant financial relationships.

Damian McNamara is a staff journalist based in Miami. He covers a wide range of medical specialties, including infectious diseases, gastroenterology and critical care. Follow Damian on Twitter:  @MedReporter.

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