One Shot or Two? What Delays Between Each COVID-19 Dose Mean

Woman Receiving Vaccine

Editor’s Note: A new study from Israel added showed that the Pfizer vaccine is 85% effective two weeks after the first dose.

Stay tuned for news on the COVID-19 vaccine, because recently the latest on its availability has led to updated guidelines of how long patients can safely wait between receiving the first and second doses of the two-part vaccines.

On Jan. 21, the Centers for Disease Control and Prevention (CDC) said up to six weeks can safely pass between the first and second doses, which extends earlier recommendations of 21 days and 28 days between the Pfizer and Moderna vaccines, respectively, whose shorter time frames were tested by the manufacturers and approved by the US Food and Drug Administration (FDA).

Earlier in January, federal officials had suggested that it’s more important to ensure that everyone gets their first dose, so no vaccines are held back to guarantee timely second doses, creating the possibility of fluctuations in supply that could lead to the longer time frame between the first and second doses. 

Experts told MedShadow that there’s a chance that delaying the second dose could make the vaccines less effective and that, more importantly, if not communicated effectively, it could erode public trust.  

“It’s possible that if you went too far out [in administering the second dose] that you could get lower efficacy,” says Kartik Cherabuddi, MD, an infectious disease expert at the University of Florida, who spoke to MedShadow from his home. He was resting there because he had minor side effects after receiving the second dose of the vaccine. 

The Current Plan: Distributing All the Doses 

Giving out the first dose of vaccine instead of saving stock of the second dose means that more people will get the first shot quicker, but they could wait longer for the second dose if the vaccine stock runs short later.  

In the clinical trials for the Pfizer and Moderna vaccines, patients were given the first and second doses 21 or 28 days apart, respectively. The researchers tested using these relatively short intervals because the vaccines needed to be approved and distributed quickly. Longer intervals would have required more lengthy trials and more of a wait for frontline workers, for example, and the public at large to get the vaccine. The first dose of the Pfizer vaccine provides at least 52% protection and of Moderna, 80%. For both, the protection levels rise to about 95% after the second injection. However, a separate analysis of Pfizer’s clinical trial data that looked at efficacy about a week after the first dose suggested the efficacy increased to 92.6%. A recent study of over 7,000 hospital workers out of Israel led credibility to the claim, finding a single dose of Pfizer’s vaccine to be 85% protective after 15-28 days.

Under this plan, the priority is getting the vaccine to more people — even if they only get partial protection from the first dose — rather than giving both doses and nearly full protection to fewer people.

“The first dose is the most important dose. There is no telling whether people will come back to get the second dose,” says Shamard Charles, MD, MPH, an assistant professor of public health and health promotion at St. Francis University. “We have to focus on Step 1 first, which is to ensure that everyone gets the first dose.” 

However, he adds, the caveat is that those at high risk of exposure (hospital staff, associated essential workers and nursing home residents) need both doses, and that there should be “no questions asked” on that count.

The United Kingdom (UK) is under extra pressure to get its residents inoculated, as a mutated version of the virus estimated to be 50% more contagious has been circulating there and cases are mounting. The country was the first to announce it would be following a flexible protocol, allowing patients to get the second shot of the Oxford-AstraZeneca vaccine (not yet approved for use in the US, but designed to be given as two shots 21 days apart) or the Pfizer vaccine, up to three months after the first.

Since the Oxford-AstraZeneca’s clinical trial included some patients who got the two shots up to 26 weeks apart, the UK’s Medicines and Healthcare Products Regulatory Agency analyzed data from multiple trials and found that those who received the two shots farther apart ended up with even greater protection than those who received them 21 days apart (73% compared to 62% efficacy).

In the Pfizer trial, some patients were vaccinated after longer than the intended 21-day pause — up to 42 days — but an analysis has not been conducted comparing the efficacy of the vaccine in these patients to those who received the two shots within the shorter time frame. Kathleen Neuzil, an epidemiologist at the University of Maryland School of Medicine, told Science that longer intervals between the first and second shots may improve the efficacy of some vaccines, but she is hesitant about delaying the second shot for vulnerable patients (those over 65 or with comorbid conditions) whose immune systems might not respond as strongly to the vaccine. Moderna’s trials did not mention longer gaps between the two doses.

An Alternative: Cutting doses in half

There is some evidence from Moderna’s early trials that for patients ages 18 to 55, half doses may elicit just as strong an immune response as full doses, but the full dose is more effective in those patients older than 55.

The smaller dose was not tested in the larger studies to confirm that it could prevent disease.

A Possible Complication: Mixing and matching       

Since communities are receiving vaccines as they are produced, there’s a chance that fluctuations in supply could lead to healthcare professionals considering “mixing and matching” brands of the COVID-19 vaccines. For example, if a patient’s first shot was the Pfizer vaccine, their second might be the Moderna, because that’s the only one available.

We don’t have any studies comparing the efficacy of two doses of one vaccine versus one dose of each. But, Charles says, “the technology used for the Moderna and Pfizer vaccines are largely the same. In my opinion, I don’t see anything wrong with mixing and matching. But, without data to support its efficacy and low side effect profile, it may be best to provide people with the same two doses of the vaccine while we conduct clinical trials to support safety claims.”

A Key Challenge: Instilling trust 

Both Charles and Cherabuddi agree that one of the biggest issues is communication and public trust. They’re especially worried that changing the way we distribute the vaccine will make people question its safety and become less likely to get it. “My concern is the scientific approach to the messaging of it right now. We can’t tell people you should get the same vaccine if they can do it, and then also tell them it’s okay to mix and match,” says Cherabuddi. “It can’t be one institution, one city or even one state [making plans]. This has to be central and it has to be done with agreement,” among experts and with the message to the public.

Charles adds that getting the vaccine out to patients requires building trust in a variety of ways. “We must create an equitable distribution model that involves hiring BIPOC [Black, Indigenous and People of Color] healthcare workers to administer the vaccine, making sure the vaccine is widely available and free of charge, and meeting people where they are by talking at socially distanced churches and town hall meetings, and via social media.”


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