Why we shouldn't panic about the millions who missed their second vaccine dose—yet

Five million people in the U.S. missed their second jab, and some scientists see a glimmer of hope in that statistic. We dig into the nuances behind the number.

This past weekend, I became a statistic. Sitting among a sea of tables at an office building-turned-vaccination center, I received my second dose of a COVID-19 vaccine.

In just two weeks, I'll become one of more than 100 million people in the United States considered fully vaccinated. Yet not everyone who receives one of the available two-dose vaccines returns for their second shot: So far, some five million people in the U.S., roughly 8 percent of those who received a first dose, have missed their follow-up round.

Based on data from the Centers for Disease Control and Prevention and first reported by the New York Times, the statistic sent many people into a spiral of worry and spurred finger-pointing at this supposedly remiss populationYet many scientists see a glimmer of hope: 8 percent missed means 92 percent returned, which is surprisingly high.

"I see that as a really amazing win," says Saskia Popescu, an infection prevention epidemiologist at the University of Arizona’s Mel and Enid Zuckerman College of Public Health. "There’s not enough credit that goes into acknowledging how national vaccination in the middle of a pandemic is a Herculean effort."

At the same time, exactly why people are missing their second doses remains uncertain, with reports suggesting a combination of factors from fears over side effects to distribution snafus. We break down why this number has been interpreted as both worrisome and celebratory news, why it’s important to complete the two-dose series, why you don’t need to panic if you miss the second dose—and how it's still not too late to get it if you can.

Who are the 8 percent?

The CDC classifies a record of a "missed dose" as someone who received a first dose but not the second within six weeks, per their recommended schedule for vaccines requiring two doses. An earlier analysis of vaccine data through February 14, 2021, indicated a mere 3.4 percent had missed their second dose. The number has more than doubled in the latest analysis, which includes data through April 9. 

But the earlier vaccination period was largely limited to people receiving their shots through their worksite or residence, such as healthcare providers and long-term care centers, which significantly lowers the barriers for receiving the second dose. "Overall, this increase in missed second doses was expected as eligibility expands to more people," a CDC spokesperson says in an emailed statement to National Geographic.

People missing doses of multi-dose vaccines is nothing new. One study of the shingles vaccine administered between 2017 and 2019 found that only between 70 and 80 percent of recipients completed the two-dose series. The current situation with COVID-19 is even more complex, Popescu says. Healthcare systems are stressed. Vaccine distribution's been rocky. And the challenges of communicating the vaccine's efficacy and safety loom large.

Some people might have skipped the second dose because of concerns about potential side effects, which can be more severe after the second shot. The challenge may be especially acute for people who don't have childcare or can't take paid time off work and so can’t afford the downtime to recover, Popescu notes. 

Still others may not have had an option to get their shot due to pharmacy supplies running low or difficulty finding sites with doses from the same company as their first shot. On May 4, the Biden administration announced a shift in strategy to make the shots more accessible, with a goal that 70 percent of U.S. adults are at least partially vaccinated by July 4.

For now, the precise reasons for missed doses remain uncertain. Popescu emphasizes the importance of tracking future missed doses to understand why people are not returning and eliminate any hurdles.

How much protection does one dose impart?

Recent studies have provided some encouraging numbers for the immune response after a single shot of either the Moderna or Pfizer-BioNtech vaccine. A study of 3,950 healthcare personnel found that one dose of either mRNA vaccine provided roughly 80 percent protection against SARS-CoV-2 infection at least 14 days after injection. Another analysis of healthcare workers in the United Kingdom, which is not yet peer-reviewed, found that a single dose of Pfizer-BioNTech's vaccine had an effectiveness of 72 percent 21 days after injection.

And for people previously infected with SARS-CoV-2, an increasing number of studies suggest their immune systems strongly kick into gear upon their first dose of an mRNA vaccine. The result is "a second dose-like response to their primary dose," explains Sarah Cobey, epidemiologist and evolutionary biologist at the University of Chicago. "They responded beautifully." With more than 30 million reported SARS-CoV-2 infections in the United States, at least some of the 8 percent likely had past exposures to the virus.

So why does the second shot matter?

With such promising reports of protection after the first dose, why go back for the second? "Because that's not going to last forever," says Chise Broussard, a molecular biologist specializing in viral pathogenesis and host immunity at Moderna. The key is which parts of the immune system get activated by each dose.

Both the first and second doses have exactly the same ingredients, but each shot awakens different players in the immune system, Broussard says. The first dose is what's known as a primer and introduces your body to the virus. This dose activates what are known as helper T cells, which have many jobs. One vital role is assisting another part of the immune system, called B cells, in producing antibodies specific to the SARS-CoV-2 virus.

While these tiny soldiers get all the attention, "it's not all about the antibodies," Broussard says. "That’s where that second dose comes in."

The second dose is a booster, supercharging the defenses the first dose put into action. One set of crucial players in this are the so-called killer T cells, which do as their name promises, slaying the virus-infected cells, Broussard explains. While those initial vaccine-induced antibodies will eventually wane, the T cells provide much more durable protection.

"Your antibodies are your sword," she says, "but your T cells are your shield."

The second dose pushes effectiveness in preventing infection for the Pfizer-BioNTech and Moderna vaccines to roughly 90 percent in real-world settings. And results from an ongoing phase one trial of the Moderna vaccine suggest the vaccine-induced antibodies last at least six months through the end of the analysis period.

Cobey notes that there’s not yet clear evidence of benefits from the second dose for people who were previously infected. But the CDC still requires people with past SARS-CoV-2 infections to return for a second shot to be considered fully vaccinated.

Can I still get the vaccine if I missed the recommended window?

In short, yes. Currently, the CDC recommends receiving the second dose of the Pfizer-BioNTech and Moderna vaccines three or four weeks after the first shot, respectively. But if necessary, there can be a gap of up to six weeks later. Yet these officially recommended windows weren't optimized for the best immune response, but a desire to increase the speed at which people can get full vaccine protection.

"Given the urgency of the pandemic, we wanted to get people to that fully protected level as quickly as possible," says Brianne Barker, a viral immunologist at Drew University in New Jersey. A slightly longer window between doses likely will still provide adequate protection, she notes.

Study of the intervals for COVID-19 vaccines is limited. Early data from 45,965 adults in the U.K. shows that giving second doses of Pfizer-BioNTech's or Oxford-AstraZeneca's vaccine 12 weeks after the first shot still sparked robust immune responses for people of all ages.

More data on longer dosing intervals will likely soon emerge from both the U.K. and Canada, where the short supply of vaccinations led officials to delay second shots in favor of delivering first doses to more people. This strategy, known as dose sparing, will potentially save more lives than concentrating a limited availability of shots in a smaller population, University of Chicago's Cobey says.

For the people in the U.S. who missed their dose because they couldn't find a shot, it's not too late, says Abinash Virk, co-chair of Mayo Clinic's COVID-19 Vaccine Allocation and Distribution Work Group. Even 60, 80, or 90 days later, she says, "yes, still go ahead and get it."

What does partial immunization mean for new variants and breakthrough infections?

No vaccine provides 100 percent protection, so even after full vaccination for COVID-19 there will be scattered instances of infections, known as breakthroughs. As of April 26, 2021, the CDC had received reports of a total of 9,245 breakthrough infections out of the more than 95 million people fully vaccinated. While rare cases of hospitalization and death may occur from breakthrough infections, vaccination reduces the risk of severe cases of COVID-19.

The possibility of infection among people who are only partially protected has raised some scientists' concern that these instances could drive the development of variants. The idea may stem, in part, from prior work suggesting the variant first spotted in the UK, B.1.1.7, emerged during a lengthy infection in an immunocompromised patient, Cobey says.

During these infections, the virus has long periods to accrue mutations. Added pressure from partially effective treatments, such as convalescent plasma and monoclonal antibodies, might have then provided the virus with an evolutionary spark, allowing some mutations beneficial to the virus to dominate in a process similar to bacteria developing resistance to antibiotic drugs.

But the situation with vaccinations is quite different, Cobey argues. COVID-19 vaccines seem to put a damper on the viral party, causing milder infections with smaller viral populations. One study, which is not yet peer-reviewed, found that breakthrough infections after just one dose of the Pfizer-BioNtech vaccine had up to 20 times lower viral populations compared to infections in unvaccinated individuals.

Smaller viral populations mean there are fewer opportunities for the virus to replicate and accrue new mutations, staunching the chances of new variants arising, Cobey says. "Your immune system has a leg up." These lower viral populations after one shot also hint at a  lower potential to pass the infection along, so even if new variants did arise, they're less likely to spread.

What about side effects from the second shot?

All this revving of the immune system through vaccination can cause a range of side effects, including fever, headaches, body aches, and fatigue. These are commonly more intense after the second dose, which induces the most vigorous immune response, Barker explains.

But not everyone will experience side effects. And the good news is that the majority of people experience only mild effects that last one or two days. "I would put up with feeling like I have a very crummy mild flu than to ever feel the effects of COVID," Broussard says.

For individuals worried about longer-lasting vaccine side effects, Barker suggests talking with a personal physician. It's easy to blame the vaccine for a lingering headache or fatigue, but many of these symptoms are common in daily life, especially after enduring more than a year in lockdowns.

In some cases, she jokes, the answer just might be "2020 made you tired." 

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