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What to Know About the Second Dose of the COVID Vaccine

Kelsey Tyler

The Pfizer and Moderna vaccines both involve two injections a few weeks apart. The earliest COVID vaccine recipients, who rolled up their sleeves in mid-December, are now due for shot No. 2. As second doses get underway, however, some are calling them into question.

The vaccine rollout — the largest mass-immunization effort in US history — is moving slower than hoped. As of January 6, nearly 5.5 million people have received their first doses, a number far below the 20-million-by-NYE goal set by the federal government. Distribution delays, as well as surging COVID cases and the recent emergence of a new, more virulent strain of the virus, have some policymakers and members of the medical community pushing for an alternative to the two-dose schedule.

Is the second shot getting the boot? It’s unlikely, experts say. Here’s a breakdown of the one-shot-or-two debate, plus other things to know about the second shot.

Why do you need a second dose?

Based on the data we have, both the Pfizer and Moderna vaccines become maximally effective after two doses. 

The first “priming” dose introduces your body to material from the virus that causes COVID-19. In response, your body starts building antibodies to protect you against future COVID infection.  It takes a few weeks for your body to build these antibodies following the priming dose — as long as 21 days for the Pfizer vaccine and 28 days for the Moderna vaccine.  The second “booster” shot strengthens your immune response. After that, it takes about one to two weeks for the vaccine to become effective.

Efficacy after one dose of the Pfizer vaccine is estimated to be 52 percent, vs. 95 percent after two. The Moderna vaccine showed similar (though not identical) efficacy in trials, and appears to take about two weeks after the second dose to kick in. 

Do the first and second doses have similar side effects? 

Early reports indicate that side effects from the first and second doses of the Pfizer vaccine are similar in type and severity. The most common ones are pain, swelling and redness at the injection site; fatigue; headaches; and muscle and joint pain. While these post-shot symptoms might be unpleasant and unnerving, they aren’t dangerous. In fact, they’re a sign that your immune system is responding to the vaccine the way it’s supposed to.

With that said, healthcare professionals anecdotally report slightly more pronounced side effects after the second dose. 

“Based on the FDA analysis, the side effects or symptoms people complain about after getting the second Pfizer dose are very similar to those of the first dose,” says Dr. Michael Chang, an infectious disease physician at UTHealth in Houston. “But I have heard reports of people complaining more of fatigue after the second dose.”

“The first dose primed your immune system, and now your immune system is ready to react a bit more briskly.” 

Second doses of the Moderna vaccine are not yet being administered in the US. But trials indicate side effects from the second dose may last longer — “from two to three days after the first dose to four to five days for the swelling and tenderness to resolve after the second dose,” Chang says.

Chang also mentions reports of lymph nodes in the neck and under the armpit (of the vaccinated arm) becoming swollen and/or tender after the second dose. “It makes sense they’d be inflamed,” Chang says. “That’s a good thing. The first dose primed your immune system, and now your immune system is ready to react a bit more briskly.” 

Having no side effects is a normal, healthy reaction too. “Everyone responds differently,” Chang says. “If you have symptoms after both doses, or no symptoms after either, that’s fine.”

How’s the second-dose rollout going?

Well, it’s only just starting. 

“Our first round of healthcare providers is getting their second doses this week,” Chang says. “So far, as I’ve heard, that’s going well. Our hospital has a good distribution plan. The follow-up for the second dose was immediately scheduled after people got their first dose, so they are getting their second doses on time. It seems to be going smoothly.”

That said, bigger healthcare systems are dealing with logistical and even ethical issues that may lead to changes in how COVID vaccines are administered once they’re available to the general public. “Everybody is building the plane as it’s flying,” says Dr. Anne Liu, an infectious disease physician at Stanford Health Care. “Large institutions are seeing how difficult it is to do something like this quickly. We’re having to account for equity and access — lots of issues have been raised. At Stanford, we’re trying to vaccinate 36,000 healthcare professionals — it’s several orders of magnitude greater than what smaller institutions are doing. But the processes are getting smoother. When I got mine, it was quick and easy.”

Should we focus on getting single doses to as many people as possible instead?

In clinical trials for the Pfizer and Moderna vaccines, participants who received only a single vaccine dose were much less likely to get COVID than placebo group members, who got no vaccine whatsoever.

Based on that, it might seem like the best way to allocate a limited vaccine supply would be to give the vaccine to as many people as possible, even if that means only administering single doses for now. Unfortunately, it’s not as simple as choosing to give one dose to tons of people vs. two doses to a smaller group. Both the Pfizer and Moderna vaccines require two doses to work the way they’re supposed to. The FDA approved the optimal versions of the vaccines, and only those versions. 

“When you look at single-dose data from the FDA papers on both vaccines, there’s a trend that, after a single dose, it may be effective,” Chang says. “Pfizer reported that its vaccine is 82 percent effective after the first dose. But this is for a population that didn’t complete the vaccination with a second dose. For those who got the first dose, the vaccine was 51 percent effective in the 21 days between doses. There’s a chance a single dose is effective, but you’re extrapolating data the study wasn’t designed to answer.”

“From a public health messaging standpoint, changing out vaccination recommendations will be problematic, to say the least.”

He continues, “That’s a risky extrapolation. You don’t know if you expand the single dose plan to a bunch of people that you’ll achieve anything like you want to achieve. With respect to how this vaccine is going to work, lean towards the sure thing versus this might work.”

Also, the proposal to give people only enough of a vaccine to confer partial immunity implies we don’t have enough to go around. But that’s not really the case.

“I do not think we have a shortage of vaccines at the moment, where this approach may make more sense,” says Dr. Chad Sanborn, a pediatric infectious disease specialist at KIDZ Medical Services in West Palm Beach, Florida. “Rather, we have more of a problem getting it out to enough people in a timely manner. I don’t know that giving only one dose to a lot of people would be accomplished that much quicker; we need improvements in vaccine distribution and administration, not supply.”

Sanborn also points out that upending the distribution strategy we just started implementing could undermine the ongoing efforts to immunize everybody. “From a public health messaging standpoint, changing out vaccination recommendations will be problematic, to say the least,” Sanborn says. “There certainly have been issues with getting the public to trust our public health institutions with the ever-changing advice. If we do this again, that damages that trust.”

The CDC and FDA have made it clear that deviating from the current two-dose schedule poses a significant public health risk, noting that proposed changes are “premature and not rooted solidly in the available evidence.” And yet, the debate continues, even within the medical community.

“That’s the disconnect between data-driven decision-making and policy that has to happen in an emergency,” Chang says. “Wouldn’t it be great to have confidence in a single-dose solution? I wish that the study had been designed that way in the first place so the medical community could be more in agreement.”

Chang advises keeping the overall goal of a study in mind when looking at pieces of it. In this case, Pfizer and Moderna carried out clinical testing to find a safe and effective COVID vaccine — and vaccine schedule — and that’s what they’ve achieved. 

“Just because you see a result in the data doesn’t mean you can draw a conclusion from that result,” Chang says. “I’ve seen social media posts that suggest Asian people should get the Pfizer vaccine, that it works better for them. The study was not designed to answer that question, at all. This is based on one case in four — that’s not enough to make that conclusion. When you look at sub-groups, you take a lot out of it — and you’re not answering the question you thought you were.”

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