Tag: COVID shot

COVID Vaccines Are Turning Into Flu Shots

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For all the legwork that public-health experts have done over the past few years to quash comparisons between COVID-19 and the flu, there sure seems to be a lot of effort nowadays to equate the two. In an advisory meeting convened earlier today, the FDA signaled its intention to start doling out COVID vaccines just like flu shots: once a year in autumn, for just about everyone, ad infinitum. Whatever the brand, primary-series shots and boosters (which might no longer be called “boosters”) will guard against the same variants, making them interchangeable. Doses will no longer be counted numerically. “This will be a fundamental transition,” says Jason Schwartz, a vaccine policy expert at Yale—the biggest change to the COVID-vaccination regimen since it debuted.

Hints of the annual approach have been dropping, not so subtly, for years. Even in the spring of 2021, Pfizer’s CEO was floating the idea of yearly shots; Peter Marks, the director of the FDA’s Center for Biologics Evaluation and Research, teased it throughout 2022. This past September, Joe Biden officially endorsed it as “a new phase in our COVID-19 response,” and Ashish Jha, the White House’s COVID czar, memorably highlighted the convenience of combining a flu shot and a COVID shot into a single appointment: “I really believe this is why God gave us two arms.”

Still, in today’s meeting, FDA officials were pushier than ever in their advocacy for the flu-ification of COVID vaccines. “We think that simplification of the vaccination regimen would contribute to easier vaccine deployment, better communication, and improved vaccine coverage,” Jerry Weir, the FDA’s director of the division of viral products, said at the meeting. The timing is important: After renewing the U.S.’s pandemic-emergency declaration earlier this month, the Biden administration seems set to allow its expiration this coming April. That makes the present moment awfully convenient for repackaging a chaotic, crisis-caliber vaccination paradigm as a scheduled, seasonal, normal-seeming one. A once-a-year strategy, modeled on a routine recommendation, suggests that “we’re no longer in emergency mode,” says Maria Sundaram, a vaccine researcher at the Marshfield Clinic Research Institute. Or at least, that’s the message that the public is likely to hear.

But federal regulators may be trying to fit a COVID-shaped peg into a flu-shaped hole. The experts I spoke with largely agreed: Eventually, someday, annual autumn shots for COVID “will probably be sufficient,” says Gregory Poland, a vaccinologist at Mayo Clinic. “Are we ready for that yet? I’m not sure that’s the case at all.”

Even in the short term, COVID-vaccination tactics need a revamp. “It’s clear above all that the current approach isn’t working,” Schwartz told me. Despite abundant supply, demand for COVID boosters in the U.S. has been abysmal—and interest seems to be declining with each additional dose. Last fall’s bivalent shot has reached the arms of only 15 percent of Americans; even among adults over 65—a majority of whom sign up for flu shots each fall—the vaccination rate hasn’t yet reached 40 percent.

For most of the time that COVID shots have been around, figuring out when to get them has been a hassle, with different guidelines and requirements that depend on age, sex, risk factors, vaccination history, and more. Pharmacies have had to stock an absurd number of vials and syringes to accommodate the various combinations of brands and dose sizes; record-keeping on flimsy paper cards has been a total joke. “I do this for a living, and I can barely keep track,” Schwartz said. Recommendations on the proper timing and number of doses have also changed so many times that many Americans have simply checked out. After the bivalent recipe debuted, polls found that an alarming proportion of people didn’t even know the shot was available to them.

Streamlining COVID-vaccine recommendations will remove a lot of that headache, Sundaram told me. Most people would need to keep only one mantra in mind—one dose, each fall—and could top off their flu and COVID immunity at the same time. Burdens on pharmacies and clinics would be lower, and communication would be far easier—a change that could make an especially big difference for those with children, among whom COVID-vaccine uptake has been the lowest. “It’ll be more scheduled, more systematic,” says Charlotte Hobbs, a pediatric infectious-disease specialist at the University of Mississippi Medical Center. COVID shots could simply be offered at annual well-child visits, she told me. “It’s something we already know works well.”

The advantages of a flu-ified COVID shot aren’t just about convenience. If we have to shoehorn COVID vaccines into an existing paradigm, Sundaram told me, influenza’s is the best candidate. SARS-CoV-2, like the flu, is excellent at altering itself to dodge our defenses; it spreads readily in winter; and our immunity to infection tends to fade rather quickly. All of that adds up to a need for regularly updated shots. Such a system has been in place for decades for the flu: At the end of each winter, a panel of experts convenes to select the strains that should be targeted by the next formulation; manufacturers spend the next several months whipping up big batches in time for an autumn-ish rollout. The pipeline depends on a global surveillance system for flu viruses, as well as regular surveys of antibody levels in the community to suss out which strains people are still protected against. The premise has been so well vetted by now that researchers can skip the chore of running large-scale clinical trials to determine the efficacy and safety of each new, updated recipe.

But a seasonal strategy works best for a seasonal virus—and SARS-CoV-2 just isn’t there yet, says Hana El Sahly, an infectious-disease physician at Baylor College of Medicine. Though flu viruses tend to hop between the globe’s hemispheres, alternately troubling the north and the south during their respective cold months, this new coronavirus has yet to confine its spread to one part of the calendar. (Marks, of the FDA, tried to address this concern at today’s meeting, asserting that “we’re starting to see some seasonality” and that fall was indeed the very sensible for an annual rollout.) SARS-CoV-2 has also been spitting out concerning variants and subvariants at a faster rate than the flu (and flu shots already have a hard time keeping up with evolution). The FDA’s new proposal suggests picking SARS-CoV-2 variants in June to have a vaccine ready by September, a shorter timeline than is used for flu. That still might not be fast enough: “By the time we detect a variant, it will have ripped through the global population and, in a few more weeks, died down,” El Sahly told me. The world got a preview of this problem with last year’s bivalent shot, which overlapped with the dominance of its target subvariants for only a couple of months. A flu model for COVID would make more sense “if we had stable, predictable dynamics,” says Avnika Amin, a vaccine epidemiologist at Emory University. “I don’t think we’re at that point.”

Murkiness around vaccine effectiveness makes this transition complicated too. Experts told me that it’s gotten much more difficult to tell how well our COVID vaccines are working, and for how long, fueling debates over how often they should be given and how often their composition should change. Many people have now been infected by the virus multiple times, which can muddy calculations of vaccine effectiveness; better treatments also alter risk profiles. And many researchers told me they’re concerned that the data shortcuts we use for flu—measures of antibodies as a proxy for immune protection—just won’t fly for COVID shots. “We need better clinical data,” El Sahly told me. In their absence, the hasty adoption of a flu framework could lead to our updating and distributing COVID shots too often, or not often enough.

A flu-ish approach also wouldn’t fix all of the COVID vaccines’ problems. Today’s discussion suggested that, even if a new COVID-shot strategy change goes through, officials will still need to recommend several different dose sizes for several different age groups—a more complex regimen than flu’s—and may advise additional injections for those at highest risk. At the same time, COVID shots would continue to be more of a target for misinformation campaigns than many other vaccines and, at least in the case of mRNA-based injections, more likely to cause annoying side effects. These issues and others have driven down interest—and simply pivoting to the flu paradigm “is not going to solve the uptake problem,” says Angela Shen, a vaccine-policy expert at Children’s Hospital of Philadelphia.

Perhaps the greatest risk of making COVID vaccines more like flu shots is that it could lead to more complacency. In making the influenza paradigm a model, we also threaten to make it a ceiling. Although flu shots are an essential, lifesaving public-health tool, they are by no means the best-performing vaccines in our roster. Their timeline is slow and inefficient; as a result, the formulations don’t always match circulating strains. Already, with COVID, the world has struggled to chase variants with vaccines that simply cannot keep up. If we move too quickly to the fine-but-flawed framework for flu, experts told me, it could disincentivize research into more durable, more variant-proof, less side-effect-causing COVID shots. Uptake of flu vaccines has never been stellar, either: Just half of Americans sign up for the shots each year—and despite years of valiant efforts, “we still haven’t figured out how to consistently improve that,” Amin told me.

Whenever the COVID-emergency declaration expires, vaccination will almost certainly have to change. Access to shots may be imperiled for tens of millions of uninsured Americans; local public-health departments may end up with even fewer resources for vaccine outreach. A flu model might offer some improvements over the status quo. But if the downsides outweigh the pluses, Poland told me, that could add to the erosion of public trust. Either way, it might warp attitudes toward this coronavirus in ways that can’t be reversed. At multiple points during today’s meeting, FDA officials emphasized that COVID is not the flu. They’re right: COVID is not the flu and never will be. But vaccines can sometimes become a lens through which we view the dangers they fight. By equating our frontline responses to these viruses, the U.S. risks sending the wrong message—that they carry equal threat.

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Katherine J. Wu

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January 26, 2023
Is COVID Immunity Hung Up on Old Variants?

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In the two-plus years that COVID vaccines have been available in America, the basic recipe has changed just once. The virus, meanwhile, has belched out five variants concerning enough to earn their own Greek-letter names, followed by a menagerie of weirdly monikered Omicron subvariants, each seeming to spread faster than the last. Vaccines, which take months to reformulate, just can’t keep up with a virus that seems to reinvent itself by the week.

But SARS-CoV-2’s evolutionary sprint might not be the only reason that immunity can get bogged down in the past. The body seems to fixate on the first version of the virus that it encountered, either through injection or infection—a preoccupation with the past that researchers call “original antigenic sin,” and that may leave us with defenses that are poorly tailored to circulating variants. In recent months, some experts have begun to worry that this “sin” might now be undermining updated vaccines. At an extreme, the thinking goes, people may not get much protection from a COVID shot that is a perfect match for the viral variant du jour.

Recent data hint at this possibility. Past brushes with the virus or the original vaccine seem to mold, or even muffle, people’s reactions to bivalent shots—“I have no doubt about that,” Jenna Guthmiller, an immunologist at the University of Colorado School of Medicine, told me. The immune system just doesn’t make Omicron-focused antibodies in the quantity or quality it probably would have had it seen the updated jabs first. But there’s also an upside to this stubbornness that we could not live without, says Katelyn Gostic, an immunologist and infectious-disease modeler who has studied the phenomenon with flu. Original antigenic sin is the reason repeat infections, on average, get milder over time, and the oomph that enables vaccines to work as well as they do. “It’s a fundamental part,” Gostic told me, “of being able to create immunological memory.”

This is not just basic biology. The body’s powerful first impressions of this coronavirus can and should influence how, when, and how often we revaccinate against it, and with what. Better understanding of the degree to which these impressions linger could also help scientists figure out why people are (or are not) fighting off the latest variants—and how their defenses will fare against the virus as it continues to change.

The worst thing about “original antigenic sin” is its name. The blame for that technically lies with Thomas Francis Jr., the immunologist who coined the phrase more than six decades ago after noticing that the initial flu infections people weathered in childhood could bias how they fared against subsequent strains. “Basically, the flu you get first in life is the one you respond to most avidly for the long term,” says Gabriel Victora, an immunologist at Rockefeller University. That can become somewhat of an issue when a very different-looking strain comes knocking.

In scenarios like these, original antigenic sin may sound like the molecular equivalent of a lovesick teen pining over an ex, or a student who never graduates out of immunological grade school. But from the immune system’s point of view, never forgetting your first is logically sound. New encounters with a pathogen catch the body off guard—and tend to be the most severe. A deep-rooted defensive reaction, then, is practical: It ups the chances that the next time the same invader shows up, it will be swiftly identified and dispatched. “Having good memory and being able to boost it very quickly is sometimes a very good thing,” Victora told me. It’s the body’s way of ensuring that it won’t get fooled twice.

Read: Annual COVID shots mean we can stop counting

These old grudges come with clear advantages even when microbes morph into new forms, as flu viruses and coronaviruses often do. Pathogens don’t remake themselves all at once, so immune cells that home in on familiar snippets of a virus can still in many cases snuff out enough invaders to prevent an infection’s worst effects. That’s why even flu shots that aren’t perfectly matched to the season’s most prominent strains are usually still quite good at keeping people out of hospitals and morgues. “There’s a lot of leniency in how much the virus can change before we really lose protection,” Guthmiller told me. The wiggle room should be even bigger, she said, with SARS-CoV-2, whose subvariants tend to be far more similar to one another than, say, different flu strains are.

With all the positives that immune memory can offer, many immunologists tend to roll their eyes at the negative and bizarrely moralizing implications of the phrase original antigenic sin. “I really, really hate that term,” says Deepta Bhattacharya, an immunologist at the University of Arizona. Instead, Bhattacharya and others prefer to use more neutral words such as imprinting, evocative of a duckling latching onto the first maternal figure it spots. “This is not some strange immunological phenomenon,” says Rafi Ahmed, an immunologist at Emory University. It’s more a textbook example of what an adaptable, high-functioning immune system does, and one that can have positive or negative effects, depending on context. Recent flu outbreaks have showcased a little bit of each: During the 2009 H1N1 pandemic, many elderly people, normally more susceptible to flu viruses, fared better than expected against the late-aughts strain, because they’d banked exposures to a similar-looking H1N1—a derivative of the culprit behind the 1918 pandemic—in their youth. But in some seasons that followed, H1N1 disproportionately sickened middle-aged adults whose early-life flu indoctrinations may have tilted them away from a protective response.

Read: COVID science is moving backwards

The backward-gazing immune systems of those adults may have done more than preferentially amplify defensive responses to a less relevant viral strain. They might have also actively suppressed the formation of a response to the new one. Part of that is sheer kinetics: Veteran immune cells, trained up on past variants and strains, tend to be quicker on the draw than fresh recruits, says Scott Hensley, an immunologist at the Perelman School of Medicine at the University of Pennsylvania. And the greater the number of experienced soldiers, the more likely they are to crowd out rookie fighters—depriving them of battlefield experience they might otherwise accrue. Should the newer viral strain eventually return for a repeat infection, those less experienced immune cells may not be adequately prepared—leaving people more vulnerable, perhaps, than they might otherwise have been.

Some researchers think that form of imprinting might now be playing out with the bivalent COVID vaccines. Several studies have found that the BA.5-focused shots are, at best, moderately more effective at producing an Omicron-targeted antibody response than the original-recipe jab—not the knockout results that some might have hoped for. Recent work in mice from Victora’s lab backs up that idea: B cells, the manufacturers of antibodies, do seem to have trouble moving past the impressions of SARS-CoV-2’s spike protein that they got from first exposure. But the findings don’t really trouble Victora, who gladly received his own bivalent COVID shot. (He’ll take the next update, too, whenever it’s ready.) A blunted response to a new vaccine, he told me, is not a nonexistent one—and the more foreign a second shot recipe is compared with the first, the more novice fighters should be expected to participate in the fight. “You’re still adding new responses,” he said, that will rev back up when they become relevant. The coronavirus is a fast evolver. But the immune system also adapts. Which means that people who receive the bivalent shot can still expect to be better protected against Omicron variants than those who don’t.

Historical flu data support this idea. Many of the middle-aged adults slammed by recent H1N1 infections may not have mounted perfect attacks on the unfamiliar virus, but as immune cells continued to tussle with the pathogen, the body “pretty quickly filled in the gaps,” Gostic told me. Although it’s tempting to view imprinting as a form of destiny, “that’s just not how the immune system works,” Guthmiller told me. Preferences can be overwritten; biases can be undone.

Original antigenic sin might not be a crisis, but its existence does suggest ways to optimize our vaccination strategies with past biases in mind. Sometimes, those preferences might need to be avoided; in other instances, they should be actively embraced.

For that to happen, though, immunologists would need to fill in some holes in their knowledge of imprinting: how often it occurs, the rules by which it operates, what can entrench or alleviate it. Even among flu viruses, where the pattern has been best-studied, plenty of murkiness remains. It’s not clear whether imprinting is stronger, for instance, when the first exposure comes via infection or vaccination. Scientists can’t yet say whether children, with their fiery yet impressionable immune systems, might be more or less prone to getting stuck on their very first flu strain. Researchers don’t even know for certain whether repetition of a first exposure—say, through multiple doses of the same vaccine, or reinfections with the same variant—will more deeply embed a particular imprint.

It does seem intuitive that multiple doses of a vaccine could exacerbate an early bias, Ahmed told me. But if that’s the case, then the same principle might also work the other way: Maybe multiple exposures to a new version of the virus could help break an old habit, and nudge the immune system to move on. Recent evidence has hinted that people previously infected with an early Omicron subvariant responded more enthusiastically to a bivalent BA.1-focused vaccine—available in the United Kingdom—than those who’d never encountered the lineage before. Hensley, at the University of Pennsylvania, is now trying to figure out if the same is true for Americans who got the BA.5-based bivalent shot after getting sick with one of the many Omicron subvariants.

Ahmed thinks that giving people two updated shots—a safer approach, he points out, than adding an infection to the mix—could untether the body from old imprints too. A few years ago, he and his colleagues showed that a second dose of a particular flu vaccine could help shift the ratio of people’s immune responses. A second dose of the fall’s bivalent vaccine might not be practical or palatable for most people, especially now that BA.5 is on its way out. But if next autumn’s recipe overlaps with BA.5 in ways that it doesn’t with the original variant—as it likely will to at least some degree, given the Omicron lineage’s continuing reign—a later, slightly different shot could still be a boon.

Keeping vaccine doses relatively spaced out—on an annual basis, say, à la flu shots—will likely help too, Bhattacharya said. His recent studies, not yet published, hint that the body might “forget” old variants, as it were, if it’s simply given more time: As antibodies raised against prior infections and injections fall away, vaccine ingredients could linger in the body rather than be destroyed by prior immunity on sight. That slightly extended stay might offer the junior members of the immune system—lesser in number, and slower on the uptake—more of an opportunity to cook up an Omicron-specific response.

In an ideal world, researchers might someday know enough about imprinting to account for its finickiness whenever they select and roll out new shots. Flu shots, for instance, could be personalized to account for which strains babies were first exposed to, based on birth year; combinations of COVID vaccine doses and infections could dictate the timing and composition of a next jab. But the world is not yet living that reality, Gostic told me. And after three years of an ever-changing coronavirus and a fluctuating approach to public health, it’s clear that there won’t be a single vaccine recipe that’s ideal for everyone at once.

Even Thomas Francis Jr. did not consider original antigenic sin to be a total negative, Hensley told me. According to Francis, the true issue with the “sin” was that humans were missing out on the chance to imprint on multiple strains at once in childhood, when the immune system is still a blank slate—something that modern researchers could soon accomplish with the development of universal vaccines. Our reliance on first impressions can be a drawback. But the same phenomenon can be an opportunity to acquaint the body with diversity early on—to give it a richer narrative, and memories of many threats to come.

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Katherine J. Wu

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January 11, 2023
Should Your Flu and COVID Shots Go in Different Arms?

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At a press briefing earlier this month, Ashish Jha, the White House’s COVID czar, laid out some pretty lofty expectations for America’s immunity this fall. “Millions” of Americans, he said, would be flocking to pharmacies for the newest version of the COVID vaccine in September and October, at the same appointment where they’d get their yearly flu shot. “It’s actually a good idea,” he told the press. “I really believe this is why God gave us two arms.”

That’s how I got immunized last week at my local CVS: COVID shot on the left, flu shot on the right. I spent the next day or so nursing not one but two achy upper arms. Reaching high shelves was hard; putting on deodorant was worse. And it did make me wonder what would have happened if I’d ignored Jha’s teleological advice and gotten both jabs in the same arm. Maybe my annoyance would have been lessened. Or perhaps the same-side shots would have made the soreness in my left arm way worse. When I posed this puzzle to immunologists, vaccinologists, and pharmacists, I got back a lot of hems and haws. For the millions of Americans who will be getting two-shot appointments by fall’s end, they told me, the choice really does come down to personal preference in the absence of clear data: You’ve just gotta pick a side. Or, you know, two.

On the one hand (sorry), there are the vaccine double-downers. Sallie Permar, a pediatrician at Weill Cornell Medicine, and Stephanie Langel, an immunologist at Duke University, both said they’d probably get both shots in the same shoulder; so would Rishi Goel, an immunologist at the University of Pennsylvania. “Personally, I’d rather have one arm that’s slightly uncomfortable than both,” Goel told me.

On the other hand, we’ve got Team Divide-and-Conquer. Several experts said they’d follow the White House protocol of splitting shots left and right. Ali Ellebedy, an immunologist at Washington University in St. Louis, told me he’d prefer to have two slightly sore arms to one totally dead one. Jacinda Abdul-Mutakabbir, a pharmacist at Loma Linda University, says she generally recommends that her patients get the vaccines on separate sides “for comfort.” Last year, she opted to get the flu shot and a COVID booster within a few inches of each other, and “I wanted to chop my arm off,” she told me. “Never again.”

Read: America’s fall booster plan has a fatal paradox

The deciding logic here should be pretty intuitive, Permar told me. Two shots on one side might be expected to double how sore that arm will get, though the experience of each vaccine recipient will depend on a bevy of factors, including the ingredients in the shots and that person’s infection and vaccination history, as well as their immune-system health. Also, for people like my husband—who’s prone to very heavy vaccine side effects—the choice may not matter at all. He was so knocked out by the fever and chills that came with his COVID-flu-shot combo, he couldn’t have cared less which arms got the shots.

I dug around for studies examining the consequences of the one-versus-two-arm choice and found only one: a Canadian trial from 2003, which vaccinated a few hundred sixth-graders at two dozen middle schools against group C meningitis and hepatitis B at the same time. Roughly half the kids got both shots in the same arm; the others received one on each side. (Some kids in the latter group requested that their shots be administered by a pair of nurses who could plunge both syringes at the same time.) Among students in the same-arm group, 18 percent ended up with tenderness at the injection site that they rated “moderate or severe.” But those kids fared better than the ones in the two-arm group, 28 percent of whom experienced moderate or severe tenderness in at least one arm, and 8 percent of whom had it in both arms at the same time.

But those results apply only to that group of kids in that setting, with those two specific vaccines; there’s no telling whether the same trends would be seen with flu shots and COVID shots when given to children or adults. Michela Locci, an immunologist at the University of Pennsylvania, told me she suspects that combining flu and COVID inoculations in the same arm could actually drive extra side effects: “The overall inflammation might be higher,” she said.

Many pediatricians, who often have to administer four or five shots to a baby at once, are habitual splitters. “If there’s more than one vaccine syringe to give to a baby, generally, two legs are used,” Permar told me. (Kids usually upgrade to arm shots sometime in toddlerhood—it’s all about finding a muscle that’s big enough for the needle to hit its mark.) Doctors also have a nerdy reason to split shots between arms or legs. “If there’s a local reaction to the vaccine,” Permar said, “you can identify which vaccine it was if you separate them by space.” (For the record, I had a more painful reaction in my left arm, where I got the COVID shot. Others I’ve spoken with have reported the same disparity.)

Read: Families are going rogue with rapid tests

The CDC advocates for separating vaccination shots by at least one inch of space. Per the agency, if a COVID shot is being given at the same time as a vaccine “that might be more likely to cause a local injection site reaction,” the shots should be dosed into “different limbs, if possible.” Two types of flu shots cleared for use in people 65 years and older—the high-dose vaccine and the adjuvanted one—fall into that category. But the different-limb advice doesn’t seem to apply to other flu shots, including those cleared for use in younger adults and kids.

However someone ends up taking simultaneous flu and COVID shots, the placement is unlikely to affect how much protection the vaccines provide. There could be an argument for letting “each side focus on its own thing,” says Gabriel Victora, an immunologist at Rockefeller University. “But it probably doesn’t make a whole lot of difference.” Children routinely get combo vaccines, such as DTaP and MMR, each of which combines multiple disease-fighting ingredients in a single syringe. The triple-threat formulas work just as well as injecting their individual parts. The immune system is used to multitasking: It spends all day being bombarded by microbes, so there’s good reason to believe that with vaccines, too, our body will see simultaneous shots “as independent events,” Goel told me.

Which arm gets picked for which shot, though, will affect where the jab’s contents end up. After a vaccine is injected, its immunity-inducing ingredients meander to the nearest lymph node, such as the ones in the armpits. There, hordes of immune cells fight over the vaccine’s bits, and the fittest and fiercest among them are selected to leave the lymph node and fight. Here, again, doubling up on one arm shouldn’t be an issue, Goel said: The immune-cell boot camps in these lymph nodes have “a good amount of real estate.”

It might even be a good idea to stick the same limb—and thereby, the same lymph node—every time you get another dose of a particular vaccine. After immune cells in a lymph node spot a particular bit of pathogen, some of them march off into battle, but others may hang around like reserve troops, mulling over what they’ve learned. A couple of recent studies, one of them in mice, hint that repeated delivery of the same ingredients to those veteran learners could give the body a slight edge—though the extent of that advantage “might be marginal,” Victora told me. Still, Langel, of Duke, told me jokingly that because she usually gets all of her vaccines in her “non-writing” arm, the lymph node beneath it could now be especially superpowered—a “nice bonus” for her defenses on the whole.

That said, no one should stress too much about getting a shot in the “wrong” arm. “It’s not like you’re immune on the left side and not on the right side,” Goel told me. Immune cells travel throughout the body; there is no midline DMZ. Permar even points out that getting the newly formulated COVID vaccine, which includes new ingredients tailored to fight Omicron subvariants, on the opposite side from the previous rounds could help its ingredients reach a fresher slate of cells. “I think you could convince yourself either way,” she told me. Which, honestly, leaves me totally at peace with my choice. Apart from arm achiness, I had no other side effects—and in a way, I preferred the symmetry of the one-on-each-side injections.

With all that said, it’s worth briefly acknowledging a third option: Splitting the flu and COVID vaccines into separate visits. I was, before my most recent COVID shot, some 10 months out from my previous dose. But it felt awfully early for my flu shot, which might be better timed for peak protection if taken later in the season. Still, the allure of getting it all over with was too tantalizing, especially because I happen to have a lot of travel up ahead. In the grand scheme of things, the bigger, more important choice was opting into the shots at all.

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Katherine J. Wu

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September 15, 2022