FDA’s Proposed LASIK Warning May Leave Patients Less Informed


The agency’s recommendations should balance risk with benefit

A photo of ophthalmologists performing LASIK surgery on a female client.

LASIK surgery has been studied continuously since the FDA approved the procedure nearly a quarter century ago. These studies include careful documentation of the success rates in improving vision without the need for glasses, as well as the risks for complications. This information has long been included in the labelling for the devices used in LASIK. Yet, the FDA recently decided to propose new documents revising the description of risks and benefits.

We, at the American Academy of Ophthalmology (AAO), share the goals of the FDA: to protect patient safety, and to help patients make an informed choice, meaning a choice based on complete information that includes not just risks and benefits, but a good sense of the likelihood of these outcomes. However, the FDA has produced a statementopens in a new tab or window that focuses so heavily on risks that it makes it difficult for patients to accurately assess the appropriateness of LASIK for their situation.

The efficacy of LASIK is well supported by numerous studies. A reviewopens in a new tab or window of nearly 100 research articles representing nearly 70,000 eyes has reported that more than 90% of eyes undergoing LASIK had 20/20 or better vision without glasses, and more than 99% driving vision of 20/40 or better. The U.S. military has also generated a great deal of useful information and has trusted refractive surgery to improve the vision of active servicemen and women for many years, becoming one of the largest providers of refractive surgery in the country. Rigorous studies performed by the military have described the safety and effectivenessopens in a new tab or window of LASIK in terms of night visionopens in a new tab or window, night drivingopens in a new tab or window, flight performanceopens in a new tab or window, and firing performanceopens in a new tab or window.

The FDA’s own well-conducted PROWL studyopens in a new tab or window on outcomes following LASIK found high rates of patient reported satisfaction: While most participants were satisfied, the rates of dissatisfaction with vision ranged from 1% to 4%, and the rates of dissatisfaction with surgery ranged from 1% to 2%.

As successful as refractive surgery is, it is not for everyone. Some patients have eye conditions or anatomy that are not well suited to laser treatment. Even when appropriate, no surgical intervention can be risk-free. The discussion that educates patients on whether surgery is right for them, along with the benefits and risks of LASIK based upon their unique profile and needs is a critical element of the decision-making process. AAO’s Code of Ethics dictates that it is the physician performing the procedure who is responsible for educating the patient and obtaining meaningful informed consent.

The topics covered in the guidance document — the risks for problems such as double vision, dry eyes, difficulty driving at night, and, in rare cases, persistent eye pain — are all important for the informed consent process, but they must be presented with sufficient depth and nuance for the patient to better understand what these data mean for them. We believe that effective informed consent is not merely a listing of potential poor outcomes that one must know about, but a process of shared information and decision-making that happens interactively between the physician and the patient, where both come to thoroughly understand the patient’s situation, goals, and motivations.

Beyond the ethical imperative, AAO believes that an informed patient, whether they choose to undergo surgery or not, is a more satisfied patient. This is why we have generated extensive educational resources for both ophthalmologists and their patients, including a patient guide to refractive surgeryopens in a new tab or window, which we produced in partnership with the FDA. AAO-affiliated Ophthalmic Mutual Insurance Company provides a comprehensive informed consent form in both English and Spanish that is widely used by physicians and their patients. Additionally, AAO’s EyeSmart program offers evidence-based and commercially unbiased information about eye health, including vision correction surgeriesopens in a new tab or window such as LASIK. And we offer guidelinesopens in a new tab or window to assist ophthalmology practices in providing ethical, informative advertising for refractive surgery.

Beyond the issues of balance, nuance, and personalization, we are also concerned that the proposed update to patient guidance on LASIK surgery provides information that does not reflect the most current clinical evidence. For example, the suggested guidance lists pupil size as a risk factor for complications. The issue of pupil size has been studied extensively over the years. Data from published studiesopens in a new tab or window of modern lasers fail to demonstrate a relationship between pupil size and the quality of postoperative vision. And yet, FDA lists pupil size as a risk factor for poor vision after LASIK surgery.

The FDA’s proposal is not final. More than 600 individuals and professional groups have weighed in with comments since the draft of the guidance was made public in July, and the agency is now reviewing the input while preparing the final documents. Many comments reflect these concerns, and we hope that the FDA will consider them seriously.

AAO has a long and productive relationship with the FDA. We look forward to continuing our collaboration to ensure that our common goal is met: to educate the public about LASIK and its outcomes with an evidence-based and balanced approach.

Cholera Returns With a Vengeance


Climate change, conflicts, and depleted stocks of vaccine compound mounting concerns

“Le Cholera” first appeared in 1912 in an illustrated supplement of France’s Le Petit Journal.

It has been a bad year for cholera, the fecally transmitted scourge once depicted as a supernatural reaper wielding a giant scythe. When the artwork above, “Le Choléraopens in a new tab or window,” first appeared in 1912, cholera’s pathophysiology was still a mystery, but its clinical wrath wasn’t. By then, it was public knowledge that cholera could sometimes transform a previously healthy human into a withered, gray corpse in a matter of hours.

Then came further scientific insights about cholera’s comma-shaped, toxin-bearing bacillus that forms “micro-colonies” in human intestinal crypts, where Vibrio cholerae ultimately delivers its two-fisted punch: one set of subunit toxins attaching to GM1 gangliosides on the epithelial surface of small bowel cells, which, in turn, enables a second subunit toxin to reprogram those cells to secrete sodium and water.

This molecular assault unleashes cholera’s sometimes-massive flux that far outweighs the loss of fluid and electrolytes triggered by any other gastrointestinal pathogen. One silver lining? The ability to resuscitate cholera sufferers with oral rehydration salts mixed in clean water or, in more severe cases, with IV infusions. And, starting in 2013, the World Health Organization’s (WHO) stockpile of oral cholera vaccine (OCV) has been one more boon for the global poor who might otherwise suffer cholera. Yet, in 2022, cholera has resurged to such a degree that it is now striking fear, given that there are woefully scant tools and infrastructure to contain it in many of its traditional strongholds.

Cholera’s Modern Burden

Today, experts believe, cholera still threatens more than a billion people in 69 countriesopens in a new tab or window, annually infecting 1.3 to 4 million and killing up to 143,000opens in a new tab or window. But because distinguishing one form of watery diarrhea from another isn’t easy in its largely impoverished haunts, its true burden is hard to prove. Nonetheless, newly erupting or protracted outbreaks stand out because of cholera’s “equal-opportunity” toll on children and adults.

In 2022, such outbreaks occurred in 29 countries as compared to 23 in 2021opens in a new tab or window or the previous average of 20 country outbreaks per annum over the last 5 years. In addition, according to the WHO, 2022’s global case-fatality rate climbed to 1.9%opens in a new tab or window (2.9% in Africa). Root causes and contributing factors include a lack of investment in water and sanitation combined with conflict and complex humanitarian crises; climate change (cyclones in Mozambique and Malawi, for example, or flooding in Pakistan and drought in the Horn of Africa); fragile health systems and personnel stretched thin by other diseases; and a looming shortage of OCV.

This brings us to Haiti, where after a 3.5-year disease-free intervalopens in a new tab or window, cholera resurfaced at the end of September 2022. Haiti’s story, in particular, holds significant lessons.

Cholera in Haiti: Past and Present

Louise Ivers, MD,opens in a new tab or window is an infectious diseases specialist who is now the faculty director of Harvard’s Global Health Institute and the executive director of Massachusetts General Hospital’s Center for Global Health. Before assuming these posts, Ivers worked for many years for Partners in Health, a non-profit founded by the late Paul Farmer, MD, PhDopens in a new tab or window. Her initial mandate was to expand community-based healthcare in Haiti for people with HIV and tuberculosis and malnourished children.

Then, January 2010 brought a catastrophic earthquake to Haiti followed 9 months later by the country’s first-ever cases of cholera, which were eventually linked to an ill-fated leak of sewage from a Nepalese U.N. peacekeepers’ campopens in a new tab or window. A local flurry of cases quickly rippled into a country-wide epidemicopens in a new tab or window that sickened 820,000 people and caused close to 10,000 deaths. Ivers oversaw Partners in Health’s on-the-ground operations and later partnered with the Haitian non-profit GHESKIO in a pioneering roll-out of OCV. It was clearly an unforgettable time.

“The first days and weeks we were just so busy trying to take care of thousands of people in our clinics, setting up treatment facilities, distributing water products, getting community health workers trained …” Ivers recalled in a 2017 interviewopens in a new tab or window. “The stories I heard were humbling. There was so much suffering and so much fear. People lost whole families to cholera in a wave of illness that they (and we) had never before experienced.”

This year, in contrast, when Haiti’s latest outbreak erupted and rapidly spread (by mid-December, cholera had already caused suspected infections in nearly 15,000 people and 291 registered deathsopens in a new tab or window), everyone from officials in the Ministry of Health to Haiti’s poorest residents were far better prepared to fight it. At the same time, however, they were hampered by global donors’ failure to deliver on earlier promises to improve local water.

In Haiti, 35% of residentsopens in a new tab or window currently lack access to safe water and up to 65% have inadequate sanitation or none at all; places to wash one’s hands with soap and clean water are available to less than a quarter of the population.

“People know they should wash their hands and treat their water, but they don’t have the resources to do it … some literally have to choose between food and school and soap,” Ivers recently said.

Haiti is also facing “the worst socio-political situation I’ve observed in my 20 years in the country,” she added. “The gang violence and political stranglehold have had a huge humanitarian impact.” Recent shortages of fuel have also hindered outreach and travel by healthcare workers and the pumping of potable water.

The next challenge? Local authorities must now decide who will receive rationed doses of OCV.

An Uncomfortable Question

Well before December 12, 2022, when Ivers and I spoke on the phone and Haiti was due to receive 1.6 million OCV doses, WHO was nervous about its rapidly depleting stockpile of OCV, having already dispensed two-thirds of this year’s 36 million doses.

Adding to WHO’s worry is the coming drop-out in 2023opens in a new tab or window of one of only two providers of low-cost OCV for use in humanitarian emergencies. The decision by Shantha Biotechnics, a fully owned subsidiary of Sanofi, was announced in 2020. Right now, that leaves South Korea’s EuBiologics, maker of Euvichol, as the sole OCV manufacturer.

So, here’s a question to ponder: Now that cholera has returned with a vengeance in 2022, what company or consortium will step up in light of the limited return on investment of producing vaccines exclusively meant for desperately poor countries?

What argument around investing in vaccines to fight cholera might resonate with Americans? I asked Ivers. She didn’t mince words. “To me, it’s always the moral argument. With very rare exceptions, cholera kills poor people who don’t have access to the most basic human needs of safe water, sanitation, and food to eat. In 2022, it’s just incomprehensible that we could be willing to let people die of dehydration and diarrhea because they don’t have clean water plus other preventive tools.”

In those words, I heard an echo of the impassioned vision of Ivers’ long-time mentor Farmer, who never stopped believing in the right to health of the poorest of the poor. Perhaps it’s a fitting end-of-the-year message for us all.

Three years on, the pandemic — and our response — have been jolting. Here’s what even the experts didn’t see coming


China Prepares For 20th CPC National Congress
A health worker passes a vial to be used in a Covid-19 test during the 20th National Congress of the Communist Party of China in October.

People who study infectious diseases and who work in public health have long known a bad pandemic would one day come.

They knew such an event would overwhelm hospitals, strain supply chains, and place stresses on society that we would be ill-equipped to meet. Countries like the United States have for decades prepared to respond to such a crisis.

But despite all the planning, the Covid-19 pandemic has, in myriad ways, not played out as expected. Three years after the first reports of a novel virus emerged from China, these experts admit that the microbe and the world’s response to it have continuously deviated from their forecasts.

In the hope that important lessons for next time can be found in the things we didn’t anticipate this time, STAT asked 23 experts what had surprised them the most about the pandemic.

The TL;DR version: We have a lot of learning left to do.

Containment can buy time

Ben Cowling, head of the division of epidemiology and biostatistics at the Hong Kong University School of Public Health, was working with the World Health Organization in 2019 to revise its response plan for pandemic influenza. He and his co-authors wrote that countries should focus their efforts on trying to mitigate the impact of a pandemic rather than trying to stop it.

“What we’d written on page 1 of these flu pandemic guidelines is: Containment is futile. Don’t waste too much time on containment,” Cowling said.

The report listed about 20 non-pharmaceutical measures countries could try, things like closing schools and urging people to wear masks. “We didn’t consider a shelter-in-place [order] — that wasn’t on the list,” he said. “We just couldn’t envisage something like that being considered. And then, of course, that was the go-to measure for many countries in March and April of 2020.”

After China successfully slowed the spread of the new virus with draconian measures limiting individuals’ movements, many countries instituted some versions of what came to be known as “lockdown.” In some cases the actions were too late or too inefficiently implemented to make a big difference. But a number of countries deployed these measures with significant success; New Zealand, Australia, Singapore, South Korea, and Japan, among others, lost far fewer lives than peer nations. And of course China, where the pandemic began, kept Covid largely at bay until very recently, albeit with restrictions that would not be accepted in other parts of the world.

The WHO pandemic flu response plan is being updated to incorporate what was learned about containment efforts during Covid. Cowling said it won’t advise long-term efforts to try to stop a new pandemic virus, but “temporary containment to buy time, actually, I think some places will consider.”

Hong Kong Locks Down Buildings In Mid-Levels
Residents look down from a building in an area under lockdown in Hong Kong in March 2021. Anthony Kwan/Getty Images

The quiet

When countries around the world started following China’s lead and imposing social distancing measures — some very strict, others less so — the impact was eerie. City streets that were normally traffic-clogged became vast open spaces. Office towers sat empty. Shops and restaurants were closed, in some cases boarded up.

It is not an exaggeration to say it was unlike any time anyone alive today had ever experienced.

“The sheer quiet was just striking,” said Maria Van Kerkhove, the WHO’s lead on the pandemic. “I was in several different cities in China in February 2020 and the silence. … No one on the streets. Blue skies, because there were no cars on the road. You saw pictures from around the world of the air cleaning up in India, in Paris.”

The baking bonanza

People who had spent any time thinking about pandemics anticipated and prepared for the Great Toilet Paper Shortage of spring 2020.

But some of the other shortages that occurred caught even people steeped in pandemic preparedness by surprise. Flour. Butter. Yeast. Eggs. Who could have predicted pent-up people would turn their attention, en masse, to trying to perfect sourdough bread? Certainly not Nancy Messonnier, then director of the National Center for Immunization and Respiratory Diseases at the Centers for Disease Control and Prevention. Messonnier was the official who warned Americans in late February 2020 about what was barreling towards them — and promptly got silenced by the Trump administration for her candor.

She had already purchased supplies of bottled water, toilet paper, and bread by the time Atlanta schools were closing and society in general finally grasped a life-altering event was unfolding. Still, on the day her kids’ school closed, Messonnier headed to her local grocery store. It was chockablock with people hunting for the stuff she’d already stocked up on. She was searching for ingredients for cookies.

“I just figured I’d be home and I’d have time to bake,” she said.

Later others had the same idea. For weeks that spring, flour, yeast, and other baking essentials were as rare as hen’s teeth.

How variable the illness was

Covid has killed millions around the world, including more than 1 million in the United States. But some people who have been infected have no symptoms at all. Others have the equivalent of a head cold.

Some patterns are intuitive. Many of the deaths have been in people in their 70s, 80s, and beyond. Many have been in people with chronic health conditions that undermine their ability to fight off the infection.

But sometimes the variability of the illness makes little sense, a fact that has surprised Deepta Bhattacharya, professor of immunology at the University of Arizona College of Medicine.

“For instance, my dad and my sister both got it in May. My dad barely knew. He has asthma, and so he just thought it was just his asthma flaring up,” he said. “My sister had a much rougher go of it. She had a pretty bad cough that lasted over a month.”

“And they had the same vaccine history. They both had had three shots at the time that they got it.”

How quickly people could be reinfected

While an ever-dwindling number of people have not yet experienced a Covid infection, some have been infected several times. For some, the interval between Covid bouts is amazingly short.

“Anecdotally, I know several instances where infections occurred, the infection resolved clinically, and then the person became symptomatic again with SARS-CoV-2 positivity a few weeks after the initial infection,” said Stanley Perlman, a longtime coronavirus researcher at the University of Iowa.

Human coronaviruses, which cause colds, don’t trigger long-term immunity after infection. But studies suggest reinfection occurs on average about a year after a previous infection; one study suggests the interval is much longer. So how do we make sense of intervals of mere weeks?

Perlman doesn’t know, though he notes it’s not clear if these are reinfections or relapses, because the viruses from the sequential infections were not isolated and compared.

Novel Coronavirus SARS-CoV-2 (Omicron)Colorized scanning electron micrograph of a cell infected with the Omicron strain of SARS-CoV-2 virus particles
A cell from a patient infected with the Omicron strain of SARS-CoV-2, covered with virus particles (pink). NIAID

The biggest surprise, hands down: How the virus has evolved

In the early days of the pandemic, before the new virus had a name, people who had studied coronaviruses offered reassuring predictions about the stability of the virus, which has implications for how often people might be reinfected and how frequently vaccines would need to be updated.

Coronaviruses don’t change very quickly, they aren’t as mutable as, say, influenza viruses, those experts said. In fact, the spike protein on the virus’ exterior, the one that attaches to human cells and triggers infection, cannot change too much without losing its ability to infect, they assured the rest of us.

That was the dogma. Then came the variants: Alpha, Beta, Delta, and Omicron, with its mind-boggling array of mutations. Since it emerged in late 2021, Omicron has splintered into a seemingly endless succession of subvariants, which continue to mutate and evade immunity induced by prior infection and immunization.

Many of the people STAT interviewed cited SARS-CoV-2’s evolution as their biggest surprise of the pandemic. “It’s been wild, in my view,” said Marion Koopmans, head of virology at Erasmus Medical Center in Rotterdam, the Netherlands.

Anthony Fauci, retiring head of the National Institute of Allergy and Infectious Diseases, also listed it as his number 1 surprise. “What has surprised me most about Covid is the continual evolution of new variants leading to an unprecedented persistence of the pandemic phase over three years,” he said.

Michael Diamond, a viral immunologist at Washington University, scoffed when he recalled the early proclamations about the virus’ inability to mutate much. “At some point we’re going to run out of mutational space. Well, we haven’t run out of that yet, which was surprising to us, I think, that the virus is still flexible enough to be able to accommodate these mutations. And not only do that, but increase transmissibility and increase immune escape concurrently.”

The erroneous prediction was predicated on what, after the fact, was clearly a flawed idea — that the evolutionary rate seen when a virus was moving through a totally naïve population would remain the evolutionary rate when the virus faced the challenge of infecting people who had some vaccine- or infection-acquired immunity, said Paul Bieniasz, a virologist at Rockefeller University.

Bieniasz was surprised by the role immunocompromised people — people who, once they contracted Covid, could not shake the infection for weeks, sometimes months — played in driving evolution of the virus. That phenomenon is believed to be responsible for another of the surprises about SARS-2 evolution. Most viruses evolve in a stepwise fashion known as “drift,” adding change after change to an existing strain. But some of the Covid variants look more like old versions of the virus were hyper mutated, possibly in a persistently infected person. When those viruses started to spread, they replaced the viruses that had been circulating. The Alpha, Beta, Gamma and Omicron variants of concern are examples of this type of evolution, called saltation, Thomas Peacock and colleagues wrote in a preprint article posted in late November.

“The reality is that SARS-CoV-2 had a much greater capacity for adaptation than I expected,” said Vineet Menachery, a coronavirus expert at the University of Texas Medical Branch. “While this fact was exacerbated by slow uptake and delivery of vaccines, the truth is that the sheer amount of virus and replication provide enough replication cycles to … select for mutations that provided fitness and immune evasion advantages.”

Protestors Rally At Connecticut State Capitol Against COVID-19 Stay-At-Home Order
Demonstrators stand in front of Connecticut Gov. Ned Lamont’s residence while protesting the state’s stay-at-home order to combat the coronavirus pandemic in May 2020. John Moore/Getty Images

The susceptibility of the public to charlatans

First it was a malaria drug, hydroxychloroquine. Then it was ivermectin, a drug used to eliminate parasitic worms. Heavenly silver. Bleach. Ultraviolet light. Urine therapy. The list goes on.

The Covid pandemic has been a field day for quacks and crooks. They’ve made a killing.

It is ever thus, some would surely say. But Bieniasz has been stunned by the degree to which a not-small portion of the population has been taken in by hucksters — and by the inability of the scientific community to break that spell.

“The sort of willingness of Joe Public to listen to anybody with a large Twitter following has just shocked and appalled me,” Bieniasz said. He sees this as a consequence of a huge loss of trust in the scientific community.

The reverberations of this loss of trust continue, even though the acute phase of the pandemic appears to be subsiding.

Related: Encouraged by right-wing doctor groups, desperate patients turn to ivermectin for long Covid

Malia Jones, an assistant professor in community and environmental sociology at the University of Wisconsin-Madison, studies vaccine hesitancy and rejection. She spoke to parents this autumn who refused to get their kids vaccinated against flu. The reason? A rumor that the government is bottling Covid vaccine in flu vaccine vials to surreptitiously increase Covid vaccination rates among kids.

“What? Imagine the coordination it would take to pull that off. It’s just impossible,” she sputtered. “And illegal, and a lot of other stuff, too. But also just really implausible. It’s not the way the world works.”

Unhelpful public health approaches

Bhattacharya has two very active sons, now aged 9 and 11. When schools closed and activity opportunities shrank, he wanted to take them to play tennis. But the nets were removed from local tennis courts to discourage people from using them. “Policy choices like that I think were unfortunate. That then really brought a lot of ill will to anything [public health officials] tried to do subsequently.”

Richard Hatchett worked in the George W. Bush White House on pandemic preparedness, studying the control measures that were used during the 1918 Spanish flu pandemic. His work was pivotal in reminding the world that non-pharmaceutical interventions — the types of measures Cowling was writing about in the WHO report — could reduce transmission of respiratory pathogens. Still, he was surprised at how bluntly they were applied. A future goal should be to figure out how to use non-pharmaceutical interventions “with greater subtlety and finesse to interrupt transmission but not destroy economies,” Hatchett said.

Karen Meadows
Karen Meadows, 61, comforts her son, Chris, 31, as he receives the J&J vaccine in their home in March 2021. Christopher Jones for STAT

Covid vaccines — so many surprises

For quite a few of the people interviewed for this article, the speed with which Covid vaccines were developed was truly unexpected. Ran Balicer, director of Israel’s Clalit Research Institute, encapsulated that view: “Vaccine(s) ready, tested, and launched in under a year.”

For others, the surprise was how effective the vaccines were. “I was on the Pfizer DSMB” — the data and safety monitoring board, a group of independent experts who oversee a clinical trial — “and was one of the people that unblinded that study the first time and saw the 95% efficacy. Basically it just brought tears to my eyes,” said Kathryn Edwards, a professor of pediatrics and vice-chair for clinical research at Vanderbilt University.

Still others were stunned at how many vaccine development attempts were successful. Hatchett is now the CEO of the Coalition for Epidemic Preparedness Innovations (CEPI), an organization whose mission is to spur development of vaccines for diseases that can trigger dangerous epidemics or pandemics, vaccines for which there isn’t a market — until suddenly there is. He thought there would be a Covid vaccine within 12 to 18 months of the start of the pandemic; in fact, the first vaccines were ready in 11 months. But historically, only about 1 in 10 vaccine projects succeeds. Hatchett figured that would be the case here too.

Instead, Covid vaccine after Covid vaccine worked. Old-school inactivated vaccines, the foundation of China’s vaccination effort. New messenger RNA vaccines like Pfizer’s and Moderna’s. Recombinant protein vaccines like the one made by Novavax. Viral-vectored vaccines, like the AstraZeneca and Johnson & Johnson jabs. True, there were a few failures, but far fewer than anyone anticipated. Hatchett puts it down to investments in vaccinology.

“I think we should draw encouragement from that, in that if we make a concerted effort to be ready for other threats, I think we have powerful tools that tilt the balance in our favor,” Hatchett said. “It just showed how much progress we had made before Covid arrived.”

Perhaps the biggest vaccines surprise, though, was the speed at which gobsmacking amounts of vaccine were produced. Billions and billions of doses in the first year of production alone.

Hatchett has spent nearly two decades working on pandemic preparedness. The past three years have held few surprises for him. But he marveled at what he called “this truly miraculous scaling of production.”

“A lot of cumulative advances that we had never seen mobilized all at the same time, for the same purpose, suddenly showing their power,” he said. “That was a big surprise.”

Not all the vaccine surprises were positive

For all the wondrous surprises related to the vaccines, some were disappointing.

They have been potent protectors against the worst of Covid, cutting hospitalizations and deaths dramatically. But protection against infection declines rapidly over a course of a few months — at least with the mRNA vaccines. “Going from 95% to negligible in terms of transmission in the time window in which that has occurred — that’s pretty dramatic,” said Bieniasz, the Rockefeller University virologist.

Vaccine hesitancy and rejection has been a growing problem for years, but before the pandemic, the scale of the problem in the United States was still relatively small. The vast majority of parents vaccinated their kids against childhood diseases.

And in the early days of the vaccine rollout, when supplies were tight, people jostled and misrepresented themselves and called in favors to try to get to the front of the line faster. But anti-vax forces mobilized to attack the new vaccines. Rumors flew that they attacked testicles and altered fertility. A surprising level of distrust took hold. As vaccine supplies began to swell, demand began to evaporate.

Messonnier knew all about vaccine hesitancy. But even she was taken aback by how quickly “must have” turned to “meh.”

“I expected people to see vaccines as they did at the end of 2020, as being the thing that was going to save us, the thing that was going to get life back to normal. And that moment when folks felt that way just passed so quickly,” said Messonnier, who is now dean of the Gillings School of Global Public Health at the University of North Carolina.

Claire Hannan, too, was surprised by how fleeting the keen-to-get-vaccine moment was. Hannan is the executive director of the Association of Immunization Managers, which represents leaders of state, local, and territorial immunization programs — the people who oversee the efforts to turn vaccines in vials into vaccinations in arms.

The last couple of years have been extraordinarily busy for Hannan and her members.

“The initial surge in demand and the craziness and the logistics and all of the challenges and the lack of funding and lack of staffing — expected all of that,” she said. “It was what came after that that surprised me.’’

Another vaccine-related issue Hannan wasn’t anticipating was the fact that her organization would have to fight to be involved in Covid vaccine distribution in the United States. The military was baked into the foundation of Operation Warp Speed, which not only spurred development of Covid vaccines but oversaw the rollout.

“I kind of thought that would be a done deal. I didn’t expect to have to advocate for that. I didn’t expect to have to fight for it,” Hannan said. “For me, that’s a ‘lessons learned.’ Existing systems, existing plans — in the heat of the moment, not everyone in a position of power knows about these plans and not everyone is ready to embrace something that they don’t understand or they haven’t been a part of developing.”

For Jeremy Farrar, incoming chief scientist at the WHO, the unequal access to Covid vaccines when they started to become available wasn’t a surprise, but the scale of the inequity was. “I did not expect countries would hoard vaccines they knew they were never going to use,” said Farrar, who is stepping down as director of the Wellcome Trust.

Covax India
A refrigerator truck containing cartons of Covid-19 vaccine arrives at the Mumbai airport in India in February 2021. INDRANIL MUKHERJEE/AFP via Getty Images

Pricey mRNA vaccines became the jab of choice in countries ill-equipped to use them

From the earliest days of the deployment of Covid vaccines, there were concerns about how challenging it was to use the mRNA vaccines, the first to generate proof that they worked. For starters, they needed ultra cold storage; Pfizer went so far as to make its own shipping cases that required dry ice to ensure precious doses weren’t lost to spoilage. And the vaccines were expensive; Pfizer currently charges the U.S. government $30.48 a dose while Moderna charges $26.36.

Those characteristics alone made the mRNA vaccines ill-suited for low-income countries where maintaining a regular cold chain — ensuring vaccines are stored at fridge temperature every step of the way — is a challenge. Ultra cold chain? Forget about it.

Researchers from the University of Oxford’s Jenner Institute specifically opted to design a vaccine that would be cheap to produce and easy to transport and store; AstraZeneca licensed and produced the Oxford vaccine. Peter Hotez and Maria Elena Bottazzi of Texas Children’s Hospital Center for Vaccine Development at Baylor College of Medicine did the same; India’s Bharat Biotech made theirs. Both groups trumpeted their shots as the world’s vaccine, assuming there was enormous need for inexpensive and easy-to-use shots.

But it turned out that those in lower-income countries wanted what we were having. The health intelligence and analytics firm Airfinity estimated in October that 94% of the sales of Covid vaccines in 2023 will go to Pfizer-BioNTech and Moderna.

The world’s desire for mRNA vaccines surprised Seth Berkley, CEO of Gavi, the Vaccine Alliance. Gavi was a key player in COVAX, the organization set up by the WHO and other partners to buy and distribute vaccines to countries that couldn’t otherwise have procured them.

“We had good alternatives that were high efficacy and maybe even longer duration of protection and stable at regular room temperatures, etc. But countries want mRNA,” Berkley said.

He noted that AstraZeneca and Novavax vaccines produced by the Serum Institute of India cost $3 a dose. “The normal behavior would be that the low-priced, high-quality vaccines would replace the high-quality, much more expensive vaccines that are more difficult to use. But that didn’t happen.”

Covid cleared the decks

For the first couple of years of the pandemic, other respiratory viruses seemed to be on hiatus. (Rhinoviruses, which cause the common cold, were an exception.) Social distancing measures, sharp declines in international travel, and potentially some interplay between SARS-2 and the other viruses are thought to explain their absence.

There was no flu season to speak of in the winter of 2020-2021. Last year, flu activity picked up some, and respiratory syncytial virus, or RSV, returned, but in August and September, not over the winter as was the virus’ wont in pre-Covid times. This year, flu and RSV were back with a vengeance, though unseasonably early. With a new kid on the block, it seems like everything’s a bit out of whack.

And the genetic diversity of flu viruses appears to have declined. In fact, one strain of influenza B viruses, Yamagata, hasn’t been seen since March 2020. Some flu experts think it was snuffed out; others say it’s too soon to be sure. Still, the possibility astonishes Cecile Viboud, a senior research scientist in the division of international epidemiology and population studies of the National Institute of Health’s Fogarty International Center. “The thought that we might have eradicated one part of flu — it’s just unbelievable,” she said.

Brigham and Women's Hospital
Respiratory therapist Angelika MacClellan (left) talks with nurse Natasha Cacciatore through the door of a patient’s room in the Special Pathogens Unit ICU at Brigham and Women’s Hospital in Boston in April 2020.

The health care worker roller coaster

Christine Grady has been surprised by the way society has treated health care providers during the pandemic. (She didn’t mention people who work in public health, but everything Grady said also applies to them.)

Very early on, people treated health workers like pariahs, because they feared catching the new disease from them, said Grady, who is chief of the department of bioethics at the NIH’s Clinical Center. Then for a time, health workers were heroes, during the bang-your-pots period. Later, as pandemic fatigue and denialism set in, health workers were again targeted, sometimes with threats of violence. Grady knows well of what she speaks. She is married to Fauci, the NIAID director and President Biden’s scientific adviser, who has had to have a security detail for some time.

Grady warned that “many HCPs are experiencing burnout and mental health challenges and leaving their jobs in large numbers, and fewer students are choosing health professional-related education. Currently, the strain on the capacity of hospitals and clinics caring for large numbers of patients with Covid, influenza, RSV, and other disorders is exacerbated by HCP shortages.”

“I worry what it portends for the future of healthcare,” she wrote in an email.

Unsettled science, scientific hubris, and the attack on science

One of the big surprises for Messonnier is how many scientific questions remain unanswered at this point. We still don’t know the correlates of protection — effectively what a protected immune system looks like — or which of the transmission-reduction techniques works best. There’s not a clearly accepted definition of long Covid. Her full list is longer.

“I’m not sure that people are asking the right questions in a parsimonious way that you can get solutions,” she said.

Bieniasz was surprised at how much scientific hubris was on display. Despite the fact that the coronavirology field was tiny before the pandemic and there were many gaps in our understanding of this family of viruses, some scientists made confident statements about them — statements that turned out at times to be wrong.

“I’ve been sort of repeatedly surprised by how often I see statements in the press attributable to scientists that have an unwarranted level of confidence associated with them,” he said, suggesting this has contributed to a decline in trust in science and in public health experts over the course of the pandemic.

Bieniasz thinks scientists should have started most statements with “I don’t know, but my best guess is …”

WHO’s Van Kerkhove was stunned by the way the field of science came under attack during the pandemic.

“I was absolutely shocked by the attack, the fundamental attack on science itself, which was in many respects political,” she said. “It surprised me how much this impacted every aspect of our work, how time consuming that was.”

Rally Held At Pennsylvania State Capitol To Urge Governor To Open Up Lockdown Orders
A man with an assault rifle joined a demonstration outside the Pennsylvania Capitol Building in Harrisburg to protest the closure of businesses due to the pandemic in May 2020. Mark Makela/Getty Images

So much for pulling together in a crisis

It turns out that a crisis can further polarize highly polarized nations.

“I think I naively would have predicted that it would have brought everyone together, because in the early days you felt that sense of ‘we’re all in it together,’” said Messonnier. Instead, the country cleaved into the people who were concerned about Covid and keen to reduce its spread and the people who thought the cure — school closures and the like — was substantially worse than the disease.

The fights were vicious, deepening existing divides.

“We had seen fierce arguments in the past about the nature of responses and tensions between business and public health. All of that’s structural. It’s part of the problem. But the extent to which it became associated with political identities was surprising and disappointing,” Hatchett said.

Farrar, the new WHO chief scientist, agreed. “The politicization of public health has surprised me — that wearing a mask became a political statement.”

The politicization and polarization of public health measures has hurt vaccine uptake, said Rupali Limaye, director of behavioral and implementation science at the International Vaccine Access Center at Johns Hopkins University. “It is clear that polarization has led to more extreme beliefs and has hampered our ability to speak with those that may have differing views,” she said. “My hope is that we can dial down the politicization through building back trust in health institutions, as we will need to navigate this for disease control in the future.”

The endless, tractionless fighting

Aerosol or droplet? Lab-leak or natural spillover event? There have been several long-running and nasty scientific disputes during the pandemic. And yet we’ve made little progress in fixing the underlying issues that the participants are fighting about, said Samuel Scarpino, director of AI and life sciences at Northeastern University. (He spent much of the pandemic as vice president for pathogen surveillance at the Rockefeller Foundation.)

Team airborne won the vitriolic debate about how the SARS-2 viruses spread, but little has been done to make the improvements in indoor air quality that would cut the risk of virus transmission, Scarpino said.

Likewise, regardless of whether the SARS-2 leaked from a lab or jumped to humans from animals in Wuhan’s wet markets, the world needs to be better prepared for lab accidents and natural spillovers. “The biggest surprise of all this is that we don’t seem to be coming to terms with either one of those two conclusions,” he said.

How long the damn thing has lasted

Pandemics are rare occurrences; fewer than a handful have happened in the age of modern virology, when laboratories could provide detailed knowledge of what was causing the illness and how that pathogen was evolving.

The pandemics that have been recorded have mainly been caused by flu. And in the recorded flu pandemics, there was generally a wave or two — sometimes, in some places three — and then humans and the new virus reached a detente. The new flu virus settled into causing seasonal flu activity, not pandemic flu.

A lot of people STAT spoke to thought that was the way this pandemic would play out. They didn’t anticipate that we’d be where we are now, with waves of transmission still occurring at various points in the year, rather than during the winter, as is the way of most respiratory pathogens.

“I never would have imagined that three years later we would still be dealing with this in the way that it’s ever-present in our conversations and in our society,” said Messonnier, the former CDC official.

Peacock, who studied flu before the Covid pandemic hit, was also surprised by how long the pandemic has dragged on. “From the flu perspective, within a year, or maybe a year and a half, every previous pandemic has generally hit a seasonal pattern. And although those two or three years afterwards might be the worst years for a while, it does hit a pattern, and it does start to look like seasonal flu at that point. Whereas this has just been weird.”

Farrar likewise did not expect transmission of Covid to be high this far into our experience with the SARS-2 virus. “I would not have guessed way back then, when there was natural immunity plus vaccination that we would still, three years on, have such high community transmission, and that’s really worrying to me.”

With this much transmission, there’s a “non-zero risk” of a new variant, he said. “I don’t think this virus has completed its evolutionary track yet.”

The measures governments and individuals took to slow the spread of Covid dragged out the duration of the pandemic, Viboud said. “We would have been in a much worse place if we hadn’t done it. But I mean in the end it has sort of prolonged [it]. You just keep having susceptibles.”

Kharkiv
A firefighter walks through rubble at the freight railway station in Kharkiv, Ukraine, which was partially destroyed by a Russian missile strike in September 2022. YASUYOSHI CHIBA/AFP via Getty Images

The ripple effects

Hatchett, for all his studying of previous pandemics, wasn’t anticipating the geopolitical impacts of this one. He likens it to a meteor strike.

In addition to the crushing waves of illness, the lives lost, the swamping of hospitals, and the disruption to routine health care, he points to the economic disruption of the past couple of years, the onset of inflation, the spike in energy prices, and the upheaval in supply chains as all being of a piece.

“I wouldn’t say the pandemic caused the war in Ukraine, but I think the pandemic created circumstances in which Putin, an opportunist, saw an opportunity,” he said, noting the war has contributed to global food shortages. “So you’ve got years of reverberating political impacts from this pandemic event and the initial response to it.”

Farrar added that the supply chain problems throughout the pandemic are making governments rethink some facets of globalization and international trade, particularly the offshoring of manufacturing and the reliance, in many cases, on sourcing critical supplies from a single country.

The panic-neglect cycle persists

Over the past couple of decades, the world has gone through a number of big disease scares. SARS-1. The H1N1 flu pandemic. MERS. Zika. Ebola. With each, the world raced to respond.

And each time, as the panic eased, neglect kicked in. Rather than recognizing these events as warnings that longer-term investments and structural changes were needed to safeguard the globe against the next one, the world moved on. As it appears to be doing now.

“We’ve seen in other epidemics this happening,” said Berkley, the Gavi CEO. “But you kind of thought with this one, it was so global, it was so big that I would not have expected it to have happened so quickly.”

Anna Durbin, director of the Center for Immunization Research at the Johns Hopkins Bloomberg School of Public Health, is also startled at how quickly people seem to have pushed past Covid.

“I get a sense people have forgotten how many people died, how we couldn’t visit with family and friends,” she said. “This is very similar to HIV after HAART,” — highly active antiretroviral therapy, the HIV drugs that have turned the infection from a death sentence to a chronic condition — “but it happened much more quickly.”

“Maybe this is resiliency, maybe a coping mechanism, I am not sure,” Durbin said. “But I hope the lessons learned are not also forgotten.”

Scientists freeze Great Barrier Reef coral in world-first trial


Cryogenically frozen coral reefs can be stored and later reintroduced to the wild to protect them against rising ocean temperatures

Cryogenically, frozen coral can be stored and later reintroduced to the wild. | Photo Credit: Reuters

Scientists working on Australia’s Great Barrier Reef have successfully trialled a new method for freezing and storing coral larvae they say could eventually help rewild reefs threatened by climate change.

Scientists are scrambling to protect coral reefs as rising ocean temperatures destabilise delicate ecosystems. The Great Barrier Reef has suffered four bleaching events in the last seven years, including the first-ever bleach during a La Niña phenomenon, which typically brings cooler temperatures.

Preserving corals

Cryogenically frozen coral can be stored and later reintroduced to the wild but the current process requires sophisticated equipment including lasers. Scientists say a new lightweight “cryomesh” can be manufactured cheaply and better preserves coral.

In a December lab trial, the world’s first with Great Barrier Reef coral, scientists used the cryomesh to freeze coral larvae at the Australian Institute of Marine Sciences (AIMS). The coral had been collected from the reef for the trial, which coincided with the brief annual spawning window.

“If we can secure the biodiversity of coral… then we will have tools for the future to really help restore the reefs and this technology for coral reefs in the future is a real game-changer,” said Mary Hagedorn, Senior Research Scientist at the Smithsonian National Zoo and Conservation Biology Institute. told Reuters from the AIMS lab.

The cryomesh was previously trialled on smaller and larger varieties of the Hawaiian corals. A trial on the larger variety failed.

Trials are continuing with larger varieties of Great Barrier Reef coral.

The trials involved scientists from the AIMS, the Smithsonian National Zoo and the Conservation Biology Institute, the Great Barrier Reef Foundation and the Taronga Conservation Society Australia as part of the Reef restoration and adaptation programme.

Mesh technology

The mesh technology, which will help store coral larvae at -196°C (-320.8°F), was devised by a team from the University of Minnesota’s College of Science and Engineering, including Dr. Zongqi Guo, a postdoctoral associate, and Professor John C. Bischof.

It was first tested on corals by PhD student Nikolas Zuchowicz.

“This new technology that we’ve got will allow us to do that at a scale that can actually help to support some of the aquaculture and restoration interventions,” said Jonathan Daly from the Taronga Conservation Society Australia.