Missed shots: Science revisits its 2020 Breakthrough of the Year | Science

When Science crowned the development of effective SARS-CoV-2 vaccines the scientific Breakthrough of the Year in December 2020, it was a moment of celebration. “This breakthrough is a triumph for all of science,” Editor-in-Chief Holden Thorp wrote in an editorial. “There will be plenty of time for an exegesis of what went wrong. But for now, what went right is far more important.”

One year later, what went right and what went wrong with COVID-19 vaccines cannot be so neatly divided.

The vaccines were developed at astonishing speed, and their efficacy in large-scale clinical trials—95% protection from symptomatic illness for the messenger RNA vaccines—surpassed most scientists’ dreams. But once they entered the real world, things got messy. The production and distribution of billions of shots posed huge logistical obstacles. The stellar protection began to wane. The virus proved highly adaptable, with new variants appearing in quick succession. And the shining scientific triumph entered the murkier realm of politics and patent rules, commerce and conspiracy theories. The result has been a muddle—half triumph, half tragedy.

More than 8 billion shots have now been given worldwide—easily enough to fully vaccinate everyone on most priority lists: people who are over age 60, work in health care, or suffer from underlying conditions that can worsen COVID-19. That is not what has happened. Teenagers in some countries have received three shots; people elsewhere with a much higher risk of dying are still waiting for their first.

Millions are alive today because they got vaccinated, but millions of others have declined the offer of a safe, free vaccine. Hundreds of thousands died needlessly. And any hopes that the vaccines might curb transmission enough to stop the virus from spreading have proved ill-founded. As this year draws to a close, evidence is mounting that the Omicron variant may further erode vaccines’ protection. “It is a little depressing to be here in December 2021 and just still feeling like we have an uphill battle,” says Natalie Dean, a bio-statistician at Emory University.

For any drug or vaccine, expectations help shape whether it is seen as a success. Early on, scientists worried COVID-19 shots might only prevent 50% of cases. By that standard, vaccines vastly overperformed. But many in the public expected something like the measles or rubella vaccines, which offer complete, lifetime protection from infection—an unrealistic hope. “In our excitement of having a vaccine and having one quickly, we forgot that not everyone in the general public is a vaccinologist or virologist,” says Boghuma Titanji, a virologist at Emory.

Early, hopeful speculation that widespread vaccination would create herd immunity—when so many people are protected that the virus has nowhere to go—compounded the disappointment later. Herd immunity, always an ambitious goal, slipped out of reach as the more infectious Delta variant spread around the world and the shots’ protection waned.

Overall, the vaccines have proved very safe. But in the spring, a very rare but potentially deadly clotting disorder emerged in people who had received vaccines produced by AstraZeneca and Johnson & Johnson, which are based on an adenovirus vector. Although the risk-benefit ratio was still very good, many rich countries stopped using the shots once they had alternatives, which damaged confidence in vectored vaccines elsewhere, especially in poorer countries that received large shipments of the AstraZeneca vaccine. “The perception … has been that Africa was given subpar vaccines,” says Titanji, who had to convince her own parents in Cameroon to get the shot.

Cynical peddlers of half-truths and lies about the risks of vaccines and the promise of unorthodox remedies exploited the confusion, aided by an information ecosystem that prioritizes “engagement” over veracity and politicians who would rather put their voters’ lives at risk than risk acknowledging a complex truth. In the end, many people felt more comfortable swallowing an unproven drug used to deworm horses or taking their chance with a deadly virus than getting a vaccine that had been shown to protect the vast majority of people against severe disease and death.

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It is a little depressing to be here in December 2021 and just still feeling like we have an uphill battle.

  • Natalie Dean
  • Emory University

Nonbiomedical research could have helped: studies of vaccine hesitancy, the ways people make medical decisions, and how misinformation spreads and can be fought. “That is science, too, and we do not pay enough attention to it,” Dean says. Public health agencies neglected to approach those most vulnerable to misinformation before they were bombarded with lies, Titanji says.

Many people have not had the luxury of choosing whether to get the shots. Only 8% of Africa’s population is fully vaccinated. “You had this unseemly scramble with the rich countries paying whatever they could to get hold of what they wanted, and the rest pushed to the back of the queue,” says Helen Clark, co-chair of the Independent Panel for Pandemic Preparedness and Response, which was established by the World Health Organization (WHO) to draw lessons from the pandemic.

WHO and other groups in 2020 formed the COVID-19 Vaccines Global Access (COVAX) Facility to ensure a more equitable distribution. But its approach—buying vaccines in bulk and providing them for free to poor countries—was flawed, Clark says. Rich countries were happy to donate money but cornered the market for vaccines, leaving little for COVAX. And the scheme’s main supplier, the Serum Institute of India, provided far fewer doses than promised this year. “We would have been even worse off without COVAX,” Clark says. But its modest track record—some 650 million doses shipped to low- and middle-income countries so far—“exposed the limit of optimism in multilateralism,” says John Nkengasong, director of the Africa Centres for Disease Control and Prevention.

Targeting those most at risk across the globe would not only have been more just, but also would have averted more deaths, says Maria Van Kerkhove, a top WHO epidemiologist. And if rich countries had fewer doses, they might have followed WHO’s advice not to relax public health measures such as mask wearing and limits on gatherings, which could have blunted recent surges. “Particularly in those countries with access to the vaccines, there was a sense that the worst is over,” says Jeremy Farrar, head of the Wellcome Trust. That sense also eased the pressure to ramp up vaccine production and deliver more doses to more places fast. As WHO Director-General Tedros ­Adhanom ­Ghebreyesus recently put it: “In too many countries, the bright light of vaccines has also become a blinding light for the continued need to stop this virus from spreading.”

The pandemic is raging on. It’s back with a vengeance in the Northern Hemisphere, even in countries with high vaccination coverage. So far, vaccines have held up well against new variants, from Alpha to Delta. But the virus’ continuing spread gives it every opportunity to evolve and find better ways around human immunity, as early data suggest Omicron is doing.

Booster shots have been shown to bolster waning immunity, and may be a way for rich countries to keep future waves in check, but low- and middle-income countries cannot adopt such a strategy “without destroying their health budgets,” says Gagandeep Kang, a virologist at Christian Medical College, Vellore, in India. In the long run, we may need a new generation of vaccines, says Richard Hatchett, head of the Coalition for Epidemic Preparedness Innovations. Hatchett says he always viewed the current arsenal as “rapid response vaccines,” fit for the pandemic emergency, but not for the long-term struggle with the virus.

One solution may be vaccines that ramp up the immune response in the mucosa of the respiratory tract, where the virus first takes hold. If the approach can curb transmission, Nkengasong says, “That will truly become the game changer.” Others are holding out hope for a pancoronavirus vaccine that would not only thwart new variants, but any future cousins of SARS-CoV-2 as well.

Maybe Science will anoint a new vaccine as its breakthrough next year, or the year after. But whatever vaccines the world develops next, we will also have to find ways to use them better. So far in this pandemic, it has been the virus, not humanity, that has done most of the evolving.