News Special Report

How the Pandemic Led to Disarray -- and Discovery

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In March 2020, as the world was waking up to the dawn of a global pandemic, 61 members of the Skagit Valley Chorale in northwest Washington state gathered for a 2-hour rehearsal. They followed the precautions recommended by local health officials, avoiding physical contact, using hand sanitizer, and keeping socially distanced.

Within weeks, 52 of the choir members were diagnosed with COVID, several were hospitalized, and two members died. Experts were initially baffled about the reasons.

"You knew there's only one thing everybody in that room shared and that was the air," said Kimberly Prather, PhD, a professor at Scripps Institution of Oceanography in San Diego, CA, who studies aerosol chemistry. "Without a doubt, that is what led to the spread."

It was a pivotal moment in a pandemic that has created tectonic shifts in our lives at home, work, leisure. The pandemic has also led to major changes in the world of health, medicine, and science, some of which are likely to be with us after the virus no longer dominates the daily news headlines.

The Droplet Dogma

For most of the past century, there was broad consensus among public health experts that the spread of respiratory diseases like colds and the flu largely occurred when people came into contact with larger, heavy, virus-laden droplets that are expelled when people cough or sneeze.

Under this theory, you had to be close enough to a sick person when they coughed or sneezed to catch their illness, or you had to touch a surface where some of these large droplets had recently landed.

This droplet dogma formed the rationale for the initial health measures many people became familiar with in the early days of the pandemic, such as the 6-foot social distancing and the frequent cleaning of household, business, and workplace surfaces that led to a shortage of antibacterial wipes and sprays.

True airborne spread of infections was thought to be rare. Infectious disease expert Jeffrey Shaman, PhD, listened to that early advice from health experts and broadcast newscasters about how COVID was transmitted by droplet and was incredulous.

"I'm sitting there going out of my mind yelling at the television set saying, 'How do we know this? It's a novel virus!' " said Shaman, director of the climate and health program at Columbia University in New York, whose work focuses on the modeling of the spread of infectious diseases.

More outbreaks like the one in Washington state followed. It gradually became clearer that singing and loud talking, as people might in a church or a busy restaurant or bar, were optimal settings for generating the spread of tiny floating aerosols of SARS-CoV-2 virus that could remain aloft for hours. Churches were hit hard, probably because they're a place where people stand close together and sing.

It soon became clear that COVID-19 wasn't the only infectious disease that relies on aerosols to spread.

When mask wearing became a social norm in many parts of the United States, cases of influenza and respiratory syncytial virus, a common cold, all but disappeared. These illnesses returned in 2021, after the Centers for Disease Control and Prevention recommended that fully vaccinated people could take off their masks and mask-wearing declined.

The COVID-19 pandemic has led scientists to reevaluate the role and frequency of aerosol transmission.

"I really believe there would never have been a pandemic if you just relied on droplet spray, the people spraying and coughing on each other," Prather said. "This is being driven by sharing indoor air."

Testing Methods Put to the Test

Another significant idea to evolve from the pandemic is the concept that a rapid test can tell you if you might be contagious.

Early in the pandemic, most testing for the SARS-CoV-2 virus was done with polymerase chain reaction (PCR) tests, which are very sensitive and highly accurate in detecting COVID. The rationale for this focus on PCR tests was that, because of their sensitivity, these tests could detect the virus early on, so patients could seek treatment and limit the spread of the disease to others.

Efforts at the time were focused on making PCR testing more available, with faster turnaround times.

But some experts, such as Michael Mina, PhD, head of molecular virology diagnostics at Brigham and Women's Hospital in Boston, saw flaws in this strategy. For one thing, PCR testing was too scarce to catch most people who had the virus, and it wasn't a useful tool for public health officials trying to head off transmission through contact tracing.

"Of those 1 in 10 who do get diagnosed, almost all of them are getting diagnosed after they're infectious," he explained in a podcast in July 2020.

Mina's studies showed that people infected with SARS-CoV-2 had the highest levels of virus in their bodies early in their infection, often before they showed any symptoms. And high viral loads are closely linked to transmission.

What was needed, Mina thought, was a "good enough" test that was relatively inexpensive and easy to use, so people with the virus would quickly know when they might be a risk to others.

Mina has been a champion for the type of rapid antigen tests that people are now buying at places like CVS and Walgreens -- when they can find them. A positive result means stay home, you could pass your infection to others. A negative result doesn't rule out COVID-19, but it does suggest that you're not a risk to others.

The U.S. has come to embrace rapid testing, though it hasn't yet produced enough tests or made them cheap enough for people to use often. The Biden administration just this week launched a website offering four free tests to every household in the country. Health insurance companies are also now required to reimburse for tests purchased by the public.

Stephen Kissler, PhD, a postdoctoral fellow at the Harvard T.H. Chan School of Public Health, said this realization was a watershed moment for epidemiologists.

"Up until this point, a lot of us, even those of us who are epidemiologists, have thought about these discreet separated phases where a person is susceptible to diseases, they're infected, and then they recover. And you sort of pass from one stage to the other very predictably," he said.

"How much virus is being produced and how long it is being produced really matters both in terms of your ability to spread the virus and your ability to detect the virus in someone who has been infected," Kissler said.

Once the pandemic is over, it's very likely that self-testing for pathogens will remain and become more sophisticated, said Columbia University's Shaman.

"This idea of being able to test yourself is moving toward a Star Trekkie-type thing where we're going to have devices that allow us to test for multiple pathogens and give us the information on what we have so we don't have to go out and subject other people to them," Shaman said.

Rapid Publication: "Blessing and Curse"

The pandemic also rapidly accelerated the way scientific information is shared.

Just a few years ago, if a scientist made an important new discovery, he or she would write a study and then submit that paper to a peer-reviewed academic journal. From there, the manuscript had to pass through a series of time-consuming reviews by scientists, editors, and others before final publication.

Because the most prominent journals are highly selective, it was the norm for a researcher to submit their work to several journals before their paper was accepted and finally published. The process could take months or even years.

After SARS-CoV-2 emerged and rapidly spread, such delays in sharing research from scientists around the world became an obstacle to understanding the science behind the pandemic. Thousands of people were dying each day, and the world urgently needed answers about this highly destructive virus.

Preprint servers that publish preliminary versions of scientific manuscripts, before peer review, like medRxiv (pronounced med-archive, after the name for the Greek letter X), became the preferred way to share biomedical findings quickly with other researchers, health officials, and the public.

Papers submitted to medRxiv also are not edited, although they are screened for harmful or nonscientific content, according to the server's website. Eliminating those steps cuts the time it takes to publish from months or years to 4 to 5 days. Peer review sometimes -- but not always -- comes later, after the paper has been accepted by a scientific journal.

Meanwhile, universities and other institutions have joined the stampede, churning out press releases on new COVID research by faculty members, often before those findings have been adequately vetted. That crush has created dilemmas for journalists, researchers, and others trying to understand the quality of the science.

The result has been messy. According to Retraction Watch, a website which follows scientific publishing, more than 206 COVID-19 papers have been retracted or withdrawn since the start of the pandemic. In some cases, the removals involved misconduct; in others, the results were unreliable for other reasons.

One of the most damaging was a preprint posted to the Research Square server that touted the efficacy and safety of ivermectin, an antiparasitic treatment, to prevent and treat COVID-19.

Both that study and a meta-analysis that relied heavily on it were withdrawn "due to fraudulent data," said the editor of the journal that published the paper. Another widely cited study on ivermectin, from Argentina, was called into question after reporters from BuzzFeed News tried to dig into some of its claims.

Unfortunately, the withdrawal came after the preprint was touted by politicians and others who were promoting use of that drug as a COVID treatment, according to coverage by Retraction Watch.

Another paper that claimed that cases of myocarditis in teens spiked after the COVID-19 vaccine was approved for that age group was also withdrawn by its publisher. One of its co-authors, cardiologist Peter McCullough, MD, MPH, was removed from the faculties of several universities and hospitals in Texas after he promoted the use of unproven therapies for COVID-19 and questioned the effectiveness of the COVID-19 vaccines.

But the quickening pace of publication hasn't been all bad. Significant achievements -- new vaccines created, tested, distributed in less than a year -- blossomed in record time. Within days of its identification, researchers were publishing preprints on the ability of Omicron to escape immunity and transmit at lightning speed, giving countries critical time to prepare.

"There's been a good side," Scripps' Prather said. "We had to get the solutions to some of these things out there fast, and that was the only way." Many experts believe the publishing of nonpeer reviewed studies is likely to remain a bigger part of how science is disseminated in the future.

Michael Osterholm, PhD, who directs the University of Minnesota's Center for Infectious Disease Research and Policy, thinks the overall change in scientific publishing could be a double-edged sword.

"I think it's a blessing and a curse all in the same package," Osterholm said. "I think that has led to rapid dissemination of very important information, but it's also led to I think unintentional misinformation."

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