Two years may feel like an eternity to a world weary of the coronavirus pandemic. In terms of scientific development, it’s been the blink of an eye, and we’ve learned a lot during that blink.
A century separated Charles Darwin’s “The Origin of Species” and the discovery of DNA’s double helix. Another half century or so passed before gene editing took hold.
Humanity’s ability to fight SARS-CoV-2 has gained enormously from the lessons learned during those and more recent decades. Within about a month of novel coronavirus cases being conclusively identified in December 2019, Chinese scientists had sequenced the coronavirus genome. With that, the global race to find ways to stop the virus’s spread and prevent those infected from getting seriously ill commenced. As the virus mutates and burns through vulnerable populations and the Greek alphabet, that race continues.
Ever since, the vast majority of us who aren’t scientists have had a front-row seat in the hit-or-miss world of hypothesis development and the empirical research that follows it.
What we’ve learned during the pandemic
After emptying stores of bleach and disinfecting wipes, we learned that surface transmission wasn’t in fact much of a driver of this particular disease (though it is with many others) – rather, aerosol transmission through the air we breathe was causing most infections. With that insight, we further learned that masking slows COVID-19’s spread, which we learned can happen before symptoms present (presymptomatically) or in the total absence of symptoms (asymptomatically). We learned the hard way that COVID-19 infections are nastier among the aged, the overweight and obese (perhaps because we learned that the coronavirus attacks fat tissue), those with diabetes, the immunocompromised, and other population segments. We learned that pregnant women who catch the coronavirus have a higher risk of preterm births.
We learned that infusing convalescent plasma from those who have recovered from COVID-19 doesn’t help fight coronavirus infections, nor does zinc or hydroxychloroquine. Ivermectin probably doesn’t, either, though the clinical trials proving or disproving that statement remain to be published. Those findings will soon join the more than 20,000 papers dedicated to some facet of a zombie life form of which 10 billion – a number greater than that of the global human population it continues to menace – could fit in a single layer atop your fingernail.
Greatest hits during a global pandemic
If those were misses, there have been hits. Foremost among these has been the development of mRNA vaccines. Dr. Thomas Campbell, a University of Colorado School of Medicine and UCHealth virologist, described the famous Pfizer and Moderna products as having had a “huge, huge impact,” in preventing initial infection and, more importantly, in preventing severe disease among those who end up with breakthrough infections.
“The vaccines’ job is not to prevent SARS-CoV-2 infection as much as it is to keep people out of the hospital and keep people from dying, and they’ve done that job very well,” Campbell said.
Campbell says he hesitates to think about what this pandemic would have looked like without the vaccines that have proven to reduce the risk of dying of COVID-19 by a factor of 14. UCHealth hospitals are crowded with coronavirus patients despite 76% of Colorado’s over-18 population and 87% of the over-65 population being fully immunized.
It’s easy to forget that, prior to the U.S. Food and Drug Administration’s emergency-use authorization of Pfizer and Moderna vaccines in December 2020 – less than a year after the SARS-CoV-2 virus was characterized – the speed record for vaccine development was four years (mumps, 1967). Many scientific advances over the past quarter century contributed to the blazing pace of mRNA vaccine development.
“This is the first major pandemic since the 1918 avian influenza,” Campbell said. “Sometimes I wonder what it would have been like if SARS-CoV-2 had emerged then. Would it perhaps have been even worse than what that influenza did? In 1918, we didn’t have mRNA technology; we didn’t have the communications technologies; on the patient-care side, we didn’t have ventilators – probably not much in the way of supplemental oxygen even. We could have seen many millions more people die or get seriously ill.”
Ross Kedl, a CU School of Medicine immunologist and vaccine specialist, says the mRNA vaccines have proven to trigger a burst of antibodies that latch onto the coronavirus spike proteins and prevent the virus from entering cells – “much higher than most vaccine platforms will deliver.”
The decision to provide second doses within three to four weeks of the initial dose augmented that effect, he says. Boosters coming six or so months after the second dose should provide a durable immune response, one that could last 12 to 18 months, he adds.
“The magnitude of immunity you can get out of an mRNA vaccine is really substantial,” Kedl said.
Pandemic has taught us that targets evolve
Both Campbell and Kedl said they expect mRNA vaccines to play big roles in future immunization campaigns of all sorts.
“I think the big advantage of the mRNA vaccines is that they can be created, tested, and scaled up so quickly, and once you have an mRNA vaccine that works, it’s a lot easier to produce it in large quantities than it is to produce large quantities of viral protein or whole viruses,” Campbell said, referring to alternative ways to make vaccines.
The relative ease of production translates into agility in being able to adjust the mRNA sequences as viruses mutate or new threats emerge, Kedl says. Moderna is already working on a combination coronavirus booster-flu vaccine as well as boosters for the omicron variant, which Pfizer is also developing. Both companies have said that boosters substantially increase protection against both delta and omicron variants, and that even if breakthrough infection occurs, vaccination sharply lowers the risk of serious disease.
Kedl adds that mRNA vaccines could prove to be weapons against any infectious disease in which antibodies are a primary mode of protection, “and that’s pretty much almost all infectious diseases,” he said.
On the treatment end, the advances have been more incremental, and that fact has been reflected in the stubbornly high number of fatalities among patients sick enough to be hospitalized.
Changes in how patients are given oxygen or ventilated have made a difference, as has proning ventilated patients to help open up the lungs. The steroid dexamethasone has been shown to be somewhat helpful to hospitalized patients. When given to patients before they’re too sick, monoclonal antibodies developed specifically for SARS-CoV-2 infection can reduce the chance of hospitalization by 70%. The antiviral remdesivir, which Gilead Sciences originally tested on Ebola in 2014, can benefit hospitalized patients, but like monoclonal antibodies, is most effective when given early in the course of infection.
New antivirals developed specifically to combat SARS-CoV-2 are on the way. Merck’s molnupiravir, which reduces the risk of hospitalization and death by 30% if taken within five days of symptom onset, is on the cusp of U.S. Food and Drug Administration approval. Pfizer’s entry here appears to be even more potent – 89% effective at preventing hospitalization when given within three days of symptom onset. Unlike remdesivir, which requires an infusion, the Merck and Pfizer antivirals come as pills that are much easier to administer to outpatients. They also target viral proteins important in viral replication – and not coronavirus spike proteins – and so should be effective across coronavirus variants (though, in molnupiravir’s case, potentially risky for pregnant women). The federal government has ordered both pills by the millions.
As impressive as mRNA vaccines have been, “antivirals are not easy to make,” Kedl said, and to make them within less two years of the coronavirus’s discovery bodes well for humanity’s ability to combat future pandemics.
Better models take into account lessons learned during pandemic
The scientific advances haven’t been limited to COVID-19 vaccines and treatments. Dr. Jonathan Samet, dean of the Colorado School of Public Health and leader of the Colorado COVID-19 Modeling Group, said the group’s models have become increasingly sophisticated as they’ve taken into account lessons learned during the COVID-19 pandemic. That’s improved the projections given to state leaders as guidance in implementing policies to slow COVID-19 transmission and determine the need to expand health care system capacity for COVID-19 patients.
“We now need to build in booster status and vaccination for 5- to 11-year-olds, for example,” he wrote in an email. “We also have altered the model over time to account for the more transmissible delta variant, and we are now thinking about omicron.”
Samet added that national modeling efforts are combining the results of multiple models – ensembles – much as is done in modern weather forecasting. In some ways, modeling COVID-19 is harder than modeling the weather, though, because new variants can change the model’s basic assumptions. It would be like a weather model suddenly dealing with an entirely new form of precipitation.
“All models are challenged at times by reality, particularly when the direction of the pandemic is not clear,” Samet said.
On the public health side, “we still have the same public health tools for ending the pandemic, and their utility has been diminished in some places by their politicization,” Samet said. “My impression is that the politics of NPIs [nonpharmaceutical interventions] have become more difficult over time. And we face the unanticipated challenge of large number of unvaccinated people who maintain the pandemic, unfortunately.”
Indeed, there have been failures with the successes. But taken together, scientific advances over the past two years – particularly the development of mRNA vaccines –have proven monumental both in beating back the relentless advance of the coronavirus as well as in establishing new bases from which to defend against future pandemics.