With or without a declaration from the U.S. Centers for Disease Control and Prevention, COVID-19 cases continue to rise. Fortunately, the number and severity of those new cases is nowhere near the terrible peaks of the past three years, and deaths are very low. But that’s not the whole story.
Practically since the term “long COVID” was coined, anecdotal evidence and shorter-term studies indicated that the often-debilitating condition would not only affect significant numbers of people (roughly 15% of all U.S. adults have experienced long COVID symptoms) but also that it might do so in the most serious ways.
We’re beginning to see the severity of that issue. According to a paper published today in Nature Medicine, the physical fallout from long COVID may last two years or longer–and it can take a toll on quality of life even for those whose initial cases didn’t require hospital care.
“I think this is a sobering reminder that SARS COV-2 infection can have long-lasting risks on people even among the non-hospitalized, that they really need to consider this data very seriously,” Ziyad Al-Aly, a clinical epidemiologist at Washington University in St. Louis and the senior author of the study, told me in an interview. “I mean, this is data at two years. This is not like six months or a year out.”
A long risk horizon
The study, conducted in coordination with the Veterans Affairs St. Louis Health Care system, found that those who contracted COVID-19 but didn’t require hospitalization were still at elevated risk two years later for several conditions, including diabetes, lung problems, fatigue, blood clots, and disorders affecting the gastrointestinal and musculoskeletal systems. Those whose initial cases required hospitalization within the first 30 days faced more dire outcomes, with elevated risk for both hospitalization and death, along with significant risk across all organ systems.
Al-Aly and his team analyzed about 6 million anonymous medical records in a database maintained by the V.A., and created a control set of people who from March through December of 2020 either never tested positive for COVID, tested positive but weren’t hospitalized, or tested positive and required hospitalization.
Two years out, those who’d tested positive for the virus but didn’t need hospitalization were still at elevated risk for 31% of 80 long COVID-related conditions, although their risk of death and hospitalization diminished to levels roughly the same as those who’d never tested positive. For people who had required hospitalization for their cases, the risk of death and another hospitalization remained elevated, along with 65% of the long-COVID related conditions.
Like any study, this one has parameters. For one thing, because Al-Aly wanted to study the longer-term effects of the virus, his team analyzed data of patients from the earlier stages of the pandemic. The researcher says the subsequent development of vaccines and antivirals might produce different results in a study of people who were infected more recently.
In many ways, though, that’s the point. Most of the research pertaining to long COVID has concentrated on shorter-term benchmarks: six months or one year. As the Nature Medicine paper makes it clear, science is just beginning to understand how long the tentacles of the disease may reach.
At two years post-infection, the non-hospitalized group was at 27% higher risk than the non-COVID control group for ischemic stroke, 23% higher risk of a clotting disorder, 37% higher risk for headaches, and 250% higher risk for still having loss of smell, among many other sequelae. Those who were hospitalized had a 29% higher risk for death and a 257% higher risk for hospitalization, even at two years, and dramatically higher chances of diabetes, Alzheimer’s, low oxygen, and memory loss, the study found.
Al-Aly and his team also quantified the risk in terms of disability-adjusted life years, or DALY. One DALY, Al-Aly says, is equal to one less year of healthy life. In the non-hospitalized COVID-19 group, the research found about 80 DALYs per 1,000 people. For the hospitalized group, that number shot up to 642 DALYs per 1,000. By comparison, cancer and heart disease in the U.S. claim 50 and 52 healthy-life years lost per 1,000 people, respectively.
“It’s a difficult and protracted road for recovery in people who were hospitalized to start with,” Al-Aly says. “But most importantly, even for people who are not hospitalized, it is still a long risk horizon for many, many sequelae and multiple organ systems.”
‘An empty white box’ of validated treatments
The research should shine new light on the subject of long COVID, which has generally been understudied in the U.S. despite the large number of adults who’ve already been affected by it. Eric Topol, the scientist and vice president at Scripps Research in San Diego, has written extensively about long COVID and told me he does not believe the CDC and federal government are taking it seriously enough.
Topol, who was not involved in the St. Louis study, says it provides “important new evidence of the durable multi-system sequelae of long COVID.” When I asked whether the public really understands the long-term risks associated with the disease, he replied, “No, only the people affected and their friends and families.”
How the findings of the St. Louis study might translate to a younger population remains unknown. Almost by definition, the V.A. sample skews older and male. Al-Aly says it’s one reason the study pulled from the pool of 6 million, which included more than 600,000 women. “Those could fill like six Taylor Swift stadiums,” he says, “So it’s not a small number.” About 20% of the medical records were from Black patients, and the study included multiple ages and races.
And all of the information is more than the CDC has–or any governing body, for that matter. Very few studies of this longitude have been completed, and none at this scale.
Al-Aly says one of his hopes is that the St. Louis study will prompt a closer look on the governmental level at the ways clinical trials for long COVID treatments can be initiated–now. “We need to have a coherent national strategy to accelerate clinical trials and get a treatment that works as soon as possible,” the researcher says. “That really should be a national priority. The patient community has been waiting so long, and we need to find treatments as soon as possible.”
He’d also like to see studies like this one reproduced in other countries, especially since the limited work that’s been done so far has essentially replicated the results found in the St. Louis research. Those results are serious enough, and long-lasting enough, that they ought to grab the attention of national policymakers the world over–and the U.S. should take the lead.
Where are the long COVID treatment trials? A recent report by the health news site STAT revealed that the National Institutes for Health has failed to test meaningful treatments for long COVID after two and a half years and a $1.15 billion Congressional grant. Topol, meanwhile, has repeatedly used an empty white box to depict the number of validated treatments we have from well-designed randomized trials.
So great is the urgency that researchers like Topol are advocating for digital clinical trials in which the patients don’t have to leave home–a critical need, considering that some long COVID sufferers can barely get out of bed. Whether the federal government can move to such a system to produce treatments remains to be seen–but about the extended effects of long COVID, we no longer have much doubt.
Carolyn Barber, M.D., is an internationally published science and medical writer and a 25-year emergency physician. She is the author of the book Runaway Medicine: What You Don’t Know May Kill You, and the co-founder of the California-based homeless work program Wheels of Change.
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