The health effects of Covid-19 not only can stretch for months but appear to increase the risk of death and chronic medical conditions, even in people who were never sick enough to be hospitalized, a large new study finds.
In the study, published Thursday in the journal Nature, researchers looked at medical records of more than 73,000 people across the United States whose coronavirus infections did not require hospitalization. Between one and six months after becoming infected, those patients had a significantly greater risk of death — 60 percent higher — than people who had not been infected with the virus.
The research, based on records of patients in the Department of Veterans Affairs health system, also found that nonhospitalized Covid survivors had a 20 percent greater chance of needing outpatient medical care over those six months than people who had not contracted the coronavirus.
The Covid survivors experienced a vast array of long-term medical problems that they had never had before — not just lung issues from the respiratory effects of the virus, but symptoms that could affect virtually any organ system or part of the body, from neurological to cardiovascular to gastrointestinal. They were also at greater risk of mental health problems, including anxiety and sleep disorders.
“We found it all,” said an author of the study, Dr. Ziyad Al-Aly, chief of the research and development service at the VA St. Louis Health Care System.
“What was shocking about this when you put it all together was like ‘Oh my God,’ you see the scale,” he added. “It’s still jarring, honestly.”
What’s more, some of the patients’ post-Covid medical issues — like diabetes, kidney disease and some heart problems — could become chronic conditions that would require treatment for the rest of their lives.
“People have continued respiratory disease, continued headache, this, that and the next thing,” said Dr. Laurie Jacobs, chairwoman of internal medicine at Hackensack University Medical Center, who was not involved in the study. “It’s not gone away. And we don’t yet understand the underlying cause, and it’s become chronic in some cases, disabling in other cases. In some areas, people have gotten better, but it’s very variable.”
The study is believed to be the largest yet to evaluate such a comprehensive array of health conditions. The non-hospitalized Covid survivors in the study tested positive for the virus from March 1, 2020, through November.
Most of the nearly 32 million people who have contracted the coronavirus in the United States have not needed hospitalization, so in some ways the study may be applicable to a wide swath of the population. But the Veterans Health System patients in the study may not be representative in other ways, including that 88 percent of them were male and their median age was 61. Nearly 25 percent were Black, 70 percent were white and nearly 5 percent were other races.
Researchers compared their risk of death and other characteristics with data from nearly 5 million patients in the Veterans system who did not have Covid-19 and were not hospitalized during that time. That group had a median age of 67, was 90 percent male and had a somewhat larger proportion of white patients and a somewhat smaller proportion of Black patients.
Dr. Jacobs said her clinic was seeing the wide range of symptoms in the study. But she said the risk of death among the study’s patients was considerably higher than she would have expected. “I was really shocked by the number,” she said.
Between one and six months after experiencing a relatively mild or moderate infection, 1,672 of the 73,345 patients — about 2.3 percent — died, the study reported. It did not indicate what caused the deaths or anything specific about those patients’ conditions.
The researchers also could not say if people had underlying health conditions and whether their new symptoms were direct effects of their coronavirus infection, corollary effects of medications they were taking to treat some of the symptoms, stress from other pandemic-related problems or other influences. Experts said the study’s findings reflect a cascade of issues driven not just by the virus itself but by the medical system’s struggle to grapple with Covid-19 and its long-term effects.
“We have hundreds of thousands of people with an unrecognized syndrome and we are trying to learn about the immune response and how the virus changes that response and how the immune response can include all the organ systems in the body,” said Dr. Eleftherios Mylonakis, chief of infectious diseases at Brown University’s Warren Alpert Medical School and Lifespan hospitals, who was not involved in the study. “The health system is not made to deal with something like this.”
In many cases, Dr. Mylonakis said, people experiencing new symptoms who were never acutely sick from the viral infection enter a confusing and balkanized medical world, where they seek help from primary care doctors and then are referred to various specialists who each try to figure out how to treat conditions that fall under their particular area of expertise. That helps explain why the study found that the Covid survivors had about one-and-a-half times more outpatient visits a month than patients in the general V.A. population.
“We’re dealing with silos,” Dr. Mylonakis said. “Every time that we have a transfer, something is lost. The patient loses and that may make their other long Covid symptoms worse.”
For example, “if I’m an endocrinologist, I’m going to look at the blood sugar, I’m not going to look at the 14 other systems,” he said. “But the problem with the blood sugar may be because this person has such weakness and fogginess that they cannot go to the supermarket and get healthy foods, so they’re going to order pizza.”
Dr. Mylonakis said the unified nature of the Veterans system may actually make it better at coordinating care and sharing patient information among specialists, so for patients outside that system, the frustration and confusion may add considerable stress that aggravates their symptoms.
Still, the complexity of long-term Covid is abundantly evident within the Veterans system too.
“I have patients that get out of bed for 10 minutes to prepare a salad and they can’t eat it because they’re totally exhausted, so tired by the time they put a small salad together,” said Dr. Al-Aly.
The research showed that Covid survivors were also more likely to be taking a spectrum of medications for their newly emerged health problems, including opioids, which Dr. Al-Aly said was concerning because it might portend another wave of opioid addiction problems in the future.
Dr. Al-Aly and his co-authors Yan Xie and Benjamin Bowe, both at Washington University in St. Louis, also analyzed records of 13,654 patients who had been hospitalized for their initial coronavirus infection. Unsurprisingly, they found that the sickest patients — those who needed intensive care — were at the greatest risk of long-term complications, followed by those who were hospitalized in regular wards, followed by patients who were never hospitalized.
Nonetheless, virtually every category of symptom — from chest pain to shortness of breath to diabetes to muscle weakness — were experienced by at least some of the people who were never hospitalized.
“I would interpret this as saying ‘It’s everywhere,’” Dr. Al-Aly said. “Even if you just stayed at home and then quote-unquote recovered in three or four days. And that’s very important because that segment really is the lion’s share of Covid patients. Most people, when they get Covid, they don’t get hospitalized.”
For people who were hospitalized, their experiences involved significantly greater risk of long-term health complications than people hospitalized for seasonal flu, the study found. They were more likely to develop or have persistent symptoms in a wide array of categories beyond the respiratory manifestations of Covid: neurological, cognitive, psychological, cardiovascular, metabolic gastrointestinal, anemia and blood clotting problems as well as fatigue and malaise.
Dr. Mylonakis and other experts noted that the understanding of the virus and the status of medical treatment are evolving quickly, and this progress is already translating into improvement for some patients. In addition, some people with long Covid have gotten better over time, either on their own or with the help of treatment.
Still, Dr. Al-Aly said: “What we will grapple with for years to come, maybe even for decades, is the effect of the pandemic on the long-term health of Americans.”
He added, “We got caught unprepared for Covid. Let’s not drop the ball on long Covid.”