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COVID-19 ‘long-haulers’ face increased risk of death and many other health problems

By Tristan Horrom
VA Research Communications

A year into the pandemic, most people are familiar with the immediate symptoms of COVID-19 infection, which include breathing problems and fever. But reports of COVID-19 “long-haulers” suggest that some people can have persistent, long-lasting health problems caused by the virus. In the largest post-acute COVID-19 study to date, VA Saint Louis Health Care System researchers characterize the potential long-term consequences of COVID-19 that some patients may experience.

The study shows that people who have had COVID-19 are at increased risk of a multitude of health problems, affecting not just the lungs but nearly every body system. “COVID is a multifaceted disease,” explains study author Dr. Ziyad Al-Aly of the VA Saint Louis Health Care System and Washington University. “It can affect many organs, including the brain, heart, lungs, kidneys, mental health, and other organ systems. The risk is not trivial in people who had mild disease in the acute phase of the infection.”

The results appear in the April 22, 2021, issue of the journal Nature.
Much research has focused on acute COVID-19, meaning patients’ health while they are actively infected with the virus. But less is known about possible health problems caused by the virus after the active infection subsides.

VA researchers took advantage of the large VA electronic health records database. They compared six-month outcomes of more than 73,000 VA patients who had survived COVID-19 without being hospitalized with those of nearly 5 million VA patients who did not contract COVID-19.

COVID-19 patients had a higher risk of dying in the six months after their diagnosis. Out of every 1,000 patients, about eight more COVID-19 patients than control patients were likely to die within six months. COVID-19 survivors were also more likely to use outpatient health care during that period.


COVID-19 increases risk of chronic health problems throughout body
The data show that patients who had COVID-19 were at increased risk for a myriad of potentially serious and long-term health conditions affecting multiple parts of the body. Many new health problems were seen in COVID-19 patients that were not present before infection.
Al-Aly explains that the fact the COVID-19 can affect so many different parts of the body show how serious it is long-term. “When you put the whole picture together, it is jarring,” he says. “The breadth of organ involvement and the increased risk of death after the first 30 days tells me that we are just seeing the tip of the iceberg. Long COVID is a serious problem and we must prepare for it.”

The most common health problems seen in COVID-19 long-haulers were respiratory conditions. COVID-19 patients had significantly heightened rates of a number of conditions, including respiratory failure, not getting deep enough breaths, and lower respiratory disease. They also had higher use of medications such as bronchodilators and asthma treatments.
Higher numbers of nervous system problems were also seen in COVID-19 patients, such as neurocognitive disorders and headaches.

COVID-19 infection is also linked to higher rates of mental health conditions, according to the study. COVID-19 patients showed elevated rates of sleep disorders, anxiety and fear-related disorders, and trauma and stress-related disorders. The evidence also suggests that patients who survive COVID-19 use more opioid and non-opioid pain killers, antidepressants, and sedatives to treat these conditions.
Higher metabolic disorder burden in the COVID-19 group included diabetes, obesity, and cholesterol problems.
COVID-19 infection also appears to increase the risk of cardiovascular problems down the line. COVID-19 patients had a higher burden of hypertension, irregular heartbeat, circulatory problems, chest pain, coronary atherosclerosis, and heart failure. They were also more likely to be on medications such as beta blockers and diuretics.

The gastrointestinal system also seems to be affected by COVID-19, found the study. COVID-19 patients had higher rates of esophageal disorders, gastrointestinal disorders, difficulty swallowing, and abdominal pain. These problems were associated with an increased use of medicines such as laxatives, antacids, and anti-diarrhea drugs.

In addition to all of these systemic health problems, COVID-19 long-haulers appear to have poorer general well-being compared with patients who have never had the virus. This includes feelings of malaise and fatigue, muscle disorders, musculoskeletal pain, and anemia. The COVID-19 group also had higher rates of pulmonary embolism, skin disorders, arthritis, and infections.


Taken together, the results show that COVID-19 can lead to “substantial burden of health loss” beyond the first 30 days of illness, according to the researchers.
Notably, the researchers found that the risk of all of these post-acute conditions existed even among patients whose infections did not warrant a hospital stay. However, patients who had more severe acute COVID-19 infection were at higher risk of long-haul conditions.
According to Al-Aly, around 8% to 10% of people with COVID-19 will likely have long-term effects. “We think that long COVID will likely represent a significant health crisis that will reverberate for many years and even decades,” he explains.

COVID-19 more dangerous than flu
In the study, the researchers also compared a different subset of COVID-19 patients to patients who had seasonal influenza. They looked at close to 14,000 patients hospitalized with COVID-19 and 14,000 patients hospitalized with the flu.
The COVID-19 patients had a 50% higher chance of death. They were more likely than flu patients to have more outpatient health encounters after leaving the hospital. The COVID-19 group also had much higher risk of a broad array of persistent health problems. These problems included both pulmonary conditions and other body system problems, similar to those seen in the non-hospitalized COVID-19 group studied.
The Nature study supports previous VA research that showed COVID-19 patients are at a much higher risk of death than patients with the flu.

The mechanisms underlying these chronic manifestations of COVID-19 are not entirely clear, according to the researchers. Some of the long-term problems are likely a direct effect of the viral infection. Others may involve changes in social, economic, and behavioral conditions faced by patients with COVID-19. As the pandemic continues, dealing with health problems—as well as stress from situations such as changing social interaction and job loss—could create new stress that creates new health problems or worsens existing ones.
The findings highlight the need for more study on how COVID-19 can affect a person’s health long-term, according to the researchers. The study can help provide a roadmap to plan strategies to reduce chronic and permanent health loss caused by COVID-19, they say.

“People with long COVID need integrated multidisciplinary holistic care,” explains Al-Aly. “If there ever was an exemplar in clinical medicine that best illustrates the importance of integrated multidisciplinary care, it is long COVID. Health systems should quickly adapt to this reality.”

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