Among COVID-19 survivors, an increased risk of death, serious illness
As the COVID-19 pandemic has progressed, it has become clear that many survivors -- even those who had mild cases -- continue to manage a variety of health problems long after the initial infection should have resolved. In what is believed to be the largest comprehensive study of long COVID-19 to date, researchers at Washington University School of Medicine in St. Louis showed that COVID-19 survivors -- including those not sick enough to be hospitalized -- have an increased risk of death in the six months following diagnosis with the virus.
The researchers also have catalogued the numerous diseases associated with COVID-19, providing a big-picture overview of the long-term complications of COVID-19 and revealing the massive burden this disease is likely to place on the world's population in the coming years.
The study, involving more than 87,000 COVID-19 patients and nearly 5 million control patients in a federal database, appears online April 22 in the journal Nature.
"Our study demonstrates that up to six months after diagnosis, the risk of death following even a mild case of COVID-19 is not trivial and increases with disease severity," said senior author Ziyad Al-Aly, MD, an assistant professor of medicine. "It is not an exaggeration to say that long COVID-19 -- the long-term health consequences of COVID-19 -- is America's next big health crisis. Given that more than 30 million Americans have been infected with this virus, and given that the burden of long COVID-19 is substantial, the lingering effects of this disease will reverberate for many years and even decades. Physicians must be vigilant in evaluating people who have had COVID-19. These patients will need integrated, multidisciplinary care."
In the new study, the researchers were able to calculate the potential scale of the problems first glimpsed from anecdotal accounts and smaller studies that hinted at the wide-ranging side effects of surviving COVID-19, from breathing problems and irregular heart rhythms to mental health issues and hair loss.
"This study differs from others that have looked at long COVID-19 because, rather than focusing on just the neurologic or cardiovascular complications, for example, we took a broad view and used the vast databases of the Veterans Health Administration (VHA) to comprehensively catalog all diseases that may be attributable to COVID-19," said Al-Aly, also director of the Clinical Epidemiology Center and chief of the Research and Education Service at the Veterans Affairs St. Louis Health Care System.
The investigators showed that, after surviving the initial infection (beyond the first 30 days of illness), COVID-19 survivors had an almost 60% increased risk of death over the following six months compared with the general population. At the six-month mark, excess deaths among all COVID-19 survivors were estimated at eight people per 1,000 patients. Among patients who were ill enough to be hospitalized with COVID-19 and who survived beyond the first 30 days of illness, there were 29 excess deaths per 1,000 patients over the following six months.
"These later deaths due to long-term complications of the infection are not necessarily recorded as deaths due to COVID-19," Al-Aly said. "As far as total pandemic death toll, these numbers suggest that the deaths we're counting due to the immediate viral infection are only the tip of the iceberg."
The researchers confirmed that, despite being initially a respiratory virus, long COVID-19 can affect nearly every organ system in the body. Evaluating 379 diagnoses of diseases possibly related to COVID-19, 380 classes of medications prescribed and 62 laboratory tests administered, the researchers identified newly diagnosed major health issues that persisted in COVID-19 patients over at least six months and that affected nearly every organ and regulatory system in the body, including:
- Respiratory system: persistent cough, shortness of breath and low oxygen levels in the blood.
- Nervous system: stroke, headaches, memory problems and problems with senses of taste and smell.
- Mental health: anxiety, depression, sleep problems and substance abuse.
- Metabolism: new onset of diabetes, obesity and high cholesterol.
- Cardiovascular system: acute coronary disease, heart failure, heart palpitations and irregular heart rhythms.
- Gastrointestinal system: constipation, diarrhea and acid reflux.
- Kidney: acute kidney injury and chronic kidney disease that can, in severe cases, require dialysis.
- Coagulation regulation: blood clots in the legs and lungs.
- Skin: rash and hair loss.
- Musculoskeletal system: joint pain and muscle weakness.
- General health: malaise, fatigue and anemia.
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