COVID-19 symptoms linger for months in majority of hospitalized patients, Stanford study finds

More than 70% of COVID-19 patients in studies - most of whom were hospitalized - reported 84 different symptoms and signs months after they became ill.

A wide variety of symptoms persisted in more than 70% of COVID-19 patients months after recovering from the initial phases of disease, according to a study by researchers at the Stanford School of Medicine.

Most of the patients in the study - one of the largest reviews of scientific literature on the topic - had been hospitalized due to COVID-19.

Among the most common lingering symptoms were shortness of breath, fatigue and sleep disorders. In all, 84 different symptoms and clinical signs were reported, including loss of taste and smell, cognitive disorders such as loss of memory and difficulty concentrating, depression, anxiety, chest pain and fevers.

The findings raise concern about an immense public health burden if even a portion of these patients need continuing care, said Steven Goodman , MD, PhD, senior author of the study and a professor of epidemiology and population health and of medicine.

"If something on the order of 70% of those coming out of moderate to serious COVID-19 are showing persisting symptoms, that is a huge number," Goodman said.

The study will publish May 26 in JAMA Network Open. Tahmina Nasserie , a graduate student in epidemiology, is the lead author.

’Astonishing’ number of symptoms

"It’s astonishing how many symptoms are part of what’s now being referred to as long COVID ," Goodman said. He added that the review found wide discrepancies in design and quality of the studies, making it difficult to compare results, but it remained evident that the problem of persistent symptoms is substantial. A recent initiative to study long COVID was launched by the National Institutes of Health, which will be allocating $1.15 billion toward research on the subject.

The authors collected and analyzed results from 45 different studies published in English between January 2020 and March 2021. The studies included a total of  9,751 patients diagnosed with COVID-19, 83% of whom had been hospitalized. Goodman added that there is little research available on post-COVID-19 symptoms among those with milder cases, but that two studies, reporting on 214 outpatients, showed high frequencies of persistent symptoms.

For their review, the authors defined persistent symptoms as those lasting for at least 60 days after diagnosis, symptom onset or hospital admission, or at least 30 days after recovery from acute illness or hospital discharge. The majority of the studies followed patients no more than three months, but a few followed patients for six months.

"We did this study because there have been a lot of news commentaries and scientific  articles  talking about long-term COVID symptoms," Nasserie said. "But few had dug into the scientific evidence deeply enough to show the full range, how long they lasted and whom they affected."

The authors found that 72.5% of study participants reported at least one persistent symptom. The rates were as high in two six-month studies. The symptoms indicated that a variety of systems within the body were affected, including cardiac, respiratory, neuromuscular, neurological, circulatory and immune systems, Nasserie said.

Shortness of breath, fatigue, sleep problems

The most commonly occurring symptoms were shortness of breath, fatigue, exhaustion and sleep problems. "The numbers are very shocking, especially for fatigue and shortness of breath," Nasserie said. "These were pretty debilitating symptoms, with some people reporting difficulty walking up a flight of stairs." About 40% of patients said they experienced fatigue, 36% said they experienced shortness of breath and 29% said they experienced sleep disorders. Depression and anxiety, along with general pain and discomfort, were also relatively common: About 20% of patients described these symptoms. An inability to concentrate, commonly referred to as "brain fog," was mentioned by about 25% of patients.

As an epidemiologist who studies patterns of disease, Goodman said he became increasingly concerned about the lingering effects of COVID-19 in early fall 2020 as news reports emerged of patients calling themselves "long haulers" and reporting a variety of unusual symptoms after recovering from the acute phase of the illness.

"Early on, we completely ignored the long-term consequences of getting sick with this virus," Goodman said. "People were being told this was all in their heads. The question now isn’t is this real, but how big is the problem."

Michael Hittle , a PhD candidate in epidemiology and clinical research at Stanford, also was a co-author on the study.

Stanford’s Department of Epidemiology and Population Studies supported the work.

Stanford Medicine integrates research, medical education and health care at its three institutions - Stanford University School of Medicine , Stanford Health Care (formerly Stanford Hospital & Clinics) , and Lucile Packard Children’s Hospital Stanford. For more information, please visit the Office of Communication & Public Affairs site at http://mednews.stanford.edu.

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