Two studies tie long COVID-19 to severe initial illness

Woman with sinus headache on couch
Woman with sinus headache on couch

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Two new studies, one in China and one in the United Kingdom, detail persistent COVID-19 symptoms months to a year after acute illness.

45% have at least 1 long-term symptom

Today, in JAMA Network Open, Chinese researchers describe "long COVID" symptoms of fatigue, sweating, chest tightness, anxiety, and muscle pain among 2,433 COVID-19 survivors released from one of two hospitals in Wuhan, China, from Feb 12 to Apr 10, 2020.

The team conducted phone interviews and chronic obstructive pulmonary disease (COPD) assessment tests (CATs) with the patients from Mar 1 to Mar 20, 2021.

Among 2,433 patients, median age was 60 years, 49.5% were men, 27.9% had survived severe COVID-19, 29.3% had high blood pressure, 45.0% reported having at least one persistent symptom, and 15.8% reported at least three symptoms. The most common symptoms were fatigue (27.7%), sweating (16.9%), chest tightness (13.0%), anxiety (10.4%), and muscle pain (7.9%)

While cough, anorexia, and shortness of breath decreased over the year since hospital release, several new symptoms appeared, including heart palpitations (4.2%), swelling of the lower limbs (1.4%), and changes in taste (1.4%) and smell (1.3%).

During a median hospital stay of 14 days, 2.2% required intensive care and 71.6% were given supplemental oxygen, of whom 0.9% received mechanical ventilation. Severely ill patients were older, more likely to be men, had more underlying diseases, had a longer hospital stay, and were more likely to need intensive care.

Older age (odds ratio [OR], 1.02), female sex (OR, 1.27), and severe coronavirus illness (OR, 1.43) were tied to elevated risk of fatigue. Older age (OR, 1.02) and severe illness (OR, 1.51) were linked with higher risk of having at least three long-term symptoms.

Median CAT score was 2, indicating low impact on quality of life, and 6.6% of patients had scores of 10 or higher, indicating moderate impact. Severe disease (OR, 1.84) and underlying cerebrovascular conditions (OR, 1.95) were independent risk factors for CAT scores of 10 or higher.

"The findings provide valuable information about the long-term health outcomes of COVID-19 survivors and identify risk factors for sustained symptoms and poor respiratory health status, which is of importance with the coming of the post–COVID-19 era," the study authors wrote.

Long COVID symptoms more common than those after flu

A study led by University of Oxford researchers published yesterday in PLOS Medicine identified persistent symptoms among 273,618 COVID-19 survivors 3 to 6 months after diagnosis. The cohort was also compared with 114,449 flu patients.

Patients were, on average, 46 years old, 55.6% were female, 57.0% had at least one long-term symptom in the first 6 months after diagnosis (including the acute illness), and 36.6% reported the same from 3 to 6 months after diagnosis.

Symptoms included abnormal breathing (18.7% over 6 months, 7.9% over 3 to 6 months), fatigue or malaise (11.6% and 7.2%, respectively), chest or throat pain (12.6%, 5.7%), headache (8.7%, 4.6%), other pain (11.6%, 7.2%), abdominal problems (15.6%, 8.3%), muscle pain (3.2%, 1.5%), cognitive problems (7.9%, 4.0%), and anxiety or depression (22.8%, 15.5%). Cognitive problems, but not muscle pain or headaches, were tied to more severe disease.

The risk of long COVID-19 was higher in patients who had more severe illness and somewhat higher among females and young adults. White and non-white survivors were affected equally.

A lower proportion of COVID-19 survivors 10 to 21 years old (46.2%) reported any long COVID-19 symptom than that of those 65 and older (61.1%). Likewise, patients who had been hospitalized or required intensive care were more likely than those with mild illness to report any symptom (73.2% and 63.6%, respectively).

Males reported significantly more breathing and cognitive symptoms than females, who were more likely to report headaches, abdominal issues, and anxiety or depression. Older survivors reported more breathing problems, cognitive symptoms, pain, and fatigue than younger patients, who were more likely to report headaches, abdominal difficulties, and anxiety or depression.

"It is notable that long-COVID features were also recorded in children and young adults, and in more than half of nonhospitalized patients, confirming that they occur even in young people and those who had a relatively mild illness," the authors wrote.

Most patients who still had COVID-19 symptoms at 3 to 6 months already had them in the first 3 months. Compared with patients who had recovered from flu, COVID-19 survivors more often reported symptoms (excess incidence, 16.6%, hazard ratios, 1.4 to 2.0), which also more often occurred simultaneously.

"The fact that the risk is higher after COVID-19 than after influenza suggests that their origin might, in part, directly involve infection with SARS-CoV-2 and is not just a general consequence of viral infection," the researchers wrote. "This might help in developing effective treatments against long-COVID."

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