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Nearly one-third of people with COVID-19 had lingering symptoms a median of 6 months after infection onset, a single-center prospective study suggested.

Among COVID-19 patients whose infections ranged from asymptomatic to severe, two problems -- fatigue and loss of smell or taste -- persisted most frequently, reported Helen Chu, MD, MPH, of University of Washington in Seattle, and co-authors, in a .

"The effects of COVID-19 can linger far beyond acute infection, even in individuals who experienced mild illness," said co-author Denise McCulloch, MD, MPH, also of University of Washington.

"To our knowledge, this study presents the longest follow-up symptom assessment post-illness, with individuals surveyed out to 9 months after their COVID diagnosis," she told MedPage Today.

Earlier studies focused largely on long-term effects in hospitalized COVID patients, McCulloch noted. "Our study is unique in characterizing a group consisting of mostly outpatients: 90% of our cohort experienced only a mild COVID-19 illness, yet one-third continue to have lingering effects," she said.

"Many of these individuals are young and have no pre-existing medical conditions, indicating that even relatively healthy individuals may face long-term impacts from their illness."

There's very little data about people who have long-term COVID symptoms, observed Allison Navis, MD, of Icahn School of Medicine at Mount Sinai in New York City, who wasn't involved with the study.

Early in 2021, researchers in Wuhan, China, reported that 76% of had at least one symptom that persisted 6 months after acute infection, mostly fatigue or muscle weakness. "Studies of non-hospitalized patients have shown that anywhere from 35% to 50% of non-hospitalized patients had symptoms 2 to 4 months later," Navis noted.

Fatigue, breathing issues, and cardiac concerns like chest pain are common findings, as are neurologic symptoms, she pointed out. Of patients at the Center for Post-COVID Care at Mount Sinai with neurology referrals, "about 65% come in with cognitive complaints or brain fog," Navis said.

"Brain fog means different things to different people, but usually it's some combination of short-term memory issues, attention issues, and word-finding difficulty." It's a little different for every patient, she added: "A clear phenotype hasn't really emerged yet."

The University of Washington study followed 177 people with laboratory-confirmed SARS-CoV-2 infection who completed questionnaires from August to November 2020, 3 to 9 months after their COVID-19 onset (median 169 days). Mean age was 48 and 57% were women. Hypertension was the most common comorbidity (13%).

Across the cohort, 6.2% of participants were asymptomatic, 84.7% were outpatients with mild illness, and 9.0% were hospitalized with moderate or severe disease. Patients completed followup questionnaires a median of 169 days after COVID-19 onset.

Overall, 32.7% of outpatients and 31.3% of inpatients reported at least one persistent symptom, most commonly fatigue (13.6%) and loss of sense of smell or taste (13.6%). In addition, 13.0% reported other symptoms, including brain fog (2.3%).

Among outpatients and hospitalized patients, 30.7% reported worse health-related quality of life compared with baseline; this figure was 12.5% for patients who never had overt COVID symptoms. About 8% of all participants said at least one activity of daily living suffered long-term consequences, most commonly household chores.

Study limitations include small sample size, single study location, and potential bias from self-reported symptoms, the researchers acknowledged. "We plan to continue to survey our cohort every 6 months for 2 years to continue to assess changes in long-term symptoms over time," McCulloch said. "With over 28 million cases of COVID-19 in the U.S. alone, if even a small percentage of people experience long-term debility, this could have significant and lasting health and economic consequences."

More research is needed to understand why some COVID-19 patients have lingering symptoms, Navis noted. "We don't know what's causing this. There might be different etiologies for different people; it might not be just one thing," she suggested. "Is it vascular? Is it metabolic? Is it inflammatory? It's hard to say."

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