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30% of COVID-19 patients have lingering symptoms 6 months later — Washington study

Nearly a third of people with COVID-19 had lingering symptoms a median of 6 months after infection onset, a single-centre prospective study found. Among COVID-19 patients whose infections ranged from asymptomatic to severe, two problems – fatigue and loss of smell or taste – persisted most frequently, reported Dr Helen Chu, of University of Washington in Seattle, and co-authors.

"The effects of COVID-19 can linger far beyond acute infection, even in individuals who experienced mild illness," said co-author Dr Denise McCulloch, 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 is quoted in MedPageToday as saying.

Earlier studies focused largely on long-term effects in hospitalised COVID patients, McCulloch noted. "Our study is unique in characterising 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 Dr Allison Navis, 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 hospitalised COVID-19 patients had at least one symptom that persisted 6 months after acute infection, mostly fatigue or muscle weakness. "Studies of non-hospitalised patients have shown that anywhere from 35% to 50% of non-hospitalised 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 Centre 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 follow-up 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 hospitalised 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 28m cases of COVID-19 in the US 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."


Study details
Sequelae in Adults at 6 Months After COVID-19 Infection

Jennifer K Logue; Nicholas M Franko; Denise J McCulloch; Dylan McDonald; Ariana Magedson; Caitlin R Wolf; Helen Y Chu

Published in JAMA Network Open on 19 February 2021

Many individuals experience persistent symptoms and a decline in health-related quality of life (HRQoL) after coronavirus disease 2019 (COVID-19) illness.1 Existing studies have focused on hospitalized individuals 30 to 90 days after illness onset2-4 and have reported symptoms up to 110 days after illness.3 Longer-term sequelae in outpatients have not been well characterized.
A longitudinal prospective cohort of adults with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was enrolled at the University of Washington with a concurrent cohort of healthy patients in a control group (eAppendix in the Supplement). Electronic informed consent was obtained, and the study was approved by the University of Washington human participants institutional review board. This study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline. COVID-19 symptom data were obtained at the time of acute illness or retrospectively recounted at a 30-day enrollment visit. A total of 234 participants with COVID-19 were contacted between August and November 2020 to complete a single follow-up questionnaire between 3 and 9 months after illness onset. We did not perform statistical tests for this descriptive analysis because of the small numbers in each subgroup. Data analysis was conducted in R version 4.0.2 (R Project for Statistical Computing).
A total of 177 of 234 participants (75.6%; mean [range] age, 48.0 [18-94] years; 101 [57.1%] women) with COVID-19 completed the survey. Overall, 11 (6.2%) were asymptomatic, 150 (84.7%) were outpatients with mild illness, and 16 (9.0%) had moderate or severe disease requiring hospitalization (Table). Hypertension was the most common comorbidity (23 [13.0%]). The follow-up survey was completed a median (range) of 169 (31-300) days after illness onset among participants with COVID-19 (Figure, A) and 87 (71-144) days after enrollment among 21 patients in the control group. Among participants with COVID-19, persistent symptoms were reported by 17 of 64 patients (26.6%) aged 18 to 39 years, 25 of 83 patients (30.1%) aged 40 to 64 years, and 13 of 30 patients (43.3%) aged 65 years and older. Overall, 49 of 150 outpatients (32.7%), 5 of 16 hospitalized patients (31.3%), and 1 of 21 healthy participants (4.8%) in the control group reported at least 1 persistent symptom. Of 31 patients with hypertension or diabetes, 11 (35.5%) experienced ongoing symptoms.
The most common persistent symptoms were fatigue (24 of 177 patients [13.6%]) and loss of sense of smell or taste (24 patients [13.6%]) (Figure, B). Overall, 23 patients (13.0%) reported other symptoms, including brain fog (4 [2.3%]). A total of 51 outpatients and hospitalized patients (30.7%) reported worse HRQoL compared with baseline vs 4 healthy participants and asymptomatic patients (12.5%); 14 patients (7.9%) reported negative impacts on at least 1 activity of daily living (ADL), the most common being household chores.
In this cohort of individuals with COVID-19 who were followed up for as long as 9 months after illness, approximately 30% reported persistent symptoms. A unique aspect of our cohort is the high proportion of outpatients with mild disease. Persistent symptoms were reported by one-third of outpatients in our study, consistent with a previously reported study,4 in which 36% of outpatients had not returned to baseline health by 14 to 21 days following infection. However, this has not been previously described 9 months after infection.


[link url=""]Full MedPageToday report (Restricted access)[/link]


[link url=""]JAMA Network Open research letter (Restricted access)[/link]



See also MedicalBrief archives:

[link url=""]Catching up to ‘Long COVID’ — Diagnostic and treatment information, at last[/link]


[link url=""]Long COVID may cause multiple-organ damage even in low risk patients — Coverscan Study[/link]


[link url=""]Answers to ‘long COVID’ may lie in Chronic Fatigue Syndrome research[/link]


[link url=""]Up to 60,000 in UK suffering from ‘long COVID’ beyond 3 months[/link]


[link url=""]Long COVID: Reviewing the Science and Assessing the Risk — Tony Blair Institute for Global Change report[/link]

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