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Figure.  Time of Survey Completion and Coronavirus Disease 2019 (COVID-19) Symptoms
Time of Survey Completion and Coronavirus Disease 2019 (COVID-19) Symptoms
Table.  Demographic and Clinical Characteristics of the Study Cohort
Demographic and Clinical Characteristics of the Study Cohort
1.
Del Rio  C, Collins  LF, Malani  P.  Long-term health consequences of COVID-19.   JAMA. Published online October 5, 2020. doi:10.1001/jama.2020.19719PubMedGoogle Scholar
2.
Carfì  A, Bernabei  R, Landi  F; Gemelli Against COVID-19 Post-Acute Care Study Group.  Persistent symptoms in patients after acute COVID-19.   JAMA. 2020;324(6):603-605. doi:10.1001/jama.2020.12603PubMedGoogle ScholarCrossref
3.
Garrigues  E, Janvier  P, Kherabi  Y,  et al.  Post-discharge persistent symptoms and health-related quality of life after hospitalization for COVID-19.   J Infect. 2020;81(6):e4-e6. doi:10.1016/j.jinf.2020.08.029PubMedGoogle ScholarCrossref
4.
Tenforde  MW, Billig Rose  E, Lindsell  CJ,  et al; CDC COVID-19 Response Team.  Characteristics of adult outpatients and inpatients with COVID-19—11 academic medical centers, United States, March-May 2020.   MMWR Morb Mortal Wkly Rep. 2020;69(26):841-846. doi:10.15585/mmwr.mm6926e3PubMedGoogle ScholarCrossref
5.
van der Sar-van der Brugge  S, Talman  S, Boonman-de Winter  L,  et al.  Pulmonary function and health-related quality of life after COVID-19 pneumonia.   Respir Med. 2020;176:106272. doi:10.1016/j.rmed.2020.106272PubMedGoogle Scholar
6.
World Health Organization. Weekly epidemiological update—24 November 2020. Accessed January 20, 2021. https://www.who.int/publications/m/item/weekly-epidemiological-update---24-november-2020
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    1 Comment for this article
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    Secular trend data needed
    Glen Sumner, MD FRCP (C)/MSc(HealthEc) | Libin Cardiovascular Institute, University of Calgary, Canada
    Thank-you for your very interesting and provocative study. However, without individual participant secular trend data on their HRQoL to directly compare pre-pandemic to that post COVID-19 infection, it is very challenging to discern the effect of COVID-19 illness on the prevalence of such a non-specific symptom such as fatigue, for example. Thus, although the findings of the study are indeed plausible given our knowledge of this virus and its protean manifestations in the short and long term, I remain unconvinced about the true prevalence and especially the magnitude of the symptom burden and QoL reports of these subjects. I believe that a retrospective administration of the questionnaire,  ie. a retrospective look at symptoms or QoL even 6 months to 1 year pre-pandemic would have lent more credence to the findings. Finally, I do not see an analysis of the potentially significant effect of the lockdowns themselves on QoL in Washington which certainly are independent of the viral illness. Socioeconomic position would also have been interesting to know in relation to the subjective symptom burden. Well done, though, with the data that you had at hand.
    CONFLICT OF INTEREST: None Reported
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    Research Letter
    Infectious Diseases
    February 19, 2021

    Sequelae in Adults at 6 Months After COVID-19 Infection

    Author Affiliations
    • 1Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington, Seattle
    JAMA Netw Open. 2021;4(2):e210830. doi:10.1001/jamanetworkopen.2021.0830
    Introduction

    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.

    Methods

    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).

    Results

    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.

    Discussion

    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.

    Consistent with existing literature, fatigue was the most commonly reported symptom.2-4 This occurred in 14% of individuals in this study, lower than the 53% to 71%2-4 reported in cohorts of hospitalized patients, likely reflecting the lower acuity of illness in our cohort. Furthermore, impairment in HRQoL has previously been reported among hospitalized patients who have recovered from COVID-19; we found 29% of outpatients reported worsened HRQoL.5

    Notably, 14 participants, including 9 nonhospitalized individuals, reported negative impacts on ADLs after infection. With 57.8 million cases worldwide, even a small incidence of long-term debility could have enormous health and economic consequences.6

    Study limitations include a small sample size, single study location, potential bias from self-reported symptoms during illness episode, and loss to follow-up of 57 participants. To our knowledge, this study presents the longest follow-up symptom assessment after COVID-19 infection. Our research indicates that the health consequences of COVID-19 extend far beyond acute infection, even among those who experience mild illness. Comprehensive long-term investigation will be necessary to fully understand the impact of this evolving viral pathogen.

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    Article Information

    Accepted for Publication: January 16, 2021.

    Published: February 19, 2021. doi:10.1001/jamanetworkopen.2021.0830

    Correction: This article was corrected on March 9, 2021, to fix an error in the Table.

    Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2021 Logue JK et al. JAMA Network Open.

    Corresponding Author: Helen Y. Chu, MD, MPH, Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington, 750 Republican St, Room E691, Seattle, WA 98109 (helenchu@uw.edu).

    Author Contributions: Ms Logue and Dr Chu had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Mr Franko and Ms Logue contributed equally to this study and are joint first authors.

    Concept and design: Logue, Franko, McCulloch, Magedson, Wolf, Chu.

    Acquisition, analysis, or interpretation of data: Logue, Franko, McCulloch, McDonald, Chu.

    Drafting of the manuscript: Logue, Franko.

    Critical revision of the manuscript for important intellectual content: All authors.

    Statistical analysis: Logue, Franko.

    Obtained funding: Chu.

    Administrative, technical, or material support: All authors.

    Supervision: Logue, McCulloch, Chu.

    Conflict of Interest Disclosures: Dr Chu reported receiving personal fees from Merck, Ellume, the Bill and Melinda Gates Foundation, GlaxoSmithKline, and Pfizer; receiving grants from Sanofi-Pasteur; and receiving reagents from Cepheid Research outside the submitted work. No other disclosures were reported.

    Funding/Support: This research was funded by grants from the Bill and Melinda Gates Foundation.

    Role of the Funder/Sponsor: The Bill and Melinda Gates Foundation had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

    References
    1.
    Del Rio  C, Collins  LF, Malani  P.  Long-term health consequences of COVID-19.   JAMA. Published online October 5, 2020. doi:10.1001/jama.2020.19719PubMedGoogle Scholar
    2.
    Carfì  A, Bernabei  R, Landi  F; Gemelli Against COVID-19 Post-Acute Care Study Group.  Persistent symptoms in patients after acute COVID-19.   JAMA. 2020;324(6):603-605. doi:10.1001/jama.2020.12603PubMedGoogle ScholarCrossref
    3.
    Garrigues  E, Janvier  P, Kherabi  Y,  et al.  Post-discharge persistent symptoms and health-related quality of life after hospitalization for COVID-19.   J Infect. 2020;81(6):e4-e6. doi:10.1016/j.jinf.2020.08.029PubMedGoogle ScholarCrossref
    4.
    Tenforde  MW, Billig Rose  E, Lindsell  CJ,  et al; CDC COVID-19 Response Team.  Characteristics of adult outpatients and inpatients with COVID-19—11 academic medical centers, United States, March-May 2020.   MMWR Morb Mortal Wkly Rep. 2020;69(26):841-846. doi:10.15585/mmwr.mm6926e3PubMedGoogle ScholarCrossref
    5.
    van der Sar-van der Brugge  S, Talman  S, Boonman-de Winter  L,  et al.  Pulmonary function and health-related quality of life after COVID-19 pneumonia.   Respir Med. 2020;176:106272. doi:10.1016/j.rmed.2020.106272PubMedGoogle Scholar
    6.
    World Health Organization. Weekly epidemiological update—24 November 2020. Accessed January 20, 2021. https://www.who.int/publications/m/item/weekly-epidemiological-update---24-november-2020
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