key: cord-0959065-uwjdlw64 authors: Rofail, D.; McGale, N.; Podolanczuk, A.; Rams, A.; Przydzial, K.; Sivapalasingam, S.; Mastey, V.; Marquis, P. title: The patient experience of COVID-19: A qualitative investigation with symptomatic outpatients date: 2021-06-04 journal: nan DOI: 10.1101/2021.06.02.21257739 sha: 077886e6393a89fa924e8cb820310c3b1e487ed7 doc_id: 959065 cord_uid: uwjdlw64 Background: Coronavirus disease 2019 (COVID-19) is an acute respiratory illness characterised by a range of symptoms. Severe cases of COVID-19 could lead to hospitalisation and intensive care unit admission. However, little is known about the symptomatic experience of outpatients with COVID-19, or its daily life impact; the objective of this qualitative research was to document this experience. Methods: Thirty US adult patients with COVID-19 were interviewed within 21 days of diagnosis. To be included, patients had to self-report one of the following: fever, cough, shortness of breath/difficulty breathing, change/loss of taste/smell, vomiting/diarrhoea or body/muscle aches. Patients were asked open-ended questions to elicit their symptoms and the impacts COVID-19 had on their daily lives. Interviews were transcribed and inductively coded to perform thematic analysis and propose a conceptual model. The adequacy of the sample size was assessed by conceptual saturation analysis. Five independent clinicians were also interviewed about their experience treating outpatients with COVID-19. Findings: Patient-reported concepts were organised into six symptom themes (upper respiratory, lower respiratory, systemic, gastrointestinal, smell and taste, and other) and seven impact themes (activities of daily living, broad daily activities, leisure/social activities, physical impacts, emotional impacts, professional impacts and quarantine-specific impacts). Symptom type, severity, duration and time of onset varied greatly by patient. Clinicians endorsed all symptoms reported by patients. Interpretation: The manifestation of symptoms in outpatient COVID-19 is heterogeneous and affects all aspects of daily life. While reported symptoms were in line with previously published reports, patients offered new detailed insights into their symptomatic experiences and the impacts that symptoms had on their daily lives. Future studies should explore the symptoms and impacts of COVID-19 longitudinally, to better understand their early onset, their progression/resolution and the possible long-term implications of COVID-19. Funding: This research was sponsored and paid for by Regeneron Pharmaceuticals, Inc. Background Coronavirus disease 2019 (COVID- 19) is an acute respiratory illness characterised by a range of symptoms. Severe cases of COVID-19 could lead to hospitalisation and intensive care unit admission. However, little is known about the symptomatic experience of outpatients with COVID-19, or its daily life impact; the objective of this qualitative research was to document this experience. Methods Thirty US adult patients with COVID-19 were interviewed within 21 days of diagnosis. To be included, patients had to self-report one of the following: fever, cough, shortness of breath/difficulty breathing, change/loss of taste/smell, vomiting/diarrhoea or body/muscle aches. Patients were asked open-ended questions to elicit their symptoms and the impacts COVID-19 had on their daily lives. Interviews were transcribed and inductively coded to perform thematic analysis and propose a conceptual model. The adequacy of the sample size was assessed by conceptual saturation analysis. Five independent clinicians were also interviewed about their experience treating outpatients with COVID-19. Findings Patient-reported concepts were organised into six symptom themes (upper respiratory, lower respiratory, systemic, gastrointestinal, smell and taste, and other) and seven impact themes (activities of daily living, broad daily activities, leisure/social activities, physical impacts, emotional impacts, professional impacts and quarantine-specific impacts). Symptom type, severity, duration and time of onset varied greatly by patient. Clinicians endorsed all symptoms reported by patients. Interpretation The manifestation of symptoms in outpatient COVID-19 is heterogeneous and affects all aspects of daily life. While reported symptoms were in line with previously published reports, patients offered new detailed insights into their . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. Funding This research was sponsored and paid for by Regeneron Pharmaceuticals, Inc. Word count: 298 (max 300 words) . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. Evidence before this study Databases used: PubMed. Criteria for inclusion: qualitative study of the outpatient experience of COVID-19 (December 2019 -March 2021). Search terms included "qualitative" OR "interviews" AND "COVID-19" or "coronavirus". The quality of the evidence was deemed not relevant to the current study, as the work was related to other contexts (eg, hospitalized patients or treatment of COVID-19), or data was collected quantitively (ie, questionnaire/survey) and did not include an in-depth perspective of the outpatient experience. This research fills important gaps in the literature, as the outpatient experience (ie, symptoms and daily life impacts) of COVID-19 has not been documented qualitatively. Findings of this research may be used to supplement existing knowledge of the outpatient experience of mild-to-moderate COVID-19, to further inform treatment guidelines. This work also provides an evidence base for identifying the symptoms and impacts important for evaluating potential treatment benefit in outpatients. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted June 4, 2021. Coronavirus disease 2019 (COVID-19) is a disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus, that the World Health Organization declared a pandemic in March 2020. 1 Since then there have been over 163 million documented cases and over 3 million confirmed deaths in 192 countries, as of May 2021. 2 Initial reports of common COVID-19 symptoms included fever, cough and shortness of breath. 3 By May 2020, the Centers for Disease Control (CDC) had updated its guidelines with additional symptoms: loss of smell/taste, chills, fatigue, sore throat, nasal congestion and gastrointestinal symptoms like vomiting and diarrhoea. Since then, our understanding has evolved regarding longevity of symptoms, incubation period, those at risk of severe illness, and reinfection. 4 Most of the data used to inform COVID-19 presentation is based on hospitalised patients, and the focus remains on cough, fever and loss of smell/taste as key symptoms. However, recent data from broader samples identified via community testing also confirm fatigue, loss of appetite and chills as predictive of a positive test for SARS-CoV-2. 5 Little is known about the experience of outpatients with COVID-19, especially how symptoms impact patients' daily lives (ie, the burden of living with/managing COVID-19, COVID-19's impact on patients' activities of daily living, physical functioning and emotional wellbeing). The patients' voice at the forefront of this research will help us to better understand and adequately address their needs, facilitate dialogue with their healthcare professionals, and support the development of patient-reported outcome instruments for clinical trials 6 and real-world observational studies. The aim of this qualitative research was to explore the . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. Patient interviews (~60 minutes) were conducted virtually by experienced qualitative researchers who received specific training for the current project. A semi-structured interview guide was used to explore the experience of COVID-19, including . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. questions; targeted probes were used when patients did not spontaneously detail how the symptom changed from day to day (ie, improved/worsened) or its duration (within-day and across day), severity and/or resolution. Interviewers also used structured prompts for all common symptoms of COVID-19 9 not spontaneously mentioned. The impacts of symptoms and diagnosis were also explored, including how patients were impacted emotionally and socially (ie, family/friends), as well as any disruption to daily activities (ie, work, hobbies, exercise and chores) due to COVID-19 symptoms. Clinicians were asked about symptoms observed in outpatients, the clinical presentations and symptomatic profiles of COVID-19, improvement/worsening in symptoms over time, onset/resolution of symptoms, and any clinical hierarchy of symptoms. Study documents, including the protocol, demographic and health information form, interview guide, screener and informed consent form, received ethical approval from the New England Independent Review Board (study number: 1291666) prior to any contact with patients. Interviews were audio-recorded, transcribed and anonymised. A data-driven approach was adopted whereby transcripts were coded in ATLAS.ti software 10 using an open, inductive, thematic coding approach. [10] [11] [12] [13] The first transcript was independently coded by three researchers; any inconsistencies in codes were discussed and reconciled. Researchers met regularly to discuss and adjust coding . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted June 4, 2021. ; https://doi.org/10.1101/2021.06.02.21257739 doi: medRxiv preprint Target Journal: The Lancet 9 guidelines when necessary. Following coding, a conceptual model was developed; this was a visual representation of patient-reported concepts (ie, aspects of their COVID-19 experience) using standard analytical techniques. 10, 12, 14 Codes and quotations were compared with the rest of the data (ie, other codes and quotations) and inductively categorised into higher-order overarching categories including themes and sub-themes, reflecting their conceptual underpinning. This involved an iterative process of cross-referencing and comparison between the different analytical categories, which was reviewed and fine-tuned by the research team. The adequacy of the sample size was assessed by saturation analysis 7,8 performed on quintiles of subsequent transcripts. This study was funded by Regeneron Pharmaceuticals, Inc. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted June 4, 2021. ; https://doi.org/10.1101/2021.06.02.21257739 doi: medRxiv preprint All recruited outpatients were interviewed and included in analysis (n=30). Patients were 45.0±19.4 years old (range 18-76), 60% female, and 87% white. The interview was conducted an average of 19 days after symptoms began, and an average of 12 days (median 9.5, range 6-21) after COVID-19 diagnosis. Most patients (83%) were still experiencing at least one symptom during the time of the interview; of those, 68% described the overall severity of their symptoms in the past 24 hours as 'mild' and 32% as 'moderate'. See Table 1 for full patient demographic and health information. The interviews yielded two overarching domains: symptoms and impacts on daily life. All symptoms reported by patients were identified in the first 25 interviews; the final five interviews yielded three additional impacts on daily life. Thus, conceptual saturation was achieved for reported symptoms. Symptoms were categorised into six major themes: upper respiratory tract, lower respiratory tract, systemic, gastrointestinal, smell and taste, and other. Each theme was further broken down into sub-themes, as outlined in Figure 1 . Categorisation was created for the purpose of summarising the data, but was not indicative of an underlying common theoretical underpinning. Upper respiratory tract symptoms included stuffy/congested nose, runny nose, post-nasal drip, phlegm, sneezing, sore throat (accompanied by lost voice), sinus pressure/pain, head congestion, swollen glands and earache. Symptoms were . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted June 4, 2021. Lower respiratory tract symptoms were cough, chest pressure/tightness, chest pain, shortness of breath and difficulty breathing (ie, symptoms related to lung functioning). Cough was commonly described as dry and non-productive. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The smell and taste theme comprised symptoms related to lost or altered sense of smell or taste. This theme was distinct from upper respiratory tract symptoms because of the pathophysiological mechanisms underlying these symptoms, which are different to that of other common upper-respiratory illnesses where senses are more directly related to other respiratory symptoms (eg, stuffy nose impairing smell). 15 The experience of changes in smell/taste also differed from other nasal symptoms (ie, stuffed or runny nose). Patients described their sense of taste/smell . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The systemic theme reflected symptoms that affect the entire body, rather than a single organ or body part. This theme comprised fever, chills, sweating, body aches, muscle aches, joint pain, headache/migraine, back pain, physical fatigue/sleepiness, mental fatigue, weakness, dizziness/lightheadedness, heart palpitations, loss of appetite and not feeling like yourself. The duration of systemic symptoms was variable; fever, body aches and headache persisted from 1 day to several weeks, which was similarly described in other themes. Fatigue also varied, but typically lasted for at least 1 week (up to 3 weeks for one patient). Varying experiences were also reported in terms of fluctuation of symptoms across all themes but particularly within systemic symptoms, with patients reporting consistency across days, variation within a day (ie, worse in the morning), and variation across days (ie, absent one day but present the next day). "It would change throughout the day. It always seemed that the fevers were worse at night." (Male, [18] [19] [20] [21] [22] [23] [24] . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted June 4, 2021. Other, less common, symptoms reported were skin rash, skin redness, red eyes, watery eyes and numb feet. Impacts on daily life referred to any COVID-19 related effects on activities of daily living (ADLs), broad daily activities (eg, day-to-day activities outside of self-care and hygiene), leisure and social life, professional impacts, psychological/emotional impacts, physical impacts and impacts specifically related to quarantine (Figure 1 ). Most impacts on daily life were not attributed to any singular symptom, but rather to the experience of COVID-19 infection as a whole; though the duration of symptoms was relatively short, patients reported a significant daily life impact. The ADL theme referred to changes in patients' performance of self-care tasks (ie, hygiene and dressing), eating habits, mobility or daily routine. Broad daily activities encompassed changes in activities not necessary for fundamental functioning, but which allow patients to live independently, including shopping, meal preparation, home maintenance, yard work and care of children/pets. Each of these activities was reported as central to patients' lives pre-COVID-19, and patients emphasised the disruption caused by their illness. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted June 4, 2021. [18] [19] [20] [21] [22] [23] [24] Professional impacts referred to any effects on the patient's work or schooling. Similarly, this theme comprised only changes due to COVID-19 and its symptoms, not due to quarantine (eg, transition to working from home or virtual class). anything else other than watch movies and lay in bed." (Male, [18] [19] [20] [21] [22] [23] [24] . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted June 4, 2021. [18] [19] [20] [21] [22] [23] [24] "I couldn't get comfortable, and I think that the sleep was disrupted." (Female, (25) (26) (27) (28) (29) (30) The emotional/psychological theme encompassed changes in the patients' psyche or mood, including depression, anxiety, irritability, frustration, feelings of isolation and worries about the symptoms and meaning of a COVID-19 diagnosis. Patients used a breadth of language to describe their emotional response to COVID-19 and its symptoms; sub-themes reflect patients' words with as much granularity as possible without over-emphasising the emotional impact. "I was a little bit worried because you hear stories on the news and whatnot that some people took a turn for the worse after a week." (Male, (60) (61) (62) (63) (64) (65) (66) (67) (68) (69) Patient experiences due to a mandatory quarantine period (typically 2 weeks), were classified within their own theme. These impacts included being housebound, having to stay away from others, and boredom. Five clinicians were interviewed (n=4 in the US; n=1 in South Korea, where all COVID-19 patients are hospitalised regardless of symptom severity). The Korean clinician was informed of the focus of this study and asked to comment specifically . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted June 4, 2021. ; https://doi.org/10.1101/2021.06.02.21257739 doi: medRxiv preprint on their experience treating mild-to-moderate cases. See Table 2 According to clinicians, patients often sought medical attention due to changes in taste/smell, fever, aches, weakness, cough, sore throat, joint problems, nausea, vomiting and diarrhoea. Clinicians confirmed patient reports regarding the varied nature of symptom severity and duration. Lingering symptoms were fatigue, weakness, shortness of breath, fever, joint pain, cough, loss of taste/smell and mental fatigue. Clinicians indicated that most of their patients returned to baseline health once symptom-free, but a minority took longer to return to pre-COVID-19 health due to changes in mental clarity (eg, slowed thinking, mental fatigue) or energy levels. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. One key finding not described by clinicians was the heterogeneity of altered senses of smell and taste. Clinicians commonly reported that both senses would be lost completely, most often in conjunction with one another. Patients described experiencing changes in only one of these senses, or in both senses nonconcurrently; patients also described alterations in these senses, rather than loss (ie, . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. information on the experience. Second, the participants were not of a representative racial/ethnic background and therefore further research in a more diverse population is required. A final limitation was young average age; age is a documented risk factor for COVID-19 infection, and older patients have been disproportionately affected by COVID-19 symptoms. 18 However, younger patients did report a range of symptoms and daily life impacts, emphasising the importance of infection prevention measures in younger adults. 19 Further, the types of symptoms experienced by patients did not differ by participant age; further research should be conducted to confirm differentiation of symptoms by age groups. Additional research should also be conducted to explore the symptom experience quantitatively, including the long-term effects of COVID-19, through non-interventional observational studies and clinical trials. This study provides unique and valuable insights from the patient perspective into the symptom experience in outpatients with COVID-19 and how these in turn could impact their lives more broadly, including physical, emotional and psychological functioning. Existing clinical guidelines for treating outpatients with mild-to-moderate COVID-19 are limited; as of 8 April 2021, the National Institute of Health provides guidelines for those at high risk of clinical progression but does not suggest treatment methods for the remainder of the outpatient population. 20 The current study could supplement existing knowledge in informing treatment guidelines. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted June 4, 2021. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted June 4, 2021. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted June 4, 2021. ; https://doi.org/10.1101/2021.06.02.21257739 doi: medRxiv preprint . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. 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The copyright holder for this preprint this version posted June 4, 2021. ; https://doi.org/10.1101/2021.06.02.21257739 doi: medRxiv preprint