ABSTRACT
ImportanceAt the onset of the COVID-19 pandemic, there was limited understanding of symptom experience and disease progression. ObjectiveWe developed and validated a fit-for-purpose, disease-specific instrument to assess symptoms in patients with COVID-19 to inform endpoints in an interventional trial for non-hospitalized patients. DesignThe initial drafting of the 23-item Symptoms Evolution of COVID-19 (SE-C19) Instrument was developed based on the Centers for Disease Control and Prevention symptom list and available published literature specific to patients with COVID-19 as of Spring 2020. The measurement principles in the Food and Drug Administration patient-reported outcomes guidance and the four methodological Patient-Focused Drug Development Guidances were also considered. SettingInterviews were conducted virtually with patients recruited through a healthcare research firm. ParticipantsSemi-structured qualitative interviews were conducted with a purposive sample of 30 non-hospitalized patients with COVID-19 InterventionInterviews involved two stages: (1) concept elicitation, to obtain information about the symptoms experienced as a result of COVID-19 in patients own words, and (2) cognitive debriefing, for patients to describe their understanding of the SE-C19 instructions, specific symptoms, response options, and recall period to ensure the content of the SE-C19 is relevant and comprehensive. Five clinicians treating COVID-19 outpatients were interviewed to obtain their insights on symptoms experienced by patients and provide input on the SE-C19. Main Outcome and MeasurePatients reported no issues regarding the relevance or appropriateness of the SE-C19 instructions, including the recall period. The comprehensiveness of the SE-C19 was confirmed against the conceptual model developed in the qualitative research. Minor conceptual gaps were revealed to capture nuances in the experience of nasal and gustatory symptoms, and systemic manifestations of sickness. Almost all items were endorsed by patients as being appropriate and well understood. The clinicians largely approved all items, response options, and recall period. Conclusions and RelevanceThe qualitative research provided supportive evidence of the content validity of the SE-C19 instrument to assess the symptoms of outpatients with COVID-19 and its use in clinical trials to evaluate the benefit of treatment. Minor changes may be considered to improve conceptual clarity and ease of responding. Trial RegistrationR10933-10987-COV-2067 (https://clinicaltrials.gov/ct2/show/NCT04425629)
ABSTRACT
BackgroundCoronavirus 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. MethodsThirty 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. FindingsPatient-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. InterpretationThe 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. FundingThis research was sponsored and paid for by Regeneron Pharmaceuticals, Inc. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSDatabases 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. Added value of this studyThis 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. Implications of all the available evidenceFindings 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.
