ABSTRACT
BackgroundThere is no valid and reliable patient self-reported measure assessing symptomology among outpatients with COVID-19. The Symptoms Evolution of COVID-19 (SE-C19) is a self-administered new instrument that includes 23 symptoms, each rated for severity at their worst moment within the last 24 hours. We studied the psychometric properties of SE-C19. MethodsReliability, validity, and sensitivity to change of the SE-C19 were assessed in 657 outpatients with confirmed COVID-19 enrolled in NCT04425629. SE-C19 and Patient Global Impression of Severity (PGIS) were administered daily from baseline (predose at Day 1) to end of study (Day 29). FindingsMost patients (70{middle dot}0%) were aged [≤]50 years and white (85{middle dot}5%). At baseline, patients reported an average (SD) of 6{middle dot}6 (3{middle dot}9) symptoms (ie, rated as at least Mild) with 3{middle dot}8 (3{middle dot}3) of these symptoms being rated as Moderate or Severe. By Day 29, most symptoms had resolved; 74{middle dot}4% of patients reported no symptoms and on average, only 0{middle dot}6 (SD 1{middle dot}5) symptoms were reported as at least Mild. Stable patients according to the PGIS showed scores with intraclass correlation values indicating moderate-to-good test-retest reliability (ie, 0{middle dot}50-0{middle dot}90). At baseline, 20 item scores (87%) varied significantly across PGIS defined groups supporting the validity of SE-C19. A symptom-resolution endpoint was defined after excluding the item "Sneezing", due to its low ability to discriminate severity levels, and "Confusion", "Rash", and "Vomiting", due to their low prevalence in this population. Symptoms resolution required complete absence of all remaining items, except "Cough", "Fatigue", and "Headache", which could be Mild or Moderate in severity. InterpretationWe identified 19 items that are valid and reliable to measure disease-related symptoms in COVID-19 outpatients and propose a definition of symptom resolution that could be used in future clinical trials and potentially, also in clinical practice. FundingThis research was funded by Regeneron Pharmaceuticals, Inc. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSThe majority of COVID-19-infected patients (>80%) have mild-to-moderate symptoms and are managed at an outpatient setting. Although clinical research has primarily focused on prevention of the disease and the treatment of hospitalised patients, close monitoring of the COVID-19 symptoms and their severity in outpatients is equally important and needed to prevent community transmission. Patient-reported outcome (PRO) instruments are a key method to assess COVID-19 related symptoms and associated burden as these symptoms are best known by the patient and are best measured from the patient perspective. However, a valid and reliable instrument to assess symptom severity and progression among outpatients with COVID-19 is not yet available. This study focuses on the psychometric properties (reliability, validity, and sensitivity to change) of a new recently developed self-administered PRO symptom measure (SE-C19) for COVID-19-positive outpatients. Added value of this studyThis is the first study to systematically examine the psychometric properties of a PRO symptom measure designed for COVID-19 outpatients and it provides a method for identifying symptom resolution among outpatients, which may be useful in clinical research and clinical practice contexts. The SE-C19 instrument is a self-administered questionnaire that assesses the severity of 23 COVID-19-related symptoms. The recall period is 24 hours and the response options include None, Mild, Moderate and Severe. The analyses reported here demonstrate that the SE-C19 is a valid and reliable measure to capture daily COVID-19 symptom severity from the outpatients perspective. These psychometric analyses also provide empirical evidence for a method to determine symptoms resolution based on the score of 19 of the SE-19 items; this may be useful not only in clinical trials but also in real-world studies and clinical practice. The 4 items not included in the symptoms resolution endpoint may be useful to clinicians to monitor severe disease. The SE-C19 instrument is relevant for the clinical management of outpatients, as it measures a large number of symptoms that are relevant in the outpatient setting and reflect the heterogeneity of symptom experience, and it is sensitive to the longitudinal changes in the severity of these symptoms. Implications of all the available evidenceThe SE-C19 can be used to monitor COVID-19-related symptoms over time in outpatients. The definition of symptoms resolution established here can be used to inform clinical trial endpoints and may also be useful in clinical practice to aid discussions between healthcare professionals and patients, and inform treatment decisions. Symptoms resolution is based on 19 of the 23 items included in the SE-C19 instrument.
