Discussion
This study reports the psychometric properties of the SIC, a PRO measure with potential application in future vaccine and treatment trials for COVID-19. The results support the reliability and validity of the SIC items and composite scores as appropriate and useful measures of COVID-19 symptom severity. Results of the qualitative exit interviews in a diverse and potentially vulnerable population described a broad range of signs and symptoms of COVID-19 and were consistent with previous qualitative research, further supporting the content validity and format of the SIC. Exit interview participants further endorsed the SIC, noting that it was an accurate and easy method to describe COVID-19 symptom onset and changes over time. In the ENSEMBLE2 clinical trial, longitudinal psychometric data collected in a global population supported the test-retest reliability, known-groups validity, responsiveness, and meaningful change thresholds of the SIC composite scores.Effective survey instruments for health care research should be easy and quick to administer, inexpensive, accessible, and convenient [Our goal in developing the SIC was to include, as much as possible and to the best of our knowledge, all symptoms experienced by COVID-19 patients based on literature reviews, patient input, and expert opinion. Although the cross-sectional study was limited to US patients, analyses were also conducted on a subset of data from ENSEMBLE2, a multinational, phase 3, COVID-19 vaccine trial. This dataset supports the validity of the SIC to assess signs and symptoms of COVID-19 in a variety of regions and settings. Because a vaccine trial is not optimal to establish meaningful change thresholds, further studies will be needed to more definitively establish these thresholds. Furthermore, symptoms experienced by COVID-19 patients are heterogeneous, with variability among patients in both type and severity of symptoms. SARS-CoV-2 is also changing rapidly; for example, with the continuous emergence of new variants [