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Objective: To assess the ability of 2 commercially available smartwatches to accurately detect clinically significant hypoxia in patients hospitalized with coronavirus-19 (COVID-19). Patients and Methods: A prospective multicenter validation study was performed from November 1, 2021, to August 31, 2022, assessing the Apple Watch Series 7 and Withings ScanWatch inbuilt pulse oximetry, against simultaneous ward-based oximetry as the reference standard. Patients hospitalized with active COVID-19 infection not requiring intensive care admission were recruited. Results: A total of 750 smartwatch pulse oximetry measurements and 400 ward oximetry readings were successfully obtained from 200 patients (male 54%, age 66±18 years). For the detection of clinically significant hypoxia, the Apple Watch had a sensitivity and specificity of 34.8% and 97.5%, respectively with a positive predictive value of 78.1% and negative predictive value of 85.6%. The Withings ScanWatch had a sensitivity and specificity of 68.5% and 80.8%, respectively with a positive predictive value of 44.7% and negative predictive value of 91.9%. The overall accuracy was 84.9% for the Apple Watch and 78.5% for the Withings ScanWatch. The Spearman rank correlation coefficients reported a moderate correlation to ward-based photoplethysmography (Apple: rs=0.61; Withings: rs=0.51, both P<.01). Conclusion: Although smartwatches are able to provide SpO2 readings, their overall accuracy may not be sufficient to replace the standard photoplethysmography technology in detecting hypoxia in patients with COVID-19.