Facilitating Safe Discharge Through Predicting Disease Progression in Moderate Coronavirus Disease 2019 (COVID-19): A Prospective Cohort Study to Develop and Validate a Clinical Prediction Model in Resource-Limited Settings

Background In locations where few people have received COVID-19 vaccines, health systems remain vulnerable to surges in SARS-CoV-2 infections. Tools to identify patients suitable for community-based management are urgently needed. Methods We prospectively recruited adults presenting to two hospitals in India with moderate symptoms of laboratory-confirmed COVID-19 in order to develop and validate a clinical prediction model to rule-out progression to supplemental oxygen requirement. The primary outcome was defined as any of the following: SpO2 < 94%; respiratory rate > 30 bpm; SpO2/FiO2 < 400; or death. We specified a priori that each model would contain three clinical parameters (age, sex and SpO2) and one of seven shortlisted biochemical biomarkers measurable using commercially-available rapid tests (CRP, D-dimer, IL-6, NLR, PCT, sTREM-1 or suPAR), to ensure the models would be suitable for resource-limited settings. We evaluated discrimination, calibration and clinical utility of the models in a held-out temporal external validation cohort. Results 426 participants were recruited, of whom 89 (21.0%) met the primary outcome. 257 participants comprised the development cohort and 166 comprised the validation cohort. The three models containing NLR, suPAR or IL-6 demonstrated promising discrimination (c-statistics: 0.72 to 0.74) and calibration (calibration slopes: 1.01 to 1.05) in the validation cohort, and provided greater utility than a model containing the clinical parameters alone. Conclusions We present three clinical prediction models that could help clinicians identify patients with moderate COVID-19 suitable for community-based management. The models are readily implementable and of particular relevance for locations with limited resources.