Cardiovascular vulnerability predicts hospitalisation in primary care clinically suspected and confirmed COVID-19 patients: a model development and validation study

Introduction Cardiovascular disease and diabetes have shown to be predictive of clinical deterioration towards critical illness or death in the hospitalised COVID-19 patient population. The aim of this study was to determine the incremental value of cardiovascular vulnerability - defined by the number of cardiovascular diseases and/or diabetes - in predicting the risk of escalation of care towards hospital referral in primary care patients with clinically suspected or confirmed COVID-19. Methods Data were retrospectively collected from three large Dutch primary care registries with routine care data of approximately 850,000 people. A prognostic prediction model was developed in two databases to assess the incremental value of cardiovascular vulnerability. Data from the first wave of COVID-19 infections in the Netherlands (March 1, 2020 to June 1, 2020) was used for derivation. A multivariable logistic regression model was fitted to predict hospital referral within 90 days follow-up after first consultation in consecutive adult patients seen in primary care for COVID-19 symptoms. Age, sex, the interaction between age and sex, and the number of underlying cardiovascular diseases and/or diabetes (0, 1, or <1) were pre-specified as predictors prior to the analyses. The model was (i) compared to a simpler model without the predictor number of cardiovascular diseases and/or diabetes and (ii) externally validated in COVID-19 confirmed patients during the second wave (June 1, 2020 to April 15, 2021) in all three databases. Results There were 5,475 patients included for model development and 6.8% had the primary outcome hospital referral. The model with number of cardiovascular diseases included as a predictor performed better than a model without this predictor (likelihood ratio test p<0.001). Older male patients with multiple cardiovascular diseases and/or diabetes had the highest predicted risk of hospital referral, reaching risks above 15-20% in these patients. The model was externally validated in a population of 16,693 COVID-19 patients. The observed risk was lower in this temporal validation cohort (4.7% versus 6.8%). The temporally validated c-statistic was 0.747 (95%CI 0.729-0.764) and the model showed good calibration. Conclusion In this general population study, risk of clinical deterioration after suspected or confirmed COVID-19 was on average 5.1% in the development and validation cohorts combined. This risk increased with age and was higher in males compared to females. Importantly, patients with concurrent cardiovascular disease and/or diabetes had higher predicted risks. Identifying those at risk for hospital referral could have clinical implications for COVID-19 early disease management in primary care.