A Symptom-Based Rule for Diagnosis of COVID-19

Smith, David S.; Richey, Elizabeth A.; Brunetto, Wendy L.

SARS-CoV-19 PCR testing has a turn-around time that makes it impractical for real-time decision-making, and current point-of-care tests have limited sensitivity, with frequent false negatives. The study objective was to develop a clinical prediction rule to use with a point-of-care test to diagnose COVID-19 in symptomatic outpatients. A standardized clinical questionnaire was administered prior to SARS-CoV-2 PCR testing. Data was extracted by a physician blinded to the result status. Individual symptoms were combined into 326 unique clinical phenotypes. Multivariable logistic regression was used to identify independent predictors of COVID-19, from which a weighted clinical prediction rule was developed, to yield stratified likelihood ratios for varying scores. A retrospective cohort of 120 SARS-CoV-2-positive cases and 120 SARS-CoV-2-negative matched controls among symptomatic outpatients in a Connecticut HMO was used for rule development. A temporally distinct cohort of 40 cases was identified for validation of the rule. Clinical phenotypes independently associated with COVID-19 by multivariable logistic regression include loss of taste or smell (olfactory phenotype, 2 points) and fever and cough (febrile respiratory phenotype, 1 point). Wheeze or chest tightness (reactive airways phenotype, − 1 point) predicted non-COVID-19 respiratory viral infection. The AUC of the model was 0.736 (0.674–0.798). Application of a weighted C19 rule yielded likelihood ratios for COVID-19 diagnosis for varying scores ranging from LR 15.0 for 3 points to LR 0.1 for − 1 point. Using a Bayesian diagnostic approach, combining community prevalence with the evidence-based C19 rule to adjust pretest probability, clinicians can apply a point of care test with limited sensitivity across a range of clinical scenarios to differentiate COVID-19 infection from influenza and respiratory viral infection.