Differential diagnosis of COVID-19 and influenza

Abstract

This study uses two existing data sources to examine how patients' symptoms can be used to differentiate COVID-19 from other respiratory diseases. One dataset consisted of 839,288 laboratory-confirmed, symptomatic, COVID-19 positive cases reported to the Centers for Disease Control and Prevention (CDC) from March 1, 2019, to September 30, 2020. The second dataset provided the controls and included 1,814 laboratory-confirmed influenza positive, symptomatic cases, and 812 cases with symptomatic influenza-like-illnesses. The controls were reported to the Influenza Research Database of the National Institute of Allergy and Infectious Diseases (NIAID) between January 1, 2000, and December 30, 2018. Data were analyzed using case-control study design. The comparisons were done using 45 scenarios, with each scenario making different assumptions regarding prevalence of COVID-19 (2%, 4%, and 6%), influenza (0.01%, 3%, 6%, 9%, 12%) and influenza-like-illnesses (1%, 3.5% and 7%). For each scenario, a logistic regression model was used to predict COVID-19 from 2 demographic variables (age, gender) and 10 symptoms (cough, fever, chills, diarrhea, nausea and vomiting, shortness of breath, runny nose, sore throat, myalgia, and headache). The 5-fold cross-validated Area under the Receiver Operating Curves (AROC) was used to report the accuracy of these regression models. The value of various symptoms in differentiating COVID-19 from influenza depended on a variety of factors, including (1) prevalence of pathogens that cause COVID-19, influenza, and influenza-like-illness; (2) age of the patient, and (3) presence of other symptoms. The model that relied on 5-way combination of symptoms and demographic variables, age and gender, had a cross-validated AROC of 90%, suggesting that it could accurately differentiate influenza from COVID-19. This model, however, is too complex to be used in clinical practice without relying on computer-based decision aid. Study results encourage development of web-based, stand-alone, artificial Intelligence model that can interview patients and help clinicians make quarantine and triage decisions.

Fig 1. Impact of symptoms on diagnosis of COVID-19 in different scenarios.

The red dotted line indicates the point which the symptom switches from predictive of to ruling out COVID-19. The solid blue line indicates the average across scenarios. Square grey markers show impact of symptom in different scenarios.