Background and Objective: At-home rapid antigen tests provide a convenient and expedited resource to learn about severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection status. However, low sensitivity of at-home antigen tests presents a challenge. This study examines the accuracy of at-home tests, when combined with computer-facilitated symptom screening. Methods: The study used primary data sources with data collected during 2 phases at different periods (phase 1 and phase 2): one during the period in which the alpha variant of SARS-CoV-2 was predominant in the United States and another during the surge of the delta variant. Four hundred sixty-one study participants were included in the analyses from phase 1 and 374 subjects from phase 2. Phase 1 data were used to develop a computerized symptom screening tool, using ordinary logistic regression with interaction terms, which predicted coronavirus disease-2019 (COVID-19) reverse transcription polymerase chain reaction (RT-PCR) test results. Phase 2 data were used to validate the accuracy of predicting COVID-19 diagnosis with (1) computerized symptom screening; (2) at-home rapid antigen testing; (3) the combination of both screening methods; and (4) the combination of symptom screening and vaccination status. The McFadden pseudo-R 2 was used as a measure of percentage of variation in RT-PCR test results explained by the various screening methods. Results: The McFadden pseudo-R 2 for the first at-home test, the second at-home test, and computerized symptom screening was 0.274, 0.140, and 0.158, respectively. Scores between 0.2 and 0.4 indicated moderate levels of accuracy. The first athome test had low sensitivity (0.587) and high specificity (0.989). Adding a second at-home test did not improve the sensitivity of the first test. Computerized symptom screening improved the accuracy of the first at-home test (added 0.131 points to sensitivity and 6.9% to pseudo-R 2 of the first at-home test). Computerized symptom screening and vaccination status was the most accurate method to screen patients for COVID-19 or an active infection with SARS-CoV-2 in the community (pseudo-R 2 = 0.476). Conclusion: Computerized symptom screening could either improve, or in some situations, replace at-home antigen tests for those individuals experiencing COVID-19 symptoms.

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.

Background: The importance of various patient-reported signs and symptoms to the diagnosis of coronavirus disease 2019 (COVID-19) changes during, and outside, of the flu season. None of the current published studies, which focus on diagnosis of COVID-19, have taken this seasonality into account. Objective: To develop predictive algorithm, which estimates the probability of having COVID-19 based on symptoms, and which incorporates the seasonality and prevalence of influenza and influenza-like illness data. Methods: Differential diagnosis of COVID-19 and influenza relies on demographic characteristics (age, race, and gender), and respiratory (eg, fever, cough, and runny nose), gastrointestinal (eg, diarrhea, nausea, and loss of appetite), and neurological (eg, anosmia and headache) signs and symptoms. The analysis was based on the symptoms reported by COVID-19 patients, 774 patients in China and 273 patients in the United States. The analysis also included 2885 influenza and 884 influenza-like illnesses in US patients. Accuracy of the predictions was calculated using the average area under the receiver operating characteristic (AROC) curves. Results: The likelihood ratio for symptoms, such as cough, depended on the flu season—sometimes indicating COVID-19 and other times indicating the reverse. In 30-fold cross-validated data, the symptoms accurately predicted COVID-19 (AROC of 0.79), showing that symptoms can be used to screen patients in the community and prior to testing. Conclusion: Community-based health care providers should follow different signs and symptoms for diagnosing COVID-19 during, and outside of, influenza season.