Symptoms and symptom clusters associated with SARS-CoV-2 infection in community-based populations: Results from a statewide epidemiological study

Dixon, Brian E.; Wools-Kaloustian, Kara; Fadel, William F.; Duszynski, Thomas J.; Yiannoutsos, Constantin; Halverson, Paul K.; Menachemi, Nir

BACKGROUND: Prior studies examining symptoms of COVID-19 are primarily descriptive and measured among hospitalized individuals. Understanding symptoms of SARS-CoV-2 infection in pre-clinical, community-based populations may improve clinical screening, particularly during flu season. We sought to identify key symptoms and symptom combinations in a community-based population using robust methods. METHODS: We pooled community-based cohorts of individuals aged 12 and older screened for SARS-CoV-2 infection in April and June 2020 for a statewide seroprevalence study. Main outcome was SARS-CoV-2 positivity. We calculated sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for individual symptoms as well as symptom combinations. We further employed multivariable logistic regression and exploratory factor analysis (EFA) to examine symptoms and combinations associated with SARS-CoV-2 infection. RESULTS: Among 8214 individuals screened, 368 individuals (4.5%) were RT-PCR positive for SARS-CoV-2. Although two-thirds of symptoms were highly specific (>90.0%), most symptoms individually possessed a PPV <50.0%. The individual symptoms most greatly associated with SARS-CoV-2 positivity were fever (OR=5.34, p<0.001), anosmia (OR=4.08, p<0.001), ageusia (OR=2.38, p=0.006), and cough (OR=2.86, p<0.001). Results from EFA identified two primary symptom clusters most associated with SARS-CoV-2 infection: (1) ageusia, anosmia, and fever; and (2) shortness of breath, cough, and chest pain. Moreover, being non-white (13.6% vs. 2.3%, p<0.001), Hispanic (27.9% vs. 2.5%, p<0.001), or living in an Urban area (5.4% vs. 3.8%, p<0.001) was associated with infection. CONCLUSIONS: Symptoms can help distinguish SARS-CoV-2 infection from other respiratory viruses, especially in community or urgent care settings where rapid testing may be limited. Symptoms should further be structured in clinical documentation to support identification of new cases and mitigation of disease spread by public health. These symptoms, derived from asymptomatic as well as mildly infected individuals, can also inform vaccine and therapeutic clinical trials.