RESUMO
Significant barriers to the diagnosis of latent and acute SARS-CoV-2 infection continue to hamper population-based screening efforts required to contain the COVID-19 pandemic in the absence of effective antiviral therapeutics or vaccines. We report an aptamer-based SARS-CoV-2 salivary antigen assay employing only low-cost reagents ($3.20/test) and an off-the-shelf glucometer. The test was engineered around a glucometer as it is quantitative, easy to use, and the most prevalent piece of diagnostic equipment globally making the test highly scalable with an infrastructure that is already in place. Furthermore, many glucometers connect to smartphones providing an opportunity to integrate with contract tracing apps, medical providers, and electronic medical records. In clinical testing, the developed assay detected SARS-CoV-2 infection in patient saliva across a range of viral loads - as benchmarked by RT-qPCR - within one hour, with 100% sensitivity (positive percent agreement) and distinguished infected specimens from off-target antigens in uninfected controls with 100% specificity (negative percent agreement). We propose that this approach can provide an inexpensive, rapid, and accurate diagnostic for distributed screening of SARS-CoV-2 infection at scale.
RESUMO
BackgroundAssigning meaningful probabilities of SARS-CoV-2 infection risk presents a diagnostic challenge across the continuum of care. MethodsWe integrated patient symptom and test data using machine learning and Bayesian inference to quantify individual patient risk of SARS-CoV-2 infection. We trained models with 100,000 simulated patient profiles based on thirteen symptoms, estimated local prevalence, imaging, and molecular diagnostic performance from published reports. We tested these models with consecutive patients who presented with a COVID-19 compatible illness at the University of California San Diego Medical Center over 14 days starting in March 2020. ResultsWe included 55 consecutive patients with fever (78%) or cough (77%) presenting for ambulatory (n=11) or hospital care (n=44). 51% (n=28) were female, 49% were age <60. Common comorbidities included diabetes (22%), hypertension (27%), cancer (16%) and cardiovascular disease (13%). 69% of these (n=38) were RT-PCR confirmed positive for SARS-CoV-2 infection, 11 had repeated negative nucleic acid testing and an alternate diagnosis. Bayesian inference network, distance metric-learning, and ensemble models discriminated between patients with SARS-CoV-2 infection and alternate diagnoses with sensitivities of 81.6 - 84.2%, specificities of 58.8 - 70.6%, and accuracies of 61.4 - 71.8%. After integrating imaging and laboratory test statistics with the predictions of the Bayesian inference network, changes in diagnostic uncertainty at each step in the simulated clinical evaluation process were highly sensitive to location, symptom, and diagnostic test choices. ConclusionsDecision support models that incorporate symptoms and available test results can help providers diagnose SARS-CoV-2 infection in real world settings.
