Rapid Differential Diagnosis of COVID-19 and Common Respiratory Infections

摘要新型冠状病毒病（COVID-19）和常见呼吸道感染的快速鉴别诊断快速通道SBIR NOT-AI-20-031持续的新型冠状病毒病（COVID-19）大流行正在地球仪迅速蔓延，截至2020年4月29日，确诊病例超过320万例。大多数COVID-19病例症状轻微（发热、咳嗽）或无症状，但严重并发症（包括呼吸急促和双侧肺炎）在估计3-5%的确诊病例中是致命的。流感和呼吸道合胞病毒（RSV）是最常见的病毒性呼吸道疾病，通常表现出与COVID-19报告的症状相似的症状。没有可预见的COVID-19的根除，随着“流感季节”在秋季和冬季的到来，将迫切需要对分布式位置的患者进行鉴别诊断（例如，紧急护理、初级护理、儿科医生办公室、零售免预约诊所、驾车通过测试站点等）。非医院环境中的鉴别诊断将允许对住院的急性病例进行分类，提供适当的靶向治疗，并减少社区传播。我们概述了一种创新的、简单易用的鉴别诊断面板，该面板将使用基于核酸的检测同时检测COVID-19、两种甲型流感亚型（H1N1和H3 N2）、流感B和RSV。该平台将被CLIA豁免用于分布式护理环境，并将在样本采集后10分钟内提供诊断结果。这些测试将在我们的小型数字微流体测试平台上自动进行，该平台目前已获得CE认证，并正在等待FDA的510（k）许可。我们的系统将提供集成样本处理的独特优势，并将提供快速的结果，很容易适合典型的紧急护理，初级或儿科医生护理，或零售预约诊所。我们正在与杜克人类疫苗研究所合作，该研究所目前正在进行COVID-19测试，以实现这个快速通道项目的临床前目标。迫切需要改进的COVID-19诊断检测方法来监测疾病的传播，识别轻度受影响的个体和无症状携带者，以通过适当的隔离减少社区传播，并确保对需要住院的危重患者采取适当的保护措施。由于我们公司的使命专注于儿科护理，我们特别感兴趣的是识别可能在儿科初级保健诊所出现COVID-19、流感或RSV症状的新生儿、婴儿和年龄较大的儿童。我们创新的数字微流体平台将消除繁琐的手动样品处理方案的要求，并在患者等待的同时提供结果。该技术的未来迭代将扩展呼吸道病毒检测组，以包括十几种病原体（即副流感病毒），并在同一检测盒中添加血清学检测，以提供过去病毒暴露的数据。

ABSTRACT Rapid Differential Diagnosis of COVID-19 and Common Respiratory Infections Fast Track SBIR NOT-AI-20-031 The ongoing novel coronavirus disease (COVID-19) pandemic is spreading rapidly across the globe with over 3.2 million confirmed cases as of April 29, 2020. Most cases of COVID-19 have mild symptoms (fever, cough) or are asymptomatic, however severe complications including shortness of breath and bilateral pneumonia are lethal in an estimated 3-5% of confirmed cases. Influenza and respiratory syncytial virus (RSV) are the most common viral respiratory diseases and typically present with symptoms similar to those reported for COVID-19. There is no foreseeable eradication of COVID-19, and as the “flu season” arrives in the fall and winter, there will be an acute need to perform differential diagnosis of patients in distributed locations (e.g., urgent care, primary care, pediatric physician offices, retail walk-in clinics, drive through testing sites, etc.). A differential diagnosis in non-hospital settings will allow triaging of acute cases for hospitalization, provide appropriate targeted therapies, and decrease community spread. We outline an innovative, simple-to-use differential diagnostics panel that will simultaneously test for COVID-19, two influenza A subtypes (H1N1 and H3N2), influenza B, and RSV using nucleic acid based tests. The platform will be CLIA-waived for use in a distributed care setting and will provide diagnostic results within 10 minutes of sample collection. The tests will be automated on our small footprint digital microfluidics testing platform, which is currently CE marked and pending 510(k) clearance from the FDA. Our system will provide unique advantages of integrated sample processing and will provide rapid results that easily fit within a typical urgent care, primary or pediatric physician care, or retail walk-in clinic appointment. We are collaborating with the Duke Human Vaccine Institute, who are currently running COVID-19 tests, on the preclinical aims of this Fast Track project. Improved COVID-19 diagnostic assays are desperately needed to monitor the spread of the disease, identify mildly affected individuals and asymptomatic carriers to reduce community spread through appropriate quarantine, and ensure proper protective measures for critical patients requiring hospitalization. As our company mission is focused on pediatric care, we are especially interested in identifying newborns, infants, and older children who may present at pediatric primary care clinics with symptoms indicative of COVID-19, influenza, or RSV. Our innovative digital microfluidics platform will remove the requirements for tedious manual sample processing protocols and deliver the results while the patient is waiting. Future iterations of this technology will expand the respiratory virus test panel to include over a dozen pathogens (i.e. parainfluenza viruses) and add serology testing to the same test cartridge to provide data on past viral exposure.