Comparing variability in diagnosis of upper respiratory tract infections in patients using syndromic, next generation sequencing, and PCR-based methods.
Comparing variability in diagnosis of upper respiratory tract infections in patients using syndromic, next generation sequencing, and PCR-based methods.
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DOI：
10.1371/journal.pgph.0000811
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发表时间：
2022
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及早准确诊断呼吸道病原体和相关暴发可控制传播、流行病学建模、有针对性的治疗和决策--当前的新冠肺炎大流行就证明了这一点。许多呼吸道感染都有共同的症状，仅凭症状表现很难诊断。然而，随着获得参考实验室测试的延迟，以及护理点测试的有限可用性和较低的敏感度，综合征诊断是当今临床实践中最依赖的方法。在这里，我们通过将综合征诊断与聚合酶链式反应(PCR)和基于测序的方法进行比较，来检验新墨西哥州北部年度感染周期中呼吸道感染诊断的可变性，目的是评估我们目前识别呼吸道病原体能力的差距。在97名出现呼吸道感染症状的人中，经测序证实，只有23人对至少一种RNA病毒呈阳性。在这一感染周期中，我们还发现了冠状病毒(n=7)、呼吸道合胞病毒(n=8)、副流感病毒(n=4)和人偏肺病毒(n=1)。4名患者同时感染了两种病毒。在用聚合酶链式反应检测呈阳性的21个个体中，只有12个个体(57%)的RNA序列完全匹配。少数人(37.1%)通过症状诊断被诊断为上呼吸道感染或病毒综合征，并且只能在1例患者中区分病毒类型。因此，目前的综合症诊断方法不能准确地识别与感染有关的呼吸道病原体，不适合准确地捕捉新出现的威胁。我们得出结论，迫切需要分层不可知性诊断方法来跟踪已知和未知的病原体，以控制未来的暴发。
Early and accurate diagnosis of respiratory pathogens and associated outbreaks can allow for the control of spread, epidemiological modeling, targeted treatment, and decision making–as is evident with the current COVID-19 pandemic. Many respiratory infections share common symptoms, making them difficult to diagnose using only syndromic presentation. Yet, with delays in getting reference laboratory tests and limited availability and poor sensitivity of point-of-care tests, syndromic diagnosis is the most-relied upon method in clinical practice today. Here, we examine the variability in diagnostic identification of respiratory infections during the annual infection cycle in northern New Mexico, by comparing syndromic diagnostics with polymerase chain reaction (PCR) and sequencing-based methods, with the goal of assessing gaps in our current ability to identify respiratory pathogens. Of 97 individuals that presented with symptoms of respiratory infection, only 23 were positive for at least one RNA virus, as confirmed by sequencing. Whereas influenza virus (n = 7) was expected during this infection cycle, we also observed coronavirus (n = 7), respiratory syncytial virus (n = 8), parainfluenza virus (n = 4), and human metapneumovirus (n = 1) in individuals with respiratory infection symptoms. Four patients were coinfected with two viruses. In 21 individuals that tested positive using PCR, RNA sequencing completely matched in only 12 (57%) of these individuals. Few individuals (37.1%) were diagnosed to have an upper respiratory tract infection or viral syndrome by syndromic diagnostics, and the type of virus could only be distinguished in one patient. Thus, current syndromic diagnostic approaches fail to accurately identify respiratory pathogens associated with infection and are not suited to capture emerging threats in an accurate fashion. We conclude there is a critical and urgent need for layered agnostic diagnostics to track known and unknown pathogens at the point of care to control future outbreaks.