Section of Infectious Diseases, Hospital Universitario San Vicente Fundación, Medellín, Colombia.
GRIPE, Universidad de Antioquia, Medellín, Colombia.
PLoS One. 2021 Sep 29;16(9):e0257474. doi: 10.1371/journal.pone.0257474. eCollection 2021.
Timely and accurate diagnostics are essential to fight the COVID-19 pandemic, but no test satisfies both conditions. Dogs can scent-identify the unique odors of volatile organic compounds generated during infection by interrogating specimens or, ideally, the body of a patient. After training 6 dogs to detect SARS-CoV-2 by scent in human respiratory secretions (in vitro diagnosis), we retrained 5 of them to search and find the infection by scenting the patient directly (in vivo screening). Then, efficacy trials were designed to compare the diagnostic performance of the dogs against that of the rRT-PCR in 848 human subjects: 269 hospitalized patients (COVID-19 prevalence 30.1%), 259 hospital staff (prevalence 2.7%), and 320 government employees (prevalence 1.25%). The limit of detection in vitro was lower than 10-12 copies ssRNA/mL. During in vivo efficacy experiments, our 5 dogs detected 92 COVID-19 positive patients among the 848 study subjects. The alert (lying down) was immediate, with 95.2% accuracy and high sensitivity (95.9%; 95% C.I. 93.6-97.4), specificity (95.1%; 94.4-95.8), positive predictive value (69.7%; 65.9-73.2), and negative predictive value (99.5%; 99.2-99.7) in relation to rRT-PCR. Seventy-five days after finishing in vivo efficacy experiments, a real-life study (in vivo effectiveness) was executed among the riders of the Metro System of Medellin, deploying the human-canine teams without previous training or announcement. Three dogs were used to examine the scent of 550 volunteers who agreed to participate, both in test with canines and in rRT-PCR testing. Negative predictive value remained at 99.0% (95% C.I. 98.3-99.4), but positive predictive value dropped to 28.2% (95% C.I. 21.1-36.7). Canine scent-detection in vivo is a highly accurate screening test for COVID-19, and it detects more than 99% of infected individuals independent of key variables, such as disease prevalence, time post-exposure, or presence of symptoms. Additional training is required to teach the dogs to ignore odoriferous contamination under real-life conditions.
及时准确的诊断对于抗击 COVID-19 大流行至关重要,但没有一种检测方法能同时满足这两个条件。狗可以通过嗅探受感染患者的样本,或者通过嗅探患者的身体,来识别感染过程中产生的挥发性有机化合物的独特气味。在训练 6 只狗通过嗅探人类呼吸道分泌物来识别 SARS-CoV-2(体外诊断)后,我们又重新训练了其中 5 只狗,通过嗅探患者的身体直接寻找和发现感染(体内筛查)。然后,我们设计了疗效试验,将狗的诊断性能与 rRT-PCR 进行比较,共有 848 名受试者参与:269 名住院患者(COVID-19 患病率为 30.1%),259 名医院工作人员(患病率为 2.7%)和 320 名政府雇员(患病率为 1.25%)。体外检测的检测下限低于 10-12 拷贝 ssRNA/mL。在体内疗效实验中,我们的 5 只狗在 848 名研究对象中检测到了 92 名 COVID-19 阳性患者。狗的警报(躺下)是即时的,准确率为 95.2%,具有很高的灵敏度(95.9%,95%置信区间为 93.6-97.4%)、特异性(95.1%,94.4-95.8%)、阳性预测值(69.7%,65.9-73.2%)和阴性预测值(99.5%,99.2-99.7%),与 rRT-PCR 相比。在完成体内疗效实验 75 天后,在麦德林地铁系统的骑手中间进行了一项真实世界的研究(体内有效性),无需事先培训或宣布,就使用了人和犬的团队。三只狗被用来检查 550 名同意参加犬科测试和 rRT-PCR 测试的志愿者的气味。阴性预测值仍保持在 99.0%(95%置信区间为 98.3-99.4%),但阳性预测值下降到 28.2%(95%置信区间为 21.1-36.7%)。狗的体内气味检测是一种高度准确的 COVID-19 筛查测试,它可以检测到超过 99%的感染个体,不受疾病流行率、暴露后时间或症状出现等关键变量的影响。需要进一步的培训,以教导狗忽略真实环境下的气味污染。