Virus-induced genetics revealed by multidimensional precision medicine transcriptional workflow applicable to COVID-19.
- 作者列表："Prokop JW","Shankar R","Gupta R","Leimanis ML","Nedveck D","Uhl K","Chen B","Hartog NL","Van Veen J","Sisco JS","Sirpilla O","Lydic T","Boville B","Hernandez A","Braunreiter C","Kuk CC","Singh V","Mills J","Wegener M","Adams M","Rhodes M","Bachmann AS","Pan W","Byrne-Steele ML","Smith DC","Depinet M","Brown BE","Eisenhower M","Han J","Haw M","Madura C","Sanfilippo DJ","Seaver LH","Bupp C","Rajasekaran S
:Precision medicine requires the translation of basic biological understanding to medical insights, mainly applied to characterization of each unique patient. In many clinical settings, this requires tools that can be broadly used to identify pathology and risks. Patients often present to the intensive care unit with broad phenotypes, including multiple organ dysfunction syndrome (MODS) resulting from infection, trauma, or other disease processes. Etiology and outcomes are unique to individuals, making it difficult to cohort patients with MODS, but presenting a prime target for testing/developing tools for precision medicine. Using multitime point whole blood (cellular/acellular) total transcriptomics in 27 patients, we highlight the promise of simultaneously mapping viral/bacterial load, cell composition, tissue damage biomarkers, balance between syndromic biology versus environmental response, and unique biological insights in each patient using a single platform measurement. Integration of a transcriptome workflow yielded unexpected insights into the complex interplay between host genetics and viral/bacterial specific mechanisms, highlighted by a unique case of virally induced genetics (VIG) within one of these 27 patients. The power of RNA-Seq to study unique patient biology while investigating environmental contributions can be a critical tool moving forward for translational sciences applied to precision medicine.
: 精准医学要求将基本的生物学理解转化为医学见解，主要应用于每个独特患者的表征。在许多临床环境中，这需要广泛用于识别病理和风险的工具。患者通常以广泛的表型出现在重症监护室，包括由感染、创伤或其他疾病过程引起的多器官功能障碍综合征 (MODS)。病因和结局是个体特有的，使得MODS患者难以队列，但为测试/开发精准医疗工具提供了首要目标。使用 27 例患者的多时间点全血 (细胞/无细胞) 总转录组学，我们强调了同时绘制病毒/细菌载量、细胞组成、组织损伤生物标志物的承诺，综合征生物学与环境反应之间的平衡，以及使用单一平台测量的每个患者的独特生物学见解。转录组工作流的整合对宿主遗传学和病毒/细菌特异性机制之间复杂的相互作用产生了意想不到的见解，通过病毒诱导遗传学 (VIG) 的独特案例突出显示这 27 名患者中的一名。RNA-Seq在研究独特的患者生物学的同时研究环境贡献的力量可以成为转化科学应用于精准医学的关键工具。
METHODS::Since mid-December of 2019, coronavirus disease 2019 (COVID-19) infection has been spreading from Wuhan, China. The confirmed COVID-19 patients in South Korea are those who came from or visited China. As secondary transmissions have occurred and the speed of transmission is accelerating, there are rising concerns about community infections. The 54-year old male is the third patient diagnosed with COVID-19 infection in Korea. He is a worker for a clothing business and had mild respiratory symptoms and intermittent fever in the beginning of hospitalization, and pneumonia symptoms on chest computerized tomography scan on day 6 of admission. This patient caused one case of secondary transmission and three cases of tertiary transmission. Hereby, we report the clinical findings of the index patient who was the first to cause tertiary transmission outside China. Interestingly, after lopinavir/ritonavir (Kaletra, AbbVie) was administered, β-coronavirus viral loads significantly decreased and no or little coronavirus titers were observed.
METHODS::In December 2019, a novel coronavirus (2019-nCoV) caused an outbreak in Wuhan, China, and soon spread to other parts of the world. It was believed that 2019-nCoV was transmitted through respiratory tract and then induced pneumonia, thus molecular diagnosis based on oral swabs was used for confirmation of this disease. Likewise, patient will be released upon two times of negative detection from oral swabs. However, many coronaviruses can also be transmitted through oral-fecal route by infecting intestines. Whether 2019-nCoV infected patients also carry virus in other organs like intestine need to be tested. We conducted investigation on patients in a local hospital who were infected with this virus. We found the presence of 2019-nCoV in anal swabs and blood as well, and more anal swab positives than oral swab positives in a later stage of infection, suggesting shedding and thereby transmitted through oral-fecal route. We also showed serology test can improve detection positive rate thus should be used in future epidemiology. Our report provides a cautionary warning that 2019-nCoV may be shed through multiple routes.
METHODS::There is a current worldwide outbreak of a new type of coronavirus (2019-nCoV), which originated from Wuhan in China and has now spread to 17 other countries. Governments are under increased pressure to stop the outbreak spiraling into a global health emergency. At this stage, preparedness, transparency, and sharing of information are crucial to risk assessments and beginning outbreak control activities. This information should include reports from outbreak sites and from laboratories supporting the investigation. This paper aggregates and consolidates the virology, epidemiology, clinical management strategies from both English and Chinese literature, official news channels, and other official government documents. In addition, by fitting the number of infections with a single-term exponential model, we report that the infection is spreading at an exponential rate, with a doubling period of 1.8 days.