瑞士，星期四，2020年4月30日2:30 PM 欧洲中部时间*
作为全球首家发现COVID-191精准病因和病理的AI生物医药公司，我们致力于公益发布Demiurge的COVID-19科学发现并公开验证Demiurge的COVID-19临床预测。
出院患者中存在无症状SARS-CoV-2持续感染/携带者是我们基于精准病理模型做出的一个与大多数专家意见相反的临床预测。因为所有已知的冠状病毒类型均未表现出病毒会长期潜伏，绝大多数专家认为恢复期血浆中的中和抗体会完全消除残留的SARS-CoV-2。但是：
“SARS-CoV-2与世界上迄今已知的所有其他病毒都有根本不同。” 1
“新冠病毒采用独特的无偏向性生存策略，平衡病毒复制与病毒扩散之间的差异，这与其他通常会相互取舍的病毒形成鲜明的对比。” 1
“因此， 必须严谨合理地设计COVID-19的治疗方法，以避免诱发的适应性突变和持续性感染。针对SARS-CoV-2平衡病毒复制和病毒扩散的无偏见性生存策略，对COVID-19的特效治疗方案也也必须同时抑制病毒复制和调节免疫反应。” 1
“尽管非特效的治疗方法可能会诱导SARS-CoV-2切换为无症状感染模式，但SARS-CoV-2仍然可以通过影响多器官属主细胞中ACE2的基准表达量来长期干扰全身基因组、蛋白质组、离子、能量、以及免疫系统的稳态。当多级稳态累积的破坏足以将SARS-CoV-2切换回有症状的感染模式时， SARS-CoV-2的持续携带者将呈现病情加速发展，并引发严重的细胞因子风暴和致命的并发症。” 1
在以上预测于2020年3月7日首次公布时，尚无任何有关COVID-19已出院患者中复阳人群（核酸检测呈阳性患者，或RP复阳患者）和无复阳人群 （核酸检测呈阴性患者，或NRP无复阳患者）的临床特征数据。
数据验证
2020年3月30日，针对RP患者的第一项研究“已治愈的COVID-19患者核酸检测复阳的临床特征”3已上载至medRxiv。其关于中国262名已出院患者的数据强有力地验证了Demiurge关于出院患者中存在大量无症状SARS-CoV-2持续感染/携带者的临床预测4。但是该研究没有证据表情无症状持续感染/携带者体内的SARS-CoV-2是死的病毒碎片还是活性病毒颗粒。
2020年4月28日，在Cell Research上发表的一篇通讯文章5首次发现了在满足出院标准的COVID-19患者的体内中发现了活性病毒颗粒的直接证据。该满足出院标准的COVID-19患者在因心脏骤停意外死亡前，连续进行了3次新冠病毒的PCR核算检测，均呈阴性。但经电子显微镜观察显示，在肺组织的细支气管上皮细胞和II型肺泡上皮细胞中均存在直径为70nm-100nm的清晰的SARS-CoV-2完整病毒颗粒（参见下图1）4：
因此，Demiurge与大多数专家意见相反的临床预测得到了真实世界数据的多重验证： 治愈后出院的COVID-19患者中约20%是RP复阳患者，而且RP复阳患者体内与NRP非复阳患者体内的SARS-CoV-2抗体水平并无显著差异4。此外，RP复阳患者体内的SARS-CoV-2是活性病毒而不是病毒碎片。
现实世界的数据进一步证明，对于缺少临床数据和开发时间的新型疾病，基于AI的疾病建模和临床预测与传统方法相比，可提供更好的预测能力和解释能力。
疗法设计原则
我们进一步预测，目前在全球范围内普遍采用的有偏向性的非特效治疗方法，会增加无症状的SARS-CoV-2的持续感染/携带者的数量，从长远来看将加剧COVID-19的大流行。持续感染/携带者不仅会在不知不觉中将病毒传播给健康人群，而且会增加自身发展为重症至危重症患者的概率：
“当多级稳态累积的破坏足以将SARS-CoV-2切换回有症状的感染模式时， SARS-CoV-2的持续携带者将呈现病情加速发展，并引发严重的细胞因子风暴和致命的并发症。”1
因此，尽快发现同时抑制病毒复制和调节免疫反应的COVID-19特效治疗方案和长效疫苗可能是终结COVID-19大流行的唯一有效手段。
Demiurge是全球第一家基于精准病因和病理模型发现了COVID-19完整的预防和治疗方法的公司：
1. 伊立替康+依托泊苷作为危重症患者的特殊治疗方法（正在开展二期临床试验NCT04356690）
2. PI3K抑制剂可作为中重度患者的治疗方法（正在进行体外细胞研究）
3. 针对健康人群的广谱疫苗的非S病毒蛋白最佳靶标（正在进行前期开发）。
参考文献
1. Lovetrue, B. The AI-Discovered Aetiology of COVID-19 and Rationale of the Irinotecan+Etoposide Combination Therapy for Critically Ill COVID-19 Patients. (2020). doi:10.20944/PREPRINTS202003.0341.V1
2. Demiurge AI Discovers the Complete Aetiology of COVID-19 and the Optimal Treatment Strategy for COVID-19. Available at: http://www.prweb.com/releases/demiurge_ai_discovers_the_complete_aetiology_of_covid_19_and_the_optimal_treatment_strategy_for_covid_19/prweb16966447.htm. (Accessed: 1st April 2020)
3. An, J. et al. Clinical characteristics of the recovered COVID-19 patients with re-detectable positive RNA test. doi:10.1101/2020.03.26.20044222
4. Clinically Validated Pathology-based AI Prediction of Persistent Infection of SARS-CoV-2 - English. Available at: https://www.demiurge.technology/blog/clinically-validated-pathology-based-ai-prediction-of-persistent-infection-of. (Accessed: 30th April 2020)
5. Yao, X. et al. Pathological evidence for residual SARS-CoV-2 in pulmonary tissues of a ready-for-discharge patient. Cell Res. 2–4 (2020). doi:10.1038/s41422-020-0318-5
关于Demiurge Technologies AG
Demiurge Technologies是一家以研究为基础的AI技术与生物医药公司，致力于将公开的海量生命科学数据转换为精确疾病模型。Demiurge创新地建立了利用全球医药三期临床试验结果预测的准确性来验证并改良精准疾病模型的科学进化闭环。同时Demiurge 致力于将精准疾病模型发现的创新药物进行商业化开发。 Demiurge于2016年开始运营，总部位于瑞士。
AI已成为一种新型强大的技术方法，它可以帮助人类更深入地了解疾病和更快地发现药物。但AI必须经过严格的测试，在公众的监督下证明其价值。Demiurge已经完成了90多个三期临床试验结果的预测，实现了大于80%的准确率。同时，我们在推特（Twitter）上邀请公众参与见证我们对正在进行中的全球新药三期临床试验结果的预测（@DemiurgeTech）。
因此，我们在这里基于AI提出了COVID-19的完整致病机理和最佳治疗方案的科学假设，并公开邀请世界各地验证。Demiurge敦促大众在任何相关临床数据公布之前，不应将任何COVID-19候选治疗方案等同于COVID-19的治疗药物擅自使用。
* 本文译自于2020年4月30日发布的英文通告“Clinically Validated Pathology-based AI Prediction of Persistent Infection of Active SARS-CoV-2” 中英文通告的最终解释以英文为准。
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