Epidemiology, transmission and immunology of COVID-19 in nursing home residents

在2019年末和2020年的头几周，疑似一大群 中国武汉市的肺炎病例被确认为一种新的冠状病毒。SARS-CoV-2致病原因 新冠肺炎，并在几个月内爆发了一场大流行。截至2010年3月30日，世卫组织表示，有 全球729,100例确诊病例和34,689例死亡，其中美国现在病例最多。目前没有 疫苗或已被证明有效的治疗方法的存在，使得传播控制措施依赖于严厉的 感染控制程序。严重感染率极高，需要住院治疗，重症监护 护理和呼吸支持加上前所未有的人与人之间接触的限制，导致了 对个人的健康、死亡率、旅行、生活质量和 经济舱。武汉市72314例高危病例报告致死率达14.8% ≥年龄80岁，8.0%的人年龄在70-79岁之间，2.3%的人总体上是这样。 截至3月30日，新冠肺炎已经扩展到西雅图地区的30家养老院(NH)和150多家NH 3月23日之前在全国范围内。西雅图第一家有120张床位的NH医院有81名COVID+居民，导致35人在 死亡率为29%。重要的是，至少有47名工作人员也出现了症状或呈COVID+。这些 死亡率突显了我们目前无法检测感染和监测传播的后果 在拥有大量工作人员的护理机构中，照顾高密度常驻人口的人数最多 易受感染的。美国有超过15,000个NH为超过140万人提供住房。 这些NH居民通常非常年老、虚弱，并患有多发性疾病。还有数百万人在 美国有着相似的临床状况，但生活在辅助生活中或在家人照顾他们的家里。有必要 了解新冠肺炎在NH中的易感性、传播并制定有效的治疗策略 居民绝对是危急关头。 传染病暴发中最大的挑战之一是确定哪些患者患有 轻微的疾病形式，可以被隔离，哪些患者已经或可能进展为严重 这些患者可能患有多种疾病，需要在另一家医疗机构接受额外护理或住院治疗。此外，早期的 将发展为严重形式的疾病需要进一步入院的患者的识别 ICU对于增加他们的生存机会至关重要。在这里，我们建议进行一项监视和 通过传播研究，我们将获得样本，使我们能够识别COVID的早期生物标志物- 19疾病严重程度或潜在的疾病严重程度，可与临床信息一起使用以帮助 以预测性的方式作出临床决策，将患者分层到适当的护理水平。 目标1.流行病学：确定无症状、症状前和 长期护理居民的症状性新冠肺炎及其纵向感染的临床病程 目标2.传播：在事件发生后评估SARS-CoV-2传播的频率和动态 COVID+居民是在长期护理环境中确定的。 目标3.免疫生物学和生物标记物：使用系统生物学方法来表征和遵循 病毒：COVID+长期护理居民的宿主界面和纵向宿主免疫反应。 我们团队在过去5年中进行了多项基于NH的研究，包括一系列大型 群组随机研究，每个超过800个NH的国家到一个多点疫苗RCT到流行病学 筛查研究。我们完全有能力获得我们提出的样本和数据。此外, 针对冠状病毒，我们增加了马克·卡梅伦博士(CWRU的合作者)，他有很大的前科 在2003年多伦多SARS-CoV疫情期间担任首席调查员的经验。

During late 2019 and the first weeks of 2020 the suspected etiological agent of a large cluster of pneumonia cases in the Chinese city of Wuhan was identified as a novel coronavirua. SARS-CoV-2 causes COVID-19, and has erupted as a pandemic in a matter of months. As of 3/30/20 WHO states that there are 729,100 confirmed cases globally and 34,689 deaths with the US now having the most cases. Currently no vaccines or proven effective therapies exist, leaving transmission control measures to rely on draconian infection control procedures. Exceptionally high rates of severe infection requiring hospitalization, intensive care and respiratory support paired with unprecedented restriction of person-to-person contact has resulted in previously unseen global consequences on individuals' health, mortality, travel, quality of life and the economy. A report of, 72,314 cases in Wuhan resulted in an enormous case-fatality rate of 14.8% in those aged ≥80 years, 8.0% age 70-79 years, and 2.3% overall. COVID-19 has spread to 30 nursing homes (NH) in the Seattle area as of March 30th and over 150 NH nationally by March 23rd. The first 120-bed NH in Seattle had 81 COVID+ residents, resulting in 35 deaths at mortality rate of 29%. Importantly, at least 47 staff also developed symptoms or were COVID+. These mortality rates highlight the consequence of our current inability to detect infection and monitor transmission in care facilities with a large number of staff that care for a high-density resident population that is the most vulnerable to infection. There are over 15,000 NH in the US providing housing to over 1.4 million individuals. These NH residents are typically very elderly, frail, and have multimorbidities. Many millions more within the US share a similar clinical status but live in assisted living or at home where family care for them. The need to understand vulnerability, transmission and develop efficacious therapeutic strategies for COVID-19 in the NH resident is absolutely critical. One of the greatest challenges in an infectious disease outbreak is in determining which patients have mild forms of illness and may be quarantined in place and which patients have or may progress to severe forms of illness and require additional care or hospitalization in another facility. Furthermore, the early identification of those patients that will progress to severe forms of the disease needing further admission to the ICU is crucial to increase their chances of survival. Here we propose to conduct a surveillance and transmission study through which we will obtain samples that allow us to identify early biomarkers of COVID- 19 disease severity or potential for disease severity, that could be used with clinical information to assist clinical decisions in a predictive fashion to stratify patients to the appropriate level of care. Aim 1. Epidemiology: Determine the incidence and prevalence of asymptomatic, presymptomatic, and symptomatic COVID-19 in long-term care residents and the clinical course of their infection longitudinally. Aim 2. Transmission: Assess frequency and dynamics of SARS-CoV-2 transmission after an incident COVID+ resident is identified in the long-term care setting. Aim 3. Immunobiology and Biomarkers: Use systems biology approaches to characterize and follow the virus:host interface and longitudinal host immune responses in COVID+ long-term care residents. Our group has performed multiple NH-based studies in the last 5 years including a series of large cluster randomized studies, each over 800 NH nationally to a multisite vaccine RCT to epidemiologic screening studies. We are perfectly positioned to obtain the samples and data we propose. In addition, specific to coronavirus we have added Dr. Mark Cameron (Co-PI at CWRU) who has substantial prior experience with the SARS-CoV outbreak as a lead investigator during that outbreak in 2003 in Toronto.