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

疗养院居民中 COVID-19 的流行病学、传播和免疫学

• 批准号: 10326526
• 负责人: DAVID H CANADAY
• 金额: $ 133.24万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-23 至 2023-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10326526
• 关键词: 2019-nCoV; Address; Admission activity; Adult; Affect; Age; Area; Assisted Living Facilities; Beds; Biological Markers; Blood; COVID-19; COVID-19 severity; Canada; Caring; Case Fatality Rates; Cessation of life; China; Chinese People; Cities; Clinical; Communicable Diseases; Coronavirus; Data; Disease; Disease Outbreaks; Early identification; Elderly; Epidemiology; Etiology; Evaluation; Event; Family; Frequencies; Health; Health care facility; Healthcare; Healthcare Systems; Home; Hospitalization; Hospitals; Housing; Immune; Immune response; Immunobiology; Immunology; Incidence; Individual; Infection; Infection Control; Integration Host Factors; Intensive Care; Interferons; Italy; Lead; Long COVID; Long-Term Care; Measures; Mediating; Monitor; Nursing Homes; Pathogenesis; Pathology; Patients; Persons; Pneumonia; Population; Positioning Attribute; Prevalence; Procedures; Province; Quality of life; Quarantine; Randomized; Reporting; Research; Research Personnel; Resources; SARS coronavirus; SARS-CoV-2 transmission; Sampling; Series; Severe Acute Respiratory Syndrome; Severity of illness; Symptoms; Systems Biology; Testing; Therapeutic; Time; Travel; Vaccines; Virus; Virus Diseases; adaptive immune response; aged; base; care providers; coronavirus disease; density; early detection biomarkers; effective therapy; experience; human old age (65+); infection management; mortality; multiple chronic conditions; novel; novel coronavirus; pandemic disease; patient stratification; respiratory; screening; symptomatic COVID-19; transmission process

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.

2019 年末和 2020 年头几周，出现了一大群疑似病原体 中国武汉市的肺炎病例被确定为新型冠状病毒引起。 截至 2020 年 3 月 30 日，COVID-19 已爆发为大流行病。 全球确诊病例为 729,100 例，死亡病例为 34,689 例，其中美国目前病例最多。 疫苗或行之有效的疗法已经存在，传播控制措施只能依靠严厉的措施 需要住院治疗的感染控制程序非常高。 护理和支持呼吸系统加上前所未有的人与人接触限制导致 对个人健康、死亡率、旅行、生活质量和 武汉报告72,314例病例，病死率高达14.8%。 年龄≥80岁，70-79岁占8.0%，总体占2.3%。 截至 3 月 30 日，COVID-19 已传播至西雅图地区的 30 家疗养院 (NH)，其中 150 多家疗养院 截至 3 月 23 日，西雅图第一家拥有 120 个床位的 NH 共有 81 名新冠肺炎患者，导致 35 人死亡。 重要的是，至少有 47 名员工出现了症状或呈新冠病毒阳性。 死亡率凸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、照顾高密度常住人口的护理机构中，这是最 美国有超过 15,000 个 NH 为超过 140 万人提供住房。 这些新罕布什尔州居民通常年老体弱，并且患有多种疾病。 美国有着类似的临床状况，但生活在辅助生活中或需要家人照顾。 了解新罕布什尔州 COVID-19 的脆弱性、传播情况并制定有效的治疗策略 居民绝对至关重要。 传染病爆发中最大的挑战之一是确定哪些患者患有 轻度疾病，可以就地隔离，患者已经或可能发展为重症 形式的疾病，需要在其他机构接受额外护理或住院治疗。 识别那些将发展为严重疾病、需要进一步入院治疗的患者 重症监护病房对于增加他们的生存机会至关重要。在此，我们建议进行监测和治疗。 通过传播研究，我们将获得样本，使我们能够识别新冠病毒的早期生物标志物 19 疾病严重程度或疾病严重程度的可能性，可与临床信息一起使用来协助 以预测方式做出临床决策，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、症状前和症状的发生率和患病率 长期护理居民中出现症状的 COVID-19 及其感染的纵向临床过程。 目标 2. 传播：评估事件后 SARS-CoV-2 传播的频率和动态 在长期护理机构中识别出 COVID+ 居民。 目标 3. 免疫生物学和生物标志物：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。 我们的团队在过去 5 年中进行了多项基于 NH 的研究，包括一系列大型研究 整群随机研究，每项研究针对全国 800 多个 NH 进行多中心疫苗 RCT 流行病学研究 我们对我们获得的样本和数据进行了完美的定位。 针对冠状病毒，我们添加了 Mark Cameron 博士（CWRU 的联合 PI），他之前有丰富的经验 2003 年多伦多 SARS 冠状病毒爆发期间，作为首席研究员参与了 SARS 冠状病毒爆发的研究。

项目成果

Reduced BNT162b2 Messenger RNA Vaccine Response in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)-Naive Nursing Home Residents.

• DOI: 10.1093/cid/ciab447
• 发表时间: 2021-12-06
• 期刊: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
• 作者: Canaday DH;Carias L;Oyebanji OA;Keresztesy D;Wilk D;Payne M;Aung H;St Denis K;Lam EC;Rowley CF;Berry SD;Cameron CM;Cameron MJ;Wilson B;Balazs AB;Gravenstein S;King CL
• 通讯作者: King CL

Does a lack of vaccine side effects correlate with reduced BNT162b2 mRNA vaccine response among healthcare workers and nursing home residents?

• DOI: 10.1007/s40520-021-01987-9
• 发表时间: 2021-11
• 期刊: Aging clinical and experimental research
• 影响因子: 4
• 作者: Oyebanji OA;Wilson B;Keresztesy D;Carias L;Wilk D;Payne M;Aung H;Denis KS;Lam EC;Rowley CF;Berry SD;Cameron CM;Cameron MJ;Schmader KE;Balazs AB;King CL;Canaday DH;Gravenstein S
• 通讯作者: Gravenstein S

Male sex and age biases viral burden, viral shedding, and type 1 and 2 interferon responses during SARS-CoV-2 infection in ferrets.

• DOI: 10.1101/2021.01.12.426381
• 发表时间: 2021-01-12
• 期刊: bioRxiv : the preprint server for biology
• 作者: Francis, Magen E;Richardson, Brian;Kelvin, Alyson A
• 通讯作者: Kelvin, Alyson A

Adjuvant effect of type I interferon induced by many but not all commercial influenza vaccines.

• DOI: 10.1016/j.vaccine.2020.12.051
• 发表时间: 2021-01-29
• 期刊: Vaccine
• 影响因子: 5.5
• 作者: Damjanovska S;Smith C;Sayin I;Burant CJ;Gravenstein S;Canaday DH
• 通讯作者: Canaday DH

Sex and age bias viral burden and interferon responses during SARS-CoV-2 infection in ferrets.

• DOI: 10.1038/s41598-021-93855-9
• 发表时间: 2021-07-15
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Francis ME;Richardson B;Goncin U;McNeil M;Rioux M;Foley MK;Ge A;Pechous RD;Kindrachuk J;Cameron CM;Richardson C;Lew J;Machtaler S;Cameron MJ;Gerdts V;Falzarano D;Kelvin AA
• 通讯作者: Kelvin AA