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.

在2019年底和2020年的前几周，可疑的一大群群 中国城市武汉的肺炎病例被确定为新颖的冠心王。 SARS-COV-2原因 COVID-19，并在几个月内爆发为大流行。截至3/30/20谁声明 729,100例确认的案件在全球范围内，与美国的34,689例死亡人数最多。目前没有 疫苗或证明存在有效的疗法，留下传输控制措施依靠严厉 感染控制程序。严重感染的率极高，需要住院，密集型 护理和呼吸支持与人与人之间的空前限制相结合，导致 以前看不见的全球影响对个人的健康，死亡率，旅行，生活质量和 经济。武汉中有72,314例病例的报告导致巨大的病例态度为14.8％ 年龄≥80岁，年龄8.0％70-79岁，总体2.3％。 截至3月30日，Covid-19已蔓延到西雅图地区的30家护士房屋（NH），超过150 NH 在3月23日之前在全国范围内。西雅图的前120张NH有81个Covid+居民，导致35例死亡 死亡率为29％。重要的是，至少有47名员工也出现了症状或共同+。这些 死亡率突出了我们目前无法检测感染和监测传播的结果 在有大量员工的护理机构中，照顾高密度的居民人口最多 容易感染。美国有超过15,000 NH为超过140万个人提供住房。 这些NH居民通常非常脆弱，并且具有多种症状。在 美国具有类似的临床状况，但生活在辅助生活中或家庭护理中的家中。需要 了解NH中的COVID-19 居民绝对至关重要。 传染病暴发中最大的挑战之一是确定哪些患者 轻度的疾病形式，可能被隔离到位，患者有或可能会陷入严重 疾病的形式，需要在其他设施中进行额外的护理或住院治疗。此外，早期 鉴定那些将发展为严重形式疾病的患者，需要进一步入院 ICU对于增加其生存机会至关重要。在这里，我们建议进行监视和 传输研究我们将获得样品，使我们能够鉴定出covid的早期生物标志物 19疾病的严重程度或疾病严重程度的潜力，可以与临床信息一起使用以帮助 以预测方式将患者分类为适当的护理水平的临床决策。 AIM 1。流行病学：确定渐近，预胞病毒和患病率 长期护理居民及其感染的临床病程中有症状的Covid-19。 AIM 2。传输：评估事件后SARS-COV-2传输的频率和动力学 在长期护理环境中确定了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：宿主界面和纵向宿主免疫反应在covid+长期护理居民中。 在过去的5年中，我们的小组已经进行了多项基于NH的研究，包括一系列大型研究 集群随机研究，每项全国800 nh至多现场疫苗RCT到流行病学 筛查研究。我们非常适合获取我们提出的样本和数据。此外， 特定于冠状病毒，我们添加了Mark Cameron博士（CWRU的Co-Pi） 在2003年在多伦多爆发期间，SARS-COV爆发的经验。

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