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

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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.