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1.
Cell ; 184(11): 2927-2938.e11, 2021 05 27.
Article in English | MEDLINE | ID: mdl-34010620

ABSTRACT

Defining long-term protective immunity to SARS-CoV-2 is one of the most pressing questions of our time and will require a detailed understanding of potential ways this virus can evolve to escape immune protection. Immune protection will most likely be mediated by antibodies that bind to the viral entry protein, spike (S). Here, we used Phage-DMS, an approach that comprehensively interrogates the effect of all possible mutations on binding to a protein of interest, to define the profile of antibody escape to the SARS-CoV-2 S protein using coronavirus disease 2019 (COVID-19) convalescent plasma. Antibody binding was common in two regions, the fusion peptide and the linker region upstream of the heptad repeat region 2. However, escape mutations were variable within these immunodominant regions. There was also individual variation in less commonly targeted epitopes. This study provides a granular view of potential antibody escape pathways and suggests there will be individual variation in antibody-mediated virus evolution.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/immunology , Epitopes/immunology , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Algorithms , COVID-19/therapy , COVID-19/virology , Cell Line , Gene Library , Humans , Immunization, Passive , Mutation , Protein Domains , SARS-CoV-2/genetics , Software , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/genetics , COVID-19 Serotherapy
3.
bioRxiv ; 2020 Nov 16.
Article in English | MEDLINE | ID: mdl-33236010

ABSTRACT

Defining long-term protective immunity to SARS-CoV-2 is one of the most pressing questions of our time and will require a detailed understanding of potential ways this virus can evolve to escape immune protection. Immune protection will most likely be mediated by antibodies that bind to the viral entry protein, Spike (S). Here we used Phage-DMS, an approach that comprehensively interrogates the effect of all possible mutations on binding to a protein of interest, to define the profile of antibody escape to the SARS-CoV-2 S protein using COVID-19 convalescent plasma. Antibody binding was common in two regions: the fusion peptide and linker region upstream of the heptad repeat region 2. However, escape mutations were variable within these immunodominant regions. There was also individual variation in less commonly targeted epitopes. This study provides a granular view of potential antibody escape pathways and suggests there will be individual variation in antibody-mediated virus evolution.

4.
J Gen Intern Med ; 35(11): 3302-3307, 2020 11.
Article in English | MEDLINE | ID: mdl-32875494

ABSTRACT

BACKGROUND: Skilled nursing facilities (SNFs) are high-risk settings for SARS-CoV-2 transmission. Infection rates among employees are infrequently described. OBJECTIVE: To describe SARS-CoV-2 rates among SNF employees and residents during a non-outbreak time period, we measured cross-sectional SARS-CoV-2 prevalence across multiple sites in the Seattle area. DESIGN: SARS-CoV-2 testing was performed for SNF employees and residents using quantitative real-time reverse transcription polymerase chain reaction. A subset of employees completed a sociodemographic and symptom questionnaire. PARTICIPANTS: Between March 29 and May 13, 2020, we tested 1583 employees and 1208 residents at 16 SNFs for SARS-CoV-2. MAIN MEASURE: SARS-CoV-2 testing results and symptom report among employees and residents. KEY RESULTS: Eleven of the 16 SNFs had one or more resident or employee test positive. Overall, 46 (2.9%) employees had positive or inconclusive testing for SARS-CoV-2, and among those who completed surveys, most were asymptomatic and involved in direct patient care. The majority of employees tested were female (934, 73%), and most employees were Asian (392, 30%), Black (360, 28%), or white (360, 28%). Among the 1208 residents tested, 110 (9.1%) had positive or inconclusive results. There was no association between the presence of positive residents and positive employees within a SNF (p = 0.62, McNemar's test). CONCLUSIONS: In the largest study of SNFs to date, SARS-CoV-2 infections were detected among both employees and residents. Employees testing positive were often asymptomatic and involved in direct patient care. Surveillance testing is needed for SNF employees and residents during the pandemic response.


Subject(s)
COVID-19 Testing/methods , COVID-19/epidemiology , Health Personnel/statistics & numerical data , Skilled Nursing Facilities/statistics & numerical data , Adolescent , Adult , Aged , Aged, 80 and over , COVID-19/diagnosis , COVID-19 Testing/statistics & numerical data , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Occupational Diseases/epidemiology , Prevalence , SARS-CoV-2 , Skilled Nursing Facilities/organization & administration , Surveys and Questionnaires , Washington/epidemiology , Young Adult
5.
J Athl Train ; 51(11): 880-886, 2016 Nov.
Article in English | MEDLINE | ID: mdl-27710093

ABSTRACT

CONTEXT: Part-time personnel are an integral part of the Australian Army. With operational deployments increasing, it is essential that medical teams identify the patterns of injuries sustained by part-time personnel in order to mitigate the risks of injury and optimize deployability. OBJECTIVE: To compare the patterns of reported work health and safety incidents and injuries in part-time and full-time Australian Army personnel. DESIGN: Retrospective cohort study. SETTING: The Australian Army. PATIENTS OR OTHER PARTICIPANTS: Australian Army Reserve and Australian regular Army populations, July 1, 2012, through June 30, 2014. MAIN OUTCOME MEASURE(S): Proportions of reported work health and safety incidents that resulted in injuries among Army Reserve and regular Army personnel and specifically the (a) body locations affected by incidents, (b) nature of resulting injuries, (c) injury mechanisms, and (d) activities being performed when the incidents occurred. RESULTS: Over 2 years, 15 065 work health and safety incidents and 11 263 injuries were reported in Army Reserve and regular Army populations combined. In the Army Reserve population, 85% of reported incidents were classified as involving minor personal injuries; 4% involved a serious personal injury. In the regular Army population, 68% of reported incidents involved a minor personal injury; 5% involved a serious personal injury. Substantially lower proportions of Army reservist incidents involved sports, whereas substantially higher proportions were associated with combat training, manual handling, and patrolling when compared with regular Army incidents. CONCLUSIONS: Army reservists had a higher proportion of injuries from Army work-related activities than did regular Army soldiers. Proportions of incidents arising from combat tasks and manual handling were higher in the Army Reserve. Understanding the sources of injuries will allow the medical teams to implement injury-mitigation strategies.


Subject(s)
Health Status , Military Personnel , Sports , Wounds and Injuries/epidemiology , Adult , Australia/epidemiology , Female , Humans , Male , Retrospective Studies , Safety
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