Impact of prior infection on SARS-CoV-2 antibody responses in vaccinated long-term care facility staff

SARS-CoV-2 emerged in 2019 and has resulted in millions of deaths worldwide. Certain populations are at higher risk for infection, especially staff and residents at long term care facilities (LTCF), due to the congregant living setting, and residents with many comorbidities. Prior to vaccine availability, these populations represented a large fraction of total COVID-19 cases and deaths in the U.S. Due to the high-risk setting and outbreak potential, staff and residents were among the first groups to be vaccinated. To define the impact of prior infection on response to vaccination, we measured antibody responses in a cohort of staff members at a LTCF, many of whom were previously infected by SARS-CoV-2. We found that neutralizing, receptor-binding-domain (RBD) and nucleoprotein (NP) binding antibody levels were significantly higher post-full vaccination course in individuals that were previously infected, and NP antibody levels could discriminate individuals with prior infection from vaccinated individuals. While an anticipated antibody titer increase was observed after vaccine booster dose in naive individuals, boost response was not observed in individuals with previous COVID-19 infection. We observed a strong relationship between neutralizing antibodies and RBD-binding antibodies post-vaccination across all groups, suggesting RBD-binding antibodies may be used as a correlate of neutralization. One individual with high levels of neutralizing and binding antibodies experienced a breakthrough infection (prior to the introduction of Omicron), demonstrating that the presence of antibodies is not always sufficient for complete protection against infection. These results highlight that history of COVID-19 exposure significantly increases SARS-CoV-2 antibody responses following vaccination. ImportanceLong-term care facilities (LTCFs) have been disproportionately impacted by COVID-19, due to their communal nature, high-risk profile of residents and vulnerability to respiratory pathogens. In this study, we analyzed the role of prior natural immunity to SARS-CoV-2 on post-vaccination antibody responses. The LTCF in our cohort experienced a large outbreak with almost 40% of staff becoming infected. We found that individuals that were infected prior to vaccination, had higher levels of neutralizing and binding antibodies post-vaccination. Importantly, the second vaccine dose significantly boosted antibody levels in those that were immunologically naive prior to vaccination, but not those that had prior immunity. Regardless of pre-vaccination immune status, levels of binding and neutralizing antibodies were highly correlated. The presence of NP-binding antibodies can be used to identify individuals that were previously infected when pre-vaccination immune status is not known. Our results reveal that vaccination antibody responses differ depending on prior natural immunity.

Model-based Evaluation of Continued COVID-19 Risk at Long Term Care Facilities

The COVID-19 pandemic severely impacted long-term care facilities resulting in the death of approximately 8% of residents nationwide. As COVID-19 case rates decline and state and county restrictions are lifted, facility managers, local and state health agencies are challenged with defining their own policies moving forward to appropriately mitigate disease transmission. The continued emergence of variants of concern has highlighted the need for a readily available tool that can be employed at the facility-level to determine best practices for mitigation and ensure resident and staff safety. To assist leadership in determining the impact of various infection surveillance and response strategies, we developed an agent-based model and an online dashboard interface that simulates COVID-19 infection within congregate care settings under various mitigation measures. In this paper, we demonstrate how this dashboard can be used to quantify the continued risk for COVID-19 infections within a facility given a designated testing schedule and vaccine requirements. Our results highlight the critical nature of testing cadence, test sensitivity and specificity, and the impact of removing asymptomatic infected individuals from the workplace. We also show that monthly surveillance testing at long-term care facilities is unlikely to successfully mitigate SARS-CoV-2 outbreaks in congregate care settings. DisclosuresThis work was supported by Colorado State Universitys Center for Healthy Aging, the Center for Vector-Bourne Infectious Disease, the Office of the Vice President for Research, the College of Health and Human Sciences, the Collage of Natural Sciences, the College of Veterinary Medicine and Biomedical Sciences, and the Walter Scott Jr College of Engineering.

Durable antibody responses in staff at two long-term care facilities, during and post SARS-CoV-2 outbreaks

SARS-CoV-2 has had a disproportionate impact on non-hospital healthcare settings such as long-term care facilities (LTCFs). The communal nature of these facilities, paired with the high-risk profile of residents, has resulted in thousands of infections and deaths and a high case fatality rate. To detect pre-symptomatic infections and identify infected workers, we performed weekly surveillance testing of staff at two LTCFs which revealed a large outbreak at one of the sites. We collected serum from staff members throughout the study and evaluated it for binding and neutralization to measure seroprevalence, seroconversion, and type and functionality of antibodies. At the site with very few incident infections, we detected that over 40% of the staff had preexisting SARS-CoV-2 neutralizing antibodies, suggesting prior exposure. At the outbreak site, we saw rapid seroconversion following infection. Neutralizing antibody levels were stable for many weeks following infection, suggesting a durable, long-lived response. Receptor-binding domain antibodies and neutralizing antibodies were strongly correlated. The site with high seroprevalence among staff had two unique introductions of SARS-CoV-2 into the facility through seronegative infected staff during the period of study but these did not result in workplace spread or outbreaks. Together our results reveal that high seroprevalence rate among staff can contribute to herd immunity within a workplace and protect against subsequent infection and spread within a facility.

Low prevalence of COVID-19 Exposure is Coincident with Self-reported Compliance with Public Health Guidelines among Essential Employees at an Institute of Higher Education

ImportanceDetailed analysis of infection rates paired with behavioral and employee reported risk factors are vital to understanding how COVID-19 transmission may be inflamed or mitigated in the workplace. Institutes of Higher Education are heterogeneous work units that supported continued in person employment during COVID-19, providing an excellent test site for occupational health evaluation. ObjectiveTo evaluate self-reported behaviors and SARS-CoV-2 among essential in-person employees during the first six months of the COVID-19 pandemic. DesignCross-sectional, conducted from July 13-September 2, 2020. SettingInstitute of Higher Education in Fort Collins, Colorado. ParticipantsEmployees identified to be an essential in-person employee during the first six months of the pandemic (1,522 invited, 1,507 qualified, 603 (40%) completed the survey). Of those completing the survey, 84.2% (508) elected to participate in blood and nasal swab sample collection to assess active SARS-CoV-2 infection via qRT-PCR, and past infection by serology (overall completion rate of 33.7%). Eligibility included > 18 years old, able to read and understand English, not currently experiencing cough, shortness of breath or difficulty breathing, fever >100.4F (38C), chills/shaking with chills, muscle pain, new or worsening headaches, sore throat or new loss of sense of taste/smell. ExposureSelf-reported COVID-19 protective behaviors Main Outcome(s) and Measure(s)Current SARS-CoV-2 infection detected by qRT-PCR or previous SARS-CoV-2 infection detected by IgG SARS-CoV-2 testing platform. ResultsThere were no qRT-PCR positive tests, and only 2 (0.39%) contained seroreactive IgG antibodies. Participants were 60% female, 90% non-Hispanic white, mean age 41 years (18-70 years). Handwashing and mask wearing were reported frequently both at work (98% and 94% respectively) and outside work (91% and 95% respectively) while social distancing was reported less frequently at work (79%) then outside of work (92%) [p < .001]. Participants were more highly motivated to avoid exposures out of concern for spreading to others (83%) than for personal implications (63%) [p < .001]. Conclusions and RelevanceThis is one of the first reports to document that complex work environments can be operated safely during the COVID-19 pandemic when employees report compliance with public health practices both at and outside work.

Longitudinal Surveillance for SARS-CoV-2 RNA Among Asymptomatic Staff in Five Colorado Skilled Nursing Facilities: Epidemiologic, Virologic and Sequence Analysis.

SARS-CoV-2 emerged in 2019 and has become a major global pathogen in an astonishingly short period of time. The emergence of SARS-CoV-2 also has been notable due to its impacts on individuals residing within skilled nursing facilities (SNFs) such as rehabilitation centers and nursing homes. SNF residents tend to possess several risk factors for the most severe outcomes of SARS-CoV-2 infection, including advanced age and the presence of multiple comorbidities. Indeed, residents of long-term care facilities represent approximately 40 percent of US SARS-CoV-2 deaths. To assess the prevalence and incidence of SARS-CoV-2 among SNF workers, determine the extent of asymptomatic infection by SARS-CoV-2, and provide information on the genomic epidemiology of the virus within these unique care settings, we sampled workers weekly at five SNFs in Colorado using nasopharyngeal swabs, determined the presence of viral RNA and infectious virus among these workers, and sequenced 48 nearly complete genomes. This manuscript reports results from the first five to six weeks of observation. Our data reveal a strikingly high degree of asymptomatic infection, a strong correlation between RNA detection and the presence of infectious virus in NP swabs, persistent RNA in a subset of individuals, and declining incidence over time. Our data suggests that asymptomatic individuals infected by SARS-CoV-2 may contribute to virus transmission within the workplace.