Effectiveness and Duration of Protection of a Fourth Dose of COVID-19 mRNA Vaccine among Long-Term Care Residents in Ontario, Canada

BackgroundAs of December 30, 2021, Ontario long-term care (LTC) residents who received a third dose of COVID-19 vaccine [≥]84 days previously were offered a fourth dose to prevent a surge in COVID-19-related morbidity and mortality due to the Omicron variant. Seven months have passed since fourth doses were implemented, allowing for the examination of fourth dose protection over time. MethodsWe used a test-negative design and linked databases to estimate the marginal effectiveness (4 versus 3 doses) and vaccine effectiveness (VE; 2, 3, or 4 doses versus no doses) of mRNA vaccines among Ontario LTC residents aged [≥]60 years who were tested for SARS-CoV-2 between December 30, 2021 and August 3, 2022. Outcome measures included any Omicron infection, symptomatic infection, and severe outcomes (hospitalization or death). ResultsWe included 21,275 Omicron cases and 273,466 test-negative controls. The marginal effectiveness of a fourth dose <84 days ago compared to a third dose received [≥]84 days ago was 23% (95% Confidence Interval [CI] 17-29%), 36% (95%CI 26-44%), and 37% (95%CI 24-48%) against SARS-CoV-2 infection, symptomatic infection, and severe outcomes, respectively. Additional protection provided by a fourth dose compared to a third dose was negligible against all outcomes [≥]168 days after vaccination. Compared to unvaccinated individuals, vaccine effectiveness (VE) of a fourth dose decreased from 49% (95%CI 44%-54%) to 18% (95%CI 5-28%) against infection, 69% (95%CI 62-75%) to 44% (95%CI 24-59%) against symptomatic infection, and 82% (95%CI 77-86%) to 74% (95%CI 62-82%) against severe outcomes <84 days versus [≥]168 days after vaccination. ConclusionsOur findings suggest that fourth doses of mRNA COVID-19 vaccines provide additional protection against Omicron-related outcomes in LTC residents, but the protection wanes over time, with more waning seen against infection than severe outcomes.

Association between nursing home crowding and outbreak-associated respiratory infection and death prior to the COVID-19 pandemic between 2014 and 2019 in Ontario, Canada

ImportanceResident crowding in nursing homes is associated with larger SARS-CoV-2 outbreaks. However, this association has not been previously documented for non-SARS-CoV-2 respiratory infections. ObjectiveWe sought to measure the association between nursing home crowding and respiratory infections in Ontario nursing homes prior to the COVID-19 pandemic. Design, Setting, and ParticipantsWe conducted a retrospective cohort study of nursing home residents in Ontario, Canada over a five-year period prior to the COVID-19 pandemic, between September 2014 and August 2019. ExposureUsing administrative data, we estimated the crowding index equal to the mean number of residents per bedroom and bathroom (residents / [0.5*bedrooms+0.5*bathrooms]). OutcomesThe incidence of outbreak-associated infections and mortality per 100 nursing home residents per year. We also examined infection and mortality outcomes for outbreaks due to 7 specific pathogens: coronaviruses (OC43, 229E, NL63, HKU1), influenza A, influenza B, human metapneumovirus, parainfluenza virus, respiratory syncytial virus, rhinovirus/enterovirus. ResultsThere was one or more respiratory outbreak in 93.9% (588/626) nursing homes in Ontario. There were 4,921 outbreaks involving 64,829 cases of respiratory infection, and 1,969 deaths. Outbreaks attributable to a single identified pathogen were principally caused by influenza A (29%), rhinovirus (11.7%), influenza B (8.1%), and respiratory syncytial virus (6.1%). Among homes, 42.7% (251/588) homes had a high crowding index ([≥] 2.0). After adjustment, more crowded homes had higher outbreak-associated respiratory infection incidence (aRR 1.89; 95% 1.64-2.18) and mortality incidence (aRR 2.28; 95% 1.84-2.84). More crowded homes had higher adjusted estimates of the incidence of infection and mortality for each of the 7 respiratory pathogens examined. Conclusions and RelevanceResidents of crowded nursing homes experienced more respiratory-outbreak infections and mortality due to influenza and other non-SARS-CoV-2 respiratory pathogens. Decreasing crowding in nursing homes is an important patient safety target beyond the COVID-19 pandemic.

Protection from Omicron infection in residents of nursing and retirement homes in Ontario, Canada

ObjectivesTo identify factors that contribute to protection from infection with the Omicron variant of SARS-CoV-2 in older adults in nursing and retirement homes. DesignLongitudinal cohort study with retrospective analysis of infection risk. Setting and Participants997 residents of nursing and retirement homes from Ontario, Canada, in the COVID-in-LTC study. MethodsResidents with three mRNA dose vaccinations were included in the study. SARS-CoV-2 infection was determined by positive nasopharyngeal PCR test and/or circulating anti-nucleocapsid IgG antibodies. Cumulative probability of Omicron infection after recent COVID-19 was assessed by log-rank test of Kaplan-Meier curves. Cox regression was used to assess risk of Omicron infection by age, sex, mRNA vaccine combination, whether individuals received a fourth dose, as well as recent COVID-19. Results171 residents (17.2%) had a presumed Omicron variant SARS-CoV-2 infection between December 15, 2021 (local start of the first Omicron wave) and May 3, 2022. Risk of Omicron infection was not different by age [hazard ratio (95% confidence interval): 1.01 (0.99-1.02)], or in women compared to men [0.97 (0.70-1.34)], but infection risk decreased 47% with three vaccine doses of mRNA-1273 (Moderna) compared to BNT162b2 (Pfizer) [0.53 (0.31-0.90)], 81% with any fourth mRNA vaccine dose [0.19 (0.12-0.30)], and 48% with SARS-CoV-2 infection in the 3 months prior to beginning of the Omicron wave [0.52, (0.27-0.99)]. Conclusions and ImplicationsVaccine type (i.e., mRNA-1273/Spikevax vs BNT162b2/Cominarty), any fourth vaccine dose, and hybrid immunity from recent COVID-19, were protective against infection with the Omicron variant. These data emphasize the importance of vaccine type, and number of vaccine doses, in maintenance of protective immunity and reduction of risk of Omicron variant breakthrough infection. These findings promote continued public health efforts to support vaccination programs and monitor vaccine immunogenicity in older adults. Brief summaryRisk of infection with the SARS-CoV-2 Omicron variant in older adults in early 2022 was reduced with triple mRNA-1273 vaccination, any fourth dose vaccine, and within three months of prior COVID-19.

CMV seropositivity in older adults changes T cell functionality, but does not prevent antibody or cellular SARS-CoV-2 vaccine responses

Chronic infection with human cytomegalovirus (CMV) may contribute to poor vaccine efficacy in older adults. We assessed effects of CMV serostatus on antibody quantity and quality, as well as cellular memory recall responses, after 2 and 3 SARS-CoV-2 mRNA vaccine doses, in older adults in assisted living facilities. CMV serostatus did not affect anti-Spike and anti-RBD IgG antibody levels, nor neutralization capacity against wildtype or beta variants of SARS-CoV-2 several months after vaccination. CMV seropositivity altered T cell expression of senescence-associated markers and increased TEMRA cell numbers, as has been previously reported; however, this did not impact Spike-specific CD4+ T cell memory recall responses. CMV seropositive individuals did not have a higher incidence of COVID-19, though prior infection influenced humoral immunity. Therefore, CMV seropositivity may alter T cell composition but does not impede the durability of humoral protection or cellular memory responses after SARS-CoV-2 mRNA vaccination in older adults. Key PointsCMV seropositive older adults have more EMRA and terminally differentiated T cells CMV seropositivity does not prevent antibody maintenance after SARS-CoV-2 vaccination CMV seropositivity does not impede SARS-CoV-2 vaccine T cell memory recall responses

Effectiveness of a Fourth Dose of COVID-19 Vaccine among Long-Term Care Residents in Ontario, Canada

BackgroundAs of December 30, 2021, Ontario long-term care (LTC) residents who received a third dose of COVID-19 vaccine [≥]84 days previously were offered a fourth dose to prevent a surge in COVID-19-related morbidity and mortality due to the Omicron variant. MethodsWe used a test-negative design and linked databases to estimate the marginal effectiveness (4 versus 3 doses) and vaccine effectiveness (VE; 2, 3, or 4 doses versus no doses) of mRNA vaccines among Ontario LTC residents aged [≥]60 years who were tested for SARS-CoV-2 between December 30, 2021 and April 27, 2022. Outcome measures included any Omicron infection, symptomatic infection, and severe outcomes (hospitalization or death). ResultsWe included 13,654 Omicron cases and 205,862 test-negative controls. The marginal effectiveness of a fourth dose (with 95% of fourth dose vaccine recipients receiving mRNA-1273) [≥]7 days after vaccination versus a third dose received [≥]84 days prior was 19% (95% Confidence Interval [CI], 12-26%) against infection, 31% (95%CI, 20-41%) against symptomatic infection, and 40% (95%CI, 24-52%) against severe outcomes. VE (compared to an unvaccinated group) increased with each additional dose, and for a fourth dose was 49% (95%CI, 43-54%), 69% (95%CI, 61-76%), and 86% (95%CI, 81-90%), against infection, symptomatic infection, and severe outcomes, respectively. ConclusionsOur findings suggest that compared to a third dose received [≥]84 days ago, a fourth dose improved protection against infection, symptomatic infection, and severe outcomes caused by Omicron among long-term care residents. Compared to unvaccinated individuals, fourth doses provide strong protection against severe outcomes, but the duration of protection remains unknown.

Antibody Responses to 3rd Dose mRNA Vaccines in Nursing Home and Assisted Living Residents

A comparison of SARS-CoV-2 wild-type and the beta variant virus neutralization capacity between 2 and 3 mRNA vaccine series in nursing home residents, and between nursing home and assisted living residents strongly supports 3rd dose vaccine recommendations, and equivalent polices for nursing homes and assisted living settings. Findings suggest that residents mount a robust humoral response to a 3rd mRNA vaccination, and have greater neuralization capacity compared to a 2 dose series.

Risk factors for retirement home COVID-19 outbreaks in Ontario, Canada: A population-level cohort study

BackgroundThe epidemiology of COVID-19 in retirement homes (also known as assisted living facilities) is largely unknown. We examined the association between retirement home and community level characteristics and the risk of COVID-19 outbreaks in retirement homes during the first wave of the COVID-19 epidemic. MethodsWe conducted a population-based retrospective cohort study of licensed retirement homes in Ontario, Canada, from March 1st - September 24th, 2020. Our primary outcome was a COVID-19 outbreak ([≥]1 resident or staff confirmed case by validated nucleic acid amplification assay). We used time-dependent proportional hazards methods to model the associations between retirement home and community level characteristics and COVID-19 outbreaks. ResultsOur cohort included all 770 licensed retirement homes in Ontario, which housed 56,491 residents. There were 172 (22.3%) COVID-19 retirement home outbreaks involving 1,045 (1.9%) residents and 548 staff (1.5%). COVID-19 cases were distributed unevenly across retirement homes, with 1,593 (92.2%) resident and staff cases occurring in 77 (10%) of homes. The adjusted hazard of a COVID-19 outbreak in a retirement home was positively associated with homes that had a large resident capacity, homes that were co-located with a long-term care facility, large corporate owned chains, homes that offered many services onsite, increases in regional COVID-19 incidence, and a higher community-level ethnic concentration. InterpretationReadily identifiable retirement home-level characteristics are independently associated with COVID-19 outbreaks and may support risk identification. A higher ethnic concentration of the community surrounding a retirement home is associated COVID-19 outbreaks, with an uncertain mechanism.

Increased Prescribing of Psychotropic Medications to Ontario Nursing Home Residents during the COVID-19 Pandemic

In this population-based study of all Ontario nursing home residents, we found increased prescribing of psychotropic drugs at the onset of the COVID-19 pandemic that persisted through September 2020. Increases in prescribing were out of proportion to expected secular trends, and distinct from observed prescribing changes in other drugs during the pandemic. Our findings underscore the urgency of balancing infection prevention and control measures in nursing homes with the mental wellbeing of residents.

Impact of a public policy restricting staff mobility between long-term care homes in Ontario, Canada during the COVID-19 pandemic

ObjectivesTo assess changes in the mobility of staff between long-term care homes in Ontario, Canada before and after enactment of public policy restricting staff from working at multiple homes. DesignPre-post observational study. Setting and Participants623 long-term cares homes in Ontario, Canada between March 2020 and June 2020. MethodsWe used anonymized mobile device location data to approximate connectivity between all 623 long-term care homes in Ontario during the 7 weeks before (March 1 - April 21) and after (April 22 - June 13) the policy restricting staff movement was implemented. We visualized connectivity between long-term care homes in Ontario using an undirected network and calculated the number of homes that had a connection with another long-term care home and the average number of connections per home in each period. We calculated the relative difference in these mobility metrics between the two time periods and compared within-home changes using McNemars test and the Wilcoxon rank-sum test. ResultsIn the period preceding restrictions, 266 (42.7%) long-term care homes had a connection with at least one other home, compared to 79 (12.7%) homes during the period after restrictions, a drop of 70.3% (p <0.001). The average number of connections in the before period was 3.90 compared to 0.77 in after period, a drop of 80.3% (p < 0.001). In both periods, mobility between long-term care homes was higher in homes located in larger communities, those with higher bed counts, and those part of a large chain. Conclusions and ImplicationsMobility between long-term care homes in Ontario fell sharply after an emergency order by the Ontario government limiting long-term care staff to a single home, though some mobility persisted. Reducing this residual mobility should be a focus of efforts to reduce risk within the long-term care sector during the COVID-19 pandemic.

For-profit nursing homes and the risk of COVID-19 outbreaks and resident deaths in Ontario, Canada

BackgroundNursing homes have become the epicentre of the coronavirus disease 2019 (COVID-19) pandemic in Canada. Previous research demonstrates that for-profit nursing homes deliver inferior care across a variety of outcome and process measures, raising the question of whether for-profit homes have had worse COVID-19 outcomes than non-profit homes. MethodsWe conducted a retrospective cohort study of all nursing homes in Ontario, Canada from March 29-May 20, 2020 using a COVID-19 outbreak database maintained by the Ontario Ministry of Long-Term Care. We used hierarchical logistic and count-based methods to model the associations between nursing home profit status (for-profit, non-profit or municipal) and nursing home COVID-19 outbreaks, COVID-19 outbreak sizes, and COVID-19 resident deaths. ResultsThe analysis included all 623 Ontario nursing homes, of which 360 (57.7%) were for-profit, 162 (26.0%) were non-profit, and 101 (16.2%) were municipal homes. There were 190 (30.5%) COVID-19 nursing home outbreaks involving 5218 residents (mean of 27.5 {+/-} 41.3 residents per home), resulting in 1452 deaths (mean of 7.6 {+/-} 12.7 residents per home) with an overall case fatality rate of 27.8%. The odds of a COVID-19 outbreak was associated with the incidence of COVID-19 in the health region surrounding a nursing home (adjusted odds ratio [aOR], 1.94; 95% confidence interval [CI] 1.23-3.09) and number of beds (aOR, 1.40; 95% CI 1.20-1.63), but not profit status. For-profit status was associated with both the size of a nursing home outbreak (adjusted risk ratio [aRR], 1.96; 95% CI 1.26-3.05) and the number of resident deaths (aRR, 1.78; 95% CI 1.03-3.07), compared to non-profit homes. These associations were mediated by a higher prevalence of older nursing home design standards in for-profit homes. Interpretation: For-profit status is associated with the size of a COVID-19 nursing home outbreak and the number of resident deaths, but not the likelihood of outbreaks. Differences between for profit and non-profit homes are largely explained by older design standards, which should be a focus of infection control efforts and future policy.