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Background/ObjectivesCoronavirus disease 2019 (COVID-19) is associated with a hypercoagulable state and increased thrombotic risk in infected individuals. Several complex and varied coagulation abnormalities were proposed for this association1. Acetylsalicylic acid(ASA, aspirin) is known to have inflammatory, antithrombotic properties and its use was reported as having potency to reduce RNA synthesis and replication of some types of coronaviruses including human coronavirus-299E (CoV-229E) and Middle East Respiratory Syndrome (MERS)-CoV 2,3. We hypothesized that chronic low dose aspirin use may decrease COVID-19 mortality relative to ASA non-users. MethodsThis is a retrospective, observational cohort analysis of residents residing at Veterans Affairs Community Living Centers from December 13, 2020, to September 18, 2021, with a positive SARS-CoV-2 PCR test. Low dose aspirin users had low dose (81mg) therapy (10 of 14 days) prior to the positive COVID date and were compared to aspirin non-users (no ASA in prior 14 days). The primary outcome was mortality at 30 and 56 days post positive test and hospitalization. ResultsWe identified 1.823 residents who had SARS-CoV-2 infection and 1,687 residents were eligible for the study. Aspirin use was independently associated with a reduced risk of 30 days of mortality (adjusted HR, 0.60, 95% CI, 0.40-0.90) and 56 days of mortality (adjusted HR, 0.67, 95% CI, 0.47-0.95) ConclusionChronic low dose aspirin use for primary or secondary prevention of cardiovascular events is associated with lower COVID-19 mortality. Although additional randomized controlled trials are required to understand these associations and the potential implications more fully for improving care, aspirin remains a medication with known side effects and clinical practice should not change based on these findings.
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BackgroundA SARS-CoV-2 vaccine booster dose has been recommended for all nursing home residents. However, we lack effectiveness data on boosters preventing infection, death and hospitalization in this frail population. MethodsWe emulated nested target trials in two large nursing home systems in parallel to evaluate the effectiveness of a SARS-CoV-2 mRNA vaccine booster at preventing infection, hospitalization, or death. Residents who completed a 2-dose series of the mRNA vaccine and were eligible for a booster were included in from September 22, 2021 to November 5, 2021. Outcomes were measured through December 18, 2021, including test-confirmed SARS-CoV-2 infection, hospitalization, or death. The vaccine effectiveness at day 42 was estimated with a Kaplan-Meier estimator, both unadjusted and weighted with the inverse probability of treatment. ResultsThe two NH systems were large and multi-state, System 1 included 200 NH (8,538 control and 5,721 boosted residents) and System 2 included 127 NHs (4,100 control and 2,291 boosted residents). Booster vaccination reduced infections by 50.4% (95% Confidence Interval [CI]: 29.4%, 64.7%) SARS-CoV-2 infections in System 1 and 58.2% (32.3%, 77.8%) in System 2. Boosted residents in System 1 also had a 97.3% (86.9%, 100.0%) reduction in SARS-CoV-2 associated death, but too few events for comparison in System 2. ConclusionsDuring a Delta predominant period, SARS-CoV-2 booster vaccination significantly reduced infection in two U.S. nursing home systems. In the larger System 1 a 97% reduction in SARS-CoV-2 related death was also observed. These findings strongly support administration of vaccine boosters to nursing home residents.
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Nursing home (NH) residents have experienced significant morbidity and mortality to SARS-CoV-2 throughout the pandemic. Vaccines initially curbed NH resident morbidity and mortality, but antibody levels and protection have declined with time since vaccination, prompting introduction of booster vaccination. This study assesses humoral immune response to booster vaccination in 85 NH residents and 44 health care workers (HCW) that we have followed longitudinally since initial SARS-CoV-2 BNT162b2 mRNA vaccination. The findings reveal that booster vaccination significantly increased anti-spike, anti-receptor binding domain, and neutralization titers above the pre-booster levels in almost all NH residents and HCW to significantly higher levels than shortly after the completion of the initial vaccine series. These data support the CDC recommendation to offer vaccine boosters to HCWs and NH residents on an immunological basis. Notably, even the older, more frail and more multi-morbid NH residents have sizable antibody increases with boosting.
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High COVID-19 mortality among nursing home (NH) residents led to their prioritization for SARS-CoV-2 vaccination; most NH residents received BNT162b2 mRNA vaccination under the Emergency Use Authorization due to first to market and its availability. With NH residents poor initial vaccine response, the rise of NH breakthrough infections and outbreaks, characterization of the durability of immunity to inform public health policy on the need for boosting is needed. We report on humoral immunity from 2 weeks to 6-months post-vaccination in 120 NH residents and 92 ambulatory healthcare worker controls with and without pre-vaccination SARS-CoV-2 infection. Anti-spike and anti-receptor binding domain (RBD) IgG, and serum neutralization titers, were assessed using a bead-based ELISA method and pseudovirus neutralization assay. Anti-spike, anti-RBD and neutralization levels dropped more than 84% over 6 months time in all groups irrespective of prior SARS-CoV-2 infection. At 6 months post-vaccine, 70% of the infection-naive NH residents had neutralization titers at or below the lower limit of detection compared to 16% at 2 weeks after full vaccination. These data demonstrate a significant reduction in levels of antibody in all groups. In particular, those infection-naive NH residents had lower initial post-vaccination humoral immunity immediately and exhibited the greatest declines 6 months later. Healthcare workers, given their younger age and relative good-health, achieved higher initial antibody levels and better maintained them, yet also experienced significant declines in humoral immunity. Based on the rapid spread of the delta variant and reports of vaccine breakthrough in NH and among younger community populations, boosting NH residents may be warranted.
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ObjectivesCOVID-19 has had a severe impact on morbidity and mortality among nursing home (NH) residents. Earlier detection of SARS-CoV-2 may position us to better mitigate risk of spread. Both asymptomatic or pre-symptomatic transmission are common in outbreaks, and threshold temperatures, such as 38C, for screening for infection could miss timely detection in the majority. DesignRetrospective cohort study using electronic health records MethodsWe hypothesized that in long-term care residents, temperature trends with SARS-CoV-2 infection could identify infection in pre-symptomatic and asymptomatic individuals earlier. We collected information about age and other demographics, baseline temperature, and specific comorbidities. We created standardized definitions, and an alternative hypothetical model to test measures of temperature variation and compare outcomes to the VA reality. Settings and participantsOur subjects were 6,176 residents of the VA NHs who underwent SARS-CoV-2 trigger testing. ResultsWe showed that a change from baseline of >0.4C identifies 47% of the SARS-CoV-2 positive NH residents early, and achieves earlier detection by 42.2 hours. Range improves early detection to 55% when paired with a 37.2C cutoff, and achieves earlier detection by 44.4 hours. Temperature elevation >0.4C from baseline, when combined with a 0.7C range, would detect 52% early, leading to earlier detection by more than 3 days in 22% of the residents. This earlier detection comes at the expense of triggering 57,793 tests, as compared to the number of trigger tests ordered in the VA system of 40,691. Conclusion and implicationsOur model suggests that current clinical screening for SARS-CoV-2 in NHs can be substantially improved upon by triggering testing using a patient-derived baseline temperature with a 0.4C degree relative elevation or temperature variability of 0.7C trigger threshold for SARS-CoV2 testing. Such triggers could be automated in facilities that track temperatures in their electronic records.
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The SARS-CoV-2 pandemic impact on nursing home (NH) residents prompted their prioritization for early vaccination. To fill the data gap for vaccine immunogenicity in NH residents, we examined antibody levels after BNT162b2 mRNA vaccine to spike, receptor binding domain (RBD) and for virus neutralization in 149 NH residents and 111 health care worker controls. SARS-CoV-2-naive NH residents mount antibody responses with nearly 4-fold lower median neutralization titers and half the anti-spike level compared to SARS-CoV-2-naive healthcare workers. By contrast, SARS-CoV-2-recovered vaccinated NH residents had neutralization, anti-spike and anti-RBD titers similar to SARS-CoV-2-recovered vaccinated healthcare workers. NH residents blunted antibody responses have important implications regarding the quality and durability of protection afforded by neoantigen vaccines. We urgently need better longitudinal evidence on vaccine effectiveness specific to NH resident populations to inform best practices for NH infection control measures, outbreak prevention and potential indication for a vaccine boost.