Ecological Analysis of the Decline in Incidence Rates of COVID-19 Among Nursing Home Residents Associated with Vaccination,United States,December 2020-January 2021

ObjectiveTo evaluate if facility-level vaccination after an initial vaccination clinic was independently associated with COVID-19 incidence adjusted for other factors in January 2021 among nursing home residents.DesignEcological analysis of data from the CDC's National Healthcare Safety Network (NHSN) and from the CDC's Pharmacy Partnership for Long-Term Care Program.Setting and ParticipantsCMS-certified nursing homes participating in both NHSN and the Pharmacy Partnership for Long-Term Care Program.MethodsA multivariable, random intercepts, negative binomial model was applied to contrast COVID-19 incidence rates among residents living in facilities with an initial vaccination clinic during the week ending January 3, 2021 (n = 2843), vs those living in facilities with no vaccination clinic reported up to and including the week ending January 10, 2021 (n = 3216). Model covariates included bed size, resident SARS-CoV-2 testing, staff with COVID-19, cumulative COVID-19 among residents, residents admitted with COVID-19, community county incidence, and county social vulnerability index (SVI).ResultsIn December 2020 and January 2021, incidence of COVID-19 among nursing home residents declined to the lowest point since reporting began in May, diverged from the pattern in community cases, and began dropping before vaccination occurred. Comparing week 3 following an initial vaccination clinic vs week 2, the adjusted reduction in COVID-19 rate in vaccinated facilities was 27% greater than the reduction in facilities where vaccination clinics had not yet occurred (95% confidence interval: 14%-38%, P < .05).Conclusions and ImplicationsVaccination of residents contributed to the decline in COVID-19 incidence in nursing homes; however, other factors also contributed. The decline in COVID-19 was evident prior to widespread vaccination, highlighting the benefit of a multifaced approach to prevention including continued use of recommended screening, testing, and infection prevention practices as well as vaccination to keep residents in nursing homes safe.     

Temperature in Nursing Home Residents Systematically Tested for SARS-CoV-2

ObjectivesMany nursing home residents infected with SARS-CoV-2 fail to be identified with standard screening for the associated COVID-19 syndrome. Current nursing home COVID-19 screening guidance includes assessment for fever, defined as a temperature of at least 38.0°C. The objective of this study was to describe the temperature changes before and after universal testing for SARS-CoV-2 in nursing home residents.DesignCohort study.Setting and ParticipantsThe Veterans Administration (VA) operates 134 Community Living Centers (CLC), similar to nursing homes, that house residents who cannot live independently. VA guidance to CLCs directed daily clinical screening for COVID-19 that included temperature assessment.MeasuresAll CLC residents (n = 7325) underwent SARS-CoV-2 testing. We report the temperature in the window of 14 days before and after universal SARS-CoV-2 testing among CLC residents. Baseline temperature was calculated for 5 days before the study window.ResultsSARS-CoV-2 was identified in 443 (6.0%) residents. The average maximum temperature in SARS-CoV-2–positive residents was 37.66 (0.69) compared with 37.11 (0.36) (P = .001) in SARS-CoV-2–negative residents. Temperatures in those with SARS-CoV-2 began rising 7 days before testing and remained elevated during the 14-day follow-up. Among SARS-CoV-2–positive residents, only 26.6% (n = 118) met the fever threshold of 38.0°C during the survey period. Most residents (62.5%, n = 277) with confirmed SARS-CoV-2 did experience 2 or more 0.5°C elevations above their baseline values. One cohort of SARS-CoV-2 residents' (20.3%, n = 90) temperatures never deviated >0.5°C from baseline.Conclusions and ImplicationsA single screening for temperature is unlikely to detect nursing home residents with SARS-CoV-2. Repeated temperature measurement with a patient-derived baseline can increase sensitivity. The current fever threshold as a screening criteria for SARS-CoV-2 infection should be reconsidered.     

Risk of Death in Nursing Home Residents After COVID-19 Vaccination

ObjectivesIn the first months of 2021, the Dutch COVID-19 vaccination campaign was disturbed by reports of death in Norwegian nursing homes (NHs) after vaccination. Reports predominantly concerned persons >65 years of age with 1 or more comorbidities. Also, in the Netherlands adverse events were reported after COVID-19 vaccination in this vulnerable group. Yet, it was unclear whether a causal link between vaccination and death existed. Therefore, we investigated the risk of death after COVID-19 vaccination in Dutch NH residents compared with the risk of death in NH residents prior to the COVID-19 pandemic.DesignPopulation-based longitudinal cohort study with electronic health record data.Setting and ParticipantsWe studied Dutch NH residents from 73 NHs who received 1 or 2 COVID-19 vaccination(s) between January 13 and April 16, 2021 (n = 21,762). As a historical comparison group, we included Dutch NH residents who were registered in the same period in 2019 (n = 27,591).MethodsData on vaccination status, age, gender, type of care, comorbidities, and date of NH entry and (if applicable) discharge or date of death were extracted from electronic health records. Risk of death after 30 days was evaluated and compared between vaccinated residents and historical comparison residents with Kaplan-Meier and Cox regression analyses. Regression analyses were adjusted for age, gender, comorbidities, and length of stay.ResultsRisk of death in NH residents after one COVID-19 vaccination (regardless of whether a second vaccination was given) was decreased compared with historical comparison residents from 2019 (adjusted HR 0.77, 95% CI 0.69-0.86). The risk of death further decreased after 2 vaccinations compared with the historical comparison group (adjusted HR 0.57, 95% CI 0.50-0.64).Conclusions and ImplicationsWe found no indication that risk of death in NH residents is increased after COVID-19 vaccination. These results indicate that COVID-19 vaccination in NH residents is safe and could reduce fear and resistance toward vaccination.     

Third dose of COVID-19 mRNA vaccine closes the gap in immune response between naïve nursing home residents and healthy adults

BackgroundNursing home residents, a frail and old population group, respond poorly to primary mRNA COVID-19 vaccination. A third dose has been shown to boost protection against severe disease and death in this immunosenescent population, but limited data is available on the immune responses it induces.MethodsIn this observational cohort study, peak humoral and cellular immune responses were compared 28 days after the second and third doses of the BNT162b2 mRNA COVID-19 vaccine in residents and staff members of two Belgian nursing homes. Only individuals without evidence of previous SARS-CoV-2 infection at third dose administration were included in the study. In addition, an extended cohort of residents and staff members was tested for immune responses to a third vaccine dose and was monitored for vaccine breakthrough infections in the following six months. The trial is registered on ClinicalTrials.gov (NCT04527614).FindingsAll included residents (n = 85) and staff members (n = 88) were SARS-CoV-2 infection naïve at third dose administration. Historical blood samples from 28 days post second dose were available from 42 residents and 42 staff members. Magnitude and quality of humoral and cellular immune responses were strongly boosted in residents post third compared to post second dose. Increases were less pronounced in staff members than in residents. At 28 days post third dose, differences between residents and staff had become mostly insignificant. Humoral, but not cellular, responses induced by a third dose were predictive of subsequent incidence of vaccine breakthrough infection in the six months following vaccination.InterpretationThese data show that a third dose of mRNA COVID-19 vaccine largely closes the gap in humoral and cellular immune response observed after primary vaccination between NH residents and staff members but suggest that further boosting might be needed to achieve optimal protection against variants of concern in this vulnerable population group.     

COVID-19 outbreak in an elderly care home: Very low vaccine effectiveness and late impact of booster vaccination campaign

BackgroundElderly people in long-term care facilities (LTCF) are at higher risk for (severe) COVID-19, yet evidence of vaccine effectiveness (VE) in this population is scarce. In November 2021 (Delta period), a COVID-19 outbreak occurred at a LTCF in the Netherlands, continuing despite measures and booster vaccination campaign. We investigated the outbreak to assess VE of primary COVID-19 vaccination against SARS-CoV-2 infection and mortality, and to describe the impact of the booster vaccination.MethodsWe calculated attack rate (AR) and case fatality (CF) per vaccination status (unvaccinated, primarily vaccinated and boostered). We calculated VE – at on average 6 months after vaccination – as 1- risk ratio (RR) using the crude risk ratio (RR) with 95% confidence intervals (CI) for the association between vaccination status (primary vaccination versus unvaccinated) and outcomes (SARS-CoV-2 infection and mortality < 30 days after testing positive for SARS-CoV-2).ResultsThe overall AR was 67% (70/105). CF was 33% (2/6) among unvaccinated cases, 12% among primarily vaccinated (7/58) and 0% (0/5) among boostered. The VE of primary vaccination was 17% (95% CI ?28%; 46%) against SARS-CoV-2 infection and 70% (95% CI ?44%; 96%) against mortality. Among boostered residents (N = 55), there were 25 cases in the first week after receiving the booster dose, declining to 5 in the second and none in the third week.ConclusionVE of primary vaccination in residents of LTCF was very low against SARS-CoV-2 infection and moderate against mortality. There were few cases at 2 weeks after the booster dose and no deaths, despite the presence of susceptible residents. These data are consistent with the positive impact of the booster vaccination in curbing transmission. Timely booster vaccination in residents of LTCF is therefore important.     

Quantifying Risk for SARS-CoV-2 Infection Among Nursing Home Workers for the 2020-2021 Winter Surge of the COVID-19 Pandemic in Georgia,USA

ObjectivesEstimate incidence of and risks for SARS-CoV-2 infection among nursing home staff in the state of Georgia during the 2020-2021 Winter COVID-19 Surge in the United States.DesignSerial survey and serologic testing at 2 time points with 3-month interval exposure assessment.Setting and ParticipantsFourteen nursing homes in the state of Georgia; 203 contracted or employed staff members from those 14 participating nursing homes who were seronegative at the first time point and provided a serology specimen at second time point, at which time they reported no COVID-19 vaccination or only very recent vaccination (≤4 weeks).MethodsInterval infection was defined as seroconversion to antibody presence for both nucleocapsid protein and spike protein. We estimated adjusted odds ratios (aORs) and 95% CIs by job type, using multivariable logistic regression, accounting for community-based risks including interval community incidence and interval change in resident infections per bed.ResultsAmong 203 eligible staff, 72 (35.5%) had evidence of interval infection. In multivariable analysis among unvaccinated staff, staff SARS-CoV-2 infection–induced seroconversion was significantly higher among nurses and certified nursing assistants accounting for race and interval infection incidence in both the community and facility (aOR 5.3, 95% CI 1.0-28.4). This risk persisted but was attenuated when using the full study cohort including those with very recent vaccination.Conclusions and ImplicationsMidway through the first year of the pandemic, job type continues to be associated with increased risk for infection despite enhanced infection prevention efforts including routine screening of staff. These results suggest that mitigation strategies prior to vaccination did not eliminate occupational risk for infection and emphasize critical need to maximize vaccine utilization to eliminate excess risk among front-line providers.     

Previous SARS-CoV-2 Infection,Age, and Frailty Are Associated With 6-Month Vaccine-Induced Anti-Spike Antibody Titer in Nursing Home Residents

ObjectivesOlder nursing home residents make up the population at greatest risk of morbidity and mortality from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. No studies have examined the determinants of long-term antibody responses post vaccination in this group.DesignLongitudinal cohort study.Setting and ParticipantsResidents from 5 nursing homes assessed before vaccination, and 5 weeks and 6 months post vaccination, with the BNT162b2 messenger RNA SARS-CoV-2 vaccine.MethodsComprehensive clinical assessment was performed, including assessment for comorbidity, frailty, and SARS-CoV-2 infection history. Serum nucleocapsid and anti-spike receptor binding domain (RBD) antibodies were analyzed at all timepoints. An in vitro angiotensin-converting enzyme (ACE2) receptor-spike RBD neutralization assay assessed serum neutralization capacity.ResultsOf 86 participants (81.1 ± 10.8 years; 65% female), just under half (45.4%; 39 of 86) had evidence of previous SARS-CoV-2 infection. All participants demonstrated a significant antibody response to vaccination at 5 weeks and a significant decline in this response by 6 months. SARS-CoV-2 infection history was the strongest predictor of antibody titer (log-transformed) at both 5 weeks [β: 3.00; 95% confidence interval (CI): 2.32–3.70; P < .001] and 6 months (β: 3.59; 95% CI: 2.89–4.28; P < .001). Independent of SARS-CoV-2 infection history, both age in years (β: ?0.05; 95% CI: ?0.08 to ?0.02; P < .001) and frailty (β: ?0.22; 95% CI: ?0.33 to ?0.11; P < .001) were associated with a significantly lower antibody titer at 6 months. Anti-spike antibody titers at both 5 weeks and 6 months significantly correlated with in vitro neutralization capacity.Conclusions and ImplicationsIn older nursing home residents, SARS-CoV-2 infection history was the strongest predictor of anti-spike antibody titers at 6 months, whereas age and frailty were independently associated with lower titers at 6 months. Antibody titers significantly correlated with in vitro neutralization capacity. Although older SARS-CoV-2 naïve nursing home residents may be particularly vulnerable to breakthrough SARS-CoV-2 infection, the relationship between antibody titers, SARS-CoV-2 infection, and clinical outcomes remains to be fully elucidated in this vulnerable population.     

Risk of Adverse Events and Delirium after COVID-19 Vaccination in Patients Living with Dementia

ObjectivesThe aim of this study was to compare incidences of adverse events of special interest (AESI) and delirium in 3 cohorts: after COVID-19 vaccination, prepandemic, and SARS-CoV-2 polymerase chain reaction (PCR) test positive.DesignThis is a population-based cohort study using electronic medical records linked with vaccination records in Hong Kong.Setting and ParticipantsA total of 17,449 older people with dementia received at least 1 dose of CoronaVac (n = 14,719) or BNT162b2 (n = 2730) between February 23, 2021, and March 31, 2022. Moreover, 43,396 prepandemic and 3592 SARS-CoV-2 test positive patients were also included in this study.MethodsThe incidences of AESI and delirium up to 28 days after vaccination in the vaccinated dementia cohort were compared with the prepandemic and SARS-CoV-2 test positive dementia cohorts by calculating incidence rate ratios (IRRs). Patients who received multiple doses were followed up separately for each dose, up to the third dose.ResultsWe did not detect an increased risk of delirium and most AESI following vaccination compared to the prepandemic period and those tested positive for SARS-CoV-2. No AESI group nor delirium incidence exceeded 10 per 1000 person-days in vaccinated individuals.Conclusions and ImplicationsThe findings provide evidence for the safe use of COVID-19 vaccines in older patients with dementia. In the short run, benefit appears to outweigh the harm due to vaccine; however, longer follow-up should be continued to identify remote adverse events.     

Adverse events following mRNA SARS-CoV-2 vaccination among U.S. nursing home residents

BackgroundThe devastating impact of the SARS-CoV-2 pandemic prompted the development and emergency use authorization of two mRNA vaccines in early 2020. Vaccine trials excluded nursing home (NH) residents, limiting adverse event data that directly apply to this population.MethodsTo prospectively monitor for potential adverse events associated with vaccination, we used Electronic Health Record (EHR) data from Genesis HealthCare, the largest NH provider in the United States. EHR data on vaccinations and pre-specified adverse events were updated daily and monitored for signal detection among residents of 147 facilities who received the first dose of vaccine between December 18, 2020 and January 3, 2021. For comparison, unvaccinated residents during the same time period were included from 137 facilities that started vaccinating at least 15 days after the vaccinating-facilities.ResultsAs of January 3, 2021, 8553 NH residents had received one dose of SARS-CoV-2 vaccine and by February 20, 2021, 8371 residents had received their second dose of vaccine; 11,072 were included in the unvaccinated comparator group. No significant associations were noted for neurologic outcomes, anaphylaxis, or cardiac events.ConclusionsNo major safety problems were detected following the first or second dose of the vaccine to prevent COVID-19 in the study cohort from December 18, 2020 through March 7, 2021.     

Delay between COVID-19 complete vaccination and SARS-CoV-2 infection among healthcare workers

ObjectivesHealthcare workers (HCWs), at increased risk of coronavirus disease 2019 (COVID-19) were among the primary targets for vaccination, which became mandatory for them on September 15th, 2021 in France. In November they were confronted to the fifth COVID-19 wave despite excellent vaccine coverage. We aimed to estimate the incidence of SARS-CoV-2 infection after complete vaccination among HCWs with different vaccination schemes, and its determinants.MethodsWe enrolled all HCWs in the university hospital of Rennes, France who had received complete vaccination (two doses of COVID-19 vaccine). The delay from last vaccination dose to SARS-CoV-2 infection was computed. Fitted mixed Cox survival model with a random effect applied to exposure risk periods to account for epidemic variation was used to estimate the determinants of SARS-CoV-2 infection after complete vaccination.ResultsOf the 6674 (82%) HCWs who received complete vaccination (36% BNT162b2, 29% mRNA-1273, and 34% mixed with ChAdOx1 nCoV-19) and were prospectively followed-up for a median of 7.0 [6.3–8.0] months, 160 (2.4%) tested positive for SARS-CoV-2 by RT-PCR. Incidence density of SARS-CoV-2 infection after complete vaccination was 3.39 [2.89–3.96] infections per 1000 person-month. Median time from vaccine completion to SARS-CoV-2 infection was 5.5 [3.2–6.6] months. Using fitted mixed Cox regression with the delay as a time-dependent variable and random effect applied to exposure risk periods, age (P < 0.001) was independently associated with the incidence of SARS-CoV-2 infection. Vaccine schemes were not associated with SARS-CoV-2 infection (P = 0.068). A period effect was significantly associated with the incidence of SARS-CoV-2 infection (P < 0.001).ConclusionsIn this real-world study, incidence of SARS-CoV-2 infection increases with time in fully vaccinated HCWs with no differences according to the vaccination scheme. The short delay between complete vaccination and incident SARS-CoV-2 infection highlights the need for sustained barrier measures even in fully vaccinated HCWs.     

Metformin is Associated with Decreased 30-Day Mortality Among Nursing Home Residents Infected with SARS-CoV2

ObjectivesThe COVID-19 pandemic presents an urgent need to investigate whether existing drugs can enhance or even worsen prognosis; metformin, a known mammalian target of rapamycin (m-TOR) inhibitor, has been identified as a potential agent. We sought to evaluate mortality benefit among older persons infected with SARS-CoV-2 who were taking metformin as compared to those who were not.DesignRetrospective cohort study.Setting and Participants775 nursing home residents infected with SARS-CoV-2 who resided in one of the 134 Community Living Centers (CLCs) of the Veterans Health Administration (VHA) during March 1, 2020, to May 13, 2020, were included.MethodsUsing a window of 14 days prior to SARS-CoV-2 testing, bar-coded medication administration records were examined for dispensing of medications for diabetes. The COVID-19–infected residents were divided into 4 groups: (1) residents administered metformin alone or in combination with other medications, (2) residents who used long-acting or daily insulin, (3) residents administered other diabetes medications, and (4) residents not administered diabetes medication, including individuals without diabetes and patients with untreated diabetes. Proportional hazard models adjusted for demographics, hemoglobin A1c, body mass index, and renal function.ResultsRelative to those not receiving diabetes medications, residents taking metformin were at significantly reduced hazard of death [adjusted hazard ratio (HR) 0.48, 95% confidence interval (CI) 0.28, 0.84] over the subsequent 30 days from COVID-19 diagnosis. There was no association with insulin (adjusted HR 0.99, 95% CI 0.60, 1.64) or other diabetes medications (adjusted HR 0.71, 95% CI 0.38, 1.32).Conclusions and ImplicationsOur data suggest a reduction in 30-day mortality following SARS-CoV-2 infection in residents who were on metformin-containing diabetes regimens. These findings suggest a relative survival benefit in nursing home residents on metformin, potentially through its mTOR inhibition effects. A prospective study should investigate the therapeutic benefits of metformin among persons with COVID-19.     

Risk of COVID-19 and major adverse clinical outcomes among people with disabilities in South Korea

BackgroundEvidence regarding the risk of coronavirus disease (COVID-19) and the major adverse clinical outcomes of COVID-19 among people with disabilities (PwDs) is scarce.ObjectiveThis study investigated the association of disability status with the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test positivity and the risk of major adverse clinical outcomes among participants who tested positive for SARS-CoV-2.MethodsThis study included all patients (n = 8070) who tested positive for SARS-CoV-2 and individuals without COVID-19 (n = 121,050) in South Korea from January 1 to May 30, 2020. The study variables included officially registered disability status from the government, SARS-CoV-2 test positivity, and major adverse clinical outcomes of COVID-19 (admission to the intensive care unit, invasive ventilation, or death).ResultsThe study participants included 129,120 individuals (including 7261 PwDs), of whom 8070 (6.3%) tested positive for SARS-CoV-2. After adjusting for potential confounding factors, PwDs had an increased risk of SARS-CoV-2 test positivity compared with people without disabilities (odds ratio [OR]: 1.36, 95% confidence interval [CI]: 1.24–1.48). Among participants who tested positive for SARS-CoV-2, PwDs were associated with an increased risk of major adverse clinical outcomes from COVID-19 compared to those without disabilities (OR: 1.43, 95% CI: 1.11–1.86).ConclusionsPwDs had an increased risk of COVID-19 and major adverse clinical outcomes of COVID-19 compared with people without disabilities. Given the higher vulnerability of PwDs to COVID-19, tailored policy and management to protect against the risk of COVID-19 are required.     

Association between history of SARS-CoV-2 infection and severe systemic adverse events after mRNA COVID-19 vaccination among U.S. adults

BackgroundRisk of experiencing a systemic adverse event (AE) after mRNA coronavirus disease 2019 (COVID-19) vaccination may be greater among persons with a history of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection; data on serious events are limited. We assessed if adults reporting systemic AEs resulting in emergency department visits or hospitalizations during days 0–7 after mRNA COVID-19 vaccine dose 1 were more likely to have a history of prior SARS-CoV-2 infection compared with persons who reported no or non-severe systemic AEs.MethodsWe conducted a nested case-control study using v-safe surveillance data. Participants were ≥ 18 years and received dose 1 during December 14, 2020─May 9, 2021. Cases reported severe systemic AEs 0–7 days after vaccination. Three controls were frequency matched per case by age, vaccination date, and days since vaccination. Follow-up surveys collected SARS-CoV-2 histories.ResultsFollow-up survey response rates were 38.6 % (potential cases) and 56.8 % (potential controls). In multivariable analyses including 3,862 case-patients and 11,586 controls, the odds of experiencing a severe systemic AE were 2.4 (Moderna, mRNA-1273; 95 % confidence interval [CI]: 1.89, 3.09) and 1.5 (Pfizer-BioNTech, BNT162b2; 95 % CI: 1.17, 2.02) times higher among participants with pre-vaccination SARS-CoV-2 histories compared with those without. Medical attention of any kind for symptoms during days 0–7 following dose 2 was not common among case-patients or controls.ConclusionsHistory of SARS-CoV-2 infection was significantly associated with severe systemic AEs following dose 1 of mRNA COVID-19 vaccine; the effect varied by vaccine received. Most participants who experienced severe systemic AEs following dose 1 did not require medical attention of any kind for symptoms following dose 2. Vaccine providers can use these findings to counsel patients who had pre-vaccination SARS-CoV-2 infection histories, experienced severe systemic AEs following dose 1, and are considering not receiving additional mRNA COVID-19 vaccine doses.     

T-Cell Mediated Response after Primary and Booster SARS-CoV-2 Messenger RNA Vaccination in Nursing Home Residents

ObjectivesNursing home (NH) residents have been significantly affected by the coronavirus disease 2019 (COVID-19) pandemic. Studies addressing the immune responses induced by COVID-19 vaccines in NH residents have documented a good postvaccination antibody response and the beneficial effect of a third booster vaccine dose. Less is known about vaccine-induced activation of cell-mediated immune response in frail older individuals in the long term. The aim of the present study is to monitor messenger RNA SARS-CoV-2 vaccine-induced T-cell responses in a sample of Italian NH residents who received primary vaccine series and a third booster dose and to assess the interaction between T-cell responses and humoral immunity.DesignLongitudinal cohort study.Setting and ParticipantsThirty-four residents vaccinated with BNT162b2 messenger RNA SARS-CoV-2 vaccine between February and April 2021 and who received a third BNT162b2 booster dose between October and November 2021 were assessed for vaccine-induced immunity 6 (prebooster) and 12 (postbooster) months after the first BNT162b2 vaccine dose.MethodsPre- and postbooster cell-mediated immunity was assessed by intracellular cytokine staining of peripheral blood mononuclear cells stimulated in vitro with peptides covering the immunodominant sequence of SARS-CoV-2 spike protein. The simultaneous production of interferon-γ, tumor necrosis factor-α, and interleukin-2 was measured. Humoral immunity was assessed in parallel by measuring serum concentration of antitrimeric spike IgG antibodies.ResultsBefore the booster vaccination, 31 out of 34 NH residents had a positive cell-mediated immunity response to spike. Postbooster, 28 out of 34 had a positive response. Residents without a previous history of SARS-CoV-2 infection, who had a lower response prior the booster administration, showed a greater increase of T-cell responses after the vaccine booster dose. Humoral and cell-mediated immunity were, in part, correlated but only before booster vaccine administration.Conclusions and ImplicationsThe administration of the booster vaccine dose restored spike-specific T-cell responses in SARS-CoV-2 naïve residents who responded poorly to the first immunization, while a previous SARS-CoV-2 infection had an impact on the magnitude of vaccine-induced cell-mediated immunity at earlier time points. Our findings imply the need for a continuous monitoring of the immune status of frail NH residents to adapt future SARS-CoV-2 vaccination strategies.     

Immunogenicity and Safety of Intradermal Trivalent Influenza Vaccination in Nursing Home Older Adults: A Randomized Controlled Trial

ObjectiveTo compare the immunogenicity and safety between full-dose (15 μg) intramuscular (IM) and full-dose (15 μg) intradermal (ID) immunization of the trivalent influenza vaccine in nursing home older adults.DesignA single-center, randomized, controlled, open-label, parallel group trial from October 2013 to April 2014.SettingNine nursing homes in Hong Kong.ParticipantsHundred nursing home older adults (mean age: 82.9 ± 7.4 years).InterventionFifty received ID (Intanza) and 50 received IM (Vaxigrip) vaccination.MeasurementsBaseline measurements included demographics, comorbidity, frailty and nutritional status. Day 21 and day 180 immunogenicity (seroconversion rate, seroprotection rate, geometric mean titer [GMT] fold increase in antibody titer) using hemagglutination-inhibition and adverse events were measured. Noninferiority and superiority of ID compared with IM vaccination in immunogenicity were analyzed. The study was registered on ClinicalTrials.gov; identifier: NCT 01967368.ResultsAt day 21, noninferiority in immunogenicity of the ID vaccination was demonstrated. The seroconversion rate of the H1N1 strain was significantly higher in the ID group. At day 180, immunogenicity of both groups fell but the GMT of all strains in ID group was higher and the difference was significant for H3N2 strain. The seroconversion rate and GMT fold increase of H3N2 strain was significantly higher in the ID group. Local adverse events was significantly more in ID group, but they were mild and resolved in 72 hours.ConclusionsID vaccination is noninferior, and even superior in some parts of immunogenicity assessment, to IM vaccination without compromising safety in nursing home older adults. ID vaccination is a good alternative to IM vaccination in this population.     

Seropositivity to Nucleoprotein to detect mild and asymptomatic SARS-CoV-2 infections: A complementary tool to detect breakthrough infections after COVID-19 vaccination?

BackgroundWith COVID-19 vaccine roll-out ongoing in many countries globally, monitoring of breakthrough infections is of great importance. Antibodies persist in the blood after a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Since COVID-19 vaccines induce immune response to the Spike protein of the virus, which is the main serosurveillance target to date, alternative targets should be explored to distinguish infection from vaccination.MethodsMultiplex immunoassay data from 1,513 SARS-CoV-2 RT-qPCR-tested individuals (352 positive and 1,161 negative) without COVID-19 vaccination history were used to determine the accuracy of Nucleoprotein-specific immunoglobulin G (IgG) in detecting past SARS-CoV-2 infection. We also described Spike S1 and Nucleoprotein-specific IgG responses in 230 COVID-19 vaccinated individuals (Pfizer/BioNTech).ResultsThe sensitivity of Nucleoprotein seropositivity was 85% (95% confidence interval: 80–90%) for mild COVID-19 in the first two months following symptom onset. Sensitivity was lower in asymptomatic individuals (67%, 50–81%). Participants who had experienced a SARS-CoV-2 infection up to 11 months preceding vaccination, as assessed by Spike S1 seropositivity or RT-qPCR, produced 2.7-fold higher median levels of IgG to Spike S1 ≥ 14 days after the first dose as compared to those unexposed to SARS-CoV-2 at ≥ 7 days after the second dose (p = 0.011). Nucleoprotein-specific IgG concentrations were not affected by vaccination in infection-naïve participants.ConclusionsSerological responses to Nucleoprotein may prove helpful in identifying SARS-CoV-2 infections after vaccination. Furthermore, it can help interpret IgG to Spike S1 after COVID-19 vaccination as particularly high responses shortly after vaccination could be explained by prior exposure history.     

Neither Race nor Ethnicity Impact the Mortality of Residents of Veterans Affairs Community Living Center With COVID-19

ObjectivesCOVID-19 disproportionately affected nursing home residents and people from racial and ethnic minorities in the United States. Nursing homes in the Veterans Affairs (VA) system, termed Community Living Centers (CLCs), belong to a national managed care system. In the period prior to the availability of vaccines, we examined whether residents from racial and ethnic minorities experienced disparities in COVID-19 related mortality.DesignRetrospective cohort study.Setting and ParticipantsResidents at 134 VA CLCs from April 14 to December 10, 2020.MethodsWe used the VA Corporate Data Warehouse to identify VA CLC residents with a positive SARS-CoV-2 polymerase chain reaction test during or 2 days prior to their admission and without a prior case of COVID-19. We assessed age, self-reported race/ethnicity, frailty, chronic medical conditions, Charlson comorbidity index, the annual quarter of the infection, and all-cause 30-day mortality. We estimated odds ratios and 95% confidence intervals of all-cause 30-day mortality using a mixed-effects multivariable logistic regression model.ResultsDuring the study period, 1133 CLC residents had an index positive SARS-CoV-2 test. Mortality at 30 days was 23% for White non-Hispanic residents, 15% for Black non-Hispanic residents, 10% for Hispanic residents, and 16% for other residents. Factors associated with increased 30-day mortality were age ≥70 years, Charlson comorbidity index ≥6, and a positive SARS-CoV-2 test between April 14 and June 30, 2020. Frailty, Black race, and Hispanic ethnicity were not independently associated with an increased risk of 30-day mortality.Conclusions and ImplicationsAmong a national cohort of VA CLC residents with COVID-19, neither Black race nor Hispanic ethnicity had a negative impact on survival. Further research is needed to determine factors within the VA health care system that mitigate the influence of systemic racism on COVID-19 outcomes in US nursing homes.