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.     

Adverse Events Following One Dose of mRNA COVID-19 Vaccination Among US Nursing Home Residents With and Without a Previous SARS-CoV-2 Infection

ObjectivesTo compare rates of adverse events following Coronavirus Disease 2019 (COVID-19) vaccination among nursing home residents with and without previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.DesignProspective cohort.Setting and ParticipantsA total of 20,918 nursing home residents who received the first dose of messenger RNA COVID-19 vaccine from December 18, 2020, through February 14, 2021, in 284 facilities within Genesis Healthcare, a large nursing home provider spanning 24 US states.MethodsWe screened the electronic health record for adverse events, classified by the Brighton Collaboration, occurring within 15 days of a resident’s first COVID-19 vaccine dose. All events were confirmed by physician chart review. To obtain risk ratios, multilevel logistic regression model that accounted for clustering (variability) across nursing homes was implemented. To balance the probability of prior SARS-CoV-2 infection (previous positive test or diagnosis by the International Classification of Diseases, 10^th Revision, Clinical Modification) more than 20 days before vaccination, we used inverse probability weighting. To adjust for multiplicity of adverse events tested, we used a false discovery rate procedure.ResultsStatistically significant differences existed between those without (n = 13,163) and with previous SARS-CoV-2 infection [symptomatic (n = 5617) and asymptomatic (n = 2138)] for all baseline characteristics assessed. Only 1 adverse event was reported among those with previous SARS-CoV-2 infection (asymptomatic), venous thromboembolism [46.8 per 100,000 residents 95% confidence interval (CI) 8.3–264.5], which was not significantly different from the rate reported for those without previous infection (30.4 per 100,000 95% CI 11.8–78.1). Several other adverse events were observed for those with no previous infection, but were not statistically significantly higher than those reported with previous infection after adjustments for multiple comparisons.Conclusions and ImplicationsAlthough reactogenicity increases with preexisting immunity, we did not find that vaccination among those with previous SARS-CoV-2 infection resulted in higher rates of adverse events than those without previous infection. This study stresses the importance of monitoring novel vaccines for adverse events in this vulnerable population.     

Multisystem Inflammatory Syndrome in Children after SARS-CoV-2 Vaccination

Multisystem inflammatory syndrome in children (MIS-C) is a hyperinflammatory state that occurs after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We present 2 cases of MIS-C after SARS-CoV-2 vaccination; 1 patient had evidence of recent SARS-CoV-2 infection. Our findings suggest that vaccination modulates the pathogenesis of MIS-C.     

SARS-CoV-2 and Wisconsin Nursing Homes: Temporal Dynamics During the COVID-19 Pandemic

ObjectivesEvidence suggests that quality, location, and staffing levels may be associated with COVID-19 incidence in nursing homes. However, it is unknown if these relationships remain constant over time. We describe incidence rates of COVID-19 across Wisconsin nursing homes while examining factors associated with their trajectory during 5 months of the pandemic.DesignRetrospective cohort study.Setting/ParticipantsWisconsin nursing homes.MethodsPublicly available data from June 1, 2020, to October 31, 2020, were obtained. These included facility size, staffing, 5-star Medicare rating score, and components. Nursing home characteristics were compared using Pearson chi-square and Kruskal-Wallis tests. Multiple linear regressions were used to evaluate the effect of rurality on COVID-19.ResultsThere were a total of 2459 COVID-19 cases across 246 Wisconsin nursing homes. Number of beds (P < .001), average count of residents per day (P < .001), and governmental ownership (P = .014) were associated with a higher number of COVID-19 cases. Temporal analysis showed that the highest incidence rates of COVID-19 were observed in October 2020 (30.33 cases per 10,000 nursing home occupied-bed days, respectively). Urban nursing homes experienced higher incidence rates until September 2020; then incidence rates among rural nursing homes surged. In the first half of the study period, nursing homes with lower-quality scores (1-3 stars) had higher COVID-19 incidence rates. However, since August 2020, incidence was highest among nursing homes with higher-quality scores (4 or 5 stars). Multivariate analysis indicated that over time rural location was associated with increased incidence of COVID-19 (β = 0.05, P = .03).Conclusions and ImplicationsHigher COVID-19 incidence rates were first observed in large, urban nursing homes with low-quality rating. By October 2020, the disease had spread to rural and smaller nursing homes and those with higher-quality ratings, suggesting that community transmission of SARS-CoV-2 may have propelled its spread.     

Multisystem Inflammatory Syndrome after SARS-CoV-2 Infection and COVID-19 Vaccination

We report 3 patients in California, USA, who experienced multisystem inflammatory syndrome (MIS) after immunization and severe acute respiratory syndrome coronavirus 2 infection. During the same period, 3 adults who were not vaccinated had MIS develop at a time when ≈7% of the adult patient population had received >1 vaccine.     

Incidence and Outcomes of SARS-CoV-2 in Post-Acute Skilled Nursing Facility Care

ObjectivesTo examine the risk of contracting SARS-CoV-2 during a post-acute skilled nursing facility (SNF) stay and the associated risk of death.DesignCohort study using Minimum Data Set and electronic health record data from a large multistate long-term care provider. Primary outcomes included testing positive for SARS-CoV-2 during the post-acute SNF stay, and death among those who tested positive.Setting and ParticipantsThe sample included all new admissions to the provider's 286 SNFs between January 1 and December 31, 2020. Patients known to be infected with SARS-CoV-2 at the time of admission were excluded.MethodsSARS-CoV-2 infection and mortality rates were measured in time intervals by month of admission. A parametric survival model with SNF random effects was used to measure the association of patient demographic factors, clinical characteristics, and month of admission, with testing positive for SARS-CoV-2.ResultsThe sample included 45,094 post-acute SNF admissions. Overall, 5.7% of patients tested positive for SARS-CoV-2 within 100 days of admission, with 1.0% testing positive within 1-14 days, 1.4% within 15-30 days, and 3.4% within 31-100 days. Of all newly admitted patients, 0.8% contracted SARS-CoV-2 and died, whereas 6.7% died without known infection. Infection rates and subsequent risk of death were highest for patients admitted during the first and third US pandemic waves. Patients with greater cognitive and functional impairment had a 1.45 to 1.92 times higher risk of contracting SARS-CoV-2 than patients with less impairment.Conclusions and ImplicationsThe absolute risk of SARS-CoV-2 infection and death during a post-acute SNF admission was 0.8%. Those who did contract SARS-CoV-2 during their SNF stay had nearly double the rate of death as those who were not infected. Findings from this study provide context for people requiring post-acute care, and their support systems, in navigating decisions around SNF admission during the SARS-CoV-2 pandemic.     

Decomposing Racial and Ethnic Disparities in Nursing Home Influenza Vaccination

ObjectivesQuantify how observable characteristics contribute to influenza vaccination disparities among White, Black, and Hispanic nursing home (NH) residents.DesignRetrospective cohort.Setting and ParticipantsShort- and long-stay U.S. NH residents aged ≥65 years.MethodsWe linked Minimum Data Set (MDS) and Medicare data to LTCFocUS and other facility data. We included residents with 6-month continuous enrollment in Medicare and an MDS assessment between October 1, 2013, and March 31, 2014. Residents were classified as short-stay (<100 days in NH) or long-stay (≥100 days in NH). We fit multivariable logistic regression models to assess the relationships between 27 resident and NH-level characteristics and receipt of influenza vaccination. Using nonlinear Oaxaca-Blinder decomposition, we decomposed the disparity in influenza vaccination between White versus Black and White versus Hispanic NH residents. Analyses were repeated separately for short- and long-stay residents.ResultsOur study included 630,373 short-stay and 1,029,593 long-stay residents. Proportions vaccinated against influenza included 67.2% of White, 55.1% of Black, and 54.5% of Hispanic individuals among short-stay residents and 84.2%, 76.7%, and 80.8%, respectively among long-stay residents. Across 4 comparisons, the crude disparity in influenza vaccination ranged from 3.4 to 12.7 percentage points. By equalizing 27 prespecified characteristics, these disparities could be reduced 37.7% to 59.2%. Living in a predominantly White facility and proxies for NH quality were important contributors across all analyses. Characteristics unmeasured in our data (eg, NH staff attitudes and beliefs) may have also contributed significantly to the disparity.Conclusions and ImplicationsThe racial/ethnic disparity in influenza vaccination was most dramatic among short-stay residents. Intervening on factors associated with NH quality would likely reduce these disparities; however, future qualitative research is essential to explore potential contributors that were unmeasured in our data and to understand the degree to which these factors contribute to the overall disparity in influenza vaccination.     

Fatal Systemic Capillary Leak Syndrome after SARS-CoV-2Vaccination in Patient with Multiple Myeloma

A young man with smoldering multiple myeloma died of hypotensive shock 2.5 days after severe acute respiratory syndrome coronavirus 2 vaccination. Clinical findings suggested systemic capillary leak syndrome (SCLS); the patient had experienced a previous suspected flare episode. History of SCLS may indicate higher risk for SCLS after receiving this vaccine.     

Evidence on the Effects of the Federal COVID-19 Vaccine Mandate on Nursing Home Staffing Levels

ObjectiveTo assess the federal COVID-19 vaccine mandate's effects on nursing homes' nurse aide and licensed nurse staffing levels in states both with and without state-level vaccine mandates.DesignCross-sectional study using data from Centers for Medicare and Medicaid Services, Centers for Disease Control and Prevention, and Economic Innovation Group. Including nursing home facility fixed effects provides evidence on the intertemporal effects of the federal vaccine mandate within nursing homes.Setting and ParticipantsThe sample contains 15,031 nursing homes, representing all US nursing homes with available data.MethodsOn January 13, 2022, the US Supreme Court upheld the federal COVID-19 vaccine mandate for health care workers in Medicare- and Medicaid-eligible facilities, with workers generally required to be vaccinated by March 20, 2022 (ie, the compliance date). We examined actual nursing home staffing levels in 3 time periods: (1) pre-Court decision; (2) precompliance date; and (3) postcompliance date. We separately examined staffing levels for nurse aides and licensed nursing staff. Because 28% of nursing homes were in states with state-imposed vaccine mandates that predated the Supreme Court's ruling, we divided the sample into 2 groups (nursing homes in mandate states vs nonmandate states) and performed all analyses separately.ResultsStaff vaccination rates and staffing levels were higher in mandate states than nonmandate states in all 3 time periods. After the Court's decision, staff vaccination rates increased 5% in nonmandate states and 1% in mandate states (on average). We find little evidence that the Court's vaccine mandate ruling materially affected nurse aide and licensed nurse staffing levels, or that nursing homes in mandate states and nonmandate states were differentially affected by the Court's ruling. Staffing levels over time were generally flat, with some evidence of a modestly greater increase for nurse aide staffing in mandate states than nonmandate states, and a modestly smaller decrease for licensed nurse staffing in mandate states than nonmandate states. Finally, regression results suggest that for both nurse aides and licensed nurses, staffing levels were lower in rural and for-profit nursing homes, and higher in Medicare-only, higher quality, and hospital-based nursing homes.Conclusions and ImplicationsResults suggest the federal COVID-19 vaccine mandate has not caused clinically material changes in nursing home's nurse aide and licensed nurse staffing levels, which continue to be primarily associated with factors that are well-known to researchers and practitioners.     

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.     

A Proactive Nursing Home Risk Stratification Model for Disaster Response: Lessons Learned from COVID-19 to Optimize Resource Allocation

A coordinated emergency management response to disaster management in nursing homes is desperately needed globally.During the most recent COVID-19 pandemic, aside from a few exemplary countries, most countries have struggled to protect their nursing home populations. Timely and appropriate allocation of resources to nursing homes during disaster response is a challenging yet crucial task to prevent morbidity and mortality of residents.The responsibility for the management of nursing homes during the pandemic was multifaceted, and responsibilities lay at the national, jurisdictional, and regional levels. Success in managing COVID-19 in nursing homes required all these levels to be aligned and supportive, ideally through management by an emergency response leadership team. However, globally there is a paucity of effective management strategies.This article uses the example of the COVID-19 pandemic to propose a risk stratification system to ensure timely and appropriate allocation of resources to nursing homes during disaster preparation and management. Nursing homes should be risk-stratified according to 4 domains: risk of intrusion, capability for outbreak containment, failure in organizational capability, and failure in the availability of community and health care supports. Risk stratification should also consider factors such as current levels of community transmission, if applicable, and geographic location of nursing homes and services.Early identification of nursing homes at risk for infectious disease, or disasters, and targeted allocation of resources might help reduce the number of outbreaks, lower the mortality, and preserve community supports such as acute hospital services. The next step is to debate this concept to validate the selected variables and then develop and pilot test a risk stratification tool for use.     

Increase in Frailty in Nursing Home Survivors of Coronavirus Disease 2019: Comparison With Noninfected Residents

ObjectivesInstitutionalized older adults have a high prevalence of frailty and disability, which may make them more vulnerable to the negative consequences of coronavirus disease 2019 (COVID-19). We investigated the impact of COVID-19 on the level of frailty, physical, and cognitive performance in nursing home residents.DesignNested case-control study.Setting and ParticipantsThe study included nursing home residents who were infected with COVID-19 (case group, n = 76), matched by age to a control group (n = 76).MethodsParticipants’ sociodemographic and medical data were collected, and they were also assessed for physical function (handgrip and walking speed), cognitive performance (Mini-Mental State Examination) and frailty (Frail-NH scale) before the first wave of the COVID-19 pandemic (October to December 2019, pre-COVID-19) and after (June to July 2020, post-COVID-19). COVID-19 symptoms and clinical course were recorded for the cases.ResultsBetween the pre- and post-COVID-19 assessments, we found a 19% greater deterioration in handgrip, a 22% greater decrease in walking speed, and a 21% greater increase in Frail-NH scores in cases compared with controls. In both cases and controls, on the other hand, there was a significant 10% decrease in Mini-Mental State Examination scores over the study period. Multivariable logistic regression showed that COVID-19 survivors had a 4-fold increased chance of developing frailty compared with controls (odds ratio 4.95, 95% confidence interval 1.13–21.6, P = .03), but not cognitive decline.Conclusions and ImplicationsCOVID-19 can accelerate the aging process of institutionalized older adults in terms of physical performance and frailty by around 20%. However, we found similar levels of decline in cognitive performance in both cases and controls, likely because of the burden of social isolation and containment measures on neuropsychological health.     

Delayed Antibody and T-Cell Response to BNT162b2 Vaccination in the Elderly,Germany

We detected delayed and reduced antibody and T-cell responses after BNT162b2 vaccination in 71 elderly persons (median age 81 years) compared with 123 healthcare workers (median age 34 years) in Germany. These data emphasize that nonpharmaceutical interventions for coronavirus disease remain crucial and that additional immunizations for the elderly might become necessary.     

Type 1 Diabetes Mellitus Associated with Nivolumab after Second SARS-CoV-2 Vaccination,Japan

Recently, along with increasing use of immune checkpoint inhibitors such as nivolumab, the incidence of immune-related adverse events, including type 1 diabetes mellitus, has become a serious problem. We report a patient who had immune checkpoint inhibitor‒associated type 1 diabetes mellitus that developed after a second mRNA-based SARS-CoV-2 vaccination.     

One-year dynamics of antibody titers after three doses of SARS-CoV-2 BNT162b2 vaccine

BackgroundA third dose of the BNT162b2 SARS-CoV-2 vaccine leads to a significant increase in antibody levels, however, concerns regarding the long-term persistence of this response exist. We assessed the humoral response for one year following vaccination.MethodsA prospective study among immunocompetent healthcare workers (HCW) who received three doses of BNT162b2. anti-spike antibody titers were measured at six predefined timepoints, from before the second vaccine dose, and up to one year afterwards, which is 4–6 months after the third dose. HCW with a history of SARS-CoV-2 infection were excluded.ResultsSeventy-six HCW had all the six serological measurements. Antibody titers significantly increased shortly following the third vaccine dose, and while declining, remained higher from all previous measurements for up to six months.ConclusionsA third dose of BNT162b2 leads to a profound humoral response, which remains significantly higher than previous measurements, even after 6 months.     

Humoral response to the SARS-CoV-2 BNT162b2 mRNA vaccine: Real-world data from a large cohort of healthcare workers

BackgroundThe SARS-CoV-2 pandemic was responsible for the death of millions of people around the world, which accelerated the study of vaccines. The BNT162b2 mRNA COVID-19 is a messenger RNA vaccine that encodes the spike protein of the virus. However, the duration of the protection conferred by this vaccine and factors associated with immune responses require validation in large cohorts.MethodsHere, we present data of humoral immune response to vaccination in 4264 healthcare workers, tested before (T0) and 15 and 90 days (T1 and T2, respectively) following vaccination. Peripheral blood was collected for immunological analysis using the Quant SARS-CoV-2 IgG II Chemiluminescent Microparticle Immunoassay (CMIA) to determine anti-spike IgG, receptor binding domain (RBD), S1 subunit of SARS-CoV-2.FindingsAt T0, 96·8% (n = 4129) of participants had IgG antibodies non-reactive to anti-SARS-CoV-2. Fifteen days after completing the vaccination, the IgG overall median titer was significantly elevated (21·7x10³ AU/mL). Both for uni- and multivariate logistic regression analyses women presented higher antibody levels than men, independent of age. Titers were significantly altered among age groups, decreasing by each increase in 10-year of age. At 3 months after completing the vaccination, anti-SARS-CoV-2 IgG titers were 6·3-fold diminished.This real-world post-vaccination data confirmed production of a frequent and elevated anti-SARS-CoV-2 IgG titers, associated with high protection rates. Females and younger participants had higher titer 15 days after vaccination, and despite the significant reduction from 15-to-90 days, those with higher pre-vaccination titers maintained higher levels throughout the remaining timepoints.InterpretationThese findings support the need to track humoral immunity kinetics to uncover viral susceptibility and eventually implement re-vaccination, particularly in groups prone to lower humoral immune response.FundingNo external funding was received to conduct this study.     

Protective Effects of Lactoferrin against SARS-CoV-2 Infection In Vitro

SARS-CoV-2 is a newly emerging virus that currently lacks curative treatments. Lactoferrin (LF) is a naturally occurring non-toxic glycoprotein with broad-spectrum antiviral, immunomodulatory and anti-inflammatory effects. In this study, we assessed the potential of LF in the prevention of SARS-CoV-2 infection in vitro. Antiviral immune response gene expression was analyzed by qRT-PCR in uninfected Caco-2 intestinal epithelial cells treated with LF. An infection assay for SARS-CoV-2 was performed in Caco-2 cells treated or not with LF. SARS-CoV-2 titer was determined by qRT-PCR, plaque assay and immunostaining. Inflammatory and anti-inflammatory cytokine production was determined by qRT-PCR. LF significantly induced the expression of IFNA1, IFNB1, TLR3, TLR7, IRF3, IRF7 and MAVS genes. Furthermore, LF partially inhibited SARS-CoV-2 infection and replication in Caco-2 intestinal epithelial cells. Our in vitro data support LF as an immune modulator of the antiviral immune response with moderate effects against SARS-CoV-2 infection.     

Fatal Multisystem Inflammatory Syndrome in Adult after SARS-CoV-2 Natural Infection and COVID-19 Vaccination

We describe a fatal case of multisystem inflammatory syndrome in an adult with onset 22 days after a second dose of mRNA coronavirus disease vaccine. Serologic and clinical findings indicated severe acute respiratory syndrome coronavirus 2 infection occurred before vaccination. The immunopathology of this syndrome, regardless of vaccination status, remains poorly understood.