Immunogenicity after 6 months of BNT162b2 vaccination in frail or disabled nursing home residents: The COVID-A Study.

BACKGROUND: There is incomplete information regarding evolution of antibody titers against SARS-CoV-2 after a two-dose strategy vaccination with BNT162b2 in older adults in long-term care facilities (LTCFs) with frailty, disability, or cognitive impairment. We aimed to determine IgG antibody titer loss in older adults in LTCFs. METHODS: This is a multicenter longitudinal cohort study including 127 residents (90 females and 37 males) with a mean age of 82.7 years (range 65-99) with different frailty and disability profiles in two LTCFs in Albacete, Spain. Residents received two doses of BNT162b2 as per label, and antibody levels were determined 1 and 6 months after the second dose. Age, sex, previous history of coronavirus disease 2019 (COVID-19), comorbidity (Charlson Index), performance in activities of daily living (Barthel Index), frailty (FRAIL instrument), and cognitive status were assessed. RESULTS: The mean antibody titers 1 and 6 months after the second vaccine dose were 32,145 AU/ml (SD 41,206) and 6182 AU/ml (SD 13,316), respectively. Across all participants, the median antibody titer loss measured 77.6% (interquartile range [IQR] 23.8%). Notably, the decline of titers in individuals with pre-vaccination COVID-19 infection was significantly lower than in those without a history of SARS-CoV-2 infection (72.2% vs. 85.3%; p < 0.001). The median titer decrease per follow-up day was 0.47% (IQR 0.14%) and only pre-vaccination COVID-19 was associated with lower rate of antibody decline at 6 months (hazard ratio 0.17; 95% confidence interval 0.07-0.41; p < 0.001). Frailty, disability, older age, cognitive impairment, or comorbidity were not associated with the extent of antibody loss. CONCLUSIONS: Older adults in LTCFs experience a rapid loss of antibodies over the first 6 months after the second dose of BNT162b2 vaccine. Only pre-vaccination COVID-19 is associated with a slower rate of antibody decrease. Our data support immunization with a third dose in this vulnerable, high-risk population.

Psychological and Functional Impact of COVID-19 in Long-Term Care Facilities: The COVID-A Study.

OBJECTIVE: To analyze the psychological and functional sequelae of the COVID-19 pandemic among older adults living in long term care facilities (LTCFs). DESIGN: Cohort longitudinal study SETTING ANT PARTICIPANTS: A total of 215 residents ≥ 65 years without moderate-to-severe cognitive impairment, living in five LTCFs in Albacete (Spain). MEASUREMENTS: Baseline on-site data were collected between March - June 2020 and three-month follow-up between June to September 2020. Symptoms of depression, anxiety, posttraumatic stress disorder (PTSD), and sleep disturbances were measured as psychological variables. Disability in basic activities of daily living (BADL), ambulation and frailty were assessed as functional variables. Differences were analyzed in relation to level of comorbidity and test positivity for COVID-19. RESULTS: At baseline, residents with COVID-19 presented worse functionality, higher frailty levels and malnutrition risk compared to non-COVID-19 residents. At three-month follow-up, higher rates of clinically significant depressive symptoms (57.7%), anxiety symptoms (29.3%), PTSD symptoms (19.1%) and sleep disturbances (93.0%) were found among residents regardless of COVID status. Thus, among 215 residents, 101 (47%) experienced a decline in BADL from baseline to the 3-month follow-up (median functional loss = 5 points in Barthel Index). In multivariate analyses, COVID-19 status did not explain either the functional or the ambulation loss. By contrast, residents with low comorbidity and COVID-19 presented higher PTSD symptoms (effect 2.58; 95% CI 0.93 to 4.23) and anxiety symptoms (effect 2.10; 95% CI 0.48 to 3.73) compared to the low comorbidity/non-COVID19 group. CONCLUSION: COVID-19 pandemic was associated, after three-months, with high psychological impact in older adults in LTCFs., specifically with higher post-traumatic stress and anxiety symptoms. Functional decline did not differ in relation to COVID-19 status but could be related to isolation strategies used for pandemic control.

JAK inhibition reduces SARS-CoV-2 liver infectivity and modulates inflammatory responses to reduce morbidity and mortality.

Using AI, we identified baricitinib as having antiviral and anticytokine efficacy. We now show a 71% (95% CI 0.15 to 0.58) mortality benefit in 83 patients with moderate-severe SARS-CoV-2 pneumonia with few drug-induced adverse events, including a large elderly cohort (median age, 81 years). An additional 48 cases with mild-moderate pneumonia recovered uneventfully. Using organotypic 3D cultures of primary human liver cells, we demonstrate that interferon-α2 increases ACE2 expression and SARS-CoV-2 infectivity in parenchymal cells by greater than fivefold. RNA-seq reveals gene response signatures associated with platelet activation, fully inhibited by baricitinib. Using viral load quantifications and superresolution microscopy, we found that baricitinib exerts activity rapidly through the inhibition of host proteins (numb-associated kinases), uniquely among antivirals. This reveals mechanistic actions of a Janus kinase-1/2 inhibitor targeting viral entry, replication, and the cytokine storm and is associated with beneficial outcomes including in severely ill elderly patients, data that incentivize further randomized controlled trials.

COVID-19 outbreak in long-term care facilities from Spain. Many lessons to learn.

BACKGROUND/OBJECTIVES: To analyze mortality, costs, residents and personnel characteristics, in six long-term care facilities (LTCF) during the outbreak of COVID-19 in Spain. DESIGN: Epidemiological study. SETTING: Six open LTCFs in Albacete (Spain). PARTICIPANTS: 198 residents and 190 workers from LTCF A were included, between 2020 March 6 and April 5. Epidemiological data were also collected from six LTCFs of Albacete for the same period of time, including 1,084 residents. MEASUREMENTS: Baseline demographic, clinical, functional, cognitive and nutritional variables were collected. 1-month and 3-month mortality was determined, excess mortality was calculated, and costs associated with the pandemics were analyzed. RESULTS: The pooled mortality rate for the first month and first three months of the outbreak were 15.3% and 28.0%, and the pooled excess mortality for these periods were 564% and 315% respectively. In facility A, the percentage of probable COVID-19 infected residents were 33.6%. Probable infected patients were older, frail, and with a worse functional situation than those without COVID-19. The most common symptoms were fever, cough and dyspnea. 25 residents were transferred to the emergency department, 21 were hospitalized, and 54 were moved to the facility medical unit. Mortality was higher upon male older residents, with worse functionality, and higher comorbidity. During the first month of the outbreak, 65 (24.6%) workers leaved, mainly with COVID-19 symptoms, and 69 new workers were contracted. The mean number of days of leave was 19.2. Costs associated with the COVID-19 in facility A were estimated at € 276,281/month, mostly caused by resident hospitalizations, leaves of workers, staff replacement, and interventions of healthcare professionals. CONCLUSION: The COVID-19 pandemic posed residents at high mortality risk, mainly in those older, frail and with worse functional status. Personal and economic costs were high.