Using AI we identified baricitinib as possessing anti-viral and anti-cytokine efficacy. We now show a 71% (95% CI 0.15-0.58) 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). A further 48 cases with mild-moderate pneumonia recovered uneventfully. Using organotypic 3D cultures of primary human liver cells, we demonstrate that interferon-alpha-2 (IFNα2) significantly increases ACE2 expression and SARS-CoV-2 infectivity in parenchymal cells by >5-fold. RNA-Seq reveals gene response signatures associated with platelet activation, fully inhibited by baricitinib. Using viral load quantifications and super-resolution microscopy, baricitinib exerts activity rapidly through the inhibition of host proteins (numb associated kinases), uniquely amongst anti-virals. 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 incentivizes further randomized controlled trials.

Background/Objectives The safety and immunogenicity of the BNT162b2 coronavirus disease 2019 (COVID‐19) vaccine in older adults with different frailty and disability profiles have not been well determined. Our objective was to analyze immunogenicity of the BNT162b2 mRNA COVID‐19 vaccine in older adults across frailty and disability profiles. Design Multicenter longitudinal cohort study. Setting and participants A total of 134 residents aged ≥65 years with different frailty and disability profiles in five long‐term care facilities (LTCFs) in Albacete, Spain. Intervention and measurements Residents were administered two vaccine doses as per the label, and antibody levels were determined 21.9 days (SD 9.3) after both the first and second dose. Functional variables were assessed using activities of daily living (Barthel Index), and frailty status was determined with the FRAIL instrument. Cognitive status and comorbidity were also evaluated. Results Mean age was 82.9 years (range 65–99), and 71.6% were female. The mean antibody titers in residents with and without previous COVID‐19 infection were 49,878 AU/ml and 15,274 AU/ml, respectively (mean difference 34,604; 95% confidence interval [CI]: 27,699–41,509). No severe adverse reactions were observed, after either vaccine dose. Those with prevaccination COVID‐19 had an increased antibody level after the vaccine (B = 31,337; 95% CI: 22,725–39,950; p < 0.001). Frailty, disability, older age, sex, cognitive impairment, or comorbidities were not associated with different antibody titers. Conclusions The BNT162b2 mRNA COVID‐19 vaccine in older adults is safe and produces immunogenicity, independently of the frailty and disability profiles. Older adults in LTCFs should receive a COVID‐19 vaccine.

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.

Background: Older adults are at the highest risk of severe disease and death due to COVID-19. Randomized data have shown that baricitinib improves outcomes in these patients, but focused stratified analyses of geriatric cohorts are lacking. Our objective was to analyze the efficacy of baricitinib in older adults with COVID-19 moderate-to-severe pneumonia. Methods: This is a propensity score [PS]-matched retrospective cohort study. Patients from the COVID-AGE and Alba-Score cohorts, hospitalized for moderate-to-severe COVID-19 pneumonia, were categorized in two age brackets of age <70 years old (86 with baricitinib and 86 PS-matched controls) or ≥70 years old (78 on baricitinib and 78 PS-matched controls). Thirty-day mortality rates were analyzed with Kaplan-Meier and Cox proportional hazard models.

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 : 215 residents ≥ 65 years without moderate-to-severe cognitive impairmen, 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 - 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, among215 residents, 101 (47%) experienced a decline in BADL from baseline to the three-month follow-up (median functional loss = 5 points in Barthel Index). In multivariate analyses, COVID-19 statusdid 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. Conclusions : 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.