The specialized pro-resolving lipid mediator Protectin D1 affects macrophages differentiation and activity in Adult-onset Still's disease and COVID-19, two hyperinflammatory diseases sharing similar transcriptomic profiles.

Introduction: COVID-19 and autoinflammatory diseases, such as Adult-onset Still's Disease (AOSD), are characterized by hyperinflammation, in which it is observed massive production and uncontrolled secretion of pro-inflammatory cytokines. The specialized pro-resolving lipid mediators (SPMs) family is one the most important processes counteracting hyperinflammation inducing tissue repair and homeostasis restoration. Among SPMs, Protectin D1 (PD1) is able to exert antiviral features, at least in animal models. The aim of this study was to compare the transcriptome of peripheral blood mononuclear cells (PBMCs) from patients with AOSD and COVID-19 and to evaluate the role of PD1 on those diseases, especially in modulating macrophages polarization. Methods: This study enrolled patients with AOSD, COVID-19, and healthy donors HDs, undergoing clinical assessment and blood sample collection. Next-generation deep sequencing was performed to identify differences in PBMCs transcripts profiles. Plasma levels of PD1 were assessed by commercial ELISA kits. Monocyte-derived macrophages were polarized into M1 and M2 phenotypes. We analyzed the effect of PD1 on macrophages differentiation. At 10 days, macrophages were analyzed for surface expression of subtypes markers by flow cytometry. Cytokines production was measured in supernatants by Bio-Plex Assays. Results: In the transcriptomes from AOSD patients and COVID-19 patients, genes involved in inflammation, lipid catabolism, and monocytes activation were specifically dysregulated in AOSD and COVID-19 patients when compared to HDs. Patients affected by COVID-19, hospitalized in intensive care unit (ICU), showed higher levels of PD1 when compared to not-ICU hospitalized patients and HDs (ICU COVID-19 vs not-ICU COVID-19, p= 0.02; HDs vs ICU COVID-19, p= 0.0006). PD1 levels were increased in AOSD patients with SS ≥1 compared to patients with SS=0 (p=0.028) and HDs (p=0.048). In vitro treatment with PD1 of monocytes-derived macrophages from AOSD and COVID-19 patients induced a significant increase of M2 polarization vs control (p<0.05). Furthermore, a significant release of IL-10 and MIP-1ß from M2 macrophages was observed when compared to controls (p<0.05). Discussion: PD1 is able to induce pro-resolutory programs in both AOSD and COVID-19 increasing M2 polarization and inducing their activity. In particular, PD1-treated M2 macrophages from AOSD and COVID-19 patients increased the production of IL-10 and enhanced homeostatic restoration through MIP-1ß production.

Handgrip Strength Test and Bioelectrical Impedance Analysis in SARS-CoV-2 Patients Admitted to Sub-Intensive Unit.

Hospitalized patients with respiratory failure due to SARS-CoV-2 pneumonia are at increased risk of malnutrition and related mortality. The predictive value of the Mini-Nutritional Assessment short form (MNA-sf®), hand-grip strength (HGS), and bioelectrical impedance analysis (BIA) was determined with respect to in-hospital mortality or endotracheal intubation. The study included 101 patients admitted to a sub-intensive care unit from November 2021 to April 2022. The discriminative capacity of MNA-sf, HGS, and body composition parameters (skeletal mass index and phase angle) was assessed computing the area under the receiver operating characteristic curves (AUC). Analyses were stratified by age groups (<70/70+ years). The MNA-sf alone or in combination with HGS or BIA was not able to reliably predict our outcome. In younger participants, HGS showed a sensitivity of 0.87 and a specificity of 0.54 (AUC: 0.77). In older participants, phase angle (AUC: 0.72) was the best predictor and MNA-sf in combination with HGS had an AUC of 0.66. In our sample, MNA- sf alone, or in combination with HGS and BIA was not useful to predict our outcome in patients with COVID-19 pneumonia. Phase angle and HGS may be useful tools to predict worse outcomes in older and younger patients, respectively.

Sex differences in the efficacy and safety of SARS-CoV-2 vaccination in residents of long-term care facilities: insights from the GeroCovid Vax study.

Despite the reported sex-related variations in the immune response to vaccination, whether the effects of SARS-CoV-2 vaccination differ by sex is still under debate, especially considering old vulnerable individuals, such as long-term care facilities (LTCFs) residents. This study aimed to evaluate COVID-19 infections, adverse events, and humoral response after vaccination in a sample of LTCF residents. A total of 3259 LTCF residents (71% females; mean age: 83.4 ± 9.2 years) were enrolled in the Italian-based multicenter GeroCovid Vax study. We recorded the adverse effects occurring during the 7 days after vaccine doses and COVID-19 cases over 12 months post-vaccination. In a subsample of 524 residents (69% females), pre- and post-vaccination SARS-CoV-2 trimeric S immunoglobulin G (Anti-S-IgG) were measured through chemiluminescent assays at different time points. Only 12.1% of vaccinated residents got COVID-19 during the follow-up, without any sex differences. Female residents were more likely to have local adverse effects after the first dose (13.3% vs. 10.2%, p = 0.018). No other sex differences in systemic adverse effects and for the following doses were recorded, as well as in anti-S-IgG titer over time. Among the factors modifying the 12-month anti-S-IgG titers, mobility limitations and depressive disorder were more likely to be associated with higher and lower levels in the antibody response, respectively; a significantly lower antibody titer was observed in males with cardiovascular diseases and in females with diabetes or cognitive disorders. The study suggests that, among LTCF residents, SARS-CoV-2 vaccination was effective regardless of sex, yet sex-specific comorbidities influenced the antibody response. Local adverse reactions were more common in females.

Incidence and Outcome of Pneumomediastinum in Non-ICU Hospitalized COVID-19 Patients.

OBJECTIVES: Pneumomediastinum (PNM) is a rare complication of mechanical ventilation, but its reported occurrence in patients with acute respiratory distress syndrome secondary to COVID-19 is significant. The objective is to determine the incidence, risk factors, and outcome of PNM in non-ICU hospitalized patients with severe-to-critical COVID-19 pneumonia. DESIGN: Retrospective observational study. SETTING: Population-based, single-setting, tertiary-care level COVID treatment center. PATIENTS: Individuals hospitalized with a diagnosis of COVID-19 pneumonia and severe to critical illness were included. Those hospitalized without respiratory failure, observed for less than 24 hours, or admitted from an ICU were excluded. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: All patients underwent a complete clinical assessment and chest CT scan, and were followed up from hospitalization to discharge or death. The outcome was the number of cases of PNM, defined as the presence of free air in the mediastinal tissues diagnosed by chest CT scan, in non-ICU hospitalized patients and the subsequent risk of intubation and mortality. PNM occurred in 48 out of 331 participants. The incidence was 14.5% (95% CI, 10.9-18.8%). A CT-Scan Severity score greater than 15 was positively associated with PNM (odds ratio [OR], 4.09; p = 0.002) and was observed in 35.2% of the participants (95% CI, 26.2-44.9%). Noninvasive ventilation was also positively associated with PNM (OR, 4.46; p = 0.005), but there was no positive association with airway pressures. Fifty patients (15%) were intubated, and 88 (27%) died. Both the risk for intubation and mortality were higher in patients with PNM, with a hazard ratio of 3.72 (p < 0.001) and 3.27 (p < 0.001), respectively. CONCLUSIONS: Non-ICU hospitalized patients with COVID-19 have a high incidence of PNM, increasing the risk for intubation and mortality three- to four-fold, particularly in those with extensive lung damage. These findings help define the risk and outcome of PNM in severe-to-critical COVID-19 pneumonia in a non-ICU setting.

Frailty and hyperactive delirium in hospitalized older patients with COVID-19: an insight from GeroCovid registry.

BACKGROUND: Delirium is an acute neuropsychiatric condition associated with unfavourable outcomes, frequent in older hospitalized people. In the context of the SARS-CoV-2 pandemic, few studies have specifically focused on the inflammatory status of older, frail patients with hyperactive delirium (HD) hospitalized for COVID-19. AIM: To identify biological correlates of HD at hospital admission and to assess the independent effect of delirium and physical frailty on in-hospital mortality. METHODS: Data were retrospectively extracted by the multicenter registry GeroCovid Observational Study. Individuals aged ≥ 60 years were included if the information on the presence of HD, frailty based on the modified Fried criteria and inflammatory status had been collected. The risk of mortality was evaluated using a Kaplan-Meier estimator, according to frailty and delirium. Logistic and restricted cubic-spline regressions were employed to assess the relationship between inflammatory markers and HD. RESULTS: Three-hundred-thirty-seven older adults were included in the analysis [mean age (SD) 77.1 (9.5) years, 50.1% females], and 11.5% presented with HD. A significant association of both PaO2/FiO2 ratio (p = 0.015) and serum lactate dehydrogenase (p = 0.04) with delirium was observed. By Cox multivariable regression, frail and non-frail patients with HD had a 4.42 and 2.85 higher mortality risk compared with non-frail, non-delirious patients. CONCLUSIONS: Hyperactive delirium at hospital admission is related with markers of lung failure among older adults, especially when physical frailty coexists. Delirium is associated with increased in-hospital mortality risk, which is doubled by the coexistence of physical frailty.

Health trajectories in older patients hospitalized for COVID-19: Results from the GeroCovid multicenter study.

BACKGROUND: COVID-19 has disproportionately affected older adults. Yet, healthcare trajectories experienced by older persons hospitalized for COVID-19 have not been investigated. This study aimed at estimating the probabilities of transitions between severity states in older adults admitted in COVID-19 acute wards and at identifying the factors associated with such dynamics. METHODS: COVID-19 patients aged ≥60 years hospitalized between March and December 2020 were involved in the multicentre GeroCovid project-acute wards substudy. Sociodemographic and health data were obtained from medical records. Clinical states during hospitalization were categorized on a seven-category scale, ranging from hospital discharge to death. Based on the transitions between these states, first, we defined patients' clinical course as positive (only improvements), negative (only worsening), or fluctuating (both improvements and worsening). Second, we focused on the single transitions between clinical states and estimated their probability (through multistage Markov modeling) and associated factors (with proportional intensity models). RESULTS: Of the 1024 included patients (mean age 78.1 years, 51.1% women), 637 (62.2%) had a positive, 66 (6.4%) had a fluctuating, and 321 (31.3%) had a negative clinical course. Patients with a fluctuating clinical course were younger, had better mobility and cognitive levels, fewer diseases, but a higher prevalence of cardiovascular disease and obesity. Considering the single transitions, the probability that older COVID-19 patients experienced clinical changes was higher within a 10-day timeframe, especially for milder clinical states. Older age, male sex, lower mobility level, multimorbidity, and hospitalization during the COVID-19 first wave (compared with the second one) were associated with an increased probability of progressing towards worse clinical states or with a lower recovery. CONCLUSION: COVID-19 in older inpatients has a complex and dynamic clinical course. Identifying individuals more likely to experience a fluctuating clinical course and sudden worsening may help organize healthcare resources and clinical management across settings at different care intensity levels.

Association Between Smoking and SARS-CoV-2 Infection: Cross-sectional Study of the EPICOVID19 Internet-Based Survey.

BACKGROUND: Several studies have reported a low prevalence of current smoking among hospitalized COVID-19 cases; however, no definitive conclusions can be drawn. OBJECTIVE: We investigated the association of tobacco smoke exposure with nasopharyngeal swab (NPS) test results for SARS-CoV-2 infection and disease severity accounting for possible confounders. METHODS: The nationwide, self-administered, cross-sectional web-based Italian National Epidemiological Survey on COVID-19 (EPICOVID19) was administered to an Italian population of 198,822 adult volunteers who filled in an online questionnaire between April 13 and June 2, 2020. For this study, we analyzed 6857 individuals with known NPS test results. The associations of smoking status and the dose-response relationship with a positive NPS test result and infection severity were calculated as odds ratios (ORs) with 95% CIs by means of logistic and multinomial regression models adjusting for sociodemographic, clinical, and behavioral characteristics. RESULTS: Out of the 6857 individuals (mean age 47.9 years, SD 14.1; 4516/6857, 65.9% female), 63.2% (4334/6857) had never smoked, 21.3% (1463/6857) were former smokers, and 15.5% (1060/6857) were current smokers. Compared to nonsmokers, current smokers were younger, were more educated, were less affected by chronic diseases, reported COVID-19-like symptoms less frequently, were less frequently hospitalized, and less frequently tested positive for COVID-19. In multivariate analysis, current smokers had almost half the odds of a positive NPS test result (OR 0.54, 95% CI 0.45-0.65) compared to nonsmokers. We also found a dose-dependent relationship with tobacco smoke: mild smokers (adjusted OR [aOR] 0.76, 95% CI 0.55-1.05), moderate smokers (aOR 0.56, 95% CI 0.42-0.73), and heavy smokers (aOR 0.38, 95% CI 0.27-0.53). This inverse association also persisted when considering the severity of the infection. Current smokers had a statistically significantly lower probability of having asymptomatic (aOR 0.50, 95% CI 0.27-0.92), mild (aOR 0.65, 95% CI 0.53-0.81), and severe infections (aOR 0.27, 95% CI 0.17-0.42) compared to those who never smoked. CONCLUSIONS: Current smoking was negatively associated with SARS-CoV-2 infection with a dose-dependent relationship. Ad hoc experimental studies are needed to elucidate the mechanisms underlying this association. TRIAL REGISTRATION: ClinicalTrials.gov NCT04471701; https://clinicaltrials.gov/ct2/show/NCT04471701.

Diabetes Affects Antibody Response to SARS-CoV-2 Vaccination in Older Residents of Long-Term Care Facilities: Data From the GeroCovid Vax Study.

OBJECTIVE: Type 2 diabetes may affect the humoral immune response after vaccination, but data concerning coronavirus disease 19 (COVID-19) vaccines are scarce. We evaluated the impact of diabetes on antibody response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination in older residents of long-term care facilities (LTCFs) and tested for differences according to antidiabetic treatment. RESEARCH DESIGN AND METHODS: For this analysis, 555 older residents of LTCFs participating in the GeroCovid Vax study were included. SARS-CoV-2 trimeric S immunoglobulin G (anti-S IgG) concentrations using chemiluminescent assays were tested before the first dose and after 2 and 6 months. The impact of diabetes on anti-S IgG levels was evaluated using linear mixed models, which included the interaction between time and presence of diabetes. A second model also considered diabetes treatment: no insulin therapy (including dietary only or use of oral antidiabetic agents) and insulin therapy (alone or in combination with oral antidiabetic agents). RESULTS: The mean age of the sample was 82.1 years, 68.1% were women, and 25.2% had diabetes. In linear mixed models, presence of diabetes was associated with lower anti-S IgG levels at 2 (ß = -0.20; 95% CI -0.34, -0.06) and 6 months (ß = -0.22; 95% CI -0.37, -0.07) after the first vaccine dose. Compared with those without diabetes, residents with diabetes not using insulin had lower IgG levels at 2- and 6-month assessments (ß = -0.24; 95% CI -0.43, -0.05 and ß = -0.30; 95% CI -0.50, -0.10, respectively), whereas no differences were observed for those using insulin. CONCLUSIONS: Older residents of LTCFs with diabetes tended to have weaker antibody response to COVID-19 vaccination. Insulin treatment might buffer this effect and establish humoral immunity similar to that in individuals without diabetes.

Determinants of Cause-Specific Mortality and Loss of Independence in Older Patients following Hospitalization for COVID-19: The GeroCovid Outcomes Study.

Hospitalization for acute SARS-CoV-2 infection confers an almost five-fold higher risk of post-discharge, all-cause mortality compared to controls from the general population. A negative impact on the functional autonomy of older patients, especially in cases of severe disease and prolonged hospitalization, has been recently described. However, little is known about the determinants of cause-specific mortality and loss of independence (LOI) in the activities of daily living (ADL) following COVID-19 hospitalization. Thus, the current prospective, multicenter study is aimed at identifying the determinants of post-discharge cause-specific mortality and the loss of autonomy in at least one ADL function. Older patients hospitalized for a SARS-CoV-2 infection were consecutively enrolled in an e-Registry from 1 March 2020, until 31 December 2020. After at least six months from discharge, patients were extensively re-evaluated according to a common protocol at the outpatient clinic of eight tertiary care Italian hospitals. Of 193 patients [109 (56.4%) men, mean age 79.9 ± 9.1 years], 43 (22.3%) died during follow-up. The most common causes of death were cardiovascular diseases (46.0%), respiratory failure (26.5%), and gastrointestinal and genitourinary diseases (8.8% each). Pre-morbid ADLs qualified as an independent mortality risk factor [adjusted HR 0.77 (95%CI: 0.63-0.95)]. Of 132 patients, 28 (21.2%) lost their independence in at least one ADL. The adjusted risk of LOI declined with a lower frailty degree [aOR 0.03 (95%CI: 0.01-0.32)]. In conclusion, at long-term follow-up after hospitalization for acute SARS-CoV-2 infection, more than 40% of older patients died or experienced a loss of functional independence compared to their pre-morbid condition. Given its high prevalence, the loss of functional independence after hospitalization for COVID-19 could be reasonably included among the features of the "Long COVID-19 syndrome" of older patients.

Humoral immunity induced by mRNA COVID-19 vaccines in Nursing Home Residents previously infected with SARS-CoV-2.

BACKGROUND: Nursing home (NH) residents suffered the greatest impact of the COVID-19 pandemic. Limited data are available on vaccine-induced immunity and on the protection ensured by a prior infection in this population. AIMS: The present study aims to monitor antibody levels and their persistence over a 6-month period in NH residents according to the history of prior SARS-CoV-2 infection. METHODS: We measured anti-trimeric Spike IgG antibody levels in a sample of 395 residents from 25 NHs in 6 Italian Regions at study enrolment (prior to the first dose of vaccine, T0) and then after 2 (T1) and 6 months (T2) following the first vaccine dose. All participants received mRNA vaccines (BNT162b2 or mRNA-1273). Analyses were performed using log-transformed values of antibody concentrations and geometric means (GM) were calculated. RESULTS: Superior humoral immunity was induced in NH residents with previous SARS-CoV-2 infection. (T0: GM 186.6 vs. 6.1 BAU/ml, p < 0.001; T1: GM 5264.1 vs. 944.4 BAU/ml, p < 0.001; T2: GM 1473.6 vs. 128.7 BAU/ml, p < 0.001). Residents with prior SARS-CoV-2 infection receiving two vaccine doses presented significantly higher antibody concentration at T1 and T2. A longer interval between previous infection and vaccination was associated with a better antibody response over time. DISCUSSION: In a frail sample of NH residents, prior SARS-CoV-2 infection was associated with a higher humoral response to vaccination. Number of vaccine doses and the interval between infection and vaccination are relevant parameters in determining humoral immunity. CONCLUSIONS: These findings provide important information to plan future immunization policies and disease prevention strategies in a highly vulnerable population.

Analysis of Risk Factors of Soft Tissue Bleeding in COVID-19 Patients: A Point of View After Two Years of Pandemic.

Background: The aim of the study was to analyze the relationship between patient characteristics, including anagraphic and laboratoristic data and amount of adipose tissue measured in computed tomography (CT) scans in coronavirus disease 2019 (COVID-19) patients, and incidence of soft tissue bleeding requiring medical and/or interventional radiology management. Methods: A total of 132 patients hospitalized for COVID-19 pathology from October 2020 to May 2021 were included in the study and divided into two groups: a bleeding group of 70 cases with soft tissue bleeding occurring during hospitalization, and a control group of 62 hospitalized COVID-19 patients without bleeding events. In the bleeding group, two subgroups were considered: an embolization group including soft tissue bleeding cases requiring interventional radiology with transarterial embolization (TAE) (16/70; 22.9%) and a non-embolization group, clinically managed without TAE (54/70; 77.1%). Demographics and clinical data, visceral adipose tissue (VAT) area and subcutaneous adipose tissue (SAT) area measured on CT images and VAT/SAT ratio were compared between bleeding and control groups and between embolization and non-embolization subgroups. Results: Bleeding and control groups did not significantly differ for sex distribution, COVID-19, platelet (PLT) count, international normalized ratio (INR), SAT area, VAT area, and VAT/SAT ratio. Embolization and non-embolization groups did not significantly differ for age, COVID-19, PLT count, INR, SAT area, and VAT/SAT ratio. Bleeding group had lower body mass index (BMI) than control group as well as embolization group compared to non-embolization group. A statistically significant difference was observed between embolization and non-embolization groups for VAT area, with smaller values in embolization group (mean difference: 64.2 cm2, 95% confidence interval: 8.3 - 120.1; P < 0.05). Conclusion: Soft tissue bleeding in COVID-19 is more frequent and severe in patients with low amount of VAT, demonstrating that fat mass may have a containing function on bleeding, limiting its progression in surrounding structures. There are some other factors that influence the risk of bleeding, such as age, thromboprophylaxis therapy and BMI.

Influenza Vaccination Uptake in the General Italian Population during the 2020-2021 Flu Season: Data from the EPICOVID-19 Online Web-Based Survey.

To assess influenza vaccine uptake during the 2020/2021 flu season and compare it with that of the 2019/2020 flu season among respondents to the second phase of the web-based EPICOVID-19 survey, we performed an observational web-based nationwide online survey (January-February 2021) in which respondents to the first survey (April-June 2020) were contacted and asked to complete a second questionnaire. Factors associated with vaccine uptake in the 2020/2021 flu season were assessed by applying a multivariable multinomial logistic regression model. Out of the 198,822 respondents to the first survey, 41,473 (20.9%) agreed to fill out the follow-up questionnaire; of these, 8339 (20.1%) were vaccinated only during the 2020/2021 season, 8828 (21.3%) were vaccinated during both seasons and 22,710 (54.8%) were vaccinated in neither season. Educational level (medium (aOR 1.33 95%CI 1.13-1.56) and high (aOR 1.69 95%CI 1.44-1.97) vs. low) and socio-economic deprivation according to SES scoring (1 point aOR 0.83 (95%CI 0.78-0.89), 2 aOR 0.68 (95%CI 0.60-0.77) points or ≥3 points aOR 0.42 (95%CI 0.28-0.45) vs. 0 points) were found to be associated with flu vaccine uptake. Our study shows that social determinants seemed to affect flu vaccination uptake and identifies specific categories of the population to target during future influenza vaccination campaigns.

Epidemiology of SARS-CoV-2 Infection in Italy Using Real-World Data: Methodology and Cohort Description of the Second Phase of Web-Based EPICOVID19 Study.

Digital technologies have been extensively employed in response to the SARS-CoV-2 pandemic worldwide. This study describes the methodology of the two-phase internet-based EPICOVID19 survey, and the characteristics of the adult volunteer respondents who lived in Italy during the first (April-May 2020) and the second wave (January-February 2021) of the epidemic. Validated scales and ad hoc questionnaires were used to collect socio-demographic, medical and behavioural characteristics, as well as information on COVID-19. Among those who provided email addresses during phase I (105,355), 41,473 participated in phase II (mean age 50.7 years ± 13.5 SD, 60.6% females). After a median follow-up of ten months, 52.8% had undergone nasopharyngeal swab (NPS) testing and 13.2% had a positive result. More than 40% had undergone serological test (ST) and 11.9% were positive. Out of the 2073 participants with at least one positive ST, 72.8% had only negative results from NPS or never performed it. These results indicate that a large fraction of individuals remained undiagnosed, possibly contributing to the spread of the virus in the community. Participatory online surveys offer a unique opportunity to collect relevant data at individual level from large samples during confinement.

Accessibility to SARS-CoV-2 swab test during the Covid-19 pandemic: Did age make the difference?

Although COVID-19 affects older people more severely, health policies during the first wave of the pandemic often prioritized younger individuals. We investigated whether age had influenced the access to a diagnostic test for SARS-CoV-2 infection and whether clinical complexity and healthcare resources availability could have impacted such differences. This work included 126,741 Italian participants in the EPICOVID19 web-based survey, who reported having had contacts with known/suspected COVID-19 cases (epidemiological criterion) and/or COVID-19-like signs/symptoms (clinical criterion) from February to June 2020. Data on sociodemographic, medical history and access to SARS-CoV-2 nasopharyngeal swab (NPS) were collected. Logistic regressions estimated the probability of accessing NPS as a function of age and the possible modifying effect of chronic diseases' number and residential areas in such association. A total of 6136 (4.8%) participants had undergone an NPS. Older participants had lower NPS frequencies than the younger ones when reporting epidemiological (14.9% vs. 8.8%) or both epidemiological and clinical criteria (17.5% vs. 13.7%). After adjustment for potential confounders, including epidemiological and clinical criteria, the chance of NPS access decreased by 29% (OR=0.71, 95%CI:0.63-0.79) in older vs. younger individuals. Such disparity was accentuated in areas with greater healthcare resources. In conclusion, in the first wave of the pandemic, age may have affected the access to COVID-19 diagnostic testing, disadvantaging older people.

Atrial fibrillation and COVID-19 in older patients: how disability contributes to shape the risk profile. An analysis of the GeroCovid registry.

BACKGROUND AND AIMS: Atrial fibrillation (AF) is often complicated by disabling conditions in the elderly. COVID-19 has high mortality in older people. This study aimed at evaluating the relationship of pre-infection AF with characteristics and survival of older COVID-19 patients. METHODS: We retrospectively analyzed inpatients aged ≥ 60 years enrolled in GeroCovid Observational, a multicenter registry endorsed by the Italian and the Norwegian Societies of Gerontology and Geriatrics. Pre-COVID-19 sociodemographic, functional, and medical data were systematically collected, as well as in-hospital mortality. RESULTS: Between March and June 2020, 808 COVID-19 subjects were enrolled (age 79 ± 9 years; men 51.7%). The prevalence of AF was 21.8%. AF patients were older (82 ± 8 vs. 77 ± 9 years, p < 0.001), had a higher CHA2DS2-VASc score (4.1 ± 1.5 vs. 3.2 ± 1.5, p < 0.001) and were more likely to present almost all comorbidities. At multivariable analysis, advanced age, white blood cell count, the presence of heart and peripheral artery diseases were significantly associated with the presence of AF. In-hospital mortality was higher in AF patients (36.9 vs. 27.5%; OR = 1.55, 95% CI = 1.09-2.20; p = 0.015). A decision tree analysis showed that, in AF subjects, preserved functional status at admission was the most important factor associated with survival. In patients without AF, baseline COVID-19 severity was the most relevant variable related to clinical prognosis. CONCLUSIONS: AF is frequent in older patients with COVID-19, in whom it associates with clinical complexity and high mortality. Pre-infection disability shapes the prognosis of this extremely vulnerable segment of hospitalized subjects. CLINICAL TRIAL REGISTRATION: GeroCovid Observational was registered at www.clinicaltrials.gov (NCT04379440).

Manifesto on the Value of Adult Immunization: "We Know, We Intend, We Advocate".

Immunization through vaccination is a milestone achievement that has made a tremendous contribution to public health. Historically, immunization programs aimed firstly to protect children, who were disproportionally affected by infectious diseases. However, vaccine-preventable diseases can have significant impacts on adult mortality, health, and quality of life. Despite this, adult vaccinations have historically been overlooked in favor of other health priorities, because their benefits to society were not well recognized. As the general population is aging, the issue of vaccination in older adults is gaining importance. In high-income countries, recommendations for the routine vaccination of older adults have been gradually introduced. The Italian National Immunization Plan is considered to be among the most advanced adult vaccination plans in Europe. However, available data indicate there is low adherence to vaccination recommendations in Italy. The COVID-19 pandemic has exposed the damage that can be caused by an infectious disease, especially among adults and individuals with comorbidities. The aim of this "Manifesto", therefore, is to provide an overview of the existing evidence on the value of adult vaccination, in the Italian context, with a call to action to healthcare providers and health authorities.

Psychological Well-Being of Older Adults With Cognitive Deterioration During Quarantine: Preliminary Results From the GeroCovid Initiative.

Objectives: The spread of COVID-19 has undeniably unsettled the social, psychological and emotional life of the entire world population. Particular attention should be paid to older adults with dementia, given their vulnerability to emotional stressors. The aim of this retrospective study is to evaluate the impact of the first wave quarantine related to Covid-19 on psychological and affective well-being of older adults with mild/major neurocognitive disorders and of their caregivers. Methods: Data on participants' assessment before the quarantine (PREQ) were retrospectively collected. Patients with Mild Cognitive Impairment (MCI) or dementia were recruited from different Centers for Cognitive Decline and Dementia in Italy. During the quarantine, psychological and affective well-being were evaluated by phone through the administrations of scales measuring anxiety and depression (DASS), perceived stress (PSS), coping strategies (COPE) and the caregivers' burden (CBI). The scales' results were compared across participants' PREQ cognitive level (Mini Mental State Examination, MMSE ≥25, 23-24, and ≤ 22) with multiple linear regression models. Results: The sample included 168 patients (64% women) with a mean age of 79 ± 7 years. After adjusting for potential confounders, more severe cognitive impairment was independently associated with higher DASS and PSS score, and poorer coping strategies (p < 0.05). Cognitive functioning was also inversely associated with CBI. Conclusions: The impact of the quarantine on the psycho-affective well-being of individuals with MCI and dementia and on caregivers' burden varies according to the PREQ cognitive functioning with more severely impaired patients having worse outcomes.

Posterior Reversible Encephalopathy Syndrome and brain haemorrhage as COVID-19 complication: a review of the available literature.

BACKGROUND: SARS-CoV-2 infection has been associated with various neurological manifestations. Since patients affected by SARS-CoV-2 infection present coagulation and immune system dysregulation, ischemic or haemorragic stroke is not uncommon, irrespective of respiratory distress. However, the occurrence of focal neurological deficits together with other symptoms like headache, cortical blindness, seizure and altered mental status should prompt the diagnosis of Posterior Reversible Encephalopathy Syndrome (PRES). Antithrombotic treatment, the alteration of endothelial function, and coagulopathy due to COVID-19 and PRES leading to the breakdown of blood-brain barrier may then contribute to the occurrence of a brain haemorrhage. METHODS: We describe the case of a COVID-19 patient who developed bilateral occipital lobe haemorrhages suggestive of haemorrhagic PRES. We then reviewed the available literature about haemorrhagic evolution of PRES in COVID-19. RESULTS: We describe the clinical and radiological features of five COVID-19 patients who developed haemorrhagic PRES. CONCLUSIONS: Coagulopathy and endothelial dysfunction resulting from the massive release of cytokines during the host immune response may be key factors in the pathogenesis of COVID-19-related PRES. Antithrombotic therapy and the leakage of the blood-brain barrier can subsequently increase the risk of haemorrhagic transformation of the lesioned brain tissue. A prompt diagnosis of PRES is mandatory, since the timely interruption/reversal of antithrombotic therapy may be a key determinant for a good prognosis.

Distancing Measures in COVID-19 Pandemic: Loneliness, More than Physical Isolation, Affects Health Status and Psycho-Cognitive Wellbeing in Elderly Patients with Chronic Obstructive Pulmonary Disease.

Since the outbreak of the SARS-CoV-2 pandemic in 2020, many governments have been imposing confinement and physical distancing measures. No data exist on the effects of lockdowns on the health status of patients affected by chronic pathologies, specifically those with Chronic Obstructive Pulmonary Disease (COPD). Our study aims to establish variations across the psychological and cognitive profile of patients during the isolation period in Italy, in a cohort of patients affected by COPD, between February and May 2020. Forty patients with established COPD were comprehensively evaluated by geriatric multidimensional assessment before the spread of the epidemic in Italy, and submitted to a second evaluation during the subsequent lockdown. We assessed functional ability, basic and instrumental Activities of Daily Living (ADL and IADL), cognition and mood status. We compared the scores obtained at baseline against those obtained during the pandemic, and used mean differences for correlation with major clinical and functional indexes. The score differences from MMSE, ADL and IADL were statistically significant. Such differences were correlated to the presence of a caregiver and to the total number of family members living together. Remarkably, the loneliness dimension, more than the restrictions themselves, seemed to represent the major determinant of altered health status and depressed psycho-cognitive profile in our population. Also remarkably, we detected no correlation between the score variation and the respiratory function indexes of disease severity. The isolation measures adopted during the SARS-CoV-2 pandemic have triggered the classic clinical string associated to geriatric isolation, which leads to a deterioration of cognitive functions, independence and frailty levels in a population affected by a chronic degenerative disease, such as COPD. If considered from a multidimensional geriatric point of view, the individual benefit of isolation measures could be small or non-existent.