Efficacy Of Om-85 In Recurrent Respiratory Tract Infections.

Background In older patients, prevention of acute respiratory tract infections (RTIs) is challenging. Experimental studies have consistently underlined an immune-potentiating effect of the bacterial lysates product OM85, on both cellular and humoral responses. Objective This work aimed to assess the potential efficacy of OM-85 for RTIs' prevention in older individuals. Methods This explorative longitudinal study included 24 patients aged 65 years or older recruited in the GeroCovid Observational Study- home and outpatient care cohort. For the study purposes, we included 8 patients treated with OM-85 from December 2020 to June 2021 (group A), and a control group of 16 patients, matched for sex and age, who did not receive bacterial lysates (group B). RTIs were recorded from the participants' medical documentation in an e-registry from March 2020 to December 2021. Results In 2020, group A experienced a total of 8 RTIs, which affected 6 out of 8 patients (75%); group B reported 21 RTIs, with at least one event in 11 out of 16 patients (68.7%). In 2021, RTIs affected 2 out of 8 patients (25%) in group A (p<0.02), and 13 out of 16 patients (81.2%) in group B (within this group, 5 patients had two RTIs). The RTIs' cumulative incidence over the observation period significantly differed between groups (66.7% in group A vs. 24.3% in group B; p<0.002), as well as the decrease in RTIs frequency from 2020 to 2021. No patients in group A were affected by COVID-19 during the observation period, while among controls, two patients had SARS-CoV-2 infection, notwithstanding three doses of vaccine. Conclusion This study suggests that bacterial lysates may provide clinical benefits for preventing RTIs. Additional research involving larger cohorts is required to verify the effectiveness of OM-85 in preventing RTIs in older adults.

Clinical profile of trazodone users in a multisetting older population: data from the Italian GeroCovid Observational study.

BACKGROUND AND OBJECTIVES: Depression is highly prevalent in older adults, especially in those with dementia. Trazodone, an antidepressant, has shown to be effective in older patients with moderate anxiolytic and hypnotic activity; and a common off-label use is rising for managing behavioral and psychological symptoms of dementia (BPSD). The aim of the study is to comparatively assess the clinical profiles of older patients treated with trazodone or other antidepressants. METHODS: This cross-sectional study involved adults aged ≥ 60 years at risk of or affected with COVID-19 enrolled in the GeroCovid Observational study from acute wards, geriatric and dementia-specific outpatient clinics, as well as long-term care facilities (LTCF). Participants were grouped according to the use of trazodone, other antidepressants, or no antidepressant use. RESULTS: Of the 3396 study participants (mean age 80.6 ± 9.1 years; 57.1% females), 10.8% used trazodone and 8.5% others antidepressants. Individuals treated with trazodone were older, more functionally dependent, and had a higher prevalence of dementia and BPSD than those using other antidepressants or no antidepressant use. Logistic regression analyses found that the presence of BPSD was associated with trazodone use (odds ratio (OR) 28.4, 95% confidence interval (CI) 18-44.7 for the outcome trazodone vs no antidepressants use, among participants without depression; OR 2.17, 95% CI 1.05-4.49 for the outcome trazodone vs no antidepressants use, among participants with depression). A cluster analysis of trazodone use identified three clusters: cluster 1 included mainly women, living at home with assistance, multimorbidity, dementia, BPSD, and depression; cluster 2 included mainly institutionalized women, with disabilities, depression, and dementia; cluster 3 included mostly men, often living at home unassisted, with better mobility performance, fewer chronic diseases, dementia, BPSD, and depression. DISCUSSION: The use of trazodone was highly prevalent in functionally dependent and comorbid older adults admitted to LTCF or living at home. Clinical conditions associated with its prescription included depression as well as BPSD.

The similar expression of both ferritin and scavenger receptors activation genes in patients with COVID19 and AOSD support their role in the pathogenesis of these diseases and identify a common mechanism at the basis of the "hyperferritinemic syndromes".

A role for COVID19 in "hyperferritinemic syndromes" has been proposed based on its clinical and serological characteristics and its similarities with AOSD. To better understand the molecular pathways responsible of these similarities, we evaluated in the PBMCs of 4 active AOSD patients, 2 COVID19 patients with ARDS, and 2 HCs the expression of genes associated with iron metabolisms, with monocyte/macrophages activation, and finally with NETs formation.

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

OBJECTIVES: Nursing 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. DESIGN: Longitudinal cohort study. SETTING AND PARTICIPANTS: Thirty-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. METHODS: Pre- 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. RESULTS: Before 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 IMPLICATIONS: The 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.

COVID-19 Signs and Symptom Clusters in Long-Term Care Facility Residents: Data from the GeroCovid Observational Study

Background: Long-term care facility (LTCF) residents often present asymptomatic or paucisymptomatic features of SARS-CoV-2 infection. We aimed at investigating signs/symptoms, including their clustering on SARS-CoV-2 infection and mortality rates associated with SARS-CoV-2 infection in LTCF residents. Methods: This is a cohort study of 586 aged ≥60 year-old residents at risk of or affected with COVID-19 enrolled in the GeroCovid LTCF network. COVID-19 signs/symptom clusters were identified using cluster analysis. Cluster analyses associated with SARS-CoV-2 infection and mortality were evaluated using logistic regression and Cox proportional hazard models. Results: Cluster 1 symptoms (delirium, fever, low-grade fever, diarrhea, anorexia, cough, increased respiratory rate, sudden deterioration in health conditions, dyspnea, oxygen saturation, and weakness) affected 39.6% of residents and were associated with PCR swab positivity (OR = 7.21, 95%CI 4.78–10.80;p < 0.001). Cluster 1 symptoms were present in deceased COVID-19 residents. Cluster 2 (increased blood pressure, sphincter incontinence) and cluster 3 (new-onset cognitive impairment) affected 20% and 19.8% of residents, respectively. Cluster 3 symptoms were associated with increased mortality (HR = 5.41, 95%CI 1.56–18.8;p = 0.008), while those of Cluster 2 were not associated with mortality (HR = 0.82, 95%CI 0.26–2.56;p = 730). Conclusions: Our study highlights that delirium, fever, and low-grade fever, alone or in clusters should be considered in identifying and predicting the prognosis of SARS-CoV-2 infection in older LTCF patients.

Computed tomography findings and prognosis in older COVID-19 patients.

BACKGROUND: In older and multimorbid patients, chronic conditions may affect the prognostic validity of computed tomography (CT) findings in COVID-19. This study aims at assessing to which extent CT findings have prognostic implications in COVID-19 older patients. METHODS: Hospitalized COVID-19 patients aged 60 years or more enrolled in the multicenter, observational and longitudinal GeroCovid study who underwent chest CT were included. Patients were stratified by tertiles of age and pneumonia severity to compare CT findings. Hierarchical clustering based on CT findings was performed to identify CT-related classificatory constructs, if any. The hazard ratio (HR) of mortality was calculated for individual CT findings and for clusters, after adjusting for potential confounders. RESULTS: 380 hospitalized COVID-19 patients, with a mean age of 78 (SD:9) years, underwent chest CT scan. Ground glass opacity (GGO), consolidation, and pleural effusion were the three most common CT findings, with GGO prevalence decreasing from younger to older patients and pleural effusion increasing. More severe the pneumonia more prevalent were GGO, consolidation and pleural effusion. HR of mortality was 1.94 (95%CI 1.24-3.06) for pleural effusion and 13 (95%CI 6.41-27) for cluster with a low prevalence of GGO and a high prevalence of pleural effusion ("LH"), respectively. Out of the three CT based clusters, "LH" was the only independent predictor in the multivariable model. CONCLUSIONS: Pleural effusion qualifies as a distinctive prognostic marker in older COVID-19 patients. Research is needed to verify whether pleural effusion reflects COVID-19 severity or a coexisting chronic condition making the patient at special risk of death. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04379440.

Monitoring COVID-19 vaccine use in Italian long term care centers: The GeroCovid VAX study.

The COVID-19 pandemic has changed routine care practice for older persons, especially in those with frailty living in long term care (LTC) facilities. Due to the high mortality rates of Nursing home (NH) residents during the first wave of the COVID-19 pandemic, priority for COVID-19 vaccinations was given to this vulnerable population. However, the safety and efficacy of such vaccines in older frail elders remains questionable due to the fact that initial randomized clinical trials (RCTs) for such vaccines did not include this population. This type of discrimination in patient participation in RCTs continues and has been recognized in the literature. Nevertheless, in the context of a worldwide emergency, COVID-19 vaccination in older persons living in LTC facilities may provide a solid basis to protect against negative outcomes, such as COVID-19 infection and death. In this report, we present the protocol of the GeroCovid Vax study, an Italian study that began in February 2021 which is aimed at investigating the safety and efficacy of the anti-SARS-CoV-2 vaccinations in older persons living in LTCs. This protocol specially aims to continuously and closely monitor events related to- and following- the anti-SARS-CoV-2 vaccination in elderly living in LTC facilities. In this report, we will provide information related to the study protocol and describe baseline characteristics of the sample.

Sex- and gender-related differences linked to SARS-CoV-2 infection among the participants in the web-based EPICOVID19 survey: the hormonal hypothesis.

Objective To investigate sex- and gender-based differences linked to SARS-COV-2 infection and to explore the role of hormonal therapy (HT) in females. Study design Data from the self-administered, cross-sectional, web-based EPICOVID19 survey of 198,822 adults living in Italy who completed an online questionnaire during the first wave of the epidemic in Italy (April-May 2020) were analyzed. Main outcomes measures Multivariate binary logistic and multinomial regression models were respectively used to estimate the odds ratios (ORs) with 95% confidence intervals (CIs) for positive nasopharyngeal swab (NPS) test results and severe SARS-CoV-2 infection. Results The data from 6,873 participants (mean age 47.9 ± 14.1 years, 65.8% females) who had a known result from an NPS test were analyzed. According to the multivariate analysis, females had lower odds of a positive result from the NPS test (aOR 0.75, 95%CI 0.66-0.85) and of having a severe infection (aOR 0.46, 95%CI 0.37-0.57) than did their male counterparts. These differences were greater with decreasing age in both sexes. In addition, females aged ≥60 years receiving HT (N = 2,153, 47.6%) had a 46% lower probability of having a positive NPS test (aOR 0.54, 95%CI 0.36-0.80) than their same-aged peers who had never used HT; there were no differences in the younger age groups with respect to HT status. Conclusion Female sex was associated with an age-dependent lower risk of having a severe SARS-CoV-2 infection than their male counterparts. Age seemed to modify the relationship between HT status and infection: while the two were not related among younger participants, it was negative in the older ones. Future prospective studies are needed to elucidate the potential protective role sex hormones may play. Trial registration ClinicalTrials.gov NCT04471701.

COVID-19 sniffer dog experimental training: Which protocol and which implications for reliable sidentification?

The introduction of trained sniffer dogs for COVID-19 detection could be an opportunity, as previously described for other diseases. Dogs could be trained to detect volatile organic compounds (VOCs), the whiff of COVID-19. Dogs involved in the study were three, one male and two females from different breeds, Black German Shepherd, German Shepherd, and Dutch Shepherd. The training was performed using sweat samples from SARS-CoV2 positive patients and from SARS-Cov2 free patients admitted at the University Hospital Campus Bio-medico of Rome. Gauze with sweat was collected in a glass jar with a metal top and put in metal boxes used for dog training. The dog training protocol was performed in two phases: the olfactory conditioning and the olfactory discrimination research. The training planning was focused on the switch moment for the sniffer dog, the moment when the dog was able to identify VOCs specific for COVID-19. At this time, the dog was able to identify VOCs specific for COVID-19 with significant reliability, in terms of the number of correct versus incorrect (p < 0.0001) reporting. In conclusion, this protocol could provide a useful tool for sniffer dogs' training and their introduction in a mass screening context. It could be cheaper and faster than a conventional testing method.

Management of Older Outpatients during the COVID-19 Pandemic: The GeroCovid Ambulatory Study.

OBJECTIVES: The GeroCovid Study is a multi-setting, multinational, and multi-scope registry that includes the GeroCovid home and outpatients' care cohort. The present study aims to evaluate whether outpatient and home care services with remote monitoring and consultation could mitigate the impact of the COVID-19 pandemic on mental and affective status, perceived well-being, and personal capabilities of outpatients and home care patients with cognitive disorders. METHODS: Prospectively recorded patients in an electronic web registry provided by BlueCompanion Ltd. Up to October 31, 2020, the sample included 90 patients receiving regular care from the Center for Cognitive Disorders and Dementia in Catanzaro Lido, Italy. It was made of 52 ambulatory outpatients and 38 home care patients, mean age 83.3 ± 7.54 years. Participants underwent a multidimensional assessment at baseline (T0) and after 90 days (T1). For each patient, we administered the Mini-Mental State Examination (MMSE) for cognitive functions, the Activities of Daily Living (ADL) and Instrumental ADL (IADL) scales for functional capabilities, the Cumulative Illness Rating Scale (CIRS) for comorbidities and their impact on patients' health, the 5-items Geriatric Depression Scale (GDS) for mood, and the Euro Quality of Life (EuroQoL) for perceived quality of life. Contacts with both ambulatory and home care patients were managed in person or via telephone, preferably through video calls (WhatsApp or FaceTime). RESULTS: Contacts with patients were kept at T0 through telephone. At T1, visits were made in person for over 95% out of the cases. The ADL, IADL, CIRS, GDS, MMSE, and EuroQoL changed slightly between T0 and T1. Most of the patients were clinically stable over time on the majority of the scales explored, but behavioral changes were found in 24.4% of patients and anxiety and insomnia in 17.7% of patients. CONCLUSION: Our study suggests that contacts through telephone and video consultations are likely associated with a health status preservation of the patients.

The Cross-Talk between Age, Hypertension and Inflammation in COVID-19 Patients: Therapeutic Targets.

This paper presents a brief overview of the complex interaction between age, hypertension, the renin-angiotensin-aldosterone system (RAAS), inflammation, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection. Coronavirus disease 2019 (COVID-19) is more frequent and more severe in comorbid elderly patients, especially those with hypertension, diabetes, obesity, or cardiovascular diseases. There are concerns regarding the use of RAAS inhibitors in patients with COVID-19. Some physicians have considered the need for interrupting RAAS inhibition in order to reduce the possibility of SARS-CoV2 entering lung cells after binding to angiotensin-converting enzyme 2 (ACE2) receptors. We offer a different point of view in relation to the need for continuing to use RAAS inhibitors in patients with COVID-19. We focused our article on elderly patients because of the distinctive imbalance between the immune response, which is depressed, and the exacerbated inflammatory response, 'inflammaging', which makes the geriatric patient an appropriate candidate for therapeutic strategies aimed at modulating the inflammatory response. Indeed, COVID-19 is an inflammatory storm that starts and worsens during the course of the disease. During the COVID-19 pandemic, various therapeutic approaches have been tested, including antiviral drugs, interferon, anti-interleukins, hydroxychloroquine, anti-inflammatories, immunoglobulins from recovered patients, and heparins. Some of these therapeutic approaches did not prove to be beneficial, or even induced serious complications. Based on current evidence, in the early stages of the disease modulation of the inflammatory response through the inhibition of neprilysin and modulation of the RAAS could affect the course and outcome of COVID-19.