Vaccinations Status against Vaccine-Preventable Diseases and Willingness to Be Vaccinated in an Italian Sample of Frail Subjects.

BACKGROUND: Study aim was to investigate the vaccination status against vaccine-preventable diseases (VPD) of frail adults during the SARS-CoV-2 pandemic and, for those subjects eligible for at least one vaccine, with respect to the recommended vaccination in line with the Italian National Vaccination Prevention Plane (NPVP), to explore the willingness to be vaccinated. METHODS: A cross-sectional study was carried out among adults aged ≥ 60, immunocompromised or subjects affected by chronic conditions. RESULTS: Among the 427 participants, a vaccination coverage rate lower than the targets for all the vaccines considered was found. Of those, 72.6% of subjects stated their willingness to receive recommended vaccinations, and 75.2% of the respondents stated that the advice to undergo vaccinations was received by the General Practitioner (GP). In a multivariable logistic regression model, higher odds of recommended VPD vaccination uptake (defined as having two or more of the recommended vaccinations) were associated with the willingness towards recommended VPD vaccination (Odds Ratio = 3.55, 95% Confidence Interval: 1.39 to 9.07), university education (OR = 2.03, 95% CI: 1.03 to 3.97), but having another person in the household (OR = 0.52, 95% CI: 0.28 to 0.97), and history of oncological disease (OR = 0.39, 95% CI: 0.18 to 0.87) were predictive of lower odds of vaccination uptake. In another multivariable model, higher odds of willingness to receive vaccines were associated with kidney disease (OR = 3.3, 95% CI: 1.01 to 10.5), perceived risk of VPD (OR = 1.9, 95% CI: 1.02 to 3.3), previous influenza vaccination (OR = 3.4, 95% CI: 1.8 to 6.5), and previous pneumococcal vaccination (OR = 3.1, 95% CI: 1.3 to 7.7), but increasing age (OR = 0.93 per year, 95% CI: 0.91 to 0.97), working (OR = 0.40, 95% CI: 0.20 to 0.78), and fear of vaccine side effects (OR = 0.38, 95% CI: 0.21 to 0.68) were predictive of lower odds of willingness to receive vaccines. CONCLUSIONS: Despite specific recommendations, vaccination coverage rates are far below international targets for frail subjects. Reducing missed opportunities for vaccination could be a useful strategy to increase vaccination coverage in frail patients during the routine checks performed by GPs and specialists.

The Mental Health of Caregivers and Their Patients With Dementia During the COVID-19 Pandemic: A Systematic Review

Background: Coronavirus Disease 2019 (COVID-19) is a worldwide public health concern. It continues to spread rapidly throughout the world causing multiple physical and psychological consequences in the population. Especially, people affected by severe psychiatric or neurological diseases are highly susceptible to serious health complications not only due to the direct effect of the infection but also to the indirect effect of COVID-19 following social distancing during lockdowns and its general social consequences. Indeed, lockdown and difficulties in using the care services produced psychological consequences in caregivers such as depression, anxiety, and worsening of the quality of life which in turn affected the ability to manage patients. Our aim was to systematically review the psychological consequences of the COVID-19 lockdown in caregivers of patients with cognitive impairment and dementia and the impact on the health of their patients. Methods: A systematic literature search was conducted by searching in MEDLINE/PubMed, Scopus, and Web of Science by two independent researchers following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement guidelines. Data extraction and quality assessment were also performed. Papers were screened for eligibility by and then those which met inclusion criteria were included in this review. Results: The initial search returned 410 records. After the screening and the inclusion/exclusion criteria were applied, 315 were excluded because they were irrelevant, 30 because they were reviews, meta-analyses, letters to editors, editorials, guidelines, or case reports, and 10 because they were duplicates. Then, 38 out of 55 s/full-text articles were excluded because they did not simultaneously assess mental health of patients and caregivers. In the end, 17 papers were deemed eligible and included in the present review. Conclusion: Based on current literature, the COVID-19 pandemic and the ensuing lockdown caused severe psychological consequences for caregivers of patients with dementia, worsening their mental health, and increasing the psychological and physical burden, independently from the severity of the disease of their relatives, which resulted also independently globally worsened.

Serological Response to SARS-CoV-2 Messenger RNA Vaccine: Real-World Evidence from Italian Adult Population.

BACKGROUND: This study aims to investigate the extent of the BNT162b2 mRNA vaccine-induced antibodies against SARS-CoV-2 in a large cohort of Italian subjects belonging to the early vaccinated cohort in Italy. METHODS: A prospective study was conducted between December 2020 and May 2021. Three blood samples were collected for each participant: one at the time of the first vaccine dose (T0), one at the time of the second vaccine dose, (T1) and the third 30 days after this last dose (T2). RESULTS: We enrolled 2591 fully vaccinated subjects; 16.5% were frail subjects, and 9.8% were over 80 years old. Overall, 98.1% of subjects were seropositive when tested at T2, and 76.3% developed an anti-S IgG titer ≥4160 AU/mL, which is adequate to develop viral neutralizing antibodies. Seronegative subjects at T1 were more likely to remain seronegative at T2 or to develop a low-intermediate anti-S IgG titer (51-4159 AU/mL). CONCLUSIONS: In summary, vaccination leads to detectable anti-S IgG titer in nearly all vaccine recipients. Stratification of the seroconversion level could be useful to promptly identify high-risk groups who may not develop a viral neutralizing response, even in the presence of seroconversion, and therefore may remain at higher risk of infection, despite vaccination.

Asthma Control during COVID-19 Lockdown in Patients with Severe Asthma under Biological Drug Treatment

Introduction: Coronavirus disease 2019 (COVID-19) has deeply affected the management of patients with severe asthma, treated with add-on biological therapies. Objective: In this study, severe asthmatic patients on treatment with one of three different biologics (omalizumab, mepolizumab, benralizumab) underwent a survey to evaluate the effects of COVID-19 on the management of their clinical condition, with regard to the changes caused by the limited access to health facilities during the pandemic period. Methods: In this prospective observational study, 28 severe asthmatic outpatients referring to the Respiratory Unit of Magna Graecia University Hospital, Catanzaro (Italy), were asked to answer a telephone survey from May to July 2021. This survey included the evaluation of demographic and clinical data, as well as the number of lung function tests performed, exacerbations, biologic doses administered at hospital, or at general practitioner office, or through self-administration. Adherence to biological therapies before and during the pandemic period was also assessed. Moreover, the most recent asthma control test (ACT) score and the last forced expiratory volume in the first second (FEV1) measurement, recorded during the pandemic phase, were compared to the pre-pandemic (baseline) period. Results: When comparing the pre-pandemic data with the pandemic observations, the mean ACT score and the exacerbation rate did not significantly change [ACT, 21.5 ±2.8 to 23.0 ±3.9 (p = 0.1);exacerbation rate, 0.3 ±0.6 and 0.5 ±1.5 (p = 0.3)]. When considering some variables related to disease management in the same periods, a statistically significant difference was detected with regard to the mean number of outpatient visits (5.2 ±3.8 vs. 0.9 ±2.5, p < 0.0001), as well as to the mean number of accesses to health facilities for the administration of biological drugs (from 7.0 ±3.4 to 2.5 ±3.9, p < 0.0001). None of the patients reported to have been infected with the SARS-CoV-2 virus and no adverse drug reactions (ADR) occurred during the study. Conclusions: The above results suggest that COVID-19 pandemic did not induce any significant change related to severe asthma control. Indeed, add-on treatment with biological drugs was regularly continued, despite the obvious limited access to health facilities.

Vitamin D Serum Levels in Subjects Tested for SARS-CoV-2: What Are the Differences among Acute, Healed, and Negative COVID-19 Patients? A Multicenter Real-Practice Study.

Vitamin D might play a role in counteracting COVID-19, albeit strong evidence is still lacking in the literature. The present multicenter real-practice study aimed to evaluate the differences of 25(OH)D3 serum levels in adults tested for SARS-CoV-2 (acute COVID-19 patients, subjects healed from COVID-19, and non-infected ones) recruited over a 6-month period (March-September 2021). In a sample of 117 subjects, a statistically significant difference was found, with acute COVID-19 patients demonstrating the lowest levels of serum 25(OH)D3 (9.63 ± 8.70 ng/mL), significantly lower than values reported by no-COVID-19 patients (15.96 ± 5.99 ng/mL, p = 0.0091) and healed COVID-19 patients (11.52 ± 4.90 ng/mL, p > 0.05). Male gender across the three groups displayed unfluctuating 25(OH)D3 levels, hinting at an inability to ensure adequate levels of the active vitamin D3 form (1α,25(OH)2D3). As a secondary endpoint, we assessed the correlation between serum 25(OH)D3 levels and pro-inflammatory cytokine interleukin-6 (IL-6) in patients with extremely low serum 25(OH)D3 levels (<1 ng/mL) and in a subset supplemented with 1α,25(OH)2D3. Although patients with severe hypovitaminosis-D showed no significant increase in IL-6 levels, acute COVID-19 patients manifested high circulating IL-6 at admission (females = 127.64 ± 22.24 pg/mL, males = 139.28 ± 48.95 ng/mL) which dropped drastically after the administration of 1α,25(OH)2D3 (1.84 ± 0.77 pg/mL and 2.65 ± 0.92 ng/mL, respectively). Taken together, these findings suggest that an administration of 1α,25(OH)2D3 might be helpful for treating male patients with an acute COVID-19 infection. Further studies on rapid correction of vitamin D deficiency with fast acting metabolites are warranted in COVID-19 patients.

SARS-CoV-2 Treatment: Current Therapeutic Options and the Pursuit of Tailored Therapy

One year on from the worldwide outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), medicine has made several steps towards increasing the therapeutic options against its treatment. Despite the lack of specific therapies, international societies have introduced new guidelines and launched several trials to test the efficacy of new protocols and drugs. Drug repurposing has been a fundamental strategy to find quick ways to fight the pathogen, even if it is new compounds that are drawing the attention of the scientific community. Tailored therapy should be considered to be a milestone in treatment in order to increase drug efficacy and to reduce drug toxicity. Therefore, both drug characteristics (i.e., pharmacokinetic, pharmacodynamic and safety) and the patient characteristics (i.e., stage of disease, comorbidity, concomitant treatments and the mutation of single nucleotides) could represent the key to achieving this objective. In the present study we performed a narrative review of the pharmacological treatment used to date in the management of coronavirus disease 2019 (COVID-19).

Neuron-specific enolase serum levels in COVID-19 are related to the severity of lung injury.

The multifunctional role of neuron-specific enolase (NSE) in lung diseases is well established. As the lungs are greatly affected in COVID-19, we evaluated serum NSE levels in COVID-19 patients with and without dyspnea. In this study, we evaluated both SARS-CoV-2-infected and uninfected patients aged >18 years who were referred to hospitals in Catanzaro, Italy from March 30 to July 30, 2020. Epidemiological, clinical, and radiological characteristics, treatment, and outcome data were recorded and reviewed by a trained team of physicians. In total, 323 patients (178 men, 55.1% and 145 women, 44.9%) were enrolled; of these, 128 were COVID-19 patients (39.6%) and 195 were control patients (60.4%). Westergren's method was used to determine erythroid sedimentation rate. A chemiluminescence assay was used for measurement of interleukin-6, procalcitonin, C-reactive protein, and NSE. We detected significantly higher NSE values (P<0.05) in COVID-19 patients than in controls. Interestingly, within the COVID-19 group, we also observed a further significant increase in dyspnea (Dyspnea Scale and Exercise score: 8.2 ± 0.8; scores ranging from 0 to 10, with higher numbers indicating very severe shortness of breath). These data provide the background for further investigations into the potential role of NSE as a clinical marker of COVID-19 progression.

Histopathological findings in a COVID-19 patient affected by ischemic gangrenous cholecystitis.

BACKGROUND: Since its first documentation, a novel coronavirus (SARS-CoV-2) infection has emerged worldwide, with the consequent declaration of a pandemic disease (COVID-19). Severe forms of acute respiratory failure can develop. In addition, SARS-CoV-2 may affect organs other than the lung, such as the liver, with frequent onset of late cholestasis. We here report the histological findings of a COVID-19 patient, affected by a tardive complication of acute ischemic and gangrenous cholecystitis with a perforated and relaxed gallbladder needing urgent surgery. CASE PRESENTATION: A 59-year-old Caucasian male, affected by acute respiratory failure secondary to SARS-CoV-2 infection was admitted to our intensive care unit (ICU). Due to the severity of the disease, invasive mechanical ventilation was instituted and SARS-CoV-2 treatment (azithromycin 250 mg once-daily and hydroxychloroquine 200 mg trice-daily) started. Enoxaparin 8000 IU twice-daily was also administered subcutaneously. At day 8 of ICU admission, the clinical condition improved and patient was extubated. At day 32, patient revealed abdominal pain without signs of peritonism at examination, with increased inflammatory and cholestasis indexes at blood tests. At a first abdominal CT scan, perihepatic effusion and a relaxed gallbladder with dense content were detected. The surgeon decided to wait and see the evolution of clinical conditions. The day after, conditions further worsened and a laparotomic cholecystectomy was performed. A relaxed and perforated ischemic gangrenous gallbladder, with a local tissue inflammation and perihepatic fluid, was intraoperatively met. The gallbladder and a sample of omentum, adherent to the gallbladder, were also sent for histological examination. Hematoxylin-eosin-stained slides display inflammatory infiltration and endoluminal obliteration of vessels, with wall breakthrough, hemorrhagic infarction, and nerve hypertrophy of the gallbladder. The mucosa of the gallbladder appears also atrophic. Omentum vessels also appear largely thrombosed. Immunohistochemistry demonstrates an endothelial overexpression of medium-size vessels (anti-CD31), while not in micro-vessels, with a remarkable activity of macrophages (anti-CD68) and T helper lymphocytes (anti-CD4) against gallbladder vessels. All these findings define a histological diagnosis of vasculitis of the gallbladder. CONCLUSIONS: Ischemic gangrenous cholecystitis can be a tardive complication of COVID-19, and it is characterized by a dysregulated host inflammatory response and thrombosis of medium-size vessels.

Lung under attack by COVID-19-induced cytokine storm: pathogenic mechanisms and therapeutic implications.

The lung is a key target of the cytokine storm that can be triggered by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), responsible for the widespread clinical syndrome known as coronavirus disease 2019 (COVID-19). Indeed, in some patients, SARS-CoV-2 promotes a dysfunctional immune response that dysregulates the cytokine secretory pattern. Hypercytokinemia underlies the hyperinflammatory state leading to injury of alveolar epithelial cells and vascular endothelial cells, as well as to lung infiltration sustained by neutrophils and macrophages. Within such a pathogenic context, interleukin-6 (IL-6) and other cytokines/chemokines play a pivotal pro-inflammatory role. Therefore, cytokines and their receptors, as well as cytokine-dependent intracellular signalling pathways can be targeted by potential therapies aimed to relieve the heavy burden of cytokine storm. In particular, the anti-IL-6-receptor monoclonal antibody tocilizumab is emerging as one of the most promising pharmacologic treatments. The reviews of this paper are available via the supplemental material section.