Feasibility, Safety, and Effectiveness of Telerehabilitation in Mild-to-Moderate Parkinson's Disease.

Introduction: Parkinson's disease (PD) patients frequently engage in rehabilitation to ameliorate symptoms. During the Coronavirus disease 2019 (COVID-19) pandemic, access to rehabilitation programs has been markedly limited, consequently, telerehabilitation gained popularity. In this prospective, open-label, and pilot study, we aimed to investigate feasibility, safety, and efficacy of telerehabilitation in mild-to-moderate PD patients. Materials and Methods: Twenty-three PD patients, with Hoehn and Yahr stage <3, without gait disturbances or dementia and capable of using the televisit platform, were recruited for a 5-week telerehabilitation program, consisting of 1 remote visit with a therapist and a minimum of two sessions of >30-min of self-conducted exercises per week. Patients received video tutorials of exercises and were asked to keep a diary of sessions. At baseline (T0), at the end of the intervention (T1), and 1 month after the end of treatment (T2), patients were remotely assessed with MDS-UPDRS part I-III, PDQ-39, Functional Independence Measure (FIM), and Frontal Assessment Battery scales, respectively. Acceptable compliance to the program was defined as >60% matching of frequency and duration of sessions, whereas optimal compliance was set at >80% matching. Results: The dropout rate was 0%. Over 85% of patients reached acceptable adherence cut-off and around 70% reached optimal one. No adverse events were reported during sessions. The repeated measure analysis of variance (rANOVA) showed a significant effect of factor "time" for MDS-UPDRS-III (p < 0.0001) with a mean reduction of 4.217 points between T0 and T1 and return to baseline at T2. No significant effect was found for other outcome measures. Conclusion: Our findings demonstrate that telerehabilitation is safe, feasible, and effective on motor symptoms in mild-to-moderate PD patients.

Age-Related Dynamics of Serum Anti-Spike IgG Ab After the Third Dose of BNT162b2 Vaccine in a Naive Health Care Workers Population.

The kinetics of postvaccination serum anti-Spike IgG concentration were determined in 1,541 health care workers (Sant'Andrea Hospital of Rome, Italy) with no prior infection by SARS-COV-2. Anti-Spike IgG were measured at 3, 12, and 24 weeks after the completion of the primary vaccine cycle (two doses of the BNT162b2 vaccine by Biontech/Pfizer) and 3 weeks apart a third BNT162b2 dose. Stratification of the study population by age (decades from 21-30 to 61-70) highlighted that 24 weeks after cycle completion all age groups had an order of magnitude reduction in serum IgG titers. Considering older adults (age 61-70), they had significantly lower serum IgG titers at each time point compared with younger people, except after the booster dose, which induced similar and elevated IgG titers despite the age.

Feasibility, Safety, and Effectiveness of Telerehabilitation in Mild-to-Moderate Parkinson's Disease

Introduction Parkinson's disease (PD) patients frequently engage in rehabilitation to ameliorate symptoms. During the Coronavirus disease 2019 (COVID-19) pandemic, access to rehabilitation programs has been markedly limited, consequently, telerehabilitation gained popularity. In this prospective, open-label, and pilot study, we aimed to investigate feasibility, safety, and efficacy of telerehabilitation in mild-to-moderate PD patients. Materials and Methods Twenty-three PD patients, with Hoehn and Yahr stage <3, without gait disturbances or dementia and capable of using the televisit platform, were recruited for a 5-week telerehabilitation program, consisting of 1 remote visit with a therapist and a minimum of two sessions of >30-min of self-conducted exercises per week. Patients received video tutorials of exercises and were asked to keep a diary of sessions. At baseline (T0), at the end of the intervention (T1), and 1 month after the end of treatment (T2), patients were remotely assessed with MDS-UPDRS part I-III, PDQ-39, Functional Independence Measure (FIM), and Frontal Assessment Battery scales, respectively. Acceptable compliance to the program was defined as >60% matching of frequency and duration of sessions, whereas optimal compliance was set at >80% matching. Results The dropout rate was 0%. Over 85% of patients reached acceptable adherence cut-off and around 70% reached optimal one. No adverse events were reported during sessions. The repeated measure analysis of variance (rANOVA) showed a significant effect of factor “time” for MDS-UPDRS-III (p < 0.0001) with a mean reduction of 4.217 points between T0 and T1 and return to baseline at T2. No significant effect was found for other outcome measures. Conclusion Our findings demonstrate that telerehabilitation is safe, feasible, and effective on motor symptoms in mild-to-moderate PD patients.

SARS-CoV-2 Transmission Control Measures in the Emergency Department: The Role of Rapid Antigenic Testing in Asymptomatic Subjects.

Limiting transmission of SARS-CoV-2 from asymptomatic people assumes the paramount importance of keeping fragile subjects protected. We evaluated the utility of rapid SARS-CoV-2 antigen testing in asymptomatic subjects attending emergency departments in non-COVID-19 areas, using a single nasopharyngeal swab specimen collected in universal transport medium to perform both rapid antigen testing and rRT-PCR (used as reference standard) in a cohort of 899 patients. In the overall sample, the rapid antigen test had 43.9% sensitivity, 100% specificity, 100% positive predictive value, 93.6% negative predictive value. Considering subjects with rRT-PCR cycle threshold ≤30, the test had 80.4% sensitivity, 100% specificity, 100% positive predictive value, 98.8% negative predictive value. Considering subjects with rRT-PCR cycle threshold ≤25, the test had 94.7% sensitivity, 100% specificity, 100% positive predictive value and 99.7% negative predictive value. Despite low sensitivity, routine application of rapid antigen testing in the emergency department can lead to isolation in less than 30 min of about a half of asymptomatic COVID-19 subjects assigned to non-COVID-19 areas by clinical triage. The rapid test correctly identified 94.7% of asymptomatic patients with cycle threshold ≤ 25 that are supposed to be more infective; thus, it could be a useful measure to contain viral transmission in non-COVID-19 areas.

Management decisions of an Academic Radiology Department during COVID-19 pandemic: the important support of a business analytics software.

OBJECTIVES: To analyze the response in the management of both radiological emergencies and continuity of care in oncologic/fragile patients of a radiology department of Sant'Andrea Academic Hospital in Rome supported by a dedicated business analytics software during the COVID-19 pandemic. METHODS: Imaging volumes and workflows for 2019 and 2020 were analyzed. Information was collected from the hospital data warehouse and evaluated using a business analytics software, aggregated both per week and per quarter, stratified by patient service location (emergency department, inpatients, outpatients) and imaging modality. For emergency radiology subunit, radiologist workload, machine workload, and turnaround times (TATs) were also analyzed. RESULTS: Total imaging volume in 2020 decreased by 21.5% compared to that in 2019 (p < .001); CT in outpatients increased by 11.7% (p < .005). Median global TAT and median code-blue global TAT were not statistically significantly different between 2019 and 2020 and between the first and the second pandemic waves in 2020 (all p > .09). Radiologist workload decreased by 24.7% (p < .001) during the first pandemic wave in 2020 compared with the same weeks of 2019 and showed no statistically significant difference during the second pandemic wave, compared with the same weeks of 2019 (p = 0.19). CONCLUSIONS: Despite the reduction of total imaging volume due to the COVID-19 pandemic in 2020 compared to 2019, management decisions supported by a dedicated business analytics software allowed to increase the number of CT in fragile/oncologic outpatients without significantly affecting emergency radiology TATs, and emergency radiologist workload. KEY POINTS: • During the COVID-19 pandemic, management decisions supported by business analytics software guaranteed efficiency of emergency and preservation of fragile/oncologic patient continuity of care. • Real-time data monitoring using business analytics software is essential for appropriate management decisions in a department of radiology. • Business analytics should be gradually introduced in all healthcare institutions to identify strong and weak points in workflow taking correct decisions.

Nonthyroidal illness syndrome (NTIS) in severe COVID-19 patients: role of T3 on the Na/K pump gene expression and on hydroelectrolytic equilibrium.

BACKGROUND: Nonthyroidal Illness Syndrome (NTIS) can be detected in many critical illnesses. Recently, we demonstrated that this condition is frequently observed in COVID-19 patients too and it is correlated with the severity the disease. However, the exact mechanism through which thyroid hormones influence the course of COVID-19, as well as that of many other critical illnesses, is not clear yet and treatment with T4, T3 or a combination of both is still controversial. Aim of this study was to analyze body composition in COVID-19 patients in search of possible correlation with the thyroid function. METHODS AND FINDINGS: We report here our experience performed in 74 critically ill COVID-19 patients hospitalized in the intensive care unit (ICU) of our University Hospital in Rome. In these patients, we evaluated the thyroid hormone function and body composition by Bioelectrical Impedance Analysis (BIA) during the acute phase of the disease at admission in the ICU. To examine the effects of thyroid function on BIA parameters we analyzed also 96 outpatients, affected by thyroid diseases in different functional conditions. We demonstrated that COVID-19 patients with low FT3 serum values exhibited increased values of the Total Body Water/Free Fat Mass (TBW/FFM) ratio. Patients with the lowest FT3 serum values had also the highest level of TBW/FFM ratio. This ratio is an indicator of the fraction of FFM as water and represents one of the best-known body-composition constants in mammals. We found an inverse correlation between FT3 serum values and this constant. Reduced FT3 serum values in COVID-19 patients were correlated with the increase in the total body water (TBW), the extracellular water (ECW) and the sodium/potassium exchangeable ratio (Nae:Ke), and with the reduction of the intracellular water (ICW). No specific correlation was observed in thyroid patients at different functional conditions between any BIA parameters and FT3 serum values, except for the patient with myxedema, that showed a picture similar to that seen in COVID-19 patients with NTIS. Since the Na+/K+ pump is a well-known T3 target, we measured the mRNA expression levels of the two genes coding for the two major isoforms of this pump. We demonstrated that COVID-19 patients with NTIS had lower levels of mRNA of both genes in the peripheral blood mononuclear cells (PBMC)s obtained from our patients during the acute phase of the disease. In addition, we retrieved data from transcriptome analysis, performed on human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM)s treated with T3 and we demonstrated that in these cells T3 is able to stimulate the expression of these two genes in a dose-dependent manner. CONCLUSIONS: In conclusion, we demonstrated that measurement of BIA parameters is a useful method to analyze water and salt retention in COVID-19 patients hospitalized in ICU and, in particular, in those that develop NTIS. Our results indicate that NTIS has peculiar similarities with myxedema seen in severe hypothyroid patients, albeit it occurs more rapidly. The Na+/K+ pump is a possible target of T3 action, involved in the pathogenesis of the anasarcatic condition observed in our COVID-19 patients with NTIS. Finally, measurement of BIA parameters may represent good endpoints to evaluate the benefit of future clinical interventional trials, based on the administration of T3 in patients with NTIS.

H-Ras gene takes part to the host immune response to COVID-19.

Ras gene family members play a relevant role in cancer, especially when they are mutated. However, they may play additional roles in other conditions beside cancer. We performed gene expression analysis using the NanoString PanCancer IO 360 panel in the peripheral blood mononuclear cell (PBMC) of six COVID-19 patients and we found that H-Ras gene was significantly upregulated, while both K-Ras and N-Ras genes were downregulated. In particular, H-Ras gene upregulation was more evident in COVID-19 patients with a more severe disease. We compared our results with those obtained by analyzing two different and independent datasets, including a total of 53 COVID-19 patients, in which the gene expression analysis was performed using the Immunology_V2 panel. Comparative analysis of the H-Ras gene expression in these patients confirmed our preliminary results. In both of them, in fact, we were able to confirm the upregulation of the expression of the H-Ras gene. The exact role of this specific upregulation of the H-Ras gene in response to SARS-CoV-2 infection and its possible role in cancer still remains to be elucidated. In conclusion, H-Ras gene participates to the host immune response to SARS-CoV-2 virus infection, especially in patients affected by the most severe form of the COVID-19.

Gastrointestinal endoscopy can be safely performed during pandemic SARS-CoV-2 infection in Central Italy.

OBJECTIVES: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is highly contagious; gastrointestinal endoscopies are considered risky procedures for the endoscopy staff. Data on the SARS-CoV-2-exposure/infection rate of gastrointestinal endoscopy staff is scarce. This study aimed to assess the SARS-CoV-2-exposure/infection rate among gastrointestinal endoscopists/nurses performing gastrointestinal endoscopies before and after the adoption of specific prevention measures. PATIENTS AND METHODS: Cross-sectional study in a teaching hospital (Rome, Central Italy) on retrospective data (9 March-15 April 2020) of consecutive gastrointestinal endoscopies, characteristics of procedures, patients and endoscopy staff, SARS-CoV-2-exposure/positivity of patients and staff before and after adoption of prevention measures. Exposed staff tested for SARS-CoV-2 by nasopharyngeal swabs(RNA-PCR) and serology. RESULTS: A total of 130 gastrointestinal endoscopies were performed in 130 patients (age 66 ± 14 years, 51% women, 51% inpatients, 56.9% lower). A total of 12 (9.2%) patients were SARS-CoV-2-positive and 14(10.8%) had a high risk of potential infection. Of the endoscopy staff (n = 16, 5 endoscopists, 8 nurses and 3 residents), 14 (87.5%) were exposed to SARS-CoV-2-infected and 16 (100%) to potentially infected patients. 3/5 and 5/5 endoscopists were exposed to actual and potential, 1/3 and 3/3 residents to actual and potential and 8/8 nurses to actual and potential infection, respectively. None of the staff was found to be infected with SARS-CoV-2. None experienced fever or any other suspicious symptoms of coronavirus disease 2019. Before the adoption of prevention measures, more endoscopists/nurses were in the endoscopy room than after (3.5 ± 0.6 vs. 2.1 ± 0.3, P < 0.0001). CONCLUSIONS: Despite supposed high infection risk, gastrointestinal endoscopies may be safe for the endoscopy staff during the SARS-CoV-2 pandemic.

Circulating Vitamin D levels status and clinical prognostic indices in COVID-19 patients.

BACKGROUND: Several immune mechanisms activate in COVID-19 pathogenesis. Usually, coronavirus infection is characterized by dysregulated host immune responses, interleukine-6 increase, hyper-activation of cytotoxic CD8 T lymphocytes. Interestingly, Vitamin D deficiency has been often associated with altered immune responses and infections. In the present study, we evaluated Vitamin D plasma levels in patients affected with different lung involvement during COVID-19 infection. METHODS: Lymphocyte phenotypes were assessed by flow cytometry. Thoracic CT scan involvement was obtained by an image analysis program. RESULTS: Vitamin D levels were deficient in (80%) of patients, insufficient in (6.5%) and normal in (13.5%). Patients with very low Vitamin D plasma levels had more elevated D-Dimer values, a more elevated B lymphocyte cell count, a reduction of CD8 + T lymphocytes with a low CD4/CD8 ratio, more compromised clinical findings (measured by LIPI and SOFA scores) and thoracic CT scan involvement. CONCLUSIONS: Vitamin D deficiency is associated with compromised inflammatory responses and higher pulmonary involvement in COVID-19 affected patients. Vitamin D assessment, during COVID-19 infection, could be a useful analysis for possible therapeutic interventions. TRIAL REGISTRATION: 'retrospectively registered'.

Monitoring COVID-19 Transmission Risks by Quantitative Real-Time PCR Tracing of Droplets in Hospital and Living Environments.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) environmental contamination occurs through droplets and biological fluids released in the surroundings from patients or asymptomatic carriers. Surfaces and objects contaminated by saliva or nose secretions represent a risk for indirect transmission of coronavirus disease 2019 (COVID-19). We assayed surfaces from hospital and living spaces to identify the presence of viral RNA and the spread of fomites in the environment. Anthropic contamination by droplets and biological fluids was monitored by detecting the microbiota signature using multiplex quantitative real-time PCR (qPCR) on selected species and massive sequencing on 16S amplicons. A total of 92 samples (flocked swabs) were collected from critical areas during the pandemic, including indoor (three hospitals and three public buildings) and outdoor surfaces exposed to anthropic contamination (handles and handrails, playgrounds). Traces of biological fluids were frequently detected in spaces open to the public and on objects that are touched with the hands (>80%). However, viral RNA was not detected in hospital wards or other indoor and outdoor surfaces either in the air system of a COVID hospital but only in the surroundings of an infected patient, in consistent association with droplet traces and fomites. Handled objects accumulated the highest level of multiple contaminations by saliva, nose secretions, and fecal traces, further supporting the priority role of handwashing in prevention. In conclusion, anthropic contamination by droplets and biological fluids is widespread in spaces open to the public and can be traced by qPCR. Monitoring fomites can support evaluation of indirect transmission risks for coronavirus or other flu-like viruses in the environment.IMPORTANCE Several studies have evaluated the presence of SARS-CoV-2 in the environment. Saliva and nasopharyngeal droplets can land on objects and surfaces, creating fomites. A suitable indicator would allow the detection of droplets or biofluids carrying the virus. Therefore, we searched for viral RNA and droplets and fomites on at risk surfaces. We monitored by qPCR or next generation sequencing (NGS) droplets through their microbiota. Although the study was performed during the pandemic, SARS-CoV-2 was not significantly found on surfaces, with the only exception of environmental areas near infectious patients. Conversely, anthropic contamination was frequent, suggesting a role for biofluids as putative markers of indirect transmission and risk assessment. Moreover, all SARS-CoV-2-contaminated surfaces showed droplets' microbiota. Fomite monitoring by qPCR may have an impact on public health strategies, supporting prevention of indirect transmission similarly to what is done for other communicable diseases (e.g., influenza and influenza-like infections).

Evidence-Based Considerations Exploring Relations between SARS-CoV-2 Pandemic and Air Pollution: Involvement of PM2.5-Mediated Up-Regulation of the Viral Receptor ACE-2.

The COVID-19/SARS-CoV-2 pandemic struck health, social and economic systems worldwide, and represents an open challenge for scientists -coping with the high inter-individual variability of COVID-19, and for policy makers -coping with the responsibility to understand environmental factors affecting its severity across different geographical areas. Air pollution has been warned of as a modifiable factor contributing to differential SARS-CoV-2 spread but the biological mechanisms underlying the phenomenon are still unknown. Air quality and COVID-19 epidemiological data from 110 Italian provinces were studied by correlation analysis, to evaluate the association between particulate matter (PM)2.5 concentrations and incidence, mortality rate and case fatality risk of COVID-19 in the period 20 February-31 March 2020. Bioinformatic analysis of the DNA sequence encoding the SARS-CoV-2 cell receptor angiotensin-converting enzyme 2 (ACE-2) was performed to identify consensus motifs for transcription factors mediating cellular response to pollutant insult. Positive correlations between PM2.5 levels and the incidence (r = 0.67, p < 0.0001), the mortality rate (r = 0.65, p < 0.0001) and the case fatality rate (r = 0.7, p < 0.0001) of COVID-19 were found. The bioinformatic analysis of the ACE-2 gene identified nine putative consensus motifs for the aryl hydrocarbon receptor (AHR). Our results confirm the supposed link between air pollution and the rate and outcome of SARS-CoV-2 infection and support the hypothesis that pollution-induced over-expression of ACE-2 on human airways may favor SARS-CoV-2 infectivity.

Prevalence of Sars-Cov-2 Infection in Health Workers (HWs) and Diagnostic Test Performance: The Experience of a Teaching Hospital in Central Italy.

(1) Background: Health workers (HWs) are at high risk of acquiring SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) infections. Therefore, health authorities further recommend screening strategies for SARS-CoV-2 infection in exposed or high-risk HWs. Nevertheless, to date, the best/optimal method to screen HWs for SARS-CoV-2 infection is still under debate, and data on the prevalence of SARS-CoV-2 infection in HWs are still scarce. The present study aims to assess the SARS-CoV-2 infection rate amongst HWs in a teaching hospital in Central Italy and the diagnostic performance of SARS-CoV-2 serology (index test) in comparison with the SARS-CoV-2 RNA PCR assay (reference standard). (2) Methods: A cross-sectional study on the retrospective data of HWs tested for SARS-CoV-2 by RNA-RT-PCR on nasopharyngeal swabs and by an IgM/IgG serology assay on venous blood samples, irrespective of exposure and/or symptoms, was carried out. (3) Results: A total of 2057 HWs (median age 46, 19-69 years, females 60.2%) were assessed by the RNA RT-PCR assay and 58 (2.7%) tested positive for SARS-CoV-2 infection. Compared with negative HWs, SARS-CoV-2-positives were younger (mean age 41.7 versus 45.2, p < 0.01; 50% versus 31% under or equal to 40 years old, p < 0.002) and had a shorter duration of employment (64 versus 125 months, p = 0.02). Exposure to SARS-CoV-2 was more frequent in positive HWs than in negatives (55.2% versus 27.5%, p < 0.0001). In 44.8% of positive HWs, no exposure was traced. None of the positive HWs had a fatal outcome, none of them had acute respiratory distress syndrome, and only one required hospitalization for mild/moderate pneumonia. In 1084 (51.2%) HWs, nasopharyngeal swabs and an IgM/IgG serology assay were performed. With regard to IgM serology, sensitivity was 0% at a specificity of 98.99% (positive predictive value, PPV 0%, negative predictive value, NPV 99.2%). Concerning IgG serology and irrespective of the time interval between nasopharyngeal swab and serology, sensitivity was 50% at a specificity of 99.1% (PPV 28.6%, NPV 99.6%). IgG serology showed a higher diagnostic performance when performed at least two weeks after testing SARS-CoV-2-positive at the RNA RT-PCR assay by a nasopharyngeal swab. (4) Conclusions: Our experience in Central Italy demonstrated a low prevalence of SARS-CoV-2 infection amongst HWs, but higher than in the general population. Nearly half of the positive HWs reported no previous exposure to SARS-CoV-2-infected subjects and were diagnosed thanks to the proactive screening strategy implemented. IgG serology seems useful when performed at least two weeks after an RNA RT-PCR assay. IgM serology does not seem to be a useful test for the diagnosis of active SARS-CoV-2 infection. High awareness of SARS-CoV-2 infection is mandatory for all people, but especially for HWs, irrespective of symptoms, to safeguard their health and that of patients.