Association of Torquetenovirus Viremia with Physical Frailty and Cognitive Impairment in Three Independent European Cohorts.

INTRODUCTION: Immunosenescence and inflammaging have been implicated in the pathophysiology of frailty. Torquetenovirus (TTV), a single-stranded DNA anellovirus, the major component of the human blood virome, shows an increased replication rate with advancing age. An elevated TTV viremia has been associated with an impaired immune function and an increased risk of mortality in the older population. The objective of this study was to analyze the relation between TTV viremia, physical frailty, and cognitive impairment. METHODS: TTV viremia was measured in 1,131 nonfrail, 45 physically frail, and 113 cognitively impaired older adults recruited in the MARK-AGE study (overall mean age 64.7 ± 5.9 years), and then the results were checked in two other independent cohorts from Spain and Portugal, including 126 frail, 252 prefrail, and 141 nonfrail individuals (overall mean age: 77.5 ± 8.3 years). RESULTS: TTV viremia ≥4log was associated with physical frailty (OR: 4.69; 95% CI: 2.06-10.67, p < 0.0001) and cognitive impairment (OR: 3.49, 95% CI: 2.14-5.69, p < 0.0001) in the MARK-AGE population. The association between TTV DNA load and frailty status was confirmed in the Spanish cohort, while a slight association with cognitive impairment was observed (OR: 1.33; 95% CI: 1.000-1.773), only in the unadjusted model. No association between TTV load and frailty or cognitive impairment was found in the Portuguese sample, although a negative association between TTV viremia and MMSE score was observed in Spanish and Portuguese females. CONCLUSIONS: These findings demonstrate an association between TTV viremia and physical frailty, while the association with cognitive impairment was observed only in the younger population from the MARK-AGE study. Further research is necessary to clarify TTV's clinical relevance in the onset and progression of frailty and cognitive decline in older individuals.

Blood circulating bacterial DNA in hospitalized old COVID-19 patients.

BACKGROUND: Coronavirus disease COVID-19 is a heterogeneous condition caused by SARS-CoV-2 infection. Generally, it is characterized by interstitial pneumonia that can lead to impaired gas-exchange, acute respiratory failure, and death, although a complex disorder of multi-organ dysfunction has also been described. The pathogenesis is complex, and a variable combination of factors has been described in critically ill patients. COVID-19 is a particular risk for older persons, particularly those with frailty and comorbidities. Blood bacterial DNA has been reported in both physiological and pathological conditions and has been associated with some haematological and laboratory parameters but, to date, no study has characterized it in hospitalized old COVID-19 patients The present study aimed to establish an association between blood bacterial DNA (BB-DNA) and clinical severity in old COVID-19 patients. RESULTS: BB-DNA levels were determined, by quantitative real-time PCRs targeting the 16S rRNA gene, in 149 hospitalized older patients (age range 65-99 years) with COVID-19. Clinical data, including symptoms and signs of infection, frailty status, and comorbidities, were assessed. BB-DNA was increased in deceased patients compared to discharged ones, and Cox regression analysis confirmed an association between BB-DNA and in-hospital mortality. Furthermore, BB-DNA was positively associated with the neutrophil count and negatively associated with plasma IFN-alpha. Additionally, BB-DNA was associated with diabetes. CONCLUSIONS: The association of BB-DNA with mortality, immune-inflammatory parameters and diabetes in hospitalized COVID-19 patients suggests its potential role as a biomarker of unfavourable outcomes of the disease, thus it could be proposed as a novel prognostic marker in the assessment of acute COVID-19 disease.

Effects of Human LAV-BPIFB4 Gene Therapy on the Epigenetic Clock and Health of Aged Mice.

The homozygous genotype of the Longevity-Associated Variant (LAV) in Bactericidal/Permeability-Increasing Fold-Containing Family B member 4 (BPIFB4) is enriched in long-living individuals of three independent populations and its genetic transfer in C57BL/6J mice showed a delay in frailty progression and improvement of several biomarkers of aging and multiple aspects of health. The C57BL/6J strain is a suitable model for studying therapies aimed at extending healthy aging and longevity due to its relatively short lifespan and the availability of aging biomarkers. Epigenetic clocks based on DNA methylation profiles are reliable molecular biomarkers of aging, while frailty measurement tools are used to evaluate overall health during aging. In this study, we show that the systemic gene transfer of LAV-BPIFB4 in aged C57BL/6J mice was associated with a significant reduction in the epigenetic clock-based biological age, as measured by a three CpG clock method. Furthermore, LAV-BPIFB4 gene transfer resulted in an improvement of the Vitality Score with a reduction in the Frailty Index. These findings further support the use of LAV-BPIFB4 gene therapy to induce beneficial effects on epigenetic mechanisms associated with aging and frailty in aged mice, with potential implications for future therapies to prevent frailty in humans.

Effect of Cytomegalovirus Reactivation on Inflammatory Status and Mortality of Older COVID-19 Patients.

Herpesviridae reactivation such as cytomegalovirus (CMV) has been described in severe COVID-19 (COronaVIrusDisease-2019). This study aimed to understand if CMV reactivation in older COVID-19 patients is associated with increased inflammation and in-hospital mortality. In an observational single-center cohort study, 156 geriatric COVID-19 patients were screened for CMV reactivation by RT-PCR. Participants underwent a comprehensive clinical investigation that included medical history, functional evaluation, laboratory tests and cytokine assays (TNF-α, IFN-α, IL-6, IL-10) at hospital admission. In 19 (12.2%) of 156 COVID-19 patients, CMV reactivation was detected. Multivariate Cox regression models showed that in-hospital mortality significantly increased among CMV positive patients younger than 87 years (HR: 9.94, 95% CI: 1.66-59.50). Other factors associated with in-hospital mortality were C-reactive protein (HR: 1.17, 95% CI: 1.05-1.30), neutrophil count (HR: 1.20, 95% CI: 1.01-1.42) and clinical frailty scale (HR:1.54, 95% CI: 1.04-2.28). In patients older than 87 years, neutrophil count (HR: 1.13, 95% CI: 1.05-1.21) and age (HR: 1.15, 95% CI: 1.01-1.31) were independently associated with in-hospital mortality. CMV reactivation was also correlated with increased IFN-α and TNF-α serum levels, but not with IL-6 and IL-10 serum changes. In conclusion, CMV reactivation was an independent risk factor for in-hospital mortality in COVID-19 patients younger than 87 years old, but not in nonagenarians.

Bacterial DNAemia in Alzheimer's Disease and Mild Cognitive Impairment: Association with Cognitive Decline, Plasma BDNF Levels, and Inflammatory Response.

Microbial dysbiosis (MD) provokes gut barrier alterations and bacterial translocation in the bloodstream. The increased blood bacterial DNA (BB-DNA) may promote peripheral- and neuro-inflammation, contributing to cognitive impairment. MD also influences brain-derived neurotrophic factor (BDNF) production, whose alterations contribute to the etiopathogenesis of Alzheimer's disease (AD). The purpose of this study is to measure BB-DNA in healthy elderly controls (EC), and in patients with mild cognitive impairment (MCI) and AD to explore the effect on plasma BDNF levels (pBDNF), the inflammatory response, and the association with cognitive decline during a two-year follow-up. Baseline BB-DNA and pBDNF were significantly higher in MCI and AD than in EC. BB-DNA was positively correlated with pBDNF in AD, plasma Tumor necrosis factor-alpha (TNF-α), and Interleukin-10 (IL-10) levels in MCI. AD patients with BB-DNA values above the 50th percentile had lower baseline Mini-Mental State Examination (MMSE). After a two-year follow-up, AD patients with the highest BB-DNA tertile had a worse cognitive decline, while higher BB-DNA levels were associated with higher TNF-α and lower IL-10 in MCI. Our study demonstrates that, in early AD, the higher the BB-DNA levels, the higher the pBDNF levels, suggesting a defensive attempt; BB-DNA seems to play a role in the AD severity/progression; in MCI, higher BB-DNA may trigger an increased inflammatory response.

FKBP5 rs4713916: A Potential Genetic Predictor of Interindividual Different Response to Inhaled Corticosteroids in Patients with Chronic Obstructive Pulmonary Disease in a Real-Life Setting.

Background: Chronic obstructive pulmonary disease (COPD) is a common, preventable, and manageable lung disease characterized by large heterogeneity in disease presentation and grades impairment. Inhaled corticosteroids (ICS) are commonly used to manage COPD/COPD-exacerbation. The patient's response is characterized by interindividual variability without disease progression/survival modification. Objectives: We hypothesize that a therapeutic intervention may be more effective if single nucleotide polymorphisms (SNPs) are investigated. Methods: In 71 COPD patients under pulmonary rehabilitation, a small number of powerful SNPs, selected according to current literature, were analyzed; namely the glucocorticoid receptor gene NR3C1 (rs6190/rs6189/rs41423247), the glucocorticoid-induced transcript 1 gene (GLCCI1 rs37972), and the related co-chaperone FKBP5 gene (rs4713916). MDR1 rs2032582 was also evaluated. Lung function outcomes were assessed. Results: A significant association with functional outcomes, namely FEV1 (forced expiration volume/one second) and 6MWD (six-minutes walking distance), was found for rs4713916 and weakly for rs37972. The genotype rs4713916(GA) and, in a lesser extent, the genotype rs37972(TT), were more favorable than the wild-type. Conclusions: Our study supports a possible picture of pharmacogenomic control for COPD intervention. rs4713916 and, possibly, rs37972 may be useful predictors of clinical outcome. These results may help to tailor an optimal dose for individual COPD patients based on their genetic makeup.

Anti-inflammatory Activity of Tocotrienols in Age-related Pathologies: A SASPected Involvement of Cellular Senescence.

Tocotrienols (T3) have been shown to represent a very important part of the vitamin E family since they have opened new opportunities to prevent or treat a multitude of age-related chronic diseases. The beneficial effects of T3 include the amelioration of lipid profile, the promotion of Nrf2 mediated cytoprotective activity and the suppression of inflammation. All these effects may be the consequence of the ability of T3 to target multiple pathways. We here propose that these effects may be the result of a single target of T3, namely senescent cells. Indeed, T3 may act by a direct suppression of the senescence-associated secretory phenotype (SASP) produced by senescent cells, mediated by inhibition of NF-kB and mTOR, or may potentially remove the origin of the SASP trough senolysis (selective death of senescent cells). Further studies addressed to investigate the impact of T3 on cellular senescence "in vitro" as well as in experimental models of age-related diseases "in vivo" are clearly encouraged.

Inducers of Senescence, Toxic Compounds, and Senolytics: The Multiple Faces of Nrf2-Activating Phytochemicals in Cancer Adjuvant Therapy.

The reactivation of senescence in cancer and the subsequent clearance of senescent cells are suggested as therapeutic intervention in the eradication of cancer. Several natural compounds that activate Nrf2 (nuclear factor erythroid-derived 2-related factor 2) pathway, which is involved in complex cytoprotective responses, have been paradoxically shown to induce cell death or senescence in cancer. Promoting the cytoprotective Nrf2 pathway may be desirable for chemoprevention, but it might be detrimental in later stages and advanced cancers. However, senolytic activity shown by some Nrf2-activating compounds could be used to target senescent cancer cells (particularly in aged immune-depressed organisms) that escape immunosurveillance. We herein describe in vitro and in vivo effects of fifteen Nrf2-interacting natural compounds (tocotrienols, curcumin, epigallocatechin gallate, quercetin, genistein, resveratrol, silybin, phenethyl isothiocyanate, sulforaphane, triptolide, allicin, berberine, piperlongumine, fisetin, and phloretin) on cellular senescence and discuss their use in adjuvant cancer therapy. In light of available literature, it can be concluded that the meaning and the potential of adjuvant therapy with natural compounds in humans remain unclear, also taking into account the existence of few clinical trials mostly characterized by uncertain results. Further studies are needed to investigate the therapeutic potential of those compounds that display senolytic activity.

Different transcriptional profiling between senescent and non-senescent human coronary artery endothelial cells (HCAECs) by Omeprazole and Lansoprazole treatment.

Recent evidence suggests that high dose and/or long term use of proton pump inhibitors (PPIs) may increase the risk of adverse cardiovascular events in older patients, but mechanisms underlying these detrimental effects are not known. Taking into account that the senescent endothelial cells have been implicated in the genesis or promotion of age-related cardiovascular disease, we hypothesized an active role of PPIs in senescent cells. The aim of this study is to investigate the changes in gene expression occurring in senescent and non-senescent human coronary artery endothelial cells (HCAECs) following Omeprazole (OPZ) or Lansoprazole (LPZ) treatment. Here, we show that atherogenic response is among the most regulated processes in PPI-treated HCAECs. PPIs induced down-regulation of anti-atherogenic chemokines (CXCL11, CXCL12 and CX3CL1) in senescent but not in non-senescent cells, while the same chemokines were up-regulated in untreated senescent cells. These findings support the hypothesis that up-regulated anti-atherogenic chemokines may represent a defensive mechanism against atherosclerosis during cellular senescence, and suggest that PPIs could activate pro-atherogenic pathways by changing the secretory phenotype of senescent HCAECs. Moreover, the genes coding for fatty acid binding protein 4 (FABP4) and piezo-type mechanosensitive ion channel component 2 (PIEZO2) were modulated by PPIs treatment with respect to untreated cells. In conclusions, our results show that long-term and high dose use of PPI could change the secretory phenotype of senescent cells, suggesting one of the potential mechanisms by which use of PPI can increase adverse outcomes in older subjects.

Circadian rhythms of body temperature and locomotor activity in aging BALB/c mice: early and late life span predictors.

Impairment of one or more parameters of circadian rhythms (CR) of body temperature (BT) and locomotor activity (LMA) are considered among the hallmarks of mammalian aging. These alterations are frequently used as markers for imminent death in laboratory mice. However, there are still contradictory data for particular strains and it is also uncertain which changes might predict senescence changes later in life, including the force of mortality. In the present paper we use telemetry to study LMA and CR of BT during aging of BALB/c mice. At our knowledge this is the first time that CR of BT and LMA are investigated in this strain in a range of age covering the whole lifespan, from young adult up to very old age. CR of BT was analyzed with a cosine model using a cross sectional approach and follow-up measurements. The results show that BT, LMA, amplitude, goodness-of-fit (GoF) to circadian cycle of temperature decrease with different shapes during chronological age. Moreover, we found that the % change of amplitude and BT in early life (5-19 months) can predict the remaining lifespan of the mice. Later in life (22-32 months), best predictors are single measurements of LMA and GoF. The results of this study also offer potential measures to rapidly identifying freely unrestrained mice with the worst longitudinal outcome and against which existing or novel biomarkers and treatments may be assessed.

Association of Inflammatory Mediators with Mitochondrial DNA Variants in Geriatric COVID-19 Patients.

COVID-19 remains a serious concern for elderly individuals with underlying comorbidities. SARS-CoV-2 can target and damage mitochondria, potentially leading to mutations in mitochondrial DNA (mtDNA). This study aimed to evaluate single nucleotide substitutions in mtDNA and analyze their correlation with inflammatory biomarkers in elderly COVID-19 patients. A total of 30 COVID-19 patients and 33 older adult controls without COVID-19 (aged over 65 years) were enrolled. mtDNA was extracted from buffy coat samples and sequenced using a chip-based resequencing system (MitoChip v2.0) which detects both homoplasmic and heteroplasmic mtDNA variants (40-60% heteroplasmy), and allows the assessment of low-level heteroplasmy (<10% heteroplasmy). Serum concentrations of IL-6, IFN-α, TNF-α and IL-10 were determined in patients by a high-sensitivity immunoassay. We found a higher burden of total heteroplasmic variants in COVID-19 patients compared to controls with a selective increment in ND1 and COIII genes. Low-level heteroplasmy was significantly elevated in COVID-19 patients, especially in genes of the respiratory complex I. Both heteroplasmic variant burden and low-level heteroplasmy were associated with increased levels of IL-6, TNF-α, and IFN-α. These findings suggest that SARS-CoV-2 may induce mtDNA mutations that are related to the degree of inflammation.

Plasma cfDNA abundance as a prognostic biomarker for higher risk of death in geriatric cardiovascular patients.

The management of geriatric cardiovascular disease (CVD) patients with multimorbidity remains challenging and could potentially be improved by integrating clinical data with innovative prognostic biomarkers. In this context, the analysis of circulating analytes, including cell-free DNA (cfDNA), appears particularly promising. Here, we investigated circulating cfDNA (measured through the quantification of 247 bp and 115 bp Alu genomic fragments) in a cohort of 244 geriatric CVD patients with multimorbidity hospitalised for acute CVD or non-CVD events. Survival analysis showed a direct association between Alu 247 cfDNA abundance and risk of death, particularly evident in the first six months after admission for acute CVD events. Higher plasma cfDNA concentration was associated with mortality in the same period of time. The cfDNA integrity (Alu 247/115), although not associated with outcome, appeared to be useful in discriminating patients in whom Alu 247 cfDNA abundance is most effective as a prognostic biomarker. The cfDNA parameters were associated with several biochemical markers of inflammation and myocardial damage. In conclusion, an increase in plasma cfDNA abundance at hospital admission is indicative of a higher risk of death in geriatric CVD patients, especially after acute CVD events, and its analysis may be potentially useful for risk stratification.

Preliminary Comparison of Fractional Absorption of Zinc Sulphate, Zinc Gluconate, and Zinc Aspartate after Oral Supple-Mentation in Healthy Human Volunteers.

(1) Background: Zinc is generally used as a nutritional supplement for individuals at nutritional risk, such as older adults. This preliminary study investigated the fractional Zn absorption (FZA) after the supplementation on eight healthy volunteers with three different Zn complexes acquired with milk. (2) Methods: The design was a double-blind, three-period crossover trial. The volunteers were randomly divided into three groups. Each individual consumed 200 mL of bovine milk and rotated through a simultaneous administration of a single oral dose of 70ZnSO4, 70Zn-Gluconate (70Zn-Glu), and 70Zn-Aspartate (70Zn-Asp), equivalent to 2.0 mg 70Zn, followed by 2 weeks of wash-out. An estimation of the FZA for comparative purposes was computed by the isotopic ratio between 66Zn and 70Zn in urine collected before and 48 h after administration. (3) Results: The estimated FZA was found to be significantly higher for 70Zn-Asp when compared to the other forms, while the FZA of 70Zn-Glu was found to be significantly higher than 70ZnSO4. (4) Conclusions: The results of this study suggest that complexing Zn with aspartate in milk could be a useful tool to improve FZA in individuals at risk of Zn deficiency. These results provide a rationale for conducting further studies on Zn-Asp preparations.

Early Benefits with Potential Long-Term Risks of a Comprehensive Intervention on Serum Cortisol Levels and Cognitive Performance in Patients with Alzheimer's Disease.

Background: Elevated cortisol levels represent a risk factor for Alzheimer's disease (AD), prompting treatments to lower hormone concentrations for preventive or therapeutic purposes. Objective: To assess the efficacy of a comprehensive intervention (CI) in modulating serum cortisol levels in patients with AD. Methods: CI consisted in a 2-month protocol involving cognitive stimulation, psychological support, lifestyle guidance, leisure activities, and socialization. AD subjects were randomly assigned to experimental (EG, n = 45) and control (CG, n = 45) groups. A wide range of sociodemographic, cognitive, psychosocial, and functional conditions were evaluated before, at the conclusion, and 24 months after CI. Data about lifestyle and drug prescription were also recorded. Results: Baseline evaluations revealed that higher cortisol levels correlated with worse cognitive status (higher CDR and ADAS-Cog values and lower MMSE scores), increased depressive symptoms, and reduced physical and social engagement. Following CI, EG exhibited reduced cortisol levels, improved overall cognitive status, and enhanced verbal working memory and executive functions compared to CG. However, at the 24-month follow-up, EG displayed a rebound effect, characterized by elevated cortisol levels and cognitive decline compared to CG. Conclusions: These findings strengthen the adverse relationship between excessive cortisol and deficits in cognition/behavior in AD, demonstrate the short-term benefits of CI, and emphasize the potential long-term risks, which may be attributed to the fragile nature of the AD brain. Comprehensive interventions can yield positive results, but careful calibration of type and duration is necessary, considering disease progression and the potential need for re-administration.

Spreading Senescent Cells' Burden and Emerging Therapeutic Targets for Frailty.

The spreading of senescent cells' burden holds profound implications for frailty, prompting the exploration of novel therapeutic targets. In this perspective review, we delve into the intricate mechanisms underlying senescent cell spreading, its implications for frailty, and its therapeutic development. We have focused our attention on the emerging age-related biological factors, such as microbiome and virome alterations, elucidating their significant contribution to the loss of control over the accumulation rate of senescent cells, particularly affecting key frailty domains, the musculoskeletal system and cerebral functions. We believe that gaining an understanding of these mechanisms could not only aid in elucidating the involvement of cellular senescence in frailty but also offer diverse therapeutic possibilities, potentially advancing the future development of tailored interventions for these highly diverse patients.

Comprehensive longitudinal non-invasive quantification of healthspan and frailty in a large cohort (n = 546) of geriatric C57BL/6 J mice.

Frailty is an age-related condition characterized by a multisystem functional decline, increased vulnerability to stressors, and adverse health outcomes. Quantifying the degree of frailty in humans and animals is a health measure useful for translational geroscience research. Two frailty measurements, namely the frailty phenotype (FP) and the clinical frailty index (CFI), have been validated in mice and are frequently applied in preclinical research. However, these two tools are based on different concepts and do not necessarily identify the same mice as frail. In particular, the FP is based on a dichotomous classification that suffers from high sample size requirements and misclassification problems. Based on the monthly longitudinal non-invasive assessment of frailty in a large cohort of mice, here we develop an alternative scoring method, which we called physical function score (PFS), proposed as a continuous variable that resumes into a unique function, the five criteria included in the FP. This score would not only reduce misclassification of frailty but it also makes the two tools, PFS and CFI, integrable to provide an overall measurement of health, named vitality score (VS) in aging mice. VS displays a higher association with mortality than PFS or CFI and correlates with biomarkers related to the accumulation of senescent cells and the epigenetic clock. This longitudinal non-invasive assessment strategy and the VS may help to overcome the different sensitivity in frailty identification, reduce the sample size in longitudinal experiments, and establish the effectiveness of therapeutic/preventive interventions for frailty or other age-related diseases in geriatric animals.

Cellular senescence and frailty: a comprehensive insight into the causal links.

Senescent cells may have a prominent role in driving inflammation and frailty. The impact of cellular senescence on frailty varies depending on the assessment tool used, as it is influenced by the criteria or items predominantly affected by senescent cells and the varying weights assigned to these items across different health domains. To address this challenge, we undertook a thorough review of all available studies involving gain- or loss-of-function experiments as well as interventions targeting senescent cells, focusing our attention on those studies that examined outcomes based on the individual frailty phenotype criteria or specific items used to calculate two humans (35 and 70 items) and one mouse (31 items) frailty indexes. Based on the calculation of a simple "evidence score," we found that the burden of senescent cells related to musculoskeletal and cerebral health has the strongest causal link to frailty. We deem that insight into these mechanisms may not only contribute to clarifying the role of cellular senescence in frailty but could additionally provide multiple therapeutic opportunities to help the future development of a desirable personalized therapy in these extremely heterogeneous patients.

Plasma Bacterial DNA Load as a Potential Biomarker for the Early Detection of Colorectal Cancer: A Case-Control Study.

The gut microbiota has gained increasing attention in recent years due to its significant impact on colorectal cancer (CRC) development and progression. The recent detection of bacterial DNA load in plasma holds promise as a potential non-invasive approach for early cancer detection. The aim of this study was to examine the quantity of bacterial DNA present in the plasma of 50 patients who have CRC in comparison to 40 neoplastic disease-free patients, as well as to determine if there is a correlation between the amount of plasma bacterial DNA and various clinical parameters. Plasma bacterial DNA levels were found to be elevated in the CRC group compared to the control group. As it emerged from the logistic analysis (adjusted for age and gender), these levels were strongly associated with the risk of CRC (OR = 1.02, p < 0.001, 95% C.I.: 1.01-1.03). Moreover, an association was identified between a reduction in tumor mass and the highest tertile of plasma bacterial DNA. Our findings indicate that individuals with CRC displayed a higher plasma bacterial DNA load compared to healthy controls. This observation lends support to the theory of heightened bacterial migration from the gastrointestinal tract to the bloodstream in CRC. Furthermore, our results establish a link between this phenomenon and the size of the tumor mass.

Sensibility and Specificity of the VitaPCR™ SARS-CoV-2 Assay for the Rapid Diagnosis of COVID-19 in Older Adults in the Emergency Department.

(1) Background: During the COVID-19 pandemic, rapid and reliable diagnostic tools are needed for detecting SARS-CoV-2 infection in urgent cases at admission to the hospital. We aimed to assess the performances of the rapid molecular VitaPCR™ test (Menarini Diagnostics) in a sample of older adults admitted to the Emergency Department of two Italian hospitals (2) Methods: The comparison between the rapid VitaPCR™ and the RT-PCR was performed in 1695 samples. Two naso-pharyngeal swab samplings from each individual were obtained and processed using the VitaPCR™ and the RT-PCR for the detection of SARS-CoV-2 (3) Results: VitaPCR™ exhibited good precision (<3% CV) and an almost perfect overall agreement (Cohen's K = 0.90) with the RT-PCR. The limit of detection of the VitaPCR™ was 4.1 copies/µL. Compared to the RT-PCR, the sensitivity, the specificity, and the positive and negative predictive values of VitaPCR™ were 83.4%, 99.9%, 99.2% and 98.3%, respectively (4) Conclusions: The VitaPCR™ showed similar sensitivity and specificity to other molecular-based rapid tests. This study suggests that the VitaPCR™ can allow the rapid management of patients within the Emergency Department. Nevertheless, it is advisable to obtain a negative result by a RT-PCR assay before admitting a patient to a regular ward.