John Cunningham Virus and Progressive Multifocal Leukoencephalopathy: A Falsely Played Diagnosis.

Progressive Multifocal Leukoencephalopathy (PML) is a possibly fatal demyelinating disease and John Cunningham Polyomavirus (JCPyV) is believed to cause this condition. The so-called JCPyV was initially reported in lymphoma and Human Immunodeficiency Virus (HIV) cases, whereas nowadays, its incidence is increasing in Multiple Sclerosis (MS) cases treated with natalizumab (Tysabri). However, there are conflicting literature data on its pathology and diagnosis, whereas some misdiagnosed reports exist, giving rise to further questions towards the topic. In reality, the so-called PML and the supposed JCPyV are not what they seem to be. In addition, novel and more frequent PML-like conditions may be reported, especially after the Coronavirus Disease 2019 (COVID-19) pandemic.

C-Reactive Protein: Pathophysiology, Diagnosis, False Test Results and a Novel Diagnostic Algorithm for Clinicians.

The current literature provides a body of evidence on C-Reactive Protein (CRP) and its potential role in inflammation. However, most pieces of evidence are sparse and controversial. This critical state-of-the-art monography provides all the crucial data on the potential biochemical properties of the protein, along with further evidence on its potential pathobiology, both for its pentameric and monomeric forms, including information for its ligands as well as the possible function of autoantibodies against the protein. Furthermore, the current evidence on its potential utility as a biomarker of various diseases is presented, of all cardiovascular, respiratory, hepatobiliary, gastrointestinal, pancreatic, renal, gynecological, andrological, dental, oral, otorhinolaryngological, ophthalmological, dermatological, musculoskeletal, neurological, mental, splenic, thyroid conditions, as well as infections, autoimmune-supposed conditions and neoplasms, including other possible factors that have been linked with elevated concentrations of that protein. Moreover, data on molecular diagnostics on CRP are discussed, and possible etiologies of false test results are highlighted. Additionally, this review evaluates all current pieces of evidence on CRP and systemic inflammation, and highlights future goals. Finally, a novel diagnostic algorithm to carefully assess the CRP level for a precise diagnosis of a medical condition is illustrated.

The Deceptive COVID-19: Lessons from Common Molecular Diagnostics and a Novel Plan for the Prevention of the Next Pandemic.

The COVID-19 pandemic took place during the years 2020-2022 and the virus, named SARS-CoV-2, seems likely to have resulted in an endemic disease. Nevertheless, widespread COVID-19 has given rise to several major molecular diagnostics' facts and concerns that have emerged during the overall management of this disease and the subsequent pandemic. These concerns and lessons are undeniably critical for the prevention and control of future infectious agents. Furthermore, most populaces were introduced to several new public health maintenance strategies, and again, some critical events arose. The purpose of this perspective is to thoroughly analyze all these issues and the concerns, such as the molecular diagnostics' terminologies, their role, as well as the quantity and quality issues with a molecular diagnostics' test result. Furthermore, it is speculated that society will be more vulnerable in the future and prone to emerging infectious diseases; thus, a novel preventive medicine's plan for the prevention and control of future (re)emerging infectious diseases is presented, so as to aid the early prevention of future epidemics and pandemics.

Analysis of ADORA2A rs5760423 and CYP1A2 rs762551 Genetic Variants in Patients with Alzheimer's Disease.

Various studies have been conducted, exploring the genetic susceptibility of Alzheimer's disease (AD). Adenosine receptor subtype A2a (ADORA2A) and cytochrome P450 1A2 (CYP1A2) are implicated in pathways such as oxidative stress and caffeine metabolism, which are associated with AD. The aim of this study was to explore for any potential association between the ADORA2A rs5760423 and the CYP1A2 rs762551 genetic variants and AD. A case-control study was performed with a total of 654 subjects (327 healthy controls and 327 patients with AD). Five genetic models were assumed. We also examined the allele-allele combination of both variants. The value of 0.05 was considered as the statistical significance threshold. A statistically significant association was found between ADORA2A rs5760423 and AD, as the "T" allele was associated with increased AD risk in recessive (OR = 1.51 (1.03-2.21)) and log-additive (OR = 1.30 (1.04-1.62)) genetic modes. In the codominant model, the TT genotype was more prevalent compared to the GG genotype (OR = 1.71 (1.09-2.66)). The statistical significance was maintained after adjustment for sex. No association between CYP1A2 rs762551 or allele-allele combination and AD was detected. We provide preliminary indication for a possible association between the ADORA2A rs5760423 genetic polymorphism and AD.

Current Evidence in SARS-CoV-2 mRNA Vaccines and Post-Vaccination Adverse Reports: Knowns and Unknowns.

The novel mRNA vaccinations against COVID-19 are gaining worldwide attention for their potential efficacy, as well as for the diagnosis of some post-vaccination-reported adverse reactions. In this state-of-the-art review article, we present the current evidence regarding mainly the diagnosis of spontaneous allergic reactions, the skin occurrences, the vascular, blood, endocrine and heart events, the respiratory reports, the gastrointestinal, hepatic and kidney events, the reproductive and pregnancy issues and the muscle events, as well as the ear, eye, neurologic and psychiatric events following mRNA vaccination against COVID-19. We further present some evidence regarding the mRNA strategies, we provide important information for side effects associated with the spike protein based LNP-mRNA vaccine and its adjuvants, as well as evidence for all the possible dangerous roles of the spike protein, and we discuss our expert opinion on the knowns and the unknowns towards the topic.

Managing Viral Emerging Infectious Diseases via current Molecular Diagnostics in the Emergency Department: the Tricky Cases.

INTRODUCTION: Emerging infectious diseases' diagnosis has been a major problem in most hospitals and other senior care facilities, especially for the current Coronavirus Disease 2019 (COVID-19). The various clinical manifestations, and the several radiology and laboratory data combined with the misleading test results for identifying the virus, are responsible for certain misdiagnoses, especially for suspected cases that visit the emergency department and require urgent management and further treatment. AREAS COVERED: The major challenges for emerging infectious diseases' molecular diagnosis are being described here on a great scale, and, finally, strategies for a precise and on-the-spot molecular diagnosis are thoroughly discussed. Related literature was searched using the PubMed, Science Direct, and EMBASE databases published until May 2022 on the general information for viral infections and relevant false test results. EXPERT OPINION: Emerging diseases' molecular diagnosis via current common diagnostic assays seems to be extremely tricky, and front-line physicians and other senior care facilities should be able to recognize some falsely diagnosed cases or even prevent their existence. Further biotechnologic revolution concerning viral molecular diagnostics will be evident in the near future, thus new methods' limitations should be highlighted to physicians from the very beginning of their performances and wide utilization.

Medical/Surgical, Cloth and FFP/(K)N95 Masks: Unmasking Preference, SARS-CoV-2 Transmissibility and Respiratory Side Effects.

Background: Social distancing and mask-wearing were recommended and mandatory for people during the COVID-19 pandemic. Methods: A web-based questionnaire was disseminated through social media assessing mask type preference and COVID-19 history amongst tertiary sector services and the rates of the triad of respiratory symptoms in each mask type, along with other respiratory-related parameters. Results: Amongst 4107 participants, 63.4% of the responders, mainly women, preferred medical/surgical masks; 20.5%, mainly men, preferred cotton cloth masks; and 13.8% preferred FFP/(K)N95 masks. COVID-19 history was less common in FFP/(K)N95 compared to medical/surgical (9.2% vs. 15.6%, p < 0.001) or cloth masks (9.2% vs. 14.4%, p = 0.006). Compared to the control group (rare mask-wearing, nonsmokers and without lung conditions), those wearing one medical mask were more likely to report frequent sputum production (4.4% vs. 1.9%, p = 0.026) and frequent cough (4.4% vs. 1.6%, p = 0.013), and those wearing FFP/(K)N95 masks were more likely to report frequent cough (4.1% vs. 1.6%, p = 0.048). Compared to the control group, those preferring cotton cloth masks were more likely to report a frequent cough (7.3% vs. 1.6%, p = 0.0002), sputum production (6.3% vs. 1.9%, p = 0.003) and dyspnea (8% vs. 1.3%, p = 0.00001). Conclusions: Safe mask-wearing should be in parallel with a more personalized and social interaction approach.

COVID-19 Smart Diagnosis in the Emergency Department: all-in in Practice.

INTRODUCTION: Coronavirus Disease 19 (COVID-19) diagnosis has been a major problem in most Emergency Departments (EDs) and other senior care facilities. Various clinical manifestations, and the several radiologic and laboratory data combined with the misleading test results to identify the virus, are responsible for certain misdiagnoses, especially in suspected cases needing urgent management and treatment. Although emergency and other front-line physicians struggle to manage COVID-19 patients, still existent cases with ambiguous diagnosis trammel the ED safety and responsibility. AREAS COVERED: This review article summarizes on a large scale the common information for the medical history, clinical examinations, radiology and laboratory data for SARS-CoV-2. We summarize the available literature using the PubMed, Science Direct and EMBASE databases published until December 2021 on the general information for COVID-19 diagnosis, and, finally, we propose algorithms for a precise and on-the-spot diagnosis the disease. EXPERT OPINION: COVID-19 diagnosis has appeared to be such ambiguous, and physicians need to correlate medical history, medical examination, potential extrapulmonary manifestations, along with laboratory and radiologic data, for a prompt COVID-19 diagnosis.

COVID-19 'asymptomatic' patients: an old wives' tale.

INTRODUCTION: A novel virus, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) was reported via nucleic acid identification in December, 2019. 'Asymptomatic cases' have arised as an obstacle for an accurate diagnosis, curtailing the elimination of the ongoing pandemic. AREAS COVERED: In this review, we analyze the definition of symptoms and the principles of diagnosing COVID-19. Also, we explore the major reasons for cases presenting a phenotype with mild symptoms. Host, viral and environmental aspects for a COVID-19 leading to mild symptoms are being highlighted. A final aspect regarding a rational asymptomatic COVID-19 is presumed. EXPERT OPINION: Diagnosing a pandemic via a sole test can be risky. Epidemiological administration should be more accurate and precise, not only for the societal pandemic levels and following policies, but for the same scientific community, that studies SARS-CoV-2 and its mutants. Several other issues should be answered before analyzing human genome for the asymptomatic scenario.

Societal Criticism towards COVID-19: Assessing the Theory of Self-Diagnosis Contrasted to Medical Diagnosis.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has emerged as a pandemic introducing the mass autodiagnosis via rapid antigen testing methods, and self-tests were important for several populaces, yet with several neglected issues. In addition, hospital diagnosis was a target of many people or media, as the various COVID-19 clinical phenotypes trammel the precise emergency physicians' response. METHODS: A web-based questionnaire was disseminated through social media in the first half of August 2021 in the Greek populace, assessing the societal criticism for autodiagnosis and medical diagnosis and their issues, just before the occurrence of the fourth pandemic wave in the country. RESULTS: Two thirds of the responders characterized self-tests as unreliable and two fifths reported them dangerous. Reliability (OR 1.335; CI 0.060-0.300; p = 0.000) and danger (OR 5.068; CI 3139-8184; p = 0.000) were significant predictors for the population-based sample's volition for a self-test. Reversely, regarding medical diagnosis, half of the responders reported the lack of reliability and effectiveness in the emergency departments, which had a significant impact on willingness to visit a hospital if needed (OR 3.207; CI 1987-5182; p = 0.000 and OR 3.506; CI 2167-5670; p = 0.000). CONCLUSIONS: The importance of community-based questionnaires is highlighted for assessing people's criticism and improving the highlighted points in several topics.

Estimates of COVID-19 Risk Factors among Social Strata and Predictors for a Vulnerability to the Infection.

Coronavirus disease 2019 (COVID-19) has emerged as a potentially severe disease, especially for individuals presenting with certain underlying medical conditions. We analyzed the rates of comorbidities and symptoms to reveal the potential severity of the pandemic in Volos, one of the most air-polluted cities in Greece. Environmental and health-related predictors for SARS-CoV-2 infection were investigated. A web-based questionnaire was disseminated through social media in the first half of March 2021 during a five-month strict lockdown. Sociodemographic data, preexisting medical conditions, frequency of clinical symptoms, and COVID-19 information were recorded. The study population consisted of 2000 responders. Four-fifths of the participants reported comorbidities that could increase vulnerability to severe COVID-19. Respiratory symptoms were reported from the unemployed and from retirees, and cold-related symptoms were reported in the education sector and in undergraduates. Women and younger generations shaped social vulnerability to respiratory infections similar to the elderly. SARS-CoV-2 infection was reported in 3.7% of the study population. Common headache (OR 2; CI 1189-3013; p = 0.007) and prior pneumonia (OR 1.9; CI 1024-2898; p = 0.04) were significant predictors for susceptibility to SARS-CoV-2 infection. The importance of monitoring society through community-based questionnaires is highlighted, for predicting and preventing future widespread transmission of infectious diseases.

False-positive and false-negative COVID-19 cases: respiratory prevention and management strategies, vaccination, and further perspectives.

Introduction: A novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) was reported via nucleic acid identification in December, 2019. Accuracy of SARS-CoV-2 diagnostic assays has emerged as a major barrier to COVID-19 diagnosis, particularly in cases requiring urgent or emergent treatment.Areas covered: In this review, we explore the major reasons for false-positive and false-negative SARS-CoV-2 test results. How clinical characteristics, specific respiratory comorbidities and SARS-CoV-2 vaccination impact on existing diagnostic assays are highlighted. Different COVID-19 management algorithms based on each test and limitations are thoroughly presented.Expert opinion: The diagnostic accuracy and the capacity of every available assay, which need to be interpreted in the light of the background incidence of SARS-CoV-2 infection in the communities in which they are used, are essential in order to minimize the number of falsely tested cases. Automated testing platforms may enhance diagnostic accuracy by minimizing the potential for human error in assays' performance. Prior immunization against SARS-CoV-2 impairs the utility of serologic testing of suspected COVID-19 cases. Future avenues of research to evaluate lung tissue innate immune responses hold promise as a target for research to optimize SARS-CoV-2 and future infections' testing accuracy.

Repeated Antigen-Based Rapid Diagnostic Testing for Estimating the Coronavirus Disease 2019 Prevalence from the Perspective of the Workers' Vulnerability before and during the Lockdown.

BACKGROUND: No previous study has investigated the SARS-CoV-2 prevalence and the changes in the proportion of positive results due to lockdown measures from the angle of workers' vulnerability to coronavirus in Greece. Two community-based programs were implemented to evaluate the SARS-CoV-2 prevalence and investigate if the prevalence changes were significant across various occupations before and one month after lockdown. METHODS: Following consent, sociodemographic, clinical, and job-related information were recorded. The VivaDiag™ SARS-CoV-2 Antigen Rapid Test was used. Positive results confirmed by a real-time Reverse Transcriptase Polymerase Chain Reaction for SARS-COV-2. RESULTS: Positive participants were more likely to work in the catering/food sector than negative participants before the lockdown. Lockdown restrictions halved the new cases. No significant differences in the likelihood of being SARS-CoV-2 positive for different job categories were detected during lockdown. The presence of respiratory symptoms was an independent predictor for rapid antigen test positivity; however, one-third of newly diagnosed patients were asymptomatic at both time points. CONCLUSIONS: The catering/food sector was the most vulnerable to COVID-19 at the pre-lockdown evaluation. We highlight the crucial role of community-based screening with rapid antigen testing to evaluate the potential modes of community transmission and the impact of infection control strategies.

Social Response to the Vaccine against COVID-19: The Underrated Power of Influence.

BACKGROUND: The Coronavirus Disease 2019 (COVID-19) pandemic has highlighted the need for preventive medicine and vaccinology to be paralleled to eliminate COVID-19 cases. METHODS: A web-based questionnaire was disseminated through social media in the late November assessing the factors that may have influenced the final response to vaccination against COVID-19 in vaccinated and non-vaccinated Greek people. RESULTS: Women, the younger generations, and university graduates were more likely to accept vaccination, whereas men, those with a basic education level, and the older generation showed a hesitance to the vaccine against COVID-19. About half of the vaccinated participants were influenced in their final decision mainly by being informed from the internet (50.4%), their work (51.7%), and social life (53,1%) while half of the non-vaccinated individuals were mostly influenced by keeping updated from the internet (55.5%) and by government policies (51.3%). COVID-19 risk (OR 2.511; CI 2.149-2.934; p = 0.000), frequent vaccinations for emerging pathogens (OR 14.022; CI 11.998-16.389), and social life (OR 2.828; CI 2.417-3.309; p = 0.000) had a significant impact on people's positive response to vaccination against COVID-19. CONCLUSIONS: Monitoring and assessing the influence factors for the response to vaccination can be favourable strategies to further manage societal vaccination rates.