Validation of a MALDI-TOF MS Method for SARS-CoV-2 Detection on the Bruker Biotyper and Nasopharyngeal Swabs: A Brazil-UK Collaborative Study.

We developed a MALDI-TOF mass spectrometry method for the detection of the SARS-CoV-2 virus in saliva-gargle samples using Shimadzu MALDI-TOF mass spectrometers in the UK. This was validated in the USA to CLIA-LDT standards for asymptomatic infection detection remotely via sharing protocols, shipping key reagents, video conferencing, and data exchange. In Brazil, more so than in the UK and USA, there is a need to develop non-PCR-dependent, rapid, and affordable SARS-CoV-2 infection screening tests that also identify variant SARS-CoV-2 and other virus infections. In addition, travel restrictions necessitated remote collaboration with validation on the available clinical MALDI-TOF-the Bruker Biotyper (microflex® LT/SH)-and on nasopharyngeal swab samples, as salivary gargle samples were not available. The Bruker Biotyper was shown to be almost log103 more sensitive at the detection of high molecular weight spike proteins. A protocol for saline swab soaks out was developed, and duplicate swab samples collected in Brazil were analyzed by MALDI-TOF MS. The swab collected sample spectra that varied from that of saliva-gargle in three additional mass peaks in the mass region expected for IgG heavy chains and human serum albumin. A subset of clinical samples with additional high mass, probably spike-related proteins, were also found. Further, spectral data comparisons and analysis, subjected to machine learning algorithms in order to resolve RT-qPCR positive from RT-qPCR negative swab samples, showed 56-62% sensitivity, 87-91% specificity, and a 78% agreement with RT-qPCR scoring for SARS-CoV-2 infection.

Evaluating the Effectiveness of a Telehealth Cancer Genetics Program: A BRCA Pilot Study.

INTRODUCTION: Ashkenazi Jewish (AJ) individuals face a 1 in 40 (2.5%) risk of having a BRCA mutation, which is 10 times the general population risk. JScreen launched the PEACH BRCA Study, a telehealth-based platform for BRCA education and testing, with the goal of creating an effective model for BRCA testing in low-risk AJ individuals who do not meet national testing criteria. Other goals were to determine the rate of BRCA mutations in this group, to assess the adequacy of screening for the 3 common AJ founder mutations only, and to assess satisfaction with the telehealth model to help inform a national launch of a broader cancer genetic testing program. METHODS: Criteria for participation included those who were AJ, resided in the metro-Atlanta area, were aged 25 and older, and had no personal or close family history of BRCA-related cancers. Pre-test education was provided through a video and written summary, followed by complimentary BRCA1/2 sequencing and post-test genetic counseling. Participants responded to pre- and post-test surveys, which assessed knowledge and satisfaction. Those who were not eligible to participate were sent genetic counseling resources and later surveyed. RESULTS: Five hundred one participants were tested and the results included 4 positives (0.8% positivity rate), 494 negatives, and 3 variants of uncertain significance. Overall satisfaction with the study process was high (96.9/100), knowledge about BRCA was high (97.5% of participants passed a pre-test knowledge quiz), and satisfaction with pre- and post-test education was high (97.9% of participants were satisfied with the pre-test video and written summary, and 99.5% felt that their post-test genetic counseling session was valuable). Many participants expressed interest in receiving broader cancer testing. CONCLUSIONS: The BRCA founder mutation rate in a low-risk AJ population was significantly lower than the previously established AJ rate of 1 in 40. It was also determined that a telehealth model for a cancer genetics program is effective and acceptable to the population tested. This study established interest in broader cancer genetic testing through a telehealth platform and suggested that testing may be successful in the Jewish community at a national level and potentially in other populations, provided that patient education and genetic counseling are adequately incorporated.

German federal-state-wide seroprevalence study of 1st SARS-CoV-2 pandemic wave shows importance of long-term antibody test performance.

Background: Reliable data on the adult SARS-CoV-2 infection fatality rate in Germany are still scarce. We performed a federal state-wide cross-sectional seroprevalence study named SaarCoPS, that is representative for the adult population including elderly individuals and nursing home residents in the Saarland. Methods: Serum was collected from 2940 adults via stationary or mobile teams during the 1st pandemic wave steady state period. We selected an antibody test system with maximal specificity, also excluding seroreversion effects due to a high longitudinal test performance. For the calculations of infection and fatality rates, we accounted for the delays of seroconversion and death after infection. Results: Using a highly specific total antibody test detecting anti-SARS-CoV-2 responses over more than 180 days, we estimate an adult infection rate of 1.02% (95% CI: [0.64; 1.44]), an underreporting rate of 2.68-fold (95% CI: [1.68; 3.79]) and infection fatality rates of 2.09% (95% CI: (1.48; 3.32]) or 0.36% (95% CI: [0.25; 0.59]) in all adults including elderly individuals, or adults younger than 70 years, respectively. Conclusion: The study highlights the importance of study design and test performance for seroprevalence studies, particularly when seroprevalences are low. Our results provide a valuable baseline for evaluation of future pandemic dynamics and impact of public health measures on virus spread and human health in comparison to neighbouring countries such as Luxembourg or France.

Comparative analyses of eighteen rapid antigen tests and RT-PCR for COVID-19 quarantine and surveillance-based isolation.

Background: Rapid antigen (RA) tests are being increasingly employed to detect SARS-CoV-2 infections in quarantine and surveillance. Prior research has focused on RT-PCR testing, a single RA test, or generic diagnostic characteristics of RA tests in assessing testing strategies. Methods: We have conducted a comparative analysis of the post-quarantine transmission, the effective reproduction number during serial testing, and the false-positive rates for 18 RA tests with emergency use authorization from The United States Food and Drug Administration and an RT-PCR test. To quantify the extent of transmission, we developed an analytical mathematical framework informed by COVID-19 infectiousness, test specificity, and temporal diagnostic sensitivity data. Results: We demonstrate that the relative effectiveness of RA tests and RT-PCR testing in reducing post-quarantine transmission depends on the quarantine duration and the turnaround time of testing results. For quarantines of two days or shorter, conducting a RA test on exit from quarantine reduces onward transmission more than a single RT-PCR test (with a 24-h delay) conducted upon exit. Applied to a complementary approach of performing serial testing at a specified frequency paired with isolation of positives, we have shown that RA tests outperform RT-PCR with a 24-h delay. The results from our modeling framework are consistent with quarantine and serial testing data collected from a remote industry setting. Conclusions: These RA test-specific results are an important component of the tool set for policy decision-making, and demonstrate that judicious selection of an appropriate RA test can supply a viable alternative to RT-PCR in efforts to control the spread of disease.

Caution, "normal" BMI: health risks associated with potentially masked individual underweight-EPMA Position Paper 2021.

An increasing interest in a healthy lifestyle raises questions about optimal body weight. Evidently, it should be clearly discriminated between the standardised "normal" body weight and individually optimal weight. To this end, the basic principle of personalised medicine "one size does not fit all" has to be applied. Contextually, "normal" but e.g. borderline body mass index might be optimal for one person but apparently suboptimal for another one strongly depending on the individual genetic predisposition, geographic origin, cultural and nutritional habits and relevant lifestyle parameters-all included into comprehensive individual patient profile. Even if only slightly deviant, both overweight and underweight are acknowledged risk factors for a shifted metabolism which, if being not optimised, may strongly contribute to the development and progression of severe pathologies. Development of innovative screening programmes is essential to promote population health by application of health risks assessment, individualised patient profiling and multi-parametric analysis, further used for cost-effective targeted prevention and treatments tailored to the person. The following healthcare areas are considered to be potentially strongly benefiting from the above proposed measures: suboptimal health conditions, sports medicine, stress overload and associated complications, planned pregnancies, periodontal health and dentistry, sleep medicine, eye health and disorders, inflammatory disorders, healing and pain management, metabolic disorders, cardiovascular disease, cancers, psychiatric and neurologic disorders, stroke of known and unknown aetiology, improved individual and population outcomes under pandemic conditions such as COVID-19. In a long-term way, a significantly improved healthcare economy is one of benefits of the proposed paradigm shift from reactive to Predictive, Preventive and Personalised Medicine (PPPM/3PM). A tight collaboration between all stakeholders including scientific community, healthcare givers, patient organisations, policy-makers and educators is essential for the smooth implementation of 3PM concepts in daily practice.

Investigating the Implementation of SMS and Mobile Messaging in Population Screening (the SIPS Study): Protocol for a Delphi Study.

BACKGROUND: The use of mobile messaging, including SMS, and web-based messaging in health care has grown significantly. Using messaging to facilitate patient communication has been advocated in several circumstances, including population screening. These programs, however, pose unique challenges to mobile communication, as messaging is often sent from a central hub to a diverse population with differing needs. Despite this, there is a paucity of robust frameworks to guide implementation. OBJECTIVE: The aim of this protocol is to describe the methods that will be used to develop a guide for the principles of use of mobile messaging for population screening programs in England. METHODS: This modified Delphi study will be conducted in two parts: evidence synthesis and consensus generation. The former will include a review of literature published from January 1, 2000, to October 1, 2021. This will elicit key themes to inform an online scoping questionnaire posed to a group of experts from academia, clinical medicine, industry, and public health. Thematic analysis of free-text responses by two independent authors will elicit items to be used during consensus generation. Patient and Public Involvement and Engagement groups will be convened to ensure that a comprehensive item list is generated that represents the public's perspective. Each item will then be anonymously voted on by experts as to its importance and feasibility of implementation in screening during three rounds of a Delphi process. Consensus will be defined a priori at 70%, with items considered important and feasible being eligible for inclusion in the final recommendation. A list of desirable items (ie, important but not currently feasible) will be developed to guide future work. RESULTS: The Institutional Review Board at Imperial College London has granted ethical approval for this study (reference 20IC6088). Results are expected to involve a list of recommendations to screening services, with findings being made available to screening services through Public Health England. This study will, thus, provide a formal guideline for the use of mobile messaging in screening services and will provide future directions in this field. CONCLUSIONS: The use of mobile messaging has grown significantly across health care services, especially given the COVID-19 pandemic, but its implementation in screening programs remains challenging. This modified Delphi approach with leading experts will provide invaluable insights into facilitating the incorporation of messaging into these programs and will create awareness of future developments in this area. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/32660.

The environment has effects on infrared temperature screening for COVID-19 infection.

Infrared temperature measurement is a common form of mass screening for febrile illnesses such as COVID-19 infection. Efficacy of infrared monitoring is debated, and external factors can affect accuracy. We determine that outside temperature, wind, and humidity can affect infrared temperature measurements and partially account for inaccurate results.

Dataset on optimization and development of a point-of-care glucometer-based SARS-CoV-2 detection assay using aptamers.

We present supplementary data for the published article, "Hitting the diagnostic sweet spot: Point-of-care SARS-CoV-2 salivary antigen testing with an off-the-shelf glucometer" [1]. The assay described is designed to be performed at home or in a clinic without expensive instrumentation or professional training. SARS-CoV-2 is detected by an aptamer-based assay that targets the Nucleocapsid (N) or Spike (S) antigens. Binding of the N or S protein to their respective aptamer results in the competitive release of a complementary antisense-invertase enzyme complex. The released enzyme then catalyzes the conversion of sucrose to glucose that is measured by an off-the-shelf glucometer. The data presented here describe the optimization of the assay parameters and their contribution to developing this aptamer-based assay to detect SARS-CoV-2. The assay performance was checked in a standard buffer, contrived samples, and patient samples validated with well-established scientific methods. The resulting dataset can be used to further develop glucometer-based assays for diagnosing other communicable and non-communicable diseases.

Diabetic Retinopathy Screening and Registration in Europe-Narrative Review.

Diabetic retinopathy (DR) is a leading cause of preventable vision impairment and blindness in the European Region. Despite the fact that almost all European countries have some kind of prophylactic eye examination for people with diabetes, the examinations are not properly arranged and are not organized according to the principles of screening in medicine. In 2021, the current COVID-19 pandemic moved telemedicine to the forefront healthcare services. Due to that, a lot more patients could benefit from comfortable and faster access to ophthalmology specialist care. This study aimed to conduct a narrative literature review on current DR screening programs and registries in the European Union for the last 20 years. With the implementation of telemedicine in daily medical practice, performing screening programs became much more attainable. Remote assessment of retinal pictures simultaneously saves countries time, money, and other resources.

COVID-19 and beyond: Lessons learned from emergency department HIV screening for population-based screening in healthcare settings.

Emergency departments (EDs) have played a major role in the science and practice of HIV population screening. After decades of experience, EDs have demonstrated the capacity to provide testing and linkage to care to large volumes of patients, particularly those who do not otherwise engage the healthcare system. Efforts to expand ED HIV screening in the United States have been accelerated by a collaborative national network of emergency physicians and other stakeholders called EMTIDE (Emergency Medicine Transmissible Infectious Diseases and Epidemics). As the COVID-19 pandemic evolves, EDs nationwide are being tasked with diagnosing and managing COVID-19 in a myriad of capacities, adopting varied approaches based in part on know-how, local disease trends, and the supply chain. The objective of this article is to broadly summarize the lessons learned from decades of ED HIV screening and provide guidance for many analogous issues and challenges in population screening for COVID-19. Over time, and with the accumulated experience from other epidemics, ED screening should develop into an overarching discipline in which the disease in question may vary, but the efficiency of response is increased by prior knowledge and understanding.

SalivaDirect: A simplified and flexible platform to enhance SARS-CoV-2 testing capacity.

BACKGROUND: Scaling SARS-CoV-2 testing to meet demands of safe reopenings continues to be plagued by assay costs and supply chain shortages. In response, we developed SalivaDirect, which received Emergency Use Authorization (EUA) from the U.S. Food and Drug Administration (FDA). METHODS: We simplified our saliva-based diagnostic test by (1) not requiring collection tubes with preservatives, (2) replacing nucleic acid extraction with a simple enzymatic and heating step, and (3) testing specimens with a dualplex qRT-PCR assay. Moreover, we validated SalivaDirect with reagents and instruments from multiple vendors to minimize supply chain issues. FINDINGS: From our hospital cohort, we show a high positive agreement (94%) between saliva tested with SalivaDirect and nasopharyngeal swabs tested with a commercial qRT-PCR kit. In partnership with the National Basketball Association (NBA) and National Basketball Players Association (NBPA), we tested 3,779 saliva specimens from healthy individuals and detected low rates of invalid (0.3%) and false-positive (<0.05%) results. CONCLUSIONS: We demonstrate that saliva is a valid alternative to swabs for SARS-CoV-2 screening and that SalivaDirect can make large-scale testing more accessible and affordable. Uniquely, we can designate other laboratories to use our sensitive, flexible, and simplified platform under our EUA (https://publichealth.yale.edu/salivadirect/). FUNDING: This study was funded by the NBA and NBPA (N.D.G.), the Huffman Family Donor Advised Fund (N.D.G.), a Fast Grant from Emergent Ventures at the Mercatus Center at George Mason University (N.D.G.), the Yale Institute for Global Health (N.D.G.), and the Beatrice Kleinberg Neuwirth Fund (A.I.K.). C.B.F.V. is supported by NWO Rubicon 019.181EN.004.

Hitting the diagnostic sweet spot: Point-of-care SARS-CoV-2 salivary antigen testing with an off-the-shelf glucometer.

Significant barriers to the diagnosis of latent and acute SARS-CoV-2 infection continue to hamper population-based screening efforts required to contain the COVID-19 pandemic in the absence of widely available antiviral therapeutics or vaccines. We report an aptamer-based SARS-CoV-2 salivary antigen assay employing only low-cost reagents ($3.20/test) and an off-the-shelf glucometer. The test was engineered around a glucometer as it is quantitative, easy to use, and the most prevalent piece of diagnostic equipment globally, making the test highly scalable with an infrastructure that is already in place. Furthermore, many glucometers connect to smartphones, providing an opportunity to integrate with contact tracing apps, medical providers, and electronic health records. In clinical testing, the developed assay detected SARS-CoV-2 infection in patient saliva across a range of viral loads - as benchmarked by RT-qPCR - within 1 h, with 100% sensitivity (positive percent agreement) and distinguished infected specimens from off-target antigens in uninfected controls with 100% specificity (negative percent agreement). We propose that this approach provides an inexpensive, rapid, and accurate diagnostic for distributed screening of SARS-CoV-2 infection at scale.

The Experience of Greece as a Model to Contain COVID-19 Infection Spread.

The severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) emerged in late 2019 and has caused a pandemic known as corona virus disease 2019 (COVID-19), responsible for the death of more than 2 million people worldwide. The outbreak of COVID-19 has posed an unprecedented threat on human lives and public safety. The aim of this review is to describe key aspects of the bio-pathology of the novel disease, and discuss aspects of its spread, as well as targeted protective strategies that can help shape the outcome of the present and future health crises. Greece is used as a model to inhibit SARS-COV-2 spread, since it is one of the countries with the lowest fatality rates among nations of the European Union (E.U.), following two consecutive waves of COVID-19 pandemic. Furthermore, niche research technological approaches and scientific recommendations that emerged during the COVID-19 era are discussed.

Covid-19 pandemic by the "real-time" monitoring: the Tunisian case and lessons for global epidemics in the context of 3PM strategies.

Covid-19 is neither the first nor the last viral epidemic which societies around the world are, were and will be affected by. Which lessons should be taken from the current pandemic situation? The Covid-19 disease is still not well characterised, and many research teams all over the world are working on prediction of the epidemic scenario, protective measures to populations and sub-populations, therapeutic and vaccination issues, amongst others. Contextually, countries with currently low numbers of Covid-19-infected individuals such as Tunisia are intended to take lessons from those countries which already reached the exponential phase of the infection distribution as well as from those which have the exponential phase behind them and record a minor number of new cases such as China. To this end, in Tunisia, the pandemic wave has started with a significant delay compared with Europe, the main economic partner of the country. In this paper, we do analyse the current pandemic situation in this country by studying the infection evolution and considering potential protective strategies to prevent a pandemic scenario. The model is predictive based on a large number of undetected Covid-19 cases that is particularly true for some country regions such as Sfax. Infection distribution and mortality rate analysis demonstrate a highly heterogeneous picture over the country. Qualitative and quantitative comparative analysis leads to a conclusion that the reliable "real-time" monitoring based on the randomised laboratory tests is the optimal predictive strategy to create the most effective evidence-based preventive measures. In contrast, lack of tests may lead to incorrect political decisions causing either unnecessary over-protection of the population that is risky for a long-term economic recession, or under-protection of the population leading to a post-containment pandemic rebound. Recommendations are provided in the context of advanced predictive, preventive and personalised (3P) medical approach.

[Seroprevalence of anti-SARS-CoV-2 IgG/IgM antibodies in Borgosesia (Piedmont Region, Northern Italy) population: a surveillance strategy in post-lockdown period?] / La prevalenza della risposta immunitaria a SARS-CoV-2 nella popolazione di Borgosesia (VC): una strategia di sorveglianza in fase post-lockdown?

BACKGROUND: to avoid a new spread of the SARS-CoV-2 infection, the post lockdown period requires the implementation of effective strategies for the case finding and contact tracing. The presence of asymptomatic subjects in the population, that are responsible for about 30% of the new infections, may complicate this phase. Serological tests for the measurement of immune response could represent an effective tool for the rapid monitoring of the population with asymptomatic infections and for estimating the proportion of immune in a territory, too. OBJECTIVES: to describe the distribution of the immune response to SARS-CoV-2 infection in the population of the Municipality of Borgosesia (Piedmont Region, Northern Italy) and to estimate the efficacy of this strategy for the identification of asymptomatic cases. DESIGN: Cross-sectional study with administration of a rapid test to assess the seroprevalence of anti-SARS-CoV-2 IgG/IgM antibodies. SETTING AND PARTICIPANTS: all subjects resident in Borgosesia over the age of 18, where invited to participate. A rapid serological test was administered to enrolled participants to detect the presence of SARS-CoV-2 IgG and IgM antibodies on peripheral blood. Subjects with IgG or IgM positivity were offered to perform a swab test for viral RNA research. MAIN OUTCOME MEASURES: the prevalence of IgM and IgG, and the relative risks of having positive swab test and of having symptoms similar to those of COVID-19 in the recent past has been estimated. RESULTS: 4,987 subjects participated to study, 44.5% of the adult population of Borgosesia. The average age was 55 years. There was a greater participation of women (54.4%), of people with a higher education level (37.3%) and of people without specific previous symptoms (95.1%). 245 people had a positive test for IgM or IgG, and the estimated prevalence was of 4.9%. 209 out of 245 subjects who were positive to the rapid test underwent to the RT-PCR test and this allowed to isolate 24 positive subjects. CONCLUSIONS: the seroprevalence values ​​estimated for subjects residing in the city of Borgosesia which underwent the rapid test for the detection of type M and type G antibodies on peripheral blood, confirmed the population-based estimates reported in literature, in particular with the results of the Italian survey of seroprevalence. Furthermore, the implementation of this test allowed the identification and isolation of completely asymptomatic subjects, that could have been identified only through screening with tests for viral RNA.

Voice perturbations under the stress overload in young individuals: phenotyping and suboptimal health as predictors for cascading pathologies.

Verbal communication is one of the most sophisticated human motor skills reflecting both-the mental and physical health of an individual. Voice parameters and quality changes are usually secondary towards functional and/or structural laryngological alterations under specific systemic processes, syndrome and pathologies. These include but are not restricted to dry mouth and Sicca syndromes, body dehydration, hormonal alterations linked to pubertal, menopausal, and andropausal status, respiratory disorders, gastrointestinal reflux, autoimmune diseases, endocrinologic disorders, underweight versus overweight and obesity, and diabetes mellitus. On the other hand, it is well-established that stress overload is a significant risk factor of cascading pathologies, including but not restricted to neurodegenerative and psychiatric disorders, diabetes mellitus, cardiovascular disease, stroke, and cancers. Our current study revealed voice perturbations under the stress overload as a potentially useful biomarker to identify individuals in suboptimal health conditions who might be strongly predisposed to associated pathologies. Contextually, extended surveys applied in the population might be useful to identify, for example, persons at high risk for respiratory complications under pandemic conditions such as COVID-19. Symptoms of dry mouth syndrome, disturbed microcirculation, altered sense regulation, shifted circadian rhythm, and low BMI were positively associated with voice perturbations under the stress overload. Their functional interrelationships and relevance for cascading associated pathologies are presented in the article. Automated analysis of voice recordings via artificial intelligence (AI) has a potential to derive digital biomarkers. Further, predictive machine learning models should be developed that allows for detecting a suboptimal health condition based on voice recordings, ideally in an automated manner using derived digital biomarkers. Follow-up stratification and monitoring of individuals in suboptimal health conditions are recommended using disease-specific cell-free nucleic acids (ccfDNA, ctDNA, mtDNA, miRNA) combined with metabolic patterns detected in body fluids. Application of the cost-effective targeted prevention within the phase of reversible health damage is recommended based on the individualised patient profiling.

Pooled Testing for Expanding COVID-19 Mass Surveillance.

Diagnostic testing to identify patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) plays a key role to control the coronavirus disease (COVID-19) pandemic. While several countries have implemented the use of diagnostic testing in a massive scale as a cornerstone for infection control and surveillance, other countries affected by the pandemic are hampered by its limited testing capacity. Pooled testing was first introduced in the 1940s and is now used for screening in blood banks. Testing is done by pooling multiple individual samples together. Only in the case of a positive pool test would individual samples of the pool be tested, thus substantially reducing the number of tests needed. Several studies regarding their use for SARS CoV-2 have been done in the United States, Israel, and Germany. Studies have shown that an individual positive sample can still be detected in pools of up to 32 samples, and possibly even 64 samples, provided that additional polymerase chain reaction (PCR) amplification cycles are conducted with a sensitivity of 96%. Simulation studies to determine optimal pool size and pooling techniques have also been conducted. Based on these studies, pooled testing is shown to be able to detect positive samples with sufficient accuracy and can easily be used with existing equipment and personnel for population-wide screening.

Chatbots in the fight against the COVID-19 pandemic.

We are all together in a fight against the COVID-19 pandemic. Chatbots, if effectively designed and deployed, could help us by sharing up-to-date information quickly, encouraging desired health impacting behaviors, and lessening the psychological damage caused by fear and isolation. Despite this potential, the risk of amplifying misinformation and the lack of prior effectiveness research is cause for concern. Immediate collaborations between healthcare workers, companies, academics and governments are merited and may aid future pandemic preparedness efforts.