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Background There has been a large influx of COVID-19 seroprevalence studies, but comparability between the seroprevalence estimates has been an issue because of heterogeneities in testing platforms and study methodology. One potential source of heterogeneity is the response or participation rate. Methods We conducted a review of participation rates (PR) in SARS-CoV-2 seroprevalence studies collected by SeroTracker and examined their effect on the validity of study conclusions. PR was calculated as the count of participants for whom the investigators had collected a valid sample, divided by the number of people invited to participate in the study. A multivariable beta generalized linear model with logit link was fitted to determine if the PR of international household and community-based seroprevalence studies was associated with the factors of interest, from 1 December 2019 to 10 March 2021. Results We identified 90 papers based on screening and were able to calculate the PR for 35 out of 90 papers (39%), with a median PR of 70% and an interquartile range of 40.92; 61% of the studies did not report PR. Conclusions Many SARS-CoV-2 seroprevalence studies do not report PR. It is unclear what the median PR rate would be had a larger portion not had limitations in reporting. Low participation rates indicate limited representativeness of results. Non-probabilistic sampling frames were associated with higher participation rates but may be less representative. Standardized definitions of participation rate and data reporting necessary for the PR calculations are essential for understanding the representativeness of seroprevalence estimates in the population of interest.

We present a framework for a federated, virtual biorepository system (VBS) with locally collected and maintained specimens, based on a ‘global goods’ model and principles of equitable access and benefit sharing. The VBS is intended to facilitate timely access to biological specimens and associated data for outbreak-prone infectious diseases to accelerate the development and evaluation of diagnostics, assess vaccine efficacy, and to support surveillance and research needs. The VBS is aimed to be aligned with the WHO BioHub and other specimen sharing efforts as a force multiplier to meet the needs of strengthening global tools for countering epidemics. The purpose of our research is to lay the basis of the collaboration, management and principles of equitable sharing focused on low- and middle-income country partners. Here we report on surveys and interviews undertaken with biorepository-interested parties to better understand needs and barriers for specimen access and share examples from the ZIKAlliance partnership on the governance and operations of locally organized biorepositories.

International audience; We call into question the established dogma that viruses with envelopes and RNA genomes have limited stability by demonstrating the staggering long-term viability, ∼2 years, of chikungunya virus when stored in liquid environments at +4°C in the dark. We contend that our understanding of the infectivity of a variety of enveloped viruses requires a new approach to identify under standardized conditions the primary determinants of their viability.

Fractional flow reserve (FFR) is the ratio of distal to proximal pressure during maximal hyperemia and indirectly estimates the blood flow across a stenotic coronary artery and the related degree of myocardial ischemia. Several studies have investigated the role of FFR in the setting of percutaneous myocardial revascularization and further research is ongoing. However, current evidence on FFR-guided surgical myocardial revascularization is controversial and limited. The main scientific interest is to clarify whether FFR-guided coronary artery bypass surgery is associated with clinical benefits in terms of mortality, myocardial infarction, major adverse cardiovascular events, minimally invasive surgical access compared with sternotomy and off-pump surgery. Furthermore some data suggest that conduit selection for coronary artery bypass grafting and surgical technique might be affected by FFR value. The aim of this article is to review the most recent available evidence about FFR-guided coronary artery bypass grafting and to discuss clinical implications and future perspectives.

Chikungunya virus (CHIKV) is a re-emerging alphavirus that is transmitted to humans by mosquito bites and causes musculoskeletal and joint pain1,2. Despite intensive investigations, the human cellular factors that are critical for CHIKV infection remain unknown, hampering the understanding of viral pathogenesis and the development of anti-CHIKV therapies. Here we identified the four-and-a-half LIM domain protein 1 (FHL1)3 as a host factor that is required for CHIKV permissiveness and pathogenesis in humans and mice. Ablation of FHL1 expression results in the inhibition of infection by several CHIKV strains and o’nyong-nyong virus, but not by other alphaviruses and flaviviruses. Conversely, expression of FHL1 promotes CHIKV infection in cells that do not normally express it. FHL1 interacts directly with the hypervariable domain of the nsP3 protein of CHIKV and is essential for the replication of viral RNA. FHL1 is highly expressed in CHIKV-target cells and is particularly abundant in muscles3,4. Dermal fibroblasts and muscle cells derived from patients with Emery–Dreifuss muscular dystrophy that lack functional FHL15 are resistant to CHIKV infection. Furthermore, CHIKV infection is undetectable in Fhl1-knockout mice. Overall, this study shows that FHL1 is a key factor expressed by the host that enables CHIKV infection and identifies the interaction between nsP3 and FHL1 as a promising target for the development of anti-CHIKV therapies. FHL1 is a key factor expressed by humans and mice that is required for chikungunya virus infection and is therefore a promising target for the development of therapies against chikungunya virus.

Toscana virus (TOSV) can cause central nervous system infections in both residents of and travelers to Mediterranean countries. Data mining identified three real-time RT-qPCR assays for detecting TOSV RNA targeting non-overlapping regions in the nucleoprotein gene. Here, they were combined to create a multi-region assay named Trio TOSV RT-qPCR consisting of six primers and three probes. In this study, (i) we evaluated in silico the three RT-qPCR assays available in the literature for TOSV detection, (ii) we combined the three systems to create the Trio TOSV RT-qPCR, (iii) we assessed the specificity and sensitivity of the three monoplex assays versus the Trio TOSV RT-qPCR assay, and (iv) we compared the performance of the Trio TOSV RT-qPCR assay with one of the reference monoplex assays on clinical samples. In conclusion, the Trio TOSV RT-qPCR assay performs equally or better than the three monoplex assays, therefore, it provides a robust assay that can be used for both research and diagnostic purposes.

In 2017, a major outbreak of Zika virus (ZIKV) infection took place in Chincha Province, Peru, where arboviral circulation had never been reported before. We conducted a cross-sectional survey (March–May 2019) in two districts of Chincha Province: Pueblo Nuevo and Chincha Baja. We included residents who were 20 to 40 years old and who had lived in these districts for at least 1 year. Serological testing combined screening with a commercial NS1 protein-based Zika IgG ELISA, and confirmation by a cytopathic effect-based virus neutralization test (VNT). Prevalence ratios (PRs) were calculated using Poisson regression with robust error variance. Four hundred participants, divided equally among districts, were enrolled. Anti-ZIKV IgG ELISA was positive for 42 participants (10.5%) and borderline for 12 (3%). Fifty-two of these 54 samples were confirmed positive by ZIKV VNT (13% of the total population). The Pueblo Nuevo district exhibited a greater ZIKV seroprevalence based on VNT results than the Chincha Baja district (23.5% versus 2.5%), with participants from the Pueblo Nuevo district being 9.4 times more likely to have a positive ZIKV VNT result. Average monthly income greater than the minimum wage and adequate water storage were found to be protective factors (PR, 0.29 and 0.24, respectively). In multivariate analysis, living in the Pueblo Nuevo district and a personal history of fever and rash were strong predictors of ZIKV positivity by VNT. The low ZIKV seroprevalence should prompt health authorities to stimulate interventions to prevent potential future outbreaks. In the Pueblo Nuevo district, the seroprevalence was greater but presumably not sufficient to ensure protective herd immunity.

International audience; The molecular identification of arboviruses in West Africa is of particular interest, due to their zoonotic potential in a population living in close contact with livestock, and in a region where the livestock migration across borders raises the risk of diseases infection and dissemination. The aim of the study was the screening of potential circulating arboviruses and the assessment of their zoonotic implications. Therefore, ticks were collected on cattle located in three provinces of eastern Burkina Faso. Tick pools were tested using a panel of genus-specific real-time assays targeting conserved regions of parapoxvirus, orthopoxvirus, flavivirus and phlebovirus. On the 26 farms visited, a total of 663 ticks were collected. Four genera and six tick species were morphologically identified, with Amblyomma variegatum and Hyalomma spp. being the most represented species. No arboviruses were found. However, this study highlights the presence of pseudocowpox virus (8.2%) and bovine papular stomatitis virus (5.8%) among the positive tick pools. BPSV positive ticks were found in herds sharing water and pastures resources and with a history of seasonal transhumance. Therefore, common grazing and the seasonal transhumance are likely to support the transmission of the virus. This could have important health and economic impacts, especially regarding transboundary cattle movements

Real-time molecular techniques have become the reference methods for direct diagnosis of pathogens. The reduction of steps is a key factor in order to decrease the risk of human errors resulting in invalid series and delayed results. We describe here a process of preparation of oligonucleotide primers and hydrolysis probe in a single tube at predefined optimized concentrations that are stabilized via lyophilization (Lyoph-P&amp, P). Lyoph-P&amp, P was compared versus the classic protocol using extemporaneously prepared liquid reagents using (i) sensitivity study, (ii) long-term stability at 4 &deg, C, and (iii) long-term stability at 37 &deg, C mimicking transportation without cold chain. Two previously published molecular assays were selected for this study. They target two emerging viruses that are listed on the blueprint of the WHO as to be considered for preparedness and response actions: chikungunya virus (CHIKV) and Rift Valley fever phlebovirus (RVFV). Results of our study demonstrate that (i) Lyoph-P&amp, P is stable for at least 4 days at 37 &deg, C supporting shipping without the need of cold chain, (ii) Lyoph-P&amp, P rehydrated solution is stable at +4 &deg, C for at least two weeks, (iii) sensitivity observed with Lyoph-P&amp, P is at least equal to, often better than, that observed with liquid formulation, (iv) validation of results observed with low-copy specimens is rendered easier by higher fluorescence level. In conclusion, Lyoph-P&amp, P holds several advantages over extemporaneously preparer liquid formulation that merit to be considered when a novel real-time molecular assay is implemented in a laboratory in charge of routine diagnostic activity.

Modern imaging techniques such as blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) allow the non-invasive and indirect measurement of brain activity. Whether changes in signal intensity can be detected in small brainstem regions during a cold pressor test (CPT) has not been explored thoroughly. The aim of this study was to measure jointly whole brain and brainstem BOLD signal intensity changes in response to a modified CPT. Methods: BOLD fMRI was measured in healthy normotensive participants during unblinded a randomized crossover study (modified CPT vs. control test) using ultra-high field 7 Tesla MRI scanner. Data were analyzed using Statistical Parametric Mapping (SPM) in a whole-brain approach, and with a brainstem-specific analysis using the spatially unbiased infra-tentorial template (SUIT) toolbox. Blood pressure (BP) and hormonal responses (norepinephrine and epinephrine levels) were also measured. Paired t-test statistics were used to compare conditions. Results: Eleven healthy volunteersparticipants (6 womanwomen, mean age 28 ± 8.9 years) were enrolledanalyzed after giving written, informed consent. Mean arterial BP increased from 834 ± 121 mm Hg to 876 ± 12 mm Hg (p=0.00974) during the CPT. Whole-brain analysis revealed significant activations linked to the CPT in the right supplementary motor cortex, midcingulate (bilateral) and the right anterior insular cortex. The brainstem-specific analysis showed significant activations in the dorsal medulla. Conclusions: Changes in BOLD fMRI signal intensity in brainstem regions during a CPT can be detected, and show an increased response during a cold stress in healthy volunteers. Consequentlyvolunteers. Consequently, BOLD fMRI at 7T is a promising tool to explore and acquire new insights in the comprehension of neurogenic hypertension.

Chikungunya is an infectious disease caused by the chikungunya virus (CHIKV), an alphavirus transmitted to humans by Aedes mosquitoes, and for which there is no licensed vaccine nor antiviral treatments. By using a loss-of-function genetic screen, we have recently identified the FHL1 protein as an essential host factor for CHIKV tropism and pathogenesis. FHL1 is highly expressed in muscles cells and fibroblasts, the main CHIKV-target cells. FHL1 interacts with the viral protein nsP3 and plays a critical role in CHIKV genome amplification. Experiments in vivo performed in FHL1-deficient mice have shown that these animals are resistant to infection and do not develop muscular lesions. Altogether these observations, published in the journal Nature [1], show that FHL1 is a key host factor for CHIKV pathogenesis and identify the interaction between FHL1 and nsP3 as a promising target for the development of new antiviral strategies., Le chikungunya est une maladie infectieuse causée par le virus chikungunya (CHIKV), un alphavirus transmis à l’Homme par les moustiques Aedes et contre lequel il n’existe ni vaccin, ni traitements antiviraux. En utilisant une approche de crible génétique par perte de fonction, nous avons récemment identifié la protéine FHL1 comme un facteur cellulaire essentiel pour le tropisme et la pathogénèse du CHIKV. FHL1 est une molécule présente majoritairement dans les cellules musculaires et les fibroblastes, les cibles privilégiées de CHIKV. FHL1 interagit avec la protéine virale nsP3 et joue un rôle décisif dans le mécanisme d’amplification du génome de CHIKV. Des expériences in vivo chez des souris déficientes pour FHL1 ont montré que ces animaux sont résistants à l’infection et ne développent pas de lésions musculaires. L’ensemble de ces observations publiées dans la revue Nature [1] montrent que FHL1 est un facteur cellulaire clé pour la pathogénèse de CHIKV et identifient l’interaction entre FHL1 et nsp3 comme une cible prometteuse pour le développement de nouvelles stratégies antivirales

The GloPID-R (Global Research Collaboration for Infectious Disease Preparedness) chikungunya (CHIKV), o'nyong-nyong (ONNV) and Mayaro virus (MAYV) Working Group has been established to investigate natural history, epidemiology and clinical aspects of infection by these viruses. Here, we present a report dedicated to entomological aspects of CHIKV, ONNV and MAYV. Recent global expansion of chikungunya virus has been possible because CHIKV established a transmission cycle in urban settings using anthropophilic vectors such as Aedes albopictus and Aedes aegypti. MAYV and ONNV have a more limited geographic distribution, being confined to Africa (ONNV) and central-southern America (MAYV). ONNV is probably maintained through an enzootic cycle that has not been characterized yet, with Anopheles species as main vectors and humans as amplification hosts during epidemics. MAYV is transmitted by Haemagogus species in an enzootic cycle using non-human primates as the main amplification and maintenance hosts, and humans becoming sporadically infected when venturing in or nearby forest habitats. Here, we focused on the transmission cycle and natural vectors that sustain circulation of these viruses in their respective locations. The knowledge of the natural ecology of transmission and the capacity of different vectors to transmit these viruses is crucial to understand CHIKV emergence, and to assess the risk that MAYV and ONNV will expand on wide scale using anthropophilic mosquito species not normally considered primary vectors. Finally, the experts identified knowledge gaps and provided adapted recommendations, in order to address future entomological investigations in the right direction. ispartof: ANTIVIRAL RESEARCH vol:174 ispartof: location:Netherlands status: published

The GloPID-R (Global Research Collaboration for Infectious Disease Preparedness) chikungunya (CHIKV), o'nyong-nyong (ONNV) and Mayaro virus (MAYV) Working Group has been established to identify gaps of knowledge about the natural history, epidemiology and medical management of infection by these viruses, and to provide adapted recommendations for future investigations. Here, we present a report dedicated to ONNV epidemiological distribution. Two large-scale ONNV outbreaks have been identified in Africa in the last 60 years, interspersed with sporadic serosurveys and case reports of returning travelers. The assessment of the real scale of ONNV circulation in Africa remains a difficult task and surveillance studies are necessary to fill this gap. The identification of ONNV etiology is made complicated by the absence of multiplex tools in co-circulation areas and that of reference standards, as well as the high cross-reactivity with related pathogens observed in serological tests, in particular with CHIKV. This is a specific obstacle for seroprevalence studies, that necessitate an improvement of serological tools to provide robust results. The scarcity of existent genetic data currently limits molecular epidemiology studies. ONNV epidemiology would also benefit from reinforced entomological and environmental surveillance. Finally, the natural history of the disease deserves to be further investigated, with a specific attention paid to long-term complications. Considering our incomplete knowledge on ONNV distribution, GloPID-R CHIKV, ONNV and MAYV experts recommend that a major effort should be done to fill existing gaps. ispartof: ANTIVIRAL RESEARCH vol:172 ispartof: location:Netherlands status: published

Laurence Thirion and Laura Pezzi contributed equally.; International audience; Chikungunya virus (CHIKV) re-emerged as a globalized health threat fifteen years ago. There are dozens of RT-PCR assays published. An inventory of the latter was made, and after in silico analysis, two assays were selected for their ability to detect strains belonging to the five CHIKV genetic lineages. They were combined in order to provide a robust assay not affected by genetic point mutations and the resulting Duo CHIKV real-time RT-PCR assay was compared to the two parental single-plex tests against five strains belonging to the five genetic lineages. The Duo CHIKV assay performed equally, or better, in terms of sensitivity, specificity, linearity and signal intensity. Dual-target assays are better suited for viruses having the propensity to evolve into new variants via point mutations or major sequence deletions/insertions. Here, we demonstrated that combining two single systems into a dual-target assay did not impair sensitivity and specificity, and proved a potent diagnostic tool to face a potential emergence of CHIKV variants by newly evolving mutations.

The GloPID-R (Global Research Collaboration for Infectious Disease Preparedness) Chikungunya (CHIKV), O'nyong-nyong (ONNV) and Mayaro virus (MAYV) Working Group is investigating the natural history, epidemiology and medical management of infection by these viruses, to identify knowledge gaps and to propose recommendations for direct future investigations and rectification measures. Here, we present the first report dedicated to diagnostic aspects of CHIKV, ONNV and MAYV. Regarding diagnosis of the disease at the acute phase, molecular assays previously described for the three viruses require further evaluation, standardized protocols and the availability of international standards representing the genetic diversity of the viruses. Detection of specific IgM would benefit from further investigations to clarify the extent of cross-reactivity among the three viruses, the sensitivity of the assays, and the possible interfering role of cryoglobulinaemia. Implementation of reference panels and external quality assessments for both molecular and serological assays is necessary. Regarding sero-epidemiological studies, there is no reported high-throughput assay that can distinguish among these different viruses in areas of potential co-circulation. New specific tools and/or improved standardized protocols are needed to enable large-scale epidemiological studies of public health relevance to be performed. Considering the high risk of future CHIKV, MAYV and ONNV outbreaks, the Working Group recommends that a major investigation should be initiated to fill the existing diagnostic gaps. ispartof: ANTIVIRAL RESEARCH vol:166 pages:66-81 ispartof: location:Netherlands status: published

International audience; Background: Data on the risk of transmission of infection to health care workers (HCWs) serving ill pilgrims during the Hajj is scarce.Methods: Two cohorts of HCWs, the first serving Hajj pilgrims in Mecca and the second serving patients in Al-Ahsa, were investigated for respiratory and gastrointestinal symptoms and pathogen carriage using multi-plex polymerase chain reaction before and after the 2015 Hajj.Results: A total of 211 HCWs were enrolled of whom 92 were exposed to pilgrims (Mecca cohort), whereas 119 were not exposed (Al-Ahsa cohort). Symptoms were observed only in HCWs from the Mecca cohort, with 29.3% experiencing respiratory symptoms during the Hajj period or in the subsequent days and 3.3% having gastrointestinal symptoms. Acquisition rates of at least 1 respiratory virus were 14.7% in the Mecca cohort and 3.4% in the Al-Ahsa cohort (P = .003). Acquisition rates of at least 1 respiratory bacterium were 11.8% and 18.6% in the Mecca and Al-Ahsa cohorts, respectively (P = .09). Gastrointestinal pathogens were rarely isolated in both cohorts of HCWs and acquisition of pathogens after the Hajj was documented in only a few individuals.Conclusions: HCWs providing care for pilgrims both acquire pathogens and present symptoms (especially respiratory symptoms) more frequently than those not working during Hajj.

Patients with coronary chronic total occlusion (CTO) if symptomatic for angina or with extensive inducible ischemia at provocative tests may be revascularized percutaneously or surgically. Percutaneous revascularization can be performed by antegrade or retrograde approach. In our case, in the presence of a long CTO of the left anterior descending coronary artery, the antegrade approach was chosen using an intravascular ultrasound (IVUS) catheter positioned in a secondary branch, to accurately identify the proximal lesion cap. IVUS is useful for selecting the appropriate stent size and length to ensure lesion coverage and stent optimization and to detect related complications.

Atrial Fibrillation (AF) is associated with an increased risk of stroke and development of cognitive impairment. Our cross-sectional study aims to identify risk factors for cognitive impairment in patients with permanent AF.212 consecutive outpatients with history of permanent AF lasting more than 1 year were enrolled and the Short Portable Mental Status Questionnaire (SPMSQ) was used to assess cognitive impairment (number of errors ≥5). The type of antithrombotic therapy, the time in therapeutic range (TTR) in case of treatment with warfarin and the degree of heart rate (HR) control (upon Holter ECG monitoring) were also assessed.ROC curve analysis indicated that TTR was associated with cognitive impairment (AUC 0.85 ± 0.03; 95% CI 0.77-0.88; p 0.0001). Multivariate logistic regression analysis showed an independent association of previous cerebrovascular or cardiovascular events (OR 7.24, 95% CI 1.37-38.25; p = 0.020), aspirin therapy instead of anticoagulant therapy (OR 24.74, 95% CI 1.27-482.12; p = 0.034), warfarin use with TTR ≤60% (OR 21.71 , 95%CI 4.35-108; p 0.001) and an average daily HR either60 bpm or100 bpm (OR 6.04, 95% 1.09-33.29; p = 0.039) with cognitive impairment.Among patients with permanent AF, cognitive impairment is more frequent in those with inadequate antithrombotic therapy (aspirin therapy instead of anticoagulant therapy) and with suboptimal oral anticoagulation (TTR ≤60%) or heart rate control. Efforts should be made to optimize therapies related to these parameters.

Anti-arrhythmic properties of n-3 polyunsaturated fatty acids, at least in part mediated by anti-oxidant, anti-inflammatory and anti-fibrotic power, have been widely proved. Effect of fish oil on atrial fibrillation, both in primary and in secondary prevention and after cardiac surgery, are controversial, mostly due to lack of homogeneity between studies but also due to individual variability in response to fatty acids administration. Inclusion of measurement of incorporation of fish oil into cell membranes, appears to be essential in future studies, to assess their antiarrhythmic effect.

Cancer anorexia-cachexia syndrome (CACS), which is characterized by progressive weight loss (WL) and anorexia (A), is present in 50% of advanced cancer patients and in 80% of terminally ill cancer patients. One of the most controversial aspects of CACS is its oetiopathogenesis; experimental studies have identified certain cytokines [Tumour necrosis factor alpha (TNF-alpha), interleukin 1 (IL-1), interleukin 6 (IL-6), and gamma interferon (gamma-IFN)] as possible co-factors in the onset of the syndrome. The aim of our study was to investigate the correlation between serum levels of circulating cytokines and severity of CACS. The following series of parameters was identified in 61 patients with advanced and terminal cancer: stage of disease; Karnofsky performance status (KPS) and clinical symptoms; biohumoral, anthropometric and immunological situation; level of circulating cytokines. All these parameters were evaluated for a possible link with WL/A. Our data do not show any significant correlation between circulating cytokines and WL/A. A direct correlation was identified between WL/A and nausea (P = 0.03 and P0.001, respectively) whereas inverse correlations were observed for both factors as regards arm circumference (P0.001 for both), wrist circumference (P0.001 for both), KPS (P0.001 and P = 0.003, respectively) and creatinine (P = 0.005 and P = 0.03, respectively). Other biochemical factors, such as haemoglobin, haematocrit, glycaemia, prealbumin, sodium and chlorine were also correlated with at least one of two clinical parameters in question. Unexpected results were seen in the increases in CD20 and CD4 and in the CD4/CD8 ratio. Serum levels of these cytokines do not, therefore, appear to be critical in the onset of CACS. On the contrary, our findings confirmed the clinico-laboratory picture that is characteristic of CACS. If we consider the possibility that CACS is provoked by an aspecific response of the host's defence mechanisms against prolonged neoplastic attack, the increase in CD4 (helper lymphocytes) could be linked to the persistent response.

Sindbis virus (SINV) is a zoonotic alphavirus (family Togaviridae, genus Alphavirus) that causes human diseases in Africa, Europe, Asia, and Australia. Occasionally, SINV outbreaks were reported in South Africa and northern Europe. Birds are the main amplifying hosts of SINV, while mosquitoes play the role of the primary vector. Culex mosquitoes were collected in Algeria and subsequently tested for SINV. SINV RNA was detected in 10 pools out of 40, from a total of 922 mosquitoes tested. A strain of SINV was isolated from a pool displaying high viral load. Whole-genome sequencing and phylogenetic analysis showed that the SINV Algeria isolate was most closely related to a Kenyan strain. This was the first record of SINV in Algeria and more broadly in northwestern Africa, which can be a potential risk for human health in the circulating area. Further studies are needed to measure the impact on public health through seroprevalence studies in Algeria.