Nyt fra tidsskrifterne

Objective To assess the prevalence of burn-out syndrome in healthcare workers working on the front line (FL) in Spain during COVID-19. Design Cross-sectional, online survey-based study. Settings Sampling was performed between 21st April and 3rd May 2020. The survey collected demographic data and questions regarding participants’ working position since pandemic outbreak. Participants Spanish healthcare workers working on the FL or usual ward were eligible. A total of 674 healthcare professionals answered the survey. Main outcomes and measures Burn-out syndrome was assessed by the Maslach Burnout Inventory-Medical Personnel. Results Of the 643 eligible responding participants, 408 (63.5%) were physicians, 172 (26.8%) were nurses and 63 (9.8%) other technical occupations. 377 (58.6%) worked on the FL. Most participants were women (472 (73.4%)), aged 31–40 years (163 (25.3%)) and worked in tertiary hospitals (>600 beds) (260 (40.4%)). Prevalence of burn-out syndrome was 43.4% (95% CI 39.5% to 47.2%), higher in COVID-19 FL workers (49.6%, p<0.001) than in non- COVID-19 FL workers (34.6%, p<0.001). Women felt more burn-out (60.8%, p=0.016), were more afraid of self-infection (61.9%, p=0.021) and of their performance and quality of care provided to the patients (75.8%, p=0.015) than men. More burn-out were those between 20 and 30 years old (65.2%, p=0.026) and those with more than 15 years of experience (53.7%, p=0.035). Multivariable logistic regression analysis revealed that, working on COVID-19 FL (OR 1.93; 95% CI 1.37 to 2.71, p<0.001), being a woman (OR 1.56; 95% CI 1.06 to 2.29, p=0.022), being under 30 years old (OR 1.75; 95% CI 1.06 to 2.89, p=0.028) and being a physician (OR 1.64; 95% CI 1.11 to 2.41, p=0.011) were associated with high risk of burn-out syndrome. Conclusions This survey study of healthcare professionals reported high rates of burn-out syndrome. Interventions to promote mental well-being in healthcare workers exposed to COVID-19 need to be immediately implemented.

Introduction COVID-19 pandemic has affected people all over the world. In this context, health disparities are already evident in becoming ill and dying from this condition, further accentuating historical racial inequalities. Methods and analysis This protocol will be developed based on the recommendations of Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols. For this, searches will be carried out in PubMed, Web of Science, Scopus, Lilacs and ScienceDirect databases searching for cross-sectional studies that assessed the prevalence of black people with COVID-19 at different levels of complexity. All cross-sectional studies that analysed the prevalence of COVID-19 in black people assisted in primary care, hospital wards and intensive care units will be included. The research will be carried out by two independent researchers who will identify the articles; they will exclude duplicate studies. Through blind evaluation, they will select the articles using the Rayyan QCRI application. The instrument proposed by Downs and Black will be used to assess the risk of bias. The meta-analyses will be performed according to the data conditions included. Ethics and dissemination For this study’s development, there is no need for an ethical appraisal considering that it is a systematic review that will use secondary studies. This study’s findings will be disseminated through peer-reviewed publications, conference presentations and condensed summaries for main stakeholders and partners in the field. The database search is expected to begin on 1 February 2021. It is expected to complete the entire review process by 30 October 2021 Trial registration number CRD42020209079.

Introduction Trauma-focused cognitive behavioural therapies are the first-line treatment for posttraumatic stress disorder (PTSD) in children and adolescents. Nevertheless, open questions remain with respect to efficacy: why does this first-line treatment not work for everyone? For whom does it work best? Individual clinical trials often do not provide sufficient statistical power to examine and substantiate moderating factors. To overcome the issue of limited power, an individual participant data meta-analysis of randomised trials evaluating forms of trauma-focused cognitive behavioural therapy in children and adolescents aged 6–18 years will be conducted. Methods and analysis We will update the National Institute for Health and Care Excellence guideline literature search from 2018 with an electronic search in the databases PsycINFO, MEDLINE, Embase, Cochrane Central Register of Controlled Trials and CINAHL with the terms (trauma* OR stress*) AND (cognitive therap* OR psychotherap*) AND (trial* OR review*). Electronic searches will be supplemented by a comprehensive grey literature search in archives and trial registries. Only randomised trials that used any manualised psychological treatment—that is a trauma-focused cognitive behavioural therapy for children and adolescents—will be included. The primary outcome variable will be child-reported posttraumatic stress symptoms (PTSS) post-treatment. Proxy-reports (teacher, parent and caregiver) will be analysed separately. Secondary outcomes will include follow-up assessments of PTSS, PTSD diagnosis and symptoms of comorbid disorders such as depression, anxiety-related and externalising problems. Random-effects models applying restricted maximum likelihood estimation will be used for all analyses. We will use the Revised Cochrane Risk of Bias tool to measure risk of bias. Ethics and dissemination Contributing study authors need to have permission to share anonymised data. Contributing studies will be required to remove patient identifiers before providing their data. Results will be published in a peer-reviewed journal and presented at international conferences. PROSPERO registration number CRD42019151954.

The striking multiplicity, signal input diversity, and output specificity of c-di-GMP signaling proteins in many bacteria has brought second messenger signaling back onto the agenda of contemporary microbiology. How can several signaling pathways act in parallel in a specific manner if all of them use the same diffusible second messenger present at a certain global cellular concentration? Recent research has now shown that bacteria achieve this by flexibly combining modes of local and global c-di-GMP signaling in complex signaling networks.

Cryptosporidiosis is one of the most important causes of moderate to severe diarrhea and diarrhea-related mortality in children under 2 years of age in low- and middle-income countries. In recent decades, genotyping and subtyping tools have been used in epidemiological studies of human cryptosporidiosis. Results of these studies suggest that higher genetic diversity of Cryptosporidium spp. is present in humans in these countries at both species and subtype levels and that anthroponotic transmission plays a major role in human cryptosporidiosis. Cryptosporidium hominis is the most common Cryptosporidium species in humans in almost all the low- and middle-income countries examined, with five subtype families (namely, Ia, Ib, Id, Ie, and If) being commonly found in most regions. In addition, most Cryptosporidium parvum infections in these areas are caused by the anthroponotic IIc subtype family rather than the zoonotic IIa subtype family. There is geographic segregation in Cryptosporidium hominis subtypes, as revealed by multilocus subtyping. Concurrent and sequential infections with different Cryptosporidium species and subtypes are common, as immunity against reinfection and cross protection against different Cryptosporidium species are partial. Differences in clinical presentations have been observed among Cryptosporidium species and C. hominis subtypes. These observations suggest that WASH (water, sanitation, and hygiene)-based interventions should be implemented to prevent and control human cryptosporidiosis in low- and middle-income countries.

The family Enterobacteriaceae has undergone significant morphogenetic changes in its more than 85-year history, particularly during the past 2 decades (2000 to 2020). The development and introduction of new and novel molecular methods coupled with innovative laboratory techniques have led to many advances. We now know that the global range of enterobacteria is much more expansive than previously recognized, as they play important roles in the environment in vegetative processes and through widespread environmental distribution through insect vectors. In humans, many new species have been described, some associated with specific disease processes. Some established species are now observed in new infectious disease settings and syndromes. The results of molecular taxonomic and phylogenetics studies suggest that the current family Enterobacteriaceae should possibly be divided into seven or more separate families. The logarithmic explosion in the number of enterobacterial species described brings into question the relevancy, need, and mechanisms to potentially identify these taxa. This review covers the progression, transformation, and morphogenesis of the family from the seminal Centers for Disease Control and Prevention publication (J. J. Farmer III, B. R. Davis, F. W. Hickman-Brenner, A. McWhorter, et al., J Clin Microbiol 21:46–76, 1985, https://doi.org/10.1128/JCM.21.1.46-76.1985) to the present.

Previous results indicate the presence of an interferon (IFN) signature in type 1 diabetes (T1D), capable of inducing chronic inflammation and compromising b cell function. Here, we determined the expression of the IFN response markers MxA, PKR, and HLA-I in the islets of autoantibody-positive and T1D donors. We found that these markers can be coexpressed in the same islet, are more abundant in insulin-containing islets, are highly expressed in islets with insulitis, and their expression levels are correlated with the presence of the enteroviral protein VP1. The expression of these markers was associated with down-regulation of multiple genes in the insulin secretion pathway. The coexistence of an IFN response and a microbial stress response is likely to prime islets for immune destruction. This study highlights the importance of therapeutic interventions aimed at eliminating potentially persistent infections and diminishing inflammation in individuals with T1D.

Enteric adenoviruses, one of the main causes of viral gastroenteritis in the world, must withstand the harsh conditions found in the gut. This requirement suggests that capsid stability must be different from that of other adenoviruses. We report the 4-Å-resolution structure of a human enteric adenovirus, HAdV-F41, and compare it with that of other adenoviruses with respiratory (HAdV-C5) and ocular (HAdV-D26) tropisms. While the overall structures of hexon, penton base, and internal minor coat proteins IIIa and VIII are conserved, we observe partially ordered elements reinforcing the vertex region, which suggests their role in enhancing the physicochemical capsid stability of HAdV-F41. Unexpectedly, we find an organization of the external minor coat protein IX different from all previously characterized human and nonhuman mastadenoviruses. Knowledge of the structure of enteric adenoviruses provides a starting point for the design of vectors suitable for oral delivery or intestinal targeting.

Etching single-layer graphene to incorporate a high pore density with sub-angstrom precision in molecular differentiation is critical to realize the promising high-flux separation of similar-sized gas molecules, e.g., CO2 from N2. However, rapid etching kinetics needed to achieve the high pore density is challenging to control for such precision. Here, we report a millisecond carbon gasification chemistry incorporating high density (>1012 cm–2) of functional oxygen clusters that then evolve in CO2-sieving vacancy defects under controlled and predictable gasification conditions. A statistical distribution of nanopore lattice isomers is observed, in good agreement with the theoretical solution to the isomer cataloging problem. The gasification technique is scalable, and a centimeter-scale membrane is demonstrated. Last, molecular cutoff could be adjusted by 0.1 Å by in situ expansion of the vacancy defects in an O2 atmosphere. Large CO2 and O2 permeances (>10,000 and 1000 GPU, respectively) are demonstrated accompanying attractive CO2/N2 and O2/N2 selectivities.

During the fall of 2020, several panel discussions were held to highlight the perspectives of Black parasitologists. Here, I summarize the themes from three such discussions, held at the Molecular Parasitology Meeting, Black in Microbiology Week, and the Annual Meeting of the American Society of Tropical Medicine & Hygiene, respectively.

Protozoan parasites acquire essential ions, nutrients, and other solutes from their insect and vertebrate hosts by transmembrane uptake. For intracellular stages, these solutes must cross additional membranous barriers. At each step, ion channels and transporters mediate not only this uptake but also the removal of waste products. These transport proteins are best isolated and studied with patch-clamp, but these methods remain accessible to only a few parasitologists due to specialized instrumentation and the required training in both theory and practice.

Parasites do not read legal documents. They cannot distinguish between animals or animal products that are traded with or without permits. Bezerra-Santos et al. [1] discussed the potential risks that the illegal wildlife trade has on the spreading and emergence of zoonotic pathogens. They highlight open wildlife (‘wet’) markets, the illegal transport of wildlife or their derivatives, as well as the illegal importation of exotic pets and the risk of zoonotic pathogens in the spread and introduction of diseases.

by Joshua Hart The COVID-19 pandemic likely had an effect on the outcome of the 2020 US presidential election. Was it responsible for the defeat of incumbent President Donald Trump? The present study makes an initial attempt at, and provides a model for, understanding the pandemic’s influence on Trump support. The study employed a mixed experimental and correlational design and surveyed separate samples of adults (N = 1,763) in six waves beginning March 23, 2020 and ending June 1, 2020. Participants were randomly assigned to report their Trump support either before or after being reminded of the pandemic with a series of questions gauging their level of concern about it. Results revealed complex and dynamic effects that changed over time. Depending on survey wave, the pandemic seems to have lowered Trump support among Democrats, while (marginally) raising it among independents. Republicans’ reactions also changed over time; of particular note, Republicans who were more concerned about the pandemic reported higher Trump support after being reminded of the pandemic in its early stages, but this effect reversed by the time the economy began reopening (coinciding with a dip in Trump’s approval ratings). Although the correlational results in the present study did not converge neatly with the experimental results, the combined experimental and correlational approach has the potential to increase researchers’ confidence in the causal effects of salient national and international events on political attitudes.

by Yirong Fang, Yan Ma, Qiaoling Lu, Jiamei Sun, Yingxin Pei Background In October 2016, a senior high school student was diagnosed with sputum-smear positive [SS(+)] pulmonary tuberculosis (TB). We conducted an investigation of an outbreak in the school, including among students and teachers diagnosed with latent TB, who we followed until July 2019. Methods We defined latent TB infection (LTBI) as a tuberculin skin test (TST) induration of 15mm or larger; probable TB as a chest radiograph indicative of TB plus productive cough/hemoptysis for at least 2 weeks, or TST induration of 15mm or larger; and confirmed TB as two or more positive sputum smears or one positive sputum smear plus a chest radiograph indicative of TB or culture positive with M. tuberculosis. We conducted mycobacterial interspersed repetitive unit–variable number tandem repeat (MIRU-VNTR) typing based on 24 loci in the isolates. Results Between October 2016 and July 2019, we identified 52 cases, including nine probable, six confirmed, and 37 LTBI cases. The index case-student had attended school continuously despite having TB symptoms for almost three months before being diagnosed with TB. We obtained three isolates from classmates of the index case in 2016; all had identical MIRU-VNTR alleles with the index case. The LTBI rate was lower among students (7.41%, 30/405) than among teachers (26.92%, 7/26) (rate ratio [RR] = 0.28, 95% confidential interval [CI]: 0.13–0.57). Among the 17 students who had latent TB and refused prophylaxis in October 2016, 23.53% (4/17) became probable/confirmed cases by July 2019. None of the six teachers who also refused prophylaxis became probable or confirmed cases. Of the 176 students who were TST(-) in October 2016, 1.70% (3/176) became probable/confirmed cases, and among the 20 teachers who were TST(-), 1 became a probable case. Conclusions Delayed diagnosis of TB in the index patient may have contributed to the start of this outbreak; lack of post-exposure chemoprophylaxis facilitated spread of the outbreak. Post-exposure prophylaxis is strongly recommended for all TST-positive students; TST-negative students exposed to an SS(+) case should be followed up regularly so that prophylaxis can be started if LTBI is detected.

by Henrik Dimke, Sanne L. Larsen, Marianne N. Skov, Hanne Larsen, Gitte N. Hartmeyer, Jesper B. Moeller The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rapidly reached pandemic levels. Sufficient testing for SARS-CoV-2 has remained essential for tracking and containing the virus. SARS-CoV-2 testing capabilities are still limited in many countries. Here, we explore the use of conventional RNA purification as an alternative to automated systems for detection of SARS-CoV-2 by RT-qPCR. 87 clinical swab specimens were extracted by conventional phenol-chloroform RNA purification and compared to commercial platforms for RNA extraction and the fully integrated Cobas®6800 diagnostic system. Our results show that the conventional RNA extraction is fully comparable to modern automated systems regarding analytical sensitivity and specificity with respect to detection of SARS-CoV-2 as evaluated by RT-qPCR. Moreover, the method is easily scalable and implemented in conventional laboratories as a low cost and suitable alternative to automated systems for the detection of SARS-CoV-2.

by Russell H. Fazio, Benjamin C. Ruisch, Courtney A. Moore, Javier A. Granados Samayoa, Shelby T. Boggs, Jesse T. Ladanyi A study involving over 2000 online participants (US residents) tested a general framework regarding compliance with a directive in the context of the COVID-19 pandemic. The study featured not only a self-report measure of social distancing but also virtual behavior measures—simulations that presented participants with graphical depictions mirroring multiple real-world scenarios and asked them to position themselves in relation to others in the scene. The conceptual framework highlights three essential components of a directive: (1) the source, some entity is advocating for a behavioral change; (2) the surrounding context, the directive is in response to some challenge; and (3) the target, the persons to whom the directive is addressed. Belief systems relevant to each of these three components are predicted, and were found, to relate to compliance with the social distancing directive. The implications of the findings for public service campaigns encouraging people to engage in social distancing are discussed.

by Sourabh Soni, Yujie Jiang, Yohannes Tesfaigzi, Jason L. Hornick, Sule Çataltepe Angiotensin converting enzyme 2 (ACE2) is the putative functional receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Current literature on the abundance and distribution of ACE2 protein in the human respiratory tract is controversial. We examined the effect of age and lung injury on ACE2 protein expression in rodent and non-human primate (NHP) models. We also examined ACE2 expression in human tissues with and without coronavirus disease 19 (COVID-19). ACE2 expression was detected at very low levels in preterm, but was absent in full-term and adult NHP lung homogenates. This pattern of ACE2 expression contrasted with that of transmembrane protease serine type 2 (TMPRSS2), which was significantly increased in full-term newborn and adult NHP lungs compared to preterm NHP lungs. ACE2 expression was not detected in NHP lungs with cigarette smoke-induced airway disease or bronchopulmonary dysplasia. Murine lungs lacked basal ACE2 immunoreactivity, but responded to hyperoxia, bacterial infection, and allergen exposure with new ACE2 expression in bronchial epithelial cells. In human specimens, robust ACE2 immunoreactivity was detected in ciliated epithelial cells in paranasal sinus specimens, while ACE2 expression was detected only in rare type 2 alveolar epithelial cells in control lungs. In autopsy specimens from patients with COVID-19 pneumonia, ACE2 was detected in rare ciliated epithelial and endothelial cells in the trachea, but not in the lung. There was robust expression of ACE2 expression in F344/N rat nasal mucosa and lung specimens, which authentically recapitulated the ACE2 expression pattern in human paranasal sinus specimens. Thus, ACE2 protein expression demonstrates a significant gradient between upper and lower respiratory tract in humans and is scarce in the lung. This pattern of ACE2 expression supports the notion of sinonasal epithelium being the main entry site for SARS-CoV-2 but raises further questions on the pathogenesis and cellular targets of SARS-CoV-2 in COVID-19 pneumonia.

by Dhruv Puri, Yasir Bin Nisar, Antoinette Tshefu, Adrien Lokangaka Longombe, Fabian Esamai, Irene Marete, Adejumoke Idowu Ayede, Ebunoluwa A. Adejuyigbe, Robinson D. Wammanda, Shamim Ahmad Qazi, Rajiv Bahl Background Community-based data on the prevalence of clinical signs of possible serious bacterial infection (PSBI) and the mortality associated with them are scarce. The aim was to examine the prevalence for each sign of infection and mortality associated with infants in the first two months of life, using community surveillance through community health workers (CHW). Methods We used population-based surveillance data of infants up to two months of age from the African Neonatal Sepsis Trial (AFRINEST). In this study, CHWs visited infants up to 10 times during the first two months of life at five sites in three sub-Saharan African countries. CHW assessed the infant for signs of infection (local or systemic) and referred infants who presented with any sign of infection to a health facility. We used a longitudinal analysis to calculate the risk of death associated with the presence of a sign of infection at the time of the visit until the subsequent visit. Results During the first two months of their life, CHWs visited 84,759 live-born infants at least twice. In 11,089 infants (13.1%), one or more signs of infection were identified, of which 237 (2.1%) died. A sign of infection was detected at 2.1% of total visits. In 52% of visits, infants had one or more sign of systemic infection, while 25% had fast breathing in 7–59 days period and 23% had a local infection. All signs of infection, including multiple signs, were more frequently seen in the first week of life. The risk of mortality was very low (0.2%) for local infections and fast breathing in 7–59 days old, it was low for fast breathing 0–6 days old (0.6%), high body temperature (0.7%) and severe chest indrawing (1.0%), moderate for low body temperature (4.9%) and stopped feeding well/not able to feed at all (5.0%) and high for movement only when stimulated or no movement at all (10%) and multiple signs of systemic infection (15.5%). The risk of death associated with most clinical signs was higher (1.5 to 9 times) in the first week of life than at later age, except for low body temperature (4 times lower) as well as high body temperature (2 times lower). Conclusion Signs of infections are common in the first two months of life. The mortality risk differs with clinical signs and can be grouped as very low (local infections, fast breathing 7–59 days), low (fever, severe chest indrawing and fast breathing 0–6 days), moderate (low body temperature and stopped feeding well/not able to feed at all) and high (for movements only on stimulation or no movements at all and multiple signs of infection). New treatment strategies that consider differential mortality risk could be developed and evaluated based on these findings. Clinical trial registration The trial was registered with Australian New Zealand Clinical Trials Registry under ID ACTRN 12610000286044.

by Ishan Paranjpe, Kumardeep Chaudhary, Kipp W. Johnson, Suraj K. Jaladanki, Shan Zhao, Jessica K. De Freitas, Elisabet Pujdas, Fayzan Chaudhry, Erwin P. Bottinger, Matthew A. Levin, Zahi A. Fayad, Alexander W. Charney, Jane Houldsworth, Carlos Cordon-Cardo, Benjamin S. Glicksberg, Girish N. Nadkarni Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the associated Coronavirus Disease 2019 (COVID-19) is a public health emergency. Acute kidney injury (AKI) is a common complication in hospitalized patients with COVID-19 although mechanisms underlying AKI are yet unclear. There may be a direct effect of SARS-CoV-2 virus on the kidney; however, there is currently no data linking SARS-CoV-2 viral load (VL) to AKI. We explored the association of SARS-CoV-2 VL at admission to AKI in a large diverse cohort of hospitalized patients with COVID-19. Methods and findings We included patients hospitalized between March 13th and May 19th, 2020 with SARS-CoV-2 in a large academic healthcare system in New York City (N = 1,049) with available VL at admission quantified by real-time RT-PCR. We extracted clinical and outcome data from our institutional electronic health records (EHRs). AKI was defined by KDIGO guidelines. We fit a Fine-Gray competing risks model (with death as a competing risk) using demographics, comorbidities, admission severity scores, and log10 transformed VL as covariates and generated adjusted hazard ratios (aHR) and 95% Confidence Intervals (CIs). VL was associated with an increased risk of AKI (aHR = 1.04, 95% CI: 1.01–1.08, p = 0.02) with a 4% increased hazard for each log10 VL change. Patients with a viral load in the top 50th percentile had an increased adjusted hazard of 1.27 (95% CI: 1.02–1.58, p = 0.03) for AKI as compared to those in the bottom 50th percentile. Conclusions VL is weakly but significantly associated with in-hospital AKI after adjusting for confounders. This may indicate the role of VL in COVID-19 associated AKI. This data may inform future studies to discover the mechanistic basis of COVID-19 associated AKI.

by Safar Vafadar, Maryam Shahdoust, Ata Kalirad, Pooya Zakeri, Mehdi Sadeghi Inspired by the competition exclusion principle, this work aims at providing a computational framework to explore the theoretical feasibility of viral co-infection as a possible strategy to reduce the spread of a fatal strain in a population. We propose a stochastic-based model—called Co-Wish—to understand how competition between two viruses over a shared niche can affect the spread of each virus in infected tissue. To demonstrate the co-infection of two viruses, we first simulate the characteristics of two virus growth processes separately. Then, we examine their interactions until one can dominate the other. We use Co-Wish to explore how the model varies as the parameters of each virus growth process change when two viruses infect the host simultaneously. We will also investigate the effect of the delayed initiation of each infection. Moreover, Co-Wish not only examines the co-infection at the cell level but also includes the innate immune response during viral infection. The results highlight that the waiting times in the five stages of the viral infection of a cell in the model—namely attachment, penetration, eclipse, replication, and release—play an essential role in the competition between the two viruses. While it could prove challenging to fully understand the therapeutic potentials of viral co-infection, we discuss that our theoretical framework hints at an intriguing research direction in applying co-infection dynamics in controlling any viral outbreak’s speed.

by Ahmed Hamza Osman, Hani Moetque Aljahdali, Sultan Menwer Altarrazi, Ali Ahmed The outbreak of coronavirus disease 2019 (COVID-19) has had an immense impact on world health and daily life in many countries. Sturdy observing of the initial site of infection in patients is crucial to gain control in the struggle with COVID-19. The early automated detection of the recent coronavirus disease (COVID-19) will help to limit its dissemination worldwide. Many initial studies have focused on the identification of the genetic material of coronavirus and have a poor detection rate for long-term surgery. The first imaging procedure that played an important role in COVID-19 treatment was the chest X-ray. Radiological imaging is often used as a method that emphasizes the performance of chest X-rays. Recent findings indicate the presence of COVID-19 in patients with irregular findings on chest X-rays. There are many reports on this topic that include machine learning strategies for the identification of COVID-19 using chest X-rays. Other current studies have used non-public datasets and complex artificial intelligence (AI) systems. In our research, we suggested a new COVID-19 identification technique based on the locality-weighted learning and self-organization map (LWL-SOM) strategy for detecting and capturing COVID-19 cases. We first grouped images from chest X-ray datasets based on their similar features in different clusters using the SOM strategy in order to discriminate between the COVID-19 and non-COVID-19 cases. Then, we built our intelligent learning model based on the LWL algorithm to diagnose and detect COVID-19 cases. The proposed SOM-LWL model improved the correlation coefficient performance results between the Covid19, no-finding, and pneumonia cases; pneumonia and no-finding cases; Covid19 and pneumonia cases; and Covid19 and no-finding cases from 0.9613 to 0.9788, 0.6113 to 1 0.8783 to 0.9999, and 0.8894 to 1, respectively. The proposed LWL-SOM had better results for discriminating COVID-19 and non-COVID-19 patients than the current machine learning-based solutions using AI evaluation measures.

by Abdul Noury, Abel François, Olivier Gergaud, Alexandre Garel This article investigates the effects of the COVID-19 outbreak on electoral participation. We study the French municipal elections that took place at the very beginning of the ongoing pandemic and held in over 9,000 municipalities on March 15, 2020. In addition to the simple note that turnout rates decreased to a historically low level, we establish a robust relationship between the depressed turnout rate and the disease. Using various estimation strategies and employing a large number of potential confounding factors, we find that the participation rate decreases with city proximity to COVID-19 clusters. Furthermore, the proximity has conditioned impacts according to the proportion of elderly –who are the most threatened– within the city. Cities with higher population density, where the risk of infection is higher, and cities where only one list ran at the election, which dramatically reduces competitiveness, experienced differentiated effects of distance.

by Gabriele Pagani, Andrea Giacomelli, Federico Conti, Dario Bernacchia, Rossana Rondanin, Andrea Prina, Vittore Scolari, Arianna Rizzo, Martina Beltrami, Camilla Caimi, Cecilia Eugenia Gandolfi, Silvana Castaldi, Bruno Alessandro Rivieccio, Giacomo Buonanno, Giuseppe Marano, Cosimo Ottomano, Patrizia Boracchi, Elia Biganzoli, Massimo Galli Castiglione D’Adda is one of the municipalities more precociously and severely affected by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) epidemic in Lombardy. With our study we aimed to understand the diffusion of the infection by mass serological screening. We searched for SARS-CoV-2 IgGs in the entire population on a voluntary basis using lateral flow immunochromatographic tests (RICT) on capillary blood (rapid tests). We then performed chemioluminescent serological assays (CLIA) and naso-pharyngeal swabs (NPS) in a randomized representative sample and in each subject with a positive rapid test. Factors associated with RICT IgG positivity were assessed by uni- and multivariate logistic regression models. Out of the 4143 participants, 918 (22·2%) showed RICT IgG positivity. In multivariable analysis, IgG positivity increases with age, with a significant non-linear effect (p = 0·0404). We found 22 positive NPSs out of the 1330 performed. Albeit relevant, the IgG prevalence is lower than expected and suggests that a large part of the population remains susceptible to the infection. The observed differences in prevalence might reflect a different infection susceptibility by age group. A limited persistence of active infections could be found after several weeks after the epidemic peak in the area.

by Ozlem Yaren, Jacquelyn McCarter, Nikhil Phadke, Kevin M. Bradley, Benjamin Overton, Zunyi Yang, Shatakshi Ranade, Kunal Patil, Rishikesh Bangale, Steven A. Benner Managing the pandemic caused by SARS-CoV-2 requires new capabilities in testing, including the possibility of identifying, in minutes, infected individuals as they enter spaces where they must congregate in a functioning society, including workspaces, schools, points of entry, and commercial business establishments. Here, the only useful tests (a) require no sample transport, (b) require minimal sample manipulation, (c) can be performed by unlicensed individuals, (d) return results on the spot in much less than one hour, and (e) cost no more than a few dollars. The sensitivity need not be as high as normally required by the FDA for screening asymptomatic carriers (as few as 10 virions per sample), as these viral loads are almost certainly not high enough for an individual to present a risk for forward infection. This allows tests specifically useful for this pandemic to trade-off unneeded sensitivity for necessary speed, simplicity, and frugality. In some studies, it was shown that viral load that creates forward-infection risk may exceed 105 virions per milliliter, easily within the sensitivity of an RNA amplification architecture, but unattainable by antibody-based architectures that simply target viral antigens. Here, we describe such a test based on a displaceable probe loop amplification architecture.

R. R. Ghai et al.

C. Boodman et al.

A. Kraay et al.

Abstract Background Drug susceptibility testing (DST) patterns of Mycobacterium tuberculosis (MTB) from patients with rifampicin-resistant tuberculosis (RR-TB) or multidrug-resistant TB (MDR-TB; or resistant to rifampicin and isoniazid (INH)), are important to guide preventive therapy for their household contacts (HHCs). Methods As part of a feasibility study done in preparation for an MDR-TB preventive therapy trial in HHCs, smear, Xpert MTB/RIF, Hain MTBDRplus, culture and DST results of index MDR-TB patients were obtained from routine TB programs. A sputum sample was collected at study entry and evaluated by the same tests. Not all tests were performed on all specimens due to variations in test availability. Results Three hundred eight adults with reported RR/MDR-TB were enrolled from 16 participating sites in 8 countries. Their median age was 36 years, and 36% were HIV-infected. Routine testing on all 308 were confirmed as having RR-TB, but only 75% were documented as having MDR-TB. The majority of those not classified as having MDR-TB were because only rifampicin resistance was tested. At study entry (median 59 days after MDR-TB treatment initiation), 280 participants (91%) were able to produce sputum for the study, of whom 147 (53%) still had detectable MTB. All but 2 of these 147 had rifampicin DST done, with resistance detected in 89%. Almost half (47%) of the 147 specimens had INH DST done, with 83% resistance. Therefore, 20% of the 280 study specimens had MDR-TB confirmed. Overall, DST for second-line drugs were available in only 35% of the 308 routine specimens and 15% of 280 study specimens. Conclusions RR-TB was detected in all routine specimens but only 75% had documented MDR-TB, illustrating the need for expanded DST beyond Xpert MTB/RIF to target preventive therapy for HHC.

Abstract Background There is limited information on the difference in epidemiology, clinical characteristics and outcomes of the initial outbreak of the coronavirus disease (COVID-19) in Wuhan (the epicenter) and Sichuan (the peripheral area) in the early phase of the COVID-19 pandemic. This study was conducted to investigate the differences in the epidemiological and clinical characteristics of patients with COVID-19 between the epicenter and peripheral areas of pandemic and thereby generate information that would be potentially helpful in formulating clinical practice recommendations to tackle the COVID-19 pandemic. Methods The Sichuan & Wuhan Collaboration Research Group for COVID-19 established two retrospective cohorts that separately reflect the epicenter and peripheral area during the early pandemic. The epidemiology, clinical characteristics and outcomes of patients in the two groups were compared. Multivariate regression analyses were used to estimate the adjusted odds ratios (aOR) with regard to the outcomes. Results The Wuhan (epicenter) cohort included 710 randomly selected patients, and the peripheral (Sichuan) cohort included 474 consecutive patients. A higher proportion of patients from the periphery had upper airway symptoms, whereas a lower proportion of patients in the epicenter had lower airway symptoms and comorbidities. Patients in the epicenter had a higher risk of death (aOR=7.64), intensive care unit (ICU) admission (aOR=1.66), delayed time from illness onset to hospital and ICU admission (aOR=6.29 and aOR=8.03, respectively), and prolonged duration of viral shedding (aOR=1.64). Conclusions The worse outcomes in the epicenter could be explained by the prolonged time from illness onset to hospital and ICU admission. This could potentially have been associated with elevated systemic inflammation secondary to organ dysfunction and prolonged duration of virus shedding independent of age and comorbidities. Thus, early supportive care could achieve better clinical outcomes.

Abstract Background A large-scale global outbreak of coronavirus disease-19 (COVID-19) out of Wuhan, from China, occurred in January 2020. To examine the clinical characteristics of COVID-19 in infected patients out of Wuhan, from China. Methods Thirteen patients were confirmed to be infected with novel coronavirus-2019 (2019-nCoV) between January 27 and February 8, 2020, in Baoji city, Shannxi, northwestern China. Epidemiological and clinical information, and computed to morphology imaging data from all COVID-19 patients were collected; cases were divided into two groups according to the severity of infection (mild or severe). Results Nine (9/13) COVID-19 patients exhibited mild disease severity, and defined as second-generation human-to-human transmission cases. Most patients (11/13) had a history of travel to or from Wuhan. There were no differences in sex and age between the mild and severe cases (all P > 0.05). A moderate degree of fever (11/13), cough (13/13), and fatigue (8/13) were common symptoms; however, there was no statistical difference between mild and severe cases in this regard (all P > 0.05). Oxyhemoglobin saturation and oxygenation index decreased, and C-reactive protein (CRP) and serum amyloid A (SAA) levels were elevated in all patients with COVID-19 infection, with statistically significant differences between those with severe disease and mild infection (all P < 0.05). Twelve of 13 COVID-19 patients exhibited changes in chest CT imaging features, and time course changes were different between mild and severe cases (all P < 0.05). Conclusion Most cases of COVID-19 infection were second-generation human-to-human transmissions from Wuhan and were mild in severity. The clinical characteristics of COVID-19 varied. Oxyhemoglobin saturation, oxygenation index, CRP and SAA levels, and CT features were reliable parameters to evaluate the severity of COVID-19 infection. However, a few patients with mild COVID-19 disease lacked typical characteristics such as fever and changes in CT imaging features.

Antimicrobial resistance in intensive care units (ICUs) is one of the most challenging problems for managing critically ill patients (Johnson et al., 2020; Weiner-Lastinger et al., 2020). It is known that more than one-third of patients admitted to the ICU have sepsis; thus, antimicrobial agents could be over- and mis-prescribed to increase the chance of administering appropriate antibiotics or simply to relieve the anxiety of clinicians (Luyt et al., 2014; Vincent et al., 2006). Therefore, the antimicrobial stewardship program (ASP) is highly recommended in critical care to improve antibiotic utilization and patient outcome (Barlam et al., 2016; Luyt et al., 2014; Pickens and Wunderink, 2019; Zhang and Singh, 2015).

In light of the ongoing pandemic, development of vaccines to protect against SARS-CoV-2 infection and COVID-19 disease is an important public health priority. As of February 2021, two SARS-CoV-2 vaccines have received emergency use authorisation by the US Food and Drug Administration (FDA), both of which use mRNA technology. While the safety data are reassuring, phase 3 studies of both vaccines demonstrate an imbalance of cases of Bell's palsy in the vaccine groups compared with the placebo groups.

Journal of Medical Virology, Accepted Article.

Journal of Medical Virology, Accepted Article.

Journal of Medical Virology, Accepted Article.

The evolution of massive stars is influenced by the mass lost to stellar winds over their lifetimes. These winds limit the masses of the stellar remnants (such as black holes) that the stars ultimately produce. We use radio astrometry to refine the distance to the black hole X-ray binary Cygnus X-1, which we find to be kiloparsecs. When combined with archival optical data, this implies a black hole mass of 21.2 ± 2.2 solar masses, higher than previous measurements. The formation of such a high-mass black hole in a high-metallicity system (within the Milky Way) constrains wind mass loss from massive stars.

Ella R, Vadrevu KM, Jogdand H, et al. Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine, BBV152: a double-blind, randomised, phase 1 trial. Lancet Infect Dis 2021; published online Jan 21. https://doi.org/10.1016/S1473-3099(20)30942-7—In this Article, the Role of the funding source has been updated to “The funder of the study had no role in data collection, data analysis, data interpretation, or writing of the statistical report, but was involved in study design. Data cleaning and analysis was conducted by a third party contract research organisation (Sclin Soft Technologies).

Hoenigl M, Salmanton-García J, Walsh TJ, et al. Global guideline for the diagnosis and management of rare mould infections: an initiative of the European Confederation of Medical Mycology in cooperation with the International Society for Human and Animal Mycology and the American Society for Microbiology. Lancet Infect Dis 2021; published online Feb 16. https://doi.org/10.1016/S1473-3099(20)30784-2—In figure 3A of this Article, the arrows pointing toward the yellow treatment box have been corrected.

Since its first description, SARS-CoV-2 has been the subject of more than 59 000 publications worldwide. Although SARS-CoV-2 infection mainly results in mild disease, during the first COVID-19 wave in France, up to 3% of patients required admission to hospital, 0·8% required intensive care unit admission, and overall mortality was reported to be around 0·5%.1 The ability to predict disease severity and subsequent course might help with triaging patients, optimising resource management, and understanding modifiable and non-modifiable factors involved in patient outcomes.

WHO recommends a minimum of 80% sensitivity and 97% specificity for antigen-detection rapid diagnostic tests (Ag-RDTs), which can be used for patients with symptoms consistent with COVID-19. However, after the acute phase when viral load decreases, use of Ag-RDTs might lead to high rates of false negatives, suggesting that the tests should be replaced by a combination of molecular and serological tests. When the likelihood of having COVID-19 is low, such as for asymptomatic individuals in low prevalence settings, for travel, return to schools, workplaces, and mass gatherings, Ag-RDTs with high negative predictive values can be used with confidence to rule out infection.

Patients admitted to hospital with COVID-19 can be classified into three phenotypes that correlate with mortality. We developed and validated a simplified tool for the probabilistic assignment of patients into phenotypes. These results might help to better classify patients for clinical management, but the pathophysiological mechanisms of the phenotypes must be investigated.

Introduction Herpes zoster (HZ) and associated complications inflict substantial morbidity and associated healthcare and socioeconomic burdens. Current treatments are not fully effective, especially among the most vulnerable populations. Two HZ vaccines are available and are part of the national immunisation programmes in many countries. This review will evaluate the effectiveness of zoster vaccines against incident HZ and postherpetic neuralgia in adults 50 years and older. Methods and analysis The key information sources that will be searched include MEDLINE (Ovid), Embase (Ovid), Cochrane libraries and CINAHL. This search will consider postlicensure observational studies published in all languages between 2006 and 2020 that assessed the effectiveness of HZ/zoster vaccines in adults 50 years and older. The identification of studies will be complemented with the search of reference lists and citations, and contact with authors of papers to request missing or additional data, where required. Following the search, all identified citations will be collated, and duplicates will be removed. Titles and abstracts will then be screened by two independent reviewers for assessment against the inclusion criteria for the review. Selected studies will follow the process of critical appraisal, data extraction and data synthesis. Statistical analyses will be performed using a random-effect model. Ethics and dissemination Formal ethical approval is not required, as primary data will not be collected. The review will be disseminated in peer-reviewed publications and conference presentations.

Setting Children especially those <5 years of age exposed to pulmonary tuberculosis (TB) are at a high risk of severe TB disease and death. Isoniazid preventive therapy (IPT) has been shown to decrease disease progression by up to 90%. Kenya, a high TB burden country experiences numerous operational challenges that limit implementation of TB preventive services. IPT completion in child contacts is not routinely reported in Kenya. Objective This study aims to review the child contact management (CCM) cascade and present IPT outcomes across 10 clinics in western Kenya. Design A retrospective chart review of programmatic data of a TB Reach-funded active, clinic-based CCM strategy. Results Of 553 child contacts screened, 231 (42%) were reported symptomatic. 74 (13%) of the child contacts were diagnosed with active TB disease. Of those eligible for IPT, 427 (90%) initiated IPT according to TB REACH project data while 249 (58%) were recorded in the IPT register with 49 (11%) recorded as a transfer to other facilities. Of the 249 recorded in the IPT register, 205 (82%) were documented to complete therapy (48% of project initiation children). Conclusion Our evaluation shows gaps in the routine CCM care cascade related to completeness of documentation that require further programmatic monitoring and evaluation to improve CCM outcomes.

Objective Public cooperation to practise preventive health behaviours is essential to manage the transmission of infectious diseases such as COVID-19. We aimed to investigate beliefs about COVID-19 diagnosis, transmission and prevention that have the potential to impact the uptake of recommended public health strategies. Design An online cross-sectional survey. Participants A national sample of 1500 Australian adults with representative quotas for age and gender provided by an online panel provider. Main outcome measure Proportion of participants with correct/incorrect knowledge of COVID-19 preventive behaviours and reasons for misconceptions. Results Of the 1802 potential participants contacted, 289 did not qualify, 13 declined and 1500 participated in the survey (response rate 83%). Most participants correctly identified ‘washing your hands regularly with soap and water’ (92%) and ‘staying at least 1.5 m away from others’ (90%) could help prevent COVID-19. Over 40% (incorrectly) considered wearing gloves outside of the home would prevent them from contracting COVID-19. Views about face masks were divided. Only 66% of participants correctly identified that ‘regular use of antibiotics’ would not prevent COVID-19. Most participants (90%) identified ‘fever, fatigue and cough’ as indicators of COVID-19. However, 42% of participants thought that being unable to ‘hold your breath for 10 s without coughing’ was an indicator of having the virus. The most frequently reported sources of COVID-19 information were commercial television channels (56%), the Australian Broadcasting Corporation (43%) and the Australian Government COVID-19 information app (31%). Conclusions Public messaging about hand hygiene and physical distancing to prevent transmission appears to have been effective. However, there are clear, identified barriers for many individuals that have the potential to impede uptake or maintenance of these behaviours in the long term. We need to develop public health messages that harness these barriers to improve future cooperation. Ensuring adherence to these interventions is critical.

The COVID-19 pandemic has led to an explosion of online research using rating scales. While this approach can be useful, two of the major challenges affecting the quality of this type of research include selection bias and the use of non-validated scales. Online research is prone to various forms of selection bias, including self-selection bias, non-response bias or only reaching specific subgroups. The use of rating scales requires contextually validated scales that meet psychometrical properties such as validity, reliability and—for cross-country comparisons—invariance across settings. We discuss options to prevent or tackle these challenges. Researchers, readers, editors and reviewers need to take a critical stance towards research using this type of methodology.

Objective The adherence to public health recommendations to control COVID-19 spread is influenced by public knowledge, attitudes and practices (KAP). We performed this cross-sectional study to assess the levels and determinants of public KAP towards COVID-19 in a large, multinational sample. Design Cross-sectional study (survey). Setting The questionnaire was distributed to potential respondents via online platforms. Participants 71 890 individuals from 22 countries. Methods We formulated a four-section questionnaire in English, followed by validation and translation into seven languages. The questionnaire was distributed (May to June 2020) and each participant received a score for each KAP section. Results Overall, the participants had fair knowledge (mean score: 19.24±3.59) and attitudes (3.72±2.31) and good practices (12.12±1.83) regarding COVID-19. About 92% reported moderate to high compliance with national lockdown. However, significant gaps were observed: only 68.2% knew that infected individuals may be asymptomatic; 45.4% believed that antibiotics are an effective treatment; and 55.4% stated that a vaccine has been developed (at the time of data collection). 71.9% believed or were uncertain that COVID-19 is a global conspiracy; 36.8% and 51% were afraid of contacting doctors and Chinese people, respectively. Further, 66.4% reported the pandemic had moderate to high negative effects on their mental health. Female gender, higher education and urban residents had significantly (p≤0.001) higher knowledge and practice scores. Further, we observed significant correlations between all KAP scores. Conclusions Although the public have fair/good knowledge and practices regarding COVID-19, significant gaps should be addressed. Future awareness efforts should target less advantaged groups and future studies should develop new strategies to tackle COVID-19 negative mental health effects.

Objective Assessment of the expertise of medical students in evaluating vital signs and their implications for the current risk of a patient, an appropriate monitoring frequency, and a proper clinical response. Methods 251 second-year and 267 fifth-year medical students in a curriculum consisting of 6 years of medical school at Ulm University, Germany, were interviewed in a paper-based questionnaire. The students were asked to rate their proficiency in interpreting vital signs and to give pathological thresholds of vital signs. Based on the National Early Warning Score 2 (NEWS2), nine vital signs of fictional patients were created and students were asked to comment on their clinical risk, to set an appropriate monitoring frequency as well as a clinical response. Results Interviewing medical students regarding each vital sign individually, the students indicated a pathological threshold in accordance with the NEWS2 for respiratory rate, temperature, and heart rate. By contrast, inappropriate pathological limits were given regarding oxygen saturation and systolic blood pressure. Translating the vital signs into nine fictional patients, fifth-year medical students overall chose an appropriate response in 78% (67%–78%, median±IQR). In detail, fifth-year students successfully identified patients at very high or low risk and allocated them accordingly. However, cases on the edge were often stratified inappropriately. For example, a fictional case with vital signs indicating a surging sepsis was frequently underappreciated (48.5%) and allocated to an insufficient clinical response by fifth-year students. Conclusions Recognising the healthy as well as the deteriorating patient is a key ability for future physicians. NEWS2-based education might be a valuable tool to assess and give feedback on student’s knowledge in this vital professional activity.

Objectives Mothers with young children are particularly vulnerable to the impacts of the lifestyle changes brought about by the COVID-19 pandemic. However, the association between such changes and maternal mental health has not been examined, and comparable pre-COVID-19 baseline data were lacking. Thus, we aimed to examine the relationships between changes due to COVID-19 pandemic and the development of depressive and anxiety symptoms among mothers of infants and/or preschoolers in Japan. Design Prospective follow-up study. The baseline survey was conducted in February 2020, and the follow-up survey was conducted in June 2020. Setting All 47 prefectures in Japan. Participants At the baseline, 4700 mothers of infants and/or preschoolers (0–6 years) participated in the online survey (100 respondents per prefecture); 2489 of them also participated in the follow-up survey. After excluding 203 participants with a higher risk of severe mental illness at the baseline, 2286 were included in the analysis. Outcome measures The Kessler Psychological Distress Scale was used to measure depressive and anxiety symptoms, with a cut-off point of 13 or more. We estimated the adjusted OR (AOR) using multiple logistic regression analysis. Results During the follow-up period, 151 (6.6%) of respondents newly developed depressive and anxiety symptoms. Participants who experienced a shortage of relaxation time (AOR 1.61, 95% CI 1.06 to 2.47), increased difficulty in child rearing (AOR 1.89, 95% CI 1.32 to 2.70), increased partner aggression (AOR 2.93, 95% CI 1.42 to 6.05) and an increased sense of unfairness (AOR 1.74, 95% CI 1.10 to 2.73) were more likely to develop these symptoms. Conclusions Changes in circumstances and perceptions during COVID-19 outbreak were significantly related to the development of depressive and anxiety symptoms among mothers of young children. Strategies to reduce solo parenting and increase social awareness related to domestic violence are needed.