Rapid COVID-19 screening based on self-reported symptoms: Psychometric assessment and validation of the EPICOVID19 short diagnostic scale

Background: Confirmed COVID-19 cases have been registered in more than 200 countries, and as of July 28, 2020, over 16 million cases have been reported to the World Health Organization. This study was conducted during the epidemic peak of COVID-19 in Italy. The early identification of individuals with suspected COVID-19 is critical in immediately quarantining such individuals. Although surveys are widely used for identifying COVID-19 cases, outcomes, and associated risks, no validated epidemiological tool exists for surveying SARS-CoV-2 infection in the general population. Objective: We evaluated the capability of self-reported symptoms in discriminating COVID-19 to identify individuals who need to undergo instrumental measurements. We defined and validated a method for identifying a cutoff score. Methods: Our study is phase II of the EPICOVID19 Italian national survey, which launched in April 2020 and included a convenience sample of 201,121 adults who completed the EPICOVID19 questionnaire. The Phase II questionnaire, which focused on the results of nasopharyngeal swab (NPS) and serological tests, was mailed to all subjects who previously underwent NPS tests. Results: Of 2703 subjects who completed the Phase II questionnaire, 694 (25.7%) were NPS positive. Of the 472 subjects who underwent the immunoglobulin G (IgG) test and 421 who underwent the immunoglobulin M test, 22.9% (108/472) and 11.6% (49/421) tested positive, respectively. Compared to NPS-negative subjects, NPS-positive subjects had a higher incidence of fever (421/694, 60.7% vs 391/2009, 19.5%; P<.001), loss of taste and smell (365/694, 52.6% vs 239/2009, 11.9%; P<.001), and cough (352/694, 50.7% vs 580/2009, 28.9%; P<.001). With regard to subjects who underwent serological tests, IgG-positive subjects had a higher incidence of fever (65/108, 60.2% vs 43/364, 11.8%; P<.001) and pain in muscles/bones/joints (73/108, 67.6% vs 71/364, 19.5%; P<.001) than IgG-negative subjects. An analysis of self-reported COVID-19 symptom items revealed a 1-factor solution, the EPICOVID19 diagnostic scale. The following optimal scores were identified: 1.03 for respiratory problems, 1.07 for chest pain, 0.97 for loss of taste and smell 0.97, and 1.05 for tachycardia (ie, heart palpitations). These were the most important symptoms. For adults aged 18-84 years, the cutoff score was 2.56 (sensitivity: 76.56%; specificity: 68.24%) for NPS-positive subjects and 2.59 (sensitivity: 80.37%; specificity: 80.17%) for IgG-positive subjects. For subjects aged ≥60 years, the cutoff score was 1.28, and accuracy based on the presence of IgG antibodies improved (sensitivity: 88.00%; specificity: 89.58%). Conclusions: We developed a short diagnostic scale to detect subjects with symptoms that were potentially associated with COVID-19 from a wide population. Our results support the potential of self-reported symptoms in identifying individuals who require immediate clinical evaluations. Although these results come from the Italian pandemic period, this short diagnostic scale could be optimized and tested as a screening tool for future similar pandemics

Self-reported symptoms of SARS-CoV-2 infection in a non-hospitalized population : results from the large Italian web-based EPICOVID19 cross-sectional survey. (Preprint)

Background: Understanding the occurrence of Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2)-like symptoms in a large non-hospitalized population, when the epidemic peak was occurring in Italy, is of paramount importance but data are scarce. Objective: Aims of this study were to evaluate the association of self-reported symptoms with SARS-CoV-2 nasopharyngeal swab (NPS) test in non-hospitalized individuals and to estimate the occurrence of COVID-19-like symptoms in a larger non-tested population. Methods: This is an Italian countrywide self-administered cross-sectional web-based survey on voluntary adults who completed an anonymous questionnaire in the period 13-21 April 2020. The associations between symptoms potentially related to SARS-CoV-2 infection and NPS results were calculated as adjusted odds ratios with 95% confidence intervals (aOR, 95%CI) by means of multiple logistic regression analysis controlling for age, sex, education, smoking habits, and the number of co-morbidities. Thereafter, for each symptom and for their combination, we calculated sensitivity, specificity, accuracy and AUC in a ROC analysis to estimate the occurrence of COVID-19-like infections in the non-tested population. Results: A total of 171,310 responded to the survey (59.9% females, mean age 47.4 years). Out of the 4,785 respondents with known NPS test result, 4,392 were not hospitalized. Among them, the NPS positive respondents (n=856) most frequently reported myalgia (61.6%), olfactory and/or taste disorders (OTDs, 59.2%), cough (54.4%), and fever (51.9%) whereas 7.7% were asymptomatic. Multiple regression analysis showed that OTDs (aOR 10.3, [95%CI 8.4-12.7]), fever (2.5, 95%CI 2.0-3.1), myalgia (1.5, 95%CI 1.2-1.8), and cough (1.3, 95%CI 1.0-1.6) were associated with NPS positivity. Having two to four of these symptoms increased the aOR from 7.4 (95%CI, 5.6-9.7) to 35.5 (95%CI, 24.6-52.2). The combination of the four symptoms showed an AUC of 0.810 (95%CI 0.795-0.825) in classifying NPS-P, and was applied to the non-hospitalized and non-tested sample (n=165,782). We found that from 4.4% to 12.1% of respondents had experienced symptoms suggestive of COVID-19 infection. Conclusions: Our results suggest that self-reported symptoms may be reliable indicators of SARS-CoV-2 infection in a pandemic context. A not negligible part (up to 12.1%) of the symptomatic respondents were left undiagnosed and potentially contributed to the spread of the infection

GSK-3 Activity Is Critical for the Orientation of the Cortical Microtubules and the Dorsoventral Axis Determination in Zebrafish Embryos

The formation of dorsal-ventral (D–V) axis is the earliest event that breaks the radial symmetry and determines the bilateral body plan of a vertebrate embryo, however, the maternal control of this process is not fully understood. Here, we discovered a new dorsalizing window of acute lithium treatment, which covers only less than 10 minutes after fertilization. Lithium treatment in this window was not able to reverse the ventralized phenotype in tokkeabi (tkk) mutant embryos, and its dorsalizing activity on wild-type embryos was inhibited by nocodazole co-treatment. These evidences indicate that the underlying mechanism is independent of a direct activation of Wnt/β-catenin signaling, but depends on the upstream level of the microtubule mediated dorsal determinant transport. In order to identify the target of lithium in this newly discovered sensitive window, GSK-3 inhibitor IX as well as the IMPase inhibitor L690, 330 treatments were performed. We found that only GSK-3 inhibitor IX treatment mimicked the lithium treatment in the dorsalizing activity. Further study showed that the parallel pattern of cortical microtubules in the vegetal pole region and the directed migration of the Wnt8a mRNA were randomized by either lithium or GSK-3 inhibitor IX treatment. These results thus revealed an early and critical role of GSK-3 activity that regulates the orientation of the cortical microtubules and the directed transport of the dorsal determinants in zebrafish embryos

Deletion of the WD40 Domain of LRRK2 in Zebrafish Causes Parkinsonism-Like Loss of Neurons and Locomotive Defect

LRRK2 plays an important role in Parkinson's disease (PD), but its biological functions are largely unknown. Here, we cloned the homolog of human LRRK2, characterized its expression, and investigated its biological functions in zebrafish. The blockage of zebrafish LRRK2 (zLRRK2) protein by morpholinos caused embryonic lethality and severe developmental defects such as growth retardation and loss of neurons. In contrast, the deletion of the WD40 domain of zLRRK2 by morpholinos targeting splicing did not induce severe embryonic developmental defects; rather it caused Parkinsonism-like phenotypes, including loss of dopaminergic neurons in diencephalon and locomotion defects. These neurodegenerative and locomotion defects could be rescued by over-expressing zLRRK2 or hLRRK2 mRNA. The administration of L-dopa could also rescue the locomotion defects, but not the neurodegeneration. Taken together, our results demonstrate that zLRRK2 is an ortholog of hLRRK2 and that the deletion of WD40 domain of zLRRK2 provides a disease model for PD

A mobile phone intervention to improve obesity-related health behaviors of adolescents across Europe: An iterative co-design and feasibility study

Background:Promotion of physical activity, healthy eating, adequate sleep and reduced sedentary behavior in adolescents is a major priority globally given the current increase in population health challenges of non-communicable diseases and risk factors such as obesity. Adolescents are highly engaged with mobile technology, but the challenge is to engage them with mHealth technology. Recent innovations in mobile technology provide opportunities to promote a healthy lifestyle in adolescents. An increasingly utilized approach to facilitate increased engagement with mHealth technology is to involve potential users in the creation of the technology.Objective:To describe the process of and findings from co-designing and prototyping components of the PEGASO Fit for Future mHealth intervention for adolescents from different cultural backgrounds.Methods:Seventy-four adolescents aged 13-16 years from Spain, Italy and the United Kingdom participated in the co-design of the PEGASO Fit for Future technology. In three iterative cycles over 12 months, participants were involved in the co-design, refinement and feasibility testing of a system consisting of diverse mobile applications with a variety of functions and facilities to encourage healthy weight promoting behaviors. In the first iteration, participants attended a single workshop session and were presented with mock-ups or early-version prototypes of different apps for user requirements assessment and review. During the second iteration, prototypes of all apps were tested by participants for one week at home or school. In the third iteration, further developed prototypes were tested for two weeks. Participants’ use experience feedback and development ideas were collected from focus groups and completion of questionnaires.Results:For the PEGASO Fit for Future technology to be motivating and engaging, participants suggested that it should (i) allow personalization of the interface, (ii) have age-appropriate and easy to understand language (of icons, labels, instructions, notifications), (iii) provide easily accessible tutorials on how to use the app or navigate through a game, (iv) present a clear purpose and end goal, (v) have an appealing and self-explanatory reward systems, (vi) offer variation in gamified activities within apps and the serious game, and (vii) allow to seek peer-support and connect with peers for competitive activities within the technology.Conclusions:Incorporating adolescents’ preferences, the PEGASO Fit for Future technology combines the functions of a self-monitoring, entertainment, advisory, and social support tool. This was the first study demonstrating that it is possible to develop a complex smartphone-based technological system applying the principles of co-design to mHealth technology with adolescents across three countries. Findings of this study informed the development of an mHealth system for healthy weight promotion to be tested in a controlled multi-national pilot trial

Using fish models to investigate the links between microbiome and social behaviour: the next step for translational microbiome research?

Recent research has revealed surprisingly important connections between animals’ microbiome and social behaviour. Social interactions can affect the composition and function of the microbiome; conversely, the microbiome affects social communication by influencing the hosts’ central nervous system and peripheral chemical communication. These discoveries set the stage for novel research focusing on the evolution and physiology of animal social behaviour in relation to microbial transmission strategies. Here, we discuss the emerging roles of teleost fish models and their potential for advancing research fields, linked to sociality and microbial regulation. We argue that fish models, such as the zebrafish (Danio rerio, Cyprinidae), sticklebacks (‎Gasterosteidae), guppies (Poeciliidae) and cleaner–client dyads (e.g., obligate cleaner fish from the Labridae and Gobiidae families and their visiting clientele), will provide valuable insights into the roles of microbiome in shaping social behaviour and vice versa, while also being of direct relevance to the food and ornamental fish trades. The diversity of fish behaviour warrants more interdisciplinary research, including microbiome studies, which should have a strong ecological (field‐derived) approach, together with laboratory‐based cognitive and neurobiological experimentation. The implications of such integrated approaches may be of translational relevance, opening new avenues for future investigation using fish models

Detecting asymptomatic Trichomonas vaginalis in females using the BD ProbeTec™ Trichomonas vaginalis Qx nucleic acid amplification test.

Trichomonas vaginalis (TV) rates in women are increasing and many are asymptomatic. Nucleic acid amplification tests (NAATs) are becoming the 'gold standard' for diagnosis. We aimed to establish our asymptomatic TV rates by testing all women attending Oxfordshire's Sexual Health service, regardless of symptoms, using the BD ProbeTec™ TV Q(x) NAATs (BDQ(x)). During BDQ(x)'s verification process, the sensitivity and specificity were calculated using results of 220 endocervical samples from symptomatic women, compared with culture. BDQ(x) was subsequently implemented and prospectively evaluated over 6 months in female attendees. Wet mount microscopy was also performed in symptomatics. Demographic and clinical characteristics of those diagnosed were analysed. From 220 samples tested by BDQ(x) and culture: 5 were positive on both and one solely using BDQ(x), giving a sensitivity and specificity of 100% and 99.53%, respectively. In the prospective cohort, of 5775 BDQ(x) tests, 33 (0.57%) were positive. 11/33 (33%) patients were asymptomatic. All patients diagnosed had risk factors: age >25 years (85%), residence in a deprived area (79%) and black ethnicity (21%). Despite BDQ(x) being highly sensitive and specific, with our low TV prevalence universal screening may not be justified. Targeted screening using local demographic data merits further investigation