N-glycosylation as a Modulator of Protein Conformation and Assembly in Disease (preprint)

Glycosylation, a prevalent post-translational modification, plays a pivotal role in regulating intricate cellular processes by covalently attaching glycans to macromolecules. Dysregulated glycosylation is linked to a spectrum of diseases, encompassing cancer, neurodegenerative disorders, congenital disorders, infections, and inflammation. This review delves into the intricate interplay between glycosylation and protein conformation, with a specific focus on the profound impact of N-glycans on the selection of distinct protein conformations, characterized by distinct interactomes – namely protein assemblies - under normal and pathological conditions across various diseases. We begin by examining the spike protein of the SARS virus, illustrating how N-glycans regulate the infectivity of pathogenic agents. Subsequently, we utilize the prion protein and the chaperone glucose-regulated protein 94 as examples, exploring instances where N-glycosylation transforms physiological protein structures into disease-associated forms. Unraveling these connections provides valuable insights into potential therapeutic avenues and a deeper comprehension of the molecular intricacies that underlie disease conditions. This exploration of glycosylation's influence on protein conformation effectively bridges the gap between the glycome and disease, offering a comprehensive perspective on the therapeutic implications of targeting conformational mutants and their pathologic assemblies in various diseases. The goal is to unravel the nuances of these post-translational modifications, shedding light on how they contribute to the intricate interplay between protein conformation, assembly and disease.

Quantitative and qualitative analysis of medical students’ symptoms and feelings during COVID-19 pandemic (preprint)

Background Due to the COVID-19 pandemic, traditional face-to-face teaching was disrupted, leading to a transition to online activities. Social restrictions and isolation during this period may have contributed to various physical and emotional disorders, such as anxiety, depression, reduced perception of happiness, and a decline in overall quality of life. The objective of our study was to assess the perceptions of medical students regarding their emotions, anxiety and depression symptoms, and daily experiences during the pandemic.Methods We conducted a prospective study with both quantitative and qualitative components involving students in their 1st to 4th year of medicine at a private university in São Paulo, Brazil in 2020 and 2021. Participants completed online questionnaires, including the State-Trait Anxiety Inventory (STAI), Beck Depression Inventory (BDI), Oxford Happiness Questionnaire (OHQ), and Medical Student Quality-of-Life Questionnaire (VERAS-Q). Additionally, they engaged in online focus group discussions.Results A total of 313 students completed the questionnaires, and 200 participated in the focus group. Women exhibited higher scores for anxiety (p = 0.002) and depression (p = 0.007), while men demonstrated better quality of life (p = 0.042). The students aged 18 to 24 years (p = 0.048) presented better quality of life and lower trait anxiety (p = 0.001). Both trait and state anxiety were strongly associated with depression (p < 0.01) and inversely related to quality of life, showing a moderate association with happiness (p < 0.01). Depression was strongly linked to both trait and state anxiety (p < 0.01) and moderately negatively correlated with happiness and quality of life (p < 0.01). The focus groups revealed recurring negative feelings among students, such as anxiety, depression, tiredness, discouragement, loneliness, difficulty managing time, poor sleep quality, exacerbation of harmful habits, and challenges in relationships, resulting in reduced mental and physical health during the pandemic. Coping strategies were discussed, including the adoption of new healthy habits, religious practices, and reconnection with family.Conclusion Depression and anxiety symptoms were more prevalent among females, while quality of life improved for younger and male students. The qualitative analysis enhanced our understanding of the determinants and consequences of students' recurring negative feelings, and also showed positive aspects like greater proximity to family and religiosity.

Primate-specific BTN3A2 protects against SARS-CoV-2 infection by interacting with and reducing ACE2 (preprint)

Coronavirus disease 2019 (COVID-19) is an immune-related disorder caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 invades cells via the entry receptor angiotensin-converting enzyme 2 (ACE2). While several attachment factors and co-receptors for SARS-CoV-2 have been identified, the complete pathogenesis of the virus remains to be determined. Unraveling the molecular mechanisms governing SARS-CoV-2 interactions with host cells is crucial for the formulation of effective prophylactic measures and the advancement of COVID-19 therapeutics. Here, we identified butyrophilin subfamily 3 member A2 (BTN3A2) as a potent inhibitor of SARS-CoV-2 infection. The mRNA level of BTN3A2 was correlated with COVID-19 severity. Upon re-analysis of a human lung single-cell RNA sequencing dataset, BTN3A2 expression was predominantly identified in epithelial cells. Moreover, this expression was elevated in pathological epithelial cells from COVID-19 patients and co-occurred with ACE2 expression in the same cellular subtypes in the lung. Additionally, BTN3A2 primarily targeted the early stage of the viral life cycle by inhibiting SARS-CoV-2 attachment through direct interactions with the receptor-binding domain (RBD) of the Spike protein and ACE2. Furthermore, BTN3A2 inhibited ACE2-mediated SARS-CoV-2 infection by reducing ACE2 in vitro and in a BTN3A2 transgenic mouse model. These results reveal a key role of BTN3A2 in the fight against COVID-19 and broaden our understanding of the pathobiology of SARS-CoV-2 infection. Identifying potential monoclonal antibodies that target BTN3A2 may facilitate disruption of SARS-CoV-2 infection, providing a therapeutic avenue for COVID-19.

Offspring cardiometabolic outcomes and postnatal growth trajectories after exposure to maternal SARS-CoV-2 infection (preprint)

Context. Prior birth cohorts have suggested an association between maternal infection in pregnancy and offspring risk for childhood obesity. Whether maternal SARS-CoV-2 infection is similarly associated with increased cardiometabolic risk for offspring is not known. Objective. To determine whether in utero exposure to SARS-CoV-2 is associated with increased risk for cardiometabolic diagnoses by 18 months after birth, compared with unexposed offspring born during the COVID-19 pandemic. Design. This retrospective cohort study included the live offspring of all individuals who delivered during the COVID-19 pandemic (April 1, 2020 - December 31, 2021) at 8 hospitals within 2 health systems in Massachusetts. Exposure. SARS-CoV-2 positivity on polymerase chain reaction (PCR) test during pregnancy. Main Outcome Measures. Electronic health record documentation of International Statistical Classification of Diseases and Related Health Problems, Tenth Revision diagnostic codes corresponding to cardiometabolic disorders. Offspring weight-for-age, length-for-age, and body mass index (BMI)-for-age z-scores at birth, 6 months, 12 months, and 18 months of age. Results. The full study cohort includes 29,510 live born offspring (1,599 exposed and 27,911 unexposed offspring). 6.7% of exposed and 4.4% of unexposed offspring had received a cardiometabolic diagnosis by 18 months of age (crude OR 1.47 [95% CI: 1.10-1.94], p=0.007; adjusted OR 1.37 [1.01-1.83]; p=0.04). These diagnoses were preceded by significantly greater mean BMI-for-age z-scores in exposed versus unexposed offspring at 6 months (mean z-score difference 0.19, 95% CI: 0.10, 0.29, p<0.001), and a greater proportion of offspring at risk of, or meeting criteria for, overweight/obesity (16.5% vs. 12.2%, p=0.006). Conclusions. Exposure to maternal SARS-CoV-2 infection was associated with an increased risk of receiving a cardiometabolic diagnosis by 18 months and greater BMI-for-age at 6 months.

Exploring Perceptions of Pregnant Women on Antenatal Care visit during their First Trimester at Area 25 Health Center in Lilongwe, Malawi – A Qualitative Study (preprint)

Background Initiation of antenatal care during the first trimester is crucial for reducing maternal and neonatal morbidity and mortality. Unfortunately, only 24% of pregnant women in Malawi initiate antenatal care during this time with even lower rates of 15% at Area 25 Health Centre in Lilongwe. Despite such cases, there is scarce literature on obstacles that prevent women from accessing first-trimester antenatal care in Malawi.Aim To explore perceptions of pregnant women and how they influence attendance during the first-trimester at Area 25 Health Centre in Lilongwe, Malawi.Methods We employed a qualitative exploratory study on 55 purposely identified pregnant women, aged between 18 and 42 years with gestational period of up to 36 weeks who were attending antenatal care at Area 25 Health Centre in Lilongwe urban, Malawi. Data was collected through a total of 15 In-depth Interviews (IDIs) and four Focus Group Discussions (FGDs) and were manually analyzed using thematic analysis, which included categorization and deductive theme identification with reference to the study objectives and the Health Belief Model (HBM).Results Pregnant women perceived that the first-trimester antenatal care visits are only for those experiencing ill health conditions like backache, headache, and HIV/AIDS during pregnancy. First trimester pregnancy was perceived as too small not worthy of seeking antenatal care, the women placed a low value on it. Majority of those who initiated antenatal care in the first trimester had previously experienced disorders and complications such as previous caesarean section and abortions. In addition to limited knowledge about the required total number of ANC visit, challenges such as long-distance, preoccupation with business, multiple antenatal visits, scheduling of antenatal care visits, negative attitude of health workers, adherence to COVID-19 containment measures, and inadequate partner support were identified as barriers to seeking early antenatal care.Conclusion Negative perceptions among pregnant women, coupled with various economic and infrastructure barriers, attribute to low attendance rates for first trimester antenatal care in Malawi. Addressing knowledge gaps and overcoming barriers related to economic, infrastructure and health care delivery can improve women’s early antenatal care visits. Future research should consider including pregnant women from diverse socioeconomic backgrounds to gain a better understanding of these perceptions and barriers.

A Systematic Review on the Relationship Between Socioeconomic Conditions and Emotional Disorder Symptoms During Covid-19: Unearthing the Potential Role of Economic Concerns and Financial Strain (preprint)

Background Covid-19 has disrupted the lives of many and resulted in high prevalence rates of mental disorders. Despite a vast amount of research into the social determinants of mental health during Covid-19, little is known about whether the results are consistent with the social gradient in mental health. Here we report a systematic review of studies that investigated how SEC indicators, such as education and income, predict emotional health (depression and anxiety) risk during the pandemic. Furthermore, we examined which classes of SEC indicators would best predict symptoms of emotional disorders.Methods Following PRISMA guidelines, we conducted search over six databases, including Scopus, PubMed, etc., between November 4, 2021 and November 11, 2021 for studies that investigated how SEC indicators predict emotional health risks during Covid-19, after obtaining approval from PROSPERO (ID: CRD42021288508). Using Covidence as the platform, 362 articles (324 cross-sectional/repeated cross-sectional and 38 longitudinal) were included in this review according to the eligibility criteria. We categorized SEC indicators into ‘actual versus perceived’ and ‘static versus fluid’ classes to explore their differential effects on emotional health.Results Out of the 1479 SEC indicators used in these 362 studies, our results showed that 43.68% of the SEC indicators showed ‘expected’ results (i.e., higher SEC predicting better emotional health outcomes); 51.86% reported non-significant results and 4.46% reported the reverse. Economic concerns (67.16% expected results) and financial strains (64.16%) emerged as the best predictors while education (26.85%) and living conditions (30.14%) were the worst.Conclusions This review summarizes how different SEC indicators influenced emotional health risks across 98 countries, with a total of 5,677,007 participants, ranging from high to low-income countries. Our findings showed that not all SEC indicators were strongly predictive of emotional health risks. In fact, over half of the SEC indicators studied showed a null effect. We found that perceived and fluid SEC indicators, particularly economic concerns and financial strain could best predict depressive and anxiety symptoms. These findings have implications for policymakers to further understand how different SEC classes affect mental health during a pandemic in order to tackle associated social issues effectively.

Investigation of the Psychological Status of COVID-19 Patients and its Influence on Defecation in Jinshan Fangcang Shelter Hospital in Shanghai, China (preprint)

Objective: To investigate the psychological state of asymptomatic COVID-19-infected patients in Fangcang Shelter Hospital and the influence of the psychological state on defecation. Methods:The psychological status, defecation disorder and anorectal diseases of asymptomatic COVID-19-infected patients admitted to a shelter hospital in the Jinshan District of Shanghai were investigated using an online questionnaire from May 1 to May 7, 2022. Results: A total of 568 valid questionnaires were received, and the respondents who had defecation disorders before entering the Fangcang Shelter Hospital were excluded. A total of 452 questionnaires were included for data analysis; 111 subjects had anxiety, and the detection rate of anxiety was 24.6% (111/452). The detection rate of difficult defecation was 39.6% (179/452). The incidence of difficult defecation was 57.7% (64/111) among the subjects with anxiety, and 33.7% (115/341) among the subjects without anxiety. The incidence of difficult defecation in the subjects with anxiety was significantly higher than that in subjects without anxiety (P<0.001). The proportion of patients with dry stool (Bristol type 1-2), anal mass prolapse after defecation and perianal pain was higher in the group with difficulty in defecation than in the group without difficulty in defecation (P < 0.05). Conclusion: Asymptomatic COVID-19 patients had anxiety at the Fangcang Shelter Hospital. Anxiety may lead to difficulty in defecation and induce anorectal diseases.

Distinct intrathecal inflammatory signatures following relapse and anti- COVID-19 mRNA vaccination in Multiple Sclerosis. A cross-sectional study. (preprint)

Background: The role of off-target inflammatory response to vaccination in exacerbating multiple sclerosis (MS) is a matter of debate. Methods: In this cross-sectional study, we compared the CSF cytokine profiles associated with MS relapses and anti-COVID-19 mRNA vaccinations in patients with relapsing-remitting MS (RRMS). We also compared central inflammatory responses between RRMS patients and individuals without neuroinflammatory disorders. All patients were recruited in the Neuromed Research Institute, Pozzilli (IS). Results: We enrolled 97 consecutives unvaccinated RRMS patients with a clinical relapse occurring within 100 days from the diagnostic lumbar puncture (LP), 29 consecutive RRMS in clinical remission, and 24 consecutive controls. The latter groups of patients received anti-COVID-19 mRNA vaccine within 100 days from LP. In the first group, we observed a significant negative correlation between relapse distance and CSF concentrations of IL-2 (Spearman’s rho= -0.305, p = 0.002), IL-6 (Spearman’s rho= -0.291, p= 0.004), and IL-17 (Spearman’s rho= -0.275, p = 0.006). Linear regression confirmed a significant association for IL-2 (beta = -0.265, 95% CI -0.004 - 0, p = 0.016), IL-6 (beta = -0.284, 95% CI -0.005 - -0.001, p = 0.01), and IL-17 (beta = -0.224, 95% CI -0.004 - 0, p = 0.044), considering possible confounders (age, sex, OCB presence, EDSS). In the second group, distance from vaccination was positively correlated with CSF levels of IL-12 (Spearman’s rho = 0.539, p= 0.003), IL-13 (Spearman’s rho = 0.512, p = 0.005), IL-1ra (Spearman’s rho = 0.481, p = 0.008), MIP-1a (Spearman’s rho = -0.371, p = 0.047). Linear regression confirmed a significant association for IL-12 (beta = 0.536, 95%CI 0.004-0.016, p = 0.004), IL-13 (beta = 0.416, 95%CI 0.001-0.02, p = 0.035), and IL-1ra (beta = 0.506, 95%CI 0.259-2.344, p = 0.016), also considering the effect of other possible confounders (age, sex). No significant associations between vaccine distance and CSF cytokines levels emerged in the control group. Conclusion: Our results indicate that COVID-19 vaccination causes in RRMS patients a central inflammatory response significantly different from that associated with disease relapses. The lack of central inflammatory response observed in control patients indicates that MS patients are suscptible to the central inflammatory effects of vaccination.

Prevalence of smell, taste and chemesthesis disorders among patients with the Omicron Variant of SARS-CoV-2 in China (preprint)

Many studies have confirmed that chemosensory disorder (including smell, taste and chemesthesis) is one of the symptoms of COVID-19 infection. However, new data indicated that the changes of chemosensory sensation caused by COVID-19 may be different among different populations and COVID-19 variants. At present, there are few studies focusing on the influence of Omicron on qualitative changes and quantitative reductions of chemosensory in China. We conducted a cross-sectional study on COVID-19 Omicron variant patients to investigate the prevalence of chemosensory disorders and their chemosensory function before and during infection by online questionnaire. A total of 1245 patients with COVID-19 completed the study. The prevalence of smell, taste and chemesthesis disorder was 69.2%, 67.7% and 31.4% respectively. Sex, age, smoking and COVID-19-related symptoms such as lack of appetite, dyspnea and fatigue may have association with chemosensory disorders during COVID-19. Self-ratings of chemosensory function revealed that patients experienced a decline in the function of smell, taste and chemesthesis generally. Further studies are needed to combine the data using objective assessment and investigate the factors affecting chemosensory in COVID-19 through longitudinal research.

Efficacy of Internet-Delivered Transdiagnostic Cognitive Behavior Therapy on Emotion Regulation, Repetitive Negative Thought and Social Adjustment in Adolescents with Sub- clinical Diagnosis of Emotional Disorders (preprint)

Objective: The Unified Protocol for Transdiagnostic Treatment of Emotional Disorders in Adolescents has been shown to be effective in reducing symptoms of anxiety and depression in adolescents with emotional disorders. The present study aims to assess the effectiveness of Internet-based UP-A in reducing repetitive negative thoughts, improving emotion regulation and social adjustment of adolescents with subclinical features of emotional disorder during the COVID-19 pandemic. Methods: This is a longitudinal randomized clinical trial conducted on 40 adolescents aged 12-17 years with subclinical features of emotional disorder. They were randomly divided into two groups of intervention (n=20) and control (n=20). They first completed the Depression Anxiety Stress Scale- 21 item (DASS-21) and the Acceptance and Action Questionnaire (AAQ-2) online. Then, the intervention group received twelve 45-minute sessions of UP-A through video calls on WhatsApp two days a week. The control group received no treatment. Immediately and 3 months after the intervention, the questionnaires were completed again. The collected data were analyzed using longitudinal marginal modeling. Results: The results of the data analysis indicated that Unified Transdiagnostic Therapy was effective in reducing the sub-clinical symptoms of emotional disorders, repetitive negative thoughts, increasing the use of adaptive strategies and reducing the use of maladaptive emotion regulation strategies. Regarding the social adaptation variable, there was not any effectiveness in the evaluation after the intervention and three months after the intervention. Conclusion: The results of the research represent that the adolescent version of the Unified Transdiagnostic Protocol can be effective in preventing emotional disorders in adolescents.

The Smoldering Pandemic: Self-Reported Prevalence Assessment of Prolonged Grief Disorder. A cross sectional study of bereaving adults during the Covid Pandemic in Pakistan. (preprint)

Introduction: The Covid-19 pandemic brought forward unprecedented psycho-social challenges for the world. The devastating loss of human lives created a burden of grief throughout the world. The bereaved were put at a greater risk of grief complications with high death tolls, strict social isolation guidelines and a halt to communal funeral practices. Prolonged Grief Disorder is a young psychiatric condition which refers to an abnormal grief reaction that exceeds the normal cultural, social and religious norms. In this study, we assessed the prevalence of Prolonged Grief Disorder (PGD), as mentioned in ICD-11 in Pakistan, along with its correlation to anxiety, depression and psychological distress. Severity of grief reactions were compared with the place of death and relationship with the deceased. Methods: A cross sectional online survey was conducted during the month of October 2021. Sample size was calculated using OpenEpi and data was collected through non probability sampling. The questionnaire was validated and shared through multiple social forums. A total of 737 participants residing in Lahore Pakistan, who had lost a close one due to Covid-19 participated in the study. Demographics, loss related information, and self-reported symptoms measured by 13-item Prolonged Grief Disorder Scale, Patient Health Questionnaire-4 and Kessler-6 scales were obtained. Results:The prevalence of Prolonged Grief Disorder was found to be 15.4%. There was a significant correlation of grief intensity with depression and anxiety.Prolonged Grief Disorder puts individuals at greater risk of suffering from serious mental illnesses. People who were closely related to the deceased were more likely to experience severe Prolonged Grief Disorder symptoms. Conclusion: Early detection and treatment of high risk individuals is necessary to mitigate the burden of grief and associated risk of anxiety and depression. Overall we conclude that discussions pertaining to grief and measures to curb the psychological effects are crucial in the post-pandemic world.

Effectiveness of the Unified Protocol for the Transdiagnostic Treatment of Emotional Disorders in Online and Group format in Argentina: study protocol for a randomized controlled trial (preprint)

Background The Unified Protocol (UP) is a transdiagnostic intervention based on emotional regulation for the treatment of emotional disorders. Its application in individual and group formats has been studied worldwide, obtaining similar results to specific protocols but with a lower drop-out rate and improving the cost-benefit ratio, since a larger number of patients can benefit from it. Moreover, the inclusion of digital technologies in psychotherapy aims to improve the accessibility of treatments, especially since the pandemic of Covid-19 that forced the implementation of treatments through teletherapy increasing its use. To date, no studies have been carried out in Argentina on the application of the UP in a group format and through teletherapy. The aim of the present study is to evaluate the efficacy of the UP in a group format and through teletherapy in the argentine population. Methods A parallel-group, controlled, randomized trial, with a pre-post and repeated follow-up measures intergroup design will be conducted. 180 patients will be randomized to one of the following conditions: an online, group-based UP intervention or a waiting list. The Beck Depression Inventory II and the Beck Anxiety Inventory will be used to compare primary outcomes and the Beck Hopelessness Scale, Difficulties in Emotion Regulation Scale, Positive Affect and Negative Affect Scale, and Multicultural Quality of life Index will be administered for secondary outcomes at baseline, post-intervention, and 3 months follow-up. Ad-doc questionnaires will be used to assess patients' experiences and treatment satisfaction. Discussion The purpose of this trial is to evaluate the efficacy of the online and group application of the UP in the Argentine population, as well as to evaluate the patient's experience and satisfaction with the treatment. It is expected that the findings of this study will be useful in reducing anxious and depressive symptomatology, will allow us to adapt the UP to our culture, and will improve accessibility to treatment. Trial registration: ClinicalTrials.gov ID: NCT05275322 Registered on 11 March 2022,

Prevalence, Symptoms and Professional Profile of the Burnout Syndrome among Healthcare Professionals during the COVID-19 Pandemic: a Cross-Sectional Study (preprint)

The Burnout Syndrome (BOS) is a psycho-emotional disorder generating sustained stress over time, and inability to cope with the demands in an adaptive manner. The aims of the study were (1) to describe the prevalence of BOS during the third COVID-19 pandemic wave (May-June 2021); (2) to explore the relation of BOS with physical symptoms, and (3) to determine the profile favoring the development of BOS. This cross-sectional descriptive study was conducted amongst a sample of 759 healthcare professionals (HCPs). Data on sociodemographic variables, physical symptoms, the Maslach Burnout Inventory, Cervical Disability Index, and Numeric Pain Rating Scale were collected. The prevalence of BOS was 58.9% (447 subjects); 382 subjects (50.3%) showed high levels of Emotional Exhaustion (EE), whereas 219 participants (28.9%) had high Depersonalization (DP) levels, whilst 135 individuals (17.8%) showed low levels of Personal Fulfillment (PF). Women showed higher levels of EE (Z=-3.46; p = 0.001), whilst men showed higher levels of DP (Z=-2.69; p = 0.007). A total of 579 participants (76.3%) experienced muscle pain. A young nurse working in a hospital, or an emergency department emerges as a specific vulnerable profile. The current study confirms the need to overcome BOS in HCPs, implementing multidimensional tailored intervention to decrease the symptoms.

The Eating Disorders Genetics Initiative (EDGI) United Kingdom (preprint)

Objective The Eating Disorders Genetics Initiative United Kingdom (EDGI UK), part of the National Institute for Health and Care Research (NIHR) Mental Health BioResource, aims to deepen our understanding of the environmental and genetic aetiology of eating disorders. EDGI UK launched in February 2020 and is partnered with the UK eating disorders charity, Beat. There are multiple EDGI branches worldwide. Method EDGI UK recruits via media and clinical services. Anyone living in England, at least 16 years old, with a lifetime probable or clinical eating disorder is eligible to sign up online: edgiuk.org . Participants complete online questionnaires, donate a saliva sample for genetic analysis, and consent to medical record linkage and recontact for future studies. Results As of September 2022, EDGI UK has recruited 8,397 survey participants: 98% female, 93% white, 97.7% cisgender, 67% heterosexual, and 52% have a university degree. Half (51.7%) of participants have returned their saliva kit. The most common diagnoses are anorexia nervosa (42.7%), atypical anorexia nervosa (31.4%), bulimia nervosa (33.2%), binge-eating disorder (14.6%), and purging disorder (33.5%). Conclusion EDGI UK is the largest UK eating disorders study but needs to increase its diversity, and efforts are underway to do so. It also offers a unique opportunity to accelerate eating disorder research, and collaboration between researchers and participants with lived experience, with unparalleled sample size.

Effect of internet-based UP-A intervention on stress, anxiety, depression, and psychological flexibility during the COVID-19 pandemic: A clinical trial (preprint)

This clinical trial aims to assess the effectiveness of internet-based Unified Protocol for Transdiagnostic Treatment of Emotional Disorders in Adolescents (UP-A) during the COVID-19 pandemic in reducing stress, anxiety, and depression, and psychological flexibility of 40 adolescents with subclinical features of emotional disorder randomly divided into two groups of intervention and control. They first completed DASS-21 and AAQ-2 online. Then, the intervention group received 12 sessions of UP-A through video call on WhatsApp, 2 days per week each for 45 minutes. Their stress, anxiety, and depression levels decreased and their psychological flexibility increased immediately and 3 months after the intervention.

Suicide due to fear of COVID-19, in pregnancy, lead to Neonatal malformations: A case report (preprint)

There is limited data about various effect of COVID-19 in pregnancy. The Covid-19 pandemic can increase anxiety or schizophrenia exacerbation. Neonatal malformations from antipsychotic drugs exposures during first trimester of pregnancy have been reported. However, their effect near delivery have been less studied. Keywords: Covid-19, pregnancy, mental health, neonatal malformations

An immunoinformatics approach to study the epitopes contributed by Nsp13 of SARS-CoV-2 (preprint)

The on-going coronavirus disease-19 (COVID-19) pandemic caused by SARS-CoV-2 has infected hundreds of millions of people and killed more than two million people worldwide. Currently, there are no effective drugs available for treating SARS-CoV-2 infections; however, vaccines are now being administered worldwide to control this virus. In this study, we have studied SARS-CoV-2 helicase, Nsp13, which is critical for viral replication. We compared the Nsp13 sequences reported from India with the first reported sequence from Wuhan province, China to identify and characterize the mutations occurring in this protein. To correlate the functional impact of these mutations, we characterised the most prominent B cell and T cell epitopes contributed by Nsp13. Our data revealed twenty-one epitopes, which exhibited high antigenicity, stability and interactions with MHC class-I and class-II molecules. Subsequently, the physiochemical properties of these epitopes were also analysed. Furthermore, several of these Nsp13 epitopes harbour mutations, which were further characterised by secondary structure and per-residue disorderness, stability and dynamicity predictions. Altogether, we report the candidate epitopes of Nsp13 that may help the scientific community to understand the evolution of SARS-CoV-2 variants and their probable implications.

From loss to recovery: how to effectively assess chemosensory impairments during COVID-19 pandemic (preprint)

Chemosensory impairments have been established as a specific indicator of COVID-19. They affect most patients and may persist long past the resolution of respiratory symptoms, representing an unprecedented medical challenge. Since the SARS-CoV-2 pandemic started, we now know much more about smell, taste, and chemesthesis loss associated with COVID-19. However, the temporal dynamics and characteristics of recovery are still unknown. Here, capitalizing on data from the Global Consortium for Chemosensory Research (GCCR) crowdsourced survey, we assessed chemosensory abilities after the resolution of respiratory symptoms in participants diagnosed with COVID-19 during the first wave of the pandemic in Italy. This analysis led to the identification of two patterns of chemosensory recovery, limited (partial) and substantial, which were found to be associated with differential age, degrees of chemosensory loss, and regional patterns. Uncovering the self-reported phenomenology of recovery from smell, taste, and chemesthetic disorders is the first, yet essential step, to provide healthcare professionals with the tools to take purposeful and targeted action to address chemosensory disorders and its severe discomfort.

Exploring causal relationships between COVID-19 and cardiometabolic disorders: A bi-directional Mendelian randomization study (preprint)

Background: More than 100 million cases of COVID-19 have been reported worldwide. A number of risk factors for infection or severe infection have been identified, however observational studies were subject to confounding bias. In addition, there is still limited knowledge about the complications or medical consequences of the disease. Methods: Here we performed bi-directional Mendelian randomization (MR) analysis to evaluate causal relationships between liability to COVID-19 (and severe/critical infection) and a wide range of around 30 cardiometabolic disorders (CMD) or traits. Genetic correlation (rg) was assessed by LD score regression(LDSC). The latest GWAS summary statistics from the COVID-19 Host Genetics Initiative was used, which comprised comparisons of general population controls with critically ill, hospitalized and any infected cases. Results: Overall we observed evidence that liability to COVID-19 or severe infection may be causally associated with higher risks of type 2 diabetes mellitus(T2DM), chronic kidney disease(CKD), ischemic stroke (especially large artery stroke[LAS]) and heart failure(HF) when compared to the general population. On the other hand, our findings suggested that liability to atrial fibrillation (AF), stroke (especially LAS), obesity, diabetes (T1DM and T2DM), low insulin sensitivity and impaired renal function (low eGFR and diabetic kidney disease) may be causal risk factors for COVID-19 or severe disease. In genetic correlation analysis, T2DM, CAD, obesity, fasting insulin, CKD, gout, stroke and urate showed positive rg with critical or hospitalized infection. All above findings passed multiple testing correction at a false discovery rate (FDR)<0.05. Conclusions: In summary, this study provides evidence for tentative bi-directional causal associations between liability to COVID-19 and severe disease and a number of CM disorders. Further replications and prospective studies are required to verify the findings.

Phosphatases in Toll-Like receptor signaling: the unfairly forgotten (preprint)

Toll-like receptors (TLRs) are a highly conserved family of pattern recognition receptors that play a critical role in innate immunity. They evolved before the adaptive immune system, making them an indispensable first line of defense. TLRs are highly studied, and understanding their signaling is critical for developing treatments for autoimmune and chronic inflammatory disorders. But while kinases and E3 ubiquitin ligases are widely known TLR signaling effectors, another pathway is less well-characterized. Phosphatases are important regulators of TLR signaling through NF-κB, type I interferons, and mitogen-activated protein kinases. TLRs activate several pathways through phosphorylation, and thus an interplay must exist between kinases and phosphatases to tightly regulate TLR signaling. Many phosphatases have roles in TLR signaling, including classical protein tyrosine phosphatases and serine/threonine phosphatases. TLR regulation by phosphatases is implicated in many human diseases, including atherosclerosis, autoimmune rheumatoid arthritis, and neuroinflammatory disorders. Finally, a role may exist for TLR signaling and phosphatases – in particular those associated with TLR4 and TLR7 - in patient responses to coronaviruses such as COVID-19. While many aspects of the TLR-associated kinase-phosphatase network remain to be uncovered phosphatases could represent novel therapeutic targets to control pathogenic TLR signaling.