Refugee children are often exposed to adversities that present a threat to their healthy development. Promoting refugee children’s social-emotional capacities may be an opportune, strengths-based avenue to nurture their resilience, coping strategies, and mental health outcomes amid these risks. Furthermore, supporting caregivers’ and service providers’ capacities to provide strengths-based care may result in more sustainable, caring environments for refugee children. However, culturally adapted initiatives that aim to promote social-emotional capacities and mental health in refugee children, caregivers, and service providers are limited.In this pilot study, we aimed to assess the feasibility and efficacy of a brief, 3-week social-emotional training program for refugee caregivers of children aged between 2 and 12 years and service providers who support refugees. This study had 3 central objectives. First, we examined whether refugee caregivers’ and service providers’ knowledge of core social-emotional concepts increased from pre- to posttraining, whether these increases were maintained 2 months later, and whether caregivers and service providers reported a high use of training-based strategies after the training. Second, we assessed if refugee caregivers reported any improvements in their children’s social-emotional capacities and mental health from pre- to posttraining and 2 months later. Finally, we evaluated whether caregivers and service providers experienced any improvements in their own mental health symptoms from pre- to posttraining and 2 months later.A total of 50 Middle Eastern refugee caregivers of children (n=26) aged between 2 and 12 years and service providers (n=24) were recruited using convenience sampling and participated in a 3-week training program. Training sessions were delivered via a web-based learning management system and involved a combination of asynchronous (video-based) and synchronous (web-based live group) sessions. The training was evaluated using an uncontrolled pre-, post-, and 2-month follow-up design. Caregivers and service providers reported their understanding of social-emotional concepts and mental health at pre-, post-, and 2 months after training and reported their use of training strategies after training. Caregivers reported their children’s social-emotional capacities and mental health through a presurvey, a series of postsurveys (after each module session and 1 week after the training), and a 2-month follow-up survey. The participants also reported their demographic information.Caregivers’ and service providers’ knowledge of social-emotional concepts increased significantly from pre- to posttraining, and the service providers’ knowledge increase was sustained at the 2-month follow-up. Both caregivers and service providers reported high levels of strategy use. Furthermore, 2 markers of children’s social-emotional development  improved after training.The findings highlight the potential of strengths-based, culturally adapted social-emotional initiatives to support refugee caregivers’ and service providers’ abilities to provide high-quality social-emotional care to refugee children. The scale of forced migration in parts of the Middle East has reached unprecedented levels owing to increased violence and political instability . For exaSocial-emotional capacities characterize our abilities to monitor our emotions in different social settings, form caring relationships with others, and understand how we as individuals relate to the broader world around us . PreviouTheoretical frameworks identify the following 3 core capacities of social-emotional development: emotion regulation, other-oriented social-emotional processes , and self-oriented social-emotional processes . ImpEmotion regulation is the ability to manage the occurrence, strength, and expression of our emotions and behaviors to achieve goals and behave appropriately in our surroundings [oundings ,27. Emotoundings ,29. Furtoundings ,31. Emotoundings ,32. TherOther-oriented social-emotional processes include those capacities that characterize how children engage with and relate to others [o others . Empathyo others . Here, wo others . Empathyo others -35. Altho others  found tho others ,37. TherSelf-oriented social-emotional processes involve how children view themselves as individuals in relation to others. Sadness over wrongdoing is a self-oriented social-emotional process that includes feelings of guilt and regret that occur when children realize that their actions may have harmed another [ another . Sadness another . Self-co another ,38. Nota another . Unhealt another . Healthy another . Healthy another . FurtherDuring the early years, social-emotional capacities are all socialized to some degree. Family- and community-based socializing agents, such as caregivers  and other caregiving figures , can serve as critical supports who positively (or negatively) influence refugee children’s early social-emotional development and mental health . In the Extending socialization-based supports beyond the family level may help sustain more inclusive, caring environments that nurture refugee families’ well-being after resettlement . RefugeeAlthough trainings related to improving caregivers’ and service providers’ understanding of and ability to nurture children’s social-emotional development have shown positive effects on children’s emotional and behavioral outcomes, these initiatives often focus on typically developing children or have not been adapted to refugee populations  training was informed in part by previous social-emotional training . From this foundation, the training was carefully adapted based on the results of a community-based needs assessment of refugee caregivers and service providers . This neModule 1 overviewed child social-emotional development with a focus on the following 3 core capacities in line with the extant social-emotional theory: emotion regulation, other-oriented social-emotional processes , and self-oriented social-emotional processes . Module 2 emphasized the importance of early relationships to support healthy child social-emotional development, with an empirically based focus on following 3 core caregiving processes: connecting , caring , and coaching . Finally, Module 3 highlighted mental health and well-being and the impacts of stress on social-emotional development and mental health. This final module emphasized the importance of considering the well-being of the whole child and identified protective factors that support refugee children’s, caregivers’, and service providers’ well-being during and after stressful situations.The training lasted for 1 month and was delivered virtually through 3 core modules, with each module delivered weekly in Arabic (for refugee caregivers) and English (for service providers). There was also a brief introductory session 1 week before the training and 2 follow-up sessions . To support flexible and interactive learning, each module included an asynchronous individual (prerecorded video) and synchronous group (web based) session. key points review and group discussion of that week’s asynchronous module session, and (3) small and large group activities. The synchronous sessions emphasized reflection and practice, with participants being given the opportunity to share their experiences and actively practice applying concepts and strategies in a respectful and culturally friendly setting, which allowed them to learn from others’ diverse experiences and share creative ideas on implementing the material.The asynchronous sessions included three 15-minute prerecorded videos that caregivers and service providers watched on their own time during the week. Each asynchronous session included key definitions of concepts, their developmental importance, their typical development from ages 2 to 12 years, and practical strategies to support them. After each asynchronous session, participants received activities to practice applying what they learned with their children at home or with children in their programming, ensuring that the use of strategies was well integrated into daily interactions. The synchronous sessions were 1-hour long and used the following three-part structure: (1) a group mindfulness exercise, (2) a Given that very limited work exists evaluating culturally adapted trainings, we did not form a specific directional hypothesis for this pilot study. Instead, we were interested in evaluating the efficacy of the training in either direction (increase or decrease) on participants’ knowledge, mental health, and children’s mental health. This study had 3 central objectives. First, we examined whether refugee caregivers’ and service providers’ knowledge of core social-emotional concepts increased from pre- to posttraining, whether these increases were maintained after 2 months , and whether caregivers and service providers reported high use of training-based strategies after the training. Second, we assessed if refugee caregivers reported any improvements in their children’s social-emotional capacities and mental health from pre- to posttraining and after 2 months. Finally, we evaluated whether caregivers and service providers experienced any improvements in their own mental health symptoms from pre- to posttraining and after 2 months.A total of 50 Middle Eastern refugee caregivers (n=26) and service providers (n=24) participated in the 3-week pilot training in fall of 2021. Participants were recruited using convenience sampling from 2 sites in Canada, the Greater Toronto and Hamilton Area in Ontario and Calgary in Alberta, using social media flyers and through word of mouth in collaboration with our community partners at the Calgary Catholic Immigration Society and the Muslim Council of Greater Hamilton. Eligibility criteria included being a resettled Syrian or Middle Eastern refugee caregiver of a child aged 2-12 years or being a service provider who works with refugee families. Service providers’ years of work experience ranged between 2 months and 33 years  in varied positions . The study was conducted in accordance with the guidelines of the Declaration of Helsinki and was approved by the University of Toronto Research Ethics Board (39028). The caregivers and service providers provided written informed consent before participation. The consent form was available in both Arabic and English. Each participant received a CAD $50 (US $37) gift card and a confirmation of completion document as a token of appreciation for their participation. The confidentiality of participants’ identities was maintained by deidentifying all study data and assigning participants a unique ID number.The training was evaluated using an uncontrolled pre-, post-, and 2-month follow-up design. To facilitate training evaluation, caregivers and service providers completed a presurvey, a series of postsurveys (after each module session and 1 week after the training), and a 2-month follow-up survey. Caregivers with multiple children were asked to choose one of their children in the age range of 2-12 years to report for the purposes of evaluation. The training was delivered virtually via a learning management system and was facilitated by a developmental psychologist with a PhD and a research assistant with experience in refugee services.For the presurvey, caregivers and service providers completed a demographic questionnaire to collect information regarding age, gender, work, and immigration status in Canada. In addition, caregivers completed the Alberta Language Environment Questionnaire-4  to provivery dissatisfied, 4=somewhat dissatisfied, 7=somewhat satisfied, 10=very satisfied).After each asynchronous and synchronous training session, caregivers and service providers rated a single item evaluating their satisfaction with the session . In addition, 1 week after the training, caregivers and service providers rated their satisfaction with the training in general on a single item . These items were developed by the second, third, and final authors and were rated on a 10-point scale  and was developed by the second, third, and final authors.A week after the training was completed, caregivers and service providers reported their use of training-based strategies  using a single item; “”). These items were developed by the second, third, and final authors. Individual scores across the 18 items were averaged to form the pretraining, posttraining (responses of each asynchronous and synchronous training session were averaged to create a single posttraining score), and 2-month follow-up scores. The internal consistency of the composite scores was high at each time point .At pretraining, after each asynchronous and synchronous training session, and at the 2-month follow-up, caregivers and service providers rated their understanding of core social-emotional training-based concepts using 18 items. The items assessing knowledge of the training content were developed based on adult education principles, emphasizing the importance of adult learning opportunities informing knowledge, competencies, and reflective practice . In totanot at all, 1: several days, 2: over half the days, and 3: nearly every day) and were averaged to form a composite anxiety score. Bivariate correlations suggested that the 2 items held together adequately as a single construct at each time point .At pretraining, 1-week posttraining, and the 2-month follow-up, caregivers and service providers reported their anxiety symptoms over the previous 2 weeks using 2 items from the Generalized Anxiety Disorder-2  and were averaged to form a composite depression score. Bivariate correlations suggested that the 2 items held together adequately as a single construct over time .At pretraining, 1-week posttraining, and the 2-month follow-up, caregivers and service providers reported their depressive symptoms over the previous 2 weeks using 2 items from the Patient Health questionnaire-2  and were averaged to form emotion regulation, empathy, and sadness over wrongdoing scores.At pretraining, 1-week posttraining, and the 2-month follow-up, caregivers reported their child’s emotion regulation, empathy for others, and sadness over wrongdoing using the Social-Emotional Responding Task ,68. Thesnot true, 1: somewhat true, and 2: certainly true). The items were averaged to form a total mental health challenge variable, with higher scores reflecting higher mental health challenges .At pretraining, 1-week posttraining, and the 2-month follow-up, caregivers reported their children’s mental health challenges using the Arabic version of the Strengths and Difficulties Questionnaire ,70, a wiservice provider and 1: caregiver) as a between-subjects factor in these repeated measures ANOVAs. The Greenhouse-Geisser results were reported when Mauchly test of sphericity was statistically significant. When significant univariate effects emerged, follow-up pairwise comparisons were performed using Bonferroni corrections. To evaluate our research question regarding the prevalence of posttraining strategy use, we used a descriptive analysis of the means, SDs, and ranges of caregiver and service provider reports on this variable.To address our research questions, we conducted 7 repeated measures ANOVAs  using SPSS 28 (IBM Corp). To assess differences in caregivers’ versus service providers’ changes in knowledge, anxiety, and depressive symptoms, we included group status  suggesting that the missing data did not violate the assumption of missing completely at random. To handle missing data, we used multiple imputations (n=10) in SPSS 28 to maximize the power of the analysis. The 10 imputed data sets were averaged to generate single final scores for each variable .On average, the participants completed 64% (32/50) of the training evaluation surveys. To evaluate patterns of missingness, Little test of missing completely at random was conducted for all study variables and was nonsignificant  and from pretraining to the 2-month follow-up  but did not change from posttraining to the 2-month follow-up . The latter effect indicated that increases in service provider knowledge were sustained 2 months after the training was completed. Among refugee caregivers, knowledge significantly increased from pretraining to posttraining . However, caregiver knowledge did not increase significantly from pretraining to the 2-month follow-up , and there was a significant decline in knowledge from posttraining to 2-month follow-up . Thus, the initial increases in refugee caregivers’ knowledge upon finishing the training partially subsided 2 months after training.The repeated measures ANOVA results revealed there was a statistically significant effect of time, ver time . Serviceoften (7) and very often (10), and 74% (37/50) of respondents reported using training-based strategies often or more. Caregivers and service providers reported similar strategy use, t48=−1.72, P=.09.The descriptive analysis of strategy use indicated that caregivers and service providers reported high strategy use after training , as the mean scores were between the anchor points of F1.67,41.83=7.87, P=.002, η2=0.24. Follow-up pairwise comparisons revealed a significant increase in child emotion regulation from pre- to posttraining . However, the changes from pretraining to the 2-month follow-up  and from posttraining to the 2-month follow-up were not statistically significant  and from pretraining to the 2-month follow-up , with no significant change in sadness over wrongdoing from posttraining to the 2-month follow-up . There was no significant change in anxiety symptoms from pre- to posttraining  or from pretraining to the 2-month follow-up . However, there was a statistically significant decrease in anxiety symptoms from posttraining to the 2-month follow-up  and the 2-month follow-up , but not at pretraining  improved from pre- to posttraining. Furthermore, significant improvements were sustained 2 months after the training for children’s sadness over wrongdoing. Improvements in child emotion regulation and sadness over wrongdoing underscore the potential utility of brief social-emotional trainings directed at refugee families and their children, as well as their potential compatibility with other resilience- and family-based training . This fiThere were no significant parent-reported changes in children’s mental health challenges. It is possible that improvements in children’s mental health symptoms may emerge further downstream through changes in other factors, such as improved parenting behaviors, improved parent-child relationship quality, and improved child social-emotional capacities . It is aThis study has several limitations. First, and perhaps most importantly, the lack of a control group prevented us from drawing firm conclusions regarding the efficacy of the training. Given that the training was a pilot, we thought it would be more ethical to include all participants in the experimental group, and given the project’s short timeline, having a delayed group was also not an option. Future studies should include a control group to allow for more precise conclusions. Another limitation of this study is the relatively small sample size, which, albeit appropriate for a pilot study, limits the power and generalizability of our results. Future training evaluations should strive for larger sample size. Moreover, despite efforts to encourage attendance, participant attendance was understandably low given that the training took place during COVID-19 and frequent transition between in-person and web-based school and work settings caused disruptions to participants’ schedules. Future initiatives should consider devising and implementing novel strategies to encourage participants to attend virtually.In conclusion, SPRINT training provided overall evidence of its effectiveness and feasibility. Refugee caregivers and service providers reported high satisfaction with the training, suggesting that brief strengths-based training can be beneficial for refugee populations. The current findings highlight the need for more tailored and culturally adapted training, and pave the way for more research and evaluation of social-emotional strengths among refugee families and children.


We present the case of a 41-year-old man who developed myopericarditis after receiving the Pfizer COVID-19 vaccine. The patient experienced a sudden onset of chest and abdominal pain 16 days after vaccination. Electrocardiogram findings revealed deep T-wave inversion and minimal ST-segment elevation. Further investigation through coronary artery angiography and computed tomography identified an anomalous left main coronary artery. Magnetic resonance imaging confirmed the diagnosis of myopericarditis. This case highlights the importance of considering myopericarditis as a potential cause of chest pain and elevated cardiac biomarkers following COVID-19 vaccination, particularly in young individuals. Clinicians should be aware of this adverse event and include it in the differential diagnosis for patients presenting with similar symptoms after vaccination. Myocarditis, or inflammation of the heart muscle cells, can result from infectious, viral, bacterial, protozoal, or non-infectious causes such as immune-mediated myocarditis and toxic myocarditis ,2. In EuCoronary artery anomalies are rare and are usually accidentally discovered during coronary angiography and autopsy . A studyThe most dangerous anomaly is the left main coronary artery originating from the right sinus of Valsalva, which increases the risk of sudden cardiac death if the artery has a malignant  course. However, the most frequent anomaly is the left circumflex artery originating from the right sinus of Valsalva ,11. One A 41-year-old man presented to the hospital in 2021, 16 days after receiving the second dose of the Pfizer COVID-19 vaccine. He was recently diagnosed with dyslipidemia and was a former smoker. The patient came to the emergency department with a sudden onset of chest and abdominal pain that started one day prior. The pain was progressive, stabbing in nature, radiating to both shoulders and associated with generalised body aches. It was aggravated by exertion and inspiration. The patient reported no recent history of respiratory illness, diabetes mellitus, or hypertension.Initial assessment upon arrival revealed a blood pressure of 120/75 mmHg, 97% oxygen saturation in room air, a heart rate of 65 beats per minute, a respiratory rate of 12 breaths per minute, a temperature of 35.4°C, and a body mass index of 23.88 kg/m2. Examination revealed equal bilateral air entry. Table An initial ECG showed sinus rhythm and deep T-wave inversion in leads III, augmented Vector Foot (aVF), and V3-V6 with minimal ST-segment elevation in the inferolateral leads Figure .The patient was referred to a specialised cardiac centre for coronary artery angiography and possible percutaneous coronary intervention. He was admitted to the cardiac care unit as a case of inferior-lateral myocardial infarction for percutaneous coronary intervention. He was vitally stable on admission, and a PCR test for COVID-19 was negative.Transthoracic echocardiography showed mild hypokinesia of the inferior wall and normal left ventricular size. Left ventricular systolic function was low-normal. The right ventricle was normal in size and function. The ejection fraction was 50%-55%. There was no intracardiac thrombus, significant valvular lesion, or pericardial effusion. Coronary artery angiography showed an anomalous left main coronary artery arising from the right sinus of Valsalva with no obstructive coronary artery disease. Cardiac computed tomography (CT) showed bilateral perivascular ground-glass opacities highly suggestive of infection, including atypical infection, and an anomalous origin of the left main coronary artery from the right coronary artery with a retro-aortic course Figure .The patient was moved to the cardiac ward. A cardiac MRI was done and showed mildly oedematous mid- to inferior-apical segments with mild hypokinesis and epicardial late gadolinium enhancement, consistent with myopericarditis, and normal left ventricular volume and systolic function. The left ventricular ejection fraction was 57% Figure .The final diagnosis was myopericarditis with no obstructive coronary artery disease. The patient was treated with atorvastatin 80 mg once daily, bisoprolol 2.5 mg once daily, and high-dose aspirin, and he improved clinically. He was discharged home in stable condition with close follow-up and an appointment after three months with an echocardiogram to be done before the appointment.Vaccination is one of the most important types of protection against infection. The COVID-19 vaccine provides effective protection but is not without risk of side effects. Among the potential side effects of COVID-19 vaccines, a documented adverse effect that has been reported in the literature is vaccine-related myocarditis, which may present as chest pain with an incidence of approximately 1.12% . MyoperiMyopericarditis can be an adverse effect of vaccines, as a study carried out from 2011 to 2015 of 199 cases of myopericarditis found that 149 of the patients had received the smallpox vaccine . A populWe discuss a case of COVID-19 vaccine-induced regional myopericarditis associated with an anomalous left main coronary artery (originating from the right coronary cusp with a retro-aortic course) in a 41-year-old patient complaining of chest pain and body aches after vaccination. Even in light of the small risk of developing a rare case of self-limited myopericarditis, it is recommended to take the COVID-19 vaccine because the benefits outweigh the risks. Future studies should be designed to discover predisposing factors for myopericarditis related to COVID-19 vaccines.


These findings suggest that a better therapeutic management of HIV infection might result in positive clinical and economic outcomes.This real-world analysis conducted on administrative databases of a sample of Italian healthcare entities was aimed at describing the role of therapeutic pathways and drug utilization in terms of adherence, persistence, and therapy discontinuation in HIV-infected patients under antiretroviral therapies (ART) and Tenofovir Alafenamide (TAF)-based regimens on healthcare resource consumption and related direct healthcare costs. Between 2015 and 2019, adults (≥18 years) prescribed with TAF-based therapies were identified and characterized in the year prior to the first prescription (index-date) for TAF-based therapies and followed-up until the end of data availability. Overall, 2658 ART-treated patients were included, 1198 of which were under a TAF-based regimen. TAF-based therapies were associated with elevated percentages of adherence  and persistence (78.5%). The discontinuation rate was low in TAF-treated patients, ranging from 3.3% in TAF-switchers to 5% in naïve. Persistent patients had lower overall mean annual healthcare expenditures (EUR 11,106 in persistent vs. EUR 12,380 in non-persistent,  The development and introduction of antiretroviral therapies (ART) and then the availability of combination ART in the clinical practice has dramatically changed the course of human immunodeficiency virus (HIV) infection from an acute to a chronic disease . NowadayAccording to the World Health Organization (WHO), adherence is defined as “the extent to which a person’s behaviour—taking medication, following a diet, and/or executing lifestyle changes, corresponds with agreed recommendations from a health care provider” . AdherenThis real-world analysis was aimed at describing the demographic and clinical characteristics of patients treated with ART and evaluating therapeutic pathways and drug utilization. A special focus was placed on adherence, persistence, and therapy discontinuation of Tenofovir Alafenamide (TAF)-based regimens either as multi-tablet regimens (MTR) or single-tablet regimens (STR) among naïve patients and those with previous ART who switched for the first time to TAF-based regimens and the resulting impact on healthcare resource consumptions and related direct costs for the Italian National Health Service (INHS).The present retrospective observational analysis was based on data collected from the administrative databases of a sample of Italian Local Health Units (LHUs), covering around 5.52 million health-assisted subjects belonging to Apulia, Abruzzo, Molise, Campania, Lazio, Umbria, Liguria, Piedmont, and Veneto regions. The following databases were used for the analysis: (1) demographic database to obtain data on age, gender, and mortality; (2) pharmaceutical database for information related to drug prescriptions, such as anatomical-therapeutic chemical (ATC) code, number of packages, number of units per package, costs, and prescription date; (3) hospitalization database, including all hospitalization data with discharge diagnosis codes classified according to the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM), diagnosis-related group (DRG), and DRG-related charge; and (4) outpatient specialist services database, reporting data on prescriptions, type, description of diagnostic tests, and specialist visits. To guarantee patients’ privacy, an anonymous univocal numeric code (patient ID) was assigned to each health-assisted subject by the LHUs. The patient ID code allowed the electronic linkage between the databases. The anonymous code of the patient ensures the anonymity of the extracted data in full compliance with UE Data Privacy Regulation 2016/679 (“GDPR”) and Italian D.lgs. n. 196/2003, as amended by D.lgs. n. 101/2018. All the results of the analyses were produced as aggregated summaries, which could not be connected, either directly or indirectly, to individual patients. All adult (≥18 years old) patients prescribed with ART between January 2015 and December 2019 were screened. Among them, patients with TAF-based therapies were identified during all inclusion period by presence of the following drugs: TAF (ATC code J05AF13); emtricitabine and tenofovir alafenamide (ATC code J05AR17); emtricitabine, tenofovir alafenamide, elvitegravir, and cobicistat (ATC code J05AR18); emtricitabine, tenofovir alafenamide, and rilpivirine (ATC code J05AR19); emtricitabine, tenofovir alafenamide, and bictegravir (ATC code J05AR20); and emtricitabine, tenofovir alafenamide, darunavir, and cobicistat (ATC code J05AR22). Patients with TAF-based therapies were defined as naïve if they did not present any ART prescription in the 12 months before starting TAF-based therapies and as TAF-switchers if they had switched from a non-TAF-based to a TAF-based regimen.Patients who moved to another LHU during the period considered in the analysis or with just one ART prescription or with prescription gaps greater than 12 months between subsequent prescriptions were excluded from the analysis. The date of the first prescription for TAF detected within the inclusion period was defined as the index date. Patients’ clinical characteristics were evaluated during at least 12 months prior to the index date (characterization period), while patients were followed-up until the end of database availability, which was at least 12 months for each patient. At baseline, the following comorbidities were evaluated: depression, respiratory disease, renal failure, alcohol/drugs abuse, cardiovascular disease, neoplastic diseases, diabetes, dyslipidemia, HBV/HCV, and hypertension , namely the ratio between the number of days of medication supplied and days of therapy, multiplied by 100 . To defip < 0.05. All the analyses were performed using Stata SE version 12.0 .Continuous variables are reported as mean ± standard deviation and categorical variables as numbers and percentages. A generalized linear model (GLM) with gamma distribution and identity link function was developed to assess the relationship between adherence level and non-ART costs. Statistical significance was accepted at A total of 2658 adult patients treated with ART were included in the analysis, and their demographic and clinical characteristics in the overall population and by calendar year are shown in In the total inclusion period, the mean age was 48.6 years, with the majority of patients in the age range of 36–55 years (61.6%). Male gender was more represented (71.6%). Analyzing the demographic characteristics by each year of inclusion, the male gender remained more frequent (71–73%), and a slight increase in age was noticed over the years. In the overall inclusion period, the most frequent comorbidities were hypertension (19.5%), followed by respiratory disease (15.9%) and dyslipidemia (11.2%) and mild average CCI (0.2) with 87.2% of patients with CCI score 0. The pattern of comorbidity distribution analyzed by each calendar year mirrored that of the total inclusion period. The analysis focused on 1198 patients prescribed a TAF-based regimen during inclusion period. Adherence and persistence in the subgroups and in the total sample population were then investigated. In detail, the proportion of patients adherent to TAF-based regimens was 83.3% with a PDC threshold above >95%; specifically, it was higher among TAF-switchers (85.6%), followed by TAF-STR (84.4%), TAF-MTR (81.9%), and naïve (79.9%). The proportion of adherent patients with PDC > 85% was 90.6% . Data on persistence revealed that the proportion of patients persistent to TAF-based regimens was 78.5% and reached 96% when persistence to any ART was analyzed. Switch to another ART not TAF-based occurred in 18% of patients, and 4% discontinued the therapy. The stratification in subgroups confirmed in general this overall trend, in particular for the rate of discontinuation that ranged between 3.3% (TAF-switchers) and 5% (naïve). Of note, patients under MRT regimen compared to those with STR showed a greater tendency to switch  and a lower persistence on TAF-based therapy . Overall persistence for TAF naïve patients was 74.3%.The healthcare resource consumption during first year of follow-up for TAF-based regimes patients evaluated in the last 3 years of inclusion (2017–2018–2019) showed the highest numbers for ART prescriptions and specialistic visits/diagnostic tests, followed by other drug prescriptions, with a decreasing trend over time . The relp = 0.005), and this difference was mostly appreciable in the cost item related to HIV hospitalization. Moreover, when the analysis was focused only on patients with HIV-related hospitalization, the mean costs were found to be higher for non-persistent patients (N = 25) compared to persistent ones (N = 79) .The evaluation of the role of persistence on healthcare resources consumptions during the first year of follow-up in patients with TAF-based regimen revealed that the most relevant consumptions were attributable to ART prescriptions and specialistic visits/diagnostic tests and, lastly, other drug prescriptions to a higher extent in non-persistent patients . RegardiThe healthcare resources consumption in TAF-treated patients stratified by adherence <80%, 81–95%, and >95% indicated ART prescriptions and specialistic visits/diagnostic tests as the most impactive items . ConsistHealthcare resources consumptions in non-adherent (PDC < 80%) patients treated with ART other than TAF and TAF-based regimens highlighted that even in non-adherent patients, the majority of consumptions were imputable to ART prescriptions and specialistic visits/diagnostic tests although less markedly in the patients receiving a TAF combination . p = 0.070, nearly significant), mostly driven by the expenses for other drugs  and specialistic visits and outpatient services .Cost analysis extended to the overall observation period in ART- and TAF-based regimens is shown in p < 0.001) and EUR 2265 in those over 65 . A worse comorbidity profile was also significantly predictive of higher non-ART costs   .The current awareness of the management of HIV patients chronically treated with ART and the subsequent rebounds on healthcare resource consumptions and expenditures is highly variable across the different countries ,21,22.The present analysis was conducted in a setting of real-life clinical practice in Italy to describe the state-of-art of HIV-infected patients treated with ART and more specifically with TAF-based regimens, evaluate therapeutic pathways and drug utilization, and give special attention to the impact of adherence, persistence, and therapy discontinuation of TAF-based regimens on HIV management and direct healthcare costs.The demographic characteristics of the overall ART population reported a male predominance and a mean age of around 49 years, which is in line with other Italian real-world studies on HIV ,23. HypeThere is large body of evidence from national and international studies that, despite the undeniable progression and growing availability of pharmacological options for HIV patients, the goal of maintaining an adequate therapy adherence in the long term is still far from being reached . This poPersistence to TAF-based regimens mirrored the trend observed for adherence, with a high proportion of persistent patients among those with STR or switchers. Sutton et al  found inTo the best of our knowledge, there are limited data on the actual economic burden for patients with TAF-based regimens in Italy, while the literature reports an estimation of cost-effectiveness or budget-impact analysis on such therapies ,34. The In all the scenarios depicted, cost analysis revealed that during the first year of follow-up, the weightiest item on the annual healthcare direct cost per patient was that for ART, which is consistent with previously published data for European countries ,36,37. The downward trend observed over the last 3 years of inclusion was mainly due to a halving in the costs of other drugs, hospitalizations, and outpatients’ services through the years, suggesting that the introduction of innovative ART on the market could influence the costs for the management of patients. Persistence to TAF-based therapies was associated with significantly lower mean annual costs, in particular for the cost item related to HIV hospitalization. Moreover, the comparison of mean annual healthcare direct costs by adherence (PDC > 85% vs. PDC < 85%) in TAF-based regimen revealed that increased costs not related to ART were observed in non-adherent patients; once again, this trend was evident for HIV hospitalizations. In this regard, Toh et al.  exploredConsidering the mean annual health care resource consumptions and costs during all available follow-up in TAF-treated patients with respect to adherence, we found tendentially increased consumptions and costs with growing adherence levels but this might be explained by the obviously higher burden of drug expenses in adherent patients, which is in line with the literature ,38. MultThese findings should be interpreted in the light of some limitations related to the observational retrospective design of the analysis, which was based on data extracted from administrative databases. Thus, there might be lacking or insufficient clinical information on a number of other potential confounders  that may have influenced the results. Secondly, data on the reasons for changing regimens (switch or discontinuation) are not reported within the database as well as the causes of non-adherence since not-measurable variables as patient attitudes towards medication or social status are not present; similarly, adherence and persistence were evaluated based on the drug dispensed; therefore, the actual use by the patient is unknown. Ultimately, indirect costs or out-of-pocket costs could not be evaluated, as administrative databases contain data on healthcare resources reimbursed by INHS. This real-world analysis provided an in-depth characterization of patients prescribed TAF-based regimens in terms of drug utilization and how this could have affected healthcare resource consumptions and costs. Higher levels of adherence and persistence to TAF-based regimens were detected among users of STR rather than MTR and among experienced patients that switched from an ART- to a TAF-based treatment compared to naïve patients.A declining trend over the years in healthcare resource consumption and the related direct costs could be suggestive of the changing of costs related to the management of HIV patients due to the advent of novel therapeutic options. The total healthcare costs were mainly driven by ART-related costs, which represent almost 70% of the total expenditure. Patients that showed a higher level of TAF persistence and adherence were reported to have a reduced healthcare cost related to HIV hospitalizations compared to those who were non-persistent or not adherent to TAF-based therapies, suggesting that the optimization of the drug utilization may have a positive impact not only from a clinical point of view but from the perspective of the sustainability of the INHS as well.


This cross-sectional study investigates proportions of hospital admissions with RSV and rates of associated outcomes among children and adolescents before and during the COVID-19 pandemic. What is the epidemiology of pediatric respiratory syncytial virus (RSV)–associated hospitalizations in Canada, and how has it changed with the COVID-19 pandemic?This cross-sectional study of 11 014 pediatric RSV-associated hospitalizations found that such hospitalizations in Canadian pediatric centers were frequent, particularly among children under age 6 months. After a near absence in 2020-2021, RSV admissions increased in 2021-2022 compared with prepandemic means, while severity and age distribution remained similar but with greater interregional variability in timing of RSV activity.This study found a significant burden of RSV hospitalizations in Canadian pediatric centers, particularly among children under age 6 months. The study found an increase in admissions during 2021-2022, with regional variation in RSV activity timing. Respiratory syncytial virus (RSV) is a leading cause of pediatric hospitalizations.To describe the epidemiology and burden of RSV-associated hospitalizations among children and adolescents in Canadian tertiary pediatric hospitals from 2017 to 2022, including changes during the COVID-19 pandemic.This cross-sectional study was conducted during 5 RSV seasons (2017-2018 to 2021-2022) at 13 pediatric tertiary care centers from the Canadian Immunization Monitoring Program Active (IMPACT) program. Hospitalized children and adolescents aged 0 to 16 years with laboratory-confirmed RSV infection were included.P values to adjust for multiple statistical comparisons.The proportion of all-cause admissions associated with RSV and counts and proportions of RSV hospitalizations with intensive care unit (ICU) admission, prolonged stay (≥7 days), and in-hospital mortality were calculated overall and by season, age group, and region. Seasonality was described using epidemic curves. RSV hospitalizations for 2021-2022 were compared with those in the prepandemic period of 2017-2018 through 2019-2020. Bonferroni corrections were applied to P < .001). A significant increase in RSV-associated hospitalizations was found in 2021-2022 for 3 provinces . Age, sex, ICU admission, prolonged length of stay, and case fatality rate did not change in 2021-2022 compared with the prepandemic period. Interregional differences in RSV seasonality were accentuated in 2021-2022, with peaks for 1 province in October, 4 provinces in December, and 3 provinces in April, or May.Among 11 014 RSV-associated hospitalizations in children and adolescents , 2594 hospitalizations (23.6%) had admission to the ICU, of which 1576 hospitalizations (60.8%) were among children aged less than 6 months. The median (IQR) hospital stay was 4 (2-6) days. The mean (SD) number of RSV-associated hospitalizations during prepandemic seasons was 2522 (88.8) hospitalizations. There were 58 hospitalizations reported in 2020-2021, followed by 3170 hospitalizations in 2021-2022. The proportion of all-cause hospitalizations associated with RSV increased from a mean of 3.2%  before the pandemic to 4.5%  in 2021-2022 (difference, 1.3 percentage points; 95% CI, 1.1-1.5 percentage points; corrected This study found that the burden of RSV-associated hospitalizations in Canadian pediatric hospitals was substantial, particularly among infants aged less than 6 months, and RSV hospitalizations increased in 2021-2022 compared with the prepandemic period, while severity of illness remained similar. These findings suggest that RSV preventive strategies for infants aged less than 6 months would be associated with decreased RSV disease burden in children. Monthly immunoprophylaxis with palivizumab  was until recently the only licensed measure to prevent severe RSV-associated lower respiratory tract infection in Canada, but its use was limited to infants at high risk and indications varied across Canadian provinces.4 However, healthy infants born at term account for most pediatric RSV hospitalizations.5 Long-acting monoclonal antibody prophylaxis that may be considered for all infants has recently become available in some jurisdictions, including in Canada and the US, and vaccines for use in pregnancy to protect young infants are currently under review.7Respiratory syncytial virus (RSV) is a leading cause of pediatric hospitalization worldwide, particularly in infants and young children. In North America and Europe, nearly 2% of all infants require hospitalization for RSV infection during the first year of life.9 In the Northern Hemisphere, an interseasonal surge in pediatric RSV–associated hospitalizations was observed in the summer and fall of 2021.8 To date, reports have been conflicting regarding changes in the age distribution and severity of RSV hospitalizations in children since the beginning of the COVID-19 pandemic,11 and national data from Canada, including possible interregional differences, are lacking. We aimed to describe overall, age-specific, and region-specific characteristics and in-hospital severity and outcomes of RSV-associated hospitalizations at Canadian Immunization Monitoring Program, Active (IMPACT) centers among children and adolescents aged 0 to 16 years during 5 RSV seasons (2017-2018 to 2021-2022) and to compare the 2021-2022 season with the prepandemic period.Public health measures put in place in March 2020 to counter SARS-CoV-2 transmission were associated with a marked reduction in respiratory illness attributed to bacteria and other viruses during the first year of the COVID-19 pandemic.STROBE) reporting guideline for observational studies.Institutional ethics approval was obtained at each IMPACT center for this cross-sectional study, with a waiver of informed consent due to the minimal risk of this health record review. This study follows the Strengthening the Reporting of Observational Studies in Epidemiology  and year-round for 2 years (July 2020 until June 2022) among children and adolescents admitted to 12 tertiary care pediatric centers of the IMPACT network. Another pediatric center was added during July 2020 to June 2022; however, data from this site were excluded from all statistical comparisons between time periods. IMPACT hospitals account for approximately 90% of the pediatric tertiary care beds in Canada, with referrals from all provinces and territories.All children and adolescents aged 0 to 16 years who had laboratory-confirmed RSV infection, including hospital-acquired infection, at the time of admission or during their hospitalization were included. We could not distinguish between hospital-acquired and community-acquired infections.Trained nurse monitors screened daily laboratory results and admission lists for eligible RSV cases. Data were abstracted from medical records after patient discharge using a structured electronic case report form. Data entry forms contained drop-down menus and built-in logic to minimize errors and omissions. Data collected included hospital admission and discharge dates, age, sex, RSV specimen collection date, ICU admission, and disposition at discharge or transfer (died or survived). No data on underlying medical conditions were collected for this study. In addition, we captured the total number of all-cause medical inpatient admission days for each year from each IMPACT hospital (excluding psychiatry wards and newborn nurseries).13 and considering the heterogeneity of pandemic health measures over time and across regions during that period, the 2020-2021 season was excluded from statistical comparisons. Data from the 2021-2022 season were compared with data from the 2017-2018 through 2019-2020 period using linear regression for continuous data  and χ2 for categorical data . P values ≤ .05 were considered statistically significant, and all comparisons were 2-sided. Overall and province-specific proportions of RSV-associated hospitalizations over all-cause hospitalizations were estimated. Individual proportions with 95% CIs were computed for overall and province specific proportions of RSV-associated hospitalizations over all-cause hospitalizations using prop.test in R statistical software. Changes in the proportion of RSV-associated hospitalizations were compared between means of the prepandemic period (2017-2018 to 2019-2020) and 2021-2022 using the 2 independent groups proportion test. Subgroup analyses were conducted to study disease severity differences by age group  using the 2 independent groups proportion test. Statistical analyses were performed using R statistical software version 4.1.3 . Bonferroni corrections were applied to P values to adjust for multiple statistical comparisons using the p.adjust function within the R stats package version 3.6.2. We reported individual level frequencies between 1 and 4 as less than 5 in accordance with IMPACT privacy policies.We considered 3 RSV seasons  as the prepandemic period. Given the near absence of RSV laboratory detection in Canada and 58 IMPACT RSV cases during July 2020 to June 2021During the 5-year surveillance period, 11 014 RSV-associated hospitalizations  . Changes in the proportion of RSV hospitalizations over all-cause hospitalizations in 2021-2022 were not consistent across regions; significant increases occurred in 3 provinces: Quebec , Saskatchewan , and Alberta .The mean  annual number of hospitalizations for the 3 prepandemic seasons (2017-2018 season to 2019-2020 season) was 2523  hospitalizations compared with a total of 3170 hospitalizations for the 2021-2022 season . During P < .001).Overall, 2594 hospitalizations (23.6%) had admission to the ICU (eTable in P < .001). Overall, increasing age in months was associated with longer LOS . Same-day discharges were uncommon, occurring in less than 3% of all age groups . Of a total of 29 in-hospital deaths (0.3% of admissions), 6 deaths (20.7%) occurred in children aged younger than 6 months.More than one-quarter of hospitalizations among children aged younger than 6 months  had admission to the ICU, representing 60.8% of all ICU RSV admissions. RSV ICU admission proportion declined with age during the first year of life, from 537 of 1456 admissions (36.9%) among children in the first month to 26 of 163 admissions (16.0%) among children in the twelfth month  for same-day discharge, 0.2 percentage points  for ICU admissions, −2.3 percentage points  for prolonged LOS, and 0.1 percentage points  for deaths , and in-hospital mortality did not differ in the prepandemic period vs the 2021-2022 season. The differences were 0.8 percentage points  were seen in a study of tertiary pediatric centers in the US.16 Our data did not allow us to ascertain if RSV contributed to death. Thus, our in-hospital mortality rate is potentially an overestimate of RSV-attributable mortality. A Canadian study17 of RSV mortality from 11 pediatric centers during 2003 to 2013 identified 90 deaths during RSV admissions. Death was completely unrelated to the RSV infection in 12% of deaths and due to RSV in 36% of deaths, while the virus was a contributor in 34% of deaths and played an undetermined role in 20% of deaths.Overall, in-hospital mortality occurred in 0.3% of RSV hospitalizations, which is comparable to the reported range of 0.04% to 0.90% in large US studies.19 This was most likely associated with the implementation of COVID-19 pandemic public health measures, such as school and daycare closures, masking, travel restrictions, and physical distancing.8 Similarly, no pediatric influenza–associated hospitalizations or deaths were reported at IMPACT centers during the 2020-2021 season.20The near absence of pediatric RSV hospitalizations in Canada during the first year of the COVID-19 pandemic was commensurate with exceptionally low levels of circulation of RSV and other respiratory viruses nationally, similar to observations in other countries.21 Other countries observed similar increases in RSV-associated disease, with some reports noting that it occurred without the expected proportional increases in infections and hospitalizations in older adults.24 The age distribution of children and adolescents hospitalized with RSV at IMPACT sites remained similar in 2021-2022 compared with pre-COVID-19 seasons, with approximately half of all patients younger than age 6 months. Some studies found an increase in the proportion of older children testing positive or admitted with RSV.26 In British Colombia, the median age of children aged less than 36 months testing positive for RSV increased from 6.3 months to 11.8 months in the 2021-2022 season27; however, no change in age distribution among hospitalized patients was observed. It has been hypothesized that when pandemic restrictions were loosened, the absence of circulating RSV during the 2020-2021 winter season resulted in a cohort of older infants who were RSV-naive and more susceptible to lower respiratory tract RSV infections; these illnesses required medical attention but were not severe enough to require hospital admission given that hospitalization risk decreases with age.15 We did not observe an increase in the age of children and adolescents at RSV admission or an increase in disease severity  overall or within any age stratum in 2021-2022. However, a national, population-based study10 in Denmark in 2021-2022 found an increase in the incidence rate of RSV-associated admissions and mechanical ventilation, especially among children aged 2 to 5 years, underscoring the importance of ongoing monitoring of age-specific disease incidence of RSV.We observed an overall increase in pediatric RSV–associated hospitalizations in Canada after the first year of the COVID-19 pandemic, beginning in the summer of 2021. However, this increase was primarily associated with higher RSV admission rates observed in 3 provinces; other regions had no significant change in the proportion of RSV-associated admissions in children and adolescents. This resurgence of RSV infections was likely associated with reduced population-level immunity caused by the absence of infections in the previous year, combined with children’s reengagement in social activities and the relaxing of other COVID-19 public health measures.29 Efficacy estimates of the RSV bivalent PreF vaccine in pregnancy (Pfizer) for severe medically attended RSV lower respiratory tract infection in infants are 82% through the first 90 days of life and 69% through 6 months.30Given that our observed age distribution of pediatric RSV disease was heavily weighted toward young infants, preventive strategies, such as long-acting monoclonal antibody immunoprophylaxis for all infants and RSV vaccines for pregnant persons, could be associated with profound decreases in RSV burden. The efficacy of a single dose of the monoclonal antibody nirsevimab (Sanofi and AstraZeneca) has been estimated to be 77% against RSV-associated hospital admissions through 150 days after the dose in healthy infants born at full term or before term .31Monitoring RSV seasonality is essential for pediatric health care capacity planning, including the appropriate timing of monthly palivizumab immunoprophylaxis, generally administered from November to March in Canada. During the 2021-2022 season, there was increased variability in seasonality between provinces, with some regions experiencing early peaks of RSV activity during the summer and fall of 2022, and typically small interregional differences were greatly accentuated. In Quebec, a summer 2021 surge in RSV admissions and an abrupt halt in transmission in January 2022 prompted a start and end of the provincial palivizumab program approximately 2 months earlier than planned. Prairie provinces, such as Manitoba, Saskatchewan, and Alberta, had to extend their palivizumab programs due to ongoing RSV admissions in the spring of 2022 by contrast. This highlights the importance of regional surveillance for RSV, especially considering that optimizing the cost-effectiveness of long-acting monoclonal antibodies and maternal vaccination against RSV will depend in part on the timing of their administration in relation to RSV activity.9 Despite these limitations, this study represents nearly 90% of pediatric tertiary care beds in Canada, providing a comprehensive view of RSV hospitalizations over a 5-year period and allowing for comparisons over time and across geographic areas.Our study has limitations. Surveillance was restricted to tertiary care centers in Canada; therefore, results may not be generalizable to the entirety of Canadian RSV pediatric hospitalizations. Changes in RSV testing practices likely occurred over time, particularly after the onset of the COVID-19 pandemic, and such changes may have varied across IMPACT centers, affecting case capture. It is possible that diagnostic biases may have led to an overestimation of the increase in RSV hospitalizations in 2021-2022 or an underestimation of the disease burden in older children and adolescents, who less typically experience severe RSV. Thresholds for admission and health-seeking behaviors may also have been affected during this study period due to health care system pressures related to the pandemic. Due to the limited number of variables collected, we could not identify incidental RSV infections unrelated to the reason for admission or distinguish hospital-acquired infections. Moreover, we were unable to determine the underlying medical conditions of hospitalized children. There were also gaps in the surveillance period during the first 3 seasons, in which data were not collected during summer months. However, national laboratory surveillance for RSV did not suggest significant circulation during these periods, indicating that few if any cases would have been missed.This cross-sectional study found that RSV hospitalizations were frequent in Canadian pediatric centers and that nearly 1 in 4 hospitalized children and adolescents required ICU care. The greatest burden was among children aged less than 6 months, representing approximately half of RSV hospitalizations and 60% of RSV ICU admissions. After a near absence of RSV admissions during the winter of 2020-2021, there was an overall increase in pediatric RSV admissions in 2021-2022, with regional variation. There were no changes over time in age distribution or the proportion of patients requiring ICU admission or hospital admission of 7 days or longer; however, there was greater interregional variability in the timing of RSV activity in 2021-2022. Taken together, our results suggest that RSV preventive strategies for infants aged less than 6 months may have the greatest potential for associated decreases in RSV burden in children and adolescents. Our findings also highlight the importance of ongoing surveillance of pediatric RSV hospitalizations at national and regional levels.


Coronavirus disease 2019 (COVID-19) has inflicted significant mortality and morbidity worldwide since the virus was first detected towards the end of 2019. Though it primarily affects the respiratory system, COVID-19 has been shown to have a multisystem effect. There have been literature on liver injury associated with COVID-19 in general but liver injury specific to certain risk and age groups needs to be looked into. Thus, we aim to discuss the liver injury associated with COVID-19 in various age and risk groups and revisit pathophysiology, biochemical markers and their correlation with outcomes, and current management recommendations. Coronavirus disease 2019 (COVID-19) is a viral infection caused by the SARS-CoV-2 virus [Pathophysiology of liver injury in COVID-19Located between the portal and systemic circulations and continuously being exposed to dietary antigens, viruses, and other inflammatory products, the liver is at the highest risk of getting damaged by exposure to toxins, bile duct obstruction, viral infections, and preexisting chronic liver conditions . The exaCytopathogenic Effects of the Virus on the Liver CellsIn COVID-19, liver injury might be the virus's direct effect on the liver cells. Chai et al.  performeCytokine StormDifferent types of pro-inflammatory cytokines have been found to play a role in the cytokine storm. Initiation of cytokine storm heralded by mediators such as Interleukins 2,6,7 and 11, interferon-gamma, and tumor necrotic factor alpha ultimately leads to multi-organ failure (MOF). It can also cause a hypercoagulable state. An imbalance in coagulation homeostasis as a result of systemic inflammation leads to a condition of a pro-coagulant state manifesting as micro-thrombosis, disseminated intravascular coagulation, and multiorgan failure .Ischemia and Reperfusion InjuryThere can be an initial ischemic insult to the hepatocytes in COVID-19. This is considered a localized process comprising disturbances of lipid metabolism, adenosine triphosphate scarcity, and glycogen consumption that collectively leads to cellular death. During the reperfusion phase following the ischemic injury, there is massive recruitment of pro-inflammatory immune cells from the circulation that leads to a reperfusion injury to hepatocytes .Liver Injury in COVID-19 Due to Drugs That Were Once Used or Are Currently Being Used for Treatment PurposesVarious drugs like chloroquine, azithromycin, acetaminophen, remdesivir, lopinavir/ritonavir, tocilizumab, and corticosteroids that were proposed to be used for treatment in COVID-19 or that are still in use may be the potential cause of hepatocyte injury in patients with COVID-19. An increase in bilirubin levels, along with alteration in aspartate aminotransferase/alanine transaminase (AST/ALT), was seen with the use of lopinavir/ritonavir in patients with preexisting liver disease . LopinavLiver injury in various age groups and risk populationHepatic injury in the pediatric population with COVID-19 generally manifests as mild elevation in AST and ALT without derangement in the synthetic function. Acute liver failure is reported to be uncommon in the pediatric population. However, a few cases of acute liver failure are reported in the literature. Antala et al. reported a case series of four pediatric patients with COVID-19 who did not have any pre-existing liver disease. None of them had pulmonary symptoms due to COVID-19, but two of the four patients had acute liver failure. The authors opined that it resulted from complement activation and reported that one of the children was treated successfully with eculizumab. Rest three children improved just with supportive measures . All fouGiorgio et al. performed a systematic review concluded in March of 2021. They included 105 contemporary studies with a total sample size of 369 pediatric population. The authors concluded that children get a milder liver injury as compared to adults. The authors believe that the activated lymphocytes can get rid of the stimulus  more effectively. Children have an intact effector and immunosuppressive capacity as compared to adults. They reported that all 369 pediatric patients survived. Children with chronic liver disease, autoimmune liver disease, and transplantation were all devoid of any major complications even when they were infected with COVID-19. The authors have also requested pediatricians to consider underlying chronic liver disease in children with COVID-19 with deranged liver enzymes, referring to the fact that 1 to 11% of these patients admitted with COVID-19 had underlying chronic liver disease .The impact of COVID-19 on maternal and neonatal outcomes has not been properly documented. In one study, out of 249 women who tested positive for COVID-19, 42.97% (107) had acute liver function abnormality upon admission, and 57.03% (142) had a normal liver function. Based on the severity of COVID-19, women were categorized as asymptomatic, mild, moderate, and severe COVID-19. Pregnant women with liver injury had severe COVID-19 disease and had deranged LFTs. In the group with liver dysfunction, a greater percentage of pregnant women underwent cesarean section compared to the group with normal liver function; but this difference was not statistically significant. In the group of pregnant women with hepatic dysfunction associated with SARS-CoV-2 infection, postpartum hemorrhage, the requirement for blood transfusion, complications like sepsis and failure of multiple organs, and mortality were more common .In another retrospective cohort study involving 122 pregnant women with COVID-19, 17 (13.95%) patients had abnormal LFTs during hospitalization. Critically ill patients were more in number in the abnormal LFTs group than in the normal LFTs group. In the group of pregnant women with abnormal LFT, the use of medications lopinavir/ritonavir and hydroxychloroquine was observed to be significantly higher, with prolonged treatment duration and hospitalization . These fLiver injury in COVID-19 patients with previous liver diseaseAmong the patients at risk of getting an acute liver injury in COVID-19, those with pre-existing liver conditions are at risk. We aim to focus on the prevailing evidence about this vulnerable group in this separate sub-topic. The patients with chronic liver diseases such as alcohol-related liver disease (ALD), decompensated cirrhosis, and hepatocellular carcinoma who are infected with COVID-19 have a heightened risk of mortality from COVID-19 as revealed in one study, including 867 patients with chronic liver disease with COVID-19 from 21 centers across the United States .According to the study results, both Hispanic ethnicity and the presence of decompensated cirrhosis were found to be independent risk factors for severe COVID-19 outcomes . AnotherAnother study revealed that the higher occurrence of non-alcoholic fatty liver disease (NAFLD) increases the risk of a significant portion of the population experiencing complications of COVID-19 . PatientBiochemical markers of liver injury in COVID-19 and data on their correlation to outcomesThe degree of liver injury is measured in terms of changes in liver enzymes; level of ALT >40 U/L, AST >40 U/L, gamma-glutamyl transferase (GGT) >49 U/L, alkaline phosphatase (ALP) >135 U/L, and total bilirubin (TBIL) >17.1 micromol/L were defined as abnormal liver test results . FurtherIn another hospital-based study among 1099 patients with laboratory-confirmed COVID-19, 168/757 22.2%) had elevated AST, 158/741 (21.3%) had elevated ALT, 76/722 (10.5%) had elevated total bilirubin. Those with elevated liver enzymes had severe COVID-19 disease. The main outcome measures were being admitted to an intensive care unit (ICU), receiving mechanical ventilation, and dying, and several patients with those outcomes were higher, 50% vs. 20.1% in the high AST group, 40.8% vs. 19.9% in high ALT group and 20.8% vs. 9.8% in high total bilirubin group [.2% had eIn another retrospective cohort study conducted in the United States, 2273 patients tested positive out of 3381 patients. For individuals who tested positive, liver injury was categorized based on the level of ALT elevation as none/mild , moderate , and severe . Individuals who tested positive for COVID had higher median ALT values than those who tested negative, which is evident in both the initial  and peak  values. Furthermore, values greater than two times the upper limit of normal  were more prevalent in positive cases compared to negative cases. However, there was no significant difference in peak ALT values greater than five times the upper limit of normal  between the two groups. Patients requiring care in Intensive Care Unit setting were likelier to have a moderate and severe acute liver injury (p<0.001). Among 92 patients who were discharged from the emergency department, 93% had an ALT <2 times the ULN. Out of the 529 patients who required ICU-level care, 54% had an ALT<2 times the ULN, 27% had an ALT 2-5 times the ULN, and 19% had an ALT >5 times the ULN. When all other factors were considered, such as age, body mass index, diabetes, hypertension, intubation, and renal replacement therapy (RRT), the peak ALT level was found to have a significant correlation with death or discharge to hospice  in multivariable analysis .In another retrospective cohort study done in 1827 hospitalized patients, liver tests were abnormal in patients with COVID-19 both pre-hospitalization  and peak hospitalization . The study demonstrated the correlation between abnormal liver tests and severe COVID-19, including the need for ICU admission, mechanical ventilation, and death .Current management strategyCurrently, there is a lack of information on the safety of the medications used to treat COVID-19 individuals with liver injury, and most patients' care is determined by anecdotal experience. This is not different for the population at risk as well. The American Association for the Study of Liver Diseases (AASLD) expert panel's consensus statement  has madeCOVID-19 vaccinationBesides the general management strategies for the treatment of COVID-19 infection, vaccines developed for the prevention of SARS-CoV-2 infection have been considered as the promising approach for fighting against the global pandemic. The efficacy of COVID-19 vaccines in reducing the risk of severe COVID-19-related disease and reduction in COVID-19-associated hospitalizations and deaths has been proven by various studies . The mRNThe potential for liver injury in patients with COVID-19 infection must be taken into consideration. Extra vigilance is required in patients in the high risks group and age. Mild liver injury generally tends to recover with conservative management. Patients on treatment for chronic infectious liver conditions, autoimmune hepatitis and liver transplant recipients should not have their treatment abruptly stopped. Based on the contemporary data, acute liver failure due to COVID-19 per se is not very common even in high-risk and certain age group patients except in those with shock and multiorgan dysfunction.


Then, we compared each subtype of high-calorie food images to low-calorie ones, and found craving ratings were greater for the images of salty foods and sugary drinks (ps < 0.05). Furthermore, we conducted a subgroup analysis of individuals according to whether they did or did not meet the criteria for food addiction (FA) and found that greater cravings induced by the images of high-calorie food subtypes  only appeared in the subgroup that met the FA criteria. The results show that the PLCF is practical for investigating food cravings.Cue-induced food cravings are strong desires directed toward specific foods, usually ones with high caloric content, and can lead to overeating. However, although food cravings vary according to individual preferences for specific high-calorie food subtypes, a structured library of food craving-inducing pictures including multiple categories of high-calorie foods does not yet exist. Here, we developed and validated a picture library of Chinese foods (PLCF) consisting of five subtypes of high-calorie foods  to allow for more nuanced future investigations in food craving research, particularly in Chinese cultural contexts. We collected 100 food images representing these five subtypes, with four food items per subtype depicted in five high-resolution photographs each. We recruited 241 individuals with overweight or obesity to rate the food pictures based on craving, familiarity, valence, and arousal dimensions. Of these participants, 213 reported the severity of problematic eating behaviors as a clinical characteristic. Under the condition of mixing multiple subtypes of high-calorie foods, we did not observe significant differences in craving ratings for high- and low-calorie food images ( Food cravings are defined as a strong desire or urge to eat specific foods . Many stAlthough many food picture sets have been developed over the last decade , they alFurthermore, obesity is a heterogeneous condition, and grouping all types of obesity together may lead to inconsistent findings about the phenotype of obesity because some clinical manifestations specific to certain subtypes may be masked or weakened . For exaFood addiction is commonly operationalized by the Yale Food Addiction Scale (YFAS) , which w1 Concerning the inconsistency of results finding greater cravings for high-calorie foods among people with overweight or obesity, we hypothesized that (1) the greater cravings for high-calorie foods occur only in certain subtypes of high-calorie foods rather than all high-calorie foods in general; and (2) the greater cravings for high-calorie foods are driven by individuals who meet FA criteria.Therefore, we seek to further investigate the manifestation of food cravings and resolve the inconsistency currently present in the literature regarding whether high-calorie foods evoke greater cravings in individuals with overweight or obesity by developing a structured picture library that can be used as a more sophisticated tool for measuring eating-related characteristics. Taking the above into account, we sought to develop a structured set of pictures of high-calorie foods, which we call the Picture Library of Chinese Foods (PLCF), based on the standardized International Affective Picture System (IAPS) procedure . We desi2]>24 from a Weight Loss Metabolism Clinic in China. All participants (1) were between 18 and 60 years old; (2) could read and understand the description of each item in the questionnaire; and (3) participated in the study voluntarily and agreed to fill out the online questionnaire carefully. We excluded 13 participants due to indicators that their responses may have been low quality, including outlier response times, incorrect answers to forced questions, low ratings in self-reported effort (rating <6), and abnormal responses to basic informational questions  an 48 h) . After qI had such intense cravings for certain foods that I felt like I had to eat them right away.”), measuring the frequency of cravings experiences in life, was chosen as an external criterion to validate the cravings induced by the PLCF.The YFAS 2.0 is a 35-item self-report measure that operationalizes indicators of FA . It contThe Eating Disorder Examination Questionnaire (EDE-Q) is a 28-item self-reported questionnaire designed to assess the range and severity of features associated with a diagnosis of eating disorder (ED) . It cont2We followed a planned missing data design to conduct the image rating session . First, Individuals with overweight or obesity could participate in rating sessions only after they had given informed consent. Participants reported basic demographic information , BMI, and baseline status  on an 11-point Likert scale. Then, they saw standardized rating instructions and were asked to evaluate each food image in terms of familiarity, craving, valence, and arousal from 0  to 10  separately. Finally, they completed the EDE-Q and the YFAS 2.0 to help investigate the relationship between the severity of problematic eating behaviors and the food cravings induced by high-calorie food images. Each rating session was performed consecutively within a single session.3 and jamovi (version 2.2.5).4 We reported continuous variables  as the mean±standard deviation (SD) and reported non-normal variables as the median and range. We first checked for any outlier pictures with any rating dimension exceeding the mean ± 3 SD, which would be removed from further analyses. Then, we conducted reliability and validity analyses to examine the measurement characteristics of the PLCF. Reliability analysis refers to the internal consistency coefficient , with 0.8 < α < 0.9 indicating good consistency and α > 0.9 indicating excellent consistency (I had such intense cravings for certain foods that I felt like I had to eat them right away.”). After confirming that the measurement characteristics of the PLCF were good enough, we further explored the potential influencing factors of cue-induced cravings by repeated-measures analysis of variance (ANOVA) and Pearson correlation analysis. For all analyses, we set the significance level to 0.05, performed post hoc pairwise comparisons for ANOVA using the Tukey correction, and performed multiple comparison corrections for correlation analysis using the False Discovery Rate (FDR) correction sistency . The valrrection .All images survived the outlier check and were therefore included in subsequent analyses. We evaluated the internal consistency with Cronbach’s alpha reliability coefficients and calculated each rating dimension within 20 high-calorie items as 0.949  = ) for familiarity, 0.895  for craving, 0.883  for valence and 0.899  for arousal ratings. All of the dimensions showed good reliability.ps < 0.001; for familiarity, F = 221, partial η2 (η2p) = 0.479; for craving, F = 422, η2p = 0.637; for valence, F = 430, η2p = 0.642; for arousal, F = 114, η2p = 0.322]. The results of the post hoc tests with Tukey corrections showed that the palatable food  images induced substantially greater cravings than the spoiled food images  and craving ratings  between low- and high-calorie foods. However, the valence  and arousal ratings  were significantly higher for high-calorie images than for low-calorie images, supporting that the two types of images are distinguishable. We further examined the criterion validity to verify the distinction between the two types of palatable food images. The Pearson correlation analysis showed that the frequency of craving experiences only correlated with cravings induced by the high-calorie images , not with cravings induced by low-calorie images , and post hoc analysis revealed that both salty foods  and sugary drinks  induced greater cravings than low-calorie food images. The cravings induced by other subtypes of high-calorie images did not significantly differ from those of low-calorie images . These results suggested that the absence of differences between cravings induced by high- and low-calorie food images resulted from the heterogeneity of high-calorie food subtypes.To test the impact of the high-calorie food subtypes on cue-induced cravings, we adopted a one-way repeated-measures ANOVA with five subtypes of high-calorie and low-calorie food images as repeated-measures levels. We summarized the results in p-values in r(213) was  and significant across all subtypes, all pfdr < 0.05] and with FA severity measured by YFAS 2.0 [the range of r (213) was  and significant across all subtypes]. In contrast, there was a weak correlation with the severity of ED symptoms measured by EDE-Q . These results suggested that the high-calorie cravings among individuals with overweight or obesity might also depend on their heterogeneity in eating-related characteristics, especially the severity of FA symptoms.To further explore the relationship between craving ratings and individual characteristics, we performed a Pearson correlation analysis between craving ratings and rater characteristics for all high-calorie food images and the five subtypes. We summarized the significance of all coefficients defined by the FDR corrected T-test with the FA classification as a group variable. We summarized the results in MD = 0.219, SE = 0.260, t(211) = 0.843, p = 0.400]. The craving , valence , and arousal ratings  were all higher in the subgroup that met FA criteria. We repeated the Pearson correlation analysis and only observed a positive correlation between craving ratings and daily craving experiences in the subgroup that met FA criteria . In contrast, no significant correlation was found in the subgroup that did not meet FA criteria , and post hoc analysis revealed that in the subgroup that met FA criteria, the images of salty foods  and sugary drinks  induced greater cravings than the images of low-calorie foods, however, in those who did not meet FA criteria, none of the high-calorie subtypes induced greater cravings than the low-calorie food images .To further examine whether the impact of high-calorie subtypes also arose from the subgroup that met FA criteria, we adopted a two-way repeated-measures ANOVA with food subtype as a within-subject factor  and the FA classification as a between-subject factor. We summarized the results in We attempted to develop and validate a food picture library, the PLCF, that would be more applicable to investigating high-calorie food preferences in populations with overweight or obesity. To achieve this goal, we defined five subtypes of high-calorie foods with reference to the YFAS 2.0 and collected 100 high-resolution food pictures that were later rated by 241 individuals with overweight or obesity. We observed that the greater cravings induced by high-calorie food images  were associated only with certain high-calorie subtypes . Furthermore, we conducted a subgroup analysis of individuals according to whether they did or did not meet FA criteria. We found that the greater cravings induced by certain high-calorie images were driven by the subgroup that met FA criteria.Consistent with our hypothesis that not all high-calorie food cues have the same effect, the greater cravings associated with high-calorie food images  were only present for certain subtypes of food. Salty foods and sugary drinks were the subtypes that evoked greater cravings in our Chinese sample. This result differs from the investigation in a Western cultural context that reported more significant cravings for sugary and fatty foods . More siWe further performed a subgroup analysis to investigate the impact of FA characteristics on the manifestation of food cravings. We found that the associations observed in the whole sample  only appeared in the subgroup that met FA criteria and were not present in the subgroup that did not. These results are consistent with other studies in which individuals who met FA criteria reported significantly greater subjective cravings than those who did not . Our resThese findings are preliminary and should be interpreted carefully with several limitations. First, the food pictures selected for PLCF have non-homogeneous backgrounds without a strict balance of physical parameters, which may distract the raters from the content of the food and affect the ratings. More research is needed to clarify the source of the differences between the subtypes of high-calorie foods observed in this study . Second, the BMI used to define participants as overweight or obese in the current study was converted from the participants’ self-reported height and weight, which may limit further quantitative analysis related to BMI. Third, the rating procedure was not conducted in a laboratory setting; therefore, we did not control the fasting time of the raters, which may have increased the variability of craving ratings. Fourth, the design of the PLCF, which was based on nominations of foods by local participants in a specific Chinese cultural context, may undermine its effectiveness in inducing food cravings in residents of other regions and needs to be expanded to include other regional food items. Finally, our findings mainly depend on subjective reports and could be improved by combining such reports with behavioral or physiological indicators in further studies. In addition, our previous research found that even picture-induced cravings carry the property of dynamic change, and dynamic stimulus materials  can evoke stronger cravings . Therefohttps://osf.io/hy5g8/. The original pictures and associated ratings are publicly available on the Open Science Framework website (https://osf.io/hy5g8/).The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found below: The studies involving human participants were reviewed and approved by the Ethics Committee of Shanghai Sixth People’s Hospital [2020-219-(1)]. The patients/participants provided their written informed consent to participate in this study.H-TC and H-WZ: conceptualization and investigation. H-TC and HZ: data curation, methodology, and formal analysis. J-ZD and X-DH: resources. H-TC: writing—original draft preparation and visualization. H-WZ, HZ, and T-FY: writing—review and editing. T-FY, J-ZD, and X-DH: supervision and project administration. H-WZ and T-FY: funding acquisition. All authors read and final approval of the submitted and published versions.


Despite over two years of COVID-19 worldwide, the outbreak of the Omicron variant has given rise to an unprecedented surge of infection with diverse lockdown measures implemented globally. Whether the emergence of a new wave of COVID-19 could further affect mental health in the population after nearly two years of the pandemic remains to be addressed. Furthermore, whether changes in smartphone overuse behaviours and physical activity – both of which are particularly relevant to young people – would together contribute to changes in distress symptoms during this wave of COVID-19 was also examined.A total of 248 young people from an ongoing household-based epidemiological study in Hong Kong who completed their baseline assessments prior to the Omicron variant outbreak, i.e., fifth wave of COVID-19 (July–November 2021), were invited for a 6-month follow-up study during this wave of infection (January–April 2022) . At both time points, levels of global distress symptoms, perceived stress, smartphone overuse, frequency of engagement in vigorous physical activity, and other potential risk and protective factors were assessed.p < 0.010). Significantly increased levels of smartphone overuse and reduced days of vigorous physical activity were also observed during the fifth wave. Notably, increased smartphone overuse and reduced physical activity both additively and interactively contributed to elevated distress at 6 months, even after accounting for demographic characteristics, psychiatric history, childhood adversity, as well as baseline distress symptoms, resilience, and recent personal stressors.The proportion of young people presenting moderate-to-severe distress  significantly increased from 45.6 to 54.4% during the fifth wave of COVID-19 (The findings suggest that the emergence of a new wave of COVID-19, specifically the Omicron outbreak, can further aggravate mental distress even after a protracted period of the pandemic. Awareness of the dynamic nature of COVID-19 is necessitated to address the pressing mental health needs of populations. Supporting young people in healthier patterns of smartphone use and physical activity can be helpful.The online version contains supplementary material available at 10.1186/s12888-023-04933-3. For over two years, the global society has experienced multiple waves of COVID-19 infections since its initial outbreak with new variants of concern. The Omicron variant, despite its possibly lower case fatality, has raised serious public health concerns owing to its higher transmissibility and lower vaccine efficiency . NotablyStudies across countries have raised concerns over the mental health impacts of COVID-19 on the general population, such as increased levels of depressive and anxiety symptoms, as well as psychological distress –9. Of noBased on observations from earlier studies, the World Health Organization (WHO) has published several reports to consolidate existing findings on the impact of COVID-19 as a guide for further research –14. The Specifically, maintaining regular physical activity and staying connected with others , while minimising the reading of distress-inducing pandemic news, have been raised to be helpful strategies in promoting mental well-being during COVID-19 . Indeed,Notably, several initial studies have reported significant increases both in sedentary behaviours , 26 and changes in distress over time as new waves of infection emerge has seldom been reported. Among the several longitudinal studies available, increased levels of mental distress and psychiatric symptoms have been reported during the early months of COVID-19 [Existing evidence in the literature, however, is mostly cross-sectional, with data collected during the initial outbreak of the pandemic; the investigation of COVID-19 , 29, 30.COVID-19 . InteresCOVID-19 , 32, whiCOVID-19 , 10, 29.Compared to other populations, the COVID-19 situation had generally been well-contained in Hong Kong. This was until the surge of the Omicron variant in December 2021, which resulted in the most severe wave of infection thus far , 34. By Of note, before the advent of COVID-19 in early 2020 in Hong Kong, the population has already experienced months of large-scale social unrest from June 2019, with city-wide protests evolving into police-civilian confrontations involving the use of tear gas, bean bag rounds, and rubber bullets , 42. ArrIn view of gaps in the current literature, we conducted a 6-month longitudinal study to examine changes in psychological distress among young people from an ongoing epidemiological study before and during the fifth wave of COVID-19 and the potential factors that may contribute to such changes. We hypothesised that young people would show significantly increased distress symptoms and perceived stress during this wave of the Omicron outbreak. We also anticipated a significant increase in smartphone overuse behaviours and reduction in days of vigorous physical activity during this period, which may both additively and interactively contribute to the increased levels of distress observed among these young people.Young people between the ages of 15 and 24 were consecutively invited from an ongoing household-based epidemiological study of youth mental health (HK-YES) in Hong Kong. A stratified multistage cluster sampling design was adopted in the larger HK-YES to improve sample representativeness. Specifically, invitation letters were posted to a random selection of addresses obtained from the local government estimated with a residing young person within the age range (stratified by geographic district and housing type). Data were collected through face-to-face interviews by trained researchers in the HK-YES, with the option for online video conferencing following the same procedures during COVID-19. Further details of the HK-YES have been described in our prior works , 48, 49.The current sample had a mean age of 19.7 years (SD = 2.7) and was comprised of 58.9% (n = 146) females. Seven per cent (n = 17) reported having a psychiatric history. The core demographic characteristics of this sample and the Hong Kong population are presented in Supplementary Material Written informed consents were obtained from all participants or from their parents or guardians for those below the age of 18. The study was approved by the Institutional Review Board of the University of Hong Kong/Hospital Authority Hong Kong West Cluster.Apart from participant background information collected as part of the larger HK-YES study , we obtained data including psychiatric history, global distress symptoms, resilience, as well as experience of personal life stressors, at before and during the fifth wave of COVID-19 through self-administered surveys. Examples of items and their reliability indices are included in Supplementary Material Global distress symptoms were assessed using the 6-item Kessler Psychological Distress Scale (K6) . Items wPerceived stress was assessed using the single-item subjective level of stress (SLS-1) , which dSmartphone overuse was assessed using two items adapted from the Revised Chen Internet Addiction Scale (CIAS-R)  to captuVigorous physical activity was assessed using an item from the International Physical Activity Questionnaire , which aResilience was assessed using the 2-item Connor-Davidson Resilience Scale (CD-RISC-2), which includes the items “able to adapt to change” and “tend to bounce back after illness or hardship” adapted from the original 25-item CD-RISC . The twoPersonal stressful life events (SLEs) were assessed using the Life Event Checklist for DSM-V , which cPsychiatric history was determined by asking participants whether they had received any official psychiatric diagnosis. Childhood adversity was assessed using items from the childhood section of the Composite International Diagnostic Interview 3.0 , which cDescriptive statistics at baseline and follow-up were generated for all variables . We first tested whether the proportion of participants with moderate-to-severe distress symptoms (K6 ≥ 5) would increase at follow-up during the COVID-19 surge using the McNemar test. We adopted a K6 threshold of 5 or above which corresponds to moderate-to-severe distress symptom level , 58 , were accounted for as controlled variables. To further determine the implications of smartphone overuse, another set of two-way ANOVA was applied to determine the potential additive and interaction effects of increased p = 0.009). Significant increases in global distress symptoms and perceived stress were also observed during the fifth wave of COVID-19 , both p < 0.01  to 54.4% (n = 135) during the fifth wave  and functional impact of smartphone use (29.4% vs. 25.0%), as well as reduced vigorous physical activity (27.8% vs. 36.7%), were also observed, all In this sample, 15.7% (n = 39) showed increased smartphone overuse , while 21.0% (n = 52) showed reduced vigorous physical activity  during the fifth COVID-19 wave. Descriptive statistics of these K6 distress scores are presented in Supplementary Material F = 14.0, p < 0.001, and reduced vigorous physical activity, F = 5.6, p = 0.019, as well as a significant smartphone overuse X vigorous physical activity interaction effect, F = 5.2, p = 0.024, even after adjusting for demographics, psychiatric history, childhood adversity, baseline distress symptoms, resilience, as well as recent personal SLEs. These additive and interaction effects are illustrated in Fig. Using 6-month distress symptoms as the outcome, we found significant independent main effects of both increased smartphone overuse, F, 237 = 1p < 0.05). Detailed findings are presented in Table S4 of Supplementary Material Similar findings were observed when considering the additive and interaction effects of increased functional impact of smartphone overuse and reduced vigorous physical activity on 6-month distress symptoms  suggested signs of adaption and improved resilience in community members across four waves of COVID-19 from January 2019 to January 2021 . AnotherIn addition, we did not find changes in resilience and the frequency of stressor exposure from before to during the fifth wave of COVID-19 in this sample. One of the reasons may owe to the assessment of resilience as a general trait , which may be less susceptible to change as compared to adaptation in relation to COVID-19 or towards more severe or traumatic events. The two-year period of COVID-19 prior to the Omicron outbreak may also have equipped the population in adapting to the pandemic. Indeed, more recent studies have emphasised resilience not as the absence of psychopathology, but rather a dynamic and context-dependent process influenced by interdependent systems of developmental, neurobiological, psychological, and environmental factors , 79. IdeIn contrast to existing longitudinal and cross-sectional studies conducted during the initial phases of COVID-19, the current study provided evidence to document the mental health impacts of the Omicron outbreak. With the use of a longitudinal design, the current investigation offered insights into whether distress levels could be further exacerbated in the context of protracted periods of population stress. We also examined the potential contribution of smartphone overuse and reduced physical activity – both of which are modifiable and less stigmatising – to elevated distress in young people. The observation that these two factors can potentiate the effect of one another to affect mental health outcomes, even after accounting for a wide range of potential confounding factors, suggested the potential importance of considering their roles in future interventions.change in those meeting the threshold of moderate-to-severe distress and distress severity instead of prevalence data. Due to the need for timely data collection, the use of simple self-administered measures is a common practice for tracking the differences in mental health before and since the outbreak of COVID-19 [Nonetheless, we also acknowledge some limitations in the study. While the K6 is a widely validated measure and has shown to be valid in predicting risk for psychiatric disorders, it cannot replace clinical diagnosis. Our current findings should be taken as a reference for the COVID-19 , 29, 30.In addition, brief measures indeed can be valid measures of specific phenomena and have the benefit of simple administration, which are particularly beneficial when working with young people and in time-limited settings , 80. NonThe present study underlined the need for the continued monitoring of mental health conditions and its related outcomes in the population over time amid large-scale stressors, such as COVID-19 – especially in young people, even when the situation initially appears to be well-contained. The complexity and unpredictability of the situation prevent the absolute knowledge of whether and when a next wave of infection or other public health crises will arrive. Improving future policies based on prior empirical evidence and preparing the population with adequate strategies using timely data to combat mental health challenges for future changes are imperative.Below is the link to the electronic supplementary material.Supplementary Material 1