Precision medicine for pandemics: stratification of COVID-19 molecular phenotypes defined by topological analysis of global blood gene expression. (preprint)

Precision medicine offers a promising avenue for better therapeutic responses to pandemics such as COVID-19. This study leverages independent patient cohorts in Florence and Liege gathered under the umbrella of the DRAGON consortium for the stratification of molecular phenotypes associated with COVID-19 using topological analysis of global blood gene expression. Whole blood from 173 patients was collected and RNA was sequenced on the Novaseq platform. Molecular phenotypes were defined through topological analysis of gene expression relative to the biological network using the TopMD algorithm. The two cohorts from Florence and Liege allowed for independent validation of the findings in this study. Clustering of the topological maps of differential pathway activation revealed three distinct molecular phenotypes of COVID-19 in the Florence patient cohort, which were also observed in the Liege cohort. Cluster 1, was characterised by high activation of pathways associated with ESC pluripotency, NRF2, and TGF-B; receptor signalling. Cluster 2 displayed high activation of pathways including focal adhesion-PI3K-Akt-mTOR signalling and type I interferon induction and signalling, while Cluster 3 exhibited low IRF7-related pathway activation. TopMD was also used with the Drug-Gene Interaction Database (DGIdb), revealing pharmaceutical interventions targeting mechanisms across multiple phenotypes and individuals. The data illustrates the utility of molecular phenotyping from topological analysis of blood gene expression, and holds promise for informing personalised therapeutic strategies not only for COVID-19 but also for Disease X. Its potential transferability across multiple diseases highlights the value in pandemic response efforts, offering insights before large-scale clinical studies are initiated.

Physical activity, low-grade inflammation, and psychological responses to the COVID-19 pandemic among older adults in England (preprint)

Mental health responses to the COVID-19 pandemic have been widely studied, but less is known about the potentially protective role of physical activity (PA) and the impact of low-grade inflammation. Using a sample of older adults from England, this study tested (1) if pre-pandemic PA and its changes during the pandemic were associated with mental health responses; (2) if older adults with low-grade inflammation experienced greater increases in depression and anxiety, compared to pre-pandemic levels; (3) if PA attenuated the association between inflammation and depression/anxiety. The study used data from the English Longitudinal Study of Ageing, a cohort study following a national sample aged 50+. Information on mental health and PA were collected before the pandemic (2016/17 and 2018/19) and during November and December 2020. Inflammation was ascertained using pre-pandemic C-reactive protein (CRP). Analyses were adjusted for sociodemographic and health-related factors and pre-pandemic mental health. Increasing PA from before to during the pandemic was linked to reduced odds of depression (OR = 0.955, 95%CI [0.937, 0.974]) and anxiety (OR = 0.954, 95%CI [0.927; 0.982]). Higher pre-pandemic PA was associated with reduced odds of depression (OR = 0.964, 95%CI [0.948, 0.981]) and anxiety (OR = 0.976, 95%CI [0.953, 1.000]), whereas elevated CRP was associated with 1.343 times higher odds of depression (95%CI [1.100, 1.641]). PA did not attenuate the inflammation-depression association. The findings suggest that PA may contribute to psychological resilience among older adults, independently of inflammation. Further research is needed to explore the psychobiological pathways underlying this protective mechanism.

Precision Phenotyping for Curating Research Cohorts of Patients with Post-Acute Sequelae of COVID-19 (PASC) as a Diagnosis of Exclusion (preprint)

Scalable identification of patients with the post-acute sequelae of COVID-19 (PASC) is challenging due to a lack of reproducible precision phenotyping algorithms and the suboptimal accuracy, demographic biases, and underestimation of the PASC diagnosis code (ICD-10 U09.9). In a retrospective case-control study, we developed a precision phenotyping algorithm for identifying research cohorts of PASC patients, defined as a diagnosis of exclusion. We used longitudinal electronic health records (EHR) data from over 295 thousand patients from 14 hospitals and 20 community health centers in Massachusetts. The algorithm employs an attention mechanism to exclude sequelae that prior conditions can explain. We performed independent chart reviews to tune and validate our precision phenotyping algorithm. Our PASC phenotyping algorithm improves precision and prevalence estimation and reduces bias in identifying Long COVID patients compared to the U09.9 diagnosis code. Our algorithm identified a PASC research cohort of over 24 thousand patients (compared to about 6 thousand when using the U09.9 diagnosis code), with a 79.9 percent precision (compared to 77.8 percent from the U09.9 diagnosis code). Our estimated prevalence of PASC was 22.8 percent, which is close to the national estimates for the region. We also provide an in-depth analysis outlining the clinical attributes, encompassing identified lingering effects by organ, comorbidity profiles, and temporal differences in the risk of PASC. The PASC phenotyping method presented in this study boasts superior precision, accurately gauges the prevalence of PASC without underestimating it, and exhibits less bias in pinpointing Long COVID patients. The PASC cohort derived from our algorithm will serve as a springboard for delving into Long COVID's genetic, metabolomic, and clinical intricacies, surmounting the constraints of recent PASC cohort studies, which were hampered by their limited size and available outcome data.

Exploring the Perspectives of Clients and Clinicians Regarding Digitally Delivered Psychotherapies Utilized for Trauma-Affected Populations. (preprint)

During the COVID-19 pandemic, many clinical sites shifted towards digital delivery of mental health services. However, there is still much to learn regarding tailoring interventions for trauma-affected populations, including military members, Veterans, and public safety personnel. This study examined perceptions of psychotherapies utilized for trauma-affected populations, as reported by Canadian military members, Veterans, and public safety personnel who completed such interventions and mental health clinicians who provided them. Specifically, we explored the shift to digital health use, what changed with this rapid shift, what needs, problems, and solutions arose, and important future considerations associated with delivering trauma-focused and adjunct treatments digitally.   Quantitative survey data were collected from 11 Canadian patients (military members, Veterans, and public safety personnel with post-traumatic stress injury) and 12 Canadian mental health clinicians. Survey questions were adapted from the Alberta Quality Matrix for Health (AQMH) and Unified Theory of Acceptance and Use of Technology (UTAUT) model. As a follow-up, participants were invited to participate in either a semi-structured qualitative interview or focus group to further explore their perspectives on digitally delivered trauma-focused and adjunct therapies. Four clients and 19 clinician participants participated in an interview or focus group.   In survey and interview/focus group results, patient and clinician participants reported that digitally delivered trauma and adjunct therapies offered similar treatment effectiveness as in-person delivery while also improving treatment access. Participants indicated unique advantages of digital delivery, including the increased accessibility of treatment, cost effectiveness, and more efficient use of resources. However, some participants struggled with using digital platforms and felt less comfortable working in a digital environment. Further research with a larger, more diverse population is required to corroborate our results and identify other avenues in which psychotherapies utilized for trauma-affected populations can be engaged with and improved upon.

Effectiveness of the 2023-2024 Omicron XBB.1.5-containing mRNA COVID-19 vaccine (mRNA-1273.815) in preventing COVID-19-related hospitalizations and medical encounters among adults in the United States: An interim analysis (preprint)

Background/ObjectivesCOVID-19 continues to pose a significant burden that impacts public health and the healthcare system as the SARS-CoV-2 virus continues to evolve. Regularly updated vaccines are anticipated to boost waning immunity and provide protection against circulating variants. This study evaluated vaccine effectiveness (VE) of mRNA-1273.815, a 2023-2024 Omicron XBB.1.5-containing mRNA COVID-19 vaccine, at preventing COVID-19-related hospitalizations and any medically attended COVID-19 in adults [≥]18 years, overall, and by age and underlying medical conditions. MethodsThis retrospective cohort study used the Veradigm Network EHR linked to claims data to identify US adults [≥]18 years of age who received the mRNA-1273.815 vaccine (exposed) matched 1:1 to individuals who did not receive a 2023-2024 updated COVID-19 vaccine (unexposed). Patients in the unexposed cohort were randomly matched to eligible mRNA-1273.815 recipients. Inverse probability of treatment weighting was used to adjust for differences between the two cohorts. The exposed cohort was vaccinated between September 12, 2023, and December 15, 2023, and individuals in both cohorts were followed up for COVID-19-related hospitalizations and medically attended COVID-19 until December 31, 2023. A Cox regression model was used to estimate the hazard ratio (HR). VE of the mRNA-1273.815 vaccine in preventing COVID-19-related hospitalizations and any medically attended COVID-19 was estimated as 100*(1-HR). Subgroup analyses were performed for adults [≥]50, adults [≥]65, and individuals with underlying medical conditions associated with severe COVID-19 outcomes. ResultsOverall, 859,335 matched pairs of mRNA-1273.815 recipients and unexposed adults were identified. The mean age was 63 years, and 80% of the study population was [≥]50 years old. 61.5% of the mRNA-1273.815 cohort and 66.4% of the unexposed cohort had an underlying medical condition. Among the overall adult population ([≥]18 years), VE was 60.2% (53.4-66.0%) against COVID-19-related hospitalization and 33.1% (30.2%-35.9%) against medically attended COVID-19 over a median follow-up of 63 (IQR: 44-78) days. VE estimates by age and underlying medical conditions were similar. ConclusionsThese results demonstrate the significant protection provided by mRNA-1273.815 against COVID-19-related hospitalizations and any medically attended COVID-19 in adults 18 years and older, regardless of their vaccination history, and support CDC recommendations for vaccination with the 2023-2024 Omicron XBB.1.5-containing COVID-19 vaccine to prevent COVID-19-related outcomes, including hospitalizations.

Incidence and Risk of Post-COVID-19 Thromboembolic Disease and the Impact of Aspirin Prescription; Nationwide Observational Cohort at the US Department of Veteran Affairs. (preprint)

IntroductionCOVID-19 triggers prothrombotic and proinflammatory changes, with thrombotic disease prevalent in up to 30% SARS-CoV-2 infected patients. Early work suggests that aspirin could prevent COVID-19 related thromboembolic disorders in some studies but not others. This study leverages data from the largest integrated healthcare system in the United States to better understand this association. Our objective was to evaluate the incidence and risk of COVID-19 associated acute thromboembolic disorders and the potential impact of aspirin. MethodsThis retrospective, observational study utilized national electronic health record data from the Veterans Health Administration. 334,374 Veterans who tested positive for COVID-19 from March 2, 2020, to June 13, 2022, were included, 81,830 of whom had preexisting aspirin prescription prior to their COVID-19 diagnosis. Patients with and without aspirin prescriptions were matched and the odds of post-COVID acute thromboembolic disorders were assessed. Results10.1% of Veterans had a documented thromboembolic disorder within 12 months following their COVID-19 diagnosis. Those with specific comorbidities were at greatest risk. Preexisting aspirin prescription was associated with a significant decrease risk of post-COVID-19 thromboembolic disorders, including pulmonary embolism (OR [95% CI]: 0.69 [0.65, 0.74]) and deep vein thrombosis (OR [95% CI]: 0.76 [0.69, 0.83], but an increased risk of acute arterial diseases, including ischemic stroke (OR [95% CI]: 1.54 [1.46, 1.60]) and acute ischemic heart disease (1.33 [1.26, 1.39]). ConclusionsFindings demonstrated that preexisting aspirin prescription prior to COVID-19 diagnosis was associated with significantly decreased risk of venous thromboembolism and pulmonary embolism but increased risk of acute arterial disease. The risk of arterial disease may be associated with increased COVID-19 prothrombotic effects superimposed on preexisting chronic cardiovascular disease for which aspirin was already prescribed. Prospective clinical trials may help to further assess the efficacy of aspirin use prior to COVID-19 diagnosis for the prevention of post-COVID-19 thromboembolic disorders.

Timing and Depth Selection for Sedated Gastroscopy After SARS-CoV-2 Infection—A Retrospective Cohort Study (preprint)

Background Sedated gastroscopy is a crucial procedure for patients with upper respiratory infections. SARS-CoV-2-infected patients are more susceptible to anesthesia-related complications, such as edema, pharyngeal mucosa congestion, laryngospasm, and pulmonary infections.Methods We retrospectively analyzed a total of 386 patients who underwent sedated gastroscopy at the Affiliated Hospital of Qingdao University during the SARS-CoV-2 infection period. The patients were divided into three groups based on SARS-CoV-2 status: Negative (N), Two-week post-SARS-CoV-2 infection (T), and Three-week post-SARS-CoV-2 infection (Th) groups. Based on the anesthesia method, patients were divided into mild/moderate sedation and deep sedation/general anesthesia groups. Additionally, patients were categorized into groups based on COVID-19 severity and vaccination status. We recorded the laryngeal mucosal conditions, the occurrence rates of adverse reactions such as coughing, laryngospasm, and transient oxygen desaturation during the examination, as well as the satisfaction of patients and endoscopists were recorded.Results The T group displayed a significantly higher occurrence rate of adverse reactions when compared to the N and Th group, with decreased satisfaction levels of patients and endoscopists. In the T group, the occurrence rate of adverse reactions was higher in mild to moderate sedation than in deep sedation/general anesthesia methods, while patient and endoscopist satisfaction was lower. In the Th group, there was no statistically significant difference in the examination success rate or patient satisfaction between the mild/moderate sedation and deep sedation/general anesthesia methods; however, endoscopist satisfaction was lower with mild/moderate sedation method than deep sedation/general anesthesia method. There was a significant difference in the gastroscopy success rates of patients with different COVID-19 classifications. A significant difference was observed in the gastroscopy success rates among patients with different vaccination statuses.Conclusions Sedated gastroscopy post-three weeks of SARS-CoV-2 infection is safe. Moreover, using a deep sedation/general anesthesia method for sedated gastroscopy in SARS-CoV-2-infected patients within three weeks is significantly safer.

Enhancing EQ-5D-5L sensitivity in capturing the most common symptoms in post COVID-19 patients: an exploratory cross-sectional study with focus on fatigue, memory/concentration problems and dyspnea dimensions (preprint)

This study aimed to determine whether the EQ-5D-5L tool captures the most common persistent symptoms, such as fatigue, memory/concentration problems and dyspnea in patients with post COVID-19 conditions, and if adding these symptoms improves the explained variance of the health-related quality of life (HRQoL). In this exploratory cross-sectional study, two cohorts of Swedish patients (n=177) with a history of COVID-19 infection answeared a questionnaire covering sociodemographic characteristics, clinical factors and HRQoL assessed using EQ-5D-5L with the Visual Analogue Scale (EQ-VAS). Spearman rank correlation and multiple regression analyses were employed to investigate the extent to which the most common persistent symptoms such as fatigue, memory/concentration problems and dyspnea were explained by the EQ-5D-5L. The explanatory power of EQ-5D-5L for EQ-VAS was also analysed, both with and without inclusion of symptom(s). We found that the EQ-5D-5L dimensions partly captured fatigue and memory/concentration problems but performed poorly in capturing dyspnea. Specifically, the EQ-5D-5L explained 55% of the variance in memory/concentration problems, 47% in fatigue and only 14% in dyspnea. Adding fatigue to the EQ-5D-5L increased the explained variance of the EQ-VAS by 5.7%, while the addition of memory/concentration problems and dyspnea had a comparatively smaller impact on the explained variance. Our study highlights the EQ-5D-5L’s strength in capturing fatigue and memory/concentration problems in post COVID-19 patients. However, it also underscores the challenges in assessing dyspnea in this group. Fatigue emerged as a notably influential symptom, significantly enhancing the EQ-5D-5L's predictive ability to for the EQ-VAS score in these patients.

Systems vaccinology identifies clinical and immunological correlates of SARS-CoV-2 vaccine response in solid-organ transplant recipients (preprint)

Solid organ transplant (SOT) recipients are at enhanced risk of adverse outcomes following infectious challenges due to immunosuppressive treatment and additional comorbidities. Unfortunately, SOT recipients are also poor responders to the key medical intervention to preventing infection: vaccines. Here we performed a systems vaccinology study on a cohort of 59 kidney transplant recipients and 31 lung transplant recipients who received the mRNA Pfizer-BioNTech COVID-19 vaccine. Analyzing the immunological status of the patients prior to vaccination, we were able to identify multiple immunological associates of relatively improved vaccine responses following two or three doses of mRNA-based SARS-CoV-2 vaccine. These immunological associates predicted, with 95.0% and 93.3% accuracy, vaccine response after the second and third dose, respectively. Comparison of the immunological associates with vaccine response in SOT recipients revealed two distinct immune configurations: a non-classical configuration, distinct from the immune state of healthy subjects, associated with responses to two doses of mRNA vaccine and that could be mediated partly by the presence of double negative B cell subsets which are more prominently represented in responsive SOT recipients, and a "normalized" configuration, closer to the immune state of healthy subjects, associated with potent antibody responses to three doses of mRNA vaccine. These results suggest that immunosuppression in SOT recipients can result in distinct immune states associated with different trade-offs in vaccine responsiveness. Immune phenotyping of SOT recipients for immune constellation may be an effective approach for identifying patients most at risk of poor vaccine responses and susceptibility to vaccine-preventable diseases. One-sentence summarySOT recipients showed distinct immune states at baseline associated with different profiles of vaccine-associated immune response.

A Suicide Attempt Multicomponent Intervention Treatment (SAMIT Program): Study Protocol for a Multicentric Randomised Controlled Trial (preprint)

Background: Suicide has become a first-order public health concern, especially following the negative impact of COVID-19 on the mental health of the general population. Few studies have analyzed the effects of early psychotherapeutic interventions on subjects who have attempted suicide, and even fewer have focused on those hospitalized in non-psychiatric units after a medically serious suicide attempt (MSSA). The main aim of this study is to describe the protocol designed to evaluate the effectiveness of individual psychological treatment for patients hospitalized after an MSSA. The secondary objectives of the study are: 1) to evaluate the impact on quality of life and other psychosocial variables of patients with a recent MSSA who receive early psychological intervention; 2) to analyze the biological, psychological, and clinical impact of early psychotherapeutic treatment on subjects hospitalized after an MSSA. Methods: An experimental, controlled, and randomized trial will be conducted with patients over 16 years of age admitted to two general hospitals. The case intervention group will enroll for 8-sessions of individual psychotherapy, Suicide Attempts Multi-component Intervention Treatment (SAMIT), combining Dialectical Behaviour Therapy (DBT), Mentalization-Based Therapy (MBT), and Narrative approaches, while the control group will receive a treatment-as-usual intervention (TAU). Longitudinal assessment will be conducted at baseline (before treatment), post-treatment, and 3, 6, and 12 months after. The main outcome variable will be re-attempting suicide during follow-up. Discussion: Some psychotherapeutic interventions, usually implemented in outpatient, have proven to be effective in preventing suicidal behaviours. The combination of some of these may be a powerful treatment for preventing future SA in patients hospitalised after an MSSA, which is the most severely suicidal subgroup. Moreover, assessment of the biological, clinical and psychometric impact of this new intervention on patients during the first year after the attempt may help understand some of the multi-level factors associated with the effectiveness of psychotherapeutic interventions in MSSAs. The prevalence of high suicide rates requires the design of effective psychological interventions for their prevention, and also in order to design new pharmacological and psychological treatments.

Incidence and risk factors of omicron variant SARS-CoV-2 breakthrough infection among vaccinated and boosted individuals. (preprint)

Background: SARS-CoV-2 vaccines have been shown to be safe and effective against infection and severe COVID-19 disease worldwide. Certain co-morbid conditions cause immune dysfunction and may reduce immune response to vaccination. In contrast, those with co-morbidities may practice infection prevention strategies. Thus, the real-world clinical impact of co-morbidities on SARS-CoV-2 infection in the recent post-vaccination period is not well established. We performed this study to understand the epidemiology of Omicron breakthrough infection and evaluate associations with number of comorbidities in a vaccinated and boosted population. Methods and Findings: We performed a retrospective clinical cohort study utilizing the Northwestern Medicine Enterprise Data Warehouse. Our study population was identified as fully vaccinated adults with at least one booster. The primary risk factor of interest was the number of co-morbidities. Our primary outcome was incidence and time to first positive SARS-CoV-2 molecular test in the Omicron predominant era. We performed multivariable analyses stratified by calendar time using Cox modeling to determine hazard of SARS-CoV-2. In total, 133,191 patients were analyzed. Having 3+ comorbidities was associated with increased hazard for breakthrough (HR=1.2 CI 1.2-1.6). During the second half of the study, having 2 comorbidities (HR= 1.1 95% CI 1.02-1.2) and having 3+ comorbidities (HR 1.7, 95% CI 1.5-1.9) were associated with increased hazard for Omicron breakthrough. Older age was associated with decreased hazard in the first 6 months of follow-up. Interaction terms for calendar time indicated significant changes in hazard for many factors between the first and second halves of the follow-up period. Conclusions: Omicron breakthrough is common with significantly higher risk for our most vulnerable patients with multiple co-morbidities. Age related behavioral factors play an important role in breakthrough infection with the highest incidence among young adults. Our findings reflect real-world differences in immunity and exposure risk behaviors for populations vulnerable to COVID-19.

Increased fibrinaloid microclot counts in platelet-poor plasma are associated with Long COVID (preprint)

Outcomes following SARS-CoV-2 infection are variable; whilst the majority of patients recover without serious complications, a subset of patients develop prolonged illness termed Long COVID or post-acute sequelae of SARS-CoV-2 infection (PASC). The pathophysiology underlying Long COVID remains unclear but appears to involve multiple mechanisms including persistent inflammation, coagulopathy, autoimmunity, and organ damage. Studies suggest that microclots, also known as fibrinaloids, play a role in Long COVID. In this context, we developed a method to quantify microclots and investigated the relationship between microclot counts and Long COVID. We show that as a cohort, platelet-poor plasma from Long COVID samples had a higher microclot count compared to control groups but retained a wide distribution of counts. Recent COVID-19 infections were also seen to be associated with microclot counts higher than the control groups and equivalent to the Long COVID cohort, with a subsequent time-dependent reduction of counts. Our findings suggest that microclots could be a potential biomarker of disease and/or a treatment target in some Long COVID patients.

Pre-pandemic Predictivity of Anxious-Depressive Symptoms in Post-surgical Traumatic Distress in Hysterectomy for Benign Disease and COVID-19 Outbreak: A Case-Control Study (preprint)

The Sars-Cov-2 pandemic led to several needed containing measures that conditioned the onset of depressive, anxiety and post-traumatic stress symptoms in population. These symptoms, espe-cially if not diagnosed and treated, can also occur in patients undergoing surgery with high im-pact on people’s lives, like hysterectomy. To evaluate the post-surgical distress and anx-ious-depressive symptoms following hysterectomy for benign disease focusing on the impact of COVID-19 pandemic. The prospective observational cohort study included patients undergoing hysterectomy for benign disease. Psychologic evaluation through social-demographic question-naires was obtained before surgery (T1), postoperatively (T2), and 3 months after surgery (T3). The HADS (Hospital Anxiety and Depression Scale) was used to evaluate anxious-depressive symptoms and the PCL-5 (Post-traumatic Stress Disorder Checklist for DSM-5) compared the on-set of post-surgical distress and anxiety and depressive symptoms. The pre-COVID-19 pan-demic period was compared to the post-COVID-19 pandemic phase. Patients treated after COVID-19 pandemic showed higher depressive symptoms rate compared to those treated before (p-value=0.02); conversely, pre-COVID-19 patients were more prone to develop a PTSD (p-value=0.04). A significative association between the occurrence PTSD and anxiety-depressive symptoms registered at T2 a (p-value=0.007) and T3 (p-value

Molecular epidemiology of invasive Group A Streptococcal infections before and after the COVID-19 pandemic in Switzerland (preprint)

Group A Streptococcus (GAS, aka Streptococcus pyogenes) poses a significant public health concern, causing a diverse spectrum of infections with high mortality rates. Following the COVID-19 pandemic, a resurgence of invasive GAS (iGAS) infections has been documented, necessitating efficient outbreak detection methods. Whole genome sequencing (WGS) serves as the gold standard for GAS molecular typing, albeit constrained by time and costs. This study aimed to characterize the postpandemic increased prevalence of iGAS on the molecular epidemiological level in order to assess whether new, more virulent variants have emerged, as well as to assess the performance of the rapid and cost-effective Fourier-transform infrared (FTIR) spectroscopy as an alternative to WGS for detecting and characterizing GAS transmission routes. A total of 66 iGAS strains isolated from nine Swiss hospitals during the COVID-19 post-pandemic increased GAS prevalence were evaluated and compared to 15 strains collected before and 12 during the COVID-19 pandemic. FT-IR measurements and WGS were conducted for network analysis. Demographic, clinical, and epidemiological data were collected. Skin and soft tissue infection was the most common diagnosis, followed by primary bacteremia and pneumonia. Viral co-infections were found in 25% of cases and were significantly associated with more severe disease requiring intensive care unit admission. WGS analysis did not reveal emerging GAS genetic distinct variants after the COVID-19 pandemic, indicating the absence of a pandemic-induced shift. FT-IR spectroscopy exhibited limitations in differentiating genetically distant GAS strains, yielding poor overlap with WGS-derived clusters. The emm1/ST28 gebotype was predominant in our cohort and was associated with five of the seven deaths recorded, in accordance with the molecular epidemiological data before the pandemic. Additionally, no notable shift in antibiotic susceptibility patterns was observed. Our data suggest that mainly non-pathogen related factors contributed to the recent increased prevalence of iGAS.

Life changes and mental health among Chinese children and adolescents during the pandemic: a combination of cross-sectional, longitudinal and clustering studies (preprint)

The measures to prevent COVID-19 pandemic had caused significant life changes, which could be distressing for mental health among children and adolescents. We aimed to evaluate the short- and long-term effects of life changes on children’s mental health in a large Chinese cohort. Survey-based life changes during COVID-19 lockdown were measured among 7,829 Chinese students at Grade 1–9, including social contacts, lifestyles and family financial status. Clustering analysis was applied to identify potential patterns of these changes. Depressive and anxiety symptoms were measured using the Center for Epidemiologic Studies Depression Scale and Screen for Child Anxiety Related Emotional Disorders. Logistic regression models were used to investigate the associations between these changes, their patterns and the presence of depression/anxiety symptoms using both cross-sectional and longitudinal designs. We found that the prevalence of depression and anxiety symptoms decreased during pandemic (34.6–32.6%). However, during and shortly after lockdown, students who reported negative impacts on their study, social and outside activities and diet, and decreased electronic time and sugar-sweetened consumption, as well as family income decline and unemployment had increased risks of depressive/anxiety symptoms, and students with changed sleep time had increased depressive symptoms. These associations attenuated or disappeared one year later. Similar patterns were observed in clustering analysis, while only the group with severe impact on family financial status showed a sustained increase in depression symptoms. In summary, restrictive measures that changed children and adolescents’ daily life during COVID-19 lockdown showed negative effects on their mental health, with some commonalities and distinctions patterns in the manifestation of depression and anxiety symptoms.

Evaluation and limitations of the novel chemiluminescent enzyme immunoassay technique for measuring total tau protein in the cerebrospinal fluid in patients with human prion disease: a 10-year prospective study (2011–2020) (preprint)

Background: Recently, the investigation of cerebrospinal fluid (CSF) biomarkers for diagnosing human prion diseases (HPD) has garnered significant attention. Reproducibility and accuracy are paramount in biomarker research, particularly in the measurement of total tau (t-tau) protein, which is a crucial diagnostic marker. Given the global impact of the coronavirus disease pandemic, the frequency of measuring this protein using one of the world's fully automated assays, chemiluminescent enzyme immunoassay (CLEA), has increased. At present, the diagnosis and monitoring of neurological diseases mainly rely on traditional methods, but their accuracy and responsiveness are limited.there is a limited knowledge on the accuracy of CLEA in Tau measurements. We aimed to measure t-tau protein using CLEA and to elucidate its merits and limitations. Methods: We analysed CSF samples obtained from 91 patients with rapidly progressive dementia using ELISA and CLEA. Additionally, we used western blotting to detect the presence of 14-3-3 protein and employed real-time quaking-induced conversion (RT-QuIC) assays to analyse the same set of samples. Furthermore, we examined the correlation coefficient between ELISA and CLEA results in a subset of 30 samples. Moreover, using CLEA, we evaluated the diurnal reproducibility, storage stability, dilutability, and freeze-thaw effects in three selected samples. Results:Among the 91 patients, a total of 45 (22 men and 23 women) tested positive for HPD in the RT-QuIC assay. In contrast, all CSF samples from the remaining 46 patients without HPD (23 men and 23 women) tested negative in the RT-QuIC assay. Both ELISA and CLEA showed perfect sensitivity and specificity (100%) in measuring t-tau protein levels. Furthermore, there was a strong correlation coefficient (R² = 0.9363) between ELISA and CLEA results. However, despite its advantages, CLEA analysis exhibited instability for certain samples with t-tau protein levels exceeding 2,000 pg/mL, leading to low reproducibility during dilution analysis. Conclusions: Our findings indicate that CLEA outperforms ELISA in terms of diurnal reproducibility, storage stability, and freeze-thaw effects. However, ELISA demonstrated superior performance in the dilution assay. Therefore, it is imperative to develop innovative approaches for the dilution of biomarker samples for CLEA measurements during clinical trials.