Perceptions of COVID-19 Vaccination among Organ Transplant Recipients (preprint)

Understanding vaccine hesitancy in organ transplant recipients (OTR) is critical, given clear, alt-hough attenuated, benefits from vaccination. Adult OTR were surveyed regarding vaccine-related values and a novel outcome variable called Vaccine Acceptance Composite Score (VACS) was built as the average Likert score of 7 domains of vaccination confidence. Of 46 OTR included (93.5% kidney transplant recipients), 32.6% were female, 13.3% Black, 6.77% Hispan-ic/Latino/a/x; median age was 58 years. Patients were most concerned about COVID-19 vac-cine-associated risks (46.3%), its potential effect on allograft (47.6%) and motives of government officials involved with vaccine policy (55.6%). Politically conservative patients were likely to have a significantly lower VACS, while those who lived with someone ≥65 had a higher VACS. The VACS was not significantly associated with race, income, religious beliefs, comorbidities, COVID-19 history, or influenza vaccination status. Higher VACS was significantly associated with ≥3 and ≥4 COVID-19 immunizations. This study highlighted political beliefs and elderly household members as correlates of vaccine acceptance among OTR. The VACS may be a useful tool to help standardize multifaceted analyses in vaccination-focused behavioral research, as well as identify individuals and groups at risk for vaccine hesitancy, who may benefit from tai-lored outreach and educational interventions.

Exploring the Spatial Distribution of Persistent SARS-CoV-2 Mutations - Leveraging mobility data for targeted sampling (preprint)

Given the rapid cross-country spread of SARS-CoV-2 and the resulting difficulty in tracking lineage spread, we investigated the potential of combining mobile service data and fine-granular metadata (such as postal codes and genomic data) to advance integrated genomic surveillance of the pandemic in the federal state of Thuringia, Germany. We sequenced over 6,500 SARS-CoV-2 Alpha genomes (B.1.1.7) across seven months within Thuringia while collecting patients' isolation dates and postal codes. Our dataset is complemented by over 66,000 publicly available German Alpha genomes and mobile service data for Thuringia. We identified the existence and spread of nine persistent mutation variants within the Alpha lineage, seven of which formed separate phylogenetic clusters with different spreading patterns in Thuringia. The remaining two are sub-clusters. Mobile service data can indicate these clusters' spread and highlight a potential sampling bias, especially of low-prevalence variants. Thereby, mobile service data can be used either retrospectively to assess surveillance coverage and efficiency from already collected data or to actively guide part of a surveillance sampling process to districts where these variants are expected to emerge. The latter concept proved successful as we introduced a mobility-guided sampling strategy for the surveillance of Omicron sublineage BQ.1.1. The combination of mobile service data and SARS-CoV-2 surveillance by genome sequencing is a valuable tool for more targeted and responsive surveillance.

A Critical Analysis of UK Media Characterisations of Long Covid in Children and Young People (preprint)

Long Covid is the continuation or development of symptoms related to a SARSCoV2 infection. Those with Long Covid may face epistemic injustice, where they are unjustifiably viewed as unreliable evaluators of their own illness experiences. Media articles both reflect and influence perception and subsequently how people regard children and young people (CYP) with Long Covid, and may contribute to epistemic injustice.? We aimed to explore how the UK media characterises Long Covid in CYP through examining three key actor groups: parents, healthcare professionals, and CYP with Long Covid, through the lens of epistemic injustice. A systematic search strategy resulted in the inclusion of 103 UK media articles. We used an adapted corpus-assisted Critical Discourse Analysis in tandem with thematic analysis. Specifically, we utilised search terms to locate concordances of key actor groups. In the corpus, parents highlighted minimisation of Long Covid, barriers to care, and experiences of personal attacks. Mothers were presented as also having Long Covid. Fathers were not mentioned once. Healthcare professionals emphasised the rarity of Long Covid in CYP, avoided pathologizing Long Covid, and overemphasised psychological components. CYP rarely were consulted in media articles but were presented as formerly very able. Manifestations of Long Covid in CYP were validated or invalidated in relation to adults. Media characterisations contributed to epistemic injustice. The disempowering portrayal of parents promote stigma and barriers to care. Healthcare professionals' narratives often contributed to negative healthcare experiences and enacted testimonial injustice, where CYP and parents credibility was diminished due to unfair identity prejudice, in their invalidation of Long Covid. Media characterisations reveal and maintain a lack of societal framework for understanding Long Covid in CYP. The findings of this study illustrate the discursive practices employed by journalists that contribute to experiences of epistemic injustice. Based on our findings, we propose recommendations for journalists.

Effects of the Covid-19 pandemic on the continuity of sexual and reproductive health care in the maternity ward of a health and social promotion centre in Burkina Faso: a qualitative study (preprint)

The COVID-19 pandemic has significantly impacted the continuity of maternity care in Burkina Faso. This study aimed to compare the volumes of in-person visits and explore the experiences of healthcare providers and users regarding the continuity of healthcare in the maternity ward of a Health and Social Promotion Center (HSPC) before, during, and after the lockdown during the COVID-19 pandemic in Ouagadougou, Burkina Faso. Methods We conducted a multimethod, cross-sectional exploratory study with a phenomenological approach. Monthly health administrative data regarding family planning visits, antenatal visits, deliveries, and postnatal care before, during, and after COVID-19 were collected and compared. Qualitative data were collected through semi-structured interviews with family healthcare providers and users and thematically analyzed. Results The study found that the pandemic led to a decline in the demand for healthcare, as people were afraid of contracting COVID-19. This was particularly true for pregnant women who had recently given birth. The study also found that the pandemic disrupted the supply of essential medicines and medical supplies, which made it difficult for healthcare providers to provide quality care. The qualitative analysis allowed us to highlight three themes: the representation of respondents on COVID-19, their perception of the effectiveness of barrier measures and their analysis of the continuity of care in times of COVID-19: the picture of respondents on COVID-19, their perception of the efficacy of barrier measures and their analysis of the continuity of care in times of COVID-19. Despite these challenges, the study found that healthcare providers and users could find ways to maintain continuity of care. Conclusion The study concludes that the COVID-19 pandemic has significantly impacted the continuity of maternity care in Burkina Faso. However, healthcare providers and users have found ways to maintain continuity of care, and the study provides recommendations for improving continuity of care in the future.

A spatio-temporal model to detect potential outliers in disease mapping (preprint)

Spatio-temporal disease mapping models are commonly used to estimate the relative risk of a disease over time and across areas. For each area and time point, the disease count is modelled with a Poisson distribution whose mean is the product of an offset and the disease relative risk. This relative risk is commonly decomposed in the log scale as the sum of fixed and latent effects. The Rushworth model allows for spatio-temporal autocorrelation of the random effects. We build on the Rushworth model to accommodate and identify potentially outlying areas with respect to their disease relative risk evolution, after taking into account the fixed effects. An area may display outlying behaviour at some points in time but not all. At each time point, we assume the latent effects to be spatially structured and include scaling parameters in the precision matrix, to allow for heavy-tails. Two prior specifications are considered for the scaling parameters: one where they are independent across space and one with spatial autocorrelation. We investigate the performance of the different prior specifications of the proposed model through simulation studies and analyse the weekly evolution of the number of COVID-19 cases across the 33 boroughs of Montreal and the 96 French departments during the second wave. In Montreal, 6 boroughs are found to be potentially outlying. In France, the model with spatially structured scaling parameters identified 21 departments as potential outliers. We find that these departments tend to be close to each other and within common French regions.

Completeness of the COVID-19 Vaccination Schedule among Persons Experiencing Homelessness in Brazil (preprint)

Almost four years after COVID-19 was declared a global health emergency, equitable distribution of the vaccine remains a challenge, especially among homeless people, the fastest growing population in Brazil. Therefore, we sought to identify the factors associated with completion of the COVID-19 vaccination schedule among homeless people in Brazil. Materials and Methods: We carried out a cross-sectional study in the capital cities of Brazil's Federative Units, considering people living on the streets as the target population. We used a sequential inclusion approach, with individual interviews conducted by trained professionals, using a validated questionnaire. We used descriptive statistics to analyze the data and a binary logistic regression model to identify factors associated with homeless individuals who completed the COVID-19 vaccination schedule. Results: It was identified that the highest density of homeless people and indicators related to COVID-19 is located in the Northeast, Southeast and South regions of Brazil. The primary data sample consisted of 1,392 participants, predominantly male (n: 961; 69.0%), with an average age of 38.3±15.2 years, belonging to the black/brown race/color (n: 1,097; 78.8%), with an elementary school education (n: 1,060; 76.1%). The factors associated with completing the vaccination schedule were: receiving government aid (OR: 1.58; 95%CI: 1.09 - 2.30), visits from Health Agents from the Street Clinic (OR: 3.19; 95%CI: 1.95 - 5.36), history of COVID-19 (OR: 5.77; 95%CI: 3.17 - 11.15), support for mandatory vaccination against COVID-19 (OR: 3.76; 95%CI: 2.48 - 5.76), trust in the efficacy of vaccines (OR: 3.92; 95%CI: 2.63 - 5.89), seeking information from NGOs, street clinics, community leaders (OR: 1.91; 95%CI: 1.01 - 3.88) and trust in the Federal Government's statements on vaccines (OR: 1.57; 95%CI: 1.06 - 2.31).Conclusion: The study advances knowledge by highlighting the completeness of the COVID-19 vaccination schedule among the homeless population. The source of information proved to be one of the determinants of completeness, and the Unified Health System played a leading role in raising awareness among homeless people, notably through its strategy of street clinics, when available. The evidence points to the importance of affirmative and inclusive actions that guarantee access to the vaccine for homeless people.

Psychosocial Predictors of Sleep Disturbances during COVID-19: differential contributions of demographic, psychological, pandemic-related factors to sleep health. (preprint)

Aim: Since the declaration of COVID-19 as a Public Health Emergency of International Concern on January 30, 2020, the disease escalated into a global pandemic forcing governments around the world to impose measures that affected all aspects of life. Among other countries, Greece adopted social restriction, lockdowns, and quarantines to reduce transmission from person to person.  Subjects and Methods: This cross-sectional study aimed to investigate the impact of those measures on sleep health in a Greek adult sample. An online questionnaire collected data during from 650 participant.  Results: 60% of responders scored below the clinical cut-off on the RU-SATED, indicating they experienced poor sleep health. Better sleep health was reported with increased age and years of education. On the other hand, higher trauma-related distress, depression, anxiety and stress symptomatology were related to poorer sleep health. No gender differences were observed, and degree of compliance to pandemic restrictions did not influence sleep health. Hierarchical regression analysis indicated difficulty in securing enough/healthy food, testing positive for COVID-19, experiencing an increase in verbal arguments/conflicts at home and an increase in responsibilities were the strongest predictors of poor sleep heath.  Conclusions: Results highlight the importance of maintaining good sleep health as a pillar of general physical and mental health.

Cardiovascular symptoms of PASC are associated with trace-level cytokines that affect the function of human pluripotent stem cell derived cardiomyocytes (preprint)

Globally, over 65 million individuals are estimated to suffer from post-acute sequelae of COVID-19 (PASC). A large number of individuals living with PASC experience cardiovascular symptoms (i.e. chest pain and heart palpitations) (PASC-CVS). The role of chronic inflammation in these symptoms, in particular in individuals with symptoms persisting for >1 year after SARS-CoV-2 infection, remains to be clearly defined. In this cross-sectional study, blood samples were obtained from three different sites in Australia from individuals with i) a resolved SARS-CoV-2 infection (and no persistent symptoms i.e. Recovered), ii) individuals with prolonged PASC-CVS and iii) SARS-CoV-2 negative individuals. Individuals with PASC-CVS, relative to Recovered individuals, had a blood transcriptomic signature associated with inflammation. This was accompanied by elevated levels of pro-inflammatory cytokines (IL-12, IL-1beta;, MCP-1 and IL-6) at approximately 18 months post-infection. These cytokines were present in trace amounts, such that they could only be detected with the use of novel nanotechnology. Importantly, these trace-level cytokines had a direct effect on the functionality of pluripotent stem cell derived cardiomyocytes in vitro. This effect was not observed in the presence of dexamethasone. Plasma proteomics demonstrated further differences between PASC-CVS and Recovered patients at approximately 18 months post-infection including enrichment of complement and coagulation associated proteins in those with prolonged cardiovascular symptoms. Together, these data provide a new insight into the role of chronic inflammation in PASC-CVS and present nanotechnology as a possible novel diagnostic approach for the condition.

Clustering Analysis of US COVID-19 Rates, Vaccine Participation, and Socioeconomic Factors (preprint)

The COVID-19 pandemic has presented unprecedented challenges worldwide, with its impact varying significantly across different geographic and socioeconomic contexts. This study employs a clustering analysis to examine the diversity of responses to the pandemic within the United States, aiming to provide nuanced insights into the effectiveness of various strategies. We utilize an unsupervised machine learning approach, specifically K-Means clustering, to analyze county-level data that includes variables such as infection rates, death rates, demographic profiles, and socio-economic factors. Our analysis identifies distinct clusters of counties based on their pandemic responses and outcomes, facilitating a detailed examination of "high-performing" and "lower-performing" groups. These classifications are informed by a combination of COVID-specific datasets and broader socio-economic data, allowing for a comprehensive understanding of the factors that contribute to differing levels of pandemic impact. The findings underscore the importance of tailored public health responses that consider local conditions and capabilities. Additionally, this study introduces an innovative visualization tool that aids in hypothesis testing and further research, enhancing the ability of policymakers and public health officials to deploy more effective and targeted interventions in future health crises.

Antibody Responses to SARS-Cov-2 among Health Care Workers of a Tertiary Hospital in North-Eastern, Tanzania (preprint)

BackgroundHealth Care Workers (HCWs) have been playing crucial role in treating patient with COVID-19. They have a higher occupational risk of contracting the disease than the general population, and a greater chance of them transmitting the disease to vulnerable patients under their care. Given their scarcity and low COVID-19 vaccine acceptance in Africa, it is essential that HCWs are seroprotected and their exposure to COVID-19 minimized. This study was therefore designed to determine IgG antibody response to SARS-CoV-2 among HCWs in North Eastern, Tanzania. MethodologyThis was a cross-sectional study carried out among 273 HCWs at Kilimanjaro Christian Medical Centre (KCMC), a tertiary, zonal referral hospital in Tanzanias North Eastern region. Stratified sampling was used to select study participants. Data were obtained from each consenting participant using a validated questionnaire. Blood samples were collected for SARS-CoV-2 IgG antibodies quantification by using an indirect ELISA test. RedCap software was used to enter and manage data. Statistical analysis was done by using STATA statistical software version 15 and GraphPad Prism v 9.0. A p-value of < 0.05 was considered the cut-off for statistical significance. ResultsAmong 273 HCWS only 37.9 % reported to have received COVID-19 vaccine. Except for one person, all of the participants had SARS-CoV-2 IgG antibody concentrations that were positive, with 64.5% of them having strong seropositivity. Female gender, allied health professionals, active smoking, COVID-19 patient interactions, COVID-19 vaccination receptivity, and adherence to recommended hand hygiene were found to be significant predictors of variation of median SARS-CoV-2 antibody concentration. The usage of personal protective equipment, history of previously testing PCR positive for COVID-19, the number of COVID-19 patient exposure and age were found to cause no significant variation in median antibody concentration among participants. ConclusionsThis study reports a high seroprevalence of SARS-CoV-2 antibodies among healthcare workers in Kilimanjaro Christian Medical Centre. This suggests that HCWs have significant exposure to SARS-CoV-2 despite the low rate of vaccination acceptance even among HCWs. We recommend a strengthened Infectious Prevention and Control (IPC) in hospitals through provision of technical leadership and coordination according to WHO guidelines. We also recommend continued conduction of seroprevalence studies to estimate the magnitude and trends of SARS-CoV-2 infections in different populations in Tanzania. A better understanding of the past, current, and future transmission patterns of infectious pathogens is critical for preparedness and response planning, and to inform the optimal implementation of existing and novel interventions under the current and changing climate.

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.

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.

Evaluating Masks Through the Lens of Evidence-based Medicine (preprint)

Throughout the COVID-19 pandemic, masks have been promoted as an important tool for reducing SARS-CoV-2 transmission. However, even though masks are plausible experimental interventions, their mechanistic effectiveness has not been validated by randomized clinical trials (RCTs), with reduction risks of just 1.1-fold (11%) or less. Several meta-analyses have suggested that masks effectively reduce viral transmission, but all of them rely heavily or exclusively on observational data. Indeed, there is a strong inverse correlation between the effectiveness of masks and the number of RCTs included in the meta-analysis. RCTs on alternative therapies often show similar low levels of effectiveness. Thus, masks can be compared with potential new drugs or therapies that failed clinical trials despite showing mechanistic evidence.

Integrative Systems Immunology Analysis Reveals Elevated Anti-AGTR1 Levels with Accumulating COVID-19 Symptoms (preprint)

The coronavirus disease 2019 (COVID-19) displays a broad spectrum of symptoms, with the underlying reasons for this variability still not fully elucidated. Our study investigates the potential association between specific autoantibodies (AABs), notably those that targeting G protein-coupled receptors (GPCRs) and renin-angiotensin system (RAS) related molecules, and the diverse clinical manifestations of COVID-19, commonly observed in patients with autoimmune conditions, including rheumatic diseases, such as systemic sclerosis. In a cross-sectional analysis, we explored the relationship between AAB levels and the presence of key COVID-19 symptoms. Hierarchical clustering analysis revealed a robust correlation between certain AABs and symptoms such as fever, muscle ache, anosmia, and dysgeusia, which emerged as significant predictors of disease severity. Specifically, AABs against CHRM5 and CXCR3 were strongly linked to fever, while AABs against CHRM5 and BDKRB1 correlated with muscle ache. Anosmia was predominantly associated with AABs against F2R and AGTR1, while dysgeusia was linked to AABs against BDKRB1 and AGTR1. Furthermore, we observed a rise in AAB levels with the accumulation of these symptoms, with the highest levels detected in patients presenting all four predictors. Multinomial regression analysis identified AABs targeting AGTR1 as a key predictor for one or more of these core symptoms. Additionally, our study indicated that anti-AGTR1 antibodies triggered a concentration-dependent degradation of eGC, which could be mitigated by the AGTR1 antagonist Losartan. This suggests a potential mechanistic connection between eGC degradation, the observed COVID-19 symptoms, and rheumatic diseases. In conclusion, our research underscores a substantial correlation between AABs, particularly those against GPCRs and RAS-related molecules, and the severity of COVID-19 symptoms. These findings open avenues for potential therapeutic interventions in the management of COVID-19.

N-protein vaccine Convacell(R) is effective against COVID-19: phase 3, randomized, double-blind, placebo-controlled clinical trial (preprint)

We have developed a Convacell(R), a COVID-19 vaccine based on the conservative viral nucleocapsid (N) protein. The N protein is evolutionary conservative and is abundantly expressed on the surface of infected cells, allowing anti-N immune response generated by Convacell(R) to rapidly clear infected cells and provide long-lasting protection against COVID-19. Convacell(R) has been demonstrated to be safe and highly immunogenic, creating immune responses lasting over a year, in phase I/II and IIb clinical trials. Phase IIb clinical trial has also demonstrated that a single dose vaccination regimen with Convacell(R) is sufficient to provide an immune response. Here we report the finding of the phase III clinical trial of Convacell(R). Two groups of volunteers from Russia have been either vaccinated with a single dose of Convacell(R) or injected with placebo, and then monitored for incidence of COVID-19 and adverse effects. Anti-N antibody titers at admission were also analyzed, to take into account for potential effects of previous virus encounters. Disease incidence over 6 months results indicate an overall vaccine efficacy of 85.2% (95% confidence interval: 67.4-93.3%). Additionally, Convacell(R) has shown a good safety profile. Overall, Convacell(R) demonstrated highly desirable qualities and good performance as a vaccine and can be considered as valuable COVID-19 preventative measure.

The effect of home-based and remote exercises on low back pain during the COVID-19 pandemic: a systematic review (preprint)

Purpose: The prevalence of low back pain (LBP) surged during the COVID-19 pandemic, posing challenges to face-to-face treatment. Therefore, this systematic review aims to determine the effectiveness of various digital solutions for controlling and treatment of LBP during the COVID-19 pandemic. Methods: The systematic review was performed from 2019 until 2023 across databases, including Google Scholar, ScienceDirect, Scopus, and PubMed, according to the eligibility criteria. This review fulfilled the following criteria according to the PICO system: population (individuals using virtual exercises at home for LBP), interventions (distance rehabilitation and digital application), comparison (intervention group performing exercises virtually at home, and control group receiving in-person services), outcome (methods used in the diagnosis of LBP). Only high-quality randomized controlled trial studies were included and assessed using the PEDro scale. All the studies were assessed to be of high quality. Results: After the final review, 15 articles with 3789 subjects met the inclusion criteria. Digital tools such as video calls, Artificial Intelligence programs, Virtual Reality Exercises, and video-based programs were commonly used in studies addressing LBP management. The included articles' scores ranged from 6.2 on the PEDro scale, which has a maximum of 10 points. Conclusions: The COVID-19 pandemic prompted heightened attention to digital treatments, yielding relatively acceptable results for patients and therapists. However, recent technological advances indicate future expansion in this field. Key aspects of this method include training individuals in self-management of LBP and promoting adherence. Nonetheless, the high diversity in the use of digital methods poses limitations on conclusive outcomes. Registration: The systematic review has been registered on the International Prospective Register of Systematic Reviews (PROSPERO) [CRD42022377172;28/11/2022].

The COVID-19 pandemic immediately increased the suicide rate in Kobe, Japan, especially among populations without psychiatry and primary care physician visits: Interrupted time-series analysis using a population-based database (preprint)

Background Japan has one of the lowest numbers of deaths due to coronavirus disease (COVID-19). However, the annual number of suicides increased for the first time in 2020, after a downward trend since 2007. Objective This study aimed to identify high-risk populations and assess the impact of medical visits on suicide trends in Japan following the COVID-19 pandemic. Method This quasi-experimental study used a population-based database from Hyogo Prefecture between 2012 and 2022. Interrupted time-series analyses were used to identify immediate and slope changes in the monthly number of suicides during the exposure period (2020-2022) compared with the control (2012-2019). The analysis was stratified according to the status of psychiatric department and primary care physician visits. Results: A totalof 2181 cases were included. Two-thirds of the cases were male, with a median age of 54. Primary care physicians and psychiatric history were present in 69% and 40% of the patients, respectively. The level change was 4.46 (95%CI; 1.83, 7.09), 3.04 (95%CI; 1.45, 4.64), and 3.07 (95%CI; 0.60, 5.53), in the overall, no primary care physician visit, and no psychiatric visits groups, respectively, which were significant. The level change was not significant in the groups with primary care and psychiatric department visits, at 1.07 (95%CI; -0.84, 2.98) and 0.64 (95%CI; -1.05, 2.33), respectively. The slope changes were not significant in any group. Conclusion: This study suggests that visits to a medical institution may have helped prevent the rapid increase in suicides during the early stages of the COVID-19 pandemic.

Epitope-anchored contrastive transfer learning for paired CD8+ T cell receptor-antigen recognition (preprint)

Understanding the mechanisms of T-cell antigen recognition that underpin adaptive immune responses is critical for the development of vaccines, immunotherapies, and treatments against autoimmune diseases. Despite extensive research efforts, the accurate identification of T cell receptor (TCR)-antigen binding pairs remains a significant challenge due to the vast diversity and cross-reactivity of TCRs. Here, we propose a deep-learning framework termed Epitope-anchored Contrastive Transfer Learning (EPACT) tailored to paired human CD8+ TCRs from single-cell sequencing data. Harnessing the pre-trained representations and the contrastive co-embedding space, EPACT demonstrates state-of-the-art model generalizability in predicting TCR binding specificity for unseen epitopes and distinct TCR repertoires, offering potential values for practical outcomes in real-world scenarios. The contrastive learning paradigm achieves highly precise predictions for immunodominant epitopes and facilitates interpretable analysis of epitope-specific T cells. The TCR binding strength predicted by EPACT aligns well with the surge in spike-specific immune responses targeting SARS-CoV-2 epitopes after vaccination. We further fine-tune EPACT on TCR-epitope structural data to decipher the residue-level interactions involved in T-cell antigen recognition. EPACT not only exhibits superior capabilities in quantifying inter-chain distance matrices and identifying contact residue pairs but also corroborates the presence of molecular mimicry across multiple tumor-associated antigens. Together, EPACT can serve as a useful AI approach with significant potential in practical applications and contribute toward the development of TCR-based diagnostics and immunotherapies.