External Quality Assessment (EQA) scheme for serological diagnostic test for SARS-CoV-2 detection in Sicily Region (Italy), in the period 2020-2022.

OBJECTIVES: Since December 2019, worldwide public health has been exposed to a severe acute respiratory syndrome caused by Coronavirus-2. Serological testing is necessary for retrospective assessment of seroprevalence rates, and the determination of vaccine response and duration of immunity. For this reason, it was necessary to introduce a panel of tests able to identify and quantify Covid-19 antibodies. METHODS: As a Regional Reference Centre, the CRQ Laboratory (Regional Laboratory for the Quality Control) developed and conducted an External Quality Assessment (EQA) panel of assays, to evaluate the quality of various methods, that were used by 288 Sicilian laboratories, previously authorized on behalf of the Public Health Service. RESULTS: The performance test was based on pooled samples with different levels of concentration of antibodies. 97 , 98, and 95 % of the participating laboratories tested all samples correctly in 2020, 2021, and 2022 respectively. The best performance was observed in the test of total Ig. The general performance of laboratories improved over the years. CONCLUSIONS: The incorrect diagnosis had and could still have important implications on vaccination cycles. Only through the effort of laboratory professionals, and the extension of the EQA scheme, a better harmonization of methods, protocols, and thus results, to guarantee a better healthcare system, will be possible.

Epidemiological evolution and economic impact of the COVID-19 pandemic in the European Union and worldwide and effects of control strategies on them: An ecological study.

OBJECTIVE: To evaluate the epidemiological evolution and economic impact of COVID-19 pandemic in the European Union (EU) and worldwide, and the effects of control strategies on them. MATERIAL AND METHODS: We collected incidence, mortality, and gross domestic product (GDP) data between the first quarter of 2020 and of 2023. Then, we reviewed the effectiveness of the mitigation and zero-COVID control strategies. The statistical analysis was done calculating the incidence rate ratio (IRR) of two rates and its 95% confidence interval (CI). RESULTS: In the EU, COVID-19 presented six epidemic waves. The sixth one at the beginning of 2022 was the biggest. Globally, the biggest wave occurred at the beginning of 2023. Highest mortality rates were observed in the EU during 2020-2021 and globally at the beginning of 2021. In mitigation countries, mortality was much higher than in zero-COVID countries (IRR=6.82 [95% CI: 6.14-7.60]; p<0.001). A GDP reduction was observed worldwide, except in Asia. None of the eight zero-COVID countries presented a GDP growth percentage lower than the EU percentage in 2020, and 3/8 in 2022 (p=0.054). COVID-19 pandemic caused epidemic waves with high mortality rates and a negative impact on GDP. CONCLUSION: The zero-COVID strategy was more effective in avoiding mortality and potentially had a lower impact on GDP in the first pandemic year.

Preclinical in vivo assessment of the activity of AZD7442 anti-SARS-CoV-2 monoclonal antibodies against Omicron sublineages.

Therapeutic monoclonal antibodies have been successful in protecting vulnerable populations against SARS-CoV-2. However, their effectiveness has been hampered by the emergence of new variants. To adapt the therapeutic landscape, health authorities have based their recommendations mostly on in vitro neutralization tests. However, these do not provide a reliable understanding of the changes in the dose-effect relationship and how they may translate into clinical efficacy. Taking the example of EvusheldTM (AZD7442), we aimed to investigate how in vivo data can provide critical quantitative results and project clinical effectiveness. We used the Golden Syrian hamster model to estimate 90 % effective concentrations (EC90) of AZD7442 in vivo against SARS-CoV-2 Omicron BA.1, BA.2 and BA.5 variants. While our in vivo results confirmed the partial loss of AZD7442 activity for BA.1 and BA.2, they showed a much greater loss of efficacy against BA.5 than that obtained in vitro. We analyzed in vivo EC90s in perspective with antibody levels measured in a cohort of immunocompromised patients who received 300 mg of AZD7442. We found that a substantial proportion of patients had serum levels of anti-SARS-CoV-2 spike protein IgG above the estimated in vivo EC90 for BA.1 and BA.2 (21 % and 92 % after 1 month, respectively), but not for BA.5. These findings suggest that AZD7442 is likely to retain clinical efficacy against BA.2 and BA.1, but not against BA.5. Overall, the present study illustrates the importance of complementing in vitro investigations by preclinical studies in animal models to help predict the efficacy of monoclonal antibodies in humans.

Inequalities in the Ability for People With Type 2 Diabetes and Prediabetes to Adapt to the Reduction in In-Person Health Support and Increased Use of Digital Support During the COVID-19 Pandemic and Beyond: Qualitative Study.

BACKGROUND: The COVID-19 pandemic created unprecedented challenges for people with type 2 diabetes (T2D) and prediabetes to access in-person health care support. Primary care teams accelerated plans to implement digital health technologies (DHTs), such as remote consultations and digital self-management. There is limited evidence about whether there were inequalities in how people with T2D and prediabetes adjusted to these changes. OBJECTIVE: This study aimed to explore how people with T2D and prediabetes adapted to the reduction in in-person health support and the increased provision of support through DHTs during the COVID-19 pandemic and beyond. METHODS: A purposive sample of people with T2D and prediabetes was recruited by text message from primary care practices that served low-income areas. Semistructured interviews were conducted by phone or video call, and data were analyzed thematically using a hybrid inductive and deductive approach. RESULTS: A diverse sample of 30 participants was interviewed. There was a feeling that primary care had become harder to access. Participants responded to the challenge of accessing support by rationing or delaying seeking support or by proactively requesting appointments. Barriers to accessing health care support were associated with issues with using the total triage system, a passive interaction style with health care services, or being diagnosed with prediabetes at the beginning of the pandemic. Some participants were able to adapt to the increased delivery of support through DHTs. Others had lower capacity to use DHTs, which was caused by lower digital skills, fewer financial resources, and a lack of support to use the tools. CONCLUSIONS: Inequalities in motivation, opportunity, and capacity to engage in health services and DHTs lead to unequal possibilities for people with T2D and prediabetes to self-care and receive care during the COVID-19 pandemic. These issues can be addressed by proactive arrangement of regular checkups by primary care services and improving capacity for people with lower digital skills to engage with DHTs.

A Metric of Societal Burden Based on Virus Succession to Determine Economic Losses and Health Benefits of China's Lockdown Policies: Model Development and Validation.

BACKGROUND: The COVID-19 pandemic had a profound impact on the global health system and economic structure. Although the implementation of lockdown measures achieved notable success in curbing the spread of the pandemic, it concurrently incurred substantial socioeconomic costs. OBJECTIVE: The objective of this study was to delineate an equilibrium between the economic losses and health benefits of lockdown measures, with the aim of identifying the optimal boundary conditions for implementing these measures at various pandemic phases. METHODS: This study used a model to estimate the half-lives of the observed case fatality rates of different strains. It was based on global infection and death data collected by the World Health Organization and strain sequence time series data provided by Nextstrain. The connection between the health benefits and economic losses brought by lockdown measures was established through the calculation of disability-adjusted life years. Taking China's city lockdowns as an example, this study determined the cost-benefit boundary of various lockdown measures during the evolution of COVID-19. RESULTS: The study reveals a direct proportionality between economic losses due to lockdowns and the observed case fatality rates of virus strains, a relationship that holds true irrespective of population size or per capita economic output. As SARS-CoV-2 strains evolve and population immunity shifts, there has been a notable decrease in the observed case fatality rate over time, exhibiting a half-life of roughly 8 months. This decline in fatality rates may offset the health benefits of maintaining unchanged lockdown measures, given that the resultant economic losses might exceed the health benefits. CONCLUSIONS: The initial enforcement of lockdown in Wuhan led to significant health benefits. However, with the decline in the observed case fatality rate of the virus strains, the economic losses increasingly outweighed the health benefits. Consequently, it is essential to consistently refine and enhance lockdown strategies in accordance with the evolving fatality and infection rates of different virus strains, thereby optimizing outcomes in anticipation of future pandemics.

Incidence and management of the main serious adverse events reported after COVID-19 vaccination.

Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2n first appeared in Wuhan, China in 2019. Soon after, it was declared a pandemic by the World Health Organization. The health crisis imposed by a new virus and its rapid spread worldwide prompted the fast development of vaccines. For the first time in human history, two vaccines based on recombinant genetic material technology were approved for human use. These mRNA vaccines were applied in massive immunization programs around the world, followed by other vaccines based on more traditional approaches. Even though all vaccines were tested in clinical trials prior to their general administration, serious adverse events, usually of very low incidence, were mostly identified after application of millions of doses. Establishing a direct correlation (the cause-effect paradigm) between vaccination and the appearance of adverse effects has proven challenging. This review focuses on the main adverse effects observed after vaccination, including anaphylaxis, myocarditis, vaccine-induced thrombotic thrombocytopenia, Guillain-Barré syndrome, and transverse myelitis reported in the context of COVID-19 vaccination. We highlight the symptoms, laboratory tests required for an adequate diagnosis, and briefly outline the recommended treatments for these adverse effects. The aim of this work is to increase awareness among healthcare personnel about the serious adverse events that may arise post-vaccination. Regardless of the ongoing discussion about the safety of COVID-19 vaccination, these adverse effects must be identified promptly and treated effectively to reduce the risk of complications.

Population mobility, well-mixed clustering and disease spread: a look at COVID-19 Spread in the United States and preventive policy insights.

The epidemiology of pandemics is classically viewed using geographical and political borders; however, these artificial divisions can result in a misunderstanding of the current epidemiological state within a given region. To improve upon current methods, we propose a clustering algorithm which is capable of recasting regions into well-mixed clusters such that they have a high level of interconnection while minimizing the external flow of the population towards other clusters. Moreover, we analyze and identify so-called core clusters, clusters that retain their features over time (temporally stable) and independent of the presence or absence of policy measures. In order to demonstrate the capabilities of this algorithm, we use USA county-level cellular mobility data to divide the country into such clusters. Herein, we show a more granular spread of SARS-CoV-2 throughout the first weeks of the pandemic. Moreover, we are able to identify areas (groups of counties) that were experiencing above average levels of transmission within a state, as well as pan-state areas (clusters overlapping more than one state) with very similar disease spread. Therefore, our method enables policymakers to make more informed decisions on the use of public health interventions within their jurisdiction, as well as guide collaboration with surrounding regions to benefit the general population in controlling the spread of communicable diseases.

Automated local lockdowns for SARS-CoV-2 epidemic control-assessment of effect by controlled interrupted time series analysis.

Objectives: During the COVID-19 pandemic, broad non-pharmaceutical interventions such as national lockdowns were effective but had significant drawbacks, prompting targeted approaches, such as Denmark's localized lockdowns, based on specific epidemiological criteria. This study evaluates the effect of Denmark's automated local lockdown strategy on epidemic control to inform future response. Methods: This was a register-based controlled interrupted time series analysis, examining SARS-CoV-2 infection rates in Danish parishes from March to September 2021. The matching of control parishes was based on location, time, and pre-lockdown infection trends, with the lockdown's start defined as the day after a parish exceeded the lockdown criteria. Follow-up included 3-week pre-lockdown and 2-week post-lockdown. Results: A total of 30 parishes were mandated to lockdown, approximately 3.5% of the population of Denmark. A total of 94 control parishes were used as 109 controls. The decrease in the incidence during the 2-week follow-up period after the initiation of the lockdown was 13% points higher in case parishes: in case parishes, the incidence was reduced by 78% compared with 65% in control parishes. Conclusions: Our findings demonstrate that local lockdowns did have a positive effect in mitigating the spread of the SARS-CoV-2 virus, making them valuable in the fight against the COVID-19 pandemic and an important alternative to national lockdowns.

Access to COVID-19 vaccination by socio-economic status in older Singaporean adults: a population-based cohort study.

OBJECTIVES: Socio-economic status (SES) disparities exist in the uptake of COVID-19 vaccination; however, most studies were conducted during the initial pandemic wave when vaccination was less discretionary, limiting generalizability. We aimed to determine whether differences in vaccination uptake across SES strata widened after the removal of vaccination-differentiated measures prior to the rollout of the second boosters, in a nationwide cohort of older Singaporeans at higher risk of severe-COVID-19. STUDY DESIGN: Retrospective population-based cohort study. METHODS: Retrospective population-based cohort study of all Singaporeans aged ≥60 years from 22nd February 2021-14th February 2023. Cox regression models controlling for demographics and comorbidities were used to estimate hazard-ratios (HRs) for the uptake of primary vaccination as well as first/second boosters, as recorded in the national vaccination registry, according to SES (housing type). RESULTS: 836,170 individuals were included for completion of a primary vaccine series; 784,938 individuals for completion of the first booster and 734,206 individuals for the completion of the second booster. Differences in vaccination uptake by SES strata were observed (e.g. vaccination uptake in lowest-SES [1-2 room public-housing] versus highest-SES [private housing]: second booster, 47.6% vs. 58.1%; first booster, 93.9% vs. 98.0%). However, relative differences did not markedly widen during second booster rollout when vaccination was more discretionary (e.g. amongst those aged 60-69 years: 0.75 [95% CI = 0.73-0.76] for the first booster; 0.81 [95% CI = 0.79-0.84] for the second booster). CONCLUSION: While differences in vaccination uptake across SES strata by housing type persisted during the rollout of primary vaccination and subsequent boosters in a nationwide cohort of older Singaporeans, differences did not widen substantially when vaccination was made more discretionary.

Mathematical Assessment of the Role of Human Behavior Changes on SARS-CoV-2 Transmission Dynamics in the United States.

The COVID-19 pandemic has not only presented a major global public health and socio-economic crisis, but has also significantly impacted human behavior towards adherence (or lack thereof) to public health intervention and mitigation measures implemented in communities worldwide. This study is based on the use of mathematical modeling approaches to assess the extent to which SARS-CoV-2 transmission dynamics is impacted by population-level changes of human behavior due to factors such as (a) the severity of transmission (such as disease-induced mortality and level of symptomatic transmission), (b) fatigue due to the implementation of mitigation interventions measures (e.g., lockdowns) over a long (extended) period of time, (c) social peer-pressure, among others. A novel behavior-epidemiology model, which takes the form of a deterministic system of nonlinear differential equations, is developed and fitted using observed cumulative SARS-CoV-2 mortality data during the first wave in the United States. The model fits the observed data, as well as makes a more accurate prediction of the observed daily SARS-CoV-2 mortality during the first wave (March 2020-June 2020), in comparison to the equivalent model which does not explicitly account for changes in human behavior. This study suggests that, as more newly-infected individuals become asymptomatically-infectious, the overall level of positive behavior change can be expected to significantly decrease (while new cases may rise, particularly if asymptomatic individuals have higher contact rate, in comparison to symptomatic individuals).

Monitoring and assessment of CO2 and NO2 in schools within the Sentinel Schools Network of Catalonia during the COVID-19 era.

In response to the global impact of the COVID-19 pandemic, international and national authorities, including those in Catalonia (Spain), recognized the crucial need to ensure proper ventilation in classrooms, emphasizing the importance of safe and healthy indoor environments for face-to-face learning. The present work, conducted within the COVID-19 Sentinel Schools Network of Catalonia (CSSNC) framework, aimed to monitor carbon dioxide (CO2) and nitrogen dioxide (NO2) concentrations in 23 schools, ensuring a comprehensive sample regarding educational levels, daily scholar schedules, and classroom typologies distributed across the four provinces of Catalonia. The research spanned three study periods: March and April 2021, October 2021 to January 2022, and March to June 2022. Briefly, 28%, 25%, and 37% of classrooms surpassed the 700 parts per million (ppm) CO2 limit in each study period, respectively. Generally, CO2 averages were lower in preschool classrooms (mean ± SD = 486 ± 106 ppm), while high school classrooms displayed the highest CO2 concentrations (mean ± SD = 710 ± 253 ppm). Moreover, classrooms in towns (<30000 inhabitants) exhibited higher CO2 levels as compared to classrooms from schools located in cities. As for NO2, the highest averages were obtained in urban areas, particularly in the Barcelona metropolitan area (e.g. mean indoor levels of 24.56 µg m-3 as compared to 11.05 µg m-3 in towns). In addition, the Indoor/Outdoor ratio (I/O ratio) in towns was the lowest (0.60). These results, together with the higher concentration of CO2 indoors, could indicate poorer ventilation in town schools. The results of this study are anticipated to contribute to implementing evidence-based measures to improve indoor air quality (IAQ) in educational settings.

New-onset diabetes in children during the COVID-19 Pandemic: an assessment of biomarkers and psychosocial risk factors at play in Mississippi.

PURPOSE: The coronavirus disease 2019 (COVID-19) pandemic has led to an association between COVID-19 and pediatric diabetes. Studies have indicated the increased likelihood of children with COVID-19 infection developing diabetes. Our objective was to assess not only the increase in pediatric diabetes at our hospital and identify possible risk factors, but also to correlate the psychosocial changes resulting from the pandemic with new-onset diabetes. METHODS: We analyzed data from 58 children aged 1 to 18 years admitted to our hospital with new-onset diabetes between March 2020 and December 2021. The data included inflammatory biomarkers and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies (Abs), as well as the results of a lifestyle questionnaire. RESULTS: The average number of hospital admissions per month for new-onset diabetes increased from 10 to 18 with the start of the pandemic. Of the 58 children in our analysis, 33% had positive SARS-CoV-2 IgG Ab, 31% had type 1 diabetes mellitus, and 62% had type 2 diabetes mellitus (T2DM). More than half (54%) were experiencing diabetic ketoacidosis. Those with T2DM were older, majority African American, had higher median body mass index (BMI) percentiles, and lower vitamin D levels. There were no significant correlations between any psychosocial risk factors and either diabetes type or SARS-CoV2 Ab status. CONCLUSION: Despite the increased incidence of new-onset diabetes among children in Mississippi during the pandemic, this study was unable to demonstrate a significant correlation between COVID-19 infection and new-onset diabetes. The findings of this study highlighted the correlation between increased BMI and type 2 diabetes, underscoring the significant problems of obesity and diabetes in our study region. Further research is warranted.

External Quality Assessment (EQA) for SARS-CoV-2 RNA Point-of-Care Testing in Primary Healthcare Services: Analytical Performance over Seven EQA Cycles.

In April 2020, the Aboriginal and Torres Strait Islander COVID-19 Point-of-Care (POC) Testing Program was initiated to improve access to rapid molecular-based SARS-CoV-2 detection in First Nations communities. At capacity, the program reached 105 health services across Australia. An external review estimated the program contributed to averting between 23,000 and 122,000 COVID-19 infections within 40 days of the first infection in a remote community, equating to cost savings of between AU$337 million and AU$1.8 billion. Essential to the quality management of this program, a customised External Quality Assessment (EQA) program was developed with the Royal College of Pathologists of Australasia Quality Assurance Programs (RCPAQAP). From July 2020 to May 2022, SARS-CoV-2 EQA participation ranged from 93 to 100%. Overall concordance of valid EQA results was high (98%), with improved performance following the first survey. These results are consistent with those reported by 12 Australian and 4 New Zealand laboratories for three SARS-CoV-2 RNA EQA surveys in March 2020, demonstrating that SARS-CoV-2 RNA POC testing in primary care settings can be performed to an equivalent laboratory analytical standard. More broadly, this study highlights the value of quality management practices in real-world testing environments and the benefits of ongoing EQA program participation.

Application of Interferon-γ Release Assay in the Assessment of T-Cell Immunity to SARS-CoV-2 Antigens in the Cohort of Pediatric Patients with Juvenile Idiopathic Arthritis.

Background: an accurate assessment of the immunity against SARS-CoV-2 can facilitate a better understanding and management of not only the recent coronavirus but similar pathogens as well. Objective: the aim of this study was to evaluate T-cell immunity with reference to antibody titers in a group of pediatric patients with autoimmune arthritides utilizing the widely known Interferon-γ Release Assay (IGRA). Materials and Methods: This study was conducted in the cohort of 55 children suffering from Juvenile Idiopathic Arthritis (JIA). This research analyzed the SARS-CoV-2 T-cell response measured by a specific quantitative IGRA, followed by a serological ELISA test measuring the presence and quantity of IgG, IgM, and IgA antibodies in serum. Results: The cellular response to SARS-CoV-2 measured by the IGRA test significantly correlated with the antibody titers, IgA (p < 0.00003, R = 0.537), IgG (p < 0.0001, R = 0.668), and IgG nucleocapsid protein (NCP) (p < 0.003, R = 0.0399), with no correlation with IgM levels. The antibody levels in patients receiving biological agents were significantly lower compared to the rest of the cohort (p = 0.0369), while traditional disease-modifying antirheumatic drugs had no such effect. Limitations: the main limitation of the research is the small sample size, mostly due to the specific cohort of patients and the lack of a healthy control. Conclusions: IGRA appears to be a viable tool in the accurate evaluation of T-cell responses to SARS-CoV-2, and serodiagnostics alone is not always sufficient in the assessment of immune responses.

Mapping the scientific output of organoids for animal and human modeling infectious diseases: a bibliometric assessment.

The escalation of antibiotic resistance, pandemics, and nosocomial infections underscores the importance of research in both animal and human infectious diseases. Recent advancements in three-dimensional tissue cultures, or "organoids", have revolutionized the development of in vitro models for infectious diseases. Our study conducts a bibliometric analysis on the use of organoids in modeling infectious diseases, offering an in-depth overview of this field's current landscape. We examined scientific contributions from 2009 onward that focused on organoids in host‒pathogen interactions using the Web of Science Core Collection and OpenAlex database. Our analysis included temporal trends, reference aging, author, and institutional productivity, collaborative networks, citation metrics, keyword cluster dynamics, and disruptiveness of organoid models. VOSviewer, CiteSpace, and Python facilitated this analytical assessment. The findings reveal significant growth and advancements in organoid-based infectious disease research. Analysis of keywords and impactful publications identified three distinct developmental phases in this area that were significantly influenced by outbreaks of Zika and SARS-CoV-2 viruses. The research also highlights the synergistic efforts between academia and publishers in tackling global pandemic challenges. Through mostly consolidating research efforts, organoids are proving to be a promising tool in infectious disease research for both human and animal infectious disease. Their integration into the field necessitates methodological refinements for better physiological emulation and the establishment of extensive organoid biobanks. These improvements are crucial for fully harnessing the potential of organoids in understanding infectious diseases and advancing the development of targeted treatments and vaccines.

Epidemiology of respiratory syncytial virus in hospitalized children over a 9-year period and preventive strategy impact.

Background: Respiratory Syncytial Virus (RSV) is the primary cause of respiratory infections and hospitalizations in young children globally, leading to substantial disease burden and mortality. The aim of the present study was to review and provide updates on how the SARS-CoV-2 pandemic have significantly influenced RSV epidemiology on hospitalized children due to RSV infection. A potential impact of the available preventive strategies on the same population were provided. Methods: All children aged 0-6 years hospitalized at Meyer Children's Hospital IRCCS for RSV infection from September 2014 to March 2023 were retrospectively recorded. Seasonal trends before and after SARS-CoV-2 pandemic, age distribution, ICU admission and co-infections, comorbidities and prematurity were retrieved. Predictions on the number of hospitalizations avoided by the deployment of different preventive strategies were provided. Results: A total of 1,262 children with RSV infection were included in the study. The 70% of them had less than 1 year-of-age at the moment of hospitalization and almost 50% less than 3 months. In the post-pandemic seasons, a 317% increase in the number of hospitalizations was recorded with a significant increase in older children compared to the pre-pandemic seasons. ICU support was required for 22% of children, the majority of whom were under 3 months of age. Almost 16% of hospitalized children were born preterm and only 27% of hospitalized children had prior comorbidities. The rate of comorbidities among RSV hospitalized children increased with age. Nirsevimab prophylaxis could have prevented more than 46% of hospitalizations in this cohort. A preventive strategy addressing also children aged 7 months to 6 years of age with co-existing comorbidities would increase that rate above 57%. Discussion: The identification of RSV hospitalization-related features is informing the decision-maker for the deployment of the wisest preventive approach on a population scale.

The mortality burden related to COVID-19 in 2020 and 2021 - years of life lost and excess mortality in 13 countries and sub-national regions in Southern and Eastern Europe, and Central Asia.

Introduction: Between 2021 and 2023, a project was funded in order to explore the mortality burden (YLL-Years of Life Lost, excess mortality) of COVID-19 in Southern and Eastern Europe, and Central Asia. Methods: For each national or sub-national region, data on COVID-19 deaths and population data were collected for the period March 2020 to December 2021. Unstandardized and age-standardised YLL rates were calculated according to standard burden of disease methodology. In addition, all-cause mortality data for the period 2015-2019 were collected and used as a baseline to estimate excess mortality in each national or sub-national region in the years 2020 and 2021. Results: On average, 15-30 years of life were lost per death in the various countries and regions. Generally, YLL rates per 100,000 were higher in countries and regions in Southern and Eastern Europe compared to Central Asia. However, there were differences in how countries and regions defined and counted COVID-19 deaths. In most countries and sub-national regions, YLL rates per 100,000 (both age-standardised and unstandardized) were higher in 2021 compared to 2020, and higher amongst men compared to women. Some countries showed high excess mortality rates, suggesting under-diagnosis or under-reporting of COVID-19 deaths, and/or relatively large numbers of deaths due to indirect effects of the pandemic. Conclusion: Our results suggest that the COVID-19 mortality burden was greater in many countries and regions in Southern and Eastern Europe compared to Central Asia. However, heterogeneity in the data (differences in the definitions and counting of COVID-19 deaths) may have influenced our results. Understanding possible reasons for the differences was difficult, as many factors are likely to play a role (e.g., differences in the extent of public health and social measures to control the spread of COVID-19, differences in testing strategies and/or vaccination rates). Future cross-country analyses should try to develop structured approaches in an attempt to understand the relative importance of such factors. Furthermore, in order to improve the robustness and comparability of burden of disease indicators, efforts should be made to harmonise case definitions and reporting for COVID-19 deaths across countries.

Preclinical assessment of a recombinant RBD-Fc fusion protein as SARS-CoV-2 candidate vaccine.

Background: Waning immunity and emergence of new variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), highlight the need for further research in vaccine development. Methods: A recombinant fusion protein containing the receptor-binding domain (RBD) fused to the human IgG1 Fc (RBD-Fc) was produced in CHO-K1 cells. RBD-Fc was emulsified with four adjuvants to evaluate its immunogenicity. The RBD-specific humoral and cellular immune responses were assessed by ELISA. The virus neutralizing potency of the vaccine was investigated using four neutralization methods. Safety was studied in mice and rabbits, and Antibody-Dependent Enhancement (ADE) effects were investigated by flow cytometry. Results: RBD-Fc emulsified in Alum induced a high titer of anti-RBD antibodies with remarkable efficacy in neutralizing both pseudotyped and live SARS-CoV-2 Delta variant. The neutralization potency dropped significantly in response to the Omicron variant. RBD-Fc induced both TH2 and particularly TH1 immune responses. Histopathologic examinations demonstrated no substantial pathologic changes in different organs. No changes in serum biochemical and hematologic parameters were observed. ADE effect was not observed following immunization with RBD-Fc. Conclusion: RBD-Fc elicits highly robust neutralizing antibodies and cellular immune responses, with no adverse effects. Therefore, it could be considered a promising and safe subunit vaccine against SARS-CoV-2.

Assessment of an in-house IgG ELISA targeting SARS-CoV-2 RBD: Applications in infected and vaccinated individuals.

The study evoluated an in-house Spike Receptor Binding Domain Enzyme-Linked Immunosorbent Assay (RBD-IgG-ELISA) for detecting SARS-CoV-2 IgG antibodies in infected and vaccinated individuals. The assay demonstrated a sensitivity of 91%, specificity of 99.25%, and accuracy of 95.13%. Precision and reproducibility were highly consistent. The RBD-IgG-ELISA was able to detect 96.25% of Polymerase chain reaction (PCR) confirmed cases for SARS-CoV-2 infection, demonstrating positive and negative predictive values of 99,18% and 91,69%, respectively. In an epidemiological survey, ELISA, lateral flow immunochromatographic assay (LFIA), and electrochemiluminescence immunoassay (ECLIA) exhibited diagnostic sensitivities of 68.29%, 63.41%, and 70.73%, respectively, along with specificities of 82.93%, 80.49%, and 80.49%, respectively. Agreement between RBD-IgG-ELISA/PCR was moderate (k index 0.512). However, good agreement between different assays (RBD-IgG-ELISA/LFIA k index 0.875, RBD-IgG-ELISA/ECLIA k index 0.901). Test performance on individuals' samples were inferior due to seroconversion time and chronicity. The IgG-RBD-ELISA assay demonstrated its effectiveness in monitoring antibody levels among healthcare professionals, revealing significant differences both before and after the administration of the third vaccine dose, with heightened protection levels observed following the third dose in five Coronavirus disease (COVID-19) vaccine regimens. In conclusion, the RBD-IgG-ELISA exhibits high reproducibility, specificity, and sensitivity, making it a suitable assay validated for serosurveillance and for obtaining information about COVID-19 infections or vaccinations.

The role of area deprivation index in health care disruptions among cancer survivors during the SARS-CoV-2 pandemic.

OBJECTIVE: To examine the associations between demographic/medical and geographic factors with follow-up medical care and health-related quality of life (HRQoL) among cancer survivors during the SARS-CoV-2 pandemic. STUDY DESIGN: Cross-sectional survey. METHODS: An online survey was sent to cancer survivors between May 2020 and January 2021, exploring their experience with SARS-CoV-2, follow-up care, and HRQoL. PolicyMap was used to geocode home addresses. Both geographic and demographic/medical factors were examined for their associations with SARS-CoV-2 experience, follow-up care, and HRQoL (FACT-G7). RESULTS: Geographic data were available for 9651 participants. Patients living in the highest area deprivation index (ADI) neighborhoods (most deprived) had higher odds of avoiding in-person general (odds ratio [OR] = 7.20; 95% confidence interval [CI] = 2.79-18.60), cancer (OR = 8.47; 95% CI = 3.73-19.30), and emergency (OR = 14.2; 95% CI = 5.57-36.30) medical care, as well as lower odds of using telemedicine (OR = 0.61; 95% CI = 0.52-0.73) compared to the lowest ADI group. Race/ethnicity was not associated with follow-up care after controlling for ADI. The effect of ADI on HRQoL was generally in the expected direction, with higher ADI being associated with worse HRQoL. CONCLUSIONS: ADI influenced follow-up medical care more than age, race/ethnicity, or health insurance type. Healthcare providers and institutions should focus on decreasing barriers to in-person and telemedicine health care that disproportionally impact those living in more deprived communities, which are exacerbated by health care disruptions like those caused by the SARS-CoV-2 pandemic.