A quantitative evaluation of the impact of vaccine roll-out rate and coverage on reducing deaths: insights from the first 2 years of COVID-19 epidemic in Iran.

BACKGROUND: Vaccination has played a pivotal role in reducing the burden of COVID-19. Despite numerous studies highlighting its benefits in reducing the risk of severe disease and death, we still lack a quantitative understanding of how varying vaccination roll-out rates influence COVID-19 mortality. METHODS: We developed a framework for estimating the number of avertable COVID-19 deaths (ACDs) by vaccination in Iran. To achieve this, we compared Iran's vaccination roll-out rates with those of eight model countries that predominantly used inactivated virus vaccines. We calculated net differences in the number of fully vaccinated individuals under counterfactual scenarios where Iran's per-capita roll-out rate was replaced with that of the model countries. This, in turn, enabled us to determine age specific ACDs for the Iranian population under counterfactual scenarios where number of COVID-19 deaths are estimated using all-cause mortality data. These estimates covered the period from the start of 2020 to 20 April 2022. RESULTS: We found that while Iran would have had an approximately similar number of fully vaccinated individuals under counterfactual roll-out rates based on Bangladesh, Nepal, Sri Lanka, and Turkey (~ 65-70%), adopting Turkey's roll-out rates could have averted 50,000 (95% confidence interval: 38,100-53,500) additional deaths, while following Bangladesh's rates may have resulted in 52,800 (17,400-189,500) more fatalities in Iran. Surprisingly, mimicking Argentina's slower roll-out led to only 12,600 (10,400-13,300) fewer deaths, despite a higher counterfactual percentage of fully vaccinated individuals (~ 79%). Emulating Montenegro or Bolivia, with faster per capita roll-out rates and approximately 50% counterfactual full vaccination, could have prevented more deaths in older age groups, especially during the early waves. Finally, replicating Bahrain's model as an upper-bound benchmark, Iran could have averted 75,300 (56,000-83,000) deaths, primarily in the > 50 age groups. CONCLUSIONS: Our analysis revealed that faster roll-outs were consistently associated with higher numbers of averted deaths, even in scenarios with lower overall coverage. This study offers valuable insights into future decision-making regarding infectious disease epidemic management through vaccination strategies. It accomplishes this by comparing various countries' relative performance in terms of timing, pace, and vaccination coverage, ultimately contributing to the prevention of COVID-19-related deaths.

Repertoire analysis of γδ T cells in the chicken enables functional annotation of the genomic region revealing highly variable pan-tissue TCR gamma V gene usage as well as identifying public and private repertoires.

BACKGROUND: Despite increasing interest in γδ T cells and their non-classical behaviour, most studies focus on animals with low numbers of circulating γδ T cells, such as mice and humans. Arguably, γδ T cell functions might be more prominent in chickens where these cells form a higher proportion of the circulatory T cell compartment. The TCR repertoire defines different subsets of γδ T cells, and such analysis is facilitated by well-annotated TCR loci. γδ T cells are considered at the cusp of innate and adaptive immunity but most functions have been identified in γδ low species. A deeper understanding of TCR repertoire biology in γδ high and γδ low animals is critical for defining the evolution of the function of γδ T cells. Repertoire dynamics will reveal populations that can be classified as innate-like or adaptive-like as well as those that straddle this definition. RESULTS: Here, a recent discrepancy in the structure of the chicken TCR gamma locus is resolved, demonstrating that tandem duplication events have shaped the evolution of this locus. Importantly, repertoire sequencing revealed large differences in the usage of individual TRGV genes, a pattern conserved across multiple tissues, including thymus, spleen and the gut. A single TRGV gene, TRGV3.3, with a highly diverse private CDR3 repertoire dominated every tissue in all birds. TRGV usage patterns were partly explained by the TRGV-associated recombination signal sequences. Public CDR3 clonotypes represented varying proportions of the repertoire of TCRs utilising different TRGVs, with one TRGV dominated by super-public clones present in all birds. CONCLUSIONS: The application of repertoire analysis enabled functional annotation of the TCRG locus in a species with a high circulating γδ phenotype. This revealed variable usage of TCRGV genes across multiple tissues, a pattern quite different to that found in γδ low species (human and mouse). Defining the repertoire biology of avian γδ T cells will be key to understanding the evolution and functional diversity of these enigmatic lymphocytes in an animal that is numerically more reliant on them. Practically, this will reveal novel ways in which these cells can be exploited to improve health in medical and veterinary contexts.

Addressing the unmet need for a comprehensive lung cancer registry in Romania.

In this perspective article, we describe the vital need for a well-organized cancer registry in Romania, where lung cancer prevalence and mortality rates are alarmingly high. We discuss contributing factors such as increased use of chest X-rays and CT scans during the COVID-19 pandemic and delayed diagnoses due to limited medical care access. With the nation's characteristically limited access to healthcare, it is plausible that the surge in acute imaging for COVID-19 has inadvertently resulted in a higher detection rate of lung cancer. This inadvertent early detection underscores the vital need for a well-organized cancer registry in Romania, where lung cancer prevalence and mortality rates are alarmingly high. Although impactful, these factors are not the primary causes of the high lung cancer cases in the country. We provide an overview of current options and propose future perspectives for epidemiological monitoring of lung cancer patients in Romania, aiming to enhance patient care, bolster research, and promote data-driven policy-making. While our primary focus is establishing a national registry for lung cancer, we address challenges, considerations, and best practices applicable to all cancer types. Through our proposed strategies and recommendations, we aim to contribute to the development and improvement of a comprehensive national cancer registry system in Romania.

Ancient chicken remains reveal the origins of virulence in Marek's disease virus.

The pronounced growth in livestock populations since the 1950s has altered the epidemiological and evolutionary trajectory of their associated pathogens. For example, Marek's disease virus (MDV), which causes lymphoid tumors in chickens, has experienced a marked increase in virulence over the past century. Today, MDV infections kill >90% of unvaccinated birds, and controlling it costs more than US$1 billion annually. By sequencing MDV genomes derived from archeological chickens, we demonstrate that it has been circulating for at least 1000 years. We functionally tested the Meq oncogene, one of 49 viral genes positively selected in modern strains, demonstrating that ancient MDV was likely incapable of driving tumor formation. Our results demonstrate the power of ancient DNA approaches to trace the molecular basis of virulence in economically relevant pathogens.

The influences of microbial colonisation and germ-free status on the chicken TCRß repertoire.

Microbial colonisation is paramount to the normal development of the immune system, particularly at mucosal sites. However, the relationships between the microbiome and the adaptive immune repertoire have mostly been explored in rodents and humans. Here, we report a high-throughput sequencing analysis of the chicken TCRß repertoire and the influences of microbial colonisation on tissue-resident TCRß+ cells. The results reveal that the microbiome is an important driver of TCRß diversity in both intestinal tissues and the bursa of Fabricius, but not in the spleen. Of note, public TCRß sequences (shared across individuals) make a substantial contribution to the repertoire. Additionally, different tissues exhibit biases in terms of their V family and J gene usage, and these effects were influenced by the gut-associated microbiome. TCRß clonal expansions were identified in both colonised and germ-free birds, but differences between the groups were indicative of an influence of the microbiota. Together, these findings provide an insight into the avian adaptive immune system and the influence of the microbiota on the TCRß repertoire.

Engaging Religious Institutions and Faith-Based Communities in Public Health Initiatives: A Case Study of the Romanian Orthodox Church During the COVID-19 Pandemic.

The success of public health interventions is highly dependent on the compliance of the general population. State authorities often implement policies without consulting representatives of faith-based communities, thereby overlooking potential implications of public health measures for these parts of society. Although ubiquitous, these challenges are more readily observable in highly religious states. Romania serves as an illustrative example for this, as recent data identify it as the most religious country in Europe. In this paper, we discuss the contributions of the Romanian Orthodox Church (ROC), the major religious institution in the country, to the national COVID-19 mitigation efforts. We present not only the positive outcomes of productive consultations between public health authorities and religious institutions but also the detrimental impact of unidirectional communication. Our work highlights that an efficient dialogue with faith-based communities can greatly enhance the results of public health interventions. As the outlined principles apply to a variety of contexts, the lessons learned from this case study can be generalized into a set of policy recommendations for the betterment of future public health initiatives worldwide.

Prospects of COVID-19 Vaccination in Romania: Challenges and Potential Solutions.

The rapid advancement in vaccine development represents a critical milestone that will help humanity tackle the COVID-19 pandemic. However, the success of these efforts is not guaranteed, as it relies on the outcomes of national and international vaccination strategies. In this article, we highlight some of the challenges that Romania will face and propose a set of solutions to overcome them. With this in mind, we discuss issues such as the infrastructure of vaccine storage and delivery, the deployment and administration of immunisations, and the public acceptance of vaccines. The ways in which Romanian society will respond to a national COVID-19 vaccination campaign will be contingent on appropriate and timely actions. As many of the problems encountered in Romania are not unique, the proposed recommendations could be adapted and implemented in other countries that face similar issues, thereby informing better practices in the management of the COVID-19 pandemic.

Lessons for preparedness and reasons for concern from the early COVID-19 epidemic in Iran.

INTRODUCTION: Many countries with an early outbreak of SARS-CoV-2 struggled to gauge the size and start date of the epidemic mainly due to limited testing capacities and a large proportion of undetected asymptomatic and mild infections. Iran was among the first countries with a major outbreak outside China. METHODS: We constructed a globally representative sample of 802 genomes, including 46 samples from patients inside or with a travel history to Iran. We then performed a phylogenetic analysis to identify clades related to samples from Iran and estimated the start of the epidemic and early doubling times in cases. We leveraged air travel data from 36 exported cases of COVID-19 to estimate the point-prevalence and the basic reproductive number across the country. We also analysed the province-level all-cause mortality data during winter and spring 2020 to estimate under-reporting of COVID-19-related deaths. Finally, we use this information in an SEIR model to reconstruct the early outbreak dynamics and assess the effectiveness of intervention measures in Iran. RESULTS: By identifying the most basal clade that contained genomes from Iran, our phylogenetic analysis showed that the age of the root is placed on 2019-12-21 (95 % HPD: 2019-09-07 - 2020-02-14). This date coincides with our estimated epidemic start date on 2019-12-25 (95 %CI: 2019-12-11 - 2020-02-24) based air travel data from exported cases with an early doubling time of 4.0 (95 %CI: 1.4-6.7) days in cases. Our analysis of all-cause mortality showed 21.9 (95 % CI: 16.7-27.2) thousand excess deaths by the end of summer. Our model forecasted the second epidemic peak and suggested that by 2020-08-31 a total of 15.0 (95 %CI: 4.9-25.0) million individuals recovered from the disease across the country. CONCLUSION: These findings have profound implications for assessing the stage of the epidemic in Iran despite significant levels of under-reporting. Moreover, the results shed light on the dynamics of SARS-CoV-2 transmissions in Iran and central Asia. They also suggest that in the absence of border screening, there is a high risk of introduction from travellers from areas with active outbreaks. Finally, they show both that well-informed epidemic models are able to forecast episodes of resurgence following a relaxation of interventions, and that NPIs are key to controlling ongoing epidemics.

The Successes and Failures of the Initial COVID-19 Pandemic Response in Romania.

In the context of the COVID-19 pandemic, countries around the world varied in the strength and timeliness of their responses. In Romania, specific challenges were faced with regards to managing the spread and limiting the impact of the disease, ranging from healthcare infrastructure to demographic and sociocultural aspects. As the country has a sizeable diaspora, major difficulties were faced when large numbers of individuals from highly affected areas returned to Romania. However, the fast implementation of control measures successfully averted a surge in the number of COVID-19 cases. This delayed the overburdening of an already challenged healthcare system during the initial phases of the epidemic. Furthermore, early control was facilitated by the exploitation of communication channels that penetrated all layers of society, from ordinary citizens to governmental authorities and high-ranking religious figures. The management of the COVID-19 crisis in Romania illustrates the importance of a fast initial response which takes into account the role played by sociocultural aspects in the context of an epidemic. As the challenges faced by Romania are not unique, these results could inform future public health strategies worldwide.

Measles Epidemics in Romania: Lessons for Public Health and Future Policy.

Measles is a highly infectious viral disease that continues to be a challenge for many countries worldwide. Although significant improvements have been observed since the introduction of vaccines, measles remains endemic in Romania. Contributing factors include vaccine hesitancy, difficulties in delivering doses to the population, and even the lack of sufficient vaccine supplies. These problems are further exacerbated by an inadequate implementation of public health measures, ranging from inefficient communication programs to the absence of a legislative framework concerning immunization. Moreover, many of the recent outbreaks were associated with chains of transmission in other countries, thus making the control of measles in Romania relevant at an international level. As many difficulties exist, understanding the key factors that limit the success of public health programs may provide guidance in shaping future strategies. Because similar issues are being faced in various other countries, the management of measles in Romania offers valuable lessons for researchers and policy-makers alike.