The emergence of SARS-CoV-2 variants has reduced antibody effectiveness, affecting vaccine protection. This study evaluated neutralizing antibodies against Wuhan strain and several variants, including Alpha, Beta, Gamma, Delta, and Omicron, in Brazilians vaccinated twice with CoronaVac, ChAdOx1-S, or BNT162b2 before Delta and Omicron emerged. After the booster, strong antibody responses to the Wuhan strain were seen in all groups, but BNT162b2 resulted in higher anti-Spike and anti-RBD IgG levels. While all vaccines showed some cross-neutralization against Alpha, Beta, Gamma, and Delta, only BNT162b2 was effective against Omicron BA.2 and BA.4/5 subvariants. Furthermore, BNT162b2 vaccination showed a positive correlation between Wuhan RBD-specific IgG and Omicron neutralizing antibodies. This group demonstrated distinct clustering patterns of neutralizing antibodies against all variants, unlike those from CoronaVac and ChAdOx1-S. The findings suggest BNT162b2 offers broader neutralization capability, highlighting the benefit of booster shots with bivalent mRNA vaccines to enhance immune responses against emerging variants.

It has been five years since the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and we are also approaching the five-year mark of the COVID-19 pandemic. The vaccine is a significant weapon in combating infectious diseases like SARS-CoV-2. Several vaccines were developed against SARS-CoV-2, and they demonstrated efficacy and safety during these five years. The rapid development of multiple next-generation vaccine candidates in different platforms with very little time is the success story of the vaccine development endeavor. This remarkable success of rapid vaccine development is a new paradigm for fast vaccine development that might help develop infectious diseases and fight against the pandemic. With the completion of five years since the beginning of SARS-CoV-2 origin, we are looking back on the five years and reviewing the milestones, vaccine platforms, animal models, clinical trials, successful collaborations, vaccine safety, real-world effectiveness, and challenges. Lessons learned during these five years will help us respond to public health emergencies and to fight the battle against future pandemics.

The impact of COVID-19 varied significantly by deprivation, ethnicity, and policy measures. We analyzed individual-level data on 12,310,485 first SARS-CoV-2 Pillar 2-PCR-confirmed infections, 439,083 hospitalizations, 107,823 deaths, and vaccination records in England from May 2020 to February 2022. Poisson regression models adjusted for demographic and temporal factors showed higher incidence rate ratios (IRRs) for severe outcomes in the most deprived areas compared to the least. We note higher IRRs for severe outcomes for all non-white relative to white ethnicities. The magnitude of IRRs for both deprivation and ethnicities declined from the wild-type to the omicron periods for severe outcomes. For infections, we observed IRRs above one for non-white ethnicities during the wild-type and alpha periods. Vaccination significantly reduced risks across all groups. For severe outcomes, preexisting health inequalities led to large and persistent disparities. For infections, measures must be structured with ethnicity and deprivation in mind early in a pandemic.

The JAK family, particularly JAK3, plays a crucial role in immune signaling and inflammatory responses. Dysregulated JAK3 activation in SARS-CoV-2 infections has been associated with severe inflammation and respiratory complications, making JAK inhibitors a viable therapeutic option. However, their use raises concerns regarding immunosuppression, which could increase susceptibility to secondary infections. While long-term adverse effects are less of a concern in acute COVID-19 treatment, patient selection and monitoring remain critical. Furthermore, adverse effects associated with oral JAK3 inhibitors necessitate the exploration of alternative strategies to optimize therapeutic efficacy while minimizing risks. This review highlights the role of JAK3 in immune and epithelial cells, examines the adverse effects of oral JAK3 inhibitors in COVID-19 and other treatments, and discusses alternative therapeutic strategies for improving patient outcomes.

We investigated the effectiveness of different COVID-19 vaccinations administered in Pakistan by studying the effect of inactivated virus, mRNA and vector formulations. This study in 916 participants was conducted between October 2021 and July 2022. Subjects receiving inactivated (A), mRNA (B), one-dose vector (C), and two-dose vector (D) vaccines were sampled at baseline, 6, 12, and 24 weeks. Serum IgG antibodies to wildtype Spike and its receptor binding domain (RBD) were measured. Pseudovirus particle-based neutralizing assays against wildtype, Delta, and JN.1 variants were performed. T cell IFN-γ responses to SARS-CoV-2 antigens were measured. Participants were aged 37.05 ± 14.44 years and comprised 48.6 % females. Baseline Spike seropositivity rose from 90 % to 96 % by 24 weeks; and 40 % to 90 % against RBD. Group B participants had the highest anti-RBD levels which peaked by 6 weeks. IgG RBD in group A and C increased up until 24 weeks. Anti-RBD levels were reduced in those over 50 years. At baseline neutralizing titers were present at 38.5 % against wildtype and in 34.2 % against Delta variants. Titers doubled in vaccine groups A-C by 12 weeks, with highest titers in B and lowest in group C participants. At baseline, neutralizing titers against the JN.1 variant were absent but low titers were evident in 10 % of participants after 12 weeks. T cell reactivity to SARS-CoV-2 increased from 31 % at baseline to 50 % in group A and 73 % in group B participants by 6 weeks after vaccination. Presence of immunity against wildtype and Delta variants in one-third of participants at baseline could be due to sub-clinical infections. Increase in humoral and cellular immunity was greater after mRNA as compared with inactivated vaccinations. As COVID-19 morbidity in the population remained low, our data supports effectiveness of multiple vaccine formulations in protecting against severe COVID-19 in this high transmission population.

RNA therapeutics represent a rapidly expanding and innovative group of pharmaceuticals. These new modalities necessitate the establishment of Occupational Exposure Limits (OELs) to ensure safe occupational handling. While there is an established methodology for setting OELs for small molecule therapeutics, this methodology is not readily applicable to large molecule RNA therapeutics that deserve additional considerations in their safety assessment, particularly for aspects related to their unique modes of action. This research, which involves an extensive review of the data available for RNA therapeutics to derive substance-specific OELs and to propose a strategy for low-characterized RNA therapeutics, fills this crucial gap. It is recommended to apply an activity correction factor (ACF) in the OEL formula for large molecules, as representative of the "α" in the OEL formula for small molecules, considering differences in route of administration, critical effects, mechanism of action, and the RNA delivery platform. Additionally, it is proposed to consider lower OEL values for mRNA vaccines as compared to other RNA therapeutics. Finally, it is suggested that the exposure assessment experience that has already been acquired when handling therapeutic proteins can also be used to define containment strategies for RNA therapeutics.

Several COVID-19 vaccines have been licensed. To support the assessment of safety signals, we developed a toolkit to support COVID-19 vaccine monitoring and benefit-risk assessment. We aim to show the application of our toolkit in the EU using thrombosis with thrombocytopenia syndrome (TTS) associated with the Vaxzevria (AstraZeneca) vaccine as a use case.

In this population-based study, we used a model incorporating data from multiple EU sources such as The European Surveillance System and EudraVigilance, and estimated the benefits of COVID-19 vaccines by comparing the observed COVID-19 confirmed cases, hospitalisations, intensive care unit (ICU) admissions, and deaths across Europe to the expected numbers in the absence of Vaxzevria vaccination. Risks of TTS associated with Vaxzevria were calculated by comparing the observed number of TTS events in individuals who received Vaxzevria to the expected number of events based on background incidence rates. To visualise the results, we developed a toolkit with an interactive web application.

62 598 505 Vaxzevria vaccines (32 763 183 to females and 29 835 322 to males) had been administered in Europe by Feb 10, 2021. Our results showed that a first dose of Vaxzevria provided benefits across all age groups. Based on vaccine effectiveness estimates and reported coverage in Europe, from Dec 13, 2020 to Dec 31, 2021, vaccination with Vaxzevria was estimated to prevent (per 100 000 doses) 12 113 COVID-19 cases, 1140 hospitalisations, 184 ICU admissions, and 261 deaths. Women aged 30-59 years and males aged 20-29 years had the highest frequency of TTS events. The benefits of vaccination outweighed the risks of TTS in all age groups, with the highest benefits and risks observed in individuals aged 60-69 years.

Our toolkit and underlying model contextualised the risk of TTS associated with Vaxzevria relative to its benefits. The methodology employed could be applied to other serious adverse events related to COVID-19 or other vaccines. The adaptability and versatility of such toolkits might contribute to strengthening preparedness for future public health emergencies.

European Medicines Agency.

The World Health Organization (WHO) announced the end of the emergency phase of Corona Virus Disease 2019 (COVID-19) in May 2023. Nations across the world address the effects of the pandemic and the need to plan for future pandemics. Ireland heavily focused on isolation and social distancing to curb the infection rate early in the pandemic. These long and extended lockdowns gave Ireland a very unique experience during the COVID-19 pandemic.

Ireland's COVID-19 pandemic management was discussed by an expert panel on the strengths in our national pandemic action plans, areas not sufficiently addressed and requirements to ensure future pandemic preparedness plans are robust.

Recommendations include having a more strategic plan to protect society's most vulnerable people, a flexible national policy that swiftly implements advances in scientific knowledge and good practices, a robust communication plan including localised information to prevent "pandemic fatigue," and address challenges from restrictions, lockdowns and isolation such as mental health and wellbeing.

Lessons learnt from the Irish COVID-19 pandemic experience can be utilised for pandemic preparedness plans, nationally and internationally.

Vaccination has been instrumental in curbing the transmission of SARS-CoV-2 and mitigating the severity of clinical manifestations associated with COVID-19. Numerous COVID-19 vaccines have been developed to this effect, including BioNTech-Pfizer and Moderna's mRNA vaccines, as well as adenovirus vector-based vaccines such as Oxford-AstraZeneca. However, the emergence of new variants and subvariants of SARS-CoV-2, characterized by enhanced transmissibility and immune evasion, poses significant challenges to the efficacy of current vaccination strategies. In this review, we aim to comprehensively outline the landscape of emerging SARS-CoV-2 variants of concern (VOCs) and sub-lineages that have recently surfaced in the post-pandemic years. We assess the effectiveness of existing vaccines, including their booster doses, against these emerging variants and subvariants, such as BA.2-derived sub-lineages, XBB sub-lineages, and BA.2.86 (Pirola). Furthermore, we discuss the latest advancements in vaccine technology, including multivalent and pan-coronavirus approaches, along with the development of several next-generation coronavirus vaccines, such as exosome-based, virus-like particle (VLP), mucosal, and nanomaterial-based vaccines. Finally, we highlight the key challenges and critical areas for future research to address the evolving threat of SARS-CoV-2 subvariants and to develop strategies for combating the emergence of new viral threats, thereby improving preparedness for future pandemics.

With the emergence of Omicron during the pandemic and the establishment of antibody waning over time, vaccine effectiveness, especially against infection, declined sharply from the original levels seen after the initial rollout. However, studies have demonstrated that they still provided substantial protection vs severe/fatal disease even with Omicron and after waning. Social media has been rife with reports claiming vaccines provided no benefit and some even claiming they made things worse, often driven by simple presentations of raw observational data using erroneous arguments involving epidemiologic fallacies including the base rate fallacy, Simpson's paradox, and the ecological fallacy and ignoring the extensive bias especially from confounding that is an inherent feature of these data. Similar fallacious arguments have been made by some in promoting vaccination policies, as well. Generally, vaccine effectiveness cannot be accurately estimated from raw population summaries but instead require rigorous, careful studies using epidemiologic designs and statistical analysis tools attempting to adjust for key confounders and sources of bias. This article summarizes what aggregated evidence across studies reveals about effectiveness of the mRNA vaccines as the pandemic has evolved, chronologically summarized with emerging variants and highlighting some of the fallacies and flawed arguments feeding social media-based claims that have obscured society's collective understanding.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been widespread since 2020 and will likely continue to cause substantial recurring epidemics. However, understanding the underlying infection burden and dynamics, particularly since late 2021 when the Omicron variant emerged, is challenging. Here, we leverage extensive surveillance data available in New York City (NYC) and a comprehensive model-inference system to reconstruct SARS-CoV-2 dynamics therein through August 2023.

We fit a metapopulation network SEIRSV (Susceptible-Exposed-Infectious-(re)Susceptible-Vaccination) model to age- and neighborhood-specific data of COVID-19 cases, emergency department visits, and deaths in NYC from the pandemic onset in March 2020 to August 2023. We further validate the model-inference estimates using independent SARS-CoV-2 wastewater viral load data.

The validated model-inference estimates indicate a very high infection burden-the number of infections (i.e., including undetected asymptomatic/mild infections) totaled twice the population size ( > 5 times documented case count) during the first 3.5 years. Estimated virus transmissibility increased around 3-fold, whereas estimated infection-fatality risk (IFR) decreased by >10-fold during this period. The detailed estimates also reveal highly complex variant dynamics and immune landscape, and higher infection risk during winter in NYC over the study period.

This study provides highly detailed epidemiological estimates and identifies key transmission dynamics and drivers of SARS-CoV-2 during its first 3.5 years of circulation in a large urban center (i.e., NYC). These transmission dynamics and drivers may be relevant to other populations and inform future planning to help mitigate the public health burden of SARS-CoV-2.

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has caused an unprecedented pandemic in human history. To date, more than 6.5 million lives have been lost to COVID-19 (coronavirus disease 2019). Following widespread efforts for COVID-19 vaccination in Brazil, there has been a drastic reduction in COVID-19 deaths, which was particularly evident in the city of Botucatu, SP, Brazil, after a campaign to a mass vaccination. Our objective was to assess the temporal and epidemiological spread of variants of concern (VOC) of SARS-CoV-2 in the four weeks preceding the massive vaccination campaign in the municipality. After randomizing 400 samples, Next-Generation Sequencing was used to produce sequences and determine the variants. Among high-quality sequences, 98.4% belonged to the VOC Gamma, with P.1 and P.1.14 being the most prevalent lineages. P.1 was more frequent in both men and women, and in younger individuals and adults (0-59 years) compared to P.1.14. There was no correlation between the variants and the presence of comorbidities or between them and moderate to severe clinical cases of COVID-19 or death. However, P.1 was more frequent than P.1.14 in people with mild forms of the disease and in those who exhibited symptoms. In the phylogenetic analyses, a small cluster of 9 P.1.14 samples containing mutations in ORF1a: M584V and A3620V was observed, which had not been found in any Gamma sequences to date. The importance of genomic surveillance of SARS-CoV-2 is evident in assisting public health decision-making and the management of COVID-19 and other diseases.

The efficacy of COVID-19 vaccines against the Delta variant has been observed to be high, both against severe disease and infection. The full population level vaccine effectiveness, however, also contains the indirect effects of vaccination, which require analysis of transmission dynamics to uncover. Finland was close to naïve to SARS-CoV-2 infections before the Delta dominant era, and non-pharmaceutical interventions (NPIs) were at an internationally low level. We utilize Finnish register data and a mathematical model for transmission and COVID-19 disease burden to construct a completely unvaccinated control population and estimate the different components of the vaccine effectiveness. The estimated direct effectiveness was 72% against COVID-19 cases and 87-96% against severe disease outcomes, but the estimated indirect effectiveness was even better, 93% against cases and 94-97% against severe disease. The total and overall effectiveness, including both direct and indirect effects of vaccination, were thus excellent. Our results show how well the population was protected by vaccination during the Delta era, especially by the indirect effectiveness, providing protection also to the unvaccinated part of the population. The estimated averted numbers of hospitalizations, ICU admissions, and deaths in Finland during the Delta era under the implemented NPIs were about 100 times the observed numbers.

Within an infrastructure to monitor vaccine effectiveness (VE) against hospitalization due to COVID-19 and COVID-19 related deaths from November 2022 to July 2023 in seven countries in real-world conditions (VEBIS network), we compared two approaches: (a) estimating VE of the first, second or third COVID-19 booster doses administered during the autumn of 2022, and (b) estimating VE of the autumn vaccination dose regardless of the number of prior doses (autumnal booster approach). Retrospective cohorts were constructed using Electronic Health Records at each participating site. Cox regressions with time-changing vaccination status were fit and site-specific estimates were combined using random-effects meta-analysis. VE estimates with both approaches were mostly similar, particularly shortly after the start of the vaccination campaign, and showed a similar timing of VE waning. However, autumnal booster estimates were more precise and showed a clearer trend, particularly compared to third booster estimates, as calendar time increased after the vaccination campaign and during periods of lower SARS-CoV-2 activity. Moreover, the decrease in protection by increasing calendar time was more clear and precise than when comparing protection by number of doses. Therefore, estimating VE under an autumnal booster framework emerges as a preferred method for future monitoring of COVID-19 vaccination campaigns.

We followed the COVID-19 pandemic in Manaus, one of the epicenters of COVID-19 in Brazil, using an epidemiological mathematical model and made five main conclusions. First, in early 2022, the actual cases exceed officially reported data by up to 8 times. Second, despite vaccination campaigns, the collective immunity threshold necessary was insufficient to contain severe cases of COVID-19. Next, the low observed mortality demonstrated the effectiveness of vaccination. Next, the drop in the vaccination rate combined with immune escape by the Omicron sub-variants (BA.2.12.1, BA.4, and BA.5) resulted in new wave after November 2022. Finally, to minimize severe cases of COVID-19, we need to raise vaccination thresholds above 90-95% of the entire population including children aged 6 months and older and require booster doses at least in four-month intervals. This approach would help to prevent severe cases of COVID-19 that cause hospitalizations and deaths.

Background/Objectives: Metabolic syndrome (MetS) is a predisposing factor for severe COVID-19. The effectiveness of COVID-19 vaccines in patients with MetS has been poorly investigated. The aim of this study was to evaluate the effectiveness of COVID-19 vaccination before (BO) and after the Omicron (AO) SARS-CoV-2 variant in patients with MetS. Methods: This retrospective observational study was carried out in a total of 3194 patients with MetS and a COVID-19 PCR or rapid antigen test. The main outcomes were vaccine effectiveness against infection, hospitalization and death resulting from COVID-19. Results: BO, only two doses of BNT162b2 were effective against infection, this effectiveness was lost AO. Also, with two doses, BNT162b2, ChAdOx1 and CoronaVac were effective against hospitalization BO; however, AO, only BNT162b2 and CoronaVac were effective. Regarding death as an outcome of COVID-19, two doses of BNT162b2 were effective BO, whereas AO, BNT162b2 and CoronaVac were 100% effective. BO the presentation of a sore throat increased after two doses of COVID-19 vaccine regardless of the type, and the presentation of dyspnea diminished after two doses of BNT162b2 and CoronaVac. Conclusions: The SARS-CoV-2 Omicron variant has impacted vaccines' effectiveness against hospitalization and death in patients with MetS. A tailored vaccination scheme for patients with MetS should be implemented due to the varying effectiveness rates observed in our study.

Cardiovascular disease remains a leading cause of global mortality, with many unresolved issues in current clinical treatment strategies despite years of extensive research. Due to the great progress in nanotechnology and gene therapy in recent years, the emerging gene therapy based on nanocarriers has provided a promising therapeutic alternative for cardiovascular diseases. This review outlines the status of nanocarriers as vectors in gene therapy for cardiovascular diseases, including coronary heart disease, pulmonary hypertension, hypertension, and valvular heart disease. It discusses challenges and future prospects, aiming to support emerging clinical treatments. This review is the first to summarize gene therapy using nanocarriers for valvular heart disease, highlighting their potential in targeting challenging tissues.

Prior studies have demonstrated the effectiveness of COVID-19 vaccines in children and adolescents. However, the benefits of vaccination in these age groups with prior infection remain underexplored.

To evaluate the effectiveness of COVID-19 vaccination in preventing reinfection with various Omicron subvariants (BA.1/2, BA.4/5, XBB, and later) among 5- to 17-year-olds with prior SARS-CoV-2 infection.

A target trial emulation through nested designs with distinct study periods.

The study utilized data from the Research COVID to Enhance Recovery (RECOVER) initiative, a national electronic health record (EHR) database comprising 37 U.S. children's hospitals and health institutions.

Individuals aged 5-17 years with a documented history of SARS-CoV-2 infection prior to the study start date during a specific variant-dominant period (Delta, BA.1/2, or BA.4/5) who received a subsequent dose of COVID-19 vaccine during the study periods were compared with those with a documented history of infection who did not receive SARS-CoV-2 vaccine during the study period. Those infected within the Delta-Omicron composite period (December 1, 2021, to December 31, 2021) were excluded. The study period was from January 1, 2022, to August 30, 2023, and focused on adolescents aged 12 to 17 years and children aged 5 to 11 years.

At least received one COVID-19 vaccination during the study period vs. no receipt of any COVID-19 vaccine during the study period.

The primary outcome is documented SARS-CoV-2 reinfection during the study period (both asymptomatic and symptomatic cases). The effectiveness of the COVID-19 vaccine was estimated as (1- hazard ratio) *100%, with confounders adjusted by a combination of propensity score matching and exact matching.

The study analyzed 87,573 participants during the BA.1/2 period, 229,326 during the BA.4/5 period, and 282,981 during the XBB or later period. Among vaccinated individuals, significant protection was observed during the BA.1/2 period, with effectiveness rates of 62% (95% CI: 38%-77%) for children and 65% (95% CI: 32%-81%) for adolescents. During the BA.4/5 period, vaccine effectiveness was 57% (95% CI: 25%-76%) for children, but not statistically significant for adolescents (36%, 95% CI: -16%-65%). For the XBB period, no significant protection was observed in either group, with effectiveness rates of 22% (95% CI: -36%-56%) in children and 34% (95% CI: -10%-61%) in adolescents.

COVID-19 vaccination provides significant protection against reinfection for children and adolescents with prior infections during the early and mid-Omicron periods. This study also highlights the importance of addressing low vaccination rates in pediatric populations to enhance protection against emerging variants.

Surgical care has been significantly affected by the COVID-19 pandemic. This study was conducted to evaluate the effects of the pandemic on lung cancer and mediastinal tumor surgery.

Changes in the number of surgical procedures for lung cancer and mediastinal tumors were analyzed using the National Clinical Database of Japan. Patient characteristics, including disease stage and histological type, from 2019 to 2022 were evaluated using annual datasets.

Comparisons with 2019 showed that the number of patients who underwent surgery for primary lung cancer or a mediastinal tumor decreased in 2020 and then remained stable. There were no clinically significant changes in the trend over the four-year period regarding the number of patients for each clinical and pathological stage of lung cancer. Regarding mediastinal tumors, there was no significant difference in tumor size between years. There was a slight change in the selection of surgical indication during the second quarter of 2020, although its impact on annual trends in the stage distribution for lung cancer and primary disease for mediastinal tumors was minimal.

Analyses of lung cancer and mediastinal tumor surgery cases in Japan during the COVID-19 pandemic showed no significant disease profile changes related to treatment delay.

A growing body of evidence suggests a potential link between the SARS-CoV-2 vaccine and menstrual changes in women who were menstruating at the time of vaccination. Nevertheless, the prevalence of this event in those with secondary amenorrhea for different causes, i.e. formerly menstruating women, remains unclear. It is plausible that, analogous to those observed in currently menstruating women, they experienced some degree of alteration in their reproductive health, defined here as menstrual-related disturbances.

The aim was to analyze this phenomenon and identify the factors associated with the occurrence of menstrual-related disturbances in this subpopulation. Study design: A retrospective observational cross-sectional study was conducted among adult Spanish in December 2021 using an online survey (N = 17,512). The present analysis includes a subpopulation of vaccinated and formerly menstruating women (N = 548). General characteristics, medical history, and adverse events following COVID-19 vaccination were recorded. Chi-square, Mann-Whitney U and McNemar mid-P tests were performed. Bivariate logistic regression was then used to identify the key factors influencing this unexpected event.

In comparison with the first dose, significantly higher percentages of respondents experienced menstrual-related disturbances (dose 1: 38.5 percent vs. dose 2: 44.8 percent) after receiving the second one. Among them, those related to the length and flow stand out, being of long-term nature in about 17-20 percent of cases. Interindividual factors influencing this unexpected event after receiving the dose 1 may include weight, perimenopause, preexisting diagnoses of non-autoimmune rheumatic/articular conditions, use of hormonal contraceptives, suffering from other vaccine side effects - such as arm pain and the number of previous pregnancies; for dose 2, these factors may include suffering from menstrual-related alterations after receiving dose 1, as well as the use of hormonal contraceptives and perimenopause.

Formerly menstruating women might experience long-term menstrual-related disturbances following COVID-19 vaccination. Potential influencing factors include weight, perimenopause, rheumatic/articular conditions, hormonal contraceptives, vaccine side effects and previous pregnancies.

The SARS-CoV-2-induced disease, COVID-19, remains a worldwide public health concern due to its high rate of transmission, even in vaccinated and previously infected people. In the endemic state, it continues to cause significant pathology. To elu- cidate the viral mutational changes and screen the emergence of new variants of concern, we conducted this study in Bangladesh. The viral RNA genomes extracted from 25 ran- domly collected samples of COVID-19-positive patients from March 2021 to February 2022 were sequenced using Illumina COVID Seq protocol and genomic data processing, as well as evaluations performed in DRAGEN COVID Lineage software. In this study, the percentage of Delta, Omicron, and Mauritius variants identified were 88%, 8%, and 4%, respectively. All of the 25 samples had 23,403 A>G (D614G, S gene), 3037 C>T (nsp3), and 14,408 C>T (nsp12) mutations, where 23,403 A>G was responsible for increased transmis- sion. Omicron had the highest number of unique mutations in the spike protein (i.e., sub- stitutions, deletions, and insertions), which may explain its higher transmissibility and immune-evading ability than Delta. A total of 779 mutations were identified, where 691 substitutions, 85 deletions, and 3 insertion mutations were observed. To sum up, our study will enrich the genomic database of SARS-CoV-2, aiding in treatment strategies along with understanding the virus's preferences in both mutation type and mutation site for predicting newly emerged viruses' survival strategies and thus for preparing to coun- teract them.

Determining COVID-19 vaccination strategies presents many challenges in light of limited vaccination capacity and the heterogeneity of affected communities. Who should be prioritized for early vaccination when different groups manifest different levels of risks and contact rates? Answering such questions often becomes computationally intractable given that network size can exceed millions. We obtain a framework to compute the optimal vaccination strategy within seconds to minutes from among all strategies, including highly dynamic ones that adjust vaccine allocation as often as required, and even with modest computation resources. We then determine the optimal strategy for a large range of parameter values representative of various US states, countries, and case studies including retirement homes and prisons. The optimal is almost always one of a few candidate strategies, and, even when not, the suboptimality of the best among these candidates is minimal. Further, we find that many commonly deployed vaccination strategies, such as vaccinating the high risk group first, or administering second doses without delay, can often incur higher death rates, hospitalizations, and symptomatic infection counts. Our framework can be easily adapted to future variants or pandemics through appropriate choice of the compartments of the disease and parameters.

Large-scale population studies are important to monitor and evaluate aspects of a vaccination programme including vaccine coverage, real-world effectiveness, and post-licensure vaccine safety. These types of epidemiological studies often come under the remit of public health agencies, such as the UK Health Security Agency (UKHSA) in England, which are required to undertake surveillance of vaccine-preventable diseases, including via seroepidemiological studies and data linkage studies using national-level electronic healthcare data. An individual-level national vaccine register with an accurate denominator can be the key to gaining insights into vaccine coverage, effectiveness, and safety. During the coronavirus disease 2019 pandemic, England's first vaccine register was developed. This enabled timely estimates of real-world vaccine effectiveness in the whole population of England, as well as enabling epidemiological investigations of rare potential risks from vaccines in specific populations. Population-based research studies, including prospective cohort studies, are complementary to surveillance and combined, enable more comprehensive assessments. As there was an unprecedented investment into research studies and infrastructure during the pandemic, the scale of these studies meant they were able to contribute to vaccine programme evaluations in a way that had not been possible for previous vaccine programmes. In this review, we summarise the different large-scale surveillance and research studies that have been used to evaluate and inform vaccine policy from the time of the first data linkage studies undertaken in England in the 1990s to the present-day post-COVID-19 pandemic.

Vaccination is the most effective method of preventing and controlling the transmission of infectious diseases within populations. However, the phenomenon of waning immunity can induce periodic fluctuations in epidemic spreading. This study proposes a coupled epidemic-vaccination dynamic model to analyze the influence of immunity waning on the epidemic spreading within the context of voluntary vaccination. First, we establish an SIRSV (susceptible-infected-recovered-susceptible-vaccinated) compartment model to describe the transmission mechanism of infectious diseases based on the mean-field theory. Within this model, we incorporate a nonlinear infection rate with network topology and consider the waning natural and vaccine-induced immunity at the individual level. The evolutionary model of voluntary vaccination strategy is integrated into the SIRSV model to characterize the impact of vaccination behavior on the infectious disease transmission. We also consider two individual risk assessment methods, namely, the individual-based risk assessment (IB-RA) method and the society-based risk assessment (SB-RA) method, originating from local and global perspectives, respectively. Then, utilizing the next-generation matrix method, we derive the time-varying effective reproduction numbers of the model. Also, the theoretical analysis of optimal strategy thresholds in the individual decision-making process is also conducted. The results indicate that the thresholds obtained from the agent-based model (ABM) simulation method are consistent with the theoretical analysis, demonstrating the effectiveness of our model. Finally, we apply the coupled model to the COVID-19 pandemic in France, Germany, Italy, and the United Kingdom. This study analyzes the impact of waning immunity and provides early warning for the outbreak of the epidemics.

To estimate the effectiveness of several vaccine brands-Pfizer, Astra, and Sinovac-against symptomatic COVID-19 without information on vaccination at the individual level.

We use data of mass vaccination programs-specifically, for sexagenarians and quinquagenarians-in three large municipalities of Mexico (Monterrey, Guadalupe, and San Nicolás) to conduct a two-step time series estimation procedure involving a synthetic control group. The data covers the period between the first week of March 2020 and the first week of October 2021.

Vaccine effectiveness is a concave function of time. At the peak, Pfizer reaches 92.6 % effectiveness, Astra 83.6 % and Sinovac 65.6 %. This occurs 9 to 12 weeks after the first shot.

The results indicate that the three vaccines protect against symptomatic COVID-19. Nevertheless, they offer different levels of protection. The results also suggest that VE-under a two-shot scheme-reaches its peak 9 to 16 weeks after the first shot. Moreover, there seems to be a trade-off between achieving higher efficiency by administering the 2nd shot earlier or extending the protection period by administering it later.

With the ongoing emergence of SARS-CoV-2 variants, there is a need for standard approaches to characterize the risk of vaccine breakthrough. We aimed to estimate the association between variant and vaccination status in case-only surveillance data. Included cases were symptomatic adult laboratory-confirmed COVID-19 cases, with onset between January 2021 and April 2022, reported by five European countries (Estonia, Ireland, Luxembourg, Poland, and Slovakia) to The European Surveillance System. Associations between variant and vaccination status were estimated using conditional logistic regression, within strata of country and calendar date, and adjusting for age and sex. We included 80,143 cases including 20,244 Alpha (B.1.1.7), 152 Beta (B.1.351), 39,900 Delta (B.1.617.2), 361 Gamma (P.1), 10,014 Omicron BA.1, and 9,472 Omicron BA.2. Partially vaccinated cases were more likely than unvaccinated cases to be Beta than Alpha (adjusted odds ratio [aOR] 2.48, 95% CI 1.29-4.74), and Delta than Alpha (aOR 1.75, 1.31-2.34). Fully vaccinated cases were relative to unvaccinated cases more frequently Beta than Alpha (aOR 4.61, 1.89-11.21), Delta than Alpha (aOR 2.30, 1.55-3.39), and Omicron BA.1 than Delta (aOR 1.91, 1.60-2.28). We found signals of increased breakthrough infections for Delta and Beta relative to Alpha, and Omicron BA.1 relative to Delta.

We investigate the impact of differential vaccine effectiveness, waning immunity, and natural cross-immunity on the capacity for vaccine-induced strain replacement in two-strain models of infectious disease spread. We focus specifically on the case where the first strain is more transmissible but the second strain is more immune-resistant. We consider two cases on vaccine-induced immunity: (1) a monovalent model where the second strain has immune escape with respect to vaccination; and (2) a bivalent model where the vaccine remains equally effective against both strains. Our analysis reaffirms the capacity for vaccine-induced strain replacement under a variety of circumstances; surprisingly, however, we find that which strain is preferred depends sensitively on the degree of differential vaccine effectiveness. In general, the monovalent model favors the more immune-resistant strain at high vaccination levels while the bivalent model favors the more transmissible strain at high vaccination levels. To further investigate this phenomenon, we parametrize the bifurcation space between the monovalent and bivalent model.

COVID-19 vaccine programmes must account for variable immune responses and waning protection. Existing descriptions of antibody responses to COVID-19 vaccination convey limited information about the mechanisms of antibody production and maintenance. We describe antibody dynamics after COVID-19 vaccination with two biologically motivated mathematical models. We fit the models using Markov chain Monte Carlo to seroprevalence data from 14 602 uninfected individuals in England between May 2020 and September 2022. We analyse the effect of age, vaccine type, number of doses and the interval between doses on antibody production and longevity. We find evidence that individuals over 35 years old twice vaccinated with ChAdOx1-S generate a persistent antibody response suggestive of long-lived plasma cell induction. We also find that plasmablast productive capacity is greater in: younger people than older people (≤4.5-fold change in point estimates); people vaccinated with two doses than one dose (≤12-fold change); and people vaccinated with BNT162b2 than ChAdOx1-S (≤440-fold change). We find the half-life of an antibody to be 23-106 days. Routinely collected seroprevalence data are invaluable for characterizing within-host mechanisms of antibody production and persistence. Extended sampling and linking seroprevalence data to outcomes would enable conclusions about how humoral kinetics protect against disease.

Infectious diseases pose significant challenges to public health, leading to illness and even death. Vaccinations are vital for protecting society, yet beliefs in conspiracy theories related to infectious diseases increase vaccine hesitancy. This paper delves into vaccination decisions in the context of COVID-19, which continues to strain the health care system. While past research focuses on countering conspiratorial beliefs with cognitive persuasion interventions, we propose a social intervention as an alternative. Our novel intervention seeks to mitigate the effects of conspiratorial beliefs by fostering individuals' interdependent self-construal - viewing oneself in the context of social relationships. Interdependent self-construal was operationalized in multiple ways (measured in Studies 1, 2 and 3; manipulated to test causality in Studies 4 and 5). Conspiratorial beliefs were also manipulated in Study 5. The results show that the association between conspiratorial beliefs and vaccine hesitancy is weakened among individuals whose interdependent self-construal is more accessible. Moreover, this effect was mediated by prosocial motivation. We discuss the implications of our findings for developing and communicating health policies and propose potential contexts where this intervention may be relevant, thereby providing valuable insights into enhancing societal well-being in the face of conspiratorial beliefs.

Up-to-date evidence from European studies on long-term vaccine effectiveness (VE) of COVID-19 vaccines is lacking. This review aimed to evaluate effectiveness and durability of primary vaccine series and boosters in preventing infection and severe outcomes in the European population.

We conducted systematic searches of PubMed and Embase up to 22 January 2024. We included observational studies that evaluated VE against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or severe disease (hospitalisation, intensive care unit admission or death) for primary series and boosters in Europe. We applied a random-effects meta-analysis model.

We included 33 studies and over 56 million participants. The overall VE of the complete primary series against infection with any SARS-CoV-2 variant was 70.7%. VE was lower for Omicron, at 26.1%, than for pre-Omicron strains, at 77.0%. Over time, VE against infection by any variant decreased from 68.9% to 38.9% after 6 months. Boosters restored VE to 76.4% and maintained at 58.4% after 3 months. The overall VE of a complete primary series for severe outcomes due to any variant was 87.4%, with 93.3% for pre-Omicron and 62.8% for Omicron strains. Protection against severe outcomes declined less than for infection. 6 months after the primary series, the vaccine still provided over 50% protection against severe outcomes caused by Omicron. Boosters restored VE to 87.9% and maintained at 78.5% after 3 months.

VE against SARS-CoV-2 infection declines markedly with time and Omicron variants. Protection against severe outcomes was more durable and resistant to viral mutation. Boosters restored protection, emphasising the need for timely booster vaccination for vulnerable populations.

With an ever growing and expanding body of literature on the newly developed vaccines against the COVID-19, there is an urgent need for a comprehensive analysis of the current state of research on vaccine effectiveness (VE). This study conducted a comprehensive bibliometric analysis to critically examine the productivity and impact of retrieved publications on COVID-19 VE and to predict the future directions of research in the field.

The global literature on COVID-19 VE from 2021 to 2024 was extracted from the VIEW-hub website. Using bibliometric analysis tools, specifically Microsoft Excel, the R package "bibliometrix, biblioshiny" and VOSviewer, we analyzed publications for trends in productivity, citations, and global collaboration. Key metrics assessed include publication and citation trends, influential authors, collaborative networks, and thematic evolution, offering a comprehensive view of the research landscape on COVID-19 VE.

A total of 490 publications were authored by 5031 authors from 934 institutions and 78 countries and published in 119 journals. Most retrieved publications were original articles (99.6 %). The United States was the most productive country with 205 publications (41.8 %). Global research collaborations were mainly within developed countries. Analysis of the thematic evolution of the field illustrated changing research focus over three distinct time clusters. Throughout 2021, studies were focused on outlining infection prevention and control measures, as well as examining the efficacy of novel mRNA vaccines. In 2022, the linchpin of research was shifted towards dissecting the epidemiological correlates of the pandemic in light of the widespread use of vaccines. The final cluster showed special emphasis on the new variants of COVID-19 and the long-term outcomes of vaccines.

Our study identified geopolitical disparities and weak engagement from developing countries in the ongoing efforts regarding COVID-19 VE. This study can inform researchers, policymakers, and funding agencies as they assess ongoing research and future directions in COVID-19 VE.

To optimize vaccination strategies, it is useful to detect breakthrough infections and assess vaccine effectiveness in programmatic use. Monitoring emerging SARS-CoV-2 variants and vaccine effectiveness against them is also essential to determine the most effective vaccine options. This study aims to monitor SARS-CoV-2 breakthrough infections, the emergence of new SARS-CoV-2 variants, and host immune response during the peri-infection period of COVID-19. The study will also assess the uptake of the COVID-19 vaccine booster doses, and associated barriers or motivations among healthcare workers (HCWs).

Leveraging an existing HCW cohort in Bangladesh, HCWs will be enrolled from purposively selected health facilities from four different administrative divisions across Bangladesh. We captured cohort data on HCW's demographic information, clinical information, COVID-19 illness, and exposure, and vaccination histories for COVID-19. However, no biological specimens were collected for testing during the first phase of the cohort. In the current study, we plan to follow enrolled HCWs biweekly for suspected COVID-19 illness and capture relevant data including illness outcomes. Respiratory swab samples from symptomatic and a subset of asymptomatic HCWs will be tested for SARS-CoV-2 by rRT-PCR and positive samples will undergo Sanger sequencing to identify the SARS-CoV-2 variants of concern (VOCs). We will also perform Whole Genome Sequencing on a subset of SARS-CoV-2 positive samples with low CT values (Ct ≤ 30) to identify emerging SARS-CoV-2 variants. To examine the antibody response, we will collect blood samples from the participants at 12-week intervals for one year. We will use the EUROIMMUN kit and will also perform in-house ELISA to assess host immune factors with Luminex platform.

This proposed study will generate useful data on COVID-19 breakthrough infection and the durability of anti-SARS-CoV-2 antibodies among HCWs following vaccination. The findings on booster vaccination intention and uptake will inform government COVID-19 vaccination strategies. Information on circulating and emerging strains of SARS-CoV-2 and vaccine performance against those strains will help understand population-level risks of COVID-19 infection. The study will generate data on facilitators and barriers to COVID-19 booster uptake among HCWs which can inform health communication messaging to improve booster acceptance in this population.

Recombinant protein vaccines represent a well-established, reliable and safe approach for pandemic vaccination. SpikoGen® is a recombinant spike protein trimer manufactured in insect cells and formulated with Advax-CpG55.2 adjuvant. In murine, hamster, ferret and non-human primate studies, SpikoGen® consistently provided protection against a range of SARS-CoV-2 variants. A pivotal Phase 3 placebo-controlled efficacy trial involving 16,876 participants confirmed the ability of SpikoGen® to prevent infection and severe disease caused by the virulent Delta strain. SpikoGen® subsequently received a marketing authorization from the Iranian FDA in early October 2021 for prevention of COVID-19 in adults. Following a successful pediatric study, its approval was extended to children 5 years and older. Eight million doses of SpikoGen® have been delivered, and a next-generation booster version is currently in development. This highlights the benefits of adjuvanted protein-based approaches which should not overlook when vaccine platforms are being selected for future pandemics.

This study aimed to explore the clinical profile and the impact of vaccination status on various health outcomes among COVID-19 patients diagnosed in different phases of the pandemic, during which several variants of concern (VOCs) circulated in South Carolina (SC). The current study included 861,526 adult COVID-19 patients diagnosed between January 2021 and April 2022. We extracted their information about demographic characteristics, vaccination, and clinical outcomes from a statewide electronic health record database. Multiple logistic regression models were used to compare clinical outcomes by vaccination status in different pandemic phases, accounting for key covariates (e.g. historical comorbidities). A reduction in mortality was observed among COVID-19 patients during the whole study period, although there were fluctuations during the Delta and Omicron dominant periods. Compared to non-vaccinated patients, full-vaccinated COVID-19 patients had lower mortality in all dominant variants, including Pre-alpha (adjusted odds ratio [aOR]: 0.33; 95%CI: 0.15-0.72), Alpha (aOR: 0.58; 95%CI: 0.42-0.82), Delta (aOR: 0.28; 95%CI: 0.25-0.31), and Omicron (aOR: 0.29; 95%CI: 0.26-0.33) phases. Regarding hospitalization, full-vaccinated parties showed lower risk of hospitalization than non-vaccinated patients in Delta (aOR: 0.44; 95%CI: 0.41-0.47) and Omicron (aOR: 0.53; 95%CI: 0.50-0.57) dominant periods. The findings demonstrated the protection effect of the COVID-19 vaccines against all VOCs, although some of the full-vaccinated population still have symptoms to varying degrees from COVID-19 disease at different phases of the pandemic.