SARS-CoV-2 Omicron variants: burden of disease, impact on vaccine effectiveness and need for variant-adapted vaccines.

The highly transmissible Omicron (B.1.1.529) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first detected in late 2021. Initial Omicron waves were primarily made up of sub-lineages BA.1 and/or BA.2, BA.4, and BA.5 subsequently became dominant in mid-2022, and several descendants of these sub-lineages have since emerged. Omicron infections have generally caused less severe disease on average than those caused by earlier variants of concern in healthy adult populations, at least, in part, due to increased population immunity. Nevertheless, healthcare systems in many countries, particularly those with low population immunity, have been overwhelmed by unprecedented surges in disease prevalence during Omicron waves. Pediatric admissions were also higher during Omicron waves compared with waves of previous variants of concern. All Omicron sub-lineages exhibit partial escape from wild-type (Wuhan-Hu 1) spike-based vaccine-elicited neutralizing antibodies, with sub-lineages with more enhanced immuno-evasive properties emerging over time. Evaluating vaccine effectiveness (VE) against Omicron sub-lineages has become challenging against a complex background of varying vaccine coverage, vaccine platforms, prior infection rates, and hybrid immunity. Original messenger RNA vaccine booster doses substantially improved VE against BA.1 or BA.2 symptomatic disease. However, protection against symptomatic disease waned, with reductions detected from 2 months after booster administration. While original vaccine-elicited CD8+ and CD4+ T-cell responses cross-recognize Omicron sub-lineages, thereby retaining protection against severe outcomes, variant-adapted vaccines are required to expand the breadth of B-cell responses and improve durability of protection. Variant-adapted vaccines were rolled out in late 2022 to increase overall protection against symptomatic and severe infections caused by Omicron sub-lineages and antigenically aligned variants with enhanced immune escape mechanisms.

COVID-19 Epidemiology, Immunity, and Vaccine Development in Children: A Review.

Although pediatric populations experienced lower COVID-19 severity and mortality than adults, the epidemiology of this disease continues to evolve. COVID-19 clinical manifestations in pediatrics commonly include fever and cough, but may differ from adults and by variant. Serious complications, including MIS-C, rarely occur. Although early data showed a decreased likelihood of COVID-19 transmission from children versus adults, outbreaks and viral shedding studies support pediatric transmission potential. Children may mount more robust initial immune responses to SARS-CoV-2 versus adults. COVID-19 vaccines with available pediatric data include BNT162b2, mRNA-1273, CoronaVac, and BBIBP-CorV. Depending on age group and jurisdiction, BNT162b2 and mRNA-1273 have received full approval or emergency/conditional authorization in the United States and European Union from 6 months of age. Clinical trials have shown BNT162b2 and mRNA-1273 safety and high efficacy in pediatric populations, with demonstrably noninferior immune responses versus young adults. Real-world studies further support BNT162b2 safety and effectiveness against the Delta variant. mRNA vaccination benefits are considered to outweigh risks, including myocarditis; however, pediatric vaccination rates remain relatively low. Given a growing body of clinical trial and real-world data showing vaccine safety and effectiveness, pediatric vaccination should be prioritized as an important strategy to control the pandemic.

Addressing COVID-19 vaccine hesitancy.

Immunization programmes have been globally recognized as one of the most successful medical interventions against infectious diseases. Despite the proven efficacy and safety profiles of coronavirus disease 2019 (COVID-19) vaccines, there are still a substantial number of people who express vaccine hesitancy. Factors that influence vaccine decision-making are heterogenous, complex, and context specific and may be caused or amplified by uncontrolled online information or misinformation. With respect to COVID-19, the recent emergence of novel variants of concern that give rise to milder disease also drives vaccine hesitancy. Healthcare professionals remain one of the most trusted groups to advise and provide information to those ambivalent about COVID-19 vaccination and should be equipped with adequate resources and information as well as practical guidance to empower them to effectively discuss concerns. This article seeks to summarize the currently available information to address the most common concerns regarding COVID-19 vaccination.

Benefit-risk evaluation of COVID-19 vaccination in special population groups of interest.

Several population groups display an increased risk of severe disease and mortality following SARS-CoV-2 infection. These include those who are immunocompromised (IC), have a cancer diagnosis, human immunodeficiency virus (HIV) infection or chronic inflammatory disease including autoimmune disease, primary immunodeficiencies, and those with kidney or liver disease. As such, improved understanding of the course of COVID-19 disease, as well as the efficacy, safety, and benefit-risk profiles of COVID-19 vaccines in these vulnerable groups is paramount in order to inform health policy makers and identify evidence-based vaccination strategies. In this review, we seek to summarize current data, including recommendations by national health authorities, on the impact and benefit-risk profiles of COVID-19 vaccination in these populations. Moving forward, although significant efforts have been made to elucidate and characterize COVID-19 disease course and vaccine responses in these groups, further larger-scale and longer-term evaluation will be instrumental to help further guide management and vaccination strategies, particularly given concerns about waning of vaccine-induced immunity and the recent surge of transmission with SARS-CoV-2 variants of concern.

The Impact of Evolving SARS-CoV-2 Mutations and Variants on COVID-19 Vaccines.

The emergence of several new variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in recent months has raised concerns around the potential impact on ongoing vaccination programs. Data from clinical trials and real-world evidence suggest that current vaccines remain highly effective against the alpha variant (B.1.1.7), while some vaccines have reduced efficacy and effectiveness against symptomatic disease caused by the beta variant (B.1.351) and the delta variant (B.1.617.2); however, effectiveness against severe disease and hospitalization caused by delta remains high. Although data on the effectiveness of the primary regimen against omicron (B.1.1.529) are limited, booster programs using mRNA vaccines have been shown to restore protection against infection and symptomatic disease (regardless of the vaccine used for the primary regimen) and maintain high effectiveness against hospitalization. However, effectiveness against infection and symptomatic disease wanes with time after the booster dose. Studies have demonstrated reductions of varying magnitude in neutralizing activity of vaccine-elicited antibodies against a range of SARS-CoV-2 variants, with the omicron variant in particular exhibiting partial immune escape. However, evidence suggests that T-cell responses are preserved across vaccine platforms, regardless of variant of concern. Nevertheless, various mitigation strategies are under investigation to address the potential for reduced efficacy or effectiveness against current and future SARS-CoV-2 variants, including modification of vaccines for certain variants (including omicron), multivalent vaccine formulations, and different delivery mechanisms.

Clinical development and approval of COVID-19 vaccines.

INTRODUCTION: The coronavirus 19 (COVID-19) pandemic triggered a simultaneous global demand for preventative vaccines, which quickly became a high priority among governments as well as academia and the pharmaceutical industry. Within less than a year after COVID-19 was declared a pandemic, vaccines had received emergency approvals and vaccination campaigns were initiated. AREAS COVERED: We discuss the several factors that led to the unprecedented, accelerated development and approval of COVID-19 vaccines, which includes optimization of processes by regulatory authorities, redesign of sequential development processes, learnings from previous pandemics, and prior development of novel vaccine platforms. EXPERT OPINION: Despite unanticipated and complex challenges presented by real-time vaccine development in the context of the evolving COVID-19 pandemic and subsequent ever-changing landscape of public health measures and recommendations, important milestones were reached within extraordinarily short periods and, following roll-out to billions worldwide, the approved vaccines have proven to be well tolerated and effective. Whilst this is an exceptional feat and an example of what can be achieved with collaboration and innovation, there are lessons that can still be learned, including the need for further harmonization between regulatory authorities, modes to react to the pandemic's ever-evolving challenges, and ensuring equitable vaccine access among low-income countries.