Susceptibility to Resurgent COVID-19 Outbreaks Following Vaccine Rollouts: A Modeling Study

Using the recently proposed Susceptible–Asymptomatic–Infected–Vaccinated–Removed (SAIVR) model, we study the impact of key factors affecting COVID-19 vaccine rollout effectiveness and the susceptibility to resurgent epidemics. The SAIVR model expands the widely used Susceptible–Infectious–Removed (SIR) model for describing epidemics by adding compartments to include the asymptomatic infected (A) and the vaccinated (V) populations. We solve the model numerically to make predictions on the susceptibility to resurgent COVID-19 epidemics depending on initial vaccination coverage, importation loads, continuing vaccination, and more contagious SARS-CoV-2 variants, under persistent immunity and immunity waning conditions. The parameters of the model represent reported epidemiological characteristics of the SARS-CoV-2 virus such as the disease spread in countries with high levels of vaccination coverage. Our findings help explain how the combined effects of different vaccination coverage levels and waning immunity lead to distinct patterns of resurgent COVID-19 epidemics (either surges or endemic), which are observed in countries that implemented different COVID-19 health policies and achieved different vaccinated population plateaus after the vaccine rollouts in the first half of 2021.     

Monkeypox: A Comprehensive Review

The 2022 multi-country monkeypox outbreak in humans has brought new public health adversity on top of the ongoing coronavirus disease 2019 (COVID-19) pandemic. The disease has spread to 104 countries throughout six continents of the world, with the highest burden in North America and Europe. The etiologic agent, monkeypox virus (MPXV), has been known since 1959 after isolation from infected monkeys, and virulence among humans has been reported since the 1970s, mainly in endemic countries in West and Central Africa. However, the disease has re-emerged in 2022 at an unprecedented pace, with particular concern on its human-to-human transmissibility and community spread in non-endemic regions. As a mitigation effort, healthcare workers, public health policymakers, and the general public worldwide need to be well-informed on this relatively neglected viral disease. Here, we provide a comprehensive and up-to-date overview of monkeypox, including the following aspects: epidemiology, etiology, pathogenesis, clinical features, diagnosis, and management. In addition, the current review discusses the preventive and control measures, the latest vaccine developments, and the future research areas in this re-emerging viral disease that was declared as a public health emergency of international concern.     

Epidemiological Aspects of Equid Herpesvirus-Associated Myeloencephalopathy (EHM) Outbreaks

Equid Herpesvirus Myeloencephalopathy (EHM) is a multifactorial disease following an EHV-1 infection in Equidae. We investigated a total of 589 horses on 13 premises in Europe in search of risk factors for the development of EHM. We found that fever (p < 0.001), increasing age (p = 0.032), and female sex (p = 0.042) were risk factors for EHM in a logistic mixed model. Some breeds had a decreased risk to develop EHM compared to others (Shetland and Welsh ponies; p = 0.017; p = 0.031), and fewer EHV-1-vaccinated horses were affected by EHM compared to unvaccinated horses (p = 0.02). Data evaluation was complex due to high variability between outbreaks with regards to construction and environment; viral characteristics and the virus’s transmissibility were affected by operational management. This study confirms earlier suspected host-specific risk factors, and our data support the benefit of high vaccine coverage at high-traffic boarding facilities.     

Carboxyl-Terminal Decoy Epitopes in the Capsid Protein of Porcine Circovirus Type 2 Are Immunogenicity-Enhancers That Elicit Predominantly Specific Antibodies in Non-Vaccinated Pigs

In the context of the carboxyl-terminus (C-terminus) of the capsid protein of porcine circovirus type 2a (PCV2a) and PCV2a vaccines, this study aimed to explore its unrevealing cryptic epitope and its relation to PCV2-infected herd immunity. To discover the C-terminus of the capsid protein of PCV2a, monoclonal antibodies (mAbs) were generated in this work. Two mAbs bound the two minimal linear epitopes (₂₂₉PPLKP₂₃₃ and ₂₂₈DPPLNP₂₃₃ (or ₂₂₉PPLNP₂₃₃)), which were located at the C-terminus of the capsid proteins of PCV2a and PCV2b, respectively. One mAb bound to the minimal linear epitope (₂₂₀QFREFNLK₂₂₇, peptide P82), but it neither bound the virus-like particle (VLP) of PCV2a nor produced positive staining in PCV2a-infected cells by immunofluorescence assay. Further, the residues 220–227 were not accessible on the surface of the VLP on the three-dimensional model, but the residues 228–231 extend toward the VLP exterior. Immunoassays were conducted in this study to screen anti-viral peptide-specific IgGs, which could differentiate vaccinated pigs from non-vaccinated ones. The data show two ₂₂₀QFREFNLKDPPLKP₂₃₃-containing peptides had a significantly higher binding reactivity with sera from PCV2-infected pigs in the control group than with sera from the VLP-vaccine group, particularly seen in sera from swine aged 15 weeks to 24 weeks. However, the peptide P82 had not this phenomenon in that test. This study confirmed that C-terminal epitopes play an important role in PCV2-induced decoy of swine humoral immunity.     

Can high COVID-19 vaccination rates in adults help protect unvaccinated children? Evidence from a unique mass vaccination campaign,Schwaz/Austria,March 2021

BackgroundAfter an outbreak of the SARS-CoV-2 Beta variant in the district of Schwaz/Austria, vaccination with Comirnaty vaccine (BNT162b2 mRNA, BioNTech-Pfizer) had been offered to all adult inhabitants (≥ 16 years) in March 2021. This made Schwaz one of the most vaccinated regions in Europe at that time (70% of the adult population took up the offer). In contrast, all other Austrian districts remained with low vaccine coverage.AimWe studied whether this rapid mass vaccination campaign provided indirect protection to unvaccinated individuals such as children (< 16 years) living in the same district.MethodsTo study the effect of the campaign we used two complementary approaches. We compared infection rates among the population of children (< 16 years) in Schwaz with (i) the child population from similar districts (using the synthetic control method), and (ii) with the child population from municipalities along the border of Schwaz not included in the campaign (using an event study approach).ResultsBefore the campaign, we observed very similar infection spread across the cohort of children in Schwaz and the control regions. After the campaign, we found a significant reduction of new cases among children of −64.5% (95%-CI: −82.0 to −30.2%) relative to adjacent border municipalities (using the event study model). Employing the synthetic control method, we observed a significant reduction of −42.8% in the same cohort.ConclusionOur results constitute novel evidence of an indirect protection effect from a group of vaccinated individuals to an unvaccinated group.     

Monkeypox in Patient Immunized with ACAM2000 Smallpox Vaccine During 2022 Outbreak

We report a case of monkeypox in the United States in a patient who had been vaccinated with ACAM2000 smallpox vaccine 8 years earlier. Despite his vaccination status, he still contracted disease. He showed prodromal symptoms preceding development of painless penile lesions that later coalesced.     

Reactive vaccination as control strategy for an outbreak of invasive meningococcal disease caused by Neisseria meningitidis C:P1.5-1,10-8:F3-6:ST-11(cc11), Bergamo province,Italy, December 2019 to January 2020

In Italy, serogroup C meningococci of the clonal complex cc11 (MenC/cc11) have caused several outbreaks of invasive meningococcal disease (IMD) during the past 20 years. Between December 2019 and January 2020, an outbreak of six cases of IMD infected with MenC/cc11 was identified in a limited area in the northern part of Italy. All cases presented a severe clinical picture, and two of them were fatal. This report is focused on the microbiological and molecular analysis of meningococcal isolates with the aim to reconstruct the chain of transmission. It further presents the vaccination strategy adopted to control the outbreak. The phylogenetic evaluation demonstrated the close genetic proximity between the strain involved in this outbreak and a strain responsible for a larger epidemic that had occurred in 2015 and 2016 in the Tuscany Region. The rapid identification and characterisation of IMD cases and an extensive vaccination campaign contributed to the successful control of this outbreak caused by a hyperinvasive meningococcal strain.     

Early SARS-CoV-2 Reinfections within 60 Days and Implications for Retesting Policies

Illustrated by a clinical case supplemented by epidemiologic data, early reinfections with SARS-CoV-2 Omicron BA.1 after infection with Delta variant, and reinfection with Omicron BA.2 after Omicron BA.1 infection, can occur within 60 days, especially in young, unvaccinated persons. The case definition of reinfection, which influences retesting policies, should be reconsidered.     

Estimation of COVID-19 vaccine effectiveness against hospitalisation in individuals aged ≥ 65 years using electronic health registries; a pilot study in four EU/EEA countries,October 2021 to March 2022

By employing a common protocol and data from electronic health registries in Denmark, Navarre (Spain), Norway and Portugal, we estimated vaccine effectiveness (VE) against hospitalisation due to COVID-19 in individuals aged ≥ 65 years old, without previous documented infection, between October 2021 and March 2022. VE was higher in 65–79-year-olds compared with ≥ 80-year-olds and in those who received a booster compared with those who were primary vaccinated. VE remained high (ca 80%) between ≥ 12 and < 24 weeks after the first booster administration, and after Omicron became dominant.     

Low-frequency sonophoresis: application to the transdermal delivery of macromolecules and hydrophilic drugs

Importance of the field: Transdermal delivery of macromolecules provides an attractive alternative route of drug administration when compared to oral delivery and hypodermic injection because of its ability to bypass the harsh gastrointestinal tract and deliver therapeutics non-invasively. However, the barrier properties of the skin only allow small, hydrophobic permeants to traverse the skin passively, greatly limiting the number of molecules that can be delivered via this route. The use of low-frequency ultrasound for the transdermal delivery of drugs, referred to as low-frequency sonophoresis (LFS), has been shown to increase skin permeability to a wide range of therapeutic compounds, including both hydrophilic molecules and macromolecules. Recent research has demonstrated the feasibility of delivering proteins, hormones, vaccines, liposomes and other nanoparticles through LFS-treated skin. In vivo studies have also established that LFS can act as a physical immunization adjuvant. LFS technology is already clinically available for use with topical anesthetics, with other technologies currently under investigation.

Areas covered in this review: This review provides an overview of mechanisms associated with LFS-mediated transdermal delivery, followed by an in-depth discussion of the current applications of LFS technology for the delivery of hydrophilic drugs and macromolecules, including its use in clinical applications.

What the reader will gain: The reader will gain an insight into the field of LFS-mediated transdermal drug delivery, including how the use of this technology can improve on more traditional drug delivery methods.

Take home message: Ultrasound technology has the potential to impact many more transdermal delivery platforms in the future due to its unique ability to enhance skin permeability in a controlled manner.