COVID-19: an 'extraterrestrial' disease?

BACKGROUND: Since the beginning of the pandemic, COVID-19 has been regarded as an exceptional disease. Control measures have exclusively focused on 'the virus', while failing to account for other biological and social factors that determine severe forms of the disease. AIM: We argue that although COVID-19 was initially considered a new challenge, justifying extraordinary response measures, this situation has changed - and so should our response. MAIN ARGUMENTS: We now know that COVID-19 shares many features of common infectious respiratory diseases, and can now ascertain that SARS-CoV-2 has not suddenly presented new problems. Instead, it has exposed and exacerbated existing problems in health systems and the underlying health of the population. COVID-19 is evidently not an 'extraterrestrial' disease. It is a complex zoonotic disease, and it needs to be managed as such, following long-proven principles of medicine and public health. CONCLUSION: A complex disease cannot be solved through a simple, magic-bullet cure or vaccine. The heterogeneity of population profiles susceptible to developing a severe form of COVID-19 suggests the need to adopt varying, targeted measures that are able to address risk profiles in an appropriate way. The critical role of comorbidities in disease severity calls for short-term, virus-targeted interventions to be complemented with medium-term policies aimed at reducing the burden of comorbidities, as well as mitigating the risk of transition from infection to disease. Strategies required include upstream prevention, early treatment, and consolidation of the health system.

Primary versus secondary failure after varicella vaccination: implications for interval between 2 doses.

BACKGROUND: Two-dose varicella vaccination is recommended for optimal control of varicella in populations with high (>90%) 1-dose coverage. Optimal timing of the second dose may depend on whether breakthrough varicella results from primary vaccine failure (no protective immunity after vaccination) or secondary vaccine failure (waning protective immunity). METHODS: Published literature (1995 to 2012) on vaccine failure after varicella vaccination cited in PubMed and other online sources was reviewed. RESULTS: Nineteen publications detailed 21 varicella outbreaks with breakthrough varicella rates ranging from 0% to 42%; the publications showed no consistent trend between breakthrough varicella rate and time since vaccination. CONCLUSIONS: Literature to date indicates a relatively high rate of primary vaccine failure and limited evidence of secondary vaccine failure among 1-dose varicella vaccine recipients, suggesting that a short interval between 2 doses might be preferable in countries considering implementation of universal varicella vaccination to reduce breakthrough varicella. However, any potential disruption to well-established vaccination schedules should be considered.

Hepatitis C of genotype 2: the role of medical invasive exams.

BACKGROUND AND AIM: Hepatitis C virus genotype 2 is the third in order of frequency in Belgium. The aim of this study was to better define the genotype 2 carriers' epidemiology characteristics. METHODS: In a database comprising 1726 viremic hepatitis C virus patient from the south part of Belgium, the files of 98 genotype 2 carriers were reviewed. RESULTS: There was a strong association between genotype 2 and the mode of transmission. The rate of contamination by invasive medical exams was very high (23%), and statistically different from the one of the others genotypes. Eligibility for antiviral therapies and the rate of sustained viral response were high. CONCLUSION: HCV genotype 2 was highly associated with transmission by invasive medical exams.

Varicella vaccination in Europe - taking the practical approach.

Varicella is a common viral disease affecting almost the entire birth cohort. Although usually self-limiting, some cases of varicella can be serious, with 2 to 6% of cases attending a general practice resulting in complications. The hospitalisation rate for varicella in Europe ranges from 1.3 to 4.5 per 100,000 population/year and up to 10.1% of hospitalised patients report permanent or possible permanent sequelae (for example, scarring or ataxia). However, in many countries the epidemiology of varicella remains largely unknown or incomplete. In countries where routine childhood vaccination against varicella has been implemented, it has had a positive effect on disease prevention and control. Furthermore, mathematical models indicate that this intervention strategy may provide economic benefits for the individual and society. Despite this evidence and recommendations for varicella vaccination by official bodies such as the World Health Organization, and scientific experts in the field, the majority of European countries (with the exception of Germany and Greece) have delayed decisions on implementation of routine childhood varicella vaccination, choosing instead to vaccinate high-risk groups or not to vaccinate at all. In this paper, members of the Working Against Varicella in Europe group consider the practicalities of introducing routine childhood varicella vaccination in Europe, discussing the benefits and challenges of different vaccination options (vaccination vs. no vaccination, routine vaccination of infants vs. vaccination of susceptible adolescents or adults, two doses vs. one dose of varicella vaccine, monovalent varicella vaccines vs. tetravalent measles, mumps, rubella and varicella vaccines, as well as the optimal interval between two doses of measles, mumps, rubella and varicella vaccines). Assessment of the epidemiology of varicella in Europe and evidence for the effectiveness of varicella vaccination provides support for routine childhood programmes in Europe. Although European countries are faced with challenges or uncertainties that may have delayed implementation of a childhood vaccination programme, many of these concerns remain hypothetical and with new opportunities offered by combined measles, mumps, rubella and varicella vaccines, reassessment may be timely.

Varicella vaccination in Japan, South Korea, and Europe.

The most extensive use of varicella vaccine has been in the United States and Canada, where it is universally recommended. However, a number of other countries now have recommendations for use of the vaccine, which has been expanding in Europe and Latin America. In this article, we review information concerning varicella vaccination in Japan, where the vaccine was first developed, and in South Korea and parts of Europe. Despite the worldwide availability of an efficient vaccine, varicella vaccination policy is highly variable from country to country. The recent development of a tetravalent vaccine against measles, mumps, rubella, and varicella could modify this variability in the future. It is evident that efforts to control varicella will spread gradually to all continents.

Increasing coverage and efficiency of measles, mumps, and rubella vaccine and introducing universal varicella vaccination in Europe: a role for the combined vaccine.

Universal mass vaccination according to a 2-dose measles-mumps-rubella (MMR) vaccine schedule is recommended by the World Health Organization and is fundamental to the control of these important diseases. Very high coverage (first dose, > or =95%; second dose, > or =80%) is necessary to achieve and sustain high population immunity, and eventually interrupt indigenous transmission of these diseases. In 2006, the Advisory Committee on Immunization Practices issued a recommendation for 2 doses of varicella vaccine to be given universally to children. Coadministration of MMR and varicella vaccines, though efficacious and well tolerated, can be difficult because of the 2 separate injections and associated compliance issues. In addition to the general advantages of a combined vaccine, recently registered measles-mumps-rubella-varicella (MMRV) vaccines could facilitate introduction of varicella universal mass vaccination by simplifying administration and providing the potential to achieve high coverage rates for these 4 diseases.

Consensus: varicella vaccination of healthy children--a challenge for Europe.

The seriousness of varicella-zoster virus (VZV) infection as a public health issue is becoming clearer as country-specific epidemiologic and pharmacoeconomic data become available. In Germany, for example, studies have shown that >5.5% of immunologically healthy individuals develop varicella-related complications such as bacterial superinfections, acute neurologic disorders, pneumonia, bronchitis and otitis media; whereas in Italy, 3.5 to 5% of childhood cases of varicella cause complications such as upper respiratory tract and cutaneous infections. Varicella vaccines are now available. These live attenuated Oka strain vaccines have been shown in extensive studies to be highly immunogenic and well-tolerated in immunocompetent and immunocompromised children, with seroconversion rates ranging from 94 to 100% and 53 to 100%, respectively. These vaccines are also highly effective against clinical disease. These considerations led to a reevaluation of varicella vaccination policies. A routine varicella vaccination program targeting healthy children has already been implemented in the US, and data produced are encouraging and valuable. Similar strategies have not yet been adopted across Europe. The European Working Group on Varicella (EuroVar) was formed in 1998 to address the issues surrounding varicella epidemiology in Europe. After a series of meetings, the EuroVar members prepared a consensus statement recommending routine varicella vaccination for all healthy children between 12 and 18 months and to all susceptible children before their 13th birthday, in addition to catch-up vaccination in older children and adults who have no reliable history of varicella and who are at high risk of transmission and exposure. However, such a policy is recommended only if a very high coverage rate can be achieved. This could be reached with a measles-mumps-rubella-varicella combined vaccine.

Phosphorylation of varicella-zoster virus IE63 protein by casein kinases influences its cellular localization and gene regulation activity.

During the early phase of varicella-zoster virus (VZV) infection, Immediate Early protein 63 (IE63) is expressed rapidly and abundantly in the nucleus, while during latency, this protein is confined mostly to the cytoplasm. Because phosphorylation is known to regulate many cellular events, we investigated the importance of this modification on the cellular localization of IE63 and on its regulatory properties. We demonstrate here that cellular casein kinases I and II are implicated in the in vitro and in vivo phosphorylation of IE63. A mutational approach also indicated that phosphorylation of the protein is important for its correct cellular localization in a cell type-dependent fashion. Using an activity test, we demonstrated that IE63 was able to repress the gene expression driven by two VZV promoters and that phosphorylation of the protein was required for its full repressive properties. Finally, we showed that IE63 was capable of exerting its repressive activity in the cytoplasm, as well as in the nucleus, suggesting a regulation at the transcriptional and/or post-transcriptional level.