Reappraising 21 years of the WHI study: Putting the findings in context for clinical practice.

Menopausal hormone treatment (MHT) is recommended for the management of menopause symptoms. The Women's Health Initiative (WHI) placebo-controlled randomised study examined the effects of continuous combined or estrogen-only MHT on the risk of non-communicable diseases (NCDs) in post-menopausal women. The study was terminated prematurely after an interim analysis showed an increased risk of breast cancer diagnosis, which led to a rapid decrease in MHT use worldwide. Subsequently, limitations of the study design and its interpretation in the context of other clinical studies has contributed to a more nuanced appreciation of the risk-benefit profile of differing MHT regimens regarding risk associated with the class of progestogen prescribed, its pattern of prescription, duration of use and timing of initiation related to menopause onset. This review provides a contextual interpretation of the WHI placebo-controlled study and evaluates the impact of bioidentical MHT, with a focus on combined therapies containing micronised progesterone, on the risk of chronic NCDs in post-menopausal women.

The Role of Immunity in the Pathogenesis of SARS-CoV-2 Infection and in the Protection Generated by COVID-19 Vaccines in Different Age Groups.

This study aims to review the available data regarding the central role of immunity in combating SARS-CoV-2 infection and in the generation of protection by vaccination against COVID-19 in different age groups. Physiologically, the immune response and the components involved in it are variable, both functionally and quantitatively, in neonates, infants, children, adolescents, and adults. These immunological differences are mirrored during COVID-19 infection and in the post-vaccination period. The outcome of SARS-CoV-2 infection is greatly dependent on the reaction orchestrated by the immune system. This is clearly obvious in relation to the clinical status of COVID-19 infection, which can be symptomless, mild, moderate, or severe. Even the complications of the disease show a proportional pattern in relation to the immune response. On the contrary, the commonly used anti-COVID-19 vaccines generate protective humoral and cellular immunity. The magnitude of this immunity and the components involved in it are discussed in detail. Furthermore, many of the adverse effects of these vaccines can be explained on the basis of immune reactions against the different components of the vaccines. Regarding the appropriate choice of vaccine for different age groups, many factors have to be considered. This is a cornerstone, particularly in the following age groups: 1 day to 5 years, 6 to 11 years, and 12 to 17 years. Many factors are involved in deciding the route, doses, and schedule of vaccination for children. Another important issue in this dilemma is the hesitancy of families in making the decision about whether to vaccinate their children. Added to these difficulties is the choice by health authorities and governments concerning whether to make children's vaccination compulsory. In this respect, although rare and limited, adverse effects of vaccines in children have been detected, some of which, unfortunately, have been serious or even fatal. However, to achieve comprehensive control over COVID-19 in communities, both children and adults have to be vaccinated, as the former group represents a reservoir for viral transmission. The understanding of the various immunological mechanisms involved in SARS-CoV-2 infection and in the preparation and application of its vaccines has given the sciences a great opportunity to further deepen and expand immunological knowledge. This will hopefully be reflected positively on other diseases through gaining an immunological background that may aid in diagnosis and therapy. Humanity is still in continuous conflict with SARS-CoV-2 infection and will be for a while, but the future is expected to be in favor of the prevention and control of this disease.

A Summary of the SARS-CoV-2 Vaccines and Technologies Available or under Development.

Since the beginning of 2020, the world has been in a race to develop vaccines that can control the COVID-19 pandemic. More than 250 projects have been initiated for this purpose, but only 14 of them have been authorized for use, despite being in phase 3 clinical trials. More than 40 other vaccines are also in phase 1/2 clinical trials and show promising outcomes. Regarding the appropriate choice of vaccines for each country or region, we reviewed the currently used vaccines in light of the different influencing parameters. These factors include the mode of action, dosage protocol, age group of the vaccinee, side effects, storage conditions, mounted immune response, and cost. Technically, there are seven types of vaccines developed against SARS-CoV-2: messenger RNA (mRNA), nonreplicating and replicating vectors, inactivated viruses, protein subunits, viral-like particles, DNA vaccines, and live attenuated vaccines. The mRNA type is being used for the first time in humans. Unfortunately, mutated variants of SARS-CoV-2 have started to appear worldwide, and researchers are investigating the effects of the currently used vaccines on them. There are many concerns regarding the long-term protection afforded by these vaccines and their side effects, and whether they require future modifications to be effective against the mutated variants. The development of new vaccines using more advanced technology is paramount for overcoming the difficulties in controlling the COVID-19 pandemic across the world.