Smallpox vaccination and vaccine hesitancy in the Kingdom of the Two Sicilies (1801) and the great modernity of Ferdinand IV of Bourbon: a glimpse of the past in the era of the sars-cov-2 (Covid-19) pandemic

Objective The current health emergency caused by COVID-19 disease shows several correspondences with well-known epidemics of the past. The knowledge of their management and overcoming could give us useful tools to face the present COVID-19 pandemic and future epidemics. Study Design On 1 March 1801, the first smallpox vaccinations were carried out in Palermo and a few weeks later, the vaccine was also administered in Naples and the various provinces of the Kingdom. We aim to study the mass vaccination programme initiated by the Bourbon king Ferdinand IV that was the first large-scale campaign to be conducted in Italy and one of the first in Europe. Methods The authors searched and examined historical testimony and different aspects linked to the public health issues on vaccination. It is a topical topic in the current period with the covid pandemic. Results Albeit with the due differences determined by the passage of time and by the scientific and cultural advances of modern society, this testimony from the past can provide us with food for thought regarding how to face the present COVID-19 pandemic and to prepare for the future. Indeed, it shows us how the terrible smallpox epidemic was handled and finally overcome, thanks to vaccination.

In Vitro Evidence of Statins’ Protective Role against COVID-19 Hallmarks Comptes Rendus

Despite the progressions in COVID-19 understanding, the optimization of patient-specific therapies remains a challenge. Statins, the most widely prescribed lipid-lowering drugs, received considerable attention due to their pleiotropic effects, encompassing lipid metabolism control and immunomodulatory and anti-thrombotic effects. In COVID-19 patients, statins improve clinical outcomes, reducing Intensive Care Unit admission, the onset of ARDS, and in-hospital death. However, the safety of statins in COVID-19 patients has been debated, mainly for statins’ ability to induce the expression of the ACE2 receptor, the main entry route of SARS-CoV-2. Unfortunately, the dynamic of statins’ mechanism in COVID-19 disease and prevention remains elusive. Using different in vitro models expressing different levels of ACE2 receptor, we investigated the role of lipophilic and hydrophilic statins on ACE2 receptor expression and subcellular localization. We demonstrated that the statin-mediated increase of ACE2 receptor expression does not necessarily coincide with its localization in lipid rafts domains, particularly after treatments with the lipophilic atorvastatin that disrupt lipid rafts’ integrity. Through a proteomic array, we analyzed the cytokine patterns demonstrating that statins inhibit the release of cytokines and factors involved in mild to severe COVID-19 cases. The results obtained provide additional information to dissect the mechanism underlying the protective effects of statin use in COVID-19.

In Vitro Evidence of Statins' Protective Role against COVID-19 Hallmarks.

Despite the progressions in COVID-19 understanding, the optimization of patient-specific therapies remains a challenge. Statins, the most widely prescribed lipid-lowering drugs, received considerable attention due to their pleiotropic effects, encompassing lipid metabolism control and immunomodulatory and anti-thrombotic effects. In COVID-19 patients, statins improve clinical outcomes, reducing Intensive Care Unit admission, the onset of ARDS, and in-hospital death. However, the safety of statins in COVID-19 patients has been debated, mainly for statins' ability to induce the expression of the ACE2 receptor, the main entry route of SARS-CoV-2. Unfortunately, the dynamic of statins' mechanism in COVID-19 disease and prevention remains elusive. Using different in vitro models expressing different levels of ACE2 receptor, we investigated the role of lipophilic and hydrophilic statins on ACE2 receptor expression and subcellular localization. We demonstrated that the statin-mediated increase of ACE2 receptor expression does not necessarily coincide with its localization in lipid rafts domains, particularly after treatments with the lipophilic atorvastatin that disrupt lipid rafts' integrity. Through a proteomic array, we analyzed the cytokine patterns demonstrating that statins inhibit the release of cytokines and factors involved in mild to severe COVID-19 cases. The results obtained provide additional information to dissect the mechanism underlying the protective effects of statin use in COVID-19.

The nineteenth-century experience of the kingdom of the two Sicilies on mandatory vaccination: An Italian phenomenon?

The current health emergency caused by COVID-19 disease shows several similarities with well-known epidemics of the past. The knowledge of their management and overcoming could give us useful tools to face the present COVID-19 pandemic. The Bourbon king Ferdinand I planned the first free large-scale mass vaccination programme conducted in Italy and one of the first in Europe to counteract smallpox. The vaccination campaign was characterized by many difficulties and the efforts made by the Southern Kingdoms governors were enormous. For example, the "ante litteram communication campaign", aimed at convincing the so-called "hesitant" people and at confuting the arguments of vaccination opponents, was impressive. In 1821, the compulsory vaccination significantly reduced smallpox infections and death rates. Subsequently, several experiences followed this initiative, not without doubts and debates. Smallpox was finally eradicated worldwide only on the 9th December 1979. Despite to other countries, the "mandatory vaccination" is a topic often debated by Italian scientific and social communities.

Lessons from the 1656 Neapolitan Plague: Something to learn for the current coronavirus Pandemic?

In the spring of 1656, an epidemic of bubonic plague suddenly fell on Naples, the capital of the Kingdom of the Two Sicilies. The epidemic had put a strain on the government authorities, forcing them to take sometimes drastic measures but, in most cases, scarcely decisive. The current health emergency caused by Covid-19 disease has many similarities with the epidemics of the past. Here we report the parallelism among plague and Covid-19 in several respects. Taking as a paradigm the plague epidemic of Naples of 1656, we can easily understand how history, showing us how past epidemics were managed and overcome, even with the intrinsic differences due to the limits of time and scientific progress, can still give us a useful lesson to face the present.

Lipid homeostasis and mevalonate pathway in COVID-19: Basic concepts and potential therapeutic targets.

Despite encouraging progresses achieved in the management of viral diseases, efficient strategies to counteract infections are still required. The current global challenge highlighted the need to develop a rapid and cost-effective strategy to counteract the SARS-CoV-2 pandemic. Lipid metabolism plays a crucial role in viral infections. Viruses can use the host lipid machinery to support their life cycle and to impair the host immune response. The altered expression of mevalonate pathway-related genes, induced by several viruses, assures survival and spread in host tissue. In some infections, statins, HMG-CoA-reductase inhibitors, reduce cholesterol in the plasma membrane of permissive cells resulting in lower viral titers and failure to internalize the virus. Statins can also counteract viral infections through their immunomodulatory, anti-inflammatory and anti-thrombotic effects. Beyond statins, interfering with the mevalonate pathway could have an adjuvant effect in therapies aimed at mitigating endothelial dysfunction and deregulated inflammation in viral infection. In this review we depicted the historical and current evidence highlighting how lipid homeostasis and mevalonate pathway targeting represents a valid approach to rapidly neutralize viruses, focusing our attention to their potential use as effective targets to hinder SARS-CoV-2 morbidity and mortality. Pros and cons of statins and Mevalonate-pathway inhibitors have been also dissected.