Differential mortality of infectious disease in Italian polities: COVID-19, past plague epidemics, and currently endemic respiratory disease.

Coronavirus disease 2019 (COVID-19) has harshly impacted Italy since its arrival in February 2020. In particular, provinces in Italy's Central and Northern macroregions have dealt with disproportionately greater case prevalence and mortality rates than those in the South. In this paper, we compare the morbidity and mortality dynamics of 16th and 17th century Plague outbreaks with those of the ongoing COVID-19 pandemic across Italian regions. We also include data on infectious respiratory diseases which are presently endemic to Italy in order to analyze the regional differences between epidemic and endemic disease. A Growth Curve Analysis allowed for the estimation of time-related intercepts and slopes across the 16th and 17th centuries. Those statistical parameters were later incorporated as criterion variables in multiple General Linear Models. These statistical examinations determined that the Northern macroregion had a higher intercept than the Southern macroregion. This indicated that provinces located in Northern Italy had historically experienced higher plague mortalities than Southern polities. The analyses also revealed that this geographical differential in morbidity and mortality persists to this day, as the Northern macroregion has experienced a substantially higher COVID-19 mortality than the Southern macroregion. These results are consistent with previously published analyses. The only other stable and significant predictor of epidemic disease mortality was foreign urban potential, a measure of the degree of interconnectedness between 16th and 17th century Italian cities. Foreign urban potential was negatively associated with plague slope and positively associated with plague intercept, COVID-19 mortality, GDP per capita, and immigration per capita. Its substantial contribution in predicting both past and present outcomes provides a temporal continuity not seen in any other measure tested here. Overall, this study provides compelling evidence that temporally stable geographical factors, impacting both historical and current foreign pathogen spread above and beyond other hypothesized predictors, underlie the disproportionate impact COVID-19 has had throughout Central and Northern Italian provinces.

Art in support of life: Caravaggio and the plague.

In the struggle with COVID-19, art offered a way to face the solitude of the lockdown. The focus of this paper is primarily on Caravaggio's painting The Seven Works of Mercy, with references to other paintings to amplify some aspects of the artist's approach to life and his uniqueness in the artistic landscape of his time. Darkness was part of Caravaggio's research for spiritual truth and by entering the stories of his life and exploring the tales told through imaginative expression in his paintings, it is possible to understand his process of exploration of ancestral darkness. The author uses her imagination to reflect on how art can help to contact the profound fears buried in the unconscious which are now being awakened by the pandemic. The contemplation of this painting facilitated the emergence of emotions related to the darkness of our time, with the discovery that empathy and mercy offer a way to come to terms with the pandemic. This approach demands a different understanding of reality with Caravaggio's dark creative world becoming a companion that permits the exploration of what is not yet thinkable in daily life. Images accompany the author's research that relies on her imagination and amplifications.

Dans la bataille avec la COVID-19, l'art a offert une manière de faire face à la solitude du confinement. L'accent de cet article vient principalement du tableau du Caravage Les sept œuvres de miséricorde, avec des références à d'autres tableaux pour amplifier certains aspects de l'approche de l'artiste et sa singularité dans le paysage artistique de son époque. Pour le Caravage, la noirceur fait partie de la recherche de vérité spirituelle. En entrant dans les histoires de sa vie et en explorant les récits racontés au travers de l'expression imaginative dans ses tableaux, il est possible de comprendre son processus d'exploration de la noirceur ancestrale. L'auteur utilise sa propre imagination pour réfléchir à comment l'art peut aider à contacter les peurs enterrées dans l'inconscient et qui sont maintenant éveillées par la pandémie. La contemplation de ce tableau a facilité l'émergence d'émotions liées à la noirceur de notre époque, avec la découverte que l'empathie et la compassion offrent une voie pour se confronter à la pandémie et l'accepter. Cette approche requiert une compréhension différente de la réalité et le monde noir et créatif du Caravage devient un compagnon qui permet l'exploration de ce qui n'est pas encore pensable dans la vie quotidienne. Des images accompagnent la recherche de l'auteur qui se fie à son imagination et ses amplifications.

En la lucha con el COVID-19, el arte ofreció una vía para enfrentar la soledad del confinamiento. El foco del presente trabajo es principalmente la pintura Siete obras de Misericordia, de Caravaggio, con referencias a otras pinturas para amplificar algunos aspectos del acercamiento del artista a la vida, y su singularidad en la escena artística de su tiempo. La oscuridad fue parte de la búsqueda de Caravaggio por la verdad espiritual, y al entrar en las historias de su vida y explorar los cuentos narrados a través de su expresión imaginativa en sus pinturas, es posible comprender su proceso de exploración de la oscuridad ancestral. La autora utiliza su imaginación para reflexionar sobre cómo el arte puede ayudar a contactar miedos profundos enterrados en el inconsciente, los cuales ahora están siendo despertados por la pandemia. La contemplación de esta pintura facilitó la emergencia de emociones relacionadas con la oscuridad de nuestro tiempo, con el descubrimiento de que la empatía y la compasión ofrecen una vía para poder llegar a términos con la pandemia. Este abordaje demanda una comprensión diferente de la realidad con el mundo creativo de Caravaggio volviéndose un aliado que posibilita la exploración de lo que aún no puede ser pensado en nuestra vida cotidiana. Imágenes acompañan la investigación de la autora, que se basa en su imaginación y en amplificaciones.

History and future of pandemics / Historia y futuro de las pandemias

Este artículo presenta una historia general de las epidemias históricas y de las nuevas enfermedades emergentes, señalando sus factores desencadenantes. Se afirma que las epidemias son inevitables, y que su riesgo aumenta en proporción al tamaño, la complejidad y el poder tecnológico de nuestras sociedades. La historia enseña que las epidemias han sido casi siempre desencadenadas por cambios en el ambiente ocasionados por las propias actividades humanas. Las enfermedades infecciosas son manifestación de una interacción ecológica entre la especie humana y otra especie de microorganismos. Y las epidemias son resultado del cambio en algún factor ambiental capaz de influir en esa interacción. Las catástrofes epidémicas son inevitables: en primer lugar, porque no podemos evitar formar parte de cadenas tróficas en las que comemos y somos comidos por los microbios; en segundo lugar, porque las infecciones son mecanismos evolutivos y factores reguladores del equilibrio ecológico, que regulan sobre todo el tamaño de las poblaciones; y, en tercer lugar, porque las intervenciones técnicas humanas, al modificar los equilibrios previos, crean equilibrios nuevos que son más vulnerables. De este modo las sociedades humanas son más vulnerables cuanto más complejas. Y los éxitos humanos en la modificación de condiciones ambientales conservan, o más bien aumentan, el riesgo de catástrofes epidémicas. Todas las necesarias medidas de vigilancia y control epidemiológico imaginables pueden disminuir los daños que producen las epidemias, pero nunca podrán evitarlas.

This article presents a general history of historical epidemics, and new emerging diseases, pointing out their triggers. It is claimed that epidemics are inevitable, and that their risk increases in proportion to the size, complexity, and technological power of our societies. History teaches that epidemics have almost always been triggered by changes in the environment caused by human activities themselves. Infectious diseases are manifestations of an ecological interaction between the human species and another species of microorganisms. And epidemics are the result of a change in some environmental factor capable of influencing that interaction. Epidemic catastrophes are inevitable: firstly, because we cannot help but be part of trophic chains in which we eat and are eaten by microbes; secondly, because infections are evolutionary mechanisms and regulatory factors of ecological balance, which regulate especially the size of populations; and thirdly, because human technical interventions, in changing previous balances, create new balances that are more vulnerable. In this way human societies are more vulnerable the more complex. And human successes in modifying environmental conditions retain, or rather increase, the risk of epidemic catastrophes. All necessary epidemiological surveillance and control measures imaginable can lessen the damage caused by epidemics, but they can never prevent them.

Unmasking the unmasked.

Facial maskings have been part of the human story since time began, and the reasons for their needs and the materials that went into their making would vary according to the reasons and materials available. The health-related needs took centuries to become established, but not until the germ theory of disease became recognized. The facial mask, seen as an essential defensive tool for prevention of respiratory transmitted disease continues to be the prime personal protective piece of equipment. With air-born contaminations, such as the present pandemic SARS- CoV-2 viral infestation, why would there be opposition to the use of this personal protective cover of our airways, when until an immunologic answer is available, it is the best single prevention we have. When supported with other measures, like distancing, washing and non-crowding, society would be much safer and secure, with probable less acute and drastic outcomes due to the spread of this virus.

Protection against severe infectious disease in the past.

Before the 20th century many deaths in England, and most likely a majority, were caused by infectious diseases. The focus here is on the biggest killers, plague, typhus, smallpox, tuberculosis, cholera, typhoid, dysentery, childhood infections, pneumonia, and influenza. Many other infectious diseases including puerperal fever, relapsing fever, malaria, syphilis, meningitis, tetanus and gangrene caused thousands of deaths. This review of preventive measures, public health interventions and changes in behavior that reduced the risk of severe infections puts the response to recent epidemic challenges in historical perspective. Two new respiratory viruses have recently caused pandemics: an H1N1 influenza virus genetically related to pig viruses, and a bat-derived coronavirus causing COVID-19. Studies of infectious diseases emerging in human populations in recent decades indicate that the majority were zoonotic, and many of the causal pathogens had a wildlife origin. As hunter-gatherers, humans contracted pathogens from other species, and then from domesticated animals and rodents when they began to live in settled communities based on agriculture. In the modern world of large inter-connected urban populations and rapid transport, the risk of global transmission of new infectious diseases is high. Past and recent experience indicates that surveillance, prevention and control of infectious diseases are critical for global health. Effective interventions are required to control activities that risk dangerous pathogens transferring to humans from wild animals and those reared for food.

Protective face masks through centuries, from XVII century plague doctors to current health care professionals managing the COVID-19 pandemic.

The adoption of items similar to face masks by human beings dates back to the remote past. With specific regard to the use of face protections for medical purposes, from the beginning of the XVII century onwards in Europe physicians in charge of curing patients with plague wore a complicated, and subsequently typical, costume. The face mask included eye sockets of glass and leather headdresses with long, pointed beaks. These beaks were filled with scented spices, aromatic substances and perfumes to filter out the plague and to mask "bad air", which was considered to be the vehicle of the disease. In the XVIII and XIX centuries a number of advances regarding personal protection devices in health care were achieved. In the course of the 1918 influenza pandemic (Spanish flu), health care professionals began to use face masks in a routine way to protect themselves and their patients. From the sixties (XX century) onwards, the explosion of health care technology has led to a continuous refinement in the study of individual protection devices, also because, even in the presence of an increasing number of powerful antimicrobial agents, infectious diseases have remained dominant during these last decades. It is not by chance, therefore, that one of the consequences of the 2020 ongoing COVID-19 pandemic should be the fact that face masks have become essential again both inside and outside health care environments. Even if more than a century has passed from Fluegge's historical definition of bacteria-laden droplets, the role of certain medical-preventive achievements of the past, including the paradigmatic model of protective face masks, continues to remain pivotal in this third millennium.

Traditional Chinese medicine combined with pulmonary drug delivery system and idiopathic pulmonary fibrosis: Rationale and therapeutic potential.

Idiopathic pulmonary fibrosis (IPF) is a progressive pulmonary interstitial inflammatory disease of unknown etiology, and is also a sequela in severe patients with the Coronavirus Disease 2019 (COVID-19). Nintedanib and pirfenidone are the only two known drugs which are conditionally recommended for the treatment of IPF by the FDA. However, these drugs pose some adverse side effects such as nausea and diarrhoea during clinical applications. Therefore, it is of great value and significance to identify effective and safe therapeutic drugs to solve the clinical problems associated with intake of western medicine. As a unique medical treatment, Traditional Chinese Medicine (TCM) has gradually exerted its advantages in the treatment of IPF worldwide through a multi-level and multi-target approach. Further, to overcome the current clinical problems of oral and injectable intakes of TCM, pulmonary drug delivery system (PDDS) could be designed to reduce the systemic metabolism and adverse reactions of the drug and to improve the bioavailability of drugs. Through PubMed, Google Scholar, Web of Science, and CNKI, we retrieved articles published in related fields in recent years, and this paper has summarized twenty-seven Chinese compound prescriptions, ten single TCM, and ten active ingredients for effective prevention and treatment of IPF. We also introduce three kinds of inhaling PDDS, which supports further research of TCM combined with PDDS to treat IPF.

Historical Discoveries on Viruses in the Environment and Their Impact on Public Health.

BACKGROUND: Transmission of many viruses occurs by direct transmission during a close contact between two hosts, or by an indirect transmission through the environment. Several and often interconnected factors, both abiotic and biotic, determine the persistence of these viruses released in the environment, which can last from a few seconds to several years. Moreover, viruses in the environment are able to travel short to very long distances, especially in the air or in water. SUMMARY: Although well described now, the role of these environments as intermediaries or as reservoirs in virus transmission has been extensively studied and debated in the last century. The majority of these discoveries, such as the pioneer work on bacteria transmission, the progressive discoveries of viruses, as well as the persistence of the influenza virus in the air varying along with droplet sizes, or the role of water in the transmission of poliovirus, have contributed to the improvement of public health. Recent outbreaks of human coronavirus, influenza virus, and Ebola virus have also demonstrated the contemporaneity of these research studies and the need to study virus persistence in the environment. Key Messages: In this review, we discuss historical discoveries that contributed to describe biotic and abiotic factors determining viral persistence in the environment.

Quarantine as a tool of epidemic fight.

Until the 19th century, the factor causing epidemics was not known, and the escape from a place where it occurred as well as isolation of patients was considered to be the only effective way to avoid illness and death. Quarantine in a sense similar to modern times was used in 1377 in Ragusa, today's Dubrovnik, during the plague epidemic. It was the first administratively imposed procedure in the world's history. It was later used in Venice and other rich port cities in the Mediterranean. On the territory of today's Poland, quarantine measures were used by the so-called Mayor of the Air - LukaszDrewno in 1623 during the plague epidemic in Warsaw. The quarantine left its mark on all areas of human activity. It affected all humanity in a way that is underestimated today. Throughout history, it has been described and presented visually. It is omnipresent in the world literature, art and philosophy. However, the isolation and closure of cities, limiting trade, had an impact on the economic balance, and the dilemma between the choice of inhabitants' health and the quality of existence, i.e. their wealth, has been the subject of discussions since the Middle Ages. Since the end of the 19th century, quarantine has lost its practical meaning. The discovery of bacteria and a huge development of medical and social sciences allowed limiting its range. In the 20th century isolation and quarantine no longer had a global range, because the ability to identify factors causing the epidemic, knowledge about the incubation period, carrier, infectiousness, enabled the rational determination of its duration and territorial range. The modern SARS COV 2 pandemic has resulted in a global quarantine on a scale unprecedented for at least three hundred years. The aim of this paper is to present the history of quarantine from its beginning to the present day, including its usefulness as an epidemiological tool.

Acceleration of plague outbreaks in the second pandemic.

Historical records reveal the temporal patterns of a sequence of plague epidemics in London, United Kingdom, from the 14th to 17th centuries. Analysis of these records shows that later epidemics spread significantly faster ("accelerated"). Between the Black Death of 1348 and the later epidemics that culminated with the Great Plague of 1665, we estimate that the epidemic growth rate increased fourfold. Currently available data do not provide enough information to infer the mode of plague transmission in any given epidemic; nevertheless, order-of-magnitude estimates of epidemic parameters suggest that the observed slow growth rates in the 14th century are inconsistent with direct (pneumonic) transmission. We discuss the potential roles of demographic and ecological factors, such as climate change or human or rat population density, in driving the observed acceleration.

Learning from the past in the COVID-19 era: rediscovery of quarantine, previous pandemics, origin of hospitals and national healthcare systems, and ethics in medicine.

After the dramatic coronavirus outbreak at the end of 2019 in Wuhan, Hubei province, China, on 11 March 2020, a pandemic was declared by the WHO. Most countries worldwide imposed a quarantine or lockdown to their citizens, in an attempt to prevent uncontrolled infection from spreading. Historically, quarantine is the 40-day period of forced isolation to prevent the spread of an infectious disease. In this educational paper, a historical overview from the sacred temples of ancient Greece-the cradle of medicine-to modern hospitals, along with the conceive of healthcare systems, is provided. A few foods for thought as to the conflict between ethics in medicine and shortage of personnel and financial resources in the coronavirus disease 2019 era are offered as well.

[Scared to death? Retrospective at the time of COVID-19]. / Mourir de peur ? Rétrospective au temps du COVID-19.

TITLE: Mourir de peur ? Rétrospective au temps du COVID-19. ABSTRACT: Un proverbe allemand du XIVe siècle disait que la peste s'attaque à ceux qui ont le plus peur. Est-ce la peur du virus qui tue ou le virus ? Des observateurs étrangers1 s'étonnent que le confinement jusqu'ici ait été dans l'ensemble respecté en France sans révoltes véritables. Les héritiers de la Révolution française ont admis une restriction sans précédent de leurs libertés et se sont soumis à la décision du confinement. La peur du virus inconnu, invisible et sournois, qui a frappé la population, mais aussi la peur de l'autorité et des contrôles, celle de l'Autre et celle de l'étranger possibles porteurs, sont probablement pour beaucoup dans cette résignation. Mais cette peur n'est-elle pas en soi délétère, comme semble nous le montrer une rétrospective sur les épidémies passées ?

Biowarfare, bioterrorism and biocrime: A historical overview on microbial harmful applications.

Microbial Forensics is a field that continues to grow in interest and application among the forensic community. This review, divided into two sections, covers several topics associated with this new field. The first section presents a historic overview concerning the use of microorganisms (or its product, i.e. toxins) as harmful biological agents in the context of biological warfare (biowarfare), bioterrorism, and biocrime. Each case is illustrated with the examination of case reports that span from prehistory to the present day. The second part of the manuscript is devoted to the role of MF and highlights the necessity to prepare for the pressing threat of the harmful use of biological agents as weapons. Preventative actions, developments within the field to ensure a timely and effective response and are discussed herein.

A brief history of medical uniforms: from ancient history to the COVID-19 time.

Medical Uniforms date back from medieval times. Nursing uniforms were based on nuns clothes whereas doctors used the famous "plague costumes" and black "frock" coats from about 15th to early 19th century. In latter half 19th century medical uniforms started to change. Nursing uniforms gradually lost their similarities to religious outfits. Doctors started to use white clothing. With great emphasis on hygiene and sanitation, the idea of personal protective equipment (PPE) started to evolve with William Stewart Halsted introducing the use of rubber gloves in 1889. In the 1960s-1970s it became more usual to wear green and blue `scrubs in order to look for a greater contrast in clothing with the all-white hospital environment. In contemporary times, some specialties even stopped using specific uniforms, while others still use them. At the same time, PPE became more and more important, up to nowadays "plague costume" in the combat of the COVID-19 epidemics.

Pandemic COVID-19 Joins History's Pandemic Legion.

With great apprehension, the world is now watching the birth of a novel pandemic already causing tremendous suffering, death, and disruption of normal life. Uncertainty and dread are exacerbated by the belief that what we are experiencing is new and mysterious. However, deadly pandemics and disease emergences are not new phenomena: they have been challenging human existence throughout recorded history. Some have killed sizeable percentages of humanity, but humans have always searched for, and often found, ways of mitigating their deadly effects. We here review the ancient and modern histories of such diseases, discuss factors associated with their emergences, and attempt to identify lessons that will help us meet the current challenge.

[Infectious Socialization-The History of Contagious Bodies]. / Vergesellschaftung unter Ansteckenden ­ für eine Körpergeschichte der Seuche.

This paper is part of Forum COVID-19: Perspectives in the Humanities and Social Sciences. Being a "trauma of mankind" epidemics have been a major subject of historical research for a long time and regarding every historical period. Recurring to the concept of Rudolf Schlögl ("Vergesellschaftung unter Anwesenden") my proposal is to research epidemics as a history of the communicating body and thus including the contagium as part of this communication.