Covid-19 y gripe de 1918-1919: paralelos históricos, preguntas y respuestas / Covid-19 and the 1918-1919 influenza: historical parallels, questions and answers

Resumen El desarrollo de la pandemia de la covid-19 ha motivado un renovado interés por la gripe de 1918-1919 para buscar elementos que facilitaran la comprensión de la experiencia presente, pero también como oportunidad para reevaluar la grave crisis sanitaria del siglo XX a la luz de lo que estamos viviendo. En este contexto y con ese objetivo se inserta esta reflexión histórica sobre estos dos fenómenos pandémicos, que muestra los paralelismos existentes y la necesidad de una toma de conciencia de que nuestro modelo de sociedad está en crisis y se requiere una transformación profunda.

Abstract The rise of the covid-19 pandemic has led to renewed interest in the 1918-1919 influenza in search of aspects that might help us understand the current situation, but also as an opportunity to re-evaluate the serious twentieth-century health crisis in light of what we are experiencing now. In this context and with that goal, this historical reflection shows the parallels that exist and the need for a realization that our model of society is undergoing a crisis and requires profound transformation.

[Covid-19 and the 1918-1919 influenza: historical parallels, questions and answers]. / Covid-19 y gripe de 1918-1919: paralelos históricos, preguntas y respuestas.

The rise of the covid-19 pandemic has led to renewed interest in the 1918-1919 influenza in search of aspects that might help us understand the current situation, but also as an opportunity to re-evaluate the serious twentieth-century health crisis in light of what we are experiencing now. In this context and with that goal, this historical reflection shows the parallels that exist and the need for a realization that our model of society is undergoing a crisis and requires profound transformation.

El desarrollo de la pandemia de la covid-19 ha motivado un renovado interés por la gripe de 1918-1919 para buscar elementos que facilitaran la comprensión de la experiencia presente, pero también como oportunidad para reevaluar la grave crisis sanitaria del siglo XX a la luz de lo que estamos viviendo. En este contexto y con ese objetivo se inserta esta reflexión histórica sobre estos dos fenómenos pandémicos, que muestra los paralelismos existentes y la necesidad de una toma de conciencia de que nuestro modelo de sociedad está en crisis y se requiere una transformación profunda.

Challenges of Making Effective Influenza Vaccines.

Seasonal influenza vaccines prevent influenza-related illnesses, hospitalizations, and deaths. However, these vaccines are not as effective as other viral vaccines, and there is clearly room for improvement. Here, we review the history of seasonal influenza vaccines, describe challenges associated with producing influenza vaccine antigens, and discuss the inherent difficulties of updating influenza vaccine strains each influenza season. We argue that seasonal influenza vaccines can be dramatically improved by modernizing antigen production processes and developing models that are better at predicting viral evolution. Resources should be specifically dedicated to improving seasonal influenza vaccines while developing entirely new vaccine platforms.

Influenza update 2018-2019: 100 years after the great pandemic.

Four influenza pandemics, starting with the historic 1918 pandemic, have killed thousands of people around the world. Vaccination, still the most important means of preventing influenza, is currently recommended yearly for all people age 6 months and older, with a goal of vaccinating 80% of all Americans and 90% of at-risk populations. Neuraminidase inhibitors are underused, and a new drug with a different mechanism of action, baloxavir marboxil, is expected to be approved soon in the United States.

The Spanish Flu, Epidemics, and the Turn to Biomedical Responses.

A century ago, nonpharmaceutical interventions such as school closings, restrictions on large gatherings, and isolation and quarantine were the centerpiece of the response to the Spanish Flu. Yet, even though its cause was unknown and the science of vaccine development was in its infancy, considerable enthusiasm also existed for using vaccines to prevent its spread. This desire far exceeded the scientific knowledge and technological capabilities of the time. Beginning in the early 1930s, however, advances in virology and influenza vaccine development reshaped the relative priority given to biomedical approaches in epidemic response over traditional public health activities. Today, the large-scale implementation of nonpharmaceutical interventions akin to the response to the Spanish Flu would face enormous legal, ethical, and political challenges, but the enthusiasm for vaccines and other biomedical interventions that was emerging in 1918 has flourished. The Spanish Flu functioned as an inflection point in the history of epidemic responses, a critical moment in the long transition from approaches dominated by traditional public health activities to those in which biomedical interventions are viewed as the most potent and promising tools in the epidemic response arsenal.

100 Years of Medical Countermeasures and Pandemic Influenza Preparedness.

The 1918 influenza pandemic spread rapidly around the globe, leading to high mortality and social disruption. The countermeasures available to mitigate the pandemic were limited and relied on nonpharmaceutical interventions. Over the past 100 years, improvements in medical care, influenza vaccines, antiviral medications, community mitigation efforts, diagnosis, and communications have improved pandemic response. A number of gaps remain, including vaccines that are more rapidly manufactured, antiviral drugs that are more effective and available, and better respiratory protective devices.

The Mother of All Pandemics Is 100 Years Old (and Going Strong)!

This year marks the 100th anniversary of the deadliest event in human history. In 1918-1919, pandemic influenza appeared nearly simultaneously around the globe and caused extraordinary mortality (an estimated 50-100 million deaths) associated with unexpected clinical and epidemiological features. The descendants of the 1918 virus remain today; as endemic influenza viruses, they cause significant mortality each year. Although the ability to predict influenza pandemics remains no better than it was a century ago, numerous scientific advances provide an important head start in limiting severe disease and death from both current and future influenza viruses: identification and substantial characterization of the natural history and pathogenesis of the 1918 causative virus itself, as well as hundreds of its viral descendants; development of moderately effective vaccines; improved diagnosis and treatment of influenza-associated pneumonia; and effective prevention and control measures. Remaining challenges include development of vaccines eliciting significantly broader protection (against antigenically different influenza viruses) that can prevent or significantly downregulate viral replication; more complete characterization of natural history and pathogenesis emphasizing the protective role of mucosal immunity; and biomarkers of impending influenza-associated pneumonia.

The Doctrine of Original Antigenic Sin: Separating Good From Evil.

The term "original antigenic sin" was coined approximately 60 years ago to describe the imprinting by the initial first influenza A virus infection on the antibody response to subsequent vaccination. These studies did not suggest a reduction in the response to current antigens but instead suggested anamnestic recall of antibody to earlier influenza virus strains. Then, approximately 40 years ago, it was observed that sequential influenza vaccination might lead to reduced vaccine effectiveness (VE). This conclusion was largely dismissed after an experimental study involving sequential administration of then-standard influenza vaccines. Recent observations have provided convincing evidence that reduced VE after sequential influenza vaccination is a real phenomenon. We propose that such reduction in VE be termed "negative antigenic interaction," given that there is no age cohort effect. In contrast, the potentially positive protective effect of early influenza virus infection later in life continues to be observed. It is essential that we understand better the immunologic factors underlying both original antigenic sin and negative antigenic interaction, to support development of improved influenza vaccines and vaccination strategies.

The use of nonhuman primates in research on seasonal, pandemic and avian influenza, 1893-2014.

Attempts to reproduce the features of human influenza in laboratory animals date from the early 1890s, when Richard Pfeiffer inoculated apes with bacteria recovered from influenza patients and produced a mild respiratory illness. Numerous studies employing nonhuman primates (NHPs) were performed during the 1918 pandemic and the following decade. Most used bacterial preparations to infect animals, but some sought a filterable agent for the disease. Since the viral etiology of influenza was established in the early 1930s, studies in NHPs have been supplemented by a much larger number of experiments in mice, ferrets and human volunteers. However, the emergence of a novel swine-origin H1N1 influenza virus in 1976 and the highly pathogenic H5N1 avian influenza virus in 1997 stimulated an increase in NHP research, because these agents are difficult to study in naturally infected patients and cannot be administered to human volunteers. In this paper, we review the published literature on the use of NHPs in influenza research from 1893 through the end of 2014. The first section summarizes observational studies of naturally occurring influenza-like syndromes in wild and captive primates, including serologic investigations. The second provides a chronological account of experimental infections of NHPs, beginning with Pfeiffer's study and covering all published research on seasonal and pandemic influenza viruses, including vaccine and antiviral drug testing. The third section reviews experimental infections of NHPs with avian influenza viruses that have caused disease in humans since 1997. The paper concludes with suggestions for further studies to more clearly define and optimize the role of NHPs as experimental animals for influenza research.

From empiricism to rational design: a personal perspective of the evolution of vaccine development.

Vaccination, which is the most effective medical intervention that has ever been introduced, originated from the observation that individuals who survived a plague or smallpox would not get the disease twice. To mimic the protective effects of natural infection, Jenner - and later Pasteur - inoculated individuals with attenuated or killed disease-causing agents. This empirical approach inspired a century of vaccine development and the effective prophylaxis of many infectious diseases. From the 1980s, several waves of new technologies have enabled the development of novel vaccines that would not have been possible using the empirical approach. The technological revolution in the field of vaccination is now continuing, and it is delivering novel and safer vaccines. In this Timeline article, we provide our views on the transition from empiricism to rational vaccine design.

Influenza vaccines: from whole virus preparations to recombinant protein technology.

Vaccination against influenza represents our most effective form of prevention. Historical approaches toward vaccine creation and production have yielded highly effective vaccines that are safe and immunogenic. Despite their effectiveness, these historical approaches do not allow for the incorporation of changes into the vaccine in a timely manner. In 2013, a recombinant protein-based vaccine that induces immunity toward the influenza virus hemagglutinin was approved for use in the USA. This vaccine represents the first approved vaccine formulation that does not require an influenza virus intermediate for production. This review presents a brief history of influenza vaccines, with insight into the potential future application of vaccines generated using recombinant technology.

The National Institutes of Health Center for Human Immunology, Autoimmunity, and Inflammation: history and progress.

The Center for Human Immunology, Autoimmunity, and Inflammation (CHI) is an exciting initiative of the NIH intramural program begun in 2009. It is uniquely trans-NIH in support (multiple institutes) and leadership (senior scientists from several institutes who donate their time). Its goal is an in-depth assessment of the human immune system using high-throughput multiplex technologies for examination of immune cells and their products, the genome, gene expression, and epigenetic modulation obtained from individuals both before and after interventions, adding information from in-depth clinical phenotyping, and then applying advanced biostatistical and computer modeling methods for mining these diverse data. The aim is to develop a comprehensive picture of the human "immunome" in health and disease, elucidate common pathogenic pathways in various diseases, identify and validate biomarkers that predict disease progression and responses to new interventions, and identify potential targets for new therapeutic modalities. Challenges, opportunities, and progress are detailed.