Mortality Rates of the Spanish Flu and Coronavirus Disease 2019 in the Netherlands: A Historical Comparison.

The coronavirus disease 2019 (COVID-19) pandemic has been called the deadliest disease event in history. In this study, we compared the cause-specific mortality rate of the Spanish flu (1918-1920) with that of COVID-19 (2020-2022) in the Netherlands. During the periods of exposure, about 50 000 people died of COVID-19 and 32 000 people of the Spanish flu. In absolute numbers, COVID-19 seems to be deadlier than Spanish flu. However, the crude mortality rates for COVID-19 and Spanish flu were 287 and 486 per 100 000 inhabitants, respectively. Comparing age-standardized mortality rates, there would have been 28 COVID-19- and 194 Spanish flu-related deaths in 1918-1920, or 214 Spanish flu- and 98 COVID-19-related deaths in 2020-2022 per 100 000 inhabitants per year. Thus, taking the population differences into account, the Spanish flu would have been deadlier than COVID-19.

["God for us!": Catholic festivals and rites in times of epidemics, Salvador-BA, Brasil, 1918-1919]. / "Valha-nos a Providência!": festas e ritos católicos em tempos epidêmicos, Salvador-BA, Brasil, 1918-1919.

This article analyzes the reactions of Catholics linked to lay associations in the city of Salvador, in the period of the Spanish flu (1918) and smallpox (1919). Newspapers were the main sources used to identify the festivals and rites, both those practiced to ask for the intercession of the saints, and those that were suspended due to the need for social isolation. In spite of both diseases being transmissible and the short interval between the two epidemics, the analysis of the sources showed different reactions from the faithful regarding the measures of protection and the search for a cure.

O artigo analisa as reações dos católicos vinculados às associações leigas na cidade do Salvador, no período da gripe espanhola (1918) e da varíola (1919). Os jornais foram as principais fontes utilizadas para a identificação das festas e dos ritos, tanto dos praticados para pedir a intercessão dos santos quanto daqueles que foram suspensos em função da necessidade de isolamento social. Apesar de ambas as doenças serem transmissíveis e do curto espaço de tempo entre as duas epidemias, a análise das fontes evidenciou diferentes reações dos fiéis quanto às medidas de proteção e busca da cura.

Is COVID-19 as Lethal as the Spanish Flu? The Australian Experience in 1919 and 2020 and the Role of Nonpharmaceutical Interventions (NPIs).

We conducted a comparative historical study to interrogate Professor Peter Doherty's warning to Australians in April 2020 that 'COVID-19 is just as lethal as the Spanish flu'. We identified the epicentres of both pandemics, namely, metropolitan Sydney in 1919 and metropolitan Melbourne in 2020 and compared the lethality of the Spanish Flu and COVID-19 in these two cities. Lethality was measured by the number and rate of hospital admissions, death rates, age-specific death rates and age-standardised mortality rates (ASMRs). Using these measures, we demonstrated the strikingly different waves of infection, their severity at various points in time and the cumulative impact of the viruses by the end of our study period, i.e., 30 September in 1919 and 2020. Hospital admissions and deaths from the Spanish Flu in 1919 were more than 30 times higher than those for COVID-19 in 2020. The ASMR per 100,000 population for the Spanish Flu was 383 compared to 7 for COVID-19: The former was about 55 times higher than the latter. These results suggest that the Spanish Flu was more lethal than COVID-19. Professor Doherty's warning was perhaps taken seriously and that partly explains the findings of this study. Containing infection in 1919 and 2020 threw the burden on nonpharmaceutical interventions (NPIs) such as 'protective sequestration' (quarantine), contact tracing, lockdowns and masks. It is likely that the persistent and detailed contact tracing scheme provides the best possible explanation for why NPIs in 2020 were more effective than in 1919 and therefore contributed to the lower lethality of the COVID-19 pandemic in its first year.

Hypoxia and Activation of Neutrophil Degranulation-Related Genes in the Peripheral Blood of COVID-19 Patients.

Severe COVID-19 is characterized by systematic hyper-inflammation and subsequent damage to various organs. Therefore, it is critical to trace this cascade of hyper-inflammation. Blood transcriptome has been routinely utilized in the interrogation of host immune response in COVID-19 and other infectious conditions. In this study, consensus gene dysregulation in the blood was obtained from 13 independent transcriptome studies on COVID-19. Among the up-regulated genes, the most prominent functional categories were neutrophil degranulation and cell cycle, which is clearly different from the classical activation of interferon signaling pathway in seasonal flu. As for the potential upstream causal factors of the atypical gene dysregulation, systemic hypoxia was further examined because it is much more widely reported in COVID-19 than that in seasonal flu. It was found that both physiological and pathological hypoxia can induce activation of neutrophil degranulation-related genes in the blood. Furthermore, COVID-19 patients with different requirement for oxygen intervention showed distinctive levels of gene expression related to neutrophil degranulation in the whole blood, which was validated in isolated neutrophils. Thus, activation of neutrophil degranulation-related genes in the blood of COVID-19 could be partially attributed to hypoxia. Interestingly, similar pattern was also observed in H1N1 infection (the cause of Spanish flu) and several other severe respiratory viral infections. As for the molecular mechanism, both HIF-dependent and HIF-independent pathways have been examined. Since the activation of neutrophil degranulation-related genes is highly correlated with disease severity in COVID-19, early detection of hypoxia and active intervention may prevent further activation of neutrophil degranulation-related genes and other harmful downstream hyper-inflammation. This common mechanism is applicable to current and future pandemic as well as the severe form of common respiratory infection.

[Mandatory Reporting as the Basis of Epidemiological Statistics: The Impact of the Reporting Practice and Usage of Paper Technologies on the Informative Content of Morbidity Statistics 1886-1921]. / Die Meldepflicht als Grundlage der epidemiologischen Statistik: Die Auswirkungen der Meldepraxis und der Verwendung von paper technologies auf den Informationsgehalt von Morbiditätsstatistiken 1886­1921.

This article examines the impact of the reporting practice and paper technologies like forms on reports that were later used for national morbidity statistics by studying the Swiss reporting system for infectious diseases between 1886 and 1921. Analysing the production processes of notifications shows the difficulties and solutions in the implementation of the statutory reporting process. Two disease outbreaks-a smallpox outbreak in Schaffhausen and a typhoid outbreak in the canton of Lucerne-serve as case studies. It is shown that reports are not only objective representations of diseases, but also symbolize the medico-social interactions that produce them, timed by administrative tools like reporting forms and the act of reporting. This destabilises historical statistics and illustrates the complexity of the historical source material, as these interactions and their impact on reporting must be considered. These findings are further supported by examining the Swiss reporting system during the Spanish flu of 1918 and its failure to record influenza cases.

SPATIAL AND SOCIAL ASPECTS OF THE 1918-1919 PANDEMIC FLU IN SPLIT / Prostorna i socijalna obiljezja pandemijske gripe 1918. - 1919. u Splitu

The Spanish flu pandemic is considered the largest and most dangerous epidemic at the beginning of the 20th century affecting most of the world today. The Spanish flu pandemic did not bypass the territory of Croatia (at the time, Croatia was part of the Austro-Hungarian Monarchy), nor its southern coastal region of Dalmatia and the city of Split. Using the example of the city Split, the paper analyses the spatial and demographic determinants of population mortality from the Spanish flu between 1918 and 1919, i.e., from March 1918 to April 1919. The paper is based on the data of the Church Death registers kept in the Archbishop's Archives in Split and newspaper articles. The analysis of the spatial distribution of mortality within urban settlements showed that the number of deaths per urban settlement

Fc-mediated functions and the treatment of severe respiratory viral infections with passive immunotherapy - a balancing act.

Passive immunotherapies have been used to treat severe respiratory infections for over a century, with convalescent blood products from recovered individuals given to patients with influenza-related pneumonia as long ago as the Spanish flu pandemic. However, passive immunotherapy with convalescent plasma or hyperimmune intravenous immunoglobulin (hIVIG) has not provided unequivocal evidence of a clinical benefit for severe respiratory infections including influenza and COVID-19. Efficacy trials, primarily conducted in late-stage disease, have demonstrated inconsistent efficacy and clinical benefit for hIVIG treatment of severe respiratory infections. To date, most serological analyses of convalescent plasma and hIVIG trial samples have focused on the measurement of neutralizing antibody titres. There is, however, increasing evidence that baseline antibody levels and extra-neutralizing antibody functions influence the outcome of passive immunotherapy in humans. In this perspective, findings from convalescent plasma and hIVIG trials for severe influenza, COVID-19 and respiratory syncytial virus (RSV) will be described. Clinical trial results will be discussed in the context of the potential beneficial and deleterious roles of antibodies with Fc-mediated effector functions, with a focus on natural killer cells and antibody-dependent cellular cytotoxicity. Overall, we postulate that treating respiratory viral infections with hIVIG represents a delicate balance between protection and immunopathology.

[Traces of epidemics in the fringes of pain: memory of Spanish flu from a local history perspective, Botucatu (São Paulo state), 1918]. / Rastros epidêmicos nas fímbrias da dor: a memória da gripe espanhola na perspectiva da história local, Botucatu (SP), 1918.

This article takes a local history perspective to scrutinize how the memory of suffering that surrounded the Spanish flu epidemic of 1918 in Botucatu, São Paulo state, has been evoked, challenged, and transmuted over time, producing representations in strategies and practices, and understandings that end up constituting a meaning-making social reality. In this historiographic endeavor, historical vestiges were brought together from a variety of the city's archives between September and October 2021 in a bid to reveal the historical processes that were accreted and deposited in the social fabric and fibers, and which, under the processes of time, were changed and reworked, bringing forth the ineffable mark of Spanish flu.

O artigo perscruta sob a perspectiva da história local de que forma a memória do sofrimento que cercou a epidemia de gripe espanhola de 1918 em Botucatu (interior paulista) foi reconvocada, tensionada e transmutada ao longo do processo histórico, produzindo representações em estratégias e práticas, e apreensões como constituintes de uma realidade social que produz sentidos. Para essa operação historiográfica, coligiram-se vestígios históricos em diversos arquivos botucatuenses, entre setembro e outubro de 2021, buscando desvelar processos históricos aglutinados e depositados entre as fibras e fímbrias sociais e que, sob afecção da temporalidade, se movimentam, se reelaboram e trazem à tona a inefável marca da gripe espanhola.

Spatial comparison of London's three waves of Spanish Flu.

England and Wales experienced three waves of influenza during the 1918/19 Spanish Flu pandemic. A previous analysis showed that these three waves had fundamentally different spatial and temporal characteristics. This present study compares London's experience of the three waves to discern possible geographic differences on a metropolitan level. Borough mortality data for each wave were normalized and then scaled, with spatial autocorrelation techniques displayed by GIS software and analysed for each wave. Registrar General in England and Wales reporting provided data concerning measures of 'health' and 'wealth' for each metropolitan borough. Spearman's rank correlation determined the correlation of each wave's mortality to each of the other waves including the 'health,' 'wealth' and population density factors. The comparisons showed that there is a spatial difference among the waves. The first two are spatially similar, with both exhibiting 'random' autocorrelation patterns, while the third wave exhibits a 'clustered' pattern. The borough mortality of the first two waves strongly correlated with each other, with both having similar 'health,' 'wealth' and population density factors. However, the third wave's mortality did not correlate with any of the first two and actually behaved in an opposite manner with regard to the 'health,' 'wealth,' and population density factors. These results do not appear in the literature and create new opportunities for research to explain London's mortality during the Spanish Flu pandemic of 1918/19.

Associations between rurality and regional differences in sociodemographic factors and the 1918-20 influenza and 2020-21 COVID-19 pandemics in Missouri counties: An ecological study.

This study compares pandemic experiences of Missouri's 115 counties based on rurality and sociodemographic characteristics during the 1918-20 influenza and 2020-21 COVID-19 pandemics. The state's counties and overall population distribution have remained relatively stable over the last century, which enables identification of long-lasting pandemic attributes. Sociodemographic data available at the county level for both time periods were taken from U.S. census data and used to create clusters of similar counties. Counties were also grouped by rural status (RSU), including fully (100%) rural, semirural (1-49% living in urban areas), and urban (>50% of the population living in urban areas). Deaths from 1918 through 1920 were collated from the Missouri Digital Heritage database and COVID-19 cases and deaths were downloaded from the Missouri COVID-19 dashboard. Results from sociodemographic analyses indicate that, during both time periods, average farm value, proportion White, and literacy were the most important determinants of sociodemographic clusters. Furthermore, the Urban/Central and Southeastern regions experienced higher mortality during both pandemics than did the North and South. Analyses comparing county groups by rurality indicated that throughout the 1918-20 influenza pandemic, urban counties had the highest and rural had the lowest mortality rates. Early in the 2020-21 COVID-19 pandemic, urban counties saw the most extensive epidemic spread and highest mortality, but as the epidemic progressed, cumulative mortality became highest in semirural counties. Additional results highlight the greater effects both pandemics had on county groups with lower rates of education and a lower proportion of Whites in the population. This was especially true for the far southeastern counties of Missouri ("the Bootheel") during the COVID-19 pandemic. These results indicate that rural-urban and socioeconomic differences in health outcomes are long-standing problems that continue to be of significant importance, even though the overall quality of health care is substantially better in the 21st century.

La estigmatización de las comunidades gitanas en la pandemia de gripe española. Un estudio de caso a través de la provincia de Bizkaia en 1918 / The stigmatisation of gypsy communities in the spanish flu pandemic. A case study across the province of bizkaia in 1918

La pandemia de gripe española que tuvo lugar entre 1918 y 1920 ha sido profundamente estudiada desde numerosas perspectivas. Sin embargo, existen efectos sociales de la pandemia que todavía no se han explorado lo suficiente. La estigmatización y discriminación de ciertos grupos significados étnicamente como los gitanos fueron producto de las medidas profilácticas aplicadas para poner freno a la extensión del virus. La circulación y presencia de las comunidades gitanas sirvieron como argumento para explicar en ocasiones los desastres sociosanitarios. Por medio del estudio concreto de la provincia de Bizkaia este artículo pretende profundizar en la dimensión social del conflicto y, al mismo tiempo, analizar el encaje de los gitanos ante la situación de crisis sanitaria que dio lugar a discursos y prácticas dirigidas al control de estos grupos étnicos que históricamente han contraído relaciones complejas con las regulaciones gubernativas.(AU)

The Spanish flu pandemic that took place between 1918 and 1920 has been studied from various perspectives. However, there are social effects of the pandemic that have not yet been sufficiently explored. The stigmatization and discrimination of certain ethnically significant groups such as gypsies were the product of the prophylactic measures applied to stop the spread of the virus. The circulation and presence of the Roma communities served as an argument to explain some social and health problems. Through the specific study of the province of Biscay, this article aims to analyze the social dimension of the conflict and, at the same time, study the situation of these Roma communities in this health crisis. During the pandemic, discourses and practices aimed at controlling these ethnic groups were generated. These have historically had complex relationships with government regulations.(AU)

O lampejo dos rastros nos intervalos da montagem: notas metodológicas sobre a incursão em arquivos concernentes à febre amarela e à gripe espanhola / The flash of traces in the montage intervals: methodological notes on the incursion into Yellow Fever and Spanish Flu archives / El destello de los rastros en los intervalos del montaje: apuntes metodológicos sobre la incursión en archivos concernientes a la fiebre amarilla y a la gripe española

No presente artigo, tecemos reflexões e apresentamos conceitos que têm orientado uma pesquisa nos registros de arquivos sobre a febre amarela e a gripe espanhola, nos acervos da Fundação Oswaldo Cruz, da Biblioteca Nacional e do Arquivo Nacional. A pesquisa é centrada na busca dos rastros e das ruínas desses eventos epidêmicos, mediante o método da montagem e com a perspectiva do limiar. Buscamos, por meio dessas materialidades, criar intervalos, experimentar e tecer brechas que prefiguram outros possíveis. Defendemos que, ao manejar, por meio da fabulação crítica, as formas como uma epidemia se faz aparecer, habilitamos a elaboração de uma imaginação política capaz de conferir ao futuro outras possibilidades e outros agenciamentos que não sejam a catástrofe e a melancolia

In this article we reflect on the presented concepts that have guided research in the archival records of Yellow Fever and Spanish Flu in the collections of the Fundação Oswaldo Cruz (Oswaldo Cruz Foundation), the Biblioteca Nacional (National Library), and the Arquivo Nacional (National Archive). The research is centered on the search for the traces and ruins of those epidemic events, through the method of montage and from the perspective of the threshold. We seek, by means of these materialities, to create intervals, to experiment, and to weave gaps that prefigure other possibilities. We argue that, by coping with, through critical fabulation, the ways in which an epidemic makes itself appear, we enable the elaboration of a political imagination capable of giving the future other possibilities and arrangements that are not the catastrophe and the melancholy

En el presente artículo hacemos reflexiones y presentamos conceptos que han guiado una investigación sobre los registros archivísticos de la fiebre amarilla y la gripe española en los acervos de la Fundação Oswaldo Cruz (Fundación Oswaldo Cruz), de la Biblioteca Nacional (Biblioteca Nacional y del Arquivo Nacional (Archivo Nacional). La investigación se centra en la búsqueda de los rastros y las ruinas de esos eventos epidémicos, mediante el método del montaje y la perspectiva del umbral. Buscamos, por medio de estas materialidades, crear intervalos, experimentar y tejer brechas que prefiguren otras posibilidades. Argumentamos que manejando, a través de la fabulación crítica, las formas en que se hace aparecer una epidemia, posibilitamos la elaboración de una imaginación política que dé al futuro otras posibilidades y disposiciones que no sean la catástrofe y la melancolía

Reinfections and Cross-Protection in the 1918/19 Influenza Pandemic: Revisiting a Survey Among Male and Female Factory Workers.

Objectives: The COVID-19 pandemic highlights questions regarding reinfections and immunity resulting from vaccination and/or previous illness. Studies addressing related questions for historical pandemics are limited. Methods: We revisit an unnoticed archival source on the 1918/19 influenza pandemic. We analysed individual responses to a medical survey completed by an entire factory workforce in Western Switzerland in 1919. Results: Among the total of n = 820 factory workers, 50.2% reported influenza-related illness during the pandemic, the majority of whom reported severe illness. Among male workers 47.4% reported an illness vs. 58.5% of female workers, although this might be explained by varied age distribution for each sex (median age was 31 years old for men, vs. 22 years old for females). Among those who reported illness, 15.3% reported reinfections. Reinfection rates increased across the three pandemic waves. The majority of subsequent infections were reported to be as severe as the first infection, if not more. Illness during the first wave, in the summer of 1918, was associated with a 35.9% (95%CI, 15.7-51.1) protective effect against reinfections during later waves. Conclusion: Our study draws attention to a forgotten constant between multi-wave pandemics triggered by respiratory viruses: Reinfection and cross-protection have been and continue to be a key topic for health authorities and physicians in pandemics, becoming increasingly important as the number of waves increases.

Coping With Pandemics: A Historical Perspective About Society's Tools to Deal With Global Infectious Diseases.

ABSTRACT: Throughout history, society has dealt with several devastating pandemics. Our objective is to analyze society's coping mechanisms to deal with pandemic-related stress in history congruent with the values of the time. For that purpose, we have carefully selected some of the most significant pandemics based on their impact and the available psychosocial literature. After a brief introduction, society's coping tools are reviewed and analyzed for the Antonine Plague, the second bubonic plague, the third cholera pandemic, the Spanish flu, the HIV pandemic, and the COVID-19 pandemic. Despite occurring at different times in history, parallels can be established in the study of society's psychological reactions among different pandemics. Magical thinking, political skepticism, fake accusations, and discrimination of minorities are recurrent reactions in society among different pandemics in history.

Heat-Denatured Lysozyme is a Novel Potential Non-alcoholic Disinfectant Against Respiratory Virus.

Respiratory diseases are significant recurrent threats to global public health. Since the 1918 Spanish flu pandemic, seasonal influenza viruses continue to cause epidemics around the world each year. More recently, the COVID-19 global pandemic conducted a public health crisis with more than 6 million deaths and it also severely affected the global economy. Due to the phenomenon that people get infection from objects carrying viruses, it has aroused people's attention to home disinfection. As there is no ideal existing common domestic disinfectant, new and safer antiviral disinfectants are urgently needed. Lysozyme is a natural antibacterial agent widespread in nature and widely used in healthcare and food industry because of is recognized safety. Recently, it has been shown that thermally denatured lysozyme has the ability to kill murine norovirus and hepatitis A virus. In our study, we also demonstrated that heat-denatured lysozyme (HDLz) had an antiviral effect against H1N1 influenza A virus, and we optimized its antiviral activities by testing different heating denaturation conditions, to generalize this property, using pseudotype virus neutralization assay, we found that HDLz can also inhibit the entry of H5N1, H5N6, and H7N1 avian influenza viruses as well as SARS-CoV and SARS-CoV-2 particles in cell with IC50 at the ng/mL range. Finally, using western blot analysis, we provide evidence that HDLz polymerization correlates with antiviral effect, which may be a precious possible quality control test. Altogether, our data support HDLz as a powerful anti-respiratory virus disinfectant as a sole or additive of current disinfectants to reduce concentration of toxic component.

Interaction of COVID-19 With Common Cardiovascular Disorders.

The onset and widespread dissemination of the severe acute respiratory syndrome coronavirus-2 in late 2019 impacted the world in a way not seen since the 1918 H1N1 pandemic, colloquially known as the Spanish Flu. Much like the Spanish Flu, which was observed to disproportionately impact young adults, it became clear in the early days of the coronavirus disease 2019 (COVID-19) pandemic that certain groups appeared to be at higher risk for severe illness once infected. One such group that immediately came to the forefront and garnered international attention was patients with preexisting cardiovascular disease. Here, we examine the available literature describing the interaction of COVID-19 with a myriad of cardiovascular conditions and diseases, paying particular attention to patients diagnosed with arrythmias, heart failure, and coronary artery disease. We further discuss the association of acute COVID-19 with de novo cardiovascular disease, including myocardial infarction due to coronary thrombosis, myocarditis, and new onset arrhythmias. We will evaluate various biochemical theories to explain these findings, including possible mechanisms of direct myocardial injury caused by the severe acute respiratory syndrome coronavirus-2 virus at the cellular level. Finally, we will discuss the strategies employed by numerous groups and governing bodies within the cardiovascular disease community to address the unprecedented challenges posed to the care of our most vulnerable patients, including heart transplant recipients, end-stage heart failure patients, and patients suffering from acute coronary syndromes, during the early days and height of the COVID-19 pandemic.

Pandemics and Suicide Rates in Spain: From the Spanish Flu to COVID-19.

Objective: The aim of this study was to examine suicide rates in Spain during the COVID-19 pandemic and the influenza pandemic of 1918-1920.Methods: Data on deaths by cause for the periods 1910-1925 and 2016-2020 were obtained from the National Statistics Institute of Spain.Results: During the Spanish influenza pandemic, a peak of deaths in 1918 due to influenza, acute bronchitis, pneumonia, and other respiratory diseases coincided with an increase in suicides (from 5.9 in 1917 to 6.6 per 100,000 population in 1918). The pattern was repeated in the COVID-19 pandemic during 2020, with an increase in suicides from 7.8 in 2019 to 8.3 per 100,000 population in 2020. In both cases, the male:female suicide ratio was reduced in similar proportion, with a higher net increase in the number of suicides among males but a higher percentage increase among females.Conclusions: Albeit limited, there is evidence that the pandemics may have affected suicide rates. However, the effect was most likely due to precipitation of different diathesis-stressor factors in each setting, given the different historical contexts.

Gradual adaptation of animal influenza A viruses to human-type sialic acid receptors.

Influenza A viruses (IAVs) originating from animal reservoirs pose continuous threats to human health as demonstrated by the Spanish flu pandemic. Infection starts by attachment to host receptors, a crucial step that is targeted by immunological, prophylactic, and therapeutic intervention. Fine-tuning of virus hemagglutinin binding to host-specific receptor repertoires needs to remain balanced to receptor-destroying neuraminidase (NA) activity and is a key step in host adaptation. It determines NA-dependent virus motility, enabling IAVs to traverse the mucus layer and to bind to, and migrate over, the epithelial cell surface for reaching a location supporting endocytic uptake. Canonical adaptations in enzootic/zoonotic IAVs enhancing human-type receptor binding are well-known, but the context and timespan required for their selection pose many questions. We discuss recent developments, focusing on the dynamic nature of interactions of IAV with the heterogeneous receptor repertoires present in humans and potential intermediate hosts. Potential pre-adaption toward human-type receptor binding in intermediate hosts will be discussed.