The Potential Role of COVID-19 in the Pathogenesis of Multiple Sclerosis-A Preliminary Report.

Coronavirus 2019 (COVID-19) is an infectious respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that mainly affects the lungs. COVID-19 symptoms include the presence of fevers, dry coughs, fatigue, sore throat, headaches, diarrhea, and a loss of taste or smell. However, it is understood that SARS-CoV-2 is neurotoxic and neuro-invasive and could enter the central nervous system (CNS) via the hematogenous route or via the peripheral nerve route and causes encephalitis, encephalopathy, and acute disseminated encephalomyelitis (ADEM) in COVID-19 patients. This review discusses the possibility of SARS-CoV-2-mediated Multiple Sclerosis (MS) development in the future, comparable to the surge in Parkinson's disease cases following the Spanish Flu in 1918. Moreover, the SARS-CoV-2 infection is associated with a cytokine storm. This review highlights the impact of these modulated cytokines on glial cell interactions within the CNS and their role in potentially prompting MS development as a secondary disease by SARS-CoV-2. SARS-CoV-2 is neurotropic and could interfere with various functions of neurons leading to MS development. The influence of neuroinflammation, microglia phagocytotic capabilities, as well as hypoxia-mediated mitochondrial dysfunction and neurodegeneration, are mechanisms that may ultimately trigger MS development.

Comparing the Spanish flu and COVID-19 pandemics: Lessons to carry forward.

Just as people living in the early 1900s experienced the horrors of World War I followed by the Spanish influenza epidemic, those of us surviving the coronavirus disease 2019 pandemic will have our lives forever changed. Both pandemics defied the capabilities of prevailing healthcare and public health. Since there was no known cure in either pandemic, much depended on nurses to fight the battle against the viruses. History has shown pandemics are occurring more frequently and are unpredictable in timing and severity. Therefore, we need to place focus on the valuable lessons from the century's two pandemics to prepare for future global disease outbreaks. Lessons that will benefit nursing are the importance of continual preparation and planning, care coordination across communities and healthcare systems, and ensuring nurses have the necessary resources and training to perform their roles in an effective and safe manner.

Will prenatal exposure to SARS-CoV-2 define a birth cohort with accelerated aging in the century ahead?

The 1918 Influenza pandemic had long-term impacts on the cohort exposed in utero which experienced earlier adult mortality, and more diabetes, ischemic heart disease, and depression after age 50. It is possible that the Coronavirus Disease 2019 (COVID-19) pandemic will also have long-term impacts on the cohort that was in utero during the pandemic, from exposure to maternal infection and/or the stress of the pandemic environment. We discuss how COVID-19 disease during pregnancy may affect fetal and postnatal development with adverse impacts on health and aging. Severe maternal infections are associated with an exaggerated inflammatory response, thromboembolic events, and placental vascular malperfusion. We also discuss how in utero exposure to the stress of the pandemic, without maternal infection, may impact health and aging. Several recently initiated birth cohort studies are tracking neonatal health following in utero severe acute respiratory syndrome virus 2 (SARS-CoV-2) exposure. We suggest these cohort studies develop plans for longer-term observations of physical, behavioral, and cognitive functions that are markers for accelerated aging, as well as methods to disentangle the effects of maternal infection from stresses of the pandemic environment. In utero exposure to COVID-19 disease could cause developmental difficulties and accelerated aging in the century ahead. This brief review summarizes elements of the developmental origins of health, disease, and ageing and discusses how the COVID-19 pandemic might exacerbate such effects. We conclude with a call for research on the long-term consequences of in utero exposure to maternal infection with COVID-19 and stresses of the pandemic environment.

May the analysis of 1918 influenza pandemic give hints to imagine the possible magnitude of Corona Virus Disease-2019 (COVID-19)?

BACKGROUND: In 1918 an unknown infectious agent spread around the world infecting over one-third of the general population and killing almost 50 million people. Many countries were at war, the First World War. Since Spain was a neutral country and Spanish press could report about the infection without censorship, this condition is commonly remembered as "Spanish influenza". This review examines several aspects during the 1918 influenza pandemic to bring out evidences which might be useful to imagine the possible magnitude of the present coronavirus disease 2019 (COVID-19). METHODS: In the first part of this review we will examine the origin of the SARS-Coronavirus-2 and 1918 Spanish Influenza Virus and the role played by host and environment in its diffusion. We will also include in our analysis an evaluation of different approaches utilized to restrain the spread of pandemic and to treat infected patients. In the second part, we will try to imagine the magnitude of the present COVID-19 pandemic and the possible measures able to restrain in the present environment its spread. RESULTS: Several factors characterize the outcome in a viral pandemic infection. They include the complete knowledge of the virus, the complete knowledge of the host and of the environment where the host lives and the pandemic develops. CONCLUSION: By comparing the situation seen in 1918 with the current one, we are now in a more favourable position. The experience of the past teaches us that their success is linked to a rapid, constant and lasting application. Then, rather than coercion, awareness of the need to observe such prevention measures works better.

Estimating transportation role in pandemic diffusion in Nigeria: A consideration of 1918-19 influenza and COVID-19 pandemics.

BACKGROUND: The focus of the study is to assess the role of different transport means in the importation and diffusion of 1918-19 influenza and a novel 2019 corona virus designated as COVID-19 in Nigeria. METHODS: The study provides a review of the means by which the two pandemics were imported into the country and the roles the transport means of each period played in the local spread of the epidemics. RESULTS: The study notes that seaports and railways, being the emerging transportation modes in the country were significant to the importation and local diffusion of 1918-19 influenza, respectively, while air transport is significant to the importation of the current COVID-19 pandemic. CONCLUSIONS: The study concludes that increasing preference for the transport at a given epoch is significant to the diffusion of prevailing epidemic in the epoch.

Impacts of the 1918 flu on survivors' nutritional status: A double quasi-natural experiment.

Robust empirical evidence supports the idea that embryonic and, more generally, intrauterine disruptions induced by the 1918-flu pandemic had long-term consequences on adult health status and other conditions. In this paper we assess the 1918-flu long-term effects not just of in utero exposure but also during infancy and early childhood. A unique set of events that took place in Puerto Rico during 1918-1919 generated conditions of a "double quasi-natural experiment". We exploit these conditions to empirically identify effects of exposure to the 1918 flu pandemic and those of the devastation left by an earthquake-tsunami that struck the island in 1918. Because the earthquake-tsunami affected mostly the Western coast of the island whereas early (in utero and postnatal) exposure to the flu was restricted to those born in the interval 1917-1920, we use geographic variation to identify the effects of the quake and timing of birth variation to identify those of the flu. We benefit from availability of information on markers of nutritional status in a nationally representative sample of individuals aged 75 and older in 2002. We make two contributions. First, unlike most fetal-origins research that singles out early nutritional status as a determinant of adult health, we hypothesize that the 1918 flu damaged the nutritional status of adult survivors who, at the time of the flu, were in utero or infants. Second, we target markers of nutritional status largely set when the adult survivors were infants and young children. Estimates of effects of the pandemic are quite large mostly among females and those who were exposed to the earthquake-tsunami. Impacts of the flu in areas less affected by the earthquake are smaller but do vary by area flu severity. These findings constitute empirical evidence supporting the conjecture that effects of the 1918 flu and/or the earthquake are associated not just with disruption experienced during the fetal period but also postnatally.

In-utero determinants of adult depression: evidence from the 1918 flu pandemic.

Social scientists have dealt only glancing with potential in-utero determinants of mental health. This study looks at the enduring consequences of gestational exposure to the 1918 flu pandemic for adult depression. It does so using data collected in the first wave of the National Health and Nutrition Examination Survey (1971-1975), corresponding to when those exposed in-utero were in their early to mid-50s. The results indicate very strong effects of in-utero exposure on depression. These effects are only found, however, among men. The effects are sufficiently large to eliminate sex differences in major depression within a cohort: among those born in 1919, the prevalence of major depression is about 1 in 5 for both men and women. Additional analyses further clarify the relationship, showing effects of in-utero exposure across the full spectrum and syndrome of depressive symptoms. In addition, the effects are stronger for symptoms related to depression than for symptoms related to schizophrenia. Additional analyses show that the effect of exposure is reduced somewhat when adjusting for later socioeconomic disadvantages. In addition, the effect is reduced when controlling for broader dimensions of physical health. Yet neither of these relationships explains the effects of exposure altogether.

The pandemic of 1918 and the heart disease epidemic in middle-aged men and women in the United States.

Members of birth cohorts who were alive in 1918 and survived the influenza pandemic were likely to have been "primed" for heart disease in later life. We examine the hypothesis that the twentieth-century heart disease epidemic was a cohort effect reflecting the changing susceptibility composition of the population.We estimated heart disease death rates by single years of age for cohorts born in 1860-1949. We prepared age-specific rates for calendar years 1900-2016, as well as age-standardized cohort and calendar year rates.Males born in 1880-1919 contributed 90 per cent to 100 per cent of all heart disease deaths among males aged 40-64 from 1940 to 1959, when the heart disease epidemic was at its peak. There was no heart disease epidemic among females aged 40-64. Death from heart disease in females tends to occur at older ages.Cigarette smoking, unemployment, and other factors may have played a role in the heart disease epidemic in men and would have interacted with injury from influenza, but our results suggest that having been alive at the time of the 1918 influenza pandemic probably played an important role.

A conceptual model for the coronavirus disease 2019 (COVID-19) outbreak in Wuhan, China with individual reaction and governmental action.

The ongoing coronavirus disease 2019 (COVID-19) outbreak, emerged in Wuhan, China in the end of 2019, has claimed more than 2600 lives as of 24 February 2020 and posed a huge threat to global public health. The Chinese government has implemented control measures including setting up special hospitals and travel restriction to mitigate the spread. We propose conceptual models for the COVID-19 outbreak in Wuhan with the consideration of individual behavioural reaction and governmental actions, e.g., holiday extension, travel restriction, hospitalisation and quarantine. We employe the estimates of these two key components from the 1918 influenza pandemic in London, United Kingdom, incorporated zoonotic introductions and the emigration, and then compute future trends and the reporting ratio. The model is concise in structure, and it successfully captures the course of the COVID-19 outbreak, and thus sheds light on understanding the trends of the outbreak.

Gripe española y otras enfermedades en el Dispensario Infantil de Quito, Ecuador (1918-1919) / Spanish flu and other diseases in the Quito Children's Dispensary (1918-1919)

OBJETIVO PRINCIAPL: Analizar la morbimortalidad en el Dispensario Infantil de Quito anexo al Hospital San Juan de Dios durante la época de la epidemia de gripe española, su correlación con el contexto socioeconómico, las condiciones de salubridad de la ciudad y la morbimortalidad en otras localidades. METODOLOGÍA: Con los registros de atención conservados en el Museo Nacional de Medicina Eduardo Estrella se estructuró un estudio historiográfico médico, descriptivo y analítico de la morbimortalidad entre enero de 1918 y abril de 1919. Se analizó la morbilidad por entidades patológicas, por grupos de edad y por sus determinantes sociales. RESULTADOS PRINCIPALES: El Dispensario atendió 8.882 infantes, 4.370 niñas (49,20 %) y 4.460 varones (50,22 %). Su edad estuvo comprendida entre 1 día y 17 años. Los menores de 2 años fueron 4.598 (51,77%). La mayoría, 8.735 (98,35 %), procedía de Quito. Los registros con diagnóstico fueron 8.738. En 144 casos no hubo diagnóstico. Se registraron 9 defunciones por enfermedades diarreicas, respiratorias y otras infecciosas, entre ellas una defunción por gripe. La enfermedad más frecuente fue la gripe, con 2.780 casos (31,29 %) del total. La morbilidad prevalente fue por patología digestiva, principalmente enfermedades diarreicas y por patología respiratoria con predominio de gripe. La tosferina, endémica en Quito, tuvo prevalencia limitada. El paludismo, endémico en los valles cercanos a Quito, presentó 54 casos (0,61%) del total. Fue erradicado en la serranía en 1956. La varicela, otras enfermedades eruptivas de la infancia y las parasitosis intestinales tuvieron menor presencia, al igual que las enfermedades carenciales. Los niños con gripe recibieron principalmente lactancia materna. Aquellos con enfermedades diarreicas recibieron más frecuentemente alimentación mixta, lo cual podría reflejar las limitadas condiciones sanitarias para la preparación de los alimentos. CONCLUSIÓN PRINCIPAL: El perfil de morbi-mortalidad, con prevalencia de gripe y enfermedades digestivas y respiratorias, obedece no solo a la pandemia de gripe española, sino al empobrecimiento predominante, las condiciones socio económicas y el déficit de infraestructura sanitaria. El perfil de morbimortalidad es similar al encontrado en 1917 en el DIHSJD y en otros estudios de morbimortalidad infantil en la región y en España

OBJECTIVE: To analyze the morbidity and mortality in the Quito Children's Dispensary attached to the San Juan de Dios Hospital during the time of the Spanish flu epidemic, its correlation with the socioeconomic context, the city's health conditions and morbidity and mortality in other locations. METHODS: With the care records kept in the Eduardo Estrella National Museum of Medicine, a medical, descriptive and analytical historiographic study of morbidity and mortality between January 1918 and April 1919 was structured. Morbidity was analyzed by pathological entities, by age groups and by their social determinants. RESULTS: The Dispensary attended 8,882 infants, 4,370 girls (49.20%) and 4,460 boys (50.22%). Her age was between 1 day and 17 years. 4,598 (51.77%) children under 2 years of age. The majority, 8,735 (98.35%), came from Quito. The records with diagnosis were 8,738. In 144 cases there was no diagnosis. There were 9 deaths from diarrheal, respiratory and other infectious diseases, including one death from influenza. Pertussis, endemic in Quito, had a limited prevalence. Malaria, endemic in the valleys near Quito, presented 54 cases (0.61%) of the total. It was eradicated in the highlands in 1956. Chickenpox, other childhood eruptive diseases and intestinal parasites were less prevalent, as well as deficiency diseases. Children with the flu were primarily breastfed. Those with diarrheal illnesses more frequently received mixed feeding, which may reflect the limited sanitary conditions for food preparation. CONCLUSIONS: The morbidity and mortality profiles, with prevalence of influenza and digestive and respiratory diseases, are due not only to the Spanish flu pandemic, but also to the prevailing impoverishment, socio-economic conditions and the deficit of health infrastructure. The morbidity and mortality profiles are similar to that found in 1917 in the DIHSJD and in other studies of infant morbidity and mortality in the region and in Spain

The 1918 influenza pandemic: 100 years of questions answered and unanswered.

The 2018-2019 period marks the centennial of the "Spanish" influenza pandemic, which caused at least 50 million deaths worldwide. The unprecedented nature of the pandemic's sudden appearance and high fatality rate serve as a stark reminder of the threat influenza poses. Unusual features of the 1918-1919 pandemic, including age-specific mortality and the high frequency of severe pneumonias, are still not fully understood. Sequencing and reconstruction of the 1918 virus has allowed scientists to answer many questions about its origin and pathogenicity, although many questions remain. This Review summarizes key findings and still-to-be answered questions about this deadliest of human events.

The Long-Lasting Influenza: The Impact of Fetal Stress During the 1918 Influenza Pandemic on Socioeconomic Attainment and Health in Sweden, 1968-2012.

The 1918 influenza pandemic had not only a massive instant death toll but also lasting effects on its survivors. Several studies have shown that children born in 1919, and thus exposed to the H1N1 virus in utero, experienced worse health and socioeconomic outcomes in older ages than surrounding birth cohorts. This study combines several sources of contemporary statistics with full-population individual-level data for Sweden during 1968-2012 to examine the influence of fetal exposure to the Spanish flu on health, adulthood income, and occupational attainment. For both men and women, fetal exposure resulted in higher morbidity in ages 54-87, as measured by hospitalization. For males, exposure during the second trimester also affected mortality in cancer and heart disease. Overall, the effects on all-cause mortality were modest, with about three months shorter remaining life expectancy for the cohorts exposed during the second trimester. For socioeconomic outcomes, results fail to provide consistent evidence supporting any long-term consequences of fetal exposure. We conclude that although the immediate health effects of exposure to the 1918 pandemic were huge, the long-term effects were modest in size.

Multigenerational Effects of Early-Life Health Shocks.

A large literature has documented links between harmful early-life exposures and later-life health and socioeconomic deficits. These studies, however, have typically been unable to examine the possibility that these shocks are transmitted to the next generation. Our study uses representative survey data from the United States to trace the impacts of in utero exposure to the 1918 influenza pandemic on the outcomes of the children and grandchildren of those affected. We find evidence of multigenerational effects on educational, economic, and health outcomes.