influenza

"In the case of an influenza pandemic, existing vaccines would likely be ineffective against a radically new strain. Developing and globally distributing a new pandemic influenza vaccine will likely take 4-6 months (4 months to produce first doses of vaccine, and 6 months to produce enough to give to a large number of people), even while mathematical models demonstrate that pandemic influenza could spread globally within 6 months. Another complicating factor to pandemic influenza vaccine production involves how the vaccine is made. Since the 1940s, seasonal and pandemic influenza vaccines have been produced in chicken eggs. The virus is introduced in the allantoic fluid of the fertilized egg (this is the fluid that bathes the embryo and yolk sac), and it replicates in the membrane surround the fluid. After about three days, the virus-containing fluid is harvested from each egg, and the rest of the manufacturing process proceeds. Dependence on egg-based vaccine production is, however, problematic even with non-pandemic seasonal influenza vaccine. First, eggs must be available in large quantities when vaccine production is to begin. Any disruption in egg supply – such as disease affecting chickens, or bad weather interfering with the shipping of eggs – can mean a delay in vaccine production. Second, some influenza strains grow more slowly or less robustly than others, which can result in delays or in lower yields of vaccine virus from each egg. Third, it is possible that some viral vaccine strains, given the origin of some influenza viruses in birds, may be toxic to eggs. In that case, egg-based influenza vaccine production methods would be useless."

"The use of licensed inactivated trivalent influenza vaccine is increasing, but even if all high risk persons currently given priority for this vaccine should be vaccinated each year, influenza epidemics would continue to occur."

"Recent pandemics illustrate another problem that must be faced with an impending pandemic. The time between recognition of the emergence of a new pandemic virus and the occurrence of the first wave may be short. The lead time for the production and distribution of the currently licensed influenza vaccine, trivalent influenza vaccine is 6 months. It is highly unlikely that sufficient vaccine can be produced, distributed and administered to the entire population before the first wave of the pandemic. In 1918 and 1957, the first wave of the pandemic peaked in late October allowing less time than usually occurs before the onset of interpandemic outbreaks, in the usual sequence of vaccine production starting in January."

"Other approaches to accelerating influenza vaccine production involve use of what are referred to as dose-sparing technologies. These are innovations that allow less antigen to be used for each vaccine dose, without compromising immunogenicity or safety. Dose-sparing technologies have the potential to markedly increase vaccine production potential in a pandemic. Adjuvants (compounds that enhance the immune response to a vaccine and therefore reduce the amount of vaccine virus required for each dose) are one such technology. The most commonly used adjuvant today is an aluminum compound found in many childhood vaccines, but which is not used in influenza vaccine. Oil-in-water emulsion adjuvants show the greatest advancement and promise in terms of dose sparing for influenza vaccines. Other potential technologies might involve self-adjuvanting recombinant or molecular vaccines that have built-in antigen-sparing properties. Other promising candidates and technologies may emerge that lead to development of a universal influenza vaccine, which is the ultimate goal for many influenza vaccine programs. Such a vaccine might need to be given only once, rather than every year as with current seasonal vaccines. Such a universal vaccine would ideally provide protection against all, or at least most, of the many strains of influenza capable of making people sick, including future pandemic influenzas. Plant-produced influenza vaccines are in clinical trials and may prove to be a useful alternative to egg- and cell-based vaccines."

"In the last 100 years, numerous vaccines have become available for influenza prevention. In the United States, national vaccine policy recommends influenza vaccination annually for everyone older than age 6 months. There are multiple types of vaccine that use different inactivated, live-attenuated, and egg-free formulations. Recent efforts through WHO’s Global Action Plan for Influenza Vaccines and the Pandemic Influenza Preparedness framework supported efforts to increase vaccine manufacturing and laboratory capacity for identifying viruses for use in vaccines. The global pandemic influenza vaccine production capacity in 2015 was estimated to be 6.4 billion doses—a record level, but not enough to provide the potential need for 2 doses for even half the world’s population. The current timeline for vaccine production also limits the usefulness of pandemic vaccine, as reflected in 2009, when the bulk of pandemic vaccine was not available until after the peak of the pandemic. However, increased use of new vaccine formulations that do not rely on growing viruses in eggs, such as cell-based vaccine and recombinant protein vaccine, will reduce the time required for vaccine manufacturing. In addition, further expansion of seasonal influenza vaccine manufacturing capacity worldwide, and continued increases in use of vaccine, will facilitate pandemic vaccine production and global access to pandemic vaccines."

"Despite our modern arsenal of antibiotics, of viral and bacterial vaccines, of antiviral drugs, advanced intensive care treatment, and nonpharmaceutical interventions, we are still doing a poor job of preventing influenza deaths. The most important lesson from the devastation of the 1918 pandemic may be the need to produce better antiviral drugs and prophylactic and therapeutic monoclonal antibody therapies. We need effective vaccines against multiple bacterial pneumopathogens, especially S. aureus and S. pyogenes, and effective broadly protective “universal” influenza vaccines to prevent, or at least mitigate the impact of, future pandemics and to prevent deaths from seasonal influenza in the periods in between pandemics. Vaccines that could confer long-term broad immune responses against all influenza viruses, and especially against viruses with the most pathogenic HAs found in nature, would greatly enhance public health preparedness."

"Production capacity is another limitation to deployment of pandemic influenza vaccine. Current global capacity for pandemic influenza vaccine production is less than 3 billion doses per year, far short of the 7 billion doses that would be needed for universal coverage. To address some of these problems with egg-based vaccine production, some pharmaceutical companies are attempting to eliminate eggs from the process altogether. Novartis produces influenza vaccine from virus cultivated in cells derived from canine kidney cells (see the FDA information on this vaccine). Protein Sciences Corporation produces influenza vaccine using recombinant DNA technology and an insect virus system (see the FDA information). Other companies are developing influenza vaccine produced from different types of cell lines. Given that it takes roughly the same amount of time for influenza virus to replicate in eggs and in cell culture, shifting to cell culture will not necessarily speed up this phase of production. However, using cell culture technology will eliminate the lead time necessary to secure fertilized eggs for vaccine production and will reduce some of the variables related to the quantity of vaccine virus achieved with eggs. Additionally, egg-based influenza vaccine production requires a step in which the influenza virus is altered so that it reproduces well in eggs. If cell-based manufacturers can skip that step, they can begin vaccine production 4-6 weeks earlier than egg-based manufacturers."

"Many challenges remain to improving influenza vaccines. Current seasonal influenza vaccines, at best, are only moderately effective in preventing illness and often have low effectiveness. Greater monitoring of vaccine effectiveness is needed to better inform incremental improvements in current influenza vaccines. A more broadly protective and longer-lasting (i.e., “universal”) vaccine could decrease the current need for frequent formulation change and improve prevention of influenza worldwide, especially in low-resource and middle-income countries. Rapid development of vaccine candidates, accelerated clinical trials, and reducing the time required to formulate and distribute pandemic vaccine can reduce pandemic morbidity and deaths. Therefore, reducing the current pandemic influenza vaccine availability timeframe from 20 to 12 weeks is a key priority in the 2017 Update of the Health and Human Services Pandemic Influenza Plan."

"The virulence of the 1918 H1N1 virus intensified the situation. Epidemiologic parameters of the 1918 pandemic, which include an attack rate of 28% and an estimated basic reproduction number of 1.8, were similar in subsequent influenza pandemics of 1957 and 1968. However, the estimated case fatality proportion of 1.7% in the 1918 pandemic was more than 10 times higher than in the 1957 and 1968 pandemics. Pandemic influenza in 1918 often presented with an unusually severe and swift clinical course. Disease frequently progressed to extensive organ involvement, primary viral pneumonia, and secondary bacterial pneumonia and empyema. Some military physicians reported a rapid clinical course, with death occurring within 24–48 hours after hospital admission. Pneumonia was the cause of death for the vast majority of the deceased. The unprecedented death rate exceeded the capacity of many morgues and funeral homes, and bodies were often “stacked like cord wood” in the halls of both military and civilian hospitals. Ultimately, the death toll, particularly among previously healthy young adults, reduced life expectancy in the United States by 12 years."

"I can say that often death notices for doctors and nurses showed up in tiny print in the newspapers. In many places the rates were high; morbidity over 50%. Logic suggests that social distancing measures helped, but I am not convinced that those interventions had an effect that was anything more than random. One can’t really generalize, because morbidity and mortality rates varied so much from community to community."

"Thomas Wolfe wrote a literary masterpiece about the death of his brother. More fabled is how influenza altered the decision-making abilities of President Woodrow Wilson and his chief aide, Colonel Edward House. Both were in Europe to attend the Paris Peace Conferences—the famed gathering where Wilson hoped to sell his Points and establish a League of Nations. Colonel House, who arrived in Europe just weeks before the Armistice, contracted a severe bout of flu as he was negotiating with the other nations. In late February, as he was recuperating from his serious illness, Colonel House noted that, “When I fell ill in January, I lost the thread of affairs and I am not sure that I have ever gotten fully back.” To make matters worse, when Wilson was in Paris in mid-March, to work with the Big Four in the final stages of a comprehensive peace treaty, he, too, was stricken by influenza. Volumes have been written on how influenza may have altered the terms and negotiations of the Treaty of Versailles as it ravaged the bodies and thoughts of Woodrow Wilson and Edward House, among others. While social historians of medicine warn against focusing too heavily on the illnesses of great men or the landmark cures of great doctors, the fact remains that when a world leader is struck down by influenza, in the midst of a pandemic that is accompanied by other global crises, the microbes’ power can be amplified above and beyond the symptoms it produces or the death it causes."

"As bad as a bout of real seasonal influenza is, the H1 strain was far worse. It killed two percent or more of those stricken. In 1918, postmortem examinations helped understand if it was a case of flu. The performance of those autopsies was harrowing. Influenza defiled the lungs with bloody, frothy fluid. Instead of floating, the lungs plummeted to the bottom of water buckets during autopsies. The bronchials were fluid-filled, which explains the air hunger patients experienced. They frequently died from suffocation within 24–48 hours of developing symptoms. Some died later from secondary infections."

"There are two great tragedies: The death of a child, or the death of a young child’s parent. Society saw a lot of both in 1918. There were many orphans in 1918. Several states put together orphan trains for adoption stops, which led to the establishment of the Child Welfare Department."

"Treatment for influenza and its complications was mostly supportive care. Palliatives from pharmacies and vendors were encouraged, if not presented as cures. No antivirals or antibiotics were available; penicillin was not discovered until 1928. One potentially effective therapy for reducing the risk of death was use of convalescent sera collected from patients after their infection and administered to patients with current infection. Many more physicians, however, attempted to treat patients with “vaccines”. At the time, Haemophilus influenzae was the presumed etiologic agent for influenza, referred to as Pfeiffer’s bacillus. Vaccines were made from culture of the bacillus and may have been effective at reducing some secondary bacterial coinfections."

"The founding 1918 pandemic virus is truly the “mother” of all subsequent influenza pandemics, and we are still in its “pandemic era” today. Its descendants are still evolving, still killing tens of thousands of people every year, with no end in sight."

"A pandemic meets the propaganda machine: During this time at least 25% of doctors and nurses were in the military. Additionally, national, local, and state officials all operated in the same way. At best, they communicated half-truths, or even out-right lies. As terrifying as the disease was, the officials made it more terrifying by making little of it, and they often underplayed it. Local officials said things like “if normal precautions are taken, there is nothing to fear” but then they would close all businesses. “Worry kills more people than the disease itself,” a Chicago public health official was quoted as saying. Other quotes were: “Don’t get scared,” and “The so-called Spanish influenza is nothing more or less than old fashioned grippe.” Communication was rarely honest, because honesty would hurt morale. One of the first newspapers that started telling the truth in Milwaukee saw its editor jailed, so they stopped telling the truth. In Philadelphia, after a public health official finally closed all public gatherings and public funerals, the newspaper said, “This is not a public health measure.”"

"Navy nurse Josie Brown, who served at Naval Hospital in Great Lakes, Illinois in 1918, later described what happened there and in many hospitals around the country: The morgues were packed almost to the ceiling with bodies stacked one on top of another. The morticians worked day and night. You could never turn around without seeing a big red truck loaded with caskets for the train station so bodies could be sent home. We didn’t have the time to treat them. We didn’t take temperatures; we didn’t even have time to take blood pressure. We would give them a little hot whisky toddy; that’s about all we had time to do. They would have terrific nosebleeds with it. Sometimes the blood would just shoot across the room. You had to get out of the way or someone’s nose would bleed all over you."

"A mortality study in 17 cities in the USA during the 1918 influenza pandemic found that the cities which implemented mitigation strategies early on had a delayed, flatter epidemic curve, with a 50% lower peak mortality, and a 20% lower overall mortality. Thus, mitigating policies are of paramount importance to ensure that the burden on the health-care system remains manageable."

"At the L.H. Shattuck Company, 45.9% of the workers stayed home. At the George A. Gilchrist shipyard 54.3% stayed home. At Freeport Shipbuilding 57% stayed home. At Groton Iron Works 58.3% stayed home. Even in an industry that was crucial to the war effort, absenteeism was high. Fear and terror was akin to the Black Plague. An internal American Red Cross report concluded, “A fear and panic of the influenza, akin to the terror of the Middle Ages regarding the Black Plague, [has] been prevalent in many parts of the country.”"

"The 1918 mortality numbers alone do not adequately describe the disaster. It was not just the weak and infirm who were taken away but the flower and strength of the land. The age-specific mortality curve did not trace the “U” describe above, but resembled a “W” with very high mortality rates in healthy young adults aged 20-40 years as well as in those less than 5 years of age and those aged 65 years and older (figure 1). No adequate explanation of this mortality pattern has been presented. It was wartime and young men were crowded together in military camps, but the mortality has highest in men of the same age who remained at home. Pregnancy was a risk factor, and this may provide some explanation for the high mortality in young women (23, 24). The fulminant nature of the clinical course of the fatal pneumonia casessuggests the the virus itself possessed a virulence not seen before nor since."

"Viruses are part of nature. They have attacked human beings—sometimes dangerously—in both distant and recent history. In 1918, the Spanish Flu killed nearly 700,000 in the United States and millions elsewhere."

"Context: We were at war. It was the first total war. It was the first time the government tried to fully control the public. The pandemic was known as Spanish flu, but we know it did not start in Spain. It was called Spanish Flu because Spain was not at war, so there was a free press. Most of Europe had a censored press. The U.S. press was more open, but still the new Sedition Act was passed. This was a law that made the Patriot Act look like it was written by the ACLU (American Civil Liberties Union). To enforce the law, the Justice Department issued badges to the “American Protective League” (APL), who was identified as Secret Service. Within a year, the attorney general said 200,000 APL members were operating in 1,000 communities. In Chicago, a “flying squad” of league members and police trailed, harassed, and beat members of the International Workers of the World (IWW). In Arizona, league members and vigilantes locked 1,200 IWW members and their “collaborators” into box cars and left them on a siding across the state line in the New Mexico desert. Throughout the country, the league's American Vigilance Patrol targeted “seditious street oratory,” sometimes calling upon the police to arrest speakers for disorderly conduct, sometimes acting more directly. Everywhere, the league spied on neighbors, investigated “slackers” and “food hoarders,” and demanded to know why people didn't buy—or didn't buy more—liberty bonds. At the same time, states outlawed the teaching of German. In Providence, Rhode Island, the Providence Journal carried a banner warning that “every German or Austrian in the United States unless known by years of association should be treated as a spy.” The problem was that the single largest ethnic group in the United States was German. 1918 was a time when there was a well-run propaganda machine. The government created the Committee for Public Information (CPI). It was intended to create one white-hot mass of determination. A quote by Arthur Bullard (who directed the CPI's Russian Division) summarizes the tenets of propaganda at the time, “Truth and falsehood are arbitrary terms... There is nothing in experience to tell us that one is always preferable to the other... There are lifeless truths and vital lies... The force of an idea lies in its inspirational value. It matters very little if it is true or false.” Part of the propaganda machine included the energetic direction of Mississippi newspaper editor George Creel, an advisor to President Wilson. Under Creel, the CPI churned out national propaganda through diverse media. Creel organized the “Four-Minute Men,” a virtual army of volunteers who gave brief speeches wherever they could get an audience. There were 150,000 of the Four-Minute Men, who would propagandize for “four minutes” prior to any kind of public gathering. These men were charged with creating fear in the population because it was “an important element to be bred in the civilian population. It is difficult to unite a people by talking only on the highest ethical plain. To fight for an ideal, perhaps, must be coupled with thoughts of self-preservation.”"

"1918 case fatality rates in one-to-four year-olds is equivalent to what it would take now for 15–16 years of fatalities."

"There is a tremendous amount of wishful thinking that the virus won’t come here. In 1918 the shaping of the cognitive environment varied dramatically from location to location some places elected officials and public officials locked arms on some things. Some tentative evidence shows that social distancing interventions did help. However, Baltimore is a case example of how to do it wron g (e.g., not close the schools). In Baltimore there were fights between elected officials and public health officials. Another example of doing it wrong was Pittsburgh. In Pittsburgh, the Mayor actually told the public to ignore the public health officials."

"Los Angeles introduced interventions during the first few weeks of the epidemic, much earlier than New York, so they did not suffer the types of problems New York experienced. Baltimore newspapers published appeals to the public to minimize the use of telephones, but even at the height of the pandemic the phone system did not fail. Chicago attempted to estimate absenteeism. They estimated absenteeism averaged about 5% over a two-month period, not quite double thnormal average. Absenteeism peeked on October 22. However, the aggregate impact of absenteeism was significantly reduced. Economic impacts were modest, below 5%, when averaged out. A major recession did not ensue. Retail sales did decline in October, but they rebounded in November. New York City transit use, the Dow Jones, and business failures were indiscernible and modest when compared to the volatility of the period. Because of the short duration of the pandemic and human resiliency, it was characterized as a hit-and-run disease that only produced brief slowdowns."

"Cities were more isolated from each other. The pattern of the spread of the virus 1918 was related to troop movements. There has been a considerable amount of work on modeling from Department of Transportation (DOT) looking at connectivity of major urban centers to estimate how infectious diseases would spread now. In recent work looking at real world data, the geographic diffusion process is driven more by work-related travel."

"The 1918 influenza pandemic was the most severe pandemic in recent history. It was caused by an H1N1 virus with genes of avian origin. Although there is not universal consensus regarding where the virus originated, it spread worldwide during 1918-1919. In the United States, it was first identified in military personnel in spring 1918. It is estimated that about 500 million people or one-third of the world’s population became infected with this virus. The number of deaths was estimated to be at least 50 million worldwide with about 675,000 occurring in the United States."

"In 1918, the childhood mortality rate for children under five-years-old was one in five. Every household knew of a child who died at a very young age, often of a contagious disease or dehydration issues. Back then, the care of the ill was almost exclusively at home. Today, death has been taken out of the household. Very few people have seen someone die today. In 1918, it was probably 90%. Death issues need to be talked about. For example, what should we do if public gatherings for funerals are cancelled? How will that affect people? There are social effects of quarantine, although now we have some resources to mitigate the effects. Public health departments (municipal, state, and federal) are all funded very differently. Post 9-11, bioterrorism preparedness efforts have been good for public health, because they are not mutually exclusive problems. Whether man-made or ecological, the strategies we need to use to address these problems are not that different."

"The 1918 influenza pandemic offers the worst-case planning scenario for public health officials because it resulted in unparalleled numbers of deaths. The virus, an A(H1N1) subtype, may have infected half the world’s population and caused at least 50 million deaths, according to estimates; 675,000 deaths are thought to have occurred in the United States. The source of the 1918 H1N1 virus is unknown; avian and swine origins have been proposed. Although 3 later pandemics, in 1957, 1968, and 2009, resulted in much lower estimated rates of morbidity and death, the threat of a 1918-like severity pandemic remains, because reports of human infections with novel influenza A viruses (generally of avian or swine origin) that pose pandemic potential have increased in recent years. In particular, Asian lineage avian influenza A (H7N9) viruses caused 1,557 reported human infections and at least 605 deaths during 5 epidemics in China during 2013–2017. Now, 100 years after the 1918 pandemic, is an important time to recall the significant impact of the pandemic and to reflect on the current state of readiness to respond to the next influenza pandemic."

"The world situation in 1918 exacerbated the effects of the pandemic. Wartime conditions combined with the intrinsic pathogenicity of the virus to cause tremendous morbidity and death rates. Poor sanitation, overcrowding, and limited health services during World War I facilitated disease transmission. Wartime overcrowding was rampant. Camps for troops, hastily built to accommodate 36,000, were soon housing 45,000 young and immunologically naïve soldiers. Each day in the summer of 1918, an average of 10,000 US soldiers crammed onto ships bound for France. Civilians flooding to cities in support of war industries quickly exceeded available housing capacity. With 30% of US physicians engaged in military service, medical personnel were in short supply when the pandemic struck."

"Unlike today, there was no CDC or national public health department. The Food and Drug Administration existed but consisted of a very small group of men. Additionally, there were no antibiotics, intensive care units, ventilators, IV fluids or vaccines. “You got a bed or maybe nursing care,” Markel said. But there was an epidemiologist much like Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, who withstood criticism for publicly pressing for safety protocols, according to Forbes. “At the center of public health efforts in both states was a practical, plainspoken, bespectacled scientist: Dr. Thomas Dyer Tuttle, who became a powerful, if polarizing, figure in the fight against the Spanish flu,” according to Forbes. Scientists hadn’t even seen a virus under the microscope at that point, said Graham Mooney, a medical historian at Johns Hopkins University School of Medicine. They didn’t have the technology and they knew almost nothing of virology, which was considered a nascent science because viruses are so small, he said. In fact, some scientists thought the 1918 virus was caused by a bacteria called Haemophilus influenzae, he said."

"Doctors were at a loss as to what to recommend to their patients; many physicians urged people to avoid crowded places or simply other people. Others suggested remedies included eating cinnamon, drinking wine or even drinking Oxo's meat drink (beef broth). Doctors also told people to keep their mouths and noses covered in public. At one point, the use of aspirin was blamed for causing the pandemic, when it might actually have helped those infected. June 28, 1918, a public notice appeared in the British papers advising people of the symptoms of the flu; however, it turned out this was actually an advertisement for Formamints, a tablet made and sold by a vitamin company. Even as people were dying, there was money to be made by advertising fake "cures." The advert stated that the mints were the "best means of preventing the infective processes" and that everyone, including children, should suck four or five of these tablets a day until they felt better. Americans were offered similar advice about how to avoid getting infected. They were advised not to shake hands with others, to stay indoors, to avoid touching library books and to wear masks. Schools and theaters closed, and the New York City Department of Health strictly enforced a Sanitary Code amendment that made spitting in the streets illegal, according to a review published in the journal Public Health Reports."

"The origin of this pandemic has always been disputed and may never be resolved. However, the observations of trained observers at that time are worth noting because they may bear on later genomic analysis of the recently resurrected 1918 virus nucleotide fragments and the abortive "swine flu" epidemic of 1976. In Richard Shope's Harvey lecture of 1936, he reviews evidence that in the late summer or early autumn of 1918, a disease not previously recognized in swine, and closely resembling influenza in humans, appeared in the American Middle West. Epidemiologic-epizootiologic evidence strongly suggested that the causative virus was moving from humans to swine rather than in the reverse direction. Similar observations were made on the other side of the world and reported in a little-known paper in the National Medical Journal of China. In the spring of 1918, influenza in humans spread rapidly all over the world and was prevalent from Canton, China, to the most northern parts of Manchuria and from Shanghai to Szechuan. In October 1918, a disease diagnosed as influenza appeared in Russian and Chinese pigs in the area surrounding Harbin. Thus, epidemiologic evidence, fragmentary as it is, appears to favor the spread of virus from humans to swine, in which it remained relatively unchanged until it was recovered more than a decade later by Shope in the first isolation of influenza virus from a mammalian species. The virus of 1918 was undoubtedly uniquely virulent, although most patients experienced symptoms of typical influenza with a 3- to 5-day fever followed by complete recovery. Nevertheless, although diagnostic virology was not yet available, bacteriology was flourishing and many careful postmortem examinations of patients by academic bacteriologists and pathologists disclosed bacterial pathogens in the lungs. However, this was a time when bacterial superinfection in other virus diseases could lead to death; for example, measles in military recruits was often fatal. This information is important in considering the question of "will there ever be another 1918." To the degree that secondary bacterial infection may contribute to influenza death rates, it should at least be partially controllable by antimicrobial agents, as indeed was the case in 1957."

"“Influenza generally has a U shaped mortality curve, meaning it looks like a U, but the tops of the U are the most deadly,” Markel said. “But in 1918 it was a W shaped mortality curve and that upside-down part of the W, the V, was young people between ages 18 and 40 dying like flies. That was odd. That was not typical for previous flu pandemics or subsequent ones.” It’s also important to consider population when talking about outbreaks or disasters, said Samantha Montano of the Massachusetts Maritime Academy, who studies disasters. In 1918, the world population was much smaller with an estimated 1.8 billion people. Today, there are nearly 8 billion on the planet. Mooney echoed those remarks, saying, “We’re talking about a global population that is sort of smaller than it is now.” He said the death toll from 1918 virus likely had a great impact on the workforce who were unable to work from home or remotely like we can today. “You end up having major structural, economic and social readjustments when you have such a massive death toll like that,” he said. “We have social welfare networks ... people travel around the globe. We have different societies and economies.”"

"When the first wave of the pandemic arrived, it was not particularly deadly. The only notice British officials took of it was its effect on some workers. A report noted, “As the season for cutting grass began … people were so weak as to be unable to do a full day’s work.” By September, the story began to change. Mumbai was still the center of infection, likely due to its position as a commercial and civic hub. On Sept. 19, an English-language newspaper reported 293 influenza deaths had occurred there, but assured its readers “The worst is now reached.” Instead, the virus tore through the subcontinent, following trade and postal routes. Catastrophe and death overwhelmed cities and rural villages alike. Indian newspapers reported that crematoria were receiving between 150 to 200 bodies per day. According to one observer, “The burning ghats and burial grounds were literally swamped with corpses; whilst an even greater number awaited removal.” But influenza did not strike everyone equally. Most British people in India lived in spacious houses with gardens and yards, compared to the lower classes of city-dwelling Indians, who lived in densely populated areas. Many British also employed household staff to care for them – in times of health and sickness – so they were only lightly touched by the pandemic and were largely unconcerned by the chaos sweeping through the country. In his official correspondence in early December, the Lieutenant Governor of the United Provinces did not even mention influenza, instead noting “Everything is very dry; but I managed to get two hundred couple of snipe so far this season.”"

"The 1918 flu almost certainly didn’t originate in Spain. One popular theory for how it acquired the “Spanish” name posits that Spain was the only country where you could read about the disease. That’s because Spain remained neutral during World War I, and therefore its newspapers weren’t censoring any information deemed harmful to national morale. The disease was also rampaging through other countries, including France, Germany, Britain, and the United States, but those governments suppressed or downplayed reports on the extent of the damage. Accurate and timely information is vital to combating a pandemic, but still, some countries’ first impulses are to cover up the spread of the disease."

"Owing to suspected cases of Spanish Influenza on the reservation every one is cautioned to take every care that they do not expose themselves or their neighbors. And to observe the following rules: Do not collect in a crowd any place. Women and children remain at home. Stay in the open air and sunshine. Keep the home aired out. Have plenty of fresh air when you sleep In case of storm keep dry and do not expose yourselves. Do not mingle with others more than is necessary. Do not go near where any one is sick or where a white flag is flying. Do not go to the store unless it is necessary. If you have to go to the store or office your wants will be attended to on the porches. If you get sick go to bed, in a tent is best, and notify the doctor at once. Lie down flat on your back and stay there. Only one person in the family should go near the sick person. Every one help the Superintendent and Doctor all they can by following these instructions and they will do all they can for you."

"“You told people to wash your hands, don’t cough on people, stay at home, stay away from other people,” he said. “It was the patriotic thing to do to not cough on people or stay home if you were sick.” But the thing that really drew public backlash were mask recommendations. As it turns out, resistance to wearing the face coverings isn’t new. People during the 1918 pandemic called them dirt traps and some clipped holes so they could smoke cigars. In Europe, the Italian Supreme Command asked residents not to fail their cities by not wearing a mask. Several U.S. cities implemented mandates, describing them as a symbol of “wartime patriotism.” In San Francisco, Mayor James Rolph said, “conscience, patriotism and self-protection demand immediate and rigid compliance,” according to influenzaarchive.org. But some people refused to comply or take them seriously, Markel said."

"Combating a disease of unknown cause is a daunting task. One hundred years ago, a pandemic of poorly understood etiology and transmissibility spread worldwide, causing an estimated 50 million deaths. Initially attributed to Haemophilus influenzae, it was not until the 1930s that an H1 subtype was identified as the causative strain. Subsequent influenza pandemics in 1957, 1968, and 2009 did not approach levels of morbidity and mortality comparable to those of the 1918 “Spanish flu,” leaving unanswered for almost a century questions regarding the extraordinary virulence and transmissibility of this unique strain."

"Spanish Flu victims suffered massive pneumonia and fatal pulmonary complications: they literally drowned in their own body fluids. Lungs filled with fluid and their skin became markedly discolored from the lack of oxygen. Mysteriously, it killed more young than old. The death rate was greatest among ages 15 to 40."

"In 1918, Navy and Marine patients totaling 121,225 were admitted at Navy medical facilities with influenza. Of these patients, 4,158 died of the virus, and sick patients spent over one million sick days in these facilities worldwide."

"The site of origin of the great pandemic of 1918 is unknown, but some choose to think that it was in the United States. Scattered outbreaks of disease were detected during the spring and early summer of 1918. Excess pneumonia-influenza deaths were evident from later tabulations by Wade Hampton Frost, who directed most of the epidemiologic investigations of this pandemic for the US Public Health Service. Many of the early outbreaks occurred in military installations as recruits poured into training camps to respond to the call for troops in Europe. Outbreaks also occurred on troop ships and among the American Expeditionary Forces in France by April 1918. The disease was soon evident among allied forces. A period of quiescence was noted in the United States during the summer. In some areas it was suspected that a reintroduction from Europe occurred in late summer and early autumn. However, in retrospect, it is evident that “seeding” of many geographic areas of the United States had occurred during the previous spring, that transmission was low during the summer but picked up rapidly as schools reopened in September. The first wave of the pandemic reached a crescendo by the end of October 1918. This was followed by a decline and recrudescence in midwinter 1919. The same pattern of occurrence was observed in the United States in 1957 with the next pandemic caused by influenza A (H2N2) (20)."

"They found that during the peak of the 1918 influenza outbreak in New York City, a total of 31,589 all-cause deaths (this included death from any cause) occurred among the 5.5 million residents that lived there at the time. The all-cause mortality in the peak of the influenza pandemic in 1918 was 2.8 times higher than during the same months in previous years. In contrast, for the early 2020 COVID-19 outbreak in New York City, they found that 33,465 deaths from all causes occurred among 8.28 million residents between March 11 and May 11. The all-cause mortality in those months of 2020 were 4.15 times higher than those months between 2017 and 2019. That means that in the peak of the 1918 influenza pandemic in NYC about 287 per 100,000 people died a month from any cause in NYC, whereas during the early COVID-19 outbreak, about 202 per 100,000 people died a month in the city. So the all-cause mortality during the spring of 2020 was 70% of the all cause mortality during the fall of 1918. "When we do that, we see that COVID-19 really does have the potential and has already unfortunately caused per capita death rates that were in the same ballpark," Faust told Live Science."

"But there's another way to look at the deaths related to each pandemic: comparing deaths during a pandemic to the baseline that you'd expect during a particular time. There were more "excess deaths" during the 1918 flu than the early COVID-19 outbreak. But in relative terms, the COVID-19 outbreak in the spring actually looks worse, because the numbers quadrupled from pre-pandemic times (from a baseline of around 50 deaths per 100,000 people per month), whereas in the peak of the 1918 flu, the numbers less than tripled (from a baseline of around 100 deaths per 100,000 people per month). "Its a bigger shock to our system, but that's a little bit unfair because we started off at a lower death rate," than there was in 1918, due to advances in hygiene, medicine, public health and safety, Faust said. Really, we don't yet know if the 1918 pandemic or the COVID-19 pandemic is more deadly, he added. Maybe what happened in New York in the spring was a "freak thing," before interventions such as masks and shutdowns took hold; or maybe the numbers will slowly creep up to match the death tolls seen in the 1918 flu until an effective vaccine is found. One limitation of the study is that it's not possible to directly compare how infectious and harmful the two viruses are to people and it's unknown how many deaths from SARS-CoV-2 were prevented because of modern interventions that weren't available a century ago, the authors wrote."

"No one really knows how many people died, but the first contemporary estimates put deaths at 21 million worldwide. That estimate is often still quoted, but it was certainly far worse than that. MacFarlane Burnett spent much of his life studying influenza, and he concluded that the worldwide death toll (from the 1918–1919 pandemic) was a minimum of 50 million, possibly 100 million. He may well have been right. If you adjust for population, that could be 300 million today. In three weeks, it killed more people than AIDS has in 24 years. In the U.S., a reasonable estimate starts at 500,000 deaths. Personally, I am inclined toward a higher estimate of 700,000. There was 15–53% morbidity. In San Antonio, over 90% of households had at least one family member with the illness. Most of the deaths occurred in healthy adults. In Army camps, the death toll was routinely over 5%, sometimes as much as 10%, and in some communities as high as 30%."

"A big problem was you never knew if you were going to have the lethal kind, or normal flu. Regardless, it was gruesome. There were many with broken ribs from violent coughs. Air pockets also formed outside the lungs, and when you’d move these people it would sound like popping bubble wrap. Nose bleeds were common, less common was bleeding from mouth, and even bleeding from the eyes and ears."

"For the protection of others, if you are really sick stay at home and remain there until the fever is over. A day in bed at the very beginning may also save you from serious consequences later on. If you are up an about, protect healthy persons from infection-don’t spray others with the secretions from your nose and throat in coughing, sneezing, laughing, or talking. Cover the mouth with a handkerchief. Boil your handkerchiefs and other contaminated articles. Wash your hands frequently. Keep away from others as much as possible while you have a cough. If you become ill don’t try and keep on with your work. Fight the disease rationally and do not become unduly alarmed. In the average case recovery from acute symptoms follows in five or six days. To hasten recovery and lessen the danger of complications,, go to bed at once and keep the body a cathartic, such as 2 ½ or 3 grains of calomel, followed by a seidlitz powder or Epsom salts, is useful. Aspirin in 5 grain doses is useful for pain, but do not take large doses of aspirin, phenacetin, or other medicines. Send for the doctor."

"While the 1918 H1N1 virus has been synthesized and evaluated, the properties that made it so devastating are not well understood. With no vaccine to protect against influenza infection and no antibiotics to treat secondary bacterial infections that can be associated with influenza infections, control efforts worldwide were limited to non-pharmaceutical interventions such as isolation, quarantine, good personal hygiene, use of disinfectants, and limitations of public gatherings, which were applied unevenly."

"Maternal mortality rates peaked in 1918 with 916 per 100,000 births. That means one per 1,000 births. The multiplying factor is enormous. There is not, however, a lot of specific data about pregnancy during that time."

"In India, during the 1918 influenza pandemic, a staggering 12 to 13 million people died, the vast majority between the months of September and December. According to an eyewitness, “There was none to remove the dead bodies and the jackals made a feast.”"