The authors of the Newsweek piece assume that COVID-19 deaths are limited to those directly ascribed to COVID-19 infection on the death certificate. They seem oblivious to the possibility that a virus that can infect every organ and has been shown to cause a wide range of sequelae^2-5  might be leading to a rise in all-cause morbidity^6,7 and mortality^8-11  beyond the timescale of acute infection.  Many countries have already experienced a drop in life expectancy, including in 2020 before vaccines were widely available. Vaccine skeptics are promoting the dangerous falsehood that COVID-19 vaccines, not COVID-19 itself, are the cause of the unprecedented decline in almost every measure of public health. In reality, evidence shows that excess mortality related to COVID-19 is highest in areas with low vaccination rates¹².

By remaining silent or downplaying the ongoing risk of COVID-19, governments have abdicated their responsibility to provide their citizens with reliable public health information. Misinformation peddlers, grifters and the ill-informed have filled the gap, sowing doubt and fear about one of the most important things that might offer some protection from the harms of a widely circulating virus: vaccines. By every measure, be it reducing mortality^13,14, improving short-term morbidity^15,16, or reducing the long-term ill-health impacts^17,18, vaccines are effective at taking the sting out of COVID-19’s tail. They are less effective against transmission because of waning immunity and immune escape due to virus mutation, but they are beneficial by any measure and are not responsible for the excess mortality and morbidity being seen around the world¹⁹. Vaccination rates are in fact strongly correlated with improved survival^20,21.

Governments need to step up to correct the record loudly. The quiet warnings issued by the World Health Organization and some governments about the ongoing risks of COVID-19^22,23 need to become much, much louder. People need to be made aware of the potential harms of each and every infection, and in addition to providing accurate information and closing the knowledge gap that is allowing merchants of doubt to flourish, governments need to take urgent action to address the root cause of the problem. We need to work towards stopping transmission of COVID-19 in the community, and we need to do it with a concerted push to broaden availability of vaccines and boosters, to clean the air and normalise N95/FFP2 or better respirators in all public settings, particularly in healthcare and education^{24, 25}.

Some media organizations around the world are slowly starting to realize there is a global shortage of workers in high-contact professions. Teachers are in short supply everywhere from America to Australia^26-33. Bus drivers are scarce across Europe³⁴. Britain is running out of nursery workers³⁵, prison officers³⁶ and probation officers³⁷. Medical professionals are unable to keep pace with demand and are experiencing record levels of burnout^38-42. Healthcare workers are also suffering the impact of Long COVID^43-47. A few more attentive media organizations are making the link and warning about the ongoing harms of repeat SARS-CoV-2 infections^48-50. Long COVID is already impacting the economy by causing reduced workforce capacity⁵¹.

The general population is showing worrying signs of decline, with cognitive dysfunction being observed on a huge scale⁵². Chronic absence is generally defined as missing 10% or more of the academic year. Such absences from school have risen around the world, with 20% to 30% of students missing 10% or more of the school year in many high-income nations^53-56. Australia has experienced a chronic absence rate of more than 50% in grades 1 to 10⁵⁷. 

People complain about being persistently ill and unable to shake infections throughout social media, and this is reflected in increased healthcare demand. Long COVID continues to be a huge and growing problem, as are the many sequelae of COVID-19 that aren’t caught by the official definitions of Long COVID^58,59 which are much shorter than the symptom list curated by the Patient Led Research Collaborative⁶⁰.

There was a period in 2020 and 2021 when vocal commentators on social media sought to downplay the harms of COVID-19, but there can now be no doubt. COVID-19 damages the heart, brain, kidneys, gut, lungs, liver – in fact there is no organ or system that is untouched by this virus. Not that there ever was real doubt this would be the case – all of these effects on internal organs other than the lungs as well as the long-term damage to the lungs itself were documented during the original SARS outbreak in 2002-2004 and in the course of subsequent research^61-91. It was known that some of the damage from SARS was irreversible⁹².

COVID-19 causes an increased risk of death, heart attacks, strokes, and blood clots for at least 6 months after the infection, and is contributing to substantial disability in society⁹³. While there is some recovery in people with Long COVID, some of the damage appears to be irreversible for some people⁹³. These ongoing harms are recognized by some of the world’s leading scientific and medical organizations^94-100 but, perhaps because the predominant messaging has downplayed risks for years now, their warnings have yet to infiltrate public consciousness or influence the thinking of policymakers.

We’ve previously written about the immune system dysfunction caused by COVID-19¹⁰¹, and more evidence has now come out in this regard. Children infected by COVID-19 appear to be at more risk of RSV infection¹⁰² and Strep A¹⁰³. While often chalked up to the convenient fiction of ‘immunity debt’ (that lack of exposure has weakened humans’ immune systems—a theory that is unproven and is, frankly, contradicted by common sense and basic immunology¹⁰¹ - this is actually a signal of immune harm caused by a pernicious virus that exacts a toll for every infection and will reinfect many people many times in their lives. 

The risk of heart attacks, strokes, blood clots and other cardiovascular illnesses caused by COVID-19 is exacerbating what was already the greatest global burden of disease - cardiovascular disease - and likely the cause of much of the observed excess mortality. It is also clear that vaccines provide a measure of protection against cardiovascular outcomes of COVID-19¹⁰⁴.

With cognitive performance declining in the young, measured both by surveys as well as standardized test scores^105-107, shortages across the world in a range of professions, increased acute and long-term absences from school and work due to ill-health, rises in long-term disability and associated social security claims, we need to ask where are our leaders?

Which government minister is going to take on the task of educating the public about the true harms of COVID-19? Which government will implement the measures needed to prevent the gradual attrition of key pillars of society?

The social, economic and public health costs of maintaining the fiction that we can live normally by ignoring COVID-19 are simply too high for this “business as usual” situation to continue and the rate of attrition is too high for this to be sustainable.

We need a concerted push for properly matched, updated boosters¹⁰⁸; clean air policies; respirators to be made the standard in healthcare settings long-term and in everyday society when COVID-19 levels are high; a massive public information campaign to encourage regular testing and isolation to minimize cases and harm; and investment in next-generation vaccines and therapies that will reduce the threat posed by COVID-19. We also need massive investment in Long Covid therapies to help those already harmed by SARS-CoV-2.

This absurd pretense cannot continue. Many people already know it in their hearts. But who will be the leader brave enough to say it?

The post Where are our leaders? appeared first on John Snow Project.

3M RESPIRATORS IN BLACK

3M manufactures some of the best respirators in the world. The Aura N95/FFP2/FFP3 medical mask and particulate respirator models are firm favorites with members of the John Snow Project, a volunteer group of frontline healthcare workers and scientists who are dedicated to providing accurate information about SARS-CoV-2 and COVID-19.

As you and your colleagues are undoubtedly aware, respirators have been demonstrated to be at least 100 times more effective than surgical masks at preventing viral transmission¹. When used in clinical settings, respirators have been shown to be wholly effective at protecting people from infection^2-4. It’s no wonder respirators are used in research and clinical settings that are serious about preventing infection by harmful airborne pathogens. 

We have one suggestion to improve 3M’s product offering:

Please manufacture your N95 respirators in black.

There is a sizeable community of consumers who are cautious about COVID-19, and that community is likely to grow over the coming years as people experience the harms of reinfection by the SARS-CoV-2 virus⁵. The CDC estimates that as many as 23 million people are already living with the long-term impacts of COVID-19⁶ and that number will increase as repeat infection exposes people to more potential harm^7-9. We are often told that COVID-19 is here to stay, and so is the community of people who would like to do as much as possible to avoid the short and long-term harms of infection.

While white respirators are the obvious color of choice for industrial, scientific or clinical settings, social media is abuzz with people clamoring for highly effective black respirators. A quick search of your products on Amazon shows their popularity with end consumers and gives some indication of potential demand.

White respirators stand out in social settings and darker skinned people, especially women, tell us that they are negatively targeted for wearing them because they stand out too much. The deployment of a black respirator that matches more outfits and which has an inherently higher status as a fashion item might increase respirator usage and make it a more desirable status symbol. People can look good while protecting their health and the health of those around them.

There are manufacturers who produce black N95 respirators, but none of them perform as well as 3M products on fit tests, and we know our community would welcome the addition of black 3M respirators to the market.

We hope you will consider expanding 3M’s product line in this direction and look forward to supporting such products when they are brought to market.

Yours sincerely,

The John Snow Project

The post An Open Letter to the CEO of 3M appeared first on John Snow Project.

Those schooled in public health, immunology or working on the front line of healthcare provision know we face an uncertain future, and are aware the implications of recent events stretch far beyond SARS-CoV-2. The shifts that have taken place in attitudes and public health policy will likely damage a key pillar that forms the basis of modern civilized society, one that was built over the last two centuries; the expectation of a largely uninterrupted upwards trajectory of ever-improving health and quality of life, largely driven by the reduction and elimination of infectious diseases that plagued humankind for thousands of years. In the last three years, that trajectory has reversed.

The upward trajectory of public health in the last two centuries

Control of infectious disease has historically been a priority for all societies. Quarantine has been in common use since at least the Bronze Age and has been the key method for preventing the spread of infectious diseases ever since. The word “quarantine” itself derives from the 40-day isolation period for ships and crews that was implemented in Europe during the late Middle Ages to prevent the introduction of bubonic plague epidemics into cities¹.

Modern public health traces its roots to the middle of the 19th century thanks to converging scientific developments in early industrial societies:

1. The germ theory of diseases was firmly established in the mid-19th century, in particular after Louis Pasteur disproved the spontaneous generation hypothesis. If diseases spread through transmission chains between individual humans or from the environment/animals to humans, then it follows that those transmission chains can be interrupted, and the spread stopped.
2. The science of epidemiology appeared, its birth usually associated with the 1854 Broad Street cholera outbreak in London during which the British physician John Snow identified contaminated water as the source of cholera, pointing to improved sanitation as the way to stop cholera epidemics.
3. Vaccination technology began to develop, initially against smallpox, and the first mandatory smallpox vaccination campaigns began, starting in England in the 1850s.
4. The early industrial era generated horrendous workplace and living conditions for working class populations living in large industrial cities, dramatically reducing life expectancy and quality of life (life expectancy at birth in key industrial cities in the middle of the 19th century was often in the low 30s or even lower²). This in turn resulted in a recognition that such environmental factors affect human health and life spans. The long and bitter struggle for workers’ rights in subsequent decades resulted in much improved working conditions, workplace safety regulations, and general sanitation, and brought sharp increases in life expectancy and quality of life, which in turn had positive impacts on productivity and wealth.
5. Florence Nightingale reemphasized the role of ventilation in healing and preventing illness, ‘The very first canon of nursing… : keep the air he breathes as pure as the external air, without chilling him,’ a maxim that influenced building design at the time.

These trends continued in the 20th century, greatly helped by further technological and scientific advances. Many diseases – diphtheria, pertussis, hepatitis B, polio, measles, mumps, rubella, etc. – became things of the past thanks to near-universal highly effective vaccinations, while others that used to be common are no longer of such concern for highly developed countries in temperate climates – malaria, typhus, typhoid, leprosy, cholera, tuberculosis, and many others – primarily thanks to improvements in hygiene and the implementation of non-pharmaceutical measures for their containment.

Furthermore, the idea that infectious diseases should not just be reduced, but permanently eliminated altogether began to be put into practice in the second half of the 20th century^3-5 on a global level, and much earlier locally. These programs were based on the obvious consideration that if an infectious agent is driven to extinction, the incalculable damage to people’s health and the overall economy by a persisting and indefinite disease burden will also be eliminated.

The ambition of local elimination grew into one of global eradication for smallpox, which was successfully eliminated from the human population in the 1970s⁶ (this had already been achieved locally in the late 19th century by some countries), after a heroic effort to find and contain the last remaining infectious individuals^7,8. The other complete success was rinderpest in cattle^9,10, globally eradicated in the early 21st century.

When the COVID-19 pandemic started, global eradication programs were very close to succeeding for two other diseases – polio^11,12 and dracunculiasis¹³. Eradication is also globally pursued for other diseases, such as yaws^14,15, and regionally for many others, e.g. lymphatic filariasis^16,17, onchocerciasis^18,19, measles and rubella^20-30. The most challenging diseases are those that have an external reservoir outside the human population, especially if they are insect borne, and in particular those carried by mosquitos. Malaria is the primary example, but despite these difficulties, eradication of malaria has been a long-standing global public health goal^31-33 and elimination has been achieved in temperate regions of the globe^34,35, even though it involved the ecologically destructive widespread application of polluting chemical pesticides^36,37 to reduce the populations of the vectors. Elimination is also a public goal for other insect borne diseases such as trypanosomiasis^38,39.

In parallel with pursuing maximal reduction and eventual eradication of the burden of existing endemic infectious diseases, humanity has also had to battle novel infectious diseases⁴⁰, which have been appearing at an increased rate over recent decades^41-43. Most of these diseases are of zoonotic origin, and the rate at which they are making the jump from wildlife to humans is accelerating, because of the increased encroachment on wildlife due to expanding human populations and physical infrastructure associated with human activity, the continued destruction of wild ecosystems that forces wild animals towards closer human contact, the booming wildlife trade, and other such trends.

Because it is much easier to stop an outbreak when it is still in its early stages of spreading through the population than to eradicate an endemic pathogen, the governing principle has been that no emerging infectious disease should be allowed to become endemic. This goal has been pursued reasonably successfully and without controversy for many decades.

The most famous newly emerging pathogens were the filoviruses (Ebola^44-46, Marburg^47,48), the SARS and MERS coronaviruses, and paramyxoviruses like Nipah^49,50. These gained fame because of their high lethality and potential for human-to-human spread, but they were merely the most notable of many examples.

Such epidemics were almost always aggressively suppressed. Usually, these were small outbreaks, and because highly pathogenic viruses such as Ebola cause very serious sickness in practically all infected people, finding and isolating the contagious individuals is a manageable task. The largest such epidemic was the 2013-16 Ebola outbreak in West Africa, when a filovirus spread widely in major urban centers for the first time. Containment required a wartime-level mobilization, but that was nevertheless achieved, even though there were nearly 30,000 infections and more than 11,000 deaths⁵¹.

SARS was also contained and eradicated from the human population back in 2003-04, and the same happened every time MERS made the jump from camels to humans, as well as when there were Nipah outbreaks in Asia.

The major counterexample of a successful establishment in the human population of a novel highly pathogenic virus is HIV. HIV is a retrovirus, and as such it integrates into the host genome and is thus nearly impossible to eliminate from the body and to eradicate from the population⁵² (unless all infected individuals are identified and prevented from infecting others for the rest of their lives). However, HIV is not an example of the containment principle being voluntarily abandoned as the virus had made its zoonotic jump and established itself many decades before its eventual discovery⁵³ and recognition^54-56, and long before the molecular tools that could have detected and potentially fully contained it existed.

Still, despite all these containment success stories, the emergence of a new pathogen with pandemic potential was a well understood and frequently discussed threat^57-60, although influenza viruses rather than coronaviruses were often seen as the most likely culprit^61-65. The eventual appearance of SARS-CoV-2 should therefore not have been a huge surprise, and should have been met with a full mobilization of the technical tools and fundamental public health principles developed over the previous decades. 

The ecological context

One striking property of many emerging pathogens is how many of them come from bats. While the question of whether bats truly harbor more viruses than other mammals in proportion to their own species diversity (which is the second highest within mammals after rodents) is not fully settled yet^66-69, many novel viruses do indeed originate from bats, and the ecological and physiological characteristics of bats are highly relevant for understanding the situation that Homo sapiens finds itself in right now.

Another startling property of bats and their viruses is how highly pathogenic to humans (and other mammals) many bat viruses are, while bats themselves are not much affected (only rabies is well established to cause serious harm to bats⁶⁸). Why bats seem to carry so many such pathogens, and how they have adapted so well to coexisting with them, has been a long-standing puzzle and although we do not have a definitive answer, some general trends have become clear.

1. Bats are the only truly flying mammals and have been so for many millions of years.
2. Flying has resulted in a number of specific adaptations, one of them being the tolerance towards a very high body temperature (often on the order of 42-43ºC).
3. Bats often live in huge colonies, literally touching each other, and, again, have lived in conditions of very high density for millions of years. Such densities are rare among mammals and are certainly not the native condition of humans (human civilization and our large dense cities are a very recent phenomenon on evolutionary time scales).
4. Bats are also quite long-lived for such small mammals^70-71 – some fruit bats can live more than 35 years and even small cave dwelling species can live about a decade.

These are characteristics that might have on one hand facilitated the evolution of a considerable set of viruses associated with bat populations. In order for a non-latent respiratory virus to maintain itself, a minimal population size is necessary. For example, it is hypothesized that measles requires a minimum population size of 250-300,000 individuals⁷². And bats have existed in a state of high population densities for a very long time, which might explain the high diversity of viruses that they carry. In addition, the long lifespan of many bat species means that their viruses may have to evolve strategies to overcome adaptive immunity and frequently reinfect previously infected individuals as opposed to the situation in short-lived species in which populations turn over quickly (with immunologically naive individuals replacing the ones that die out).

On the other hand, the selective pressure that these viruses have exerted on bats may have resulted in the evolution of various resistance and/or tolerance mechanisms in bats themselves, which in turn have driven the evolution of counter strategies in their viruses, leading them to be highly virulent for other species. Bats certainly appear to be physiologically more tolerant towards viruses that are otherwise highly virulent to other mammals. Several explanations for this adaptation have been proposed, chief among them a much more powerful innate immunity and a tolerance towards infections that does not lead to the development of the kind of hyperinflammatory reactions observed in humans^73-75, the high body temperature of bats in flight, and others.

The notable strength of bat innate immunity is often explained by the constitutively active interferon response that has been reported for some bat species^76-78. It is possible that this is not a universal characteristic of all bats⁷⁹ – only a few species have been studied – but it provides a very attractive mechanism for explaining both how bats prevent the development of severe systemic viral infections in their bodies and how their viruses in turn would have evolved powerful mechanisms to silence the interferon response, making them highly pathogenic for other mammals.

The tolerance towards infection is possibly rooted in the absence of some components of the signaling cascades leading to hyperinflammatory reactions and the dampened activity of others⁸⁰.

An obvious ecological parallel can be drawn between bats and humans – just as bats live in dense colonies, so now do modern humans. And we may now be at a critical point in the history of our species, in which our ever-increasing ecological footprint has brought us in close contact with bats in a way that was much rarer in the past. Our population is connected in ways that were previously unimaginable. A novel virus can make the zoonotic jump somewhere in Southeast Asia and a carrier of it can then be on the other side of the globe a mere 24-hours later, having encountered thousands of people in airports and other mass transit systems. As a result, bat pathogens are now being transferred from bat populations to the human population in what might prove to be the second major zoonotic spillover event after the one associated with domestication of livestock and pets a few thousand years ago.

Unfortunately for us, our physiology is not suited to tolerate these new viruses. Bats have adapted to live with them over many millions of years. Humans have not undergone the same kind of adaptation and cannot do so on any timescale that will be of use to those living now, nor to our immediate descendants.

Simply put, humans are not bats, and the continuous existence and improvement of what we now call “civilization” depends on the same basic public health and infectious disease control that saw life expectancy in high-income countries more than double to 85 years. This is a challenge that will only increase in the coming years, because the trends that are accelerating the rate of zoonotic transfer of pathogens are certain to persist.

Given this context, it is as important now to maintain the public health principle that no new dangerous pathogens should be allowed to become endemic and that all novel infectious disease outbreaks must be suppressed as it ever was. 

The death of public health and the end of epidemiological comfort

It is also in this context that the real gravity of what has happened in the last three years emerges.

After HIV, SARS-CoV-2 is now the second most dangerous infectious disease agent that is 'endemic' to the human population on a global scale. And yet not only was it allowed to become endemic, but mass infection was outright encouraged, including by official public health bodies in numerous countries^81-83.

The implications of what has just happened have been missed by most, so let’s spell them out explicitly.

We need to be clear why containment of SARS-CoV-2 was actively sabotaged and eventually abandoned. It has absolutely nothing to do with the “impossibility” of achieving it. In fact, the technical problem of containing even a stealthily spreading virus such as SARS-CoV-2 is fully solved, and that solution was successfully applied in practice for years during the pandemic.

The list of countries that completely snuffed out outbreaks, often multiple times, includes Australia, New Zealand, Singapore, Taiwan, Vietnam, Thailand, Bhutan, Cuba, China, and a few others, with China having successfully contained hundreds of separate outbreaks, before finally giving up in late 2022. 

The algorithm for containment is well established – passively break transmission chains through the implementation of nonpharmaceutical interventions (NPIs) such as limiting human contacts, high quality respirator masks, indoor air filtration and ventilation, and others, while aggressively hunting down active remaining transmission chains through traditional contact tracing and isolation methods combined with the powerful new tool of population-scale testing. 

Understanding of airborne transmission and institution of mitigation measures, which have heretofore not been utilized in any country, will facilitate elimination, even with the newer, more transmissible variants. Any country that has the necessary resources (or is provided with them) can achieve full containment within a few months. In fact, currently this would be easier than ever before because of the accumulated widespread multiple recent exposures to the virus in the population suppressing the effective reproduction number (Re). For the last 18 months or so we have been seeing a constant high plateau of cases with undulating waves, but not the major explosions of infections with Re reaching 3-4 that were associated with the original introduction of the virus in 2020 and with the appearance of the first Omicron variants in late 2021. 

It would be much easier to use NPIs to drive Re to much below 1 and keep it there until elimination when starting from Re around 1.2-1.3 than when it was over 3, and this moment should be used, before another radically new serotype appears and takes us back to those even more unpleasant situations. This is not a technical problem, but one of political and social will. As long as leadership misunderstands or pretends to misunderstand the link between increased mortality, morbidity and poorer economic performance and the free transmission of SARS-CoV-2, the impetus will be lacking to take the necessary steps to contain this damaging virus.

Political will is in short supply because powerful economic and corporate interests have been pushing policymakers to let the virus spread largely unchecked through the population since the very beginning of the pandemic. The reasons are simple. First, NPIs hurt general economic activity, even if only in the short term, resulting in losses on balance sheets. Second, large-scale containment efforts of the kind we only saw briefly in the first few months of the pandemic require substantial governmental support for all the people who need to pause their economic activity for the duration of effort. Such an effort also requires large-scale financial investment in, for example, contact tracing and mass testing infrastructure and providing high-quality masks. In an era dominated by laissez-faire economic dogma, this level of state investment and organization would have set too many unacceptable precedents, so in many jurisdictions it was fiercely resisted, regardless of the consequences for humanity and the economy.

None of these social and economic predicaments have been resolved. The unofficial alliance between big business and dangerous pathogens that was forged in early 2020 has emerged victorious and greatly strengthened from its battle against public health, and is poised to steamroll whatever meager opposition remains for the remainder of this, and future pandemics.

The long-established principles governing how we respond to new infectious diseases have now completely changed – the precedent has been established that dangerous emerging pathogens will no longer be contained, but instead permitted to ‘ease’ into widespread circulation. The intent to “let it rip” in the future is now being openly communicated⁸⁴. With this change in policy comes uncertainty about acceptable lethality. Just how bad will an infectious disease have to be to convince any government to mobilize a meaningful global public health response?

We have some clues regarding that issue from what happened during the initial appearance of the Omicron “variant” (which was really a new serotype^85,86) of SARS-CoV-2. Despite some experts warning that a vaccine-only approach would be doomed to fail, governments gambled everything on it. They were then faced with the brute fact of viral evolution destroying their strategy when a new serotype emerged against which existing vaccines had little effect in terms of blocking transmission. The reaction was not to bring back NPIs but to give up, seemingly regardless of the consequences. 

Critically, those consequences were unknown when the policy of no intervention was adopted within days of the appearance of Omicron. All previous new SARS-CoV-2 variants had been deadlier than the original Wuhan strain, with the eventually globally dominant Delta variant perhaps as much as 4× as deadly⁸⁷. Omicron turned out to be the exception, but again, that was not known with any certainty when it was allowed to run wild through populations. What would have happened if it had followed the same pattern as Delta? 

In the USA, for example, the worst COVID-19 wave was the one in the winter of 2020-21, at the peak of which at least 3,500 people were dying daily (the real number was certainly higher because of undercounting due to lack of testing and improper reporting). The first Omicron BA.1 wave saw the second-highest death tolls, with at least 2,800 dying per day at its peak. Had Omicron been as intrinsically lethal as Delta, we could have easily seen a 4-5× higher peak than January 2021, i.e. as many as 12–15,000 people dying a day. Given that we only had real data on Omicron’s intrinsic lethality after the gigantic wave of infections was unleashed onto the population, we have to conclude that 12–15,000 dead a day is now a threshold that will not force the implementation of serious NPIs for the next problematic COVID-19 serotype.

Logically, it follows that it is also a threshold that will not result in the implementation of NPIs for any other emerging pathogens either. Because why should SARS-CoV-2 be special?

We can only hope that we will never see the day when such an epidemic hits us but experience tells us such optimism is unfounded. The current level of suffering caused by COVID-19 has been completely normalized even though such a thing was unthinkable back in 2019. Populations are largely unaware of the long-term harms the virus is causing to those infected, of the burden on healthcare, increased disability, mortality and reduced life expectancy. Once a few even deadlier outbreaks have been shrugged off by governments worldwide, the baseline of what is considered “acceptable” will just gradually move up and even more unimaginable losses will eventually enter the “acceptable” category. There can be no doubt, from a public health perspective, we are regressing.

We had a second, even more worrying real-life example of what the future holds with the global spread of the MPX virus (formerly known as “monkeypox” and now called “Mpox”) in 2022. MPX is a close relative to the smallpox VARV virus and is endemic to Central and Western Africa, where its natural hosts are mostly various rodent species, but on occasions it infects humans too, with the rate of zoonotic transfer increasing over recent decades⁸⁸. It has usually been characterized by fairly high mortality – the CFR (Case Fatality Rate) has been ∼3.6% for the strain that circulates in Nigeria and ∼10% for the one in the Congo region, i.e. much worse than SARS-CoV-2. In 2022, an unexpected global MPX outbreak developed, with tens of thousands of confirmed cases in dozens of countries^89,90. Normally, this would be a huge cause for alarm, for several reasons. 

First, MPX itself is a very dangerous disease. Second, universal smallpox vaccination ended many decades ago with the success of the eradication program, leaving the population born after that completely unprotected. Third, lethality in orthopoxviruses is, in fact, highly variable – VARV itself had a variola major strain, with as much as ∼30% CFR, and a less deadly variola minor variety with CFR ∼1%, and there was considerable variation within variola major too. It also appears that high pathogenicity often evolves from less pathogenic strains through reductive evolution - the loss of certain genes something that can happen fairly easily, may well have happened repeatedly in the past, and may happen again in the future, a scenario that has been repeatedly warned about for decades^91,92. For these reasons, it was unthinkable that anyone would just shrug off a massive MPX outbreak – it is already bad enough as it is, but allowing it to become endemic means it can one day evolve towards something functionally equivalent to smallpox in its impact.

And yet that is exactly what happened in 2022 – barely any measures were taken to contain the outbreak, and countries simply reclassified MPX out of the “high consequence infectious disease” category⁹³ in order to push the problem away, out of sight and out of mind. By chance, it turned out that this particular outbreak did not spark a global pandemic, and it was also characterized, for poorly understood reasons, by an unusually low CFR, with very few people dying^94,95. But again, that is not the information that was available at the start of the outbreak, when in a previous, interventionist age of public health, resources would have been mobilized to stamp it out in its infancy, but, in the age of laissez-faire, were not. MPX is now circulating around the world and represents a future threat of uncontrolled transmission resulting in viral adaptation to highly efficient human-to-human spread combined with much greater disease severity.

This is the previously unthinkable future we will live in from now on in terms of our approach to infectious disease.

What may be controlled instead is information. Another lesson of the pandemic is that if there is no testing and reporting of cases and deaths, a huge amount of real human suffering can be very successfully swept under the rug. Early in 2020, such practices – blatant denial that there was any virus in certain territories, outright faking of COVID-19 statistics, and even resorting to NPIs out of sheer desperation but under false pretense that it is not because of COVID-19 – were the domain of failed states and less developed dictatorships^96-99. But in 2023 most of the world has adopted such practices – testing is limited, reporting is infrequent, or even abandoned altogether – and there is no reason to expect this to change. Information control has replaced infection control.

After a while it will not even be possible to assess the impact of what is happening by evaluating excess mortality, which has been the one true measure not susceptible to various data manipulation tricks. As we get increasingly removed from the pre-COVID-19 baselines and the initial pandemic years are subsumed into the baseline for calculating excess mortality, excess deaths will simply disappear by the power of statistical magic. Interestingly, countries such as the UK, which has already incorporated two pandemic years in its five-year average, are still seeing excess deaths, which suggests the virus is an ongoing and growing problem.

It should also be stressed that this radical shift in our approach to emerging infectious diseases is probably only the beginning of wiping out the hard-fought public health gains of the last 150+ years. This should be gravely concerning to any individuals and institutions concerned with workers and citizens rights. 

This shift is likely to impact existing eradication and elimination efforts. Will the final pushes be made to complete the various global eradication campaigns listed above? That may necessitate some serious effort involving NPIs and active public health measures, but how much appetite is there for such things after they have been now taken out of the toolkit for SARS-CoV-2? 

We can also expect previously forgotten diseases to return where they have successfully been locally eradicated. We have to always remember that the diseases that we now control with universal childhood vaccinations have not been globally eradicated – they have disappeared from our lives because vaccination rates are high enough to maintain society as a whole above the disease elimination threshold, but were vaccination rates to slip, those diseases, such as measles, will return with a vengeance. 

The anti-vaccine movement was already a serious problem prior to COVID-19, but it was given a gigantic boost with the ill-advised vaccine-only COVID-19 strategy. Governments and their nominal expert advisers oversold the effectiveness of imperfect first generation COVID-vaccines, and simultaneously minimized the harms of SARS-CoV-2, creating a reality gap which gave anti-vaccine rhetoric space to thrive. This is a huge topic to be explored separately. Here it will suffice to say that while anti-vaxxers were a fringe movement prior to the pandemic, “vaccination” in general is now a toxic idea in the minds of truly significant portions of the population. A logical consequence of that shift has been a significant decrease in vaccination coverage for other diseases as well as for COVID-19.

This is even more likely given the shift in attitudes towards children. Child labour, lack of education and large families were the hallmarks of earlier eras of poor public health, which were characterized by high birth-rates and high infant mortality. Attitudes changed dramatically over the course of the 20th century and wherever health and wealth increased, child mortality fell, and the transition was made to small families. Rarity increased perceived value and children’s wellbeing became a central concern for parents and carers. The arrival of COVID-19 changed that, with some governments, advisers, advocacy groups and parents insisting that children should be exposed freely to a Severe Acute Respiratory Syndrome virus to ‘train’ their immune systems.

Infection, rather than vaccination, was the preferred route for many in public health in 2020, and still is in 2023, despite all that is known about this virus’s propensity to cause damage to all internal organs, the immune system, and the brain, and the unknowns of postinfectious sequelae. This is especially egregious in infants, whose naive immune status may be one of the reasons they have a relatively high hospitalization rate. Some commentators seek to justify the lack of protection for the elderly and vulnerable on a cost basis. We wonder what rationale can justify a lack of protection for newborns and infants, particularly in a healthcare setting, when experience of other viruses tells us children have better outcomes the later they are exposed to disease¹⁰⁰? If we are not prepared to protect children against a highly virulent SARS virus, why should we protect against others? We should expect a shift in public health attitudes, since ‘endemicity’ means there is no reason to see SARS-CoV-2 as something unique and exceptional.

We can also expect a general degradation of workplace safety protocols and standards, again reversing many decades of hard-fought gains. During COVID-19, aside from a few privileged groups who worked from home, people were herded back into their workplaces without minimal safety precautions such as providing respirators, and improving ventilation and indoor air quality, when a dangerous airborne pathogen was spreading. 

Can we realistically expect existing safety precautions and regulations to survive after that precedent has been set? Can we expect public health bodies and regulatory agencies, whose job it is to enforce these standards, to fight for workplace safety given what they did during the pandemic? It is highly doubtful. After all, they stubbornly refused to admit that SARS-CoV-2 is airborne (even to this very day in fact – the World Health Organization’s infamous “FACT: #COVID19 is NOT airborne” Tweet from March 28 2020 is still up in its original form¹⁰¹), and it is not hard to see why – implementing airborne precautions in workplaces, schools, and other public spaces would have resulted in a cost to employers and governments; a cost they could avoid if they simply denied they needed to take such precautions. But short-term thinking has resulted in long-term costs to those same organizations, through the staffing crisis, and the still-rising disability tsunami. The same principle applies to all other existing safety measures.

Worse, we have now entered the phase of abandoning respiratory precautions even in hospitals. The natural consequence of unmasked staff and patients, even those known to be SARS-CoV-2 positive, freely mixing in overcrowded hospitals is the rampant spread of hospital-acquired infections, often among some of the most vulnerable demographics. This was previously thought to be a bad thing. And what of the future? If nobody is taking any measures to stop one particular highly dangerous nosocomial infection, why would anyone care about all the others, which are often no easier to prevent? And if standards of care have slipped to such a low point with respect to COVID-19, why would anyone bother providing the best care possible for other conditions? This is a one-way feed-forward healthcare system degradation that will only continue.

Finally, the very intellectual foundations of the achievements of the last century and a half are eroding. Chief among these is the germ theory of infectious disease, by which transmission chains can be isolated and broken. The alternative theory, of spontaneous generation of pathogens, means there are no chains to be broken. Today, we are told that it is impossible to contain SARS-CoV-2 and we have to "just live with it,” as if germ theory no longer holds. The argument that the spread of SARS-CoV-2 to wildlife¹⁰² means that containment is impossible illustrates these contradictions further – SARS-CoV-2 came from wildlife, as did all other zoonotic infections, so how does the virus spilling back to wildlife change anything in terms of public health protocol? But if one has decided that from here on there will be no effort to break transmission chains because it is too costly for the privileged few in society, then excuses for that laissez-faire attitude will always be found.

And that does not bode well for the near- and medium-term future of the human species on planet Earth.

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This study adds to numerous others that have found evidence of persistent infection months after acute illness^2-8. A recent review of viral persistence in the context of Long COVID outlined the evidence that points towards ongoing infection or viral, protein or RNA replication⁹, but evidence of persistence is not limited to people who are exhibiting symptoms of Long COVID. One study found persistent infection in the tonsils of 25% of asymptomatic children², while other studies have found evidence of persistent infection of children in other organs⁸. SARS‑CoV‑2 proteins, including spike, have been found in Long COVID and convalescent blood up to 12 months after initial infection¹⁰. One study found spike protein in the plasma of 64% of Long COVID patients and 29% of convalescent controls. This protein is likely derived from persistent SARS‑CoV‑2 in tissue reservoir sites and "leaks" into the blood where it can be measured¹¹. 

The UCSF imaging study also adds to those studies that have found persistent T cell activation. One study¹², published as a pre-print, found an association between activation of a specific T cell subtype and the propensity to test positive after apparent recovery. In another study, the same T cell subtype was found to be elevated 12 months after acute infection in subjects whether they had suffered mild or severe illness, with no reduction in activation between the 6-month and 12-month post-infection marks¹³. Expanded T cell populations in the pharyngeal lymphoid tissue of children weeks or months after infection was observed in another study¹⁴, and activation markers CD38, HLADR, and Ki67 were similarly expressed months after acute infection in people with and without Long COVID according to another study¹⁵ out of UCSF. Immune CD8+ T cell activation was observed in plasma of convalescent patients irrespective of developing Long COVID, with participant CD4/CD8 ratios remaining low 6 months after COVID-19 diagnosis. Higher levels of plasma IgA against SARS‑CoV‑2 S and N proteins and redistribution of CD8+ T cells expressing the mucosal homing β7 Integrin were identified in Long COVID and some convalescent participants, suggesting the persistence of SARS‑CoV‑2 in mucosal tissues¹⁶.

If UCSF imaging data are verified then they suggest that everyone who has had COVID-19 might have been subjected to these effects and that ongoing immune activation might be a common feature of all COVID-19 infections regardless of perceived Long COVID status. A possible explanation of persistent activation would be persistent infection, now evidenced in a number of SARS‑CoV‑2 studies, and seen in other viral infections such as human cytomegalovirus^17-19 and Epstein-Barr virus^20,21. In immunological terms, with regard to the activation of T lymphocytes, the UCSF study suggests people who have recovered from COVID-19 might be on the same spectrum as people with symptomatic Long COVID, and just as it is possible to have asymptomatic acute COVID-19, it is possible to have asymptomatic or paucisymptomatic Long COVID where the biological effects are experienced less keenly and are controlled sufficiently by the immune system so as not to manifest symptoms or to manifest them mildly.

Persistent infection is seen in a variety of conditions that drive persistent T cell activation^22-30, and this persistent activation is associated with a variety of clinical and immunological outcomes^31-41, making it difficult to say with any certainty what will happen due to ongoing immune activation even if experienced asymptomatically. It could have a minimal impact on human health and affect only a small proportion of the population long-term. It could cause more serious harms, such as increases in neurodegenerative disease, autoimmunity, more rapid immunosenescence, or it could cause specific time-limited or longer-term immune deficiency for a small or large proportion of the population. 

There is the possibility some people with symptomatic Long COVID experience a loss of unactivated naïve B and T cells at 8 months post infection⁴², and whether this finding is related to increased cell turnover due to heightened immune activation needs further study. A follow up study to the one that showed the loss of unactivated naïve B and T cells at 8 months⁴² found immune reconstitution in the same cohort at 24 months⁴³, suggesting some degree of recovery, but, interestingly, although many of the differences between the two groups resolved, the matched controls and Long COVID cohort in the study showed the same absolute elevated markers of exhaustion at 24 months compared with 12 months, suggesting everyone infected with SARS‑CoV‑2 in this study experienced increased T cell activation as a result of infection.

An analogy for what we’re seeing may be found in Hepatitis B (HBV) where people with chronic HBV go through four phases of infection; an immune tolerant phase when host immunity is weak and viral load is high, an immune active phase when host immunity is strong and viral load decreases, an immune control phase during which host immunity can control the viral load, and a reactivation phase during which weakened host immunity can cause a loss of control of the viral load⁴⁴. In the case of HBV, T cell activation and exhaustion constrains effective viral clearance^45,46. Treatment of HBV can restore T cell phenotypes and might be used as a predictive measure for the effectiveness of the treatment⁴⁷. Lessons from Hepatitis B and HIV suggest we need effective biomarkers for the COVID-19 host immune response and the location and amount of any persistent SARS‑CoV‑2 virus or RNA. It may be that levels of T cell activation with CD38 and HLA-DR expression combined with other specific immune responses can be used to develop an effective host biomarker^13,48, and further research is needed to develop methods to identify the amount and location of persistent virus suggested by persistent peripheral T cell activation¹ and evidenced numerous studies of adults and children^{2-11, 12-16}.

A broad range of immunological outcomes would seem to be on the table based on the existing study of the immunology of Long COVID⁴⁹, from minimal to serious impact to human health. Although T cell activation has been evidenced in acute and Long COVID, it might not be the root cause of the immunological issues we have been seeing in the affected population, and, as a virus that depletes dendritic cells⁵⁰, infects macrophages⁵¹, platelets⁵², T lymphocytes^2,53,54, monocytes⁵⁵, megakaryocytes^52,56,57 bone marrow^7,57, and makes long-term alterations to the innate immune system^58,59, SARS‑CoV‑2 may have complex, multi-faceted impacts on the immune system that will only be fully elucidated over time.

The issue we face is we may not know the full extent of harm until it is too late to remedy it, and in the context of a virus that has infected most of the global population, including children, and continues to circulate and reinfect, this would seem to be an unacceptable risk. Governments, particularly those in high income countries, need to take the lead and engage in an urgent effort to develop treatments that target any persistent viral reservoirs in the body, concurrent with research efforts into developing a better understanding of Long COVID and the roles of viral persistence and immune dysfunction in the condition. We cannot risk waiting for a complete understanding before beginning urgent efforts to clear any viral reservoirs that may exist.

In light of the accumulating evidence, we propose a new paradigm for COVID-19:

This paradigm makes COVID-19 in both its acute and chronic phase a global concern and a problem that needs to be solved urgently. It means the ‘othering’ of Long COVID is not an acceptable government or public health response, and recognizes that anyone and everyone might suffer from the condition on first exposure. And the probability to move to symptomatic Long COVID may be enhanced with multiple infections where viral persistence might be exacerbated. The work cited here suggests many more people, and perhaps everyone, who has been infected with SARS‑CoV‑2 may already be experiencing the same heightened T cell activation as those suffering Long COVID with the only difference being symptom expression.

The US Department of Health and Human Services and the World Health Organization have recently warned^60,61 that we risk adding to the number of people suffering Long COVID with each reinfection, but under the new paradigm it might be that we are adding a sufficient amount of virus, or infection in new parts of the body to tip more people into symptomatic Long COVID with all that might entail⁴⁹. The burden of the condition is already significant⁶² and is being felt around the world⁶³.

We have recently surveyed countries and territories that have published specific guidelines on the prevention of Long COVID⁶⁴. In the context of a new paradigm, prevention of reinfection becomes more urgent, and measures to curtail transmission need to go hand in hand with an unprecedented push to research treatments to neutralize the virus in any persistent reservoirs, alongside a better understanding of the long-term immunology of COVID-19. As part of this better understanding, we urge governments to provide more funding for research into the long-term immunological impacts of COVID-19 in children.

We believe governments need to set the prevention of transmission of SARS‑CoV‑2 as an objective. They should invest in this objective and normalize non-pharmaceutical interventions against SARS‑CoV‑2 transmission and explain to the general public why they are doing so, and organizations and individuals should do more to protect themselves from COVID-19 and prevent transmission of SARS‑CoV‑2. We support the Vaccines-plus and Delphi Consensus recommendations^65,66 as viable models for achieving reduction in transmission with minimal social and economic disruption until work on a sterilizing vaccine and effective treatments of any persistent reservoirs is concluded.

The public health, social, and economic costs of Long COVID are already too high, so there is no downside to the recommended action. Much of the potential harm of Long COVID is still unknown as it may manifest years or decades later. If there is no further long-term harm to be discovered, preventing the harms we already know about is sufficient cause for action, but if we later discover long-term harms that are on the more serious end of the spectrum of possible outcomes, we will be very glad we acted sooner rather than later.

Click here for information on how to reduce your risk.

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Instead, governments have abdicated their duty to protect and promote public health, demanding that we each assume personal responsibility to assess risk and take individual precautions^2,3. While some government agencies technically still advise people to reduce their number of infections by getting vaccinated, testing, and wearing masks⁴, this message does not feature prominently in the public discourse and as a result the majority of the general public in most countries has returned to pre-2020 behaviours, treating SARS-CoV-2 no more seriously than a common cold. But SARS-CoV-2 is not a common cold. Acute COVID-19 is still one of the leading causes of death in many countries^5,6 and the long-term impacts of SARS-CoV-2 are likely to play some role in the excess deaths still being seen around the world⁶.

Anecdotally, many say that if the virus posed a real threat, then governments would act to protect us. Some politicians and prominent public health and scientific figures initially told the public that vaccination turns COVID-19 into a mild seasonal illness^7,8, and celebrated a return to normal^9,10. Some public figures still cling to this view despite growing evidence that infection and repeat infection can cause serious harm^11,12. The weight of this evidence has resulted in some government and public health agencies changing their guidance to warn that there are serious risks attached to infection and that reinfection can increase those risks^4,13. It seems there may be a gradual shift among public health agencies towards an acceptance that SARS-CoV-2 is not as benign as some of the messaging has suggested.

Whether communicating risk or downplaying it, governments around the world have said that each individual must perform their own risk assessment and implement their own precautions. This requires individuals to assume personal responsibility for risks for which they lack reliable data and over which they have little or no control. This has happened before with tobacco - ‘the individual decides’ was the prevailing approach until approximately the late 1980s and 1990s, when governments around the world legislated to establish common social standards around smoking¹⁴.

The difference with SARS-CoV-2 is that it is a highly communicable disease. People cannot properly assess the risk of, for example, attending a wedding, for two reasons:

1. Lack of data. The immediate information required to assess risk is absent. Most governments have stopped tracking the spread of the virus, and few countries have accurate indications of prevalence in the community¹⁵. Testing is not a habit in most countries, so there is no way to know how many people might be infected at a gathering. Variant surveillance has been curtailed around the world¹⁶, and the results of what little is still being done are not widely communicated, so it is much more difficult to assess whether prior vaccine or infection immunity will protect against infection by circulating variants. People aren’t really being asked to assess risk for themselves; they are being asked to just hope for the best each and every time they expose themselves to potential infection.
2. Lack of understanding. We don’t understand the long-term effects of SARS-CoV-2 infection¹⁷. We don’t know what repeat infection by this novel coronavirus will do to human health, but the World Health Organization, the US Department of Health and Human Services, and other public health agencies are already advising that repeat infections are harmful and to be avoided^4,13. Long Covid clinics are full of people who didn’t understand the impact SARS-CoV-2 would have on their health – they were denied critical information to enable them to properly assess risk¹⁸.

Nor do most people have the freedom and means to minimize the risk of exposure in a society that has completely given up on preventing infection. There are no COVID-19 safety precautions in most workplaces, schools and other public settings, and mask wearing is increasingly awkward¹⁹, frowned upon and even actively discouraged (as it is the "scarlet letter" of the pandemic that reminds us it is not really over²⁰).

When SARS-CoV-2 first emerged and began to claim lives, there was a lot of wartime talk from world leaders^21-23, but in reality we never engaged in the sort of concerted effort needed to meet such a persistent and challenging threat. Governments took some measures to limit infections, but that was only to "flatten the curve" (i.e. prevent total healthcare system collapse), not to properly solve the problem by fully stopping the spread; instead they relied on vaccines to enable the world to return to pre-pandemic economic and social behaviours²⁴.

The approach hasn’t worked, at least anywhere near well enough. The ongoing toll on human health is being felt around the world in higher mortality^25,26, overstretched healthcare systems^27-29, and mass disability^30,31. Even the goal of "saving the economy", in the name of which so many lives were sacrificed, hasn’t been achieved – the economic costs of the long-term impacts of infection seem unsustainable, with the Long Covid burden accumulated so far estimated to cost the US economy $3.7 trillion, through the resulting staffing crisis, and disability and health care costs³². The virus mutates quickly and so far, it has shown no signs of slowing down, which means it is constantly evolving to escape immunity^33-35.

Admitting we have a problem is the first step to finding solutions, but governments either don’t understand the scale of the problem we might be facing, or, if they do, they are deliberately minimizing the threat. Government scientists, subject matter experts and advisory bodies have variously told us, the virus isn’t airborne^36,37, children don’t catch the virus^38,39, they don’t transmit the virus^40-42, masks don’t work⁴³, immunity is long-lasting and reinfection will be rare^44-46, we can reach herd immunity^47-50, SARS-CoV-2 doesn’t infect or harm the immune system^51,52, vaccines prevent infection^53,54, the virus will be slow to evolve^55,56, efforts to prevent infection are worse than the infection itself^57,58. All these statements were false, and many of those who opposed such ill-informed views at the time were dismissed as alarmists.

The Delphi consensus¹ addresses the information gap which hinders individuals' ability to assess the risk posed in a given situation by recommending testing, genomic surveillance, and other practical public health measures that collect and disseminate relevant data in a timely manner. 

Solving the second information gap about long-term risks is more challenging, and it is here that we believe governments need to re-engage the wartime mentality so many of them spoke of in 2020. We need a Project Warpspeed 2 that focuses on answering some important questions about SARS-CoV-2, in the context of widespread repeat infection through people’s lives. We’ve set out ten priorities below. This research needs to be coordinated at government level and directed with purpose. We cannot rely on the market incentives of private industry or research priorities of academia to answer such urgent and important questions.

1. What is Long Covid and what is the extent of its impact?
   Long Covid is a patient-created term to cover a wide range of post-acute and ongoing symptoms⁵⁹. The ubiquity of the ACE2 receptor⁶⁰ and the role played by platelets (see below) during infection might go some way to explaining the wide variety of symptoms and affected organs and symptoms. The US Department of Health and Human Services has advised people that repeat infections increase the risk of developing Long Covid⁴. As a recent Nature review of current knowledge around the immunology of Long Covid suggests, our understanding of the condition is incomplete⁶¹. In the context of risk or increased risk with reinfection, it is critically important policy makers understand the condition. They also need to better understand the social and economic costs of increasing numbers of people suffering with Long Covid. The analysis by David Cutler of Harvard Kennedy School, which suggests the cost of Long Covid is $3.7 trillion³², is likely to be an underestimate in the context of reinfection. We also need to better understand the implications of Long Covid in the younger generation. The US National Institutes of Health has recently advised that children experience the same Long Covid outcomes as adults and can suffer serious complications⁶².
2. What is SARS-CoV-2 doing to immune systems young and old?
   SARS-CoV-2 infects B and T cell lymphocytes^63-66 and infects, harms and alters other immune cells^67-71. What has infection done to population health? Are we seeing ongoing surges of RSV^72,73, dengue^74-76, adenovirus^77,78, and other pathogens around the world because of harm or impairment to our immune systems? What are the long-term implications of repeat infection of B and T cell lymphocytes? What harms are being caused to the wider immune system? Looking specifically at children, while some commentators assert there have been no changes to young immune systems⁷⁹, the surges in RSV and other pathogens seem to be affecting children and young adults in unexpected ways^80-82. For example, prior research suggests monocytes may play a role in severity of adenovirus infection⁸³ in children and SARS-CoV-2 has been shown to cause depletion and dysfunction of monocytes^71,84. SARS-CoV-2 has also been found to be persistent in a significant proportion of children and has been shown to infect their lymphocytes⁶⁶. There has been a rise in type 1 diabetes in children^85,86 which is an immune mediated disease, suggesting there is immune dysfunction in at least some children as a result of SARS-CoV-2 infection. Diabetes has a significant impact on morbidity⁸⁷, mortality⁸⁸ and healthcare costs⁸⁹ and this connection needs to be better understood in the context of repeat infections. B cells have a feedback system in the thymus⁹⁰. How is SARS-CoV-2 impacting this and what will happen as the thymus involutes? Infectious disease induced immune dysfunction can often lead to autoimmune conditions such as type 1 diabetes, systemic lupus erythematosus, and many others⁹¹. Will children who have been repeatedly infected by SARS-CoV-2 be at greater risk of developing such conditions?
3. What are the neurological consequences of SARS-CoV-2 infection?
   There is growing evidence SARS-CoV-2 impacts the brain, affecting cognitive performance and increasing the risk of neurological conditions^92-95. COVID-19 has been found to cause a rapid progression of dementia⁹⁶. It has also been found to cause Alzheimer's-like signaling⁹⁷. Will these findings translate to a rise in dementia in the population? Do repeat infections represent a cumulative risk?
4. What are the consequences of SARS-CoV-2 on reproductive health?
   With accumulating evidence of changes in reproductive health^98-103, what risk is posed by reinfection by SARS-CoV-2?
5. What is the impact of SARS-CoV-2 on human development?
   There is growing evidence of the impact of in-utero SARS-CoV-2 infection on health and development^104-110. What ongoing risk does this pose in the context of reinfection?
6. What are the long-term implications of infection of the bone marrow?
   SARS-CoV-2 has been shown to infect bone marrow megakaryocytes^111,112 and disrupt normal platelet formation^111,113,114. There were suggestions prior to 2020 that coronaviruses could persist in the body in low-replication states in privileged sites¹¹⁵. Are some presentations of Long Covid a consequence of persistent infection of the bone marrow? If so, what are the implications? If not, and infection of the bone marrow clears, what are the implications of repeat acute infection of the bone marrow through the human lifetime?
7. What is the impact of repeat infections of SARS-CoV-2 on cardiac health?
   SARS-CoV-2 infection causes an increased risk of thrombotic events during the acute phase of infection and for a significant period afterwards^116,117. People with Long Covid often have abnormal clotting and microclotting¹¹⁸. Increases in thrombotic conditions such as disseminated intravascular coagulation are seen as complication of sepsis and infectious diseases such as HIV^119-121 and Dengue^122-124. True DIC (by ISTH criteria) is rare in COVID. Instead, we see a distinct pattern of sepsis-associated coagulopathy and thrombosis without it fulfilling ISTH DIC diagnostic criteria¹²⁵. Infection of bone marrow megakaryocytes is a common feature of thrombotic conditions associated with other viral infections^126-129. The link between megakaryocyte infection and COVID-19 induced cardiac injury needs to be fully understood. According to the British Heart Foundation, the UK has seen an excess of almost 100,000 cardiovascular deaths since the start of the COVID-19 pandemic¹³⁰. US research has found excess cardiovascular deaths are temporally linked with COVID-19 waves¹³¹. SARS-CoV-2 damages the cardiovascular system^132-136. It is crucial we understand the long-term impact of SARS-CoV-2 reinfection on cardiac health, elucidate the mechanisms, quantify the risks and communicate them to the public, and identify methods of  preventing and treating acute and post-acute cardiac conditions associated with SARS-CoV-2 infection.
8. What are the risks of epigenetic changes?
   There is evidence SARS-CoV-2 infection restructures the host cell^137-139. What are the risks of this process and how are they impacted by repeat infections over the course of a person’s lifetime?
9. What is the impact of repeat SARS-CoV-2 infections on cancer incidence?
   The first proposed molecular mechanisms by which SARS-CoV-2 might cause or exacerbate cancer were identified in 2020^140-142 and further research has supported those initial findings^143-147. There is accumulating evidence of increased detection and incidence of cancer after SARS-CoV-2 infection^148,149 and some evidence of a worse prognosis for cancer patients who are infected by SARS-CoV-2^150-152. Given the social, healthcare and economic costs of cancer, and increased morbidity and mortality, it is vitally important we understand the role, if any, SARS-CoV-2 might be playing in tumorigenesis and cancer progression.
10. What is the long-term impact of SARS-CoV-2 on pulmonary health?
    Severe COVID-19 can cause acute respiratory distress syndrome, which can lead to pulmonary fibrosis, irreversibly compromising respiratory function¹⁵³. Shortness of breath or dyspnoea is common more than 4 weeks after the onset of acute COVID-19  symptoms¹⁵⁴.  In a recent study, a cohort of young people with ongoing Long Covid symptoms were found to have a 10% reduction in lung volume compared to controls¹⁵⁵. Pulmonary embolism is a common complication of COVID-19¹⁵⁶ and can lead to long-term sequelae¹⁵⁷. It is important policymakers understand the potential impact of reinfection on pulmonary health and the long-term implications on the healthcare system of any impact.

Admission is essential to solve the challenges of SARS-CoV-2

We call on governments to admit there is an ongoing problem with SARS-CoV-2. This is the first step to changing course and to implementing public health and clean air policies that will reduce transmission. We recommend the resumption of data collection and reporting that will enable people to genuinely assess their individual risk, and we ask governments to urgently answer questions that might have a profound impact on the long-term health of vast numbers of people. Some of the adverse outcomes of these unanswered questions might not present themselves for years, by which time they could impact far greater numbers of people. As scientists studying Long Covid have already said⁶¹,

“The oncoming burden of long COVID faced by patients, health-care providers, governments and economies is so large as to be unfathomable, which is possibly why minimal high-level planning is currently allocated to it. If 10% of acute infections lead to persistent symptoms, it could be predicted that ~400 million individuals globally are in need of support for long COVID.”

If we keep adding to the number of people who will suffer long-term complications down the line, that burden will only increase.

If you’d like to reduce your risk of SARS-CoV-2 infection, you can find practical advice here.

The post Admission: The First Step to a Sustainable Solution appeared first on John Snow Project.

The beginning

SARS-CoV-2 emerged in late 2019 in Wuhan and began silently spreading beyond China. But it took some time for caseloads to build up and for the tsunami of severe pneumonia to hit hospitals around the world. This happened in February 2020 in the first hard hit countries (e.g., Iran and Italy), and in March-April in most others.

In that critical period, when experience of the SARS-CoV-1 outbreak told us containment should have been the sensible response, the public was subjected to a barrage of minimizing and obfuscating messages, and containment wasn’t even attempted. 

In the first days of February 2020, we regularly saw quotes such as “the risk to Americans is relatively low and there is no justification for extraordinary, draconian action”², “If panic was commensurate with the virus’s prevalence or symptoms, one might expect to see more paranoia around the flu than the coronavirus.”³, “Ordinary seasonal flu leads to about half a million deaths every year globally. Yet we barely take notice of flu but feel imperilled by new diseases”⁴, as well as statements from nominal experts openly expressing the attitude that containment should not even be tried (“resources are better used [...] treating sick patients and developing vaccines and other countermeasures”⁵).

Eventually, however, governments panicked when faced with the imminent collapse of healthcare systems and the prospect of millions being triaged and left to die at home, and finally acted to implement non-pharmaceutical interventions such as general quarantines (that came to be known as “lockdowns”), border controls and mask mandates.

At this point we transitioned from the era of minimizing the threat to the second stage of the pandemic, when many governments switched towards the pretense of doing infection control. This is when the “Flatten the curve” catchphrase entered the political dialogue. What did it mean? The pernicious idea behind it was that “slowing the spread of the infection is nearly as important as stopping it.”¹

What does it mean to “flatten the curve”?

The ideal goal in fighting an epidemic or pandemic is to completely halt the spread. But merely slowing it – mitigation — is critical. This reduces the number of cases that are active at any given time, which in turn gives doctors, hospitals, police, schools and vaccine-manufacturers time to prepare and respond, without becoming overwhelmed. Most hospitals can function with 10 percent reduction in staff, but not with half their people out at once.

Some commentators have argued for getting the outbreak over with quickly. That is a recipe for panic, unnecessary suffering and death. Slowing and spreading out the tidal wave of cases will save lives. Flattening the curve keeps society going.

The New York Times¹

The disturbing reality behind this strategy should be obvious – there was never any intention to stop the spread of the virus, and stated policy from the outset was to hope for herd immunity or failing that, make it endemic - always circulating at a constant level. Herd immunity was always an unrealistic prospect given the established body of evidence about the propensity of coronaviruses to reinfect hosts, so endemicity was the only realistic objective. The number of people who got infected was unimportant as long as healthcare systems did not succumb to a state of complete collapse. 

While the ostensible goal was to reduce overall casualties, it was not to prevent a huge number of deaths and serious long-term disability, only to stretch it out in time to make it more acceptable to society.

“Flattening the curve” would only have made sense in traditional public health terms if the following conditions were met:

1. In-hospital mortality was close to zero, therefore nearly all deaths could be prevented if nobody was left untreated.
2. There were no long-term health consequences of surviving the infection, or, at the very least, there were no such consequences if given proper treatment.
3. There were no reinfections and, once society got past the initial wave of infection, the virus would indeed largely go away (as promised by many proponents of uncontrolled infection).
4. If it was certain that eventually highly efficient vaccines would be developed that would solve the problem for good, meaning that slowing down infections in the short term rather than stopping them altogether early on with quarantine measures and non-pharmaceutical interventions (NPIs) was sufficient in terms of buying time to develop a real, much less disruptive solution.
5. It was certain that eventually highly effective treatments would be developed that would make the disease a non-issue. 

All of these assumptions were either already false the moment they were made, or they were completely unwarranted.

1. Especially early on, in-hospital mortality was in fact very high, and most of the many thousands dying every day in Europe and the United States died in a hospital bed. There was not much that could be done once severe pneumonia developed.
2. Before SARS-CoV-2, we had dealt with SARS-CoV-1^6-10 (which, fortunately, was contained). Our experience of SARS-CoV-1 told us survivors of SARS infection often have to deal with very serious long-term or permanent health issues^11-17. The moment the first SARS-CoV-2 sequence was made available, it was obvious that what later became known as Long Covid was going to be a massive problem.
3. Similarly, it had been known for decades that immunity against coronaviruses is fleeting^18-20. Therefore, basing public health policy on assumptions about lasting immunity after SARS-CoV-2 infection was the height of irresponsibility, and in fact outright malpractice. Indeed, subsequent events rapidly proved that assumption wrong, and we now know humans are expected to experience many SARS-CoV-2 infections in their lifetimes.
4. While previously endemic coronaviruses in humans had not been a major public health issue, they are in domestic animals, and a lot of experience had accumulated designing vaccines in that context²¹. That body of knowledge told us in no uncertain terms that we should not expect to be able to vaccinate our way out of this problem – coronavirus vaccines in the past had worked at best moderately well, but even when they did work, they did not last very long due to the combination of very fast antigenic evolution and rapidly waning antibody titers. Indeed, real life followed the same pattern – viral evolution rapidly destroyed the effectiveness of COVID-19 vaccines while the efforts to catch up with it have always been at least half a year behind it.
5. There was also no guarantee that effective treatments would ever be developed. Indeed, now more than three years later, in-hospital mortality has been reduced through a combination of steroids, anticoagulants, monoclonal antibodies, anti-viral drugs, and other medications, but large numbers of people continue to die of COVID all around the world every day, i.e. the disease is very far from being a solved medical problem.

Thus “flattening the curve” meant postponing death and disability, and reducing it somewhat, but not really preventing it. Because immunity is not lasting, it also meant that the curve would never go to zero.

But it is the area under the curve that matters in terms of its overall impact on the population, not its peak. What happened in the end? Early in the pandemic, the IFR (Infection Fatality Rate) in populations with unfavorable demographics were in the 1-1.5% range, reaching as high as 1.63% in the extreme²², while it was lower in countries with younger demographics.

Three years later, we have multiple countries where excess mortality (deaths in excess of that expected from pre-pandemic death rates, with peaks entirely coinciding with COVID waves) has reached or even vastly exceeded what would have been predicted if everyone got infected^23,24. Notable examples include several countries in Eastern Europe – Bulgaria, North Macedonia, Serbia, Russia, and others – that are above or closely to excess mortality of 1% of the total population, as well as countries with younger demographics like Peru and South Africa, where ∼0.3% of the population was expected to die at infection saturation but 0.5-0.6% died in practice, because of reinfections and the appearance of deadlier versions of the virus.

Other countries, such as the USA, and most large Western European countries did reduce overall mortality, but only by a factor of 2-3× – they still lost millions of lives and 0.3-0.4% of their population.

A few countries kept infections low until vaccines became available, vaccinated nearly everyone, and only then let the virus loose, which by then was mostly characterized by lower mortality Omicron lineage. Those countries have kept excess mortality in the 0.1-0.2% range, but it has to be remembered that this is only the beginning – SARS-CoV-2 is now endemic, and it will endlessly keep infecting, reinfecting and killing people.

Thus what “flattening the curve” achieved was either to only postpone deaths or to reduce them by some factor but still to what would have previously been considered unacceptable levels, while playing the role of a Trojan horse that made COVID endemic, with all that entails long-term for human health. By meekly conceding to follow such a policy approach, instead of insisting on a real solution to the problem, which would have involved proper containment the way SARS-1 was contained back in 2003, society agreed on previously unimaginable levels of death and disability, in perpetuity.

Managing up to capacity, i.e. human lives do not matter

The “flatten the curve” slogan disappeared from public discourse, but it remained the principle governing pandemic response. The pandemic has been “managed” up to healthcare capacity, i.e., if there is still room for additional critically ill with COVID people in the ICUs, then there is no problem from the perspective of governments and public health institutions. This ignores how many people will die and become permanently disabled – that is not a concern.

This is now the explicitly stated guiding principle of pandemic management, as public health bodies in most countries (if they have not already transitioned into a mode of complete suppression of information by not reporting any data at all) have switched to “monitoring” of SARS-CoV-2 spread only based on COVID-19 hospitalization and severe cases.

Few seem to appreciate what a monumental shift in public health philosophy these events represent. The traditional goal of public health has been to promote public health by eliminating the disease burden that plagued humanity for much of its existence.

No longer. It has now been firmly established that human lives and health are not the priority as long as there is “capacity” in the healthcare system and we are not yet at the point where refrigeration trucks are needed because morgues and crematoria can no longer keep up. This shift in philosophy can be expected to have devastating consequences throughout healthcare and public health. Why should COVID-19 be special and why would anyone expect these practices to apply only to it?

We already see such impacts in many hospital systems around the world, where masking rules have been dropped and no precautions are taken to prevent COVID-19 positives from mixing with other patients, which will certainly cost innumerable lives of clinically vulnerable people suffering from non-COVID conditions. The rot will only spread from there, and standards of care will erode across the board. Why wouldn’t they if we have collectively decided that serious nosocomial infections are something we will just sweep under the rug from now on? And, of course, there will be more pandemics, and we have now established how we are not going to properly deal with them.

The hypocrisy of “we need to save the healthcare system”

Another extremely negative consequence is the loss of trust towards the medical profession and public health by the general public. While most casual observers don’t seem to understand the issues outlined above, the hypocrisy of the “let’s save the healthcare system from collapsing” has been widely felt on a visceral level. After all, what does that imply? Again, it implies that human lives do not matter, yet the healthcare system somehow does.

But what is the healthcare system for if not to save human lives, and why should anyone outside of it care about the “system” and not human life and health?

This obvious contradiction also played a role (among many others) in undermining public confidence in public health institutions and sabotaging even whatever meager containment efforts were launched. It will play the same role in future when we find ourselves in similar situations.

Meaningless oaths, declarations and conventions

We also cannot avoid discussing hypocrisy in a second context. Most medical professionals, including those who actively pushed for unmitigated spread of SARS-CoV-2, as well as those who promoted “flatten the curve” as a substitute for containment, have made some form of the Hippocratic oath, which features statements such as “I will apply, for the benefit of the sick, all measures [that] are required, avoiding those twin traps of overtreatment and therapeutic nihilism.” and “I will prevent disease whenever I can, for prevention is preferable to cure.”

What happened to that? How did we suddenly switch to the view that treatment is good enough even when it falls short of actually curing patients? How is that oath compatible with the idea there is nothing to be done to prevent transmission? 

We live in the third decade of the 21st century and have advanced technology that is capable of fully solving the problem, even for a silently spreading virus such as SARS-CoV-2, through respirator-style masks, clean air and mass testing, which can be effectively combined with the traditional practices of quarantine and isolation of the infected. We’re not even using technology to try to stem transmission in settings that are either known to play a disproportionate role in spreading the virus, such as schools²⁵, nor are we attempting to do so in settings where disproportionate harm can be caused, such as hospitals^27,26 and care homes²⁸.

The World Medical Association’s Declaration of Geneva²⁹ features statements such as “The health and well-being of my patient will be my first consideration”, “I will maintain the utmost respect for human life”, “I will not permit considerations of age, disease or disability, creed, ethnic origin, gender, nationality, political affiliation, race, sexual orientation, social standing or any other factor to intervene between my duty and my patient”.

How did we go from these principles to “short-term GDP growth is more important than human life and health”, “there is no need to stop the spread of COVID because only the old and weak die”, and the numerous other examples of callous disregard for human life and well-being that we have witnessed in the last three years?

A good dose of self-reflection is due in the ranks of the medical and public health professions to reverse these dangerous trends, or there is a chance they will worsen in the future.

Healthcare as a product/service

Finally, we cannot escape the need to discuss one obvious source of the disconnect between lofty moral principles and the ugly reality of real life today, and it is the transition over the last few decades of healthcare and medicine from being a higher calling, aimed at improving the well-being of all of humanity, to a purely transactional business, the primary concern of which is profit generation. In much of the world, including, and especially in the countries with most influence over global health policies, healthcare has been reduced to a series of financial transactions and everyone involved in that process works under the mandate to maximize profits. There is obviously zero room in such a system for naive notions such as maximizing the overall health of the population, eliminating endemic diseases, and other such altruistic objectives.

Healthcare is now seen as a product/service that is received in exchange for payment. And that is all that matters. As long as the product/service is available, there is no problem, and this is how we naturally forget about the “prevention is better than treatment” principle – if by its fundamental design all the system can ever provide is treatment, there is no room in it for prevention.

Besides, prevention generates no revenue. Which has an obvious corollary – once such philosophy has been established, as twisted and perverse as it may sound, it is in fact beneficial to make people as sick as possible, because that maximizes revenue (up to a certain point, of course – there is presumably an “optimal” model for how long people need to be kept alive to maximize revenue extraction).

Again, these have been long-term trends, but there has been very little push back against them from within the ranks of the medical profession and the scientific community, so they developed unhindered. And they laid the groundwork for the official abandonment of public health as we knew it for the last more than a century when the COVID-19 pandemic hit.

Unfortunately, we can only expect even worse in the future, unless drastic course correction occurs soon.

The post Flattening the Curve appeared first on John Snow Project.

The reality is the pandemic had already been declared "over”, as a political matter, in many countries around the globe, and the impression that it is now something in the past has successfully been instilled in the mind of the public. But is this really so, and are we even thinking about the situation properly?

A key part of being able to successfully declare the pandemic “over” is to also define it as the initial period of establishment of SARS-CoV-2 in the human population. Anything that happens beyond that point is thus not part of “the pandemic”, and can be disregarded, as part of “normal” life (the new “normal”, that is).

However, that is not at all the correct way to view the situation.

Variants and serotypes

In order to clear up the confusion, we need to first understand the distinction between “variants” and “serotypes”.

The word “variant” has been used a lot during the pandemic to describe the various lineages into which SARS-CoV-2 diversified during its uncontrolled transmission around the world. It usually refers to minor variation relative to the ancestral lineage.

“Serotypes” are the next level of divergence, at which substantial antigenic differences are observed between lineages, to the point where the immune system, after having encountered one of the two strains, recognizes another poorly or not at all. One can think of the difference between serotypes as that between a domestic cat and a lion, and that between variants as analogous to a persian cat and siamese cat.

But we have never seriously talked about “serotypes” during the pandemic. That is not because the term was not needed, quite the opposite. The appearance of Omicron in late 2021² very much represented a new serotype, but beyond some limited discussion in the literature³, calling it one never gained any traction and the much more benign and reassuring term “variant” continued to be used.

The conclusion that the original BA.1 Omicron strain represents a separate serotype follows directly from the very large number of mutations in Omicron relative to the original SARS-CoV-2 isolate, numbering more than 50 overall, including more than 30 mutations in the spike (S) protein and around 15 mutations in the receptor-binding domain. These mutations confer strong escape from neutralizing antibodies targeting previous SARS-CoV-2 versions⁴, allowing Omicron to readily reinfect previously infected individuals, as well as dramatic changes in cell entry mechanisms and tissue tropism⁵. Furthermore, even more divergent Omicron variants – first BA.4 and BA.5⁶, and then a veritable zoo of second-generation saltation variants and recombinants – have appeared since then. Divergence has reached the point where the currently circulating strains are as distinct from the original 2019 SARS-CoV-2 as the latter is from the 2003 SARS-CoV-1 virus⁷.

Despite that fact, and that there is no cross-protection between SARS-CoV-2 and SARS-CoV-1⁸, we continue to refer even to the more recent lineages, such as XBB.1.16, as “Omicron” and “variants”.

Refusal to acknowledge the nature of Omicron (in all its forms) severely hampers our ability to properly understand and conceptualize the events of the last three years, and handicaps our response to what likely awaits us in the future.

Multiple SARS pandemics

As the first novel serotype to diverge, a question that Omicron naturally presents is whether it will be the last. The accumulated knowledge about other coronaviruses suggests that there is no reason to think so. Within the sarbecoviruses, viruses are known with vastly greater sequence and antigenic divergence than that between Omicron and non-Omicron SARS-CoV-2 that nevertheless still efficiently utilize ACE2 as their receptor. In other words, the virus still has plenty of options to change markedly.

Commonly cited neutralization titre reductions of SARS-CoV-2 sera include ∼50× for SARS-CoV-1, ≥100× for WIV-1, and ∼300× for SHC014⁸, and as mentioned above, Omicron has already diversified to be as different antigenically from the original SARS-CoV-2 as SARS-CoV-1 is. Nobody expected ∼10% of the receptor binding domain to mutate in the span of just three short years, and yet that is what happened. Thus, the antigenic space for future evolution is vast, and it is likely to be explored under conditions of widespread viral transmission and selection regimes dominated by the pressure to evade existing antibodies.

We have one real-life example of what the future might look like with another coronavirus – that is the history of the Infectious Bronchitis Virus (IBV), a coronavirus that often causes severe disease in poultry and is not too dissimilar from COVID (a serious respiratory infection but also combined with broader tissue tropism in other organs). After first being documented in the 1930s, IBV has widely spread around the world, and in the process has diversified into dozens of new variants and serotypes⁹. Cross-protection between them is limited, and they can be radically different from each other in spike protein sequence (the S1 subunit of the S protein can differ by more than 20-25% between different serotypes, i.e. a lot more than the difference between even the most divergent Omicron sublineages and non-Omicron SARS-CoV-2), in mutations outside the spike, and in their tissue tropism (and thus the precise symptoms of the disease they cause).

Most importantly, they can also differ drastically in their pathogenicity – some lineages rarely cause mortality, while others are highly lethal, at the level of the most dangerous viruses that infect humans such as Ebola and Nipah^9-25.

It is therefore wise to conceptualize Omicron as the first of many new serotypes that can be expected to appear over the coming decades, the properties of which may well be dramatically variable.

A reconceptualization of the events of 2019-2023 and “the COVID-19 pandemic” is necessary. So far it has been often treated as analogous to an influenza pandemic. A wide variety of constantly changing influenza strains circulate continuously, with seasonal peaks, but occasionally more pathogenic strains appear and cause notable named pandemics. The most notorious of these is the 1918-1920 pandemic, caused by a particularly deadly H1N1 strain; since then, several additional (though much less deadly) pandemics followed, in 1957-58 (H2N2), 1968-69 (H3N2), 1977 (a different H1N1 iteration), and 2009 (H1N1/09).

The apparently immense evolutionary potential of coronaviruses means we should expect the evolution of many further SARSCoV-2 serotypes in the future, as well as the possibility of further jumps from non-human animals to our species (there have already been two of these in less than two decades). It is therefore most accurate to think of “SARS” as a category of pathogen and disease of a similar rank as “influenza virus” and “influenza”. The family Coronaviridae, to which SARS viruses belong, is analogous to the Orthomyxoviridae family, which contains influenzaviruses. The Sarbecovirus subgenus (as well as the IBV Igacovirus subgenus) is best thought of as analogous to the Influenza A and Influenza B Alphainfluenzavirus and Betainfluenzavirus genera. Under this framework there have so far been two indisputable SARS pandemics – the 2019-2021 SARS-2 one, driven by the original Wuhan strain and its antigenically close derivatives, and a second, Omicron pandemic, in 2021-2023. There was also the abortive SARS-1 pandemic in 2003, which was contained, and fortunately did not spread widely.

Implications

Additional SARS pandemics are therefore expected, like those associated with influenza. Influenza viruses are at present vastly more diverse than SARS-CoV-2, but over decades we are likely to see significant diversification of SARS lineages, if IBV’s history is to guide us. The frequency of these future pandemics is unpredictable, as is their severity. Establishing the “SARS” category as proposed here is necessary for proper preparation for such future events.

Influenza pandemics have all been self-limiting, and early in the first COVID-19 pandemic it was regularly interpreted in a similar manner, i.e. as something that will naturally dissipate. More recently that has shifted towards an acceptance of “endemicity”, where “endemicity” is sold as a state of constant circulation that is not overtly disruptive to normal societal functioning rather than the actual scientific definition, which is constant circulation of the pathogen, and which tells us nothing about its impacts on humans.

If we are to instead view the first COVID-19 pandemic as the initial, and so far appearing to be permanent introduction of an entirely new type of pathogen (SARS) in the human population, and to accept the possibility of many novel SARS serotypes and strains appearing in the future, a rather different picture emerges. So far Omicron exhibits the lowest mortality rate of all sarbecoviruses known to have infected humans, but SARS-1 was much more severe than SARS-2, and the evolution of the first SARS2 serotype was towards more severe disease²⁷ and current data suggests a similar trajectory within many Omicron lineages²⁸.

Therefore it cannot be assumed that all future pandemic serotypes/strains will be “inconsequential”, or even tolerable (where “tolerable” has now been established to mean anything that does not break healthcare systems to the point where refrigeration trucks need to be called in to store the dead bodies), as subsequent iterations of viral evolution that gain a strong fitness advantage due to major antigenic innovations could revert to substantially more pathogenic states, as commentators have previously warned^4,25. An understanding of the course of SARS-CoV-2 evolution so far as having already spawned two separate pandemics is needed to raise awareness of and prepare for these possibilities.

The post A single COVID-19 pandemic or multiple SARS pandemics? appeared first on John Snow Project.

There are two key issues in such statements. The first is the fundamentally misguided idea of a virus being or not being `textbook’ – viruses objectively exist independent of human textbooks, and if textbooks make false generalizations, then the problem is with the textbooks, i.e. the properties of each novel virus need to be considered on their own, not with a reference to a textbook model. The second is whether infection of SARS-CoV-2 or, indeed, any other virus is a net benefit because it ‘sharpens’ one’s immunity, and whether any ‘textbook’ virus in fact behaves in the claimed way.

It is worth noting that this is not a new assertion. Infection as a conduit for immunity has been made by commentators throughout history, and it is usually raised as an argument to counter any impetus for change. It was raised as a reason not to treat water and has been used by people resistant to mass vaccination campaigns^1,2. Some members of the medical and scientific community, and a significant proportion of the general public, believe exposure to pathogens through infection toughens us and is a net benefit to our health.

They could not be more wrong, and ill-informed statements about infection sharpening immunity show a lack of understanding of what the textbooks actually tell us about infection.

Misunderstanding the Hygiene Hypothesis

First, we need to stress that the canard ‘infections are a good thing’ gains traction in no small part because of a widespread and fundamental misunderstanding of the so called ‘hygiene hypothesis’, which was first formulated several decades ago to explain the apparent rise of immune system dysregulation conditions (allergies, autoimmune disorders, and others) together with advanced industrialization and improved living standards^3-5. The idea is that the immune system needs to be “trained’’ during early development in order to properly develop immune tolerance, and that lack of exposure to microbes is what leads to the increased rates of chronic immune dysregulation seen in the population.

However, this is a very different proposition from the idea that being infected with highly pathogenic viruses is good for you. What the hygiene hypothesis specifically refers to is exposure to bacteria, protozoans and helminths, most of which are normally commensal, or perhaps moderately parasitic components of our microbiomes^6,7. This means exposure is beneficial, neutral or not significantly harmful to humans.

The hygiene hypothesis does not suggest repeated exposure to viruses, especially highly pathogenic ones, is a good thing. The fact that this idea has been so successfully pushed into the public consciousness in the last three years is an example of a very skillful execution of a bait-and-switch tactic⁸.

Coronavirus infections do not in fact ‘build immunity’

The second important consideration is what is in fact understood from decades of research into coronaviruses, the group of viruses to which SARS-CoV-2 belongs⁹. 

Prior to 2020, there were four known endemic human coronaviruses – OC43, NL-63, 229E, and HKU1 – which cause 10% to 15% of common colds^10,11. Since at least the 1970s, we’ve known that infection with these coronaviruses does not lead to lasting protection from reinfection^12-14 - this has been textbook knowledge for decades.

That question was revisited after the start of the pandemic using longitudinal or long-term observations of antibody levels in the same individuals over more than two decades, and the textbook knowledge was confirmed to be true – humans are subjected to regular reinfections by common cold coronaviruses (CCCs)¹⁵. 

In fact, this appears to be a property shared by most respiratory viruses (influenza, parainfluenza, RSV, coronaviruses, and others), likely because of a combination of mucosal immunity (which is what is required to stop a mucosal infection) being shorter-lived¹⁶, and quick antigenic drift or mutation of the virus itself.

Of course, it might be claimed that it is not protection from infection that matters, but protection from severe disease, i.e. people may get reinfected, but it is just a cold, so who cares, right? Implicit in this claim is the assumption that the CCCs would in fact be presenting with severe symptoms if they were to be introduced into an immunologically naive population of adults, and it is only the ‘novelty’ of SARS-CoV-2 that has resulted in the deaths of millions, i.e. if all these people had been infected many times as children, then all subsequent reinfections would be “mild”.

The available data does not support such a conclusion at all.

CCCs are in fact not just colds – they can cause severe pneumonias and exhibit a risk profile very similar to SARS-CoV-2 with age^17-19. The CCCs just pack less of a punch and cause serious adverse outcomes at a much lower rate per infection than SARS-CoV-2. If reinfection strengthened immunity against CCCs, older people would be least affected because they are people who have been infected with diverse variants of these viruses many times in the past.

During the SARS-CoV-1 outbreak of 2003, a cluster of serious symptomatic respiratory infections occurred in a care facility in Canada – 95 of 142 patients exhibited symptoms, and 8 died²⁰. Due to unexpected serological cross-reactivity, there were fears this was a SARS outbreak, but eventually it turned out to be OC43. The numerous past OC43 infections experienced by these patients did not protect them from severe outcomes.

However, most concerning are the properties of SARS-CoV-2 itself. Unlike the CCCs, sarbecoviruses (like SARS-CoV and SARS-CoV-2) have a wide array of accessory proteins that silence the innate and adaptive immune responses in various ways, and in the case of SARS-CoV-2, also have a well documented tendency to trigger immune dysregulation, including in mild cases, through these and additional other mechanisms. Of particular relevance to the question of the future of the pandemic is the observation that children infected with COVID can develop the so-called Multisystem Inflammatory Syndrome in Children (MIS-C), an often severe extreme-inflammation immune dysregulation condition²¹. As far as we can tell, CCCs do not cause this condition. If severity was indeed a consequence of novelty and SARS-CoV-2 was intrinsically similar to the CCCs, we would have seen them cause MIS-C or a similar syndrome in previously unexposed children. 

There is no reason to think that endemic SARS-CoV-2 will become a ‘common cold’ simply through repeated exposure, and without losing its intrinsic pathogenicity, which is clearly much higher than the CCCs. Other viruses such as smallpox and measles have not lost their virulence despite centuries of circulation in humans. Our ability to exist with these pathogens depends on infection acquired immunity, which comes at great cost, or vaccination, and, in the case of viruses such as measles and smallpox, generally protects against infection and lasts decades if not a lifetime.

Infections cause immunosenescence and inflammaging

Immunosenescence refers to the changes in immune function that contribute to the increased susceptibility to disease in older people. Research suggests that immunosenescence is not likely the result of primary aging, but rather is caused by environmental and lifestyle factors, even in healthy older people free of chronic illnesses²².

Serious viral infections are now well understood to accelerate the aging of the immune system, which in turn predisposes people to increased susceptibility to serious outcomes, and SARS-CoV-2 is a particularly nasty virus in this regard. Much of the mechanistic basis for severe illness associated with COVID-19 lies in the hyperactivation of our own immune systems, and this accounts for a substantial skew in the risk profile towards older individuals – as aging is associated with low-grade chronic inflammation (so called “inflammaging”), and an overall exhausted immune system, which is predisposed to such overreaction^23,24. 

In contrast to early studies of people with Long Covid which found increased inflammation and immune activation, a recent study by a team at the University of Utah found cytokine deficiencies in a small group of people with Long Covid which points to immune exhaustion as a possible driver of Long Covid^25,26. It is worth noting that prolonged immune activation could culminate in exhaustion over time^27-29.

As COVID-19 itself seems to cause inflammaging, immunosenescence, and immune exhaustion, and because there are no longer any serious efforts to stop the uncontrolled infection of the population, the possibility of a feed-forward-loop - where there are worsening outcomes over time - is an obviously grave concern, and one that has been extensively discussed in the literature^30-36. 

Various mechanisms underlie this phenomenon. One is telomere shortening. Telomeres – the terminal caps of chromosomes – become shorter as individuals age, and they are believed to play a role in biological aging. Leukocyte telomere length is associated with mortality and many chronic diseases that are thought to be manifestations of age-related functional decline. As a result, telomeres are thought to be reasonable markers for immune system aging^37-39. A leading hypothesis is that telomere attrition is due to inflammation, exposure to infectious agents, and other types of oxidative stress, which damage telomeres and impair their repair mechanisms. Indeed, researchers have been able to induce telomere shortening in mice through exposure to infection³⁸. Chronic viral infection also seems to induce telomere shortening⁴⁰, which may be particularly relevant in the context of persistent infection by SARS-CoV-2.  Poorer outcomes associated with shortened telomeres do not seem to be restricted to respiratory viruses and the senescence of the immune system may be a useful predictor of severity of outcomes in a range of “textbook” diseases⁴¹.

If telomeres aren’t your thing, the aging of the immune system through infection can be measured in other ways. Dendritic cells play a key role in initiating and directing immune responses by recognizing and capturing foreign antigens and presenting them to other immune cells to initiate an immune response. Expression of dendritic cells reduces with age⁴² and age seems to also reduce their effectiveness⁴³. Expression and effectiveness of dendritic cells also reduces with infection^44,45 and such reduction has been seen specifically in the case of SARS-CoV-2^46,47.

Finally, much attention has been devoted to the role of T-cells in the response to and pathogenesis of COVID⁴⁸. T-cell exhaustion is a frequent finding following SARS-CoV-2 infections^49-52. T-cell exhaustion is not universal, and over time, in the presence of chronic infection, certain subsets experience inflation without displaying features of exhaustion⁵³. T-cell aging following SARS-Cov-2 is an even more concerning finding⁵⁴. In order to mount an effective immune response, T-cells need to have a certain amount of proliferative potential and plasticity to be able to differentiate into different functional lineages - they must be malleable and adaptable for the best response - but the capability deteriorates from around 50 years of age and can be measured by changes in composition of naive and effector memory cells in the bone marrow, to the point where it becomes clinically significant from 70 to 100 years of age^55,56. 

One does not need to dive deep into the molecular details of this subject to know that it is a textbook feature of viruses that infection ages the immune system. And aging the immune system is not beneficial to one’s health – in fact it creates a negative feedback loop that makes people more susceptible to infection. So, rather than symptomatic infection sharpening one’s immune system, infection is likely to age the immune system in a way that will make one more susceptible to illness upon reinfection or infection with another pathogen.

To recommend infection as a method of ‘sharpening’ the immune system seems foolhardy in the context of what the literature tells us.

Infections increase the risk of autoimmune disease

Autoimmune diseases are caused by a loss of immunological tolerance for self. The immune system mistakes host for pathogen and attacks it, causing systemic or specific damage to parts of the body. Infection seems to play a role in either inducing or exacerbating predisposition to autoimmunity^57-60 and infection by SARS-CoV-2 in particular has been shown to lead to an increase in autoantibodies⁶¹ and an increase in autoimmune disease⁶². Indeed, early research seems to suggest autoantibody production is not reduced by vaccination⁶³, and if vaccination is a proxy for prior infection, each subsequent reinfection with SARS-CoV-2 may carry with it the risk of developing an autoimmune disease. Approximately 25% of people who develop an autoimmune disease will experience multiple autoimmune syndrome⁶⁴, risking a cascade of autoimmune conditions.

In this context, we believe it is the height of irresponsibility to state that infection ‘sharpens’ the immune response, when in fact infection may carry with it the risk of causing lifelong autoimmune disease.

The immune system is better prepared by vaccines

Another social media commentator recently stated, “The immune system, like the brain, must learn. Immunity doesn't just appear out of thin air. Development of immunity literally REQUIRES exposures.”

This is factually incorrect. The development of adaptive immunity like the T cell repertoire in the thymus requires no exposure to foreign antigen with exposure to self being used for positive and negative selection⁶⁵.

In addition to being factually incorrect, the statement is also poor science communication, because many people will take the ‘requirement’ of exposure to mean infection, and in the context of most governments winding down or restricting their SARS-CoV-2 vaccine programs, it’s hard to see an alternative to infection in many societies. The commentator likely also meant exposure through vaccines, but it is important to be specific; vaccines and not infection are the best way to give the immune system the protective information it requires. This is true in adults⁶⁶ and children⁶⁷, and it seems not only are vaccines quantitatively better, the quality of immune response is improved by higher avidity⁶⁸, a measure of the strength with which antibodies bind.  The benefits of vaccination over infection are not restricted to SARS-CoV-2 but are also true of diseases such as chickenpox, which have traditionally been regarded as mild⁶⁹.

Prominent social media commentators need to take greater care in their messaging, and if they are going to champion infection as a method of ‘sharpening’ the immune response, they must also communicate the risks that accompany each infection. We have outlined some of the long-term risks of SARS-CoV-2 infection here, and even if we set aside some of the more contentious aspects of immune harm, it is clear from what ‘textbook’ immunology tells us about SARS-CoV-2 and other pathogens, that infection should be avoided if at all possible. We believe vaccination is the best way to prepare one’s immune system to reduce the risk of severe acute disease, but that in the absence of sterilizing immunity, breakthrough infections still carry a risk of adverse long-term outcomes and should be avoided. 

SARS-CoV-2 infections may increase the baseline risk upon reinfection

Most of the discussion so far has focused on the role of the immune system in responding to, and mitigating the impacts of SARS-CoV-2 reinfection. But a key question is how the body as a whole will fare against repeated reinfections. The ‘mild endemicity’ model that is being pushed claims that once the pathogen is no longer ‘novel’, its impacts become inconsequential because the immune system is ‘trained’ to prevent worst-case outcomes. This hypothesis relies on framing SARS-CoV-2 as a “textbook” respiratory virus where it joins the ranks of the CCCs, RSV, rhinovirus and so on. 

However, SARS-CoV-2, like SARS-CoV-1, is both a respiratory and a systemic virus, with an extremely broad cell type and tissue tropism covering nearly the whole body. The consequence is that it causes damage to a wide range of human organs and systems. Lungs, hearts, kidneys, cardiovascular systems, and nearly everything else one can think of are well documented to be susceptible to lasting damage as a result of COVID-19^70-73. 

What does that mean for the future? Under the most optimistic ‘mild endemicity’ model, whoever has survived the first infection, without severe sequelae, is set for life and doesn’t have to worry about future infections. Under the less optimistic ‘mild endemicity’ model, it will take a few reinfections to get to that point. 

Most commentators who push ‘mild endemicity’ have pivoted away from the most optimistic scenario because it has already been completely debunked by evidence – reinfections are common⁷⁴, and people do die and get Long COVID as a result of them⁷⁵, and even though the risk of Long COVID reduces by about a third, it is far from zero⁷⁶. So, it is already clear that if you survive the first infection without severe sequelae, you are still at risk - albeit somewhat reduced - of sequelae after subsequent infection.

If each subsequent infection results in additional internal organ and immune system damage⁷⁷, then a different model needs to be considered – a balance between protection from severe outcomes due to the presence of antibodies, and the increased baseline susceptibility to severe outcomes as a result of damage from repeated infections, and the increased risk of infection over time because of the natural processes associated with aging. 

Let’s suppose someone has lost 20% of their lung capacity as a result of previous SARS-CoV-2 infection^78,79. If all else is equal, this person is at higher risk of ventilatory decompensation as well as being at higher risk for developing respiratory infection than someone with 100% intact lung capacity. Similarly, an initial SARS-CoV-2 infection may result in subclinical stage 1 kidney disease⁸⁰, with accelerated progression by repeat infection towards worsening chronic kidney disease and even end-stage kidney disease needing dialysis^81,82. Mild SARS-CoV-2 infection can increase arterial stiffness, which might put people at higher risk of complications from future SARS-CoV-2 infection or long-term vascular complications such as hypertension, stroke, or myocardial infarction^83,84.

At some point the damage accumulated, together with the accelerated immune system aging we discussed earlier plus normal aging processes, can reasonably be expected to outweigh the protective benefits of the memory B and T cells developed from previous infections. As a result, the baseline risk shifts higher - eventually much higher than what it would be at a given age for a first infection. 

Such a process would be expected to result in a dramatically reduced life expectancy and quality of life for much of the population. The excess deaths currently being witnessed around the world already point to a reduction in life expectancy. In the UK, which now includes two pandemic years in its five-year average, excess deaths are currently 7% above expectations⁸⁵ and in Holland, excess mortality is rising in younger age groups⁸⁶. 

It is important to note that some commentators who ridicule the reality of immune harm or aging through infection expect to see relentless and sustained rises in viral, bacterial or fungal infections and in the absence of this phenomena, claim there’s no evidence for infection-induced immune harm. 

However, these commentators fail to acknowledge that studies into variable immune deficiency repeatedly demonstrate that immune compromise manifests in an increased propensity to a variety of autoimmune conditions, cancers and death from diverse causes^87,88. Even in the case of HIV, possibly the most well-known virus to affect the immune system, there are those who believe infection results almost exclusively in increased susceptibility to infection and pneumonia, when in fact the immune damage caused by the virus results in increased cardiac death and disease^89-91, kidney disease⁹², and stroke^93,94 among other diverse elevated risks. 

Infection with a virus does not ‘sharpen’ the immune system, particularly when the virus is shown to in fact cause immune aging and harm. Instead, we should expect the cumulative impact of repeat infection to manifest in diverse illnesses and diseases and to shorten life expectancy.

This is our assessment of the situation based on the best available textbook evidence and it is at odds with the ‘mild endemicity’ hypothesis that underpins the policies of most governments around the world. If the current nonchalant attitudes towards uncontrolled transmission of SARS-CoV-2 remain in place, we will discover which model of endemicity is correct in the coming years. We believe the evidence is already accumulating to suggest this population-scale experiment of mass infection by SARS-CoV-2 will lead to a rejection of the ‘mild endemicity’ hypothesis, but then it will be too late.

If you’d like advice on how to reduce your risk of infection, please click here.

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Instead, those who would like to see clean air and protective measures implemented everywhere, from hospitals to schools, are presented as fearmongers, who are recklessly advocating investment in public health without precisely quantifying the benefit, and doubt is cast over the validity of any evidence that suggests COVID-19 may cause long-term or serious harm. We’ve seen this approach before, with merchants of doubt peddling uncertainty in order to undermine solid scientific evidence and dissipate the political impetus for action.

In August 1969, J W Burgard, an executive at Brown & Williamson Tobacco Corporation, sent an internal memo¹ setting out six objectives for a campaign that would educate the public on the tobacco industry’s response to the health controversy surrounding smoking. Burgard wanted to:

1. Attack science as a question of perspective and personality to dispel the ‘false belief’ smoking is associated with lung cancer and other diseases, casting such views as unscientific conjecture made by publicity-seeking opportunists.
2. Associate smoking with freedom by restoring the cigarette to its proper place of dignity in the marketplace of American free enterprise.
3. Suggest ill intent by setting out to expose the greatest criminal libel and slander ever perpetrated against any product in the history of free enterprise.
4. Associate smoking with stability by linking the attack on cigarettes to a pattern of attack on the American free enterprise system.
5. Dismiss those concerned with public health as fearmongers, by proving the attack on cigarettes is trial by lynch law engineered by uninformed, irresponsible people to induce fear.
6. Undermine faith in the scientific process in order to establish once and for all that there is no scientific evidence that cigarettes cause cancer.

Burgard went on to say he viewed “our product as doubt, our message as truth—well stated” and viewed the competition as “the body of anti-cigarette fact that exists in the public mind.”

Burgard’s audacious memo was written more than 40 years after the first published evidence of a link between smoking and cancer. In 1925, Fritz Lickint authored a report showing that smoking led to an increased incidence of gastric ulcers and stomach cancer and in 1929 he published the first formal statistical evidence linking tobacco smoking with lung cancer, in which he showed that patients with lung cancer were especially likely to be heavy smokers².

In 1931, Frederick Hoffman published Cancer and Smoking Habits in the Annals of Surgery³ in which he produced evidence showing a higher general rate of cancer and of lung cancer in particular in smokers when compared to non-smokers, enabling him to conclude, “smoking habits unquestionably increase the liability to cancer of the mouth, throat, esophagus, larynx and lungs.”

1950 saw the publication of three case control studies that demonstrated a link between lung cancer and smoking^4-6. In what became a commonplace method of ad hominem attack, doubt was cast on the strength of one of those studies with the suggestion that one of the principal researchers, Ernest Wynder, was motivated by puritanical fervor. Neville Goodman, a civil servant at the British Ministry of Health, said of Wynder:

“He is a young man ‘far gone in enthusiasm’ for the causal relationship between tobacco smoking and lung cancer. (I had been told when I was in New York this spring that he was the son of a revivalist preacher and had inherited his father’s antipathy to tobacco and alcohol). The American Cancer Society was very suspicious of his early work for this reason.”⁷

1954 saw the publication of the cohort studies that conclusively demonstrated the causal relationship between smoking and lung cancer^8,9, which helped pave the way for the first report of the Surgeon General’s Advisory Committee on Smoking and Health in 1964^10,11. The report concluded smoking was a cause of lung cancer and laryngeal cancer in men, a probable cause of lung cancer in women and the most important cause of chronic bronchitis and prompted health warnings on cigarette packages and a ban on cigarette advertising in broadcasting media.

Anyone who grew up in the 1980s and 1990s, when governments around the world finally acted to ban smoking in public places and restrict tobacco sales, might be surprised that the evidence of the harms caused by smoking had been around for so long. The public would be forgiven for assuming governments would act, and act quickly, once causation was proved.

This was not the case. For instance, the British government accepted the causal link between smoking and cancer in the early 1950s. In 1954, as pressure was mounting on the British government to publicise the links, the Health Minister Iain Macleod, who once chain-smoked through a press conference on the dangers of smoking, wrote to John Boyd-Carpenter, the Financial Secretary to the Treasury:

“I needn’t say anything about the financial implications of any ill-considered statement in this field for we all know that the Welfare State and much else is based on tobacco smoking…My only anxiety is to make whatever statement should be made as quietly as is possible but I feel that we must move soon if events are not to overtake us.”¹²

As this excerpt from Denial & Delay by David Pollock makes clear, the government of the day suspected the public would not take scientific evidence seriously unless it was endorsed by the government itself:

“Lord Salisbury’s brief for the Home Affairs Committee…recognised that an announcement ‘may well be unavoidable before long . . . But the possible effect of an announcement on the Revenue clearly cannot be ignored. The yield of the tobacco tax is about £600 millions a year – i.e., considerably more than the cost of the Health Service. The television programme [from] about two years ago…seems to have had little effect on smoking. But it may well be that people paid little attention to that programme, thinking that if the matter was really as serious as was suggested, the Government would have made an announcement. If this were so, the effect of the Minister of Health’s announcement might be to bring about a serious reduction in revenue, which it would be very difficult to replace by any tax as little objected to or as easily collected as the tobacco tax.’”¹²

In the end, the Ministry of Health issued a three-page briefing paper which subtly emphasised the doubts and uncertainties of the link between smoking and cancer. At the same time, the Health Minister accepted an offer from the tobacco industry of £250,000 to fund further study of the issue by the Medical Research Council.¹²

In 1956, the British Cabinet considered the issue of smoking as a cause of cancer. In response to the then Health Minister, Robert Turton, who suggested warning the public, the Chancellor of the Exchequer Harold Macmillan said that this was a “very serious issue. Revenue was equivalent to 3/6d on income tax: not easy to see how to replace it.” He added: “Expectation of life is 73 for smoker and 74 for non-smoker. Treasury think revenue interest outweighs this. Negligible compared with risk of crossing a street.”¹³

Burgard’s ‘doubt as product’ memo was written a full 5 years after the US Surgeon General presented unequivocal evidence that smoking caused lung cancer, more than 15 years after the British government had been forced to publicise the link as quietly as possible. Even in the face of compelling evidence and official government statements about the danger and public health advice to avoid smoking, Burgard’s approach worked, partly because there were credible clinicians and scientists who refused to accept the weight of scientific evidence of the harms and helped sustain the false dichotomy by maintaining the fiction of doubt¹⁴. It took decades for public health restrictions to finally be imposed, demonstrating to people that governments acknowledged the causal link between smoking, cancer, heart disease and other conditions. Millions of people’s lives ruined or lost, some of them likely thinking to the very end that, “if smoking was really bad, the government would take steps to protect people”.

But with the benefit of hindsight and access to official records, we can see governments didn’t take steps to protect people in the face of a proven public health risk, and consistently prioritised economic interests. Even in healthcare settings where people might be more vulnerable to the impact of secondary smoke, smoking was not discouraged until the late 1980s and wasn’t banned in hospitals and other healthcare settings until the late 1990s and early 2000s^15-17. Despite extensive scientific evidence of harm, hospitals and healthcare settings allowed people to engage in a physiologically damaging activity because it was socially and politically acceptable. To admit harm in a healthcare setting would have implied harm in other settings, which might have undermined the economic contribution being made by the tobacco industry.

Whatever one’s understanding of the harms of COVID-19, it would be a mistake to assume governments would automatically protect people from a public health threat in the face of more immediate economic considerations. In fact, history tells us there would be resistance to change that might be costly until the evidence to justify it was overwhelming, a process we’ve already seen played out during the COVID-19 pandemic.

From asymptomatic and airborne transmission to the risk of breakthrough infections and reinfections, from organ, immune system and neurological damage to the impact of Long Covid, every single serious harm of SARS-CoV-2 has been minimized by influential commentators, including experts on some public health committees, whose words seem to carry more weight with policymakers than the carefully designed studies evidencing these harms. Each of these harms increases the rationale for a change of approach - and each will be resisted by those keen to defend the status quo.

J W Burgard would be proud of his contemporary disciples who have taken on his mantle as merchants of doubt, but the public should be under no illusions about what is happening. While national and international health agencies around the world advise against infection or reinfection by SARS-CoV-2, industry lobbies and many politicians are enthusiastically promoting a return to pre-2020 social and economic practices without any mitigations against the novel virus that has transformed the risks we all face as we go about our daily lives. For while smokers choose to accept the risks inherent in satisfying their tobacco addiction, none of us can opt out of breathing.

It is important to note that no government has said COVID-19 has gone away and that we can resume unmitigated social interactions facing the same risks we did in 2019. Instead, official messaging has centered around the idea of individual responsibility, that we should each engage in our own assessment of the risks of SARS-CoV-2 infection. This feels a little like government smoking policy in the 1950s; the scientific evidence of cumulative harm is mounting, some national and international public health agencies are warning of the danger, merchants of doubt are making appeals to uncertainty in the name of individual freedom, and governments are unconcerned or worried about the costs of implementing the changes necessary to help keep people safe.

While we wait for public health policy to catch up with the scientific evidence, here are some steps we can take to reduce our risk.

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