February 21, 2021

The Next Big One

              As new cases of Covid-19 fall throughout the world but the US approaches 500,000 deaths from Covid-19 and the world nears 2.5 million deaths, it is time to start planning for the next pandemic. 

               We have known since the 1918 influenza pandemic, which killed upwards of 50 million people world-wide, that it’s not a question of if, but rather of when. Moreover, recent decades have seen the emergence of several new and terrifying diseases. These diseases have principally been caused by viruses, viruses that jumped species. They moved from their usual host, say a civet or a bat, into people for one of several reasons: climate change may have destroyed their hosts’ usual habitat, forcing them to find a new home where they came into greater contact with humans; alternatively, humans encroached on the hosts’ habitat by clearing forest or planting a crop that deprived the host of its usual food source, again leading the host to relocate; or humans may have developed a taste for certain types of wild animal, bringing the two species into unaccustomed contact and thus facilitating viral transmission.

              As a result of these factors, we have had Zika, SARS, MERS, avian influenza and now Covid-19 in the twenty-first century, and Ebola, Marburg hemorrhagic fever, and HIV in the last part of the twentieth century. These are only the best-known of “zoonoses.” Today, 75 percent of new infectious diseases are zoonotic in origin and their numbers have been rising steadily. 

            The good news is that we know a great deal about how to go about preventing outbreaks, detecting them early, and responding if they nonetheless occur. The bad news is that the world in general and the U.S. in particular have a poor track record of implementing the necessary strategies. Allocating scarce resources now to help alleviate problems that will develop at some unspecified time in the future has proved to be a hard sell. 

                The irony is that we in the U.S., as in many other countries, spend an enormous amount of money on our military. We have accepted the need to devote a large fraction of our budget to the armed forces and to equipment including both “conventional” and nuclear weapons. We have not yet acknowledged that the far greater threat to our national security and our well-being is from lowly viruses, strange biological entities that are not strictly speaking alive since they cannot survive outside a host organism, not from invading armies. 

            The current US budget consists of just under $3 trillion on “mandatory spending,” which includes Social Security, Medicare, and Medicaid; and another nearly $1.5 trillion on “discretionary spending,” over half of which is for military spending, including the VA and Homeland Security as well as the armed forces. The base budget for the Department of Defense is $636 billion.

             By comparison, the CDC (Centers for Disease Control), the site for most of the U.S. epidemic preparedness activities, has a total budget of $6.6 billion, of which $509 million is allocated to “Emerging and Zoonotic Infectious Diseases.” Other disaster preparedness activities are financed through various departments, including Homeland Security, which is part of the military. But as a very rough approximation, it is not far-fetched to say that the core budget for potential epidemics is $509 million compared to the core budget for the military of $636 billion, or .08 percent.  This comparison reveals an enormous imbalance between spending on the military and on epidemic preparedness, with too much to fight armed invasions and not nearly enough to combat microbial enemies.

            If we are to spend more on epidemics—and, arguably, less on bombs and fighter planes—what should we spend it on? A basic framework was outlined at a symposium called “Building Interdisciplinary Bridges to Health in a Globalized World,” organized by the Wildlife Conservation Society in 2004. The symposium called for an international, interdisciplinary approach to preventing disease, or “One Health, One World.” It articulated its views in a document called the Manhattan Principles which laid the foundation for what would become an international movement. The Manhattan Principles is built on  the recognition that modern epidemics stem from the inter-connections between humans, domestic animals, and wildlife, and that these interactions arise either directly from human behavior (eg agricultural practices, clear cutting forests, and eating wildlife), or indirectly, mediated by climate change that is in turn due to human behavior. Since the problem is fundamentally multidisciplinary, its solution must likewise be multidisciplinary. And since the modern world is interconnected, the solution must be international, involving sharing information.

            An implementation framework was drawn up in 2008 by a group consisting of representatives from UNICEF, WHO, the World Bank among others. Entitled “A Strategic Framework for Reducing Risks of Infectious Diseases at the Animal-Human-Ecosystems Interface,” it argued for the development of an international system of disease surveillance drawing on multidisciplinary expertise (to include veterinarians, physicians, wildlife specialists, and ecologists). In addition, it sought to help build robust public health systems across the globe and to promote good communication between those systems. Finally, it advocated support for strategic research, to be shared internationally. 

            The One Health approach was adopted by the CDC in 2009, which housed it within its National Center for Emerging and Zoonotic Infectious Diseases. It was formally endorsed by the UN, the World Bank, and the EU in 2010. More recently, the World Bank came up with a revised operational framework to fight EIDS as a means of fulfilling its mission to promote prosperity and decrease poverty.

            Our response to future epidemics, when they occur, will hinge on more than international and multidisciplinary collaboration. Scientific developments are likely to have a major impact when future EIDs arise. The new technique of vaccine design using mRNA is vastly accelerating the development of effective vaccines, the most powerful preventive tool available. Work on anti-viral medications is ongoing and could revolutionize treatment of viral diseases much as antibiotics revolutionized the treatment of bacterial diseases. Currently, the only virus for which there is effective treatment is HIV, and that treatment (which took years to develop) involves a multi-drug regimen that converts HIV into a chronic disease but rarely eradicating the infection. 

            We also need to strengthen the public health infrastructure in the U.S. Poor coordination, insufficient manpower, and inadequate communication to the public have afflicted domestic public health departments for years. WHO and the World Bank have focused on shoring up public health in much of the world but assumed that the richest countries would serve as models of success. 

            The One World framework could itself be expanded to address climate and the environment more expansively, but the basic formulation is sound. As Andrew Cunningham, Peter Daszak, and James Wood argue in their 2017 article, “One Health: Emerging Infectious Diseases and Wildlife: Two Decades of Progress?” little has been done at the policy level to address what remain major threats to health and well-being, as Covid-19 attests. It’s time to adjust our national priorities and focus on what counts. 



January 11, 2021

The Home Stretch

For Americans over age 65, the Covid-19 vaccine really is coming soon. States have varying policies on prioritizing distribution of the vaccine, with some states already giving it to those older than 65 and others planning to get to the over 75 group very soon and the 65-74-year-olds shortly thereafter. In all cases, the expectation is that by April, all older Americans will have had the opportunity to be vaccinated. 

If you are reading this post, you have made it this far—so my message today is don’t blow it now by throwing caution to the winds. The virus is striking more people each day than ever before, and despite the progress in treatment, more people are hospitalized and more people are dying than at any time in the past year. 

The US also has the dubious distinction of being number one in the world in terms of cumulative mortality from Covid-19.  

Tired as we all are of masks and social distancing and of just plain staying home, these are the only strategies we have until we are vaccinated—and even then, we’ll need to wait until most of the population has been vaccinated before we can relax. A more infectious strain, isolated in the UK, is here in the US. It may be far more widespread than we know since public health officials are not routinely testing for it. Just because we haven’t found it doesn’t mean it doesn’t exist: it just means we’re not looking for it. 

The implication of all this is that it would be prudent not merely to remain careful, but to increase your vigilance. Writing in the medical news periodical, STAT, several physicians and an engineer argue that we should wear high filtration masks such as the N-95. We should take their proposal seriously. While N-95 masks are primarily restricted to health care workers, KN-95 masks, which are in many cases equivalent, are available from Amazon, some local pharmacies, and a variety of other on-line sources. Most of these have not been tested for effectiveness or reliability by American government regulators, but many have been subjecting to assessment by one or more international agencies. The CDC has made available a list of many KN95 masks and the results of the assessments. 

My recommendation is to start wearing one of the KN-95 masks on this list, choosing one that has a minimum filtration efficiency of at least 95 percent. Wear it indoors in any public space. Do not socialize indoors except with members of your household. Do not take unnecessary risks and don’t let down your guard! 

January 01, 2021

Looking Forward

            Once the 1918-1919 influenza pandemic finally came to an end—after killing somewhere between 50 and 100 million people worldwide—Americans did their best to forget about it. Later tragedies such as AIDS and 9/11 figured prominently in much American fiction, but influenza was seemingly forgotten by American writers: Katherine Anne Porter’s short story, “Pale Horse, Pale Rider” and William Maxwell’s novella, “They Came Like Swallows,” are rare exceptions. Historians and journalists writing about the 1918 flu have hypothesized that the pain and suffering inflicted by the flu paled by comparison with that attributable to World War I, which came to an end at the same time, even though ten times more Americans died of the flu than died in combat. Or perhaps Americans were so optimistic about scientific medicine, which was just coming into its own in the twentieth century, that they chose to ignore medicine’s great failure, its inability to diagnose, treat, prevent, or cure influenza. Maybe Americans simply repressed this traumatic episode that killed people in the prime of life, leaving families without a means of support and children without a mother or father. Will the Covid-19 pandemic similarly be forgotten, or will it have a profound and enduring effect on us as individuals and on us as a society?

            The pundits are already speculating about the long-lasting effects of the pandemic on the real estate market and on the work place, on professional conferences and the movie industry. But what I would like to address is the life lessons we should take away from this devastating and unexpected year. The first is that our lives are tenuous. We in the developed world have come to expect a long healthy life, especially if we are white and middle class. Life expectancy at birth in the US is just under 79 years; if you make it to age 65, you can expect to live another 20 years. Covid-19 showed us that we should not take those years for granted: while 80 percent of the Covid deaths have been in people aged 65 or older, that means that 20 percent have been in people under 65. As of the end of December, 2020, 346,000 Americans had died from the disease, which translates to 69,000 younger people. There’s nothing like awareness of our own mortality to concentrate the mind and encourage us to live life well and to the fullest. This is the first lesson and the one we are perhaps most likely to forget.

            The second lesson is that what matters most to us as human beings is our relationships with other people. That’s what made “social distancing” so painful; it’s why eliminating family visits to nursing homes was so devastating; it’s why Zoom, FaceTime, and other video chat programs have been such a lifesaver. We need to cultivate our friendships, to nourish them, to work to improve them. The pandemic made us believe that other people are the enemy, which runs counter to our essence as social creatures.

            The third lesson that I want to emphasize is of a different sort: it is that to make decisions about most anything important and certainly to make medical decisions, we need to understand something about risk. How to behave during the epidemic was all about how to evaluate risk, how to think about risk. Just because most people who don’t wear masks and who go to group gatherings won’t get sick doesn’t mean that these are safe activities. It means that you markedly increase the chance that you will contract the virus if you go around without a mask or attend a group meeting. And understanding risk is more complicated still: how much you increase your risk depends on how widespread the virus is in the surrounding community. If very few people in the vicinity of where you live are sick, then your likelihood of getting the disease is low, even if you fail to take precautions. But as the virus begins to circulate more widely, then precisely the same behavior pattern that was only slightly unsafe before will become far more dangerous. 

            Understanding risk is tricky because the epidemiological measures designed to protect individuals, whether wearing a mask, practicing social distancing, or getting vaccinated, are not perfectly effective. Some people who wear a mask will nonetheless contract the virus; ditto for people who stay six feet away from others. Individuals who received either the Pfizer or Moderna vaccination in the clinical trials were one-twentieth as likely to get sick as those who received a placebo. But that means that just how safe you can feel if you are vaccinated  (even if the effectiveness holds up in a much larger population than was tested in the trials) also depends on how widespread the virus is: while vaccination lowers your relative risk of getting sick, if the number of infectious people in the community suddenly increases, say by a factor of ten, your chance of getting the disease also goes up by a factor of ten, even if you've been vaccinated. Grasping the concept of risk is essential—not just to dealing with an infectious disease, but also to deciding whether to undergo screening for prostate cancer, whether to take medication for borderline high blood pressure, and whether to invest in the stock market. 

           Americans, along with people across most of the globe, have lost much from our encounter with the corona virus. We have also gained something: an appreciation for life’s fragility, a recognition of the importance of relationships, and a deeper understanding of risk. It is up to us to remember, both those we have lost and what we have learned. 

December 07, 2020

Dateline: Pearl Harbor

Exactly 79 years ago today, Japanese planes bombed Pearl Harbor, an American naval base on Oahu, Hawaii, catapulting the U.S. into World War II. "A day which will live in infamy," President Franklin Roosevelt would call it--a day which lives on in the memory of the oldest Americans (though not, evidently, of the NY Times, which did not mention it in today's newspaper). The attack, which destroyed more than 300 planes and killed or wounded 3400 Americans, dealt a devastating blow to America’s sense of invulnerability and to our isolationist tendencies. It was also the last time the armed forces of a foreign nation would penetrate the American homeland. And yet, deep into the 21st century, the U.S. continues to place disproportionate weight on armed invasion as the major threat to the security of all Americans, young and old.

As the Covid-19 pandemic, the devastating wild fires on the west coast, and the unprecedented number of named storms this season demonstrate, America must address several other crucially important problems if its citizens are to remain safe and its democracy strong. Epidemics and climate change are two of the principal non-military threats; cyber-attacks and attacks on science are two additional substantial threats. 

Why do these non-traditional forms of attack constitute a threat to the national security? Epidemics have the potential to harm or kill tens of thousands, hundreds of thousands, or even millions of Americans; in addition, they can disrupt the economy (either because sick people cannot work or as society limits economic activity to protect health); and they can damage or destroy fundamental institutions such as the health care system by overwhelming its capacity. Climate change, by causing sea level rise, risks destroying coastal property or submerging entire cities; by contributing to natural disasters such as mudslides and wild fires, climate change endangers life and property. Rising maximum temperatures may make parts of the country uninhabitable or cause death from hyperthermia; they might destroy industries such as cod or lobster fishing as entire animal species migrate north in search of cooler waters. 

Cyber-attacks, whether carried out by state actors, by international terrorists, or by domestic criminals, can disrupt the financial system, the energy grid, our elections, or other fundamental institutions essential to the health and safety of Americans. Attacks on science constitute a fourth non-traditional threat, one that is just coming to be recognized as endangering both progress and our democracy: progress because a citizenry that rejects science will reject legislators who support science, resulting in diminished funding of the research essential for improvements in health and security; democracy because citizens cannot tell truth from falsehood will not have the information necessary to vote in their best interest. Undermining science will, in addition, exacerbate climate change and increase the likelihood of pandemics.

The idea that threats might not come from a foreign state actor but rather from microorganisms (in the case of a pandemic), from the anthropogenic production of greenhouse gases (in the case of climate change), from a computer hacker (in the case of cyber-attacks), or from lies and propaganda distributed via social media (in the case of the attack on science and, more generally, on truth, knowledge and expertise) represents a fundamental change in the way we need to think about national security. And just as the terrorist attacks of 9/11/2001 led to the creation of the Department of Homeland Security, so too should the current pandemic push us to reconsider the effort we devote to fending off other non-traditional types of attack. 

Consider the case of microbial threats. The idea of investing in pandemic preparedness is not new: the danger of pandemics and the importance of a coherent response strategy has been acknowledged by public health professionals since the influenza epidemic of 1918-1920. Each of the subsequent pandemics of the 20th century (Asian flu in 1957 and AIDS beginning in 1981), as well as the first pandemics of the 21st century (SARS in 2003, Swine Flu in 2009, and Ebola in 2014), brought renewed interest in both prevention and mitigation. Increased understanding of the origins of these outbreaks has led to a recognition of the importance of surveillance: we now realize that all the major pandemics have been zoonoses, they have arisen from viruses that jumped from one species, such as bats, to another species, humans, because of disruptions in the natural habitat of the original host. Furthermore, realization that global interconnectedness promotes rapid spread of the most readily transmissible organisms has resulted in an appreciation of the importance of international cooperation in combating pandemics.

Such recognition and realization emerged from thoughtful and comprehensive reports such as the workshop on "ethical and legal considerations in mitigating pandemic disease" sponsored by the Institute of Medicine. Its proceedings were published in 2007. This was followed in 2016 by a chilling report from the National Academy of Medicine, “The Neglected Dimension of Global Security: A Framework to Counter Infectious Disease Crises,” that made explicit the connection between national security and epidemics.

These documents did not just collect dust in government archives; their conclusions were, to a limited extent, translated into US public policy. Beginning with President Clinton, each presidential administration has put forward a new or revised pandemic preparedness plan. Congress authorized the establishment of a Global Emerging Infections Surveillance program within the Department of Defense in 1997, a program intended to improve surveillance, to foster prevention, and to plan for a response to potential new microbial threats. George W. Bush had his “Biodefense for the 21st Century” plan, precipitated by the anthrax scare, though this focused principally on bioterrorism, the deliberate dissemination of disease-causing organisms by state actors or individual terrorists. Obama had two: the “National Strategy for Countering Biological Threats” in 2009 and the “National Strategy for Bio-Surveillance” in 2012. Trump had his “National Biodefense Strategy” in 2018, which addressed naturally occurring, deliberate, and accidental biological threats, and theoretically centralized the federal response in the Department of Health and Human Services. 

These policies sound good on paper. But implementation, coordination, and funding have lagged. For example, the Centers for Disease Control budget allocation for prevention of zoonotic diseases in 2020 was $636 million out of a budget of $6.5 billion; Trump’s proposed 2021 budget asks for $550 million. The total Department of Defense allocation for FY 2021, by contrast, is $933 billion.

More generally, both the current (FY2020) and proposed (FY2021) federal budgets include support for combating pandemics and cyber-attacks, but do little to support combating climate change (the phrase is nowhere to be found) and nothing to defend against attacks on truth or on science. Even when the threats are acknowledged, the programs responsible for combating them are disseminated through multiple disparate agencies, are poorly coordinated, and receive only modest funding. 

Pearl Harbor Day should serve as a reminder of how threats to national security have changed in the three quarters of a century since Japanese bombers crossed the Pacific and entered American airspace. For starters, we should have a cabinet level department to take these new threats rather than embedding them into the Department of Defense, which has been structured to focus on the military. Perhaps we should simply reconfigure the Homeland Security Department, which no longer focuses on the prevention of terrorist attacks, the rationale for its establishment, but rather devotes its efforts to the enforcement of immigration policies. Immigration is not a threat to national security; but pandemics, climate change, cyber warfare, and the attacks on truth in general and on science in particular pose a real and present danger.




November 17, 2020

Now Hear This

On November 9, we learned that the preliminary data from the Pfizer/BioNTech COVID-19 vaccine trial are very promising; exactly one week later, we got similarly good news from the ModernaTX/NIH study.  What do the Moderna data show and how do they compare with the Pfizer data?

Moderna began enrolling patients last summer and has recruited 30,000 volunteers, half of whom received two doses of vaccine and half of whom got placebo, in both cases at 30-day intervals.  

The subjects, adults over the age of 18, were divided into 3 groups: people age 65 or older; people under 65 with known risk factors for coronavirus; and people under age 65 with no known risk factors. The principal outcomes that the researchers are tracking are the ability of the vaccine to safely prevent symptomatic COVID-19 infection and the capacity of the vaccine to stimulate antibody production in recipients. In addition, the researchers are looking at whether the vaccine can prevent severe COVID-19 infections and whether it can prevent asymptomatic infection (as measured by markers for COVID indicating current or previous infection despite the absence of symptoms).

The newly reported results are based on the 95 enrolled subjects who have thus far been diagnosed with COVID-19. Being diagnosed with COVID-19, according to the definition in the study, means having a positive PCR (polymerase chain reaction) nasal swab after developing symptoms consistent with the disease. What we know is that of these 95 individuals, 5 had received active vaccine and 90 had received placebo. We also know that 20 of the 95 people with the illness were over age 65 and that 11 people developed severe disease, none of whom had been vaccinated. While the specific numbers have not been reported, Moderna has asserted that the efficacy was the same among the different age groups as well as among various ethnic groups (or, more accurately, given the very small numbers of sick people, they were unable to detect any differences).

What we don’t know is the duration of the protective effect. We don’t yet know whether the vaccine prevented asymptomatic infection, although we should know something about its capacity to do so when the endpoint of the study is reached, namely when 151 enrolled individuals have been diagnosed with symptomatic disease. And we don’t know whether the vaccine is effective in children.So, how does the Moderna vaccine compare to the Pfizer vaccine 

They are both mRNA vaccines, a type of vaccine that has never been approved for human use. The efficacy rates reported thus far are extremely similar: from a statistical standpoint, the 95 percent efficacy quoted by Moderna is not any different from the 90 percent efficacy quoted by Pfizer, given the small number of sick patients.  

Both vaccines have to be kept cold to remain viable, but shipment and long-term storage of the Pfizer vaccine has to be at 70 degrees below zero Centigrade while long-term storage of the Moderna vaccine can be at 20 degrees below zero Centigrade; on arrival at your local drug store or physician’s office the Pfizer vaccine can be refrigerated at normal temperatures for up to 5 days while the Moderna vaccine can be refrigerated at normal temperatures for up to 30 days without losing potency. 

The Pfizer vaccine has been tested in children; the Moderna vaccine has not so we just don’t know whether it will work in this age group. Finally, the Pfizer vaccine is to be given as two doses separated by 3 weeks while the Moderna vaccine is given as two doses separated by 4 weeks; efficacy was tested by Pfizer beginning 1 week after the second dose and by Moderna beginning 2 weeks after the second dose. These differences may not reflect actual differences in the two vaccines, simply different protocols instituted for studying them. In sum, it looks as though the two agents are very similar except for differing refrigeration requirements. 

Quite apart from the biochemistry of these vaccine candidates and the data on their efficacy, what do we know about Pfizer and Moderna? 

Pfizer is the Goliath of pharmaceutical companies. As of March, 2020, it was the largest drug company in the world, as measured by revenue, with annual revenues of $51.75 billion. It has experience in producing vaccines and in recent times was responsible for the development of one of the major pneumonia vaccines. But Pfizer is also a leading offender among the major drug companies in unethical and illegal behavior. In 2009, it achieved notoriety for the largest settlement ever made by a drug company with the Department of Justice: It agreed to pay $2.3 billion for fraud involving the atypical antipsychotic drug Geodon and the painkillers Bextra and Lyrica. It would lose the distinction in 2012, when GlaxoSmithKline settled with the DOJ for $3 billion. 

Despite signing a “Corporate Integrity Agreement” in 2009, a quick internet search reveals that Pfizer continued to engage in bad behavior: in 2011, it paid $14.5 million for the illegal marketing of Detrol; in 2016, it paid $784.6 million to resolve a lawsuit involving Medicaid fraud; in 2018, Pfizer paid $23.85 million to resolve a suit over Medicare kickbacks. It’s worth noting that most of the big pharmaceutical companies have engaged in fraud, including such names as Johnson & Johnson, Eli Lilly, Abbott, Novartis, and Merck. They seem to regard playing fast and loose with the rules as part of doing business.

If Pfizer is the Goliath of the industry, Moderna is the David of the industry—or was until it went public in 2018, raising $604 million through the sale of its shares and gaining a valuation of $7.5 billion despite never having brought a product to market.

Moderna began as a small biotech startup in 2010 and has focused on mRNA vaccines since its inception. Questions have been raised about the integrity of the company in light of its culture of secrecy and the high-stress environment created by its CEO. 

Some have even wondered whether Moderna would be the next Theranos, the unicorn ultimately exposed as a fraud, a story detailed in the chilling account by WSJ investigative journalist John Carreyrou in “Bad Blood: Secrets and Lies in a Silicon Valley Startup.

Moderna has partnered with NIH (specifically the National Institute of Allergy and Infectious Diseases) in its COVID-19 vaccine project. Hopefully, the involvement of a highly reputable, not-for-profit, academically oriented organization has provided a layer of oversight to the drug company.

So far, the data from both the Moderna/NIH trial and the Pfizer/BioNTech trial look very auspicious (BioNTech, by the way, is a German company devoted to developing immunotherapies, principally as treatment for cancer; it has partnered with Pfizer for years in a thus far unsuccessful effort to produce an mRNA vaccine against influenza). Let’s hope that the record of American Pharma in general, and the questionable past behavior of both principal companies in particular, prove irrelevant to our health.

November 16, 2020

Vaccine Mania

Last Monday, the public woke to the news that the COVID-19 vaccine developed by Pfizer and BioNTech, which has been undergoing testing since the end of July, appears to be working. That is very good news for older people, who have been hardest hit by the coronavirus epidemic, as well as for the younger population, which is bearing the brunt of the current surge in cases. And the news is very timely, as the cumulative number of cases in the U.S. is now over 11 million, with the number of new cases every day higher than ever before. But what, exactly, do we know about how effective this vaccine is likely to be?

The statistic that is cited in the news reports is that to date, the vaccine is 90 percent effective. What that means is that among the 94 people enrolled in the Pfizer/BioNTech study who were diagnosed with symptomatic infection, only 10 percent or about 9 people had received the vaccine; the other 90 percent or about 85 people had been given placebo. This is very encouraging, since the clinical trial enrolled 44,000 volunteers, half of whom received active vaccine and half of whom received placebo: it is very unlikely that such a large differential could have happened by chance. On the other hand, there’s much we don’t know.

We don’t know, for instance, whether the 90 percent effectiveness rate will hold up in all age groups. The study population does include older individuals—the plan was to try to ensure that 40 percent of those enrolled would be over age 55, though it’s unclear what percent would be in the highest risk group, those in their 80s and older. But we don’t know anything about the age or other risk factors of the 94 people who were diagnosed with coronavirus. Since older people todare being far more risk averse on average than their younger counterparts, it’s possible that none of the 94 people with infection identified so far are older adults.

We also don’t know whether the vaccine protects people against developing asymptomatic infection. From a clinical perspective, it’s more important to know whether the vaccine prevents people from developing symptoms, but from a public health perspective, we would like to know whether the vaccine keeps the virus at bay just enough so they remain asymptomatic but not enough to prevent them from transmitting the disease to others. Since asymptomatic transmission accounts for many cases today, it would be desirable to know whether the vaccine allows people to become asymptomatic carriers. We are not going to know the answer to that question as the study protocol does not call for enrollees to be tested for COVID-19 unless they develop symptoms.

Finally, we don’t know how long immunity will last, assuming the promising early results are maintained when the study is completed, which will happen once 164 subjects have been diagnosed with COVID-19 (the pre-specified endpoint of the study). 

What does all this mean for everyone who is eagerly awaiting a vaccine to end this long period of isolation, anxiety, and loss? If the final data, when evaluated by the FDA, possibly by early December, do lead to approval and licensing of the vaccine, older people should be vaccinated as soon as possible—assuming the age-specific effectiveness holds up. 

How will life change after you have been vaccinated? First, it should be stressed that “being vaccinated” means receiving 2 injections, 3 weeks apart. The vaccine effectiveness is being measured starting one week after receipt of the second dose, so you cannot expect protection until one month after your first shot—and you should be sure to get both shots. Second, while 90 percent effectiveness is pretty good, it’s not perfect. No vaccine is perfect, so don’t wait around for a better one. While you will face a much smaller risk of becoming sick with Covid-19 if you have been vaccinated than if you have not been, how likely you are to encounter the virus will depend on how widespread it is in the surrounding community. If, to take the extreme but unfortunately not entirely improbable case in which the rate of infection in the community goes up ten-fold, then if your risk by virtue of vaccination goes down ten-fold, the net improvement is zero. Of course, if the rate in the community goes up by a factor of ten and you haven’t been vaccinated, your risk also goes up by a factor of ten. In short, you are much better off with the vaccine than without it, but how much better off you will be will be determined by what is going on around you.

So, yes, there is good news about vaccines and yes, you should get the shots as soon as they are available, assuming the early results are confirmed and apply to older people. But don’t throw out your masks and don’t expect to go to movies and concerts or other large indoor gatherings just yet.

As I prepare to publish this blog post, news is breaking about a second vaccine made by the pharmaceutical company Moderna in partnership with NIH. More to come about these results in my next post….

November 01, 2020

The Corona Century: Looking Backward, Looking Forward

For over, 50 years, epidemiologists had been expecting “the big one.” Like earthquakes in California, influenza epidemics have become an inevitable part of the landscape. From year to year, influenza mutates; every so often the strain is particularly virulent and it produces a world-wide pandemic, as happened in 1918 and, on a smaller scale, in 1957, 1968, and 2009. Every year, scientists scrutinize the prevailing type of influenza, anticipating that one day we will see the resurgence of a virus as virulent as the one that killed upwards of 50 million people in 1918-1919. Granted, we have vaccines today that prevent or attenuate many cases of the flu, we have antiviral medications with modest degree of efficacy against influenza, and we have sophisticated supportive respiratory treatments such as ventilators, none of which were available in 1918. As a result, any new influenza pandemic is unlikely to be as devastating as its counterpart 100 years ago—but nonetheless, could wreak havoc in our globalized world. So, it was very surprising when, in March, 2003, scientists in search of the causative agent of the newly described respiratory illness known as SARS (Severe Acute Respiratory Syndrome) peered through their electron microscope and discovered, not influenza, but corona virus.

Coronaviruses had first been identified in the 1960s; they were known to infect cattle, pigs, rodents and chickens; in humans, they were associated with about fifteen percent of colds, but not with any more illnesses. But there it was, with its characteristic crown-like ring of proteins—the agent responsible for the mysterious disease that had killed clusters of health care workers, families, and residents of an apartment complex, principally in China and Hong Kong.

Once the genetic identity of the virus had been established, the race was on to figure out where it came from. It was pretty clear that the virus had jumped species, making SARS a “zoonosis.” What species it came from was never definitively established, though palm civets and raccoon dogs sold in the wild meat markets of Guangdong province, China, to consumers eager for an “exotic” meal are the leading candidates. Growing evidence suggests that the true animal reservoir of the SARS virus (SARS-CoV-1) is the bat, with animals such as civets serving as an intermediary.

Due to good epidemiologic practice, the biology of SARS-CoV-1, and luck, SARS disappeared. The World Health Organization (WHO) announced the containment of the epidemic in early July, 2003, less than four months after it first issued an international alert about the dangers of the disease, and less than a year after it first appeared in China in November, 2002. A total of 8098 people developed the illness, of whom 774 died, or just under 10 percent.  All told, the virus appeared in 39 countries. Only China, Hong Kong, Singapore, and Canada had 50 or more cases each. The world breathed a sigh of relief; epidemic prevention programs were developed on paper—and shelved.

And then, in 2012, coronaviruses were back. Or rather, a new coronavirus made its debut: MERS-CoV (for Middle East Respiratory Syndrome). Originally found in Saudi Arabia, it soon travelled to the rest of the Middle East. And stayed there, with the only significant outbreak anywhere else in the world found in Korea in 2015 after the index case had travelled to the Middle East. Unlike SARS, MERS has never disappeared. It remains endemic in the Middle East, where it kills 35 percent of those it infects. Its animal reservoir is probably also a bat, but from bats it infects is camels, and from camels it reaches people. By limiting contact with camels and using case isolation and contact tracing, the total number of confirmed cases in the last eight years is only 2500. More lethal than its SARS-CoV-1 cousin, but less easily transmitted, MERS put coronavirus firmly on the map as a pathogen to be reckoned with, but a relatively minor one, compared to, say, the viruses causing Ebola or AIDS.

Until November, 2019, when yet another atypical pneumonia appeared in China, an illness that would prove to be caused by another coronavirus, this one dubbed SARS-CoV-2. The rest is history, although history that is still unfolding. As of October 30, 2020, according to WHO-COVID Dashboard, there have been a total of 44.59 million cases worldwide, with 1.18 million deaths.  In the US alone, there have been 8.83 million cases and 227,045 deaths. The pandemic is far from over, with the US reporting 81,599 new cases per day. This latest variant of the coronavirus has proved far more successful than its relatives: it seems to have found the ideal balance of transmissibility and lethality, which has enabled it to achieve far more extensive community spread than any previous coronavirus. COVID-19 (the name given to the disease caused by SARS-CoV-2) kills roughly 2.5 percent of those who are diagnosed with the condition, less than SARS (10 percent) and much less than MERS (35 percent), though in all three cases, the mortality is far higher in individuals over age 65. In addition, it ingeniously developed the ability to spread from asymptomatic hosts, allowing it to escape prompt detection and thus limiting the effectiveness of isolation to contain its spread.

Supported by governments and the WHO, several pharmaceutical companies along with university research labs are scrambling to produce a safe and effective vaccine. But with cases of COVID-19 continuing to rise in many parts of the world including the US and Europe, the prospects for an end to the pandemic any time soon are not good.  Several nations have reintroduced lockdowns: France just announced it would shut down from October 30 until December 1 and Germany declared a partial shutdown for roughly the same period. With the whole world suffering from pandemic fatigue—except, perhaps, Taiwan, which just celebrated its 200th day in a row without a single locally transmitted COVID case—it’s hard to even think about life-after-COVID except in terms of “going back to normal.” Odds are that when the disease finally goes into retreat, we will breathe a collective sigh of relief and not want to think about viruses. But that would be a grave mistake.

The current century has already seen three coronavirus epidemics, each with a different variant of this wily microorganism. Most likely, all three normally live in bats and jumped from bats to non-flying mammals and from those mammals to humans. Coronaviruses are RNA viruses, known for their extraordinarily high mutation rates—as much as a million times higher than human mutation rates, which means they will continue to develop new variants. And these new variants will now and then develop the capacity to infect people, both because humans have encroached on the territory of animals with whom we previously had little contact and because global warming drives animals out of their traditional habitats and into new arenas that are occupied by humans. The really successful ones, like COVID-19, will be transmissible from asymptomatic individuals. They will have the ability to spread to other humans quickly, without or before killing their new human host. And then they will be spread by humans from person to person, from household to household, from country to country, from continent to continent.

In short, there is no reason to believe that even if we manage to kill or contain SARS-CoV-2, we will have seen the last of the coronaviruses. However appealing it will be to resume normal life, we must not let down our guard. We have to begin now to plan for the next outbreak. We must be sure to learn from our experiences. That means, first and foremost, taking basic preparedness measures such as stocking up on personal protective equipment. It means replenishing the supply of masks and gowns, even if we go for ten years without an epidemic, just in case. 

Planning for the future, as explained by public health lawyer Lawrence Gostin, entails investing in a robust public health system. Such a system must be able to institute traditional measures such as quarantine of those exposed to disease, isolation of cases, social distancing, and mask-wearing. We have to support scientific research so that new pathogens can be identified, tests developed, and treatments tested in a timely fashion. We must restore the FDA and the CDC to their former grandeur, two organizations that, until the current pandemic, were the envy of the world because of their sophistication, wisdom, and integrity. We have to engage in surveillance, constantly monitoring bats and other species for new diseases. 

We must recognize that we live in an interconnected world, which means collaborating with other researchers and laboratories across the globe, including those of China and of the World Health Organization. And when a new, disease-causing virus appears, we need to demand transparency from our leaders and our scientists: an informed public, armed with the tools of public health and the fruits of medical science, is crucial to combatting the threats that will inevitably appear. 

October 29, 2020

Vote: Your Health Depends On It

Earlier this month, the prestigious New England Journal of Medicine took the unprecedented step of publishing a political position paper in the name of the entire editorial board. Entitled “Dying in a Leadership Vacuum,” the journal urged Americans to vote out our “current leaders.” They based their argument on the mismanagement of the Covid-19 pandemic by America’s political leaders, naming no names but asserting that “when it comes to the response to the largest public health crisis of our time, our current political leaders have demonstrated that they are dangerously incompetent. We should not abet them and enable the deaths of thousands more Americans by allowing them to keep their jobs.”

While the disastrous handling of the pandemic is the most egregious failing of President Donald Trump, Senate Majority Leader Mitch McConnell, and others who could have made a difference, it is not the only area where our leaders promoted misguided health care policy—with disastrous consequences. I argued in an earlier post that “Trump is Bad for Your Health.” Today, as we approach the end of election season, I am going to spell out why Trump, Pence, their appointees (such as Alex Azar, Secretary of Health and Human Services), their Republican supporters in the House and the Senate, and fellow travelers in state governments (both legislators and governors), will be bad for the health of all Americans, older Americans in particular. It’s not just the pandemic performance that’s the problem: it’s the limitations on access to insurance, the roll-back of regulations that protect the environment, and the attacks on Medicare and Medicaid. 

Limiting access to health insurance: One of the major “accomplishments” of the Trump administration and endorsed by Republican legislators is its relentless attacks on the Affordable Care ActThe administration eliminated the “mandate,” the tax penalty on those who do not purchase health insurance. The mandate is an important part of what allows the ACA to work without driving up the cost of insurance: the fundamental principle of insurance coverage is that it works by distributing the risk over a large population; if people can opt out, only those who are sick will remain insured, raising the cost for everyone. And indeed, with the end to the mandate, health care costs have risen—making this a leading issue for the electorate, young and old. 

Rollbacks of environmental regulations: As of October 15, according to the NY Timesthe Trump administration has rolled back or is in the process of rolling back almost 100 environmental regulations. Twenty-one involve air pollutants (plus 5 in progress); six involve water pollution (plus 3 in progress); and six involve toxic substances and safety (plus 2 in progress). Estimates are that these changes will result in thousands of extra deaths per year, affecting older people as well as those who love and care for them.

Attacks on Medicare: just this month, Trump issued an executive order designed to promote the privatization of Medicare. Ostentatiously and misleadingly titled “Protecting and Improving Medicare for Our Nation’s Seniors,” the order calls for shifting costs to beneficiaries, limiting choice of providers, and moving more and more patients into the private sector by joining Medicare Advantage Plans. 

Limiting Medicaid: among the many ways in which the Trump administration has undermined the role played by Medicaid in providing health care is a rule allowing states to cap Medicaid spending for poor adults. Through its endorsement of what are essentially block grants, the federal government is enabling states to reduce health benefits for those who gained coverage to Medicaid thanks to the ACA. In 2018, 12.2 million people were dually eligible for both Medicare and Medicaid. In addition to opting to cut back benefits under Medicaid, states have the option of refusing to allow Medicaid expansion. This is an approach authorized by the ACA that enables the near-poor to receive health insurance through Medicaid. To date, the governors and legislatures of 39 states (and the District of Columbia) have accepted Medicaid expansion; 12 states have not.

Regardless of where you stand on issues such as taxes, immigration, and reproductive rights, whatever your views on foreign policy, your health and that of your children and grandchildren is too important to allow supporters of Trumpian policies to remain in office. Whether they are found in the federal government (as senators, representatives, or in the executive branch) or state government (as legislators or governors), vote them out. Do it now. 

October 16, 2020

Lock 'em up!

            A provocative, contrarian position paper (somewhat ostentatiously and bizarrely entitled by its authors a “declaration”) is creating a stir by advocating “focused protection” as a means of dealing with the Covid-19 pandemic. The strategy of “focused protection” as defined by the 3 principal architects of the “declaration” recommends 3 different approaches for 3 different segments of the population: for those at highest risk of death from Covid-19, individuals over 85, they recommend a lockdown; for those at moderately elevated risk, including those who are “retired” (aka people over age 65), they advocate a “safer at home” policy—delivery of groceries and other essentials, and staying home  except for socially distanced outdoor visits with friends or family; for those under 65, they suggest a resumption of normal activities. This algorithm, they argue, would allow the development of herd immunity in the general population by assuring that roughly 70 percent of them be allowed to contract the virus, leading to the end of the pandemic.

            Scathing critiques of this proposal are appearing daily. They discuss issues such as the failure to take into account the burdens of Covid-19 short of death (for example, the long-term sequelae that have increasingly  been reported) and the ethical and practical problems of effectively locking up all older people who live in congregate housing of any kind, not to mention the ethical and practical problems of vastly restricting the activities of everyone over age 65 who doesn’t live in congregate housing. These are legitimate concerns. I’m going to add to the growing list of critics by focusing on two others: the ageism of the proposal and, what is more surprising, the failure to recognize that a rare event that afflicts a large number of people produces a commensurately large number of casualties.

            First, ageism.  The authors of the proposal never explicitly acknowledge that the total population over age 65 in the US is now over 53 million people. This number doesn’t include the millions of people who are in the high-risk category, who would also be locked down, who are under age 65 but have important underlying health conditions. The authors seem to imagine that the most vulnerable individuals, those over age 85, account for most of the excess deaths and that all of them live in nursing homes. In fact, only 4 percent of the elderly population live in nursing homes, or about 1.3 million people. The authors also seem to assume that limiting contact by older individuals with the rest of the world will prevent them from becoming infected; they have apparently forgotten that the effectiveness of sequestration depends on the prevalence of the disease in the surrounding community: if all the nursing assistants and grocery delivery people are allowed to get sick, then their chance of transmitting the virus, even with relatively limited contact, will go up.

             Perhaps the lead authors of the paper, all of whom are under age 60, assume that everyone age 65 or older is superannuated. They should be reminded that fully half of the members of the US Senate are over age 65, as of course is the current president and his challenger. Not only do many older people work (16.4 percent, or 8.69 million), but the 65+ set account for a disproportionate share of consumer spending. How will the rest of society be able to “go about their business” without older people to come to their restaurants, stores, and performance venues? And parenthetically, if the 8.69 million people over age 65 who are still working are exhorted to behave just like their younger counterparts, i.e. to “go about their business,” and even assuming that most of these individuals are 65-74 (though this is not strictly true—14 percent of senators, for example, are over age 75), then the projection is that about 152,000 of this group would also die of Covid-19).

            Second, a small number multiplied by a very large number can be a large number. Let’s look at the segment of the population among whom the “declaration” suggests the virus should run rampant. Americans aged 55-64, like their younger counterparts, are advised to go about  unfettered by regulations. As of 2019, this group included 42.44 million people. If herd immunity is to be achieved, an estimated 70 percent of them would have to contract Covid-19, or 32.68 million people. Now here’s the tricky part. We need to know what fraction of people in a given age group are likely to die from Covid-19. The number that is commonly cited is the case fatality rate, or the fraction of people with documented infections who die. But what we really want to know is the infection fatality rate (IFR), or the fraction of people who have contracted Covid-19, whether they know it or not, whether they are symptomatic or not, who actually die from the disease. Computing that rate depends on accurately determining the prevalence of Covid infection in a particular population and the death rate in that group. The best measure I have seen for the IFR for people age 65-74 is 2.5; the IFR for the 75-84-year-old group is 8.5; and the IFR for the 85+-year-olds is 28.3.

            But what about those who are 55-64? Their IFR is .75, so the authors of the “declaration” deem them safe. But if 32.68 million people in this age group contract Covid-19, and .75 percent of them die, then that means, by simple multiplication, that there will be 222,810 deaths in this group alone. A small number (.0075) times a large number (32.68 million) is a pretty big number when we’re talking about human lives. 

             For that matter, why stop with the 55-64-year-olds? Why not consider the 45-54-year-olds? They make up 40.88 million people. If 70 percent contract the virus (after which there should be herd immunity and the virus will vanish), that’s 28.16 million people. The IFR for this group is .068, which translates to 29,708 deaths. Is that acceptable?

            To determine what number of deaths is too many, some commentators have compared the numbers to flu deaths; others have compared them to automobile deaths. The fallacy is to assume that either you open society completely (to selected age cohorts) or you have a complete shut-down. That’s no more accurate than assuming that either people are allowed to drive cars and die in automobile accidents or they aren’t allowed to drive and no one dies. The reality for driving is that there are some mitigating steps we can take, such as seatbelt laws and speed limits on roads, which will significantly decrease the risk of death. In the case of Covid-19, mitigation means exactly what the majority of public health experts currently advocate: masks, social distancing, limiting the size of indoor gatherings, and substituting work at home for work in the office whenever possible. 

            When scientists band together to make an argument that is intended to influence public policy, they write a “position paper” or a “white paper” or an “open letter.” The “Great Barrington Declaration” reveals in its very name that it is something different. It is an ethical perspective masquerading as a technical brief. The authors claim their case for what to do in the setting of the pandemic arises logically from the data. In fact, their strategy, like all strategies for dealing with the outbreak, requires balancing personal freedom and the social good. The “declaration” implicitly assumes that the quality of life of older people is of no consequence and that a society has no special responsibility to its most vulnerable members. It dismisses the anticipated huge amount of death and disability among people under 65 by sleight of hand. Even if this policy could effectively be implemented—if allowing the virus to multiply unchecked would not overwhelm the health care system, causing people suffering from non-Covid conditions to suffer, if older people sheltering in place would remain uncontaminated as the disease becomes rampant in the workers who bring them their food and other services—this is not a policy that most Americans can endorse. The moral fiber of the American people may have been frayed in recent years, but it has not broken entirely.

October 05, 2020

Should Your Doctor Lie to You?

            The nation is riveted by President Trump's illness: whether we hate Trump or love him, we want to know how he is faring with Covid-19. We want to understand what this disease looks like in an elderly man with at least one chronic health condition. Unfortunately, what we have been told by the physicians involved in Trump's care has been marred by commissions, distortions, and downright lies.

            There is a long history of presidents wishing to mislead the public about their health and of their physicians colluding in the deception—Woodrow Wilson’s stroke was concealed, Franklin Roosevelt’s high blood pressure and heart problems were downplayed, and John F. Kennedy’s Addison’s disease and chronic back pain were not fully disclosed. But however objectionable we may find this public lack of transparency, President Trump’s personal physician has claimed a different reason for being less than forthcoming. He asserted that he had understated the seriousness of his patient’s condition because he “didn’t want to give any information that might steer the illness in another direction.” That is, Dr. Sean Conley didn’t want his patient to know that his low oxygen levels and high fever were worrisome, so he lied about his condition. Telling the truth, he was asserting, could harm his patient. But is that true?

            Truth-telling in medicine has been the subject of extensive ethical analysis and of clinical study. The bottom line is that while doctors used to routinely lie to their patients in the belief that they were protecting them, for the last 50 years the standard of care has been to keep patients informed to whatever extent they wish and, based on their accurate understanding of their situation, to engage them in decision-making about treatment.

            The change in practice occurred in the sixties and seventies: in 1961, when a questionnaire was administered to oncologists asking them if they told their patients that they had cancer, fully 90 percent of them said they did not. When the study was repeated in 1979, 97 percent of them said they would tell patients their diagnosis. The earlier view was based on the paternalistic belief that physicians always knew what was best for their patients and on the conviction that if patients knew they were seriously ill they would become depressed and possibly even suicidal. Between 1961, when the first study was conducted, and 1979, when the second study was carried out, western biomedical ethics came into its own as a field.

            Physicians and medical ethicists increasingly recognized that there was often no single optimal course of treatment: several different possible approaches might be possible, each with its own likelihood of benefit and each with its own risks; which approach was “right” for a given patient depended on that person’s preferences and values. One person with a particular type of cancer might wish to undergo treatment with chemotherapy that had a high probability of resulting in serious side effects in exchange for a small chance of life-prolongation; another individual with the same disease might opt for a different treatment that was less likely to cause severe side effects but that offered a smaller chance of life-prolongation. Whenever the choice of treatment depended on values as well as technical expertise, the patient had to be included in the decision-making along with the physician. The principle of beneficence, or doing good, and the principle of non-maleficence, or not doing harm, co-existed with the principle of autonomy, or the right of patient self-determination. 

            Choosing the right treatment for a particular patient, in many cases, required that the patient know the truth about his diagnosis. Without knowing the facts, he couldn’t possibly participate in a conversation with his physician about treatment options. Moreover, growing evidence indicated that when patients are engaged in their own health care, they do not become morbidly depressed or overtly suicidal; on the contrary, health outcomes improve. 

            The regrettable example set by the president’s personal physician notwithstanding, you should expect honesty from your doctor. Yes, you should expect that your doctor will have the communications skills necessary to impart bad news sensitively. Trust is at the core of the doctor-patient relationship, and trust cannot be built on a lie.