April 05, 2021

Covid Cathy Bites the Dust

Now that just under half of older people have been fully vaccinated against Covid-19 and only about a quarter have not received any vaccinations at all,  the burning question is, what can vaccinated people do safely? 

 

The answer comes in two parts: what can vaccinated people do that does not jeopardize their own health and what can they do without risking harming others? The CDC has weighed in on this, focusing principally on the first issue, safety of the individual. Their guidance includes the recommendations that those who are fully immunized (who are at least two weeks out from their second shot) can visit other fully immunized people indoors without masking or social distancing and that they can travel without self-quarantining upon arriving at or returning from their destination.

 

To answer the second question, the public health concern, we need to know whether a vaccinated individual can be infected with Covid-19, remain asymptomatic, and transmit the disease to an unvaccinated person. Physicians have been concerned that while the antibody response to vaccination is highly effective in squelching the virus in the lungs, what’s not clear is whether it’s also effective in killing the SARS-Cov2 virus in the nasal passages. If so, vaccinated individuals could indeed be surreptitious sources of disease, like the notorious Mary Mallon, who was an asymptomatic carrier of the bacteria causing typhoid fever, salmonella typhi. Could asymptomatic Covid carriers act like “Typhoid Mary,” perhaps earning the nickname Covid Cathy? At last, we have very reassuring data addressing this issue.

 

The current issue of MMWR, the weekly journal published by the CDC, reports on the experience of just under 4000 people during the period mid-December and mid-March, 2479 of whom received two shots of either the Pfizer or Moderna vaccines and 989 controls who remained unvaccinated. They also report on 477 people who received one dose, but for simplicity, I will ignore these partially immunized individuals. The investigators leading this small study took one crucial step that has previously been largely lacking: they tested all the participants weekly using the gold standard polymerase chain reaction (PCR) test for the SARS-Cov2 virus—whether or not they had been vaccinated and whether or not they reported symptoms. What did they find?

 

The outcomes are reported based on “person-days” since the group who were vaccinated got their shots at varying times and therefore differed in the number of days they could have become infected. They found that among the fully immunized, the number of new positive tests/1000-person-days was 0.04 whereas among the unvaccinated, it was 1.38. The bottom line: once you are fully immunized, you are far less likely to test positive for Covid-19 than if you have received no vaccinations.

 

The study also found that only 23 percent of the people who did develop an infection got sick enough to see a physician, only two people were hospitalized, and no one died. 

 

Until this admittedly small but carefully conducted study appeared, it seemed to me that while vaccinated people could feel personally quite safe, they had to exercise caution in the interest of public health. It wasn’t really true that vaccinated people could socialize indoors with other vaccinated people—until the issue of Covid Cathy was resolved, they had to be worried about about any unvaccinated household contacts their friends might have, lest an asymptomatic carrier inadvertently transmit the virus to a friend, who while also asymptomatic, manages to give the virus to an unvaccinated household member. Now it increasingly looks as though this theoretical concern is not, in practice, of great consequence. 

 

Just because fully vaccinated individuals are reasonably safe today doesn’t mean they will necessarily remain safe tomorrow. Vaccine effectiveness is calculated based on how much less likely a vaccinated person is to get the disease than an unvaccinated one. But if the disease is running rampant in the surrounding community, that is, if it is quite common among the unvaccinated, then while the relative risk of the vaccinated will be unchanged, the absolute risk will go up. And if new variants appear against which the vaccines offer only limited protection, then the relative risk itself will be affected. 

 

So, keep an ear to the ground—monitor how common the virus is in the community where you live and pay attention to the type and pervasiveness of viral variants. If the situation is stable, enjoy your freedom.

March 04, 2021

How I Taught My 95-Year-Old Mother to Make and Receive Video Calls--Most of the Time

My 95-year-old mother has been using a computer for email since our then teenage son arranged to gift her his old computer so he could get a new one. That was 25 years ago. But like most people in her age cohort, she has never been comfortable with the technology and has trouble learning anything new related to the computer. The difficulty has gotten worse over time along with her memory. But when Covid hit and visits to the independent living complex where she lives were restricted and then eliminated, the limitations of a landline telephone became all too evident. If my mother could make and/or receive video calls, she could communicate with me, with her three grandsons in California, and with friends. But using the video technology proved to be an endless source of frustration. We tried FaceTime, we tried Skype, we tried Zoom. Nothing worked. 


Now, after months of trial and error and refining the approach, I’m pleased to report that my mother can receive—and sometimes initiate—FaceTime calls. I’m so pleased that I’m going to use this blog post to describe in as much detail as I can recall every step necessary to accomplish this feat, suspecting as I do that others may find themselves in a similar predicament.

                                                Happy geriatric iPad user 
                                                (not my mother)

Step 1: Choose an appropriate device. I purchased my mother a new 10.2 inch, 32GB iPad. It’s portable, so she can use it while sitting in her favorite recliner. The screen is big enough so that people’s faces appear almost life-size and photographs are easy to see. In principle, Apple products are user-friendly, though as it turned out, my mother is a genius at outwitting the human-computer interface gurus at Apple by coming up with ways to make the system fail. Nonetheless, I think the iPad was probably as good a choice as any and better than some. The rest of the steps below apply primarily to an iPad.


Step 2: Obtain a cover that automatically turns the device off when it is closed and turns the device on when it is opened. Turning the iPad on manually was an unnecessary obstacle.


Step 3: Disable password protection for turning the device on. This may be a bit risky, but my mother was having trouble remembering her password. I “enrolled” her in touch ID, but she usually managed to put her finger in not quite the right place, so it did not work reliably. Nothing is more frustrating than being unable to even turn the thing on.


Step 4: Go to Settings, Accessibility, Assistive Touch. This setting allows my mother to use the iPad even though she has poor fine motor control and touches the screen erratically.


Step 5: Label the home button. I stuck an arrow on either side of the home button to help my mother find it. The device is designed with a very slight indentation signaling the home button, so slight that it’s hard for 95-year-old eyes to see. ➡️ ⏺ ⬅️


Step 6: Make sure Siri is disabled. I initially thought it would be easiest if my mother used Siri to make calls, simply saying “hey Siri, call Muriel Facetime video.” Wrong. She would leave out “FaceTime” or leave out “video” or forget to start with “hey Siri.” She felt compelled to speak in grammatically correct sentences, as though Siri would understand her better that way. When I left Siri enabled, just in case things changed, I found that my mother would sometimes hold the home button down too long and inadvertently invoke Siri, who would helpfully inquire “may I help you?” Having her device suddenly speak really rattled my mother.


Step 7: Put only the most essential icons in the dock. For my mother, this includes the icon for her email, Safari, and for FaceTime video. I’ve recently added the photos icon.


Step 8: Declutter the screen by putting as many of the obligatory icons, the ones you can’t get rid of, on the next screen, not the screen that is opened when the device turns on.


Step 9: Put the handful of phone numbers (with associated names) that are most likely to be used in the FaceTime contacts screen. This way, when my mother taps on the video icon, she will see 4 or 5 names and can choose which one she wants to call. Sometimes she taps on the wrong spot and calls the wrong person, but at least she’s not accidentally going to call Social Security or the Boston Globe, just a different family member from the person she intended.


Step 10: Practice! When visiting my mother, I would get her settled in her recliner with the iPad and call her from another room. For a while she had trouble with the command “slide to answer.” I finally figured out that she was carefully sliding her finger along the words “slide to answer” and assiduously avoiding the green virtual button to the left of the words. Unless she accidentally touched the button, she failed to answer the call. Now I regularly remind her that she needs to slide the button and it works like a charm. Another aspect of practicing is using the system regularly. At one point, my mother was doing great and then we didn’t make any video calls for a few days, by which time she had forgotten about sliding the button rather than the words. Making or receiving a call once a day is probably a good idea.


Sounds simple, doesn’t it? Since it literally took me months to figure this out, I thought I’d pass along what I learned, in case these steps can help someone else.

 

 

February 26, 2021

Pfizer in Practice

This week brought a medical article worth discussing: the New England Journal of Medicine published the results of a study of the efficacy of the Pfizer SARS-CoV-2 vaccine in the real world. The article provides compelling evidence that the vaccine works extremely well.

The data come from Israel, which has been doing a superior job of vaccinating its citizens. As of a week ago, two-thirds of the currently eligible population in Israel had gotten both of the recommended doses (individuals under age 16 and those who have had Covid-19 are not eligible). In Israel, health insurance is mandatory for all permanent residents; they must join one of four healthcare organizations called “funds.” The new study reports data from Israel’s largest health organization (Clalit Health Services) and includes information on a stunning 1.2 million people.

The study’s authors, led by Dr. Noa Dagan, used Clalit's integrated electronic medical record to capture health data for 596,618 people who received both doses of the Pfizer vaccine between December 20, 2020 and February 1, 2021. They then matched them, based on demographic and clinical characteristics, with another group of identical size who had not received any vaccine. Next, they looked at five different outcomes: documented Covid-19 infection; symptomatic Covid-19 infection, Covid-related hospitalization, Covid-related severe illness, and Covid-related deaths. Because the sample was so large, they were also able to collect extensive information about a number of interesting subgroups defined by age or specific co-existing health conditions such as cancer or diabetes.

The article includes an enormous amount of intriguing data. The most exciting results, from my perspective, address outcomes a week or more after receiving the second dose of the vaccine. At that point, the vaccine conferred 94% protection against symptomatic Covid-19 (95 percent confidence interval 87-98), 87 percent protection against Covid-related hospitalization (CI 55-100), and 92 percent protection against severe Covid (CI 70-100).  The efficacy in people over 70 was identical to those in younger individuals, and the rate in people with one chronic health condition such as diabetes was only slightly lower than in people without the condition. 

These numbers strongly resemble the results that Pfizer and BioNTech reported to the FDA in their application for emergency approval.  But, as the study authors point out, Pfizer drew its conclusions based on 44,000 people; the Israeli study is based on 1.2 million people. As a result, when Pfizer calculated the efficacy against severe Covid-19, they drew on a total of 10 cases (one of whom had been vaccinated and 9 of whom had not been); when the Israelis calculated the risk of severe Covid, their estimate was based on 229 cases, vastly increasing the credibility and certainty of the calculation. Moreover, Pfizer’s data was based on the somewhat artificial conditions of a clinical trial: for example, the subjects were all highly motivated to optimize their health and may have regularly worn masks and practiced social distancing; the Israeli study drew on real life experience, in which participants’ behavior reflected community norms.

The new study, like all studies, has its limitations. It excluded people living in nursing homes and medical personnel working on Covid units in the country’s hospitals, arguing that the rate of the disease in their particular communities, i.e. the nursing home or the Covid ward, was highly atypical. The study was performed during a period when the South African variant was very rare in Israel so we cannot draw conclusions about the efficacy of the vaccine against this strain. The information on the ability of the vaccine to prevent Covid-related deaths is limited because of the short follow-up period: there were nine Covid deaths in the fully vaccinated and 32 deaths in the unvaccinated group, but these numbers might change when more time elapses. The data on deaths may also be difficult to generalize as Israel has an unusually low case fatality ratio: in Israel, according to Johns Hopkins' "Our World in Data," is currently 0.7 percent whereas in the U.S. it is 1.8 percent.

Some of the study’s greatest strengths are also potential weaknesses: the “real world” nature of the investigation means it is an observational study rather than a randomized controlled trial, raising the possibility that the differences in outcomes between the vaccinated and the unvaccinated were related to some factor other than their vaccination status. Despite these limitations, the study provides very encouraging information.

The fact that the Israelis could carry out their study sends another message over and beyond the efficacy of the Pfizer BioNTech vaccine. The study could only be conducted because Israel did a good job acquiring and distributing vaccine. Early on, the country developed mass vaccination sites. Since everyone is enrolled in a health plan and the plans all have electronic records, there was no need to waste as much time on bureaucracy as we do in the U.S, where more time is spent filling out forms than on administering the shot. The study could only be conducted because of Israel’s electronic health records, which assured that information about who got what dose when, and the age, sex, and chronic medical conditions of each individual was digitally recorded. Finally, the entire rollout was centrally coordinated, assuring efficiency and consistency: from the outset of the pandemic, the Israeli Ministry of Health collected Covid-related data from all four health plans, negotiated to purchase vaccine from Pfizer, and organized distribution. The good news reported in the NEJM article is a result both of the biological properties of an mRNA vaccine that was designed in record time to deal with an international health crisis of enormous proportions, and of the characteristics of a health care delivery system that can actually deliver.

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.