Is the COVID-19 Pandemic a Traumatic Event? 

What this shared experience tells us about the nature of trauma

A terrifying fear for one’s safety and the safety of loved ones, loss of loved ones, extreme illness and death, unprecedented social isolation, chronic lack of certainty about one’s life and the future. There is no question that the COVID-19 pandemic presents a serious challenge to emotional well-being and even to mental health more specifically. The chronic lack of certainty, mass job loss, and economic hardships on their own are often enough to destabilize people, let alone the fact that we are dealing with a highly contagious and lethal illness to which any of us may fall victim at any time. While it is thus without doubt that the pandemic is a major stressor and potential threat to mental health, does it constitute an actual trauma? 

On the face of it, the pandemic does not neatly fit into models of factors that may lead to the development of post-traumatic stress reactions. For one thing, the pandemic is ongoing and many people’s stress about it has to do with potential future events rather than actual experiences in the past. On the contrary, traditional models of post-traumatic stress response by definition posit that the reaction is in response to something that happened in the past. In addition, most models of post-traumatic stress occur after direct exposure to an immediately life-threatening event. On the other hand, people’s experience of the pandemic is mostly indirect (e.g. via watching the news versus actually experiencing illness and death or near-death) and the stressful events are not immediately life-threatening but are byproducts of the pandemic such as job loss, financial instability, and social isolation. Nonetheless, several studies have already suggested that even under these unusual circumstances people are showing traditional traumatic stress responses to the pandemic. 

There are also particular circumstances related to quarantine that may result in an uptick in traumatic stress responses. Family members who may experience abuse in their homes have experienced an intensification of these behaviors during the pandemic, partly as a result of increased stress and partly as a result of more time spent in the home and fewer outlets available to seek help. In addition, healthcare workers, who have been exposed to some of the most horrifying, heart-wrenching scenes of serious illness and death, may also now be at increased risk of developing post-traumatic stress due to their particular experiences during the pandemic. 

Beyond what we are already seeing, there is reason to believe that traumatic responses to the pandemic may increase over time. In general, in the midst of a stressful event, people tend to go into “crisis mode,” and it is only when things become more calm and they have a chance to reflect that their mental health that they might start to suffer. It is definitely possible that even as a great number of people are already struggling with their mental health in the midst of this pandemic, those numbers might even increase as (hopefully) the pandemic recedes and life returns to a more normal state. A proportion of those people will likely experience some degree of trauma. 

While much remains to be seen about the connection between COVID-19 and trauma, the pandemic is a useful reminder that traumatic events can be slow to unfold, collectively experienced, and even somewhat indirect in nature. It is essential that we be mindful of the fact that even though the pandemic does not neatly fit into our usual notions of trauma, we should be sensitive to the fact that some people might still be experiencing symptoms of post-traumatic stress. This will make it easier to guide more of the many people who are suffering right now to the appropriate form of help. Whether COVID-19 constitutes a traditional trauma or not, the high degree of destruction and uncertainty left in its wake will continue to haunt many people. We must be prepared to help them recover from this terrifying experience of lack of control and persistent fear for their safety and well-being.

Ivermectin: A Popular Science Story

Important efforts are now being made, which we fully support, to help the public become more knowledgeable about and involved with science. It is increasingly clear that misinformation spreads easily among people who are not fluent with the way science works and nearly everyone agrees that a scientifically literate public will help us overcome the alarming spread of mis- and disinformation about health and science we now face.

         Perhaps the most successful example of public advocacy for scientific research we have seen occurred in the 1980s and 1990s when a sluggish research system was pressured to take action to find the causes and treatments for the human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS). That advocacy effort undoubtedly convinced politicians to put more money into HIV research and energized researchers to enter the HIV research field, resulting in the discovery of effective treatments that have made the illness manageable and far less deadly than it was when the AIDS epidemic began.

         Yet we have not come to grips with how to handle the situation when a popular notion about some health topic grips people’s attention even though it may be wrong. The situation with the medication ivermectin is an example of the dilemma between wanting people to become involved in the scientific process and trying to prevent recommendations for actual medical interventions to be made before there is adequate scientific justification for them.

Ivermectin Is An Approved Drug

         Ivermectin can be prescribed in different forms by physicians and veterinarians. The U.S. Food and Drug Administration (FDA) approved ivermectin for the treatment of two parasitic infections in humans, one called strongyloidiasis and the other called onchocerciasis (or river blindness).  It’s discoverers even won the Nobel Prize for their work. It can also be prescribed to people in a topical form for some skin conditions. Veterinarians prescribe it to prevent heartworms and other parasitic infections in animals.       

Ivermectin is an FDA-approved medication for the treatment of parasites in humans and animals. It is unclear at this moment whether it has any role in preventing or treating COVID-19 or any other viral disease.

         It turns out that ivermectin kills viruses in test tubes, including the virus that causes COVID-19, called SARS-CoV-2. That information made some scientists call for tests of the drug in animal models of COVID-19 and in people with the illness to see if the “in vitro” or test tube results might translate into benefit for humans. Almost immediately, however, scientists noted that the concentration of ivermectin needed to kill SARS-CoV-2 in test tubes was far higher than what is typically administered to people with the parasitic infections for which the drug is FDA approved. This raised the possibility that ivermectin could only work in people to treat COVID-19 if it were given in much higher doses than currently approved and that further raised multiple safety concerns.

         Finding that ivermectin does have in vitro antiviral activity does justify carefully studying the drug in humans to see if it could be a treatment for COVID-19, and studies have both been completed and are ongoing. An early clinical trial that was released as a pre-print before peer review showed that ivermectin dramatically reduced mortality rates, but the paper was withdrawn because of reported irregularities. Preliminary results from the large outpatient TOGETHER trial showed no benefits of ivermectin over placebo. Right now, there is a clear consensus among experts that there is insufficient evidence to warrant using ivermectin to prevent or treat COVID-19 in any of its manifestations. The FDA has warned the public against taking it for COVID-19.

Ivermectin and Public Discourse

Somehow, however, ivermectin has emerged into the popular media as a potential “cure” for COVID-19, even prompting legal action to force doctors to administer it. Social media commentators advise that ivermectin does work for COVID-19, either citing anecdotes or cherry-picking studies or both. Some have advanced a kind of conspiracy theory in which pharmaceutical companies are suppressing data that would support ivermectin because it is an inexpensive drug in order to promote the more expensive vaccines instead. The result is that patients with COVID-19 are requesting that their doctors prescribe ivermectin and some people have even resorted to taking veterinary ivermectin, apparently resulting in numerous instances of toxic reactions and calls to poison control centers.

         Physicians, perhaps chastened from their experience with hydroxychloroquine, another “miracle” cure for COVID-19 that achieved immense popular support but has proven ineffective against the illness in clinical trials, are understandably reluctant to prescribe ivermectin to patients regardless of their level of illness severity. Some have taken to making adamant statements that ivermectin categorically does not work for COVID-19.

         That absolute stance is also premature because there are a bevy of clinical trials of ivermectin for COVID-19 now in progress, some with results not expected for months. It is still possible that one or more of them will show a benefit for the drug. Remember that drugs can be tested to prevent the acquisition of COVID-19 or its treatment; they can be tested against mild, moderate, or severe disease; and they can be tested for multiple different types of outcomes, such as whether people with mild symptoms get worse or not or whether the drug decreases the rate of hospitalization or death. A drug might work in only one of these scenarios and still be deemed useful, so there is much yet to be learned about ivermectin.

Rigorous Clinical Trials Still Needed

As with almost all medications that work for something, ivermectin is not without adverse side effects. Doctors are right not to prescribe a drug for which there is no clear evidence of benefit and the possibility of harm. Yet some people seem determined to take ivermectin now, unwilling to wait for the clinical trials that hopefully will resolve the question.

         As scientists, including those who work at pharmaceutical companies, know all to well, many things that work in test tubes do not turn out to work in humans. Hence, merely finding that ivermectin kills viruses in the laboratory, while an important clue, hardly guarantees clinical effectiveness. One could argue that the pandemic is an emergency situation, and we should be extra careful not to withhold potentially useful medications. But even the vaccines, which were given emergency use authorization before full FDA approval, were subjected to rigorously conducted clinical trials before they were released to the public.

         After laboratory confirmation that a drug might have activity against any disease, it must always be tested in rigorously conducted, randomized clinical trials or RCTs, the gold standard for scientific proof that a medication works and is safe. In an RCT, a relatively large number of patients are randomly assigned to receive either the drug under study or a comparator, usually either a placebo or an intervention already known to work. Patients and investigators generally do not know which study participants are receiving the study drug and which are receiving the comparison intervention in order to minimize biased assessments of whether the study drug is working. These trials are usually expensive and time-consuming.

Before committing to doing an RCT, it is often the case that investigators will conduct less expensive but also less rigorous studies of a drug in order to get some early answers about its potential. For example, let’s say a drug works in the laboratory but only at a very high concentration. Before conducting large-scale RCTs of the drug on humans, scientists might do a study in which they administer escalating doses of the drug to people to see if it is tolerated and safe at higher doses. Or scientists might give the study drug to a small number of people without a comparator arm to the study, a relatively inexpensive and more rapid way to get some early information about the drug. If the study drug doesn’t work under those circumstances, it is unlikely to work in a larger study and a lot of time and money can be saved by not proceeding to an RCT. But if it does seem to work in a “quick and dirty” study like that,  it could be due to assessment bias and a full RCT is still required. Unfortunately, as in the case of ivermectin, it is possible to “cherry-pick” such lower quality studies and reach the premature conclusion that a drug works. Once again, scientists are all too familiar with the many instances in which a bunch of low-quality studies suggest an intervention works for some illness, only to be followed by higher quality RCTs that don’t pan out. There are some shortcuts to making the decision that a drug doesn’t work; unfortunately, there are few shortcuts to concluding a new drug is effective, safe, and ready to be prescribed.

How do we balance, then, our desire to support and promote “citizen” science while at the same time ensuring that only rigorously collected evidence properly evaluated by experts is used to make critical health decisions? In fact, we want people to say “hey, what about hydroxychloroquine? What about ivermectin? What about vitamin D?” just as we now recognize that the advocates for more HIV research were crucial in turning the tide against AIDS. But at the same time, we don’t want people to actually take unproven and potentially harmful medications.

We need to find better ways for scientists and concerned citizens to talk with each other about the state of evidence. Citizens need to stay informed and to advocate for research. Scientists need to evaluate the data and push back against premature conclusions. Citizens need to refrain from trying to take unproven treatments. Scientists need to listen to citizen advocates and heed their calls for more research attention to the things that concern them.

Once again, then, we’ll point out that there is insufficient high-quality data to justify prescribing ivermectin for the prevention or treatment of COVID-19. It is possible that studies now being conducted will change that verdict. Physicians should suspend judgement about ivermectin until more data are available, neither prescribing it now nor making blanket statements that it doesn’t work. In the meantime, concerned citizens should carefully monitor research progress, advocate for sufficient research funding to continue to test emerging potential interventions for COVID-19, educate themselves about what constitutes high-quality evidence, and resist falling into the trip of listening to pundits with a political agenda rather than to experts with genuine scientific credentials. We want the public to be involved in science, but not harmed by misinterpreting it.

The Other Pandemic: Erosion of Public Trust, Misinformation and Vaccine Hesitancy

Paul Spector MD

Editor’s Note: This piece is by physician and Critica contributor Paul Spector. It was originally published in Medium in a version very close to this one. We found it to be an excellent review of the vaccine hesitancy problem, both historically and in its present COVID-19 iteration.

Vaccination and opposition to it is nothing new.

Variolation, infecting someone with material from smallpox pustules to create natural immunity, was practiced in Asia and Africa in the 16th century. Cotton Mather, a Christian minister in Boston, promoted the practice in the 1700’s having learnt the technique from his African slave. Despite its effectiveness, Mather was ostracized.

The smallpox vaccination of the late 18th century promoted by Edward Jenner, an English physician, used cowpox. Although successful at preventing smallpox, one of the most feared illnesses with a death rate of 30%, anti-vaxxers of the day called it a foreign assault on traditional order.

In 1910, Sir William Osler, the father of modern medicine, famously expressed his dismay at the irrationality of the anti-vaccinationists by offering to take 10 vaccinated and 10 unvaccinated people into the next smallpox epidemic. The vaccinated group, he said, could care for the unvaccinated when they inevitably succumbed to the disease and arrange for the funerals of those who died.

The death toll for smallpox is estimated at 300 million in the 20th century alone. In 1979, smallpox became the first human infectious disease to be eradicated by vaccination.

Immunization programs have both continued to prove their worth and stir controversy

Tetanus, a bacterial infection without cure, is fatal in 10–20% of cases. About 34,000 newborns died from neonatal tetanus worldwide in 2015, a 96% reduction since 1988, when an estimated 787,000 babies died from the disease.

Polio, a highly infectious disease with a death rate of one in twenty children and one in three adults, often caused epidemics in the first half of the 20th century. In 1952, 3,145 children died in the US. The vaccine, developed in 1953, has nearly eradicated the disease.

Measles, one of the most contagious viral diseases, claimed 2.6 million lives per year globally before 1963 when a vaccine was introduced. Immunization resulted in an 84% decrease in measle deaths between 2000 and 2016 globally, preventing 20.4 million deaths worldwide.

Between the 1940s and the 1970s, antivaccine sentiment in the US receded somewhat due to three trends: huge advances in vaccine science, public awareness of widespread infectious disease outbreaks (measles, mumps, rubella, pertussis, polio) in children, and a baby boom. This golden age of vaccine acceptance resulted in dramatic decreases in outbreaks, illness and deaths.

Ironically, the unrivalled success of vaccination programs contributed to ending its golden age. By eliminating highly visible outbreaks of infectious disease, vaccines diminished public perception of disease risk. Fear of disease was replaced by fear of adverse events purportedly associated with vaccination. In the 1970s, as more vaccines were added to immunization schedules and anecdotal claims of harm were spread by the media, the antivaccination movement was reborn.

No medical intervention has saved more lives or created more conflict than vaccination.

So how are we to understand vaccine hesitancy?

Vaccine hesitancy is defined as the refusal, delay, or acceptance with doubts about vaccine usefulness and safety. It is recognized by the World Health Organization as one of the ten most important health threats in the world today. The determinants of vaccine hesitancy are complex but can be organized around three issues: confidence, complacency (low perceived usefulness), and convenience (perceived constraints to access).

Confidence, the pivotal determinant, derives from trust. To feel confident about the safety and efficacy of a vaccine is to trust science and technology, pharmaceutical manufacturers, the healthcare system, healthcare providers, policy-making government, and the media that informs the public.

A leap of faith, to say the least.

Trust is necessary when a high level of information asymmetry creates an imbalance of power. The vaccine taker does not have the time, expertise or inclination to assess the data. We choose to trust an expert to help make a risk/benefit-based decision about which we have incomplete information. Such a choice assumes that the trusted experts have correctly assessed the situation and have our best interests in mind.

If trust is lost in the vaccine-related players, it will be placed in other influencers, who may be ill-informed, indifferent to vaccination, or against it.

We live in a time when mistrust is the public’s default position. Mistrust of public health initiatives has been fueled by many things including a partisan media, prominent cases where the medical community was wrong, profiteering pharmaceutical companies, failure of regulatory agencies to protect the public, and an erosion of faith in health experts.

A Gallup poll this year examining confidence in institutions found that less than half of Americans (44%) have a great deal or quite a lot of trust in the medical system and 21% have very little. In 1975, 80% of the population had a great deal or quite a lot of confidence in the medical system and only 4% said they had very little. Loss of faith in the medical system over this period outstrips all other institutions studied.

Vaccine hesitancy also reflects a political divide. Although there is nothing inherently pro or anti-vaccination in Democratic or Republican ideology, it quickly became a polarizing issue. Whether you take COVID seriously, wear masks or get vaccinated has become a way of affiliating with one party or the other.

A poll conducted by the Pew Research Center in July 2020 found that 46% of Republicans saw COVID as a threat to US health versus 85% of Democrats. A Gallup survey at that time reported 94% of Democrats always or very often wore a mask outside the home while 46% of Republicans said the same. Recent polling by the nonpartisan Kaiser Family Foundation found that 75% of Democrats have already been vaccinated vs 41% of Republicans.

Community (also known as herd) immunity is attained when a large proportion of a population is immune to a disease. This can be measured on a global, national or community level. Immunity can be obtained either by making antibodies after an infection or from a vaccine. The percent of a population that needs to be immune to reach herd immunity varies by disease and how contagious it is.

Because measles spreads so easily, 95% of a population needs to be vaccinated to achieve herd immunity. In 2019, a measles outbreak in Clark County, Washington occurred when the vaccination rate in public schools dropped to 77%.

Early in the pandemic, community immunity was estimated to require 60–70% immunity in the US. As more infectious variants have taken hold that estimate has increased to 85%. The race between vaccines and variants is ongoing.

The devastating effects of COVID-19 (3.5 million deaths as of June 1, 2021) has sown fear among the public and healthcare workers. This has lent itself to changes in clinical and personal behavior, much of which is not evidence-based and often detrimental.

The Choosing Wisely Initiative for COVID-19 was created to promote a dialogue between patients and doctors about how to avoid unnecessary practices and choose interventions that are evidence based, safe and necessary. Their 18-member task force is drawn from the fields of public health, epidemiology, general practice, primary care, infectious disease, virology, critical care, internal medicine, pulmonology, pediatrics, oncology, health economics, clinical research, implantation science, and health policy. Patient and civil-society representatives contributed.

It has drawn up a list of things clinicians and patients should question as well as 10 recommendations, 5 for the general public and 5 for physicians. Here are the recommendations for the public.

1. Do use well-fitting masks appropriately, whenever in public.

2. Do avoid crowded places, especially while indoors.

3. Do get tested if you have symptoms of COVID-19, and isolate yourself at home if symptoms are mild.

4. Do seek medical help if you have difficulty breathing, or your oxygen saturation drops to less than 92%.

5. Do get vaccinated as soon as you are eligible, and even if you have had COVID-19 in the past (although there could be a change in expert guidelines on vaccinating previously infected people as more data are accumulated).

Vaccines exist in a very different mindset than other medicines. An individual takes a medication when she is sick and wants to get better. A vaccine is taken in health (or without the disease targeted by the vaccine) in order to remain well and, as importantly, to protect others. Prevention of illness by vaccination requires a willingness to consider future risk to yourself and those around you.

Vaccines must work on both the individual and societal level in order to be effective.

In this way, vaccine acceptance reflects a social cohesion based in sufficient trust of public institutions and a willingness to participate in creating a public good. We therefore should not be surprised at the prevalence of vaccine hesitancy. Numerous studies have documented the conditions that foster social cohesion: low levels of conflict based on wealth/income disparity, ethnicity, race or gender, impartial law enforcement, a sense of engagement in a common enterprise, facing shared challenges and a belief that they are members in equal standing of the same community.

We live in a time when these conditions seem like a utopian dream. This virus has highlighted how divided and unequal we are. Attempts at increasing vaccination rates through educational measures based only on a knowledge-deficit model will not suffice.

51% of Americans are fully vaccinated vs 23.6% of the world population and 1.3% of people in low-income countries. We have long way to go.

Perhaps, among the many ways the virus has transformed how we live, it will remind us that we are in this together. COVID is blind to gender, race, ethnicity, wealth and political persuasion. We need to adopt a similar stance.

Long Covid and the Brain

A 63-year-old woman comes to the emergency department one evening complaining of crushing chest pain that radiates down her left arm. On physical examination she appears in acute distress and her heart and respiratory rates are elevated. The emergency room physician suspects she is having a heart attack. Her electrocardiogram (EKG) and the results of a blood test called troponin  confirm the diagnosis and the woman is moved to the cardiac care unit for further treatment.

         Medical diagnoses are based on many factors; in the above scenario, several, including the patient’s report of symptoms, physical examination, and laboratory testing, all come together to confirm a likely diagnosis that leads to the initiation of a treatment plan. In the case of a heart attack, objective biological markers—the EKG and blood test—make the diagnosis initially suspected on the basis of the patient’s subjective report relatively straightforward and reliable. Unfortunately, there are many instances in which making a diagnosis is much more difficult or even impossible because there are no objective markers to confirm a subjective report. This may be the case with the illness now called Long Covid.

         Around the world, at the time of this writing, about 1.8 million people have recovered from COVID-19. Studies suggest that at least one in ten of them—and possibly many more—identify having symptoms of fatigue, “brain fog” and other forms of cognitive dysfunction, headaches, muscle aches, chest pain, and breathlessness weeks or months after recovering from the acute bout of infection, even if their original illness was only mild. Although there is no official, consensus agreement on diagnostic criteria yet, if these symptoms linger more than four weeks after recovery from acute COVID-19, the individual is now commonly said to have Long Covid, also known as Post-Acute Sequelae of SARS-CoV-2 infection or PASC. Children and adults both seem susceptible, with middle aged people more likely to be affected than younger or older people and women more likely than men.

The diagnosis of Long COVID, or PASC, is turning out not to be one of those straightforward ones, like the heart attack scenario we described earlier, but difficult because of the lack of objective markers of illness.  The symptoms of Long Covid are all non-specific and common to many illnesses—fatigue and “brain fog” are seen in a host of disorders. Millions of people will say they feel as if they have the symptoms of Long Covid, some to the point of experiencing extreme debilitation and inability to function. How to be sure which people indeed have an illness directly related to the COVID-19 virus and which are suffering from a different condition is certain to be challenging.

Another Contested Illness?

         The concern with Long Covid is that it will turn into another “contested Illness,” an illness in which there is no clear physiological cause, leading some medical experts to doubt the diagnosis. Examples include chronic Lyme disease, chronic fatigue syndrome, and fibromyalgia. This in turn could lead to various unproven and even dangerous interventions being recommended as treatments for Long Covid. We already see the making of a controversy in a recent article in the journal Science by Long Covid researcher Nisreen A. Alwan. Titled “The road to addressing Long Covid,” the article notes that “Long Covid is likely the first illness in history that has been defined by patients through social media platforms such as Twitter and Facebook.” Alwan writes that “A common theme” about Long Covid is “lack of recognition by the medical profession” and points to “people struggling to make sense of their symptoms and forming their own groups.” All of this sets the stage for an adversarial relationship between people who believe they are suffering from a syndrome caused by the COVID-19 virus and physicians, the kind of relationship that exists for other contested illnesses.

         To be sure, Long Covid follows an illness of known physiological cause, COVID-19. Post-viral syndromes are well-described in the medical literature and it is therefore not a surprise that some people will complain of a variety of non-specific symptoms following a recovery from COVID-19, but the cause of these symptoms is not clear. In the case of Long Covid, experts believe it is unlikely that continued viral infection is responsible, because evidence so far suggests that the virus is cleared from the body after a few weeks. Nor does it seem likely that organ damage is the cause of Long Covid symptoms in many cases because there is apparently no relationship between the severity of an individual’s COVID-19 illness and Long Covid symptoms; even people who had only mild COVID-19 seem susceptible to Long Covid.

Is the Brain Involved?

         People who suffer from a contested illness understandably balk at the notion that “it is all in your head,” as this implies that what the person is experiencing is somehow not real. We are clear that people with these conditions are experiencing real and very distressing symptoms. At the same time, we do think that when symptoms like fatigue, “brain fog,” memory loss, and poor concentration are at play—as they are prominently in the case of Long Covid— and when rates of depression are elevated after recovery from COVID-19, that it is important to consider whether the central nervous system, composed of the brain and spinal cord, are directly involved.

         There is no question that the brain can be involved in acute COVID-19, as conditions like stroke and delirium do sometimes occur. However, it is still unclear how the virus affects the brain during both acute COVID-19 and Long Covid. We consider three possibilities.

         The first would be if SARS-CoV-2 directly infected the main cells in the central nervous system, called neurons. Polio virus, rabies virus, and West Nile virus are examples of viruses that can directly infect neurons, but little if any SARS-CoV-2 virus has been detected in postmortem brains of people who succumbed to COVID-19 and it is not thought that it is capable of infecting neurons itself. It may, however, directly infect a second type of brain cell, called the astrocyte, which supports brain function, including the work of neurons. There is early evidence for direct invasion of astrocytes by SARS-CoV-2 and this could be one way that it produces symptoms like fatigue.

Astrocytes are cells in the brain that support a number of functions, including the work of neurons. There is evidence that they may be directly infected by the COVID-19 virus. Here they are shown tethered to small blood vessels (source: Shutterstock).

         A second mechanism is immunological. COVID-19 causes significant and sometimes overwhelming activation of the immune system. This includes the release of molecules and cells that cause inflammation. In the brain, immune cells called microglia may be activated during COVID infection. Microglia cells then release these inflammatory molecules and these can have ongoing adverse effects on cognition and mood.

Microglial cells in a brain region called the hippocampus are shown here. They are the brain’s immune cells and when activated release inflammatory molecules that can cause cognitive dysfunction and fatigue (source: Shutterstock).

         A third mechanism is vascular. SARS-CoV-2 may cause significant damage to small blood vessels in the brain, leading to reduced blood flow and leakage of blood into surrounding brain tissue. This again could cause neurological and psychiatric symptoms that persist even beyond resolution of the acute infection.

         The problem with these three mechanisms is that none of them is detectable in the brains of living human beings. Hence, while astrocyte infection, immunological activation, and vascular damage are all plausible mechanisms for the neurological and psychiatric symptoms of Long Covid, we do not have laboratory tests or imaging to provide objective markers in order to make a diagnosis. That means that the diagnosis of Long Covid will rely mainly on subjective reports, introducing the possibility for controversy about its existence, nature, and treatment.

         It is fortunate that the National Institutes of Health have announced there will be substantial research funding available for Long Covid. Hopefully, this will help scientists and clinicians come up with more rigorous diagnostic criteria. Although regarded as a long shot, maybe a biological marker will be discovered to help confirm diagnosis. For now, we can only advocate that both the public and the medical profession keep open minds, recognizing that the diagnosis of Long Covid will be complex and difficult, and trying not to make it the subject of another source of conflict.

Misinformation Vs. Scientific Dissent

Who Decides?

In recent months we have increasingly encountered what seems to be both a philosophical and a practical question: how do we distinguish scientific dissent from misinformation? Central to Critica’s mission is to “counteract misinformation about science and health” and we are now vigorously engaged in projects to do just that when it comes to COVID-19 and the vaccines that protect us from it. Yet, there have been from time to time concerns raised that too robust a response to misinformation might be stifling something that is at the heart of scientific progress: the ability to dissent from established wisdom when new data or new interpretations of existing data become relevant.

         Several social media platforms now have policies to censor misinformation about COVID-19, something generally applauded by the public health, medical, and scientific communities. If someone posts a statement like “COVID-19 vaccines cause more deaths than COVID-19” we recognize the statement as clearly wrong, worry that it might discourage people from getting vaccinated, and generally agree that it should not be spread on the internet. Remember that we are not talking about the First Amendment here—that only applies to government censorship of speech. Private companies like Facebook, Twitter, and Pinterest have the right to erase whatever they want from their platforms and we encourage them to do so when a post might harm the public’s health.

         Not everything is as clear cut as the above statement, however, or at least not immediately so. Remember when hydroxychloroquine was first touted as a potential treatment for COVID-19? The idea that hydroxychloroquine might work against the virus that causes COVID-19, SARS-CoV-2, is not a far-fetched one. The drug has activity against the organism that causes malaria, in part by blocking entry of the malaria pathogen into human cells. In the laboratory, hydroxychloroquine apparently had some similar activity against SARS-CoV-2. So talking publicly about this possibility was at one point entirely reasonable.

         It turns out that SARS-CoV-2 enters cells through a mechanism that a drug like hydroxychloroquine doesn’t block, so for biological reasons it turns out not to be a drug that will be effective against COVID-19. Indeed, clinical trials showed that hydroxychloroquine does not work in COVID-19 and saying it does so is now considered misinformation.

         At what point did openly discussing hydroxychloroquine as a treatment for COVID-19 move from a matter of legitimate scientific discourse and something the public had every right to hear about to a case of misinformation? While clinical trials were being conducted and reported, there was a period when there were also differences in how scientists interpreted the emerging database so that at first it was perfectly reasonable to speculate that the drug might work. Clearly, we don’t want to stifle that kind of discussion because it is exactly the process by which scientists ultimately come to consensus about anything under investigation. Studies are done, scientists point out shortcomings in those studies and call for more studies, differences in how data are interpreted are worked out as more data come through, and finally a conclusion is reached, one that stands (or should stand) only as long as no new data emerge to challenge it.

         If at some point a scientist wants to post on Twitter a comment like “I don’t think the data of such and such a study clearly show that hydroxychloroquine is ineffective for COVID-19 and I want to see another study done with a different dose given at a different point in the disease course,” then we would probably not want to see that comment censored. Debated maybe, but not erased. True, such a Tweet would engender the risk that retweets and journalists’ stories about the tweets would be interpreted by the public to mean the drug actually worked, but that would be the price we would need to pay to be sure that scientific dissent is allowed to flourish.

         On the other hand, to articulate now in any public forum that hydroxychloroquine is a treatment for COVID-19 would be to spread incorrect information that could potentially cause harm. It doesn’t work for COVID-19 and taking it for this purpose only puts one at risk for potentially serious adverse side effects. We now have sufficient clinical trial data and the guidance of respected health organizations telling us that hydroxychloroquine isn’t to be prescribed for COVID-19. We would have no problem with a social media company electing to censor a statement claiming efficacy for the drug from its platform.

Dissenters Are Sometimes Successful

         One can of course look throughout history to find many instances of a lone individual or small group who valiantly opposed established scientific dogma, ultimately to be proven right. We all love to cite the examples of Copernicus and Galileo, for example, whose recognition that the earth orbits the sun was initially suppressed. Those two scientific heroes persevered in their dissent nevertheless, ultimately of course proving to be right.

More recently, we’ve seen that decades of adherence to the notion that cholesterol is a major dietary cause of cardiovascular disease was slowly overturned, but only after small groups of naysayers were able to persist despite opposition in showing that the data really implicate processed foods and sugar as the principal offending agents. A combination of industry interests and organized medical organizations promoted the incorrect idea about cholesterol for generations, suppressing the data that sugar and not cholesterol is really the most seriously deleterious dietary component for heart health. How fortunate we are to have people willing to oppose these organizations despite all their power in the medical arena.

         This means, however, that almost anyone with a contrarian view can declare themselves to be the repository of truth, create an image of a lone warrior courageously standing up to the establishment, and gain attention for ideas that are plainly wrong. The community of experts in infectious diseases, for example, explains that Lyme disease is caused by a microorganism that is highly sensitive to antibiotics, making ongoing infection after an adequate course of medication very unlikely. Against that established wisdom, which is based on convincing science and expert consensus, is a group who insist that “chronic Lyme disease” is a common condition requiring prolonged administration of antibiotics. In order to protect people from the adverse consequences of being treated with medication for a condition they do not have, infectious disease experts might wish that mention of “chronic Lyme disease” be categorized as misinformation and removed from the internet. Advocates for “chronic Lyme disease,” however, would undoubtedly rail against such a media policy and declare it suppression of legitimate scientific dissent.

The Very Public Pandemic

         Today we see this tension play out all too dramatically with COVID-19. This is a very public pandemic in which every scientific twitch is immediately reported through multiple media channels. Someone somewhere says something might be effective in preventing or treating COVID-19, be it vitamin D, ultraviolet light, ivermectin, or convalescent serum, and millions of people around the world hear about the potential “breakthrough” almost instantly, often then deciding to either purchase the treatment or try to find healthcare providers who will prescribe it.

         Once again, there is the sense that we cherish this kind of transparency. If something really turns up that is effective in preventing or treating a potentially deadly illness like COVID-19, we want the public to know about it right away. We saw clearly during the early years of the AIDS epidemic that public advocacy can play a critical role in ensuring that effective interventions are developed and disseminated. Research that remains cloaked behind government bureaucratic walls or known only to scientists cannot benefit sick people.

         And yet, we have seen over and over again that in the service of transparency one ineffective intervention after another for COVID-19 has reached the public’s attention. There is insufficient evidence to recommend ivermectin as a treatment for the illness and taking vitamin D (unless possibly if you are clearly vitamin D deficient) won’t prevent you from getting it. To the extent that believing in these things as prophylactics or remedies for COVID-19 replaces taking the steps actually known to reduce viral transmission, like wearing face masks, social distancing, and, especially, getting vaccinated, then broadcasting that they work is potentially harmful and a form of misinformation.

The Ideal Remedy

         In the ideal world, the public would be informed by carefully worded stories about research developments that scrupulously delineate what has been shown not to work, what is still in the hypothesis testing stage, and what has achieved scientific consensus as a useful intervention. The authors of these stories would be people who themselves understand the science and are versed in scientific methodologies and who check with experts before making statements about the status of various proposed interventions. A scientifically informed public would then read these stories, understand different levels of scientific progress, know when it is time to pressure elected officials for more research funding in an area, and also grasp when it is time to embrace a treatment and when it is time to wait for more data.

         We are, of course, far from that ideal, leading to calls for social media companies to police their platforms more assiduously and to remove misinformation when it threatens the public’s health. That in turn leads to accusations that social media companies are either doing a terrible job at managing content and therefore enabling misinformation or that, on the other hand, they are suppressing scientific dissent and legitimate debate.

         We try at Critica to follow scientific consensus carefully while at the same time being open to new ideas and data that might challenge that consensus. Yet we hardly position ourselves as the ultimate arbiter of what the public should see when it comes to health recommendations. We don’t think the companies that run Facebook, Twitter, or YouTube are necessarily the right institutions to make those decisions either. At the same time, we think it was fairly obvious when something like recommending hydroxychloroquine to treat COVID-19 went from a matter of legitimate scientific conversation to misinformation and we very much want people to be protected from latching on to ineffective treatments that offer only adverse side effects.

         There are sources that are usually reliable to help us make the determination of what is scientific dissent and what is misinformation. We believe that we can generally rely on consensus statements from medical associations and on guidance from federal agencies like the Centers for Disease Control and Prevention (CDC), National Institutes of Health (NIH), and the Food and Drug Administration (FDA). But these are clearly not above reproach. Consensus statements take time to formulate and may not be created in time to help us make decisions during crises like the current pandemic. Moreover, the panels that make up treatment consensus statements have been criticized on conflict of interest grounds because many of their members often receive money from the same pharmaceutical companies that make the medications included in the consensus statements. With respect to federal agencies like CDC, NIH, and FDA, all are bureaucracies that can be slow-moving and occasionally subject to political interference.

         What is desperately needed, then, are independent scientific agencies composed of experts with no financial ties to industry, capable of responding rapidly to emerging evidence and making informed recommendations that can be trusted by both professionals and the general public. Creating such agencies would be a challenging task. A funding mechanism would need to be created that would ensure financial stability and independence from political and industry influence. Experts willing to participate who have no competing interests would have to be found. The public would have to be reassured that the guidelines offered by these agencies are reliable and based solely on available data.

         The COVID-19 pandemic has taught us how vulnerable we are to misinformation and how much clear, reliable sources of information are needed. We recognize that what we are calling for is a very tall order, but it seems clear that we deserve and need something close to it.

Pick Our Hospital

What Does Hospital Advertising Mean?

A television commercial for the Cleveland Clinic begins “What Defines a Legacy?” and ends with the tagline “A Century of Care.” In between we are treated to nearly a minute of dramatic footage of Cleveland Clinic surgeons operating on patients, saving lives, and insisting they are not doing it for the money. Founded in 1921, the Cleveland Clinic is indeed consistently ranked one of the world’s leading medical centers, renowned for its patient care and research.

         But it is not alone in that regard or in its dramatic use of media to advertise itself. The Mayo Clinic tells its television audience “You Know Where to Go” in a spot that features the voice of actress Viola Davis and beautiful multi-colored images from an advanced brain imaging technique called diffusion tensor imaging (DTI).

         In New York City, the Montefiore Medical Center insists it is “Doing More.” A 2016 press release about its new advertising campaign explained that:

Montefiore’s new campaign was developed with The Bloc, one of the nation’s most-awarded health-and-wellness creative agencies, and REAL, a leading insight and strategy firm. The multi-media campaign is rolling out over a variety of platforms including TV, radio, outdoor, print, digital, and social media. The campaign is an important vehicle for Montefiore to let its expanding community learn about Montefiore’s recognized excellence.

Choosing Where to go for Cancer Care

         If you or a loved one is considering where to go for cancer treatment, perhaps you will be inspired by an MD Anderson Cancer Center commercial that tells you they are “Making Cancer History.” Or maybe you would be more drawn to Harvard’s Dana-Farber Cancer Institute’s tagline “What We Do Here Changes Lives Everywhere.”

Large, medical school-affiliated teaching hospitals are among the biggest advertisers, but some question whether those advertising dollars are being put to the best possible use (image: Shutterstock).

         The prestigious medical centers we have mentioned here are all non-profit institutions that nevertheless spend millions of dollars paying for expensive advertising in multiple media outlets. Every time Critica President Jack Gorman watches a New York Yankee baseball game on television he gets to see one of the “Montefiore, Doing More” commercials, perhaps the one in which a professional dancer with the Washington ballet says “Thanks to Montefiore, cancer won’t be my last dance.”

         In fact, according to one analysis, the hospital sector spent $11.8 billion on advertising in 2018-2019. The hospitals may say that they advertise in order to help people understand what medical services are available and to make good healthcare decisions. But in fact, one study showed that the advertisements are remarkably similar from hospital to hospital, begging the question of whether they really help potential patients differentiate one from the next.

         It is clear that major cancer centers like MD Anderson Cancer Center, Dana-Farber Cancer Institute, Memorial Sloan Kettering Hospital, and several other major medical school-affiliated institutions are doing cutting edge research and have some of the finest health care professionals on their staffs. Should an advertisement in a magazine or on television factor into a cancer patient’s decision on which one of these to choose for their treatment? Perhaps for the type of cancer the individual seeing the ad has, an excellent but less famous local hospital would offer just as good care and the same outcome at a lower cost and with less travel inconvenience. What is clear is that hospitals are spending billions trying to increase market share. Memorial Sloan Kettering wants you to bring your business to them and not to Houston or Boston or any other place. The fight for market share—for patient business—is now big business with important advertising agencies designing catchy tag lines and dramatic television spots.

No Relationship to Quality of Care

         A study published last July in one of the Journals of the American Medical Association (JAMA) reflects growing concerns that hospital advertising has more downside than benefit to our overall healthcare system. The study, by investigators from Yale and the Congressional Budget Office, looked at advertising spending for all hospitals in the U.S. between 2008 and 2016 and related it to four measures of hospital performance from the Centers for Medicare and Medicaid Services Hospital Compare database. The conclusion of the study is clear: “We did not find evidence of a consistent association between hospital spending on advertising and publicly reported measures of hospital quality,” although there was a very small difference in overall mortality that favored hospitals with the highest levels of advertising. But overall, the authors concluded that “a person choosing a hospital based solely on whether they advertised would have, on average, no better odds of picking a high-performing hospital than if they were choosing at random from the set of hospitals within their” region.

Hospital advertisements are remarkably similar to each other, making it unlikely that there is sufficient information in them to actually help potential patients make better, informed decisions about where to get their care (image: Shutterstock).

         As we suspected from having seen a fair number of these advertisements, it seems unrealistic to believe that they offer information that could truly help someone make a better, more informed decision about which hospital to select for care. We can think of numerous problems that the advertisements present.

         First and foremost is that they represent more than $10 billion a year that could be spent on healthcare, not paid to advertising agencies and television outlets. Non-profit hospitals, which include most of the large teaching hospitals that spend the most advertising dollars, are supposed to provide “charity” care for uninsured patients in order to justify their tax-exempt status. A recent study, however, showed that they spend less on charity care than for-profit and government hospitals. In other words, in order to stay in business, non-profit hospitals seem to feel they need to spend millions of dollars advertising to increase market share, yet they still don’t have enough money to provide adequate levels of care to people who can’t otherwise afford it. Priorities and incentives do not seem properly aligned here.

         Second, we think the advertisements actually can give distorted views of what can reasonably be expected from healthcare. Cancer, for example, is a heterogeneous illness. A case of basal cell carcinoma of the skin can easily be treated by most dermatologists as an outpatient procedure and rarely results in significant complications. A case of glioblastoma multiforme, or malignant brain cancer, on the other hand is almost always going to result in the death of the patient no matter which cancer center they pick for treatment. Yet, as the JAMA study described above noted, “cancer center advertisements tended to be overly optimistic in relaying prognoses.”

         Finally, hospitals are among the most expensive places to get healthcare. Returning to the JAMA study on advertising and outcomes, the authors note that whereas some might justify hospital advertising as a way of helping people choose the best place to go to for their care, “policy observers have raised concerns that advertising may instead be used to increase the demand for all hospitals, not just high-quality facilities, because of the difficulty consumers have judging the quality claims made by hospitals.” In other words, advertising might be driving consumers to go to the hospital for care when less expensive alternatives would suffice. For instance, a recent report published in Kaiser Health News pointed to “enormous fees” charged by hospital trauma centers to treat minor injuries. Are patients being seduced into going to hospitals for treatment because advertising makes the hospital seem the most desirable place to get care for everything?

         That even not-for-profit hospitals must spend enormous sums to garner sufficient market share in order to meet their expenses seems like another of the many flaws in the basic structure of the American healthcare system. If those advertisements actually worked to help patients find the best care they might be justified, but it appears there is little relationship between advertising dollars spent and the quality of care a hospital administers. More likely, advertising diverts money that could be spent to help defray costs for uninsured patients and drives up overall healthcare costs.

A Misstep By the World Health Organization (WHO)

Just what anti-vaccine advocates asked for

When it comes to vaccine advice, we live in a world where every word and every nuance is sure to be made to count. That means that public health agencies have to be especially cautious when they give what might at first glance seem to be common sense, even obvious advice.

         When we looked at the website of the World Health Organization (WHO) on July 5, 2021 here is what we read with regard to vaccinating children against COVID-19:

Vaccines are usually tested in adults first, and only later assessed in children when safety has been proven in adults, because children are still developing and growing. COVID-19 has also been a more serious and dangerous disease among older people. Now that the vaccines have been determined to be safe for adults, they are being studied in children.

WHO’s Strategic Advisory Group of Experts (SAGE) has concluded that the Pfizer/BionTech vaccine is suitable for use by people aged 12 years and above. Children aged between 12 and 15 who are at higher risk of severe COVID-19 may be offered this vaccine alongside other priority groups for vaccination. Vaccine trials for children are ongoing and WHO will update its recommendations when the evidence or epidemiological situation justifies a change in policy.

While the supply of vaccines is limited, the ongoing priority is to vaccinate those most at risk of serious illness who still have not been vaccinated in many parts of the world: older people, those with chronic health conditions, and health workers.

Most children are at low risk of serious disease and vaccinating them is primarily about reducing transmission, which can also be achieved through public health measures, including: physically distancing from others, cleaning hands frequently, sneezing and coughing into their elbow, wearing a mask if age appropriate and avoiding crowded, poorly ventilated spaces.

Now, several ideas here seem like common sense. Of course, we generally test new drugs out in adults before children. Obviously, if there is a short supply of a new drug, we want to give it to the people who need it the most first. But did the WHO anticipate that anti-vaccination advocates would take the advice given in these paragraphs and twist them around to make it seem as if children do not need to be vaccinated against COVID-19? That’s exactly what Critica infodemiologists saw people saying on social media, using the WHO guidance as justification for the misinformation.

The World Health Organization (WHO) guidance on vaccinating children and adolescents against COVID-19 can be easily misinterpreted (source: Shutterstock).

The WHO statement does make clear that the Pfizer/BioNTech mRNA vaccine was tested in children aged 12-15 and found to be both safe and effective. That guidance is much stronger on the website of the U.S. Centers for Disease Control and Prevention (CDC):

  CDC recommends everyone 12 years and older should get a COVID-19 vaccination to help protect against COVID-19. Widespread vaccination is a critical tool to help stop the pandemic. People who are fully vaccinated can resume activities that they did prior to the pandemic. Learn more about what you and your child or teen can do when you have been fully vaccinated. Children 12 years and older are able to get the Pfizer-BioNTech COVID-19 Vaccine.

CDC seems to be recommending that all children twelve years old and older get vaccinated, without exception. The CDC website does mention rare cases of myocarditis, an inflammation of the heart muscle, and pericarditis, an inflammation of the membrane around the heart, that have been linked to the mRNA vaccines (Pfizer/BioNTech and Moderna/NIH), in young adults, noting CDC still recommends the vaccine for all people 12 and over. Finding the association between myocarditis/pericarditis and the vaccines in young people shows us that the surveillance system is working for vaccine adverse events, because this is so uncommon it is like finding a needle in a haystack, and yet the rare adverse event was identified and investigated and now physicians know what to look for in a case of a teenager who exhibits any of the signs or symptoms of myocarditis or pericarditis. The great majority of people who get this recover uneventfully without significant amounts of treatment.

Myocarditis/Pericarditis Noted

We would have expected anti-vaccination advocates to seize upon the myocarditis/pericarditis link and try to make it seem far more common than it is. Hundreds of cases have been reported to the Vaccine Adverse Event Reporting System (VAERS), which only seems like a lot until you consider that millions of doses of vaccine have now been given, making heart inflammation a very rare adverse event that usually resolves without much in the way of medical management. And of course, anti-vaccination advocates did exaggerate the significance of the myocarditis/pericarditis link. But unexpectedly they seized on the WHO guidance to spin a tale that undoubtedly resonated with many parents considering whether to vaccinate their children.

Myocarditis is an inflammation of the heart muscle that has been linked to the mRNA COVID-19 vaccines, especially in young adults. It is, however, rare, and usually resolves without complications (image: Shutterstock)

         We know that there have been widespread inequities in vaccine distribution, with people in low-income countries not getting enough vaccine. We also know that children and adolescents, if they do get infected with the virus that causes COVID-19, tend not to get as sick as older adults. With those two facts in mind, we would also be interested in the idea of moving some vaccine to people at higher risk of severe COVID-19 infection in low-income countries with limited supplies of vaccine. The only problem is that to our knowledge no such program of vaccine redistribution has been seriously considered by any high- or moderate-income country or by any vaccine manufacturer. Rich countries have pledged to help out with the Vaccines Global Access (COVAX) initiative, but that is not the same as designating vaccines that would otherwise have gone to children in rich countries to be sent instead to poor countries and given there to elderly people and people with serious pre-existing medical conditions. If the CDC recommendation to vaccinate children 12 and up is not followed,  we fear that, especially given the challenges of keeping mRNA vaccines frozen during storage, vaccines would simply be wasted.

         So the notion of sending vaccines to more vulnerable individuals in vaccine-deprived countries, however laudable it may sound, was a red herring. No such vaccine redistribution program was ever in the works by WHO or any other international agency.

Good Reasons to Vaccinate Children

         The reasons why it is essential to vaccinate children and adolescents against COVID-19 even though they are less at risk for serious complications were nicely explained by three physicians in a New York Times op ed piece published July 4, 2021 and titled “Covid is a Greater Risk to Young People Than the Vaccines.” The risk of a hospitalization from COVID-19 infection, they point out, is still higher than from a complication from a COVID-19 vaccine. Also, whereas myocarditis/pericarditis almost always goes away by itself, some children who get COVID-19 infection develop complications like Multisystem Inflammatory Syndrome in Children or long-COVID-19 syndrome. “So far,” the three physician authors also note, “326 Americans age 17 and younger have died of Covid-19.”

         There are serious epidemiological reasons for urging parents to get their children vaccinated. COVID-19 shows signs of sticking around. A survey conducted by the journal Nature found that most experts now believe that SARS-CoV-2 (the virus that causes COVID-19) has become an endemic virus, meaning it will persist in the population and continue to infect unvaccinated people. The more unvaccinated people there are, the greater will be the opportunity for the virus to mutate to strains that are resistant to vaccines. If we ever want to bring the pandemic under control, we cannot have a large population of people—in this case many children and adolescents—unvaccinated and serving as a pool of potentially infected hosts. A small number of those children will get very sick and some will even die from COVID-19. Beyond that, the virus will have an opportunity to battle the immune system and learn how to evade it.

         It is easy to see how the WHO guidance misleads people into thinking vaccinating children is unimportant. Epidemiologists, infectious disease experts, and immunologists all want to see everyone vaccinated as soon as possible including children; the WHO is giving advice that seems to undercut that wisdom. We doubt, of course, that experts at the WHO meant their guidance to be misinterpreted this way. Our complaint is that by now public health agencies at local, national, and international levels ought to understand that we are fighting an infodemic in which bad actors will pounce upon any piece of ambiguous advice or guidance they can find to craft misinformation. It is absolutely incumbent upon WHO and all of these agencies to think carefully about how their statements will be interpreted.

What Determines Resilience in the Face of a Crisis?

What the COVID-19 pandemic has taught us.

In the early days of the COVID-19 pandemic, experts warned of a coming surge in mental health issues in the months and years to come. Surely the collective trauma of lives being put on hold, mass job loss, frightening illness and bereavement from losing loved ones to the virus, and almost total social isolation represented a perfect storm for a rapid rise in mental health crises. 

It is still too soon to tell whether this prediction about an overwhelming global mental health crisis will actually come to pass. Experts have noted that during an emergency, people take on a mentality of “just getting through it.” But when the height of the emergency passes and people have room to breathe, they may start processing the mayhem and grief that the emergency has wreaked on their lives and this is when their mental health might suffer. 

Given the extreme nature of the pandemic, including the degree of negative economic impact and the social isolation that came with it, it might be reasonable to assume that once this “breathing room” sets in, an unusually large portion of the population might experience symptoms of mental illness. On the other hand, it is actually just as reasonable to expect that this kind of surge might not occur and, furthermore, that some people’s mental health may have actually benefited from the experience of enduring the stressors associated with the pandemic. 

Kathy Wu, an assistant professor of psychology at Widener University, has commented that some people may experience a sense of “post-traumatic growth,” in which they gain a deeper appreciation for life and a renewed sense of their own strength and resilience, which can help them more effectively face other challenges in their lives. People who experience this boost in resilience after seeing how they dealt with the pandemic may not maintain this level of resilience in the future, however. Experts note that resilience is not a “fixed factor” but a fluctuating trait that is more present at some junctures in life than at others. While this may sound like a negative, it also means that there is hope for people who appear less resilient in certain situations – since the trait is not “fixed,” there is always a possibility of getting through other challenges with higher levels of resilience. 

Despite the “fluctuating” nature of resilience, there are still factors that make some people more likely to experience it to a greater degree than others. Certain structural factors, such as racial equity, secure housing, and reasonable wages, set the stage for some people to be more resilient than others. To be certain, making changes to these structural factors is never easy, but it could help some people develop higher levels of resilience. At the same time, resilience is definitely something that can be taught and learned. Many of the factors that experts think contribute to a sense of happiness, such as practicing gratitude and mindfulness, nurturing relationships, and focusing on larger goals and intentions, also contribute to resilience. 

So are we on the cusp of a mental health crisis in this country and perhaps globally? While it is a distinct possibility, it is also important to remember that this is not the first collective trauma the world has experienced, and people have a remarkable ability to adapt and cope. While we wait to learn more about the impact of the pandemic on mental health, we should take the time to help ourselves and others strengthen our resilience muscles. The psychological fall-out from this global calamity is not inevitable and we have the power to make a difference now.

Another Vaccine Needs Our Support

The Human Papillomavirus Vaccine (HPV) Will Save Millions of Lives

We are usually in the dark when it comes to knowing what causes specific types of cancer. We may know about risk factors that increase the likelihood of some cancers, like cigarette smoking and lung cancer or alcohol consumption and liver cancer, but exactly how those risk factors work to make cells of a particular organ start to divide uncontrollably, is generally still a mystery.

         An exception to this is the case of cancer of the female cervix. We know the cause of about 90% of cases of cervical cancer—the human papillomavirus (HPV). HPV is actually a group of about 200 viruses, only a few subtypes of which cause cancer. HPV is a sexually transmitted virus and virtually all sexually active people in the U.S. are infected with HPV.

Human Papillomavirus (HPV) is a group of DNA viruses that cause cancer of the cervix and several other human cancers (source: Shutterstock).

HPV infects the cells called squamous cells that line the surface of several organs in the body. The immune system keeps most HPV infections in check, but some long-lived HPV infections have the ability to transform squamous cells into cancerous cells.

HPV Vaccine Prevents Most Cervical Cancer Cases

Vaccinating against HPV consequently prevents almost all cases of cervical cancers and is now recommended for all teenage boys and girls. Imagine that: we can actually tell people that a couple of HPV shots will virtually eliminate the risk of an entire type of cancer. A single HPV vaccine called Gardasil 9 is available in the U.S. The U.S. Centers for Disease Control and Prevention (CDC) recommends that all boys and girls aged 11-12 receive two doses of Gardasil 9, although the vaccine can be given to people up to 45-years-old. The second dose is given 6 to 12 months after the first. A three-dose regimen is recommended for people who get their first dose after age 15.

  The World Health Organization (WHO) announced a program in 2020 that would drastically reduce the incidence of cervical cancer by, among other steps, vaccinating 90% of all girls by age 15. It is estimated that, if successful, such an initiative would prevent 8.7 million cases of cervical cancer among women born between 2005 and 2014. Women in Africa and Asia would realize the greatest benefit.

         It is thus extremely difficult for us to understand why rates of HPV vaccine hesitancy seem to be increasing in the United States. In a study published earlier this year, investigators found that the rate of HPV vaccine hesitancy had risen from 50.4% of parents of vaccine-eligible children in 2012 to 64% in 2018. The authors speculated that misinformation about the HPV vaccine might be responsible for this increase in vaccine hesitancy.

The social media platform Pinterest decided in 2019 to moderate posts about HPV vaccine and a study published last year showed that while this had the effect of decreasing misinformation it also resulted in an overall decrease in posts about the vaccine. Thus, improving the quality of information about HPV vaccine on Pinterest had the unintended consequence of reducing the total amount of information available. All of this comes in the context of a general decrease in support for vaccines among parents in the U.S.

HPV Vaccine is Safe and Effective

         There appear to be unfounded concerns about the safety of the HPV vaccine. A study published in June showed that safety concerns about the HPV vaccine increased substantially between 2008 and 2019. The authors noted that “The COVID-19 pandemic has brought to the forefront the fragility of public confidence in the safety of vaccines,” which raises the possibility that such safety concerns actually increased even more dramatically in the past year.

         The HPV vaccine is clearly safe. Minor adverse reactions like fever or nausea and pain and swelling at the injection site are transient. More serious side effects are extremely rare. Anti-vaccination activists exploit the surveillance system called VAERS that CDC and the U.S. Food and Drug Administration (FDA) use to detect adverse side effects to vaccines. Anyone can report anything that happens after a person receives a vaccination to VAERS and health authorities will investigate. The adverse event is almost always a coincidence, but anti-vaccination activists relish advertising what gets reported to VAERS as if every event is proven vaccine related. It is important to emphasize once again that this is not the case; most things reported to VAERS turn out not to be vaccine related. Gardasil 9 has an excellent safety record. HPV vaccination does not make teenagers become more sexually promiscuous.

         What it does do is prevent people from getting several types of cancer. The incidence of human papillomavirus infections has been reduced dramatically since the introduction of the vaccine. HPV vaccine similarly dramatically reduces the rate of cervical cancer. It also prevents, vulvar, vaginal, anal, penile, and some head and neck cancers. HPV vaccine is also credited with a reduction in premature births.

HPV vaccine is a safe and effective intervention to prevent cervical cancer. It also reduces the risk for vulvar, vaginal, anal, penile, and some head and neck cancers (source: Shutterstock).

         Still, more than a decade after the HPV vaccine was first introduced in 2006, only about half (51.1%) of U.S. adolescent women had completed the HPV vaccine series. By 2019 that number had risen only slightly to 56.8% of girls; the rate for boys was even lower (51.8%). States that mandate HPV vaccine for children not unexpectedly have higher vaccination rates, as do states with higher availability of pediatricians.

         Preventing cancer is very difficult. Usually, to even have a shot at doing so people need to affect difficult changes in behavior, like quitting smoking, reducing alcohol consumption, and getting more exercise. Even doing those things is hardly guaranteed to work.

         Then there is the case of cancer of the cervix. Two shots when a person is 11 or 12 years old reduces the risk to close to zero, and it does so with virtually no risk because in reality adverse side effects are almost all mild and transient.  This seems like something every parent should want for their child.

         We find it shocking, therefore, that only about half of the U.S.’ boys and girls have had the full HPV vaccination series and that hesitancy among parents to get their children vaccinated is growing, mostly because of misplaced safety concerns. What is going on here?

         Insurance, both commercial and public, covers most people for HPV vaccine. Hence, financial access does not seem to be the issue. The finding noted above that vaccination rates are higher in states where there are more pediatricians suggests that there may be an awareness problem. Studies have shown that there are a variety of cost-effective programs like localizing vaccination sites in schools that work to improve HPV vaccine uptake. Renewed efforts to make parents aware of the need to have their children vaccinated against HPV are clearly needed.

         There are two aspects of this problem that we find especially disturbing. We noted above that, as expected, states that have HPV vaccine mandates have higher vaccination rates. Why don’t all states have mandates? Apparently, issues of parents’ rights to refuse and the morality of vaccinating against a sexually transmitted disease come up in state legislatures when HPV vaccine mandates are discussed. While we of course respect everyone’s right to hold personal moral and religious views, there does not seem to be anything ethically appropriate about withholding an intervention with almost no risk that prevents a deadly disease. Should parents have the right to make a decision like that for their children, any more than we give parents the right to decide it is okay for their children to engage in life threatening activities like cigarette smoking and riding in cars without a car seat?

         The second aspect that disturbs us involves the safety concerns. We believe that these are being trumped up by the well-organized anti-vaccination activist lobby and that this poses a direct threat to the public’s health. HPV vaccination saves lives and therefore it is especially morally pernicious to withhold it from someone who lacks legal decision-making capacity—i.e., minor children—and it is unethical to allow misinformation and disinformation about imaginary risks to go unchecked to the point that they influence the decision to vaccinate a child.

We do not believe merely wringing our hands is a sufficient response to low HPV vaccination rates in the U.S. or anywhere in the world. We insist that there is both a medical/scientific and a moral issue here. The medical/scientific issue is that HPV vaccination is a safe and effective method for preventing cervical and several types of cancer. The moral issue is that we are wrong to withhold a potentially lifesaving and nearly risk-free intervention from minor children. Stronger efforts should be made to increase vaccination rates against HPV among children.

A Case of False Hope from FDA

Alzheimer’s disease, the most common form of neurodegenerative disease among the elderly, is a devastating illness with a very poor prognosis. A person diagnosed with Alzheimer’s disease (AD) at age 65 has a median survival expectancy of 8.3 years. More than six million Americans are living with AD now and dementia is the cause of death in about a third of seniors.

         A few drugs have been approved that have very modest effects on slowing the relentless loss of memory and cognitive abilities that AD causes. These drugs, with brand names like Aricept and Namenda, do not cure AD. They may slow cognitive decline, but their positive effects are often so small as to go unnoticed by caretakers. There is a palpable feeling of desperation for an effective treatment that one senses among patients with AD and their loved ones.

         It was that feeling of desperation that may be behind the curious decision of the U.S. Food and Drug Administration (FDA) to approve a new medication, aducanumab (brand name: Aduhelm), for the treatment of AD even though it is entirely unclear it works. Despite an FDA advisory board voting 10 – 0 against approving Aduhelm, physicians can now prescribe monthly intravenous infusions of Aduhelm at a whopping cost of $56,000 a year.

Antibodies Against Plaques

         In fact, aducanumab is an approach to treating AD that has failed on multiple previous attempts at drug development. Alois Alzheimer noted in the seminal paper he presented in 1906 that a patient who had died with “presenile dementia” had two distinctive features in her brain when he performed an autopsy. One of these is called amyloid plaques and the other neurofibrillary tangles, which together remain the hallmarks of the pathological diagnosis of AD to this day. Understandably, scientists have focused a great deal of attention on the plaques and tangles that can be seen with an ordinary light microscope in the brain of someone who has died from AD. The amyloid plaques in particular attracted a great deal of attention. Scientists learned that they are made of a protein called beta-amyloid that in turn comes from the breakdown of another protein, called amyloid precursor protein. Amyloid plaques appear to form early in the course of AD, and it was reasonable to speculate that they could even be the driving force behind the illness.

Deposits between neurons of plaques composed of the toxic protein beta-amyloid are a diagnostic feature of Alzheimer’s disease (source: Shutterstock).

         A novel strategy was devised to try to rid the brain of amyloid plaques: give the patient antibodies manufactured to attack and destroy the protein beta-amyloid. When Critica President Jack Gorman first attended a lecture in which that strategy was described, he was among the first to wonder if the immune system would attack the anti-amyloid antibodies themselves; after all, even though beta-amyloid is a toxic protein it is still a naturally occurring protein made by the patient’s brain, he pointed out at the time, and we don’t usually try to immunize people against their own proteins. Although not much was made of the concern back then, antibodies directed against anti-amyloid antibodies given in an attempt to treat AD have been a significant safety challenge. We’ll come back to this point a bit later.

         It is very hard to study putative drugs for AD because we do not have very good animal models for the disease. No other species besides humans develops AD naturally, although it is possible that this is because no other species lives as long as we do. Dolphins and chimpanzees might get AD-like pathology if they lived long enough. It is possible to insert an abnormal human gene into mice that causes the production of the beta-amyloid protein. These transgenic mice develop memory problems, and it turns out that anti-amyloid antibodies rid the experimental mouse brain of amyloid plaques and restore memory function to them. So that looks like a reasonable animal model to test the hypothesis that giving anti-amyloid antibodies can have a positive impact on the course of Alzheimer’s dementia.

         Except that mice are not humans and the mouse models for AD are all laboratory creations, not examples of a naturally occurring disease process. Drugs that rid the transgenic mouse brain of plaques may even do so in people with Alzheimer’s disease, but that doesn’t mean they will necessarily have a positive impact on the human disease. In fact, every attempt to develop a drug that attacks amyloid plaques until recently has failed. So convincing are these failures, that it has led many scientists who study AD to doubt whether amyloid plaques are as central to the disease as once thought. Rather than causing AD, the plaques may form as a reaction to some other disease process, for example. Amyloid plaques are an attractive subject to study because they are so easily found in the brains of people with AD, but some scientists believe it is time to move on from the beta-amyloid hypothesis for Alzheimer’s diseases.

Intervening Early

         A major advance in studying AD was the introduction of positron emission tomography (PET) brain imaging of amyloid plaques. A radiotracer is injected into the patient and PET scan detectors pick up where it attaches in the brain, thus identifying plaques. Now scientists can identify patients with a significant amount of amyloid plaque burden at very early stages of the illness. They can also see if an anti-amyloid drug actually gets rid of the plaques in the living human subjects.

         This is what researchers studying the drug aducanumab, which is made by the Biogen company, and another anti-amyloid antibody drug for which there was some evidence of efficacy published last may in the New England Journal of Medicine,  donanemab, which is made by the Eli Lilly Company, did. In those studies, patients first underwent beta-amyloid PET scanning to ensure they had a significant accumulation of amyloid plaques, then received the anti-amyloid antibody drugs. For aducanumab (Aduhelm), this is where the controversy begins because in 2019 Biogen and a Japanese pharmaceutical company it is working on Aduhelm with announced that they were stopping two clinical trials because interim analysis of the data that had been so far collected indicated that the drug was not working any better than placebo. Then, in a somewhat startling reversal, the companies later said that on the basis of a new analysis of the data from the stopped clinical trials they had detected an effect of Aduhelm in slowing cognitive decline in patients who received the higher of two doses of the drug compared to placebo. The difference was a 22% reduction in cognitive decline.

         One caution has been raised about abandoning the beta-amyloid hypothesis: plaques probably form very early in the course of the disease, before it is clinically apparent that someone has symptoms. It could be that by that time it is too late to have a meaningful impact on the disease. What would be ideal would be to know that someone has begun to accumulate amyloid plaques before they start to lose memory and other cognitive functions and to be able to intervene at that point.

         FDA usually requires evidence that a new drug is effective in at least two large, also called phase three, clinical trials. Before beginning one of these trials, the sponsor (in this case the drug companies involved) must state their intended main outcome measure. This is done to prevent cherry-picking the data; analyzing data multiple times with multiple different outcome measures can lead, for statistical reasons, to statistically significant findings that are actually flukes. Most experts thought the FDA would require Biogen to perform at least one more phase three clinical trial with the higher dose to prove the drug works better than placebo. The FDA did note that Aduhelm was associated with a decrease in plaques. That is interesting, but it is still unclear if reducing the number of plaques in someone’s brain actually results in an improvement in cognitive function. 

Alzheimer’s disease is a devastating neurodegenerative illness for which there is no cure. It robs its victims of their memory and other cognitive functions; available drugs offer very modest slowing of cognitive decline (image: Shutterstock).

         But it didn’t. Despite the overwhelmingly negative opinion of its own external advisors, FDA granted approval for Aduhelm even though there is very little reason to be confident at this point it actually works. We have one study in which a reanalysis of the data suggests it might be effective and another study in which it did not separate from placebo. That is very thin evidence upon which to hang a new drug approval.

One might say, as the FDA probably considered, that anything that might have the slightest chance of working in a disease for which the outcome is always devastating and there is no cure should be made available to patients. But there are at least three objections to that argument. First, as has been the case with all the attempts at designing anti-amyloid antibody drugs to date, Aduhelm has adverse side effects that are probably at least in part due to anti-drug antibodies mentioned earlier that the brain itself produces. About one-third of patients in the clinical trials developed brain swelling and between 17 and 19% had small brain bleeds. 

Second, as mentioned earlier, the drug is extremely expensive. Because most people with Alzheimer’s disease are over age 65, Medicare will be asked to pay for Aduhelm, thus adding another significant financial burden to taxpayer supported healthcare.

Third, the argument that a lesser standard of evidence can be used for a drug that attempts to treat a very serious illness for which there are very limited existing treatment options may seem humane, but it actually undercuts our entire system of rational drug development. Not only should a drug work in order to garner FDA approval, its benefits should outweigh risks. In the case of Aduhelm we have the barest evidence of benefit and significant evidence of risk. Three members of the advisory board that voted against approval of Aduhelm have resigned their positions in protest.

         Our system of drug approvals has worked remarkably well. It is rare that the FDA approves a drug that subsequently proved harmful; instances in which that has happened, like Vioxx, come to mind so quickly because they are unusual. Patient advocacy groups and pharmaceutical companies complain all the time that the drug approval process is too slow and thus deprives people of the chance to take advantage of treatment breakthroughs, but it simply takes a long time to put together enough evidence to convince experts that a new drug is both safe and effective. As the editor of the Washington Post recently wrote in its discussion of Aduhelm “In the U.S. health-care system, patients’ interests chronically come behind the interests of big business.”

         It is a fine thing to want to give hope to people suffering with Alzheimer’s disease and to their caregivers. What we don’t want to do, however, is undermine our regulatory procedures and give people false hope. The FDA is requiring that Biogen perform another large-scale study of Aduhelm and perhaps that will yield the so far elusive evidence that the drug works. As things stand now, however, we believe the FDA acted impulsively and unscientifically to approve a drug for which there is minimal evidence of benefit and significant evidence of risk. Healthcare dollars are precious and should never be wasted on ineffective treatments.