Anders Tegnell, the Swedish epidemiologist who preached calm in the eye of the media storm/Wkimedia Commons

Could the media-driven fear of the SARS-CoV-2 virus now be making the disease worse?

The question is hard to avoid in the wake of some of the findings coming out of studies of what has come to be called “long Covid,” the lingering illness plaguing some, or many, who contracted the disease the virus causes.

Researchers at Yale University, in conjunction with colleagues at Icahn School of Medicine at Mount Sinai and the Howard Hughes Medical Institute, now claim they can identify what might be described as an immune-system signature of long Covid in the blood profiles of people who believe they are suffering from symptoms that have been linked to the illness.

“Analysis of circulating immune mediators and various hormones also revealed pronounced differences with levels of cortisol being uniformly lower among participants with Long COVID relative to matched control groups,” they reported in a paper published on MedRix earlier this month.

Cortisol can be considered as an adjunct to adrenaline, the “stress hormone” that courses through your body when you’re put in a situation that triggers the age-old, fight-or-flee response.

“During times of stress,” as the Cleveland Clinic, an academic medical center, notes, “your body can release cortisol after releasing its ‘fight or flight’ hormones, such as adrenaline, so you continue to stay on high alert. In addition, cortisol triggers the release of glucose (sugar) from your liver for fast energy during times of stress.”

Low levels of cortisol have long been linked to people suffering from high degrees of stress causing symptoms related to what has been described as the “adrenal fatigue theory.”

And the disease at play here – Covid-19 – has made these the most stressful of times. People have been cautioned for more than two years now to avoid social gatherings, to be cautious around friends and family, to limit contact with strangers, to basically avoid doing the very things the instinctively social species homo sapien does naturally.

Admittedly theory

“The adrenal fatigue theory suggests that prolonged exposure to stress could drain the adrenals leading to a low cortisol state. The adrenal depletion would cause brain fog, low energy, depressive mood, salt and sweet cravings, lightheadedness, and other vague symptoms,” Dr. Marcelo Campos observed at Harvard Health Publishing in 2020. 

There are a lot of Covid-19 symptoms on that list, but adrenal fatigue theory has been and remains controversial.

A 2016 meta-analysis of 58 studies touching on the subject concluded “that there is no substantiation that ‘adrenal fatigue’ is an actual medical condition.” A lack of substantiation, however, as Campos pointed out, doesn’t necessarily render a theory invalid.

“The review raises questions around what should get tested (blood, urine, and/or saliva), the best time, how often, what ranges are considered normal, and how reliable the tests are, to name a few,” he wrote. “In summary, there is no formal criteria to define and diagnose adrenal fatigue.”

And there is no denying the problems reported by many people who have been under stress, if only in their heads, for extended periods of time. Researchers at Carnegie Mellon University in Pittsburgh in 2011 reported finding evidence that “chronic stress results in glucocorticoid receptor resistance…which, in turn, interferes with appropriate regulation of inflammation. Because inflammation plays an important role in the onset and progression of a wide range of diseases, this model may have broad implications for understanding the role of stress in health.”

Their research was peer-reviewed and published in The Proceedings of the National Academy of Sciences in 2012.

The medical community was wrestling with how exactly to put a finger on all of this before the SARS-CoV-2 virus arrived on the scene, and they’re wrestling with it even more now.

The list of symptoms associated with “long Covid” is, as the Centers for Disease Control (CDC) outlines, long and “may not affect everyone the same way. People with post-COVID conditions may experience health problems from different types and combinations of symptoms happening over different lengths of time.”

Some of the symptoms are even hard to define.

The CDC cites as one, “tiredness or fatigue that interferes with daily life,” a very subjective standard. Some people are chronically tired, and with reason, but struggle on through life. Others, at the hint of tiredness, decide they can’t cope.

Doctors are often left to try to sort things out,  and that’s not always pretty.

“The lack of a biological explanation can be disappointing,” Campos observed. “To make things worse, it’s not unusual for doctors to say ‘there is nothing wrong with you’ or ‘this is all in your head.’ The overwhelming amount of information on the internet that recommends many types of treatment causes even more stress. Mental health conditions, such as depression or anxiety, may have symptoms similar to adrenal fatigue and may not respond well to antidepressants and counseling. And some patients do not believe that a mental health concern is the primary cause of their symptoms and many refuse medications due to concerns about their side effects.”

And the problem might well be in someone’s head, but just telling them that seldom fixes anything.

Placebo, nocebo

A controversial study published by the non-peer-reviewed JAMA Network earlier this year reported that a significant number of those struggling with long Covid in France appeared to have never even been infected with Covid-19.

“This cross-sectional analysis of data from a population-based cohort found that persistent physical symptoms 10 to 12 months after the COVID-19 pandemic first wave were associated more with the belief in having experienced COVID-19 infection than with having laboratory-confirmed SARS-CoV-2 infection,” those researchers reported.

“Two main mechanisms may account for our findings,” they added. “First, having persistent physical symptoms may have led to the belief in having had COVID-19, especially in the context of a growing concern regarding long COVID. Although adjusting for self-rated health before the pandemic did not affect our results, another disease may underlie symptoms attributed to COVID-19 infection. Second, the belief in having had COVID-19 infection may have increased the likelihood of symptoms, either directly by affecting perception or indirectly by prompting maladaptive health behaviors, such as physical activity reduction or dietary exclusion. These mechanisms are thought to contribute to the long-described persistence of physical symptoms after acute infections.”

There is a term for this: the nocebo effect, the opposite of the placebo effect.

“Some experts state that the nocebo effect may have a larger effect on clinical outcomes than the placebo effect as negative perceptions are formed much faster than positive ones,” the New Zealand Medicines and Medical Devices Safety Authority has warned in the past.

“The nocebo effect can be influenced by ‘media storms’. Widespread dissemination of concerns about an adverse reaction to a medicine leads to an increase in the number of reports of the adverse reaction. For example, in 2013, British media highlighted the adverse effects, including muscle pains, of statins following an article in the British Medical Journal. An estimated 200,000 patients stopped taking statins within six months of the story being published, many due to adverse reactions. There was also an increase in the number of adverse reaction reports of rhabdomyolysis with statins during this time. This incident has since been attributed to the nocebo effect.”

The media storm surrounding statins was nothing compared to the media storm that has surrounded Covid-19, a storm fueled at the start by Professor Neil Ferguson of Imperial College London who in March 2020 released an epidemiological model predicting astronomical death counts – 1.4 billion in Japan, 2.7 million in the U.S., 600,000 in the United Kingdom, 326,000 in Canada and 85,000 in Sweden – by the end of the year if drastic actions weren’t taken immediately to lockdown and mask up.

Most countries came down heavy on these so-called personal protective measures. Sweden didn’t. The death count there by the end of the year was 9,816. Another 5,534 died in 2021, and the body count to date this year is 4,301, according to the Worldometers tracker.

The total death count since the start of the pandemic in Sweden is now 19,651. Given that Covid-19 has become a serious killer of the old and those suffering from chronic diseases, Sweden will surely get to 85,000 Covid-19 deaths at some point, but it is not yet a quarter of the way there in a country that witnessed an average of 90,000 deaths per year from 2011 to 2019, according to the Statista website.

The annual death count shot up to just over 98,000 in 2020, the first year of the pandemic, before dropping to just under 92,000 last year, which put the annual death count behind the tally for 2018.

The U.S., which did largely lockdown and mask up for a time, is today closer to Ferguson’s end-of-2020 forecast, but it is less than halfway there despite being among the world leaders in per capita Covid-19 deaths, largely as a result of a population weighted toward the old, fat and out-of-shape –  all of which are factors that been shown to make people more vulnerable to death by Covid-19.

There were those who questioned Ferguson’s death projections from the start, but a fear-mongering media largely shouted them down, and Swedish epidemiologist Anders Tegnel, who suggested the storm could be weathered without locking people in their homes, was simply vilified.

Ethnographer Rachel Elisabeth Irwin of Sweden’s Lund University conducted a study of media coverage of the country during the early pandemic. Her research was later published in the journal Global Health in which she wrote that “at the end of March, a group of over 2,000 individuals signed an open letter to the government asking for more (Covid-19 control) measures.

“Time (magazine) described them as ‘doctors, scientists and academics,’ the Guardian (newspaper) as ‘doctors, scientists, and professors,’ Vox as ‘academics and experts’ and The Economist as ‘scientists and professors.’ Both the Economist and the Guardian pointed out that Prof Carl-Henrik Heldin, chairman of the Nobel Foundation was on the list. To support this statement Time and Vox linked to The Guardian’s live reporting from 24 March in which Jon Henley had written that ‘More than 1,500 medical and other academics in Sweden ranging from full professors to post-doc researchers have signed a petition calling on the government to change its coronavirus strategy.’

“There are several problems with this letter. Although there are a number of well-regarded public health experts on the list, the six main authors, while professors, did not work in public health. This was something pointed out by Dagens Nyheter (Sweden’s so-called ‘newspaper of record’), while international media ignored this. Moreover, there were many masters and Ph.D. students on the list, as well as a handful of researchers outside of Sweden who signed the letter. These are hopefully the experts of the future, but not necessarily current experts.”

But that was just the tip of the iceberg. Most reporters writing about the letter had never seen it, and it wasn’t exactly a tribute to academia with the first sentence proclaiming “the Swedish government must act not” when the authors meant “now,” and the second sentence misspelling the word “immediately” before referencing the “Covid-10 infections nationwide.”

Stories claiming that a “study” showed the “initial slow response in countries such as the UK, the USA, and Sweden now looks increasingly poorly judged” would follow, though there was no such study but merely the opinion of the editor-in-chief of The Lancet, a respected medical professional but one who was in this case offering an opinion based on far from complete data,” Irwin wrote.

In her conclusions, she observed that “media is how we know what we know; it constructs reality. Journalists and editors choose what stories are told and what stories are not told. Fake news is rarely totally fake and this matters for all of us. As Paul Rapacioli (a UK-trained economist and one of the founders of The Local, Sweden’s first English language news organization) has noted: ‘When it comes to news, truth is context. A lack of context doesn’t make a story false but it greatly reduces the truth of it.'”

By Rapacoili’s definition, unfortunately, much of what has been written about the pandemic would qualify as fake news because much of what was written ignored context and aimed primarily at making people fearful. The full consequences of this behavior might never be known.

Making it worse

In this situation, the nocebo effect can no more be ignored than the placebo effect, and various studies of drugs that might be repurposed to treat Covid-19 – ivermectin being but one example – have broadly underlined the placebo effect. Those studies concluded the drugs were not ineffective, per se, but unfortunately performed no better or worse than a placebo.

In other words, doctors who prescribed ivermectin and thought it worked based on their personal observations of patients getting better could have given the patients sugar pills and gotten the same result.

As the authors of a peer-reviewed study of two randomized, double-blinded, placebo-controlled clinical trials of ivermectin wrote, “we found ivermectin (37 percent) compared with placebo (28 percent) may make some difference in the complete recovery of patients on discharge day, but the length of hospital stay in the placebo group was significantly shorter than ivermectin arm.

“Our data showed, ivermectin, compared with placebo, did not have a significant potential effect on clinical improvement, reduced admission in ICU, need for invasive ventilation, and death in hospitalized patients.”

Meanwhile, the nocebo effect reared its head in the trials of Covid-19 vaccines. One peer-reviewed study looking at so-called “adverse effects’ after vaccination reported that more than a third of the people shot up with placebos in vaccination tests reported experiencing symptoms of illness.

The brain is a powerful organ. The medical problem is a lack of knowledge as to how it works. The “all in your head” ailments are the hardest to treat because the patients who are suffering are feel the consequences elsewhere in their bodies.

It’s a little frightening to think what the combined results of stress and nocebo could be in this country where 95.5 million people are now reported to have been diagnosed as having had Covid-19. If even 10 percent of them are suffering long Covid as a result of these causes, we’re looking at almost 10 million people haunted by a chronic illness doctors have no idea how to treat.

And if the number is up there in the range of those suffering “adverse effects” from a sugar pill, as in the vaccine studies, the number grows to somewhere around 32 million.

This national disaster can’t all be blamed on the “media storm,” but it certainly didn’t help things to have New York Times reporting appearing on CNN to demand Dr. David L. Katz, the founding director of the Yale-Griffin Prevention Research Center at Yale University, apologize to the nation for publicly suggesting the U.S. follow an approach to the pandemic similar to that of Sweden. 

And when the media wasn’t just plain fear mongering, it was inflaming the culture war that erupted around masks, which some saw as salvation and others as heavy-handed government intrusion in the lives of everyone.

Against that backdrop, it is worth revisiting what French scientists concluded in the first months of the pandemic:

 “Compulsory mask wearing helps resume activity but has no impact on the epidemic….In our calibration, with an 82 percent reduction in virus transmission, the total effect of compulsory mask wearing remains positive but its impact is quite small: The reported cases and cumulative deaths are nearly indistinguishable with and without masks.

“The overall dynamics of the reported number of cases is nearly unchanged, and the number of deaths weakly decreases. The lack of impact of masks on epidemic dynamics comes from a crowding out effect: Compulsory mask wearing reduces the peak distancing effort level by one sixth. This negative impact is compensated for in the transmission process by the effectiveness of the mask at protecting others. (But) if mask wearing happens to be less effective than the 82 percent we use, its overall effect can be negative on transmission. This holds even though we assume that individuals do not believe that the mask protects them.”

More than a year later, a randomized controlled trial of masks led by U.S. researchers working in Bangladesh (one of only two such so-called “gold-standard studies” of masks conducted during the pandemic; the first found masks meaningless) was hailed by the media as proof masks worked.

It reported an  “11.6 percent reduction” in infections, something far short of the 18 percent reduction the French said was needed. The reduction was in the range of which the French warned “the overall effect can be negative on transmission,” ie the masks could make things worse rather than better.

There is no sign that context made it into a single story about the Bangladesh published in what has come to be called the mainstream media.