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Preparing for the Next Pandemic: Learning from Our Mistakes Part 1

"There are no mistakes in life, there are only lessons to be learned."

- Mark Twain


"Everybody gets so much information all day long that they lose their common sense."

- Gertrude Stein




The world was ill-prepared for the COVID-19 pandemic. As the pandemic unfolded, American and other world health leaders were forced to make numerous decisions some of which turned out to be right while others were dead wrong (sometimes, quite literally). Although this pandemic is less than two years old and far from over, all epidemiologists agree that a new pandemic is inevitable. Moreover, a spate of articles has appeared recently on how to prepare for the next pandemic. In this Germ Gem post, I’ll give my opinions of some of these articles and will provide my perspective as a physician on the role of common sense in guiding decisions even before the next pandemic strikes.

Preventing the next pandemic. Is there a plan? In his New York Times opinion piece in March 2021, “One Year Later, We Still Have No Plan to Prevent the Next Pandemic,” Thomas Friedman made the case that there was little evidence that government or public health leaders had a coherent plan for preventing the next pandemic. Fortunately, recent evidence suggests that this situation has changed. (For an overview, I highly recommend Dr. Peter Hoetz’s book, Preventing the Next Pandemic: Vaccine Diplomacy in a Time of Anti-Science, published earlier this year.)


The following articles provide examples of what leaders are considering for prevention of future pandemics: “Preparing for the next pandemic,” Science, March 2021, and “Report of the Independent Panel for Pandemic Preparedness and Response: making COVID-19 the last pandemic,” Lancet, July 2021. Also, there’s been an encouraging barrage of reports indicating that leaders in government, science, and industry are indeed learning from mistakes made during the COVID-19 pandemic that they intend not to repeat.


Common sense as a guide. From my very first weekly Germ Gems post on July 20, 2019, I’ve been tempted to refer (and sometimes do) to one or more of what I’ve called the “10 Rules of Internal Medicine.” These “Rules,” developed over the course of my several decades-long career as an internist and infectious disease specialist, provide common sense “rules of thumb” for decision making by doctors and their patients. One or more of the “Rules” can almost always be called upon to guide such medical decisions. But I’ve also found that “The Rules” can be useful in making every day, non-medical decisions. For the purposes of this Germ Gems post, I’ll provide examples of how Rules 1-5 might apply to decisions about the treatment and prevention of COVID-19. (Rules 6-10 are the subject of next week’s Germ Gems post.)


Rule 1: If you don’t know what you’re doing, don’t do anything.

The grounding of this rule is in the famous precept, “First, do no harm” (Primum non nocere) of the 18th century English doctor Thomas Sydenham. (Sydenham was considered the Hippocrates of English medicine.) It is a reminder to physicians and their patients that all treatments have a potential downside, that is, they have side effects. The same can be said of new vaccines.


During fraught circumstances, like severe COVID-19, some decisions to “do something” were likely made in haste, and the consequences may be have been worse than the disease. This is why the results of properly controlled randomized clinical trials (RCTs) are enormously important. They provide scientific evidence of the pros and cons of drugs and vaccines.


Within the context of public health and COVID-19, we are reminded of how important reliable information is and of the incredibly deleterious effects of misinformation and disinformation. (Gertrude Stein’s assertion, quoted above, was right: too much information—"information overload”—can obscure common sense. And who, I ask, isn’t suffering from information overload?)


In preparing for the next pandemic, it is crucial not only to sustain but to improve the clinical trials networks built by the National Institutes of Health (NIH) in the U.S., the Randomized Evaluation of COVID-19 Therapy (RECOVERY) in the UK, and the Solidarity led by the World Health Organizattion. As NIH director, Dr. Francis Collins stated: “In the past, the world has rallied to confront new pandemics, only to lapse into complacency as the risk faded. Having now experienced the worst pandemic in 103 years, we must not make that mistake again.”


Rule 2. If what you’re doing seems to be working, think about continuing it.

Not too long ago, many Americans (I among them), felt like the end of the COVID-19 pandemic was in sight. My Germ Gems post on June 9, 2021, “Is the COVID-19 Pandemic Ending in America?,” reflected a sense of optimism and relief. Dr. Dhruv Khullar, an assistant professor at Weill Cornell Medical College, went so far as to say, “The beginning of the end is here.”


Under these positive circumstances, Rule 2 of Internal Medicine recommends against decisions that would change the direction of treatment, and in the realm of public health, that would change the prevention strategy. This idea is in keeping with the admonition attributed by some to the White Rabbit in Alice in Wonderland: “Don’t just do something, stand there!” In June, America was opening up, people were dining indoors at restaurants, and if vaccinated, they were no longer wearing a mask. But then along came the spoiler—the SARS-CoV-2 Delta variant! It was time to consider Rule 3.

Rule 3: If what you’re doing doesn’t seem to be working, think about doing something else.

Emerging in India in December 2020, a very contagious and more virulent mutant, the SARS-CoV-2 Delta variant, quickly swept the world. By July 3, it was the dominant SARS-CoV-2 strain in America. It quickly became recognized as a game changer. A Science News article on July 30, “New delta variant studies show the pandemic is far from over,” outlined five things we all should know about Delta:


1) Vaccinated people can get infected with Delta, but the vaccines are still working—especially in preventing severe and fatal disease. According to the Center for Disease Control and Prevention (CDC), unvaccinated people are about 25 times more likely to be hospitalized or die than those who are vaccinated.


2) Vaccinated people might more readily transmit Delta to others than the earlier coronavirus variants. This disturbing trait led the CDC’s director, Dr. Rochelle Walenksy, to recommend that vaccinated people wear a mask indoors under certain circumstances.


3) The Delta variant makes people sicker, increasing the risk of hospitalization, admission to intensive care units, and death. The molecular basis for Delta’s increased virulence is related, in part, to genetic changes that facilitate its entry into cells.


4) Delta is much more transmissible than previous variants. The contagiousness of Delta (expressed as R0 or “R naught”) is 5-8, compared to 2.3 to 2.7 of the initial SARS-CoV-2 strain. That is, Delta is as contagious as varicella zoster virus, the cause of chickenpox.


5) Public health measures like vaccination and masks remain crucial tools. And for the sake of the community, everyone needs to get on board for both.


In keeping with Rule 3, wouldn’t it be great if unvaccinated people were to “do something else,” that is, get vaccinated? Even though 70% of Americans now have reached President Biden’s goal of receiving at least one dose of vaccine, doctors and public health practitioners need to double their efforts to increase vaccination rates. The emergence of the fast-spreading Delta variant has pushed the threshold of reaching “herd immunity” to SARS-CoV-2 from 60% to more than 80%. Moreover, the urgency of getting everyone vaccinated ASAP is reinforced by the recent arrival in the U.S. of two new variants: Delta Plus and Epsilon—mutants that will be discussed in next week’s Germ Gem post.


Despite the amazing effectiveness and safety of the currently approved COVID-19 vaccines, experts in vaccinology are “doing something else,” that is, they’re working on new “biomaterial vaccines” that aim at warding off future pandemic threats. According to an August 6, 2021 article in WebMD, these biomaterial-based vaccines supercharge natural immunity, thereby helping the immune system respond quickly to a range of known and unknown (new) pathogens. Moreover, these vaccines are shelf-stable, meaning they wouldn’t have to be refrigerated like some COVID-19 vaccines. This is a major advantage in low-and middle-income countries.


Rule 4. Don’t agree to an invasive procedure without understanding why it’s needed—and without getting a second opinion.

All doctors are aware that “invasive” procedures using scalpels and various kinds of “scoping” devices are inherently more dangerous than solving medical problems by just thinking about them. This is the basis of Rule 4. Unlike our colleagues in surgery, gastroenterology, pulmonology, and cardiology, infectious diseases specialists don’t have any “procedures”; we are about as “noninvasive” as doctors get. We want to make sure patients know what could happen to them if a procedure were to go wrong, and if there are any effective, non-invasive alternatives.


When faced with public health threats like COVID-19, “mandates” are akin to invasive procedures in the minds of some people. Of course, everyone wants to make their own decisions about certain practices, such as getting vaccinated, wearing a mask, and social distancing. But public health is about the “public” and the risks of spreading contagious pathogens in the community. Fortunately, a majority of people, believe the preventive measures already mentioned (vaccination, wearing a mask, and social distancing) make sense. So when people refuse to adopt these common sense strategies, mandates (for hospitals, businesses, schools, and public settings) become necessary.

Rule 5. If you don’t have symptoms, a doctor can’t make you feel better.

In a New York Times article in March 2021 titled “14 Lessons for the Next Pandemic,” Akiko Iwasaki, a professor of immunobiology at Yale University, proposed that one of the key lessons learned from the COVID-19 pandemic is: “Put Science First.” I totally agree and believe that one of the only “benefits” of this devastating pandemic is that it has awakened in the general public an increased appreciation of science. This has become sorely needed in what some consider “the Age of Anti-science.” Increased respect for science by many citizens goes beyond the awe-inspiring development of vaccines against SARS-CoV-2. Happily, it includes expanding the knowledge of the general public of microbiology and infectious diseases.


As one example of this increased knowledge, a striking feature of SARS-CoV-2 infection, one that’s been mentioned in several previous Germ Gems posts, is that 20% to 30% of infected people have no symptoms. These asymptomatic individuals, however, were recognized early in the pandemic to be capable of transmitting the virus to other people.


By now, regular readers of Germ Gems posts know that many of the symptoms associated with infections, such as, fever, loss of appetite, muscle and joint pains, and sleepiness or fatigue, are caused by an activated immune system. That is, don’t blame the pathogen per se. Even infection-related mortality is often caused by a dysregulated immune response to a pathogen.


Of the many mediators that are produced by activated immune cells, protein molecules called cytokines are of pivotal importance in generating symptoms. Almost everyone has heard the terms “cytokine storm” that is precipitated by SARS-CoV-2. And on a related note, some people have learned why inhibitors of cytokines, such as interleukin-6, are prime targets of treatments of severe COVID-19.


So why on Earth, you might ask, would a doctor treat anyone who isn’t ill (i.e., asymptomatic)? The answer is that generally physicians do not want to unless there’s evidence that the treatment is beneficial in the long run. Good examples are the recommended treatment of asymptomatic patients with hypertension and of patients with early HIV infection to prevent the development of the disease called AIDS.


But what about treating people with asymptomatic COVID-19 infections? On July 30, 2021, the U.S. Food and Drug Administration (FDA) revised their emergency use authorization for the monoclonal antibody preparation REGEN-COV for use as post-exposure prophylaxis (prevention) for COVID-19 in adults and children12 years of age and older who are at high risk for progression to severe COVID-19. The FDA, however, made it clear that REGEN-COV is not authorized for pre-exposure prophylaxis to prevent COVID-19, that is, before someone is exposed to the SARS-CoV-2 virus—only after exposure to the virus. The FDA wanted to ensure that REGEN-COV would not take the place of COVID-19 vaccines.


The reasoning behind the FDA’s decision is simple: vaccination is overwhelmingly the best way to prevent not only symptomatic but also asymptomatic, SARS-CoV-2 infection. Therefore, while no doctor can make an asymptomatic patient feel better, a doctor can, by vaccination, prevent sickness altogether and in the case of the wily Delta variant prevent life-threatening disease.

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Main Page images courtesy of Shuxian Hu, MD. Dr. Hu is a scientist in the Neuroimmunology Research Laboratory at the University of Minnesota.

 

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