By David C. Pate, M.D., J.D.

Background

In May of 2020 at the World Health Assembly, a resolution was passed recognizing that managing mis-and disinformation would be critical to managing the COVID-19 pandemic, and then on September 23, 2020, the World Health Organization (“WHO”) declared an “infodemic” in a joint statement by the WHO and United Nations with respect to the COVID-19 pandemic in which “false or misleading information in digital and physical environments during a disease outbreak” had become excessive. The organizations pointed out that COVID-19 is the first pandemic in history in which technology and social media was used to further the public health aims of containing and controlling the pandemic, but also in “amplifying an infodemic that continues to undermine the global response and jeopardizes measures to control the pandemic.” They also pointed out that “Mis- and disinformation can be harmful to people’s physical and mental health; increase stigmatization; threaten precious health gains; and lead to poor observance of public health measures, thus reducing their effectiveness and endangering countries’ ability to stop the pandemic.”

https://www.who.int/news/item/23-09-202-managing-the-covid-19-infodemic-promoting-health-behaviours-and-mitigating-the-harm-from-misinformation-and-disinformation

The WHO pointed out that false and misleading information “causes confusion and risk-taking behaviours that can harm health. It also leads to mistrust in health authorities and undermines the public health response. An infodemic can intensify or lengthen outbreaks when people are unsure about what they need to do to protect their health and the health of people around them. With growing digitalization – an expansion of social media and internet use – information can spread more rapidly.”

https://www.who.int/health-topics/infodemic

On July 14, 2021, the U.S. Surgeon General issued an advisory entitled: “Confronting Health Misinformation.” In it, Surgeon General Vivek Murthy stated: “Health misinformation is a serious threat to public health. It can cause confusion, sow mistrust, harm people’s health, and undermine public health efforts. Limiting the spread of health misinformation is a moral and civic imperative that will require a whole-of-society effort.”

The report goes on to state: “Misinformation can sometimes be spread intentionally to serve a malicious purpose, such as to trick people into believing something for financial gain or political advantage. This is usually called ‘disinformation.’”

Click to access surgeon-general-misinformation-advisory.pdf

On July 29, 2021, The Federation of State Medical Boards (“FSMB”) issued a public statement entitled: “Spreading COVID-19 Vaccine Misinformation May Put Medical License at Risk” to address what it reported as a “dramatic increase in the dissemination of COVID-19 vaccine misinformation by physicians and other health care professionals on social media platforms, online and in the media.” The statement reads as follows:

Physicians who generate and spread COVID-19 vaccine misinformation or disinformation are risking disciplinary action by state medical boards, including the suspension or revocation of their medical license. Due to their specialized knowledge and training, licensed physicians possess a high degree of public trust and therefore have a powerful platform in society, whether they recognize it or not. They also have an ethical and professional responsibility to practice medicine in the best interests of their patients and must share information that is factual, scientifically grounded and consensus-driven for the betterment of public health. Spreading inaccurate COVID-19 vaccine information contradicts that responsibility, threatens to further erode public trust in the medical profession and puts all patients at risk.”

https://www.fsmb.org/advocact/news

On September 9, 2021, the American Board of Family Medicine, the American Board of Internal Medicine, and the American Board of Pediatrics issued a “Joint Statement on Dissemination of Misinformation” expressing support for the FSMB’s statement above, but going further and stating the following:

“We also want all physicians certified by our boards to know that such unethical or unprofessional conduct may prompt their respective board to take action that could put their certification at risk.

Expertise matters, and board certified physicians have demonstrated that they have stayed current in their field. Spreading misinformation or falsehoods to the public during a time of a public health emergency goes against everything our boards and our community of board certified physicians stand for. The evidence that we have safe, effective and widely available vaccines against COVID-19 is overwhelming. We are particularly concerned about physicians who use their authority to denigrate vaccination at a time when vaccines continue to demonstrate excellent effectiveness against severe hospitalization and death.”

https://www.abim.org/media-center/press-releases/joint-statement-on-dissemination-of-misinformation

On May 23, 2023, the U.S. Surgeon General issued a new advisory entitled: “Confronting Health Misinformation.” In the advisory, Surgeon General Murthy states: “Health misinformation is a serious threat to public health. It can cause confusion, sow distrust, harm people’s health, and undermine public health efforts.” A critical point, in my opinion, is the statement: “Limiting misinformation helps us make more educated decisions for ourselves, our loved ones, and our communities.” In the report, misinformation is defined as: “information that is false, inaccurate, or misleading according to the best available evidence at the time.”

The Surgeon General’s advisory also calls out the harmful effects of misinformation during the COVID-19 pandemic: “During the pandemic, health misinformation has led people to decline vaccines, reject public health measures, and use unproven treatments. Health misinformation has also led to harassment and violence against health workers, airline staff, and other frontline workers tasked with communicating evolving public health measures.”

On August 15, 2023, a study entitled Communication of COVID-19 Misinformation on Social Media by Physicians in the U.S. was published in the Journal of the American Medical Association Network Open (https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2808358). The authors point out that approximately 1/3 of the >1.1 million confirmed COVID-19-related deaths in the U.S. as of January 18, 2023, “were considered preventable if public health recommendations had been followed.”

The authors of this study examined a time period beginning just after COVID-19 vaccines became available to the public (January 2021) through the end of the following year (December 2022). They identified 52 physicians in 28 different specialties across all regions of the United States who repeatedly spread COVID-19 misinformation using social media. They found that nearly one-third of these physicians were affiliated with groups with a history of spreading medical disinformation, such as America’s Frontline Doctors.

Several books are planned for publication later this year and early next year examining the coordinated efforts by some of these physicians and organizations sponsoring them, as well as some of the money fueling these efforts. The challenge is that while there appears to be very well-funded and coordinated disinformation campaigns, the medical organizations that could respond to protect the public were very uncoordinated, and often stood on the sidelines not knowing how to respond or simply choosing not to.

Hospitals and physicians witnessed first-hand the harm of disinformation causing deceived individuals to show up in their emergency rooms and intensive care units still refusing to believe that they had COVID-19 or surprised that the ivermectin or hydroxychloroquine or other concoction of vitamins and supplements did not prevent their severe disease, while public health individuals watched in frustration as these physicians (including two physicians from America’s Frontline Doctors who served in one case as a state surgeon general and in the other a member of a public health board) undermined public health measures and thwarted efforts to protect the public.

What I present here is basically a strategic plan for the Federation of State Medical Boards; state medical licensing boards; specialty boards that certify physicians; national, state, and county medical professional associations and societies; specialty organizations; and hospitals to respond to the disinformation campaigns that will undoubtedly be repeated during future pandemics. It has commonly been said that “nature abhors a vacuum,” but it can just as well be stated that truth abhors a vacuum. That is because disinformation campaigns are enabled when true experts and authoritative organizations remain silent.

The Problem to be Addressed

This proposed national response is very focused and directed at:

1. Physicians who represent themselves as physicians and who promote their education, training, medical licensure, board certification, and/or knowledge and experience in order to gain the trust of their audience in an effort to influence the public about measures that should be taken or avoided regarding prevention, diagnosis and treatment of a disease;
2. Who utilize social media or other press, media and public forums;
3. To disseminate medical information that the physician knows to be false, should know is false or with reckless disregard as to whether the information is true or false;
4. With such information being harmful to, or having the potential to harm, the public if followed; and
5. Who continue to spread the medical information after the WHO, FDA, CDC, FSMB, state licensing boards, specialty certifying boards, and/or national professional associations have issued public statements or posted statements to their websites that indicate the information is false, incorrect, or inconsistent with the scientific evidence.

In other words, physicians who are touting their credentials to gain the public’s trust, while disseminating medical information that they know to be false or should know that is false repeatedly and over an extended period of time, and continue to do so after public statements by authoritative professional bodies or warnings (see below).

The reasons for this very limited and targeted focus include:

1. This provides the best opportunity to defeat legal challenges of adverse actions (see below for a discussion of these legal issues).
2. Science, medicine and technology evolve. With that evolution, we learn new things, we develop fuller understandings of things we previously have studied, and sometimes we learn that what was previously known is no longer true or is no longer completely true. With this evolution in our knowledge and technology, the way we evaluate, diagnose and treat conditions also evolves and new best practices emerge. The statements and practices of physicians should only be judged based upon the evidence, the consensus of experts and the prevailing practices at the time of the statements.
3. We do not want to penalize physicians who are trying to help the public and their patients during a time of uncertainty for simply being mistaken or not being aware of a recent new study. Rather, these efforts are focused on those physicians who are acting irresponsibly, in an ongoing fashion even after being put on notice or forewarned, promoting information that is contrary to the weight of the evidence or public guidance by professional and expert organizations without acknowledgement of that fact.

The Harms or Potential Harms that Need to be Addressed

Medicine has become a more complicated and expansive field given the explosive growth of knowledge in the field related to scientific discovery; new scientific methods; and advances in our studies and understanding of the fields of genetics, immunology, molecular and cell biology, virology, imaging techniques, genomics, vaccinology, proteomics, precision medicine, among others. Because of this complexity, rapid rate of new developments, and confusing messaging from advertisements for medications, supplements, treatments and non-traditional therapies, the public often relies on advice from physicians, whether during a visit with their own doctor, or from listening or reading the advice of doctors who provide guidance to the public on television and radio, in articles or on social media platforms.

Physicians are trusted sources for information by the public because of their extensive education, training, experience, expertise, ethical principles guiding the profession, and oversight and regulation. The public is generally unaware that there is little oversight and regulation of physicians providing guidance to the public, nor that some physicians may be violating their professional and ethical norms due to ideology, political aspirations and financial conflicts that place their own self-interests over the interests of the public.

An ethical and legal foundational duty imposed upon physicians in the practice of medicine is that of informed consent. Informed consent requires that we explain the medical condition to the patient or their legal decision-maker as accurately as we can as well as the treatment options, including the risks and benefits of each, as well as the risks and benefits of not undertaking any treatment. It is an abuse of the informed consent process to be untruthful or to manipulate patients to undergo treatment that is ill-advised or that places the physician’s interests over those of the patient. Doing so not only has the potential to harm patients, but undermines the public trust in the medical profession.

There is no doubt that an unscrupulous physician can harm many patients in their medical practice. But, the potential number of patients harmed will be constrained by the physical limitations of how many patients a busy physician can see and provide dangerous advice to. On the other hand, social media has enabled unscrupulous physicians to reach a much wider and broader audience, and those readers or listeners have the opportunity to further amplify these messages among those in their social networks, potentially harming far greater numbers of people.

As the article I cited above indicates, “approximately one-third of the more than 1,100,000 confirmed COVID-19-related deaths as of January 18, 2023, [in the U.S.] were considered preventable if public health recommendations had been followed.” Of course, a main focus of disinformation purveyors was sowing doubt and distrust of the COVID-19 vaccines, while not communicating any of the benefits. “As of December 2022, estimated death rates for unvaccinated persons in the US were 271 per 100,000 compared with 82 per 100,000 for those fully vaccinated, yet only 69.2% of eligible people had received the full primary vaccine series, and 15.5% had received the bivalent booster.”

Informed consent cannot be attained when physicians present a medication or treatment as perfectly safe without acknowledging potential side effects and adverse effects, nor when a medication or treatment is promoted as wholly ineffective or dangerous without acknowledging the potential benefits, nor when a medication is promoted as effective when the weight of the evidence fails to establish benefit and the FDA and the pharmaceutical company that produce and distribute the medication release public statements discouraging the use of the medication due to lack of effectiveness. In cases where a medication or treatment has benefits that outweigh the risks at the population level, a physician who knowingly promotes those medications or treatments to the public as dangerous and of no benefit is using their medical degree, license, education and training, board certification and/or expertise to manipulate people’s medical decisions at the best and harm people at the worst, in a manner that is always immoral, unethical and unprofessional. I have never read a medical practice act that didn’t prohibit these behaviors.

This focus on excess deaths in the above article resulting, in part, from disinformation campaigns, fails to capture the full breadth of harm from COVID-19 disinformation. We now know that these reported deaths undercounted the total deaths, because deaths as a consequence of COVID-19 are increased in at least the 12 months that follow recovery from the acute infection, but are often not attributed to COVID-19 in death certificates when the death occurs more than 30 days following the acute illness. Further, deaths, in of themselves, fail to capture the full impact of the harms – the consequences of the loss of a spouse to the remaining spouse, especially when the spouse who died was the main financial support for the family and source for health insurance, nor the impact on children when the death is that of a sibling or one or both parents or their caregiver. Further, death counts fail to measure the financial impact to families when the family member required a prolonged hospitalization or required prolonged follow-up medical services, when the affected family member develops Long COVID and no longer can work or must reduce the amount they work, and other consequences of COVID-19 short of dying. There are other long-term potential health consequences of SARS-CoV-2 infection that we don’t yet fully recognize or understand and that have not yet been quantified.

The Legal Issues

There are several potential legal barriers that must be overcome, but they are not insurmountable.

1. First Amendment protections for speech.

The First Amendment provides for the protection of some, but not all speech. The intents of promoting the marketplace of ideas and debate, especially debate of a political nature, are cherished rights of a free nation and democracy. While the jurisprudence around the First Amendment is not complete (e.g., there remains little guidance around the category of what is commonly referred to as professional speech), nor even always consistent, it is clear that not all speech is entitled to the same degree of protection, and some speech is not protected at all (e.g., obscenity, child pornography, and certain hate speech). Furthermore, even some protected speech can be regulated if there is a compelling government interest and the restriction is narrowly tailored to satisfy that interest.

Examples of where restrictions on free speech have been permitted include speech in courtrooms (one cannot successfully defend a charge of lying under oath (perjury) with a First Amendment defense, nor would the First Amendment allow a defendant to speak over a judge or a witness in a proceeding), false advertising, mislabeling of medications, defamation (slander and libel), impersonating a police officer, and making terroristic threats.

One can see a recurring pattern that tends to characterize speech for which restrictions are constitutional – those areas of speech that cause or may cause harm to others:

• perjury – harm to the effective administration of justice, including the potential for wrongful convictions and imprisonment of defendants;
• false advertising – financial harm to purchasers;
• mislabeling of medications – physical harm to those who take those medications;
• defamation – harm to another’s reputation and potential financial harm to a business;
• impersonating an officer – potential physical harm to someone wrongfully detained; and
• terroristic threats – harm to someone’s security and rights to be left alone.

Also, notice most of the above examples also involve false speech. In those instances, false speech that harms has no value under the First Amendment and is entitled to no protection. Supreme Court holdings in the ‘70s and ‘80s included such statements as “[u]ntruthful speech, commercial or otherwise, has never been protected for its own right,” false statements “are not protected by the First Amendment in the same manner as truthful statements,” and [f]alse statements of fact are particularly valueless [because] they interfere with the truth-seeking function of the marketplace of ideas.”

However, the Supreme Court has not gone so far as to hold that all false speech is valueless or beyond the protection of the First Amendment. Although it is not explicitly clear where the Supreme Court will draw the line, we can get a pretty good idea from at least two decided cases. In one, the Court wrote that “the knowingly false statement and the false statement made with reckless disregard of the truth, do not enjoy constitutional protection.” Garrison v. Louisiana, 379 U.S. 64, 75 (1964). This holding gives us the perspective of the Court that knowingly false statements (disinformation as opposed to misinformation) could be subject to discipline without violating the physician’s First Amendment rights to free speech. Moreover, a more recent case gives us an additional insight that ties back to the examples of prohibited speech listed above. In United States v. Alvarez, 567 U.S. 709 (2012), the plurality stated: “even where the utterance is false, the great principles of the Constitution which secure freedom of expression … preclude attaching adverse consequences to any except the knowing or reckless falsehood. Although the plurality struck down the statute in question on First Amendment grounds as being overly broad in its proscription, in a separate concurring opinion by Justice Breyer and joined by Justice Kagan, these justices suggested that a similar statute, more narrowly tailored to avoid situations where a specific harm is likely to occur, could survive a legal challenge on the basis of the First Amendment. In fact, Congress amended that statute to require proof of fraud, and so far, that statute has not been successfully challenged.

In summary, the cumulative jurisprudence on the First Amendment’s right to freedom of expression would seem to allow government regulations and actions against physicians for disinformation when the following can be shown:

• the statements are knowingly false or the false statements were made with reckless disregard of the truth;
• the statements have caused or are likely to cause harm; and
• the prohibition is narrowly tailored to prevent the speech that is causing or likely to cause harm.

• Issues relating to State Medical Board jurisdiction

As I stated above, I haven’t seen a medical practice act that doesn’t proscribe unethical or unprofessional conduct. Nevertheless, various excuses have been offered by medical boards that have declined to institute investigations into complaints about licensees spreading disinformation to the public. I will list some of these excuses and explain why they fail to be barriers to investigations and discipline.

1. Excuse #1 – Offering medical advice to the public is not the practice of medicine. Of course, medical licensing boards do regulate more than “the practice of medicine,” including such things as false or misleading advertising or even taking action against licenses of physicians convicted of felonies not involving the practice of medicine. The practice of medicine is defined in each state’s medical practice act. Many statutes may need to be updated to reflect the changing nature of medical practice. Today, the practice of medicine has expanded to virtual care and telehealth services that were not technologically possible in decades past, and when available more recently, were not particularly common until the COVID-19 pandemic. If the state legislature is inclined to revise and update the medical practice act, consideration should be given to expanding the definition of the practice of medicine to encompass situations where the physician is holding themselves out to be physicians in providing medical advice to the public, including when that advice is to refrain from receiving a treatment or medication that is ordered or prescribed by a physician.
2. Excuse #2 – The state board cannot investigate or discipline a physician for conduct outside of the physician-patient relationship, and in providing medical advice on television, the internet or social media, there is no physician-patient relationship. However, state boards do this all the time. If a physician is determined to have submitted false information to the board upon which the board relied in granting the physician a license, the board can act, even if the physician has seen no patients yet. There are many cases of persons holding themselves out as physicians who are not, and the boards regularly submit cease and desist orders. Obviously, if they are not physicians, they cannot have physician-patient relationships. Further, there are instances in which physicians and charged with or convicted of crimes that have no direct connection to a physician-patient relationship (e.g., murder, child pornography or sexual assaults) in which cases the state board may discipline or suspend a physician’s license even though no physician-patient relationship was at issue.

The Plan

1. State licensing boards
2. Examine your medical practice act to determine whether the board would have the authority to investigate and discipline a physician for disinformation under current provisions, such as unprofessional conduct.
3. If not, consider whether your legislature would be willing to consider an amendment to the medical practice act to expand the board’s authority. The key guiding principle is that the licensing boards should protect the public from unscrupulous physicians knowingly presenting disinformation holding themselves out to be licensed physicians or experts in the matters that are the subject of their false statements.
4. Strongly consider posting notices to your public website and in the board’s physician newsletters that put physicians on notice that certain medical guidance being promoted to the public is false, incorrect, misleading or unsupported by the weight of current evidence. A physician’s ongoing spread of disinformation after such notice should help demonstrate the intent necessary to support disciplinary action and overcome a First Amendment challenge.
5. An even stronger support for disciplinary action can be made by sending a physician who continues to spread disinformation notice and a demand to disclose their basis for continuing to publicly promote false statements and then issuing the physician a warning if that basis is inadequate to support those false statements.
6. If the licensing board’s general counsel still feels uncomfortable in pursuing these cases of public disinformation due to the absence of a physician-patient relationship, then the publicly promoted false statements should be sufficient basis to investigate the physician’s medical practice to determine whether the physician is advising and treating patients in accordance with their incorrect advice to the public, and if so, this would form the basis for discipline without any First Amendment challenge having a chance of being successful.
7. The Federation of State Medical Boards (FSMB)
8. The FSMB should assemble expert panels to review the evidence related to the medical disinformation physicians are providing to the public and provide the basis and the studies that support the falsity of the disinformation.
9. The expert panels should provide a review of the evidence in a report that can be posted to their website and distributed to the state licensing boards.
10. The report should also identify the current or potential harms to the public that can result from the public following the disinformation advice that physicians are presenting to the public so that state licensing boards can prove that the physician knew or should have known that the statements they were providing to the public were false, but also demonstrate the harm or potential harm that could result from the public following the misguided advice. Together, this evidence should help a state licensing board to be able to overcome a First Amendment challenge in the discipline of a physician.
11. WHO and CDC
12. The CDC and WHO must remain above the political fray and remain objective without compromising their positions to outside pressure from non-experts with political or ideological agendas.
13. It is essential that the WHO and CDC present clear, easy-to-find information on their websites that reviews and synthesizes the accumulated knowledge from epidemiological data and scientific studies along with references.
14. Ideally, reviews of our accumulated knowledge would be presented concisely and without scientific and medical jargon for the public and in a more detailed and scientific manner for health care professionals. This information should be updated regularly, with a clear indication as to the date of the update, and in the review for health care professionals, there should also be an extensive list of references from which the best evidence is derived.
15. There should also be a site on both organizations’ websites where commonly spread disinformation is refuted in a clear and convincing manner. Not only must we refute this disinformation to the public, but we must provide journalists and reporters with the information needed to avoid inadvertently further spreading that disinformation and to refute disinformation and to challenge those physicians spreading the disinformation.
16. Specialty certifying boards
17. Clear statements should be made public and disseminated to all their diplomates by all specialty boards similar in nature to the joint statement by the American Boards of Internal Medicine, Family Medicine and Pediatrics provided in the introduction above.
18. Drawing from the reports recommended to be issued by the WHO, CDC, FSMB, and state licensing boards, specialty boards should convene expert panels to review the best evidence to date and publish consensus statements as to the best evidence in their fields.
19. These reports should be regularly updated, fully referenced and a clear date indicated as to when the report was last updated.
20. So too, reports should be posted as to disinformation being propagated by physicians and a clear analysis as to why it is false and/or misleading. This information should be provided on the website and in the professional publications of the board in order to place physicians spreading disinformation to the public on notice that the information they are purveying is contrary to the weight of the current evidence.
21. Specialty boards are private organizations and thus not subject to the First Amendment free speech obligations in the way governmental agencies are. Too often, specialty boards have deferred discipline to state licensing boards, which are more limited in the actions they can take than are specialty boards. Further, lack of action on the part of specialty boards may ultimately become an existential threat. Physicians seek board certification for a number of reasons. One is the mark of distinction it has represented that a physician has mastered and is current in their knowledge and skills of the specialty. Obviously, allowing board-certified physicians who knowingly convey false medical information to the public and continue to do so even after notice that their statements are not supported by the weight of the current evidence undermine the publics and the profession’s confidence that board certification is a meaningful distinction of current knowledge and expertise in the field. Another reason for board certification is to satisfy the credentialing requirements for medical staff membership or for participation in an insurance network of providers. However, the failure to discipline diplomates, including revoking board certification, will not only undermine the credibility of board certification, but also make these requirements for board certification less legally defensible, and in the end, likely result in fewer physicians seeking board certification or recertification, fewer hospitals giving weight to board certification in their credentialing process, and fewer managed care networks using board certification as a factor for the participation in their networks.
22. Professional associations and medical societies
23. Professional organizations and medical societies should also undertake efforts to disseminate to their memberships updates as to the best evidence on emerging health issues that are receiving interest by the public in the media, press and on social media.
24. Similarly, they should be proactive in attacking disinformation head on and providing the evidence as to the falsity of that information.
25. Professional associations, and perhaps to a lesser extent, medical societies, are highly dependent upon their reputations because membership is seldom required for physician employment, medical staff membership or insurance plan participation. Therefore, professional associations and medical societies should protect those reputations and censure those among their membership who persist in spreading disinformation publicly, including revoking designations of advanced standing such as fellow or master designations.
26. Hospitals
27. Hospitals are also negatively impacted by the spread of medical disinformation. Disinformation may undermine efforts to protect their own staff, decrease the willingness of staff to employ protective measures, and result in increased absenteeism, staffing shortages, increased employee health care costs, and decreased worker productivity. Hospitals are also often one of the most trusted and valued voices in their communities. They, especially non-profit, tax-exempt hospitals, must be sources of truth and must educate their communities so that those who want to protect themselves will have the best available information to do so.
28. Hospitals should consider revising their medical staff bylaws to make clear that the role of the hospital and its medical staff is to serve the needs of their communities. Those needs can only be served when people are provided with truthful and accurate information that allows them to make an educated decision based on the risks and the benefits, as well as their own personal values in deciding the best course of action for themselves and their minor children. Health care professionals should never coerce or manipulate people’s health care decisions. Doing so can negatively impact the hospital’s reputation, harm people and is inconsistent with the mission and values of the hospital. For these reasons, ongoing spread of disinformation to the public when the physician knows or should know the statements to be false, and when those statements, if followed by the public, causes or can cause harm, should be a basis to deny medical staff membership or to discipline current members of the medical staff. Providing medical staff members who are spreading disinformation with a notice of concern and allowing them an opportunity to present their evidence to support their misstatements prior to taking adverse action will provide an opportunity for the physician to be educated and, if the physician persists in their misinformation campaign, will help satisfy due process requirements.
29. If specialty boards do not also take actionable steps to put their diplomates on notice and discipline those who continue to spread disinformation, hospitals and insurance companies should consider lessening or eliminating considerations regarding board certification for medical staff membership.

Conclusion

The popular quote, “The only thing necessary for the triumph of evil is for good men to do nothing,” is apropos to the crisis of disinformation.

There is mounting evidence and a growing consensus that health disinformation spread by physicians touting their medical credentials and expertise is harmful to the public, undermines public health efforts during public health threats, and adversely impacts trust in science, public health and medicine. This conduct on the part of physicians is also contrary to the professional and ethical guidelines of our profession.

Disinformation campaigns have benefitted from significant funding and coordination. Efforts to combat disinformation will not succeed with individual scientists and physicians carrying the responsibility on their shoulders. It is critical that the WHO, CDC, FSMB, state medical licensing boards, national specialty boards, professional associations and medical societies, and hospitals all step up and reinforce each other’s efforts to report and update the weight of the current evidence, to call out disinformation and to take action against those physicians who continue to repeatedly spread disinformation to the public on television, radio, cable networks, the internet and social media.

Concerns about legal challenges can be overcome in a number of ways as presented above. The keys to success are that these organizations must be clear about the weight of the evidence; update that evidence; refute misinformation and disinformation; place physicians on notice about their spread of disinformation; offer those physicians an opportunity to provide the evidence to support their positions, but if not persuasive and the spread of disinformation continues, then all of these organizations should take the relevant action against these physicians without deferring to other organizations to do so. The keys to successful actions are demonstrating that (1) the physician knew or should have known that their statements were false, inaccurate or misleading, or that the physician acted with reckless disregard as to the truth or falsity of their statements; and (2) that the statements harmed or had the potential to harm members of the public who followed the advice provided by the physician.

This proposed response to disinformation does not deprive physicians of their ability to challenge the medical consensus or to raise concerns. For example, one physician repeatedly reported to the public that he had seen a marked uptick in the number of cancers in his practice following the availability of COVID-19 vaccines. The proper venue to disclose his findings would be to the FDA, the CDC, or his professional organizations or to organize a clinical study to investigate the issue. It is not responsible behavior to use this assertion that was unverified and unvalidated to scare the public, when that physician would not have a basis for establishing COVID-19 vaccinations as the cause as opposed to SARS-CoV-2 infections themselves or other potential causes, was promoting other false information, a similar increase in cancer rates had not been identified anywhere else in the world despite the world-wide distribution of these vaccines, and the fact that this physician was later alleged to have made cancer misdiagnoses. Physicians remain free to express concerns or fears to the public, however, they need to be clearly identified as such, rather than represented as fact.

Boost Now or Wait for the New Booster?

I have been asked many times in the last few weeks, especially now that we are having signs of a new surge (as a reminder – when I use the word surge, I mean a significant and sustained increase in COVID-19 cases; I am not using it as an indicator of magnitude, i.e., that the number of cases, or hospitalizations, or whatever indicator one might wish to use, has or will hit some arbitrary threshold) – whether one should get a bivalent booster now (if they never received a bivalent booster or if they qualify for two and got the first, but not the second) or wait for the new monovalent boosters that are planned for this fall.

The FDA has indicated that they advised vaccine manufacturing companies of their intention to move to an annual COVID-19 vaccine update. In June of this year, the FDA provided guidance to these companies that the fall booster should be a monovalent vaccine (meaning the spike protein from on variant, as opposed to last year’s booster, which was a bivalent vaccine comprised of two spike proteins – one from the original form of the virus and the other from the BA.4/BA.5 variant) derived from the XBB.1.5 variant.

At that time, vaccine companies indicated that new vaccines could be ready in August, and perhaps even in late July. While the FDA has to approve the new vaccines, the CDC issues the specific guidance as to who is eligible for the booster, timing of vaccines and whether it is safe and effective to administer the COVID vaccines together with other vaccines.

We have a new CDC director who I have been very hopeful would be committed to more timely and more clear communication than what we got with the previous director. So far, I am disappointed. She has stated that the vaccines will likely be available to the public in October, though more recently, she has indicated that it might be as early as late September. Regardless, she has not (to my knowledge) explained to the public why the delay. Pfizer has indicated that they already have the vaccines prepared and have already submitted their paperwork for FDA approval. Novavax (currently approved only for those ages 12 years and older that is a more traditional type of vaccine as opposed to the mRNA vaccines produced by Pfizer and Moderna), has indicated that it will be filing for approval of its updated vaccine this month. So far, no explanation as to why it would take another 6 – 8 weeks to get these vaccines out to the public.

Until the CDC’s vaccine committee meets and recommends guidance and the CDC director signs off on those recommendations, the vaccines will not be made available to the public and we won’t know the answers as to who can get the vaccines, the timing of vaccines relative to prior vaccination or infection, and whether these COVID vaccines maintain their safety and effectiveness if administered with other vaccines, such as the newly approved RSV vaccines for persons over age 60 and the influenza vaccine that will be offered this fall.

So, now back to the question. Should a person who has not received the bivalent booster get boosted now, or alternatively, a high-risk patient who received one bivalent booster shot, but not the second, get a bivalent booster now or wait for the new monovalent vaccines anticipated to be available in October?

Although it is frustrating that we don’t yet have guidance from the CDC about timing for the new monovalent booster, my guess is that they are going to advise that the new booster not be administered within 4 months of a prior COVID bivalent booster shot (and I anticipate they will state 2 months for immunocompromised persons). This recommendation would be based on recent data as to the optimal spacing of boosters to generate the maximal immunological response and would be consistent with the guidelines issued last year for the bivalent vaccine booster administration. That data is not crystal clear, but seems to suggest that you want at least 2 months between boosters and that 4 months is better than 2, with some remaining question as to whether 6 months might be even slightly better than 4.

Now to answer the question. This would be how I would analyze and answer this question from a patient or their physician:

Is the patient significantly immunocompromised? If yes, go to Question 1; if no, go to Question 2.

1. If you are significantly immunocompromised and it has been 2 or more months since your last booster, ask your physician about getting another bivalent vaccine now. It will be nearly two months until the new boosters are available, and I would doubt that ACIP will recommend and the CDC director would adopt a requirement for you to wait four months from your last vaccination to get the new vaccine.
2. When was your last COVID vaccine dose? If < 3 months, wait for new vaccine. If > 4 months, go to Question 3.

(If the answer is > 3 months ago, but < 12 months, we can be fairly confident that the person has little protection against getting infected, but likely strong protection against severe disease or death, unless they have an immune deficiency or significant immunocompromising condition.)

3. Can you limit your exposures until you can be vaccinated in October (work remotely, avoid large groups of people, wear well-fitting N95 masks when around others outside your family, household family members similarly able to limit exposures, etc.)? If so, wait for new booster. If not, go to question 4.

Is the patient at high risk for severe disease – age > 65 years and/or significant underlying health conditions that would place the patient at increased risk? If no, go to Question 4; if yes, go to Question 5.

4. Do you have to or plan to engage in situations that will create high risk of exposures between now and October (for example, international travel, health care worker, school teacher in a school that is not taking precautions, daycare worker, etc.) and you did not receive the bivalent booster within the past 12 months? Consider getting bivalent vaccine booster now and then getting new monovalent vaccine as soon as you qualify (my guess is it would be 4 months after your bivalent booster dose, but in any event, wait at least 2 months before getting the new booster). If the patient has had 1 dose of the bivalent booster, wait for new monovalent booster, but add mitigation measures.

5. Do you have to or plan to engage in situations that will create high risk of exposures between now and October (for example, international travel, health care worker, school teacher in a school that is not taking precautions, daycare worker, etc.), but you have received one dose of the bivalent booster within the past 12 months? If the bivalent vaccine dose was received in the past 3 months, wait for the new monovalent vaccine booster, but add mitigation measures and consider postponing your international travel until at least several weeks after being boosted with the new booster shot. If your dose of bivalent vaccine was received more than 4 months ago, and especially if it was 6 or more months ago, consider getting a second bivalent vaccine booster shot now and then getting the new monovalent vaccine as soon as you qualify (my guess is it would be 4 months after your bivalent booster dose, but in any event, wait at least 2 months before getting another booster).

What to Know

Unfortunately, with end of the public health emergency, we can no longer see the earliest and best indicator of disease transmission levels – cases (reports to the CDC of all those testing positive by a PCR test performed at a hospital or commercial laboratory). Instead, we now have to resort to wastewater surveillance, hospitalizations for COVID and deaths from COVID, the latter two measures being late indicators of COVID-19 transmission levels. Nevertheless, all three measures are up and increasing leaving little doubt that we are having a new surge (please note that I use surge to denote a measurable and sustained increase in cases, hospitalizations and/or deaths, but the use of the word surge does not in any way indicate the magnitude of the increase relative to baseline or past surges).

Hospitalizations

An increase in hospitalizations due to COVID-19 is certainly an indication that COVID-19 cases have also increased in roughly the week prior. COVID-19 hospitalizations are up in the US and globally, but keep in mind, not only are hospitalizations a late indicator of COVID-19 cases (~ 1 week), but the reporting of hospitalizations is also delayed. I am writing this on August 14, and the most recent data on COVID-19 hospitalizations in the US from the CDC is from July 29, in other words, roughly 2 weeks ago. Further, the reporting to the CDC is not always timely or complete. Thus, there is no way of determining just from the COVID-19 hospitalizations data during a surge, whether the number of cases is still increasing, has peaked, or is even on the decline (we will have to put all of the data together to make that assessment – see below).

In the week ending July 29, there were 9,056 people hospitalized for COVID-19 in the US. That was a 12.5% increase from the week prior. To put this in perspective, the highest number of hospitalizations in the US in a week occurred in the week ending January 15, 20222 with 150,674 COVID-19 hospitalizations (which was high enough to overwhelm many of our hospitals), but keep in mind that it appears that the current surge in hospitalizations may be just beginning and very likely has not peaked yet.

In Idaho, too, there does appear to be a slight uptick in COVID-19 hospitalizations, but it is far less pronounced that what I am seeing nationally, confirming reports that seem to suggest disease transmission may be higher in other parts of the country than the Pacific NW at this time.

Wastewater Surveillance

Detection of SARS-CoV-2 virus has increased significantly in the wastewater testing from every region of the U.S. Currently, levels in the midwestern US are increasing most rapidly, and have overtaken all other areas of the country. It appears possible that wastewater levels of virus have peaked in the eastern US and the southern U.S., while levels in the western U.S. have been lower, but steadily increasing and have now reached the levels seen in the eastern and southern U.S.

In Idaho, reporting is significantly lagging, with the most recent data being roughly 3 weeks old. Keep in mind that the delay from sampling to reporting has historically been about a week, so these data are likely one month old. Nevertheless, it showed that wastewater levels of SARS-CoV-2 virus were increasing in Ada County and steady in all other parts of the state for which wastewater sampling is available. The wastewater surveillance testing/reporting is similarly lagging for the City of Boise (last reported July 24) and that time, I could not discern anything suggesting the beginnings of a surge.

Deaths

The CDC reports that COVID-19 deaths accounted for 1.1% of all deaths in the U.S. and that COVID-19 deaths had increased 10% over the last reported week. That does reflect an increase in COVID-19 deaths in the U.S., however, the numbers remain low on a relative basis, and all of this would be consistent with what would be expected early in a new surge, as we typically don’t see increases in deaths until a couple weeks after we see the increases in cases.

Looking at the Idaho reporting, we are not seeing any increase in COVID-19 deaths over the recent baseline, however, this data is two weeks old.

Variants

It’s a bit challenging to know what variant to attribute to this current surge, although I certainly have my guess. In the past, surges have generally been easily attributed to a single variant that was dominating, and we usually did not see a surge until that variant accounted for over 50% of the genetic sequences recovered and identified from infected persons. However, at this time, in the US, we have at least 18 variants circulating, of which at least 5 appear to be on the rise as a percentage of all the variants circulating. As, I mentioned, I have a guess as to the variant causing the current surge, but it is only a guess, and I base that upon the fact that it is the prevailing variant (perhaps as high as 21% – however, it may be much more now because that was as of August 5) and seems to be the fastest growing variant. That variant is EG.5, another recombinant of two Omicron variants with numerous subsequent mutations.

Unfortunately, the wastewater reporting from the City of Boise is nearly a month old, but interestingly, even then, EG.5 accounted for 11% of the variants detected. The then prevailing variant was XBB.1.9, but I would certainly expect EG.5 to have increased and XBB.1.9 to have decreased by now.

What are the implications of all of this?

There is little doubt that we are in the early part of a new surge. I can’t tell you to what magnitude this surge will manifest, and neither can anyone else. If the wastewater measures truly are peaking in the eastern and southern part of the country, then that is fantastic news and this surge is likely to be rather mild in a relative sense. Even if the surge has not peaked anywhere in the US yet, given what we know about EG.5, we would not expect a surge that would come close to the surges we dealt with in 2020, 2021 and early 2022.

However, we should take the following factors into consideration in reserving judgment as to how significant this surge may or may not be because many factors have changed since these earlier years of the pandemic:

1. We are undeniably dealing with more transmissible and more immune evasive variants now than we did in those earlier years.
2. Schools in many parts of the country will start the new school year over the next couple of weeks. While early on, the evidence seemed to defy logic and experience in that school children did not seem to play a major role in transmitting the virus (children are a significant factor in driving community transmission of most respiratory viruses, especially influenza), but now the data seem clear that in fact children do play a major role in the transmission of SARS-CoV-2), and it is likely that we will see a significant uptick in community spread once schools open.
3. Unlike earlier years when schools were implementing some mitigation measures, from what I can see, it appears that few schools are taking any mitigation measures this school year. This will promote transmission within schools and subsequently within communities. Further, while we know that schools could significantly reduce transmission through changes to their air handling systems, it appears that relatively few schools have adopted these best practices, which could have been subsidized with federal monies that likely are no longer available.
4. Similarly, work places are taking less mitigation measures, and many companies have cut back or ended remote work opportunities. This will undoubtedly promote transmission within work places.
5. Of great concern to me is the fact that up until this year, hospitals required masking in all patient care areas. It was also common for hospitals to limit visitors and screen employees and visitors. Now, many hospitals have abandoned most, if not all, of these measures. We know that as transmission increases in communities, the rate of infections in health care workers increase, as well. Further, while the U.S. does not require reporting of nosocomial SARS-CoV-2 infections (infections that patients acquire while hospitalized), and regrettably, few if any hospitals have been transparent in reporting this data publicly, we know that these infections are well documented in countries that do. It seems all but certain that as community transmission rates increase, it will become more and more dangerous for those who are hospitalized for reasons other than COVID-19.
6. We can all remember the days when masking in the community was not rare, when people avoided large gatherings, and when most larger events were held outdoors. Of course, little of this is the case today. Not only does this increase the risk for exposure to people who are infected when community transmission levels increase, but when in close contact and not masked, the viral dose is increased (the amount of virus that a person inhales), and we have some evidence to suggest that higher viral loads correlate with higher risk of severe disease.
7. Ironically, in 2021 and 2022, we had more treatment options for patients with severe disease.
8. In 2021 and 2022 there was more quarantining of those who were infected and more isolation for those who were exposed by a close contact. Now, people are returning to work and school much sooner and, in many cases, it is likely that they may still be contagious. Contact tracing and isolation are things of the past.
9. Another concerning recent behavior I have seen is that people symptomatic this summer have done a single test that was negative and declared that they have the summer flu. First of all, a single rapid antigen test early on in the development of symptoms is not sufficient to rule out COVID-19. There is a high rate of false negative tests (meaning that the person really is infected despite the fact that the test indicates no evidence of infection) when done early on in the development of symptoms or following an exposure. Thus, serial testing following onset of symptoms is required. Further, while it is possible to acquire a number of respiratory infections, including influenza, during the summer, levels of these viruses circulating in the US during the summer are typically quite low.
10. Finally, keep in mind that in 2021 and 2022, people had fairly regular boosts to their immune protection against SARS-CoV-2 from prior infection, vaccination or both. Today, that immune protection is much less than previously, and keep in mind that only the minority of the population has taken the bivalent vaccine first made available in September of 2022, and even those who did take advantage of that booster have not had another dose of vaccine since. Thus, though we can be grateful for what appears to be long-lasting protection against severe disease, there is not doubt that the immune protection for the majority of our population is waning.

We also must keep in mind that while the focus of the analysis of whether a surge is occurring is based upon hospitalization and death data now that there is so little testing and reporting of data, and while it is true as a general statement that people are less likely to be hospitalized or die today of COVID-19 than in prior years, none of this takes into consideration the risks of potentially life-altering Long COVID (PASC) or the many other potential long-term health effects from infection, and especially repeated reinfections.

Planned Parenthood Greater Northwest, et al. v. Raul Labrador in his official capacity as Attorney General of the State of Idaho, Members of the Idaho State Board of Medicine and Idaho State Board of Nursing, in their official capacities, and County Prosecuting Attorneys, in their official capacities.

Case No. 1:23-cv-00142-BLW

This case was decided on July 31, 2023.

The Background in the U.S.

Of course, the reason that we have seen so many new state abortion laws and legal challenges is that the U.S. Supreme Court overturned the long-standing precedent set out by Roe v. Wade in its decision last year in the case of Dobbs v. Jackson Women’s Health Organization. The result was that there was no longer a federally-guaranteed period of time during a pregnancy in which an elective abortion could be legally performed. Instead, the right to determine under what conditions, if any, abortion would be legal in a state would be returned to the states, and as a result, laws would be expected to vary from state-to-state.

The Background in Idaho

On March 27, 2023, Idaho Attorney General Raul Labrador issued an opinion in a letter with the subject line “Request for AG Analysis” to Idaho Rep. Brent Crane in response to a request from that legislator asking for guidance as to the following:

Do Idaho’s abortion prohibitions preclude:

1. The provision of abortion pills;
2. The promotion of abortion pills; and
3. Referring women across state lines to obtain abortion services or prescribing abortion pills that will be picked up across state lines?

The answer was yes to all of these activities in the Attorney General’s opinion letter. https://www.courthousenews.com/wp-content/uploads/2023/04/labrador-idaho-opinion-letter.pdf. (It is the AG’s response to the third activity that is the subject of this lawsuit.)

The Attorney General subsequently rescinded the letter stating: “It was not a guidance document, nor was it ever published by the Office of the Attorney General, accordingly, I hereby withdraw it.” Idaho AG walks back opinion on prohibiting referrals for out-of-state abortions | The Hill. The state of Idaho on behalf of the AG claimed to the court that the letter was intended to be a private communication, however, the letter was disseminated to and published publicly by a pro-life organization, in part to further its fundraising efforts.

Plaintiffs (Planned Parenthood Greater Northwest, Dr. Caitlin Gustafson, and Dr. Darin Weyhrich) filed suit in federal district court, challenging the Attorney General’s interpretation of Idaho’s criminal abortion statute, Idaho Code § 18-622 and asking the court to enjoin (prevent by legal order) the Attorney General, the Idaho State Board of Medicine and Board of Nursing, and the prosecuting attorneys for every Idaho county from bringing criminal or licensing actions based upon that interpretation of the law. Although the plaintiffs raised a number of legal theories, the case predominantly rested upon the issue as to whether plaintiffs’ First Amendment rights had been violated (making referrals to out of state providers is considered speech and the allegation was that the threat of prosecution for doing so and the threat of suspension of their medical or nursing licenses for doing so were restraints on their exercise of free speech.)

The Attorney General and some of the other defendants filed a motion with the court to dismiss the lawsuit on the basis of some technical legal doctrines concerning justiciability, which in layman’s terms simply mean that the plaintiffs were not in a position to bring a legal challenge and/or the matter was not one that presented a sufficient basis for a court to review it according to the Defendants. That motion was ultimately dismissed by the Judge.

The specific language in the statute in question stated:

“The professional license of any health care professional who … assists in performing or attempting to perform an abortion … shall be suspended ….” (emphasis added)

In addressing the third activity, the AG stated in his letter: “Idaho law prohibits an Idaho medical provider from … referring a woman across state lines to access abortion services …. Idaho law requires the suspension of a health care professional’s license when he or she ‘assists in performing or attempting to perform an abortion. Idaho Code § 18-622(2) (emphasis added). The plain meaning of assist is to give support or aid. An Idaho health care professional who refers a woman across state lines to an abortion provider … has given support or aid to the woman in performing or attempting to perform an abortion and has thus violated the statute.”

The statute allowed for no flexibility on the part of the licensing boards, but rather states that the provider’s license “must” be suspended for six months upon the first offense, and permanently revoked upon the second.

The letter was printed on Idaho State Attorney General office stationery and the title of Attorney General was added below General Labrador’s signature.

The Court’s Decision

The focus of the Court’s analysis rests on the Plaintiffs’ claim that the Attorney General’s interpretation of the criminal statute would violate their First Amendment rights of free speech and the Attorney General’s assertion that there is no threat to Plaintiffs because his letter opinion was withdrawn. 

It was notable to the Court that plaintiffs had previously made referrals for abortion services to out-of-state providers, but stopped doing so after the AG’s letter became public. On the other hand, the AG argued that letter could not constitute a threat of prosecution because it “was sent to one legislator as private legal advice [and] it was not published by the Attorney General or offered as guidance in any capacity.” Further, the state also claimed that there is no threat here because the AG lacks any authority to direct the county prosecutors or prosecute violations of the criminal abortion law.

The Court, however, took note of the fact that the AG’s letter was widely disseminated and became widely available to the public, and further, that this letter was issued and signed by Attorney General Labrador – Idaho’s chief legal officer – and was sent to a member of the Idaho legislature. Whether the guidance was official or not, it was the only guidance provided by the AG, and it nevertheless had a chilling effect on the plaintiffs’ First Amendment rights.

Further, while the state, in representing the AG, asserts that there is no prosecution threat because the AG’s letter was withdrawn, the Court takes notice of the fact that the AG does not disavow that opinion. The Court observed that the AG’s letter was withdrawn just hours before the first status conference in this litigation and appeared only to be for litigation positioning as opposed to a change in view or interpretation of the statute by the AG, and thus the withdrawal was not a disavowal. In fact, when counsel for the state were asked whether the AG or prosecuting attorneys disavowed the legal analysis or conclusion of the AG’s letter, they admitted that there was no such disavowal.

The Court notes that the legal theory upon which defendants seek to have the case dismissed is that of mootness – “when the issues presented are no longer ‘live’ or the parties lack a legally cognizable interest in the outcome.” However, a defendant cannot render a case moot simply by ending its unlawful conduct, because the defendant could simply resume that conduct after the case was dismissed. Instead, to prevail on a motion to dismiss the case for mootness, the defendant “has the heavy burden of persuading the court that the challenged conduct cannot reasonably be expected to start up again.” In the case of a governmental defendant, the defendant must demonstrate that the change in its behavior is “entrenched” or “permanent.” Given that the withdrawal of the AG’s opinion does not reject the statutory interpretation or provide an exception that would exempt the plaintiffs’ free speech from criminal prosecution, the matter before the Court is not rendered moot by the withdrawal of the letter. In fact, there is no evidence that the Attorney General’s position has changed.

Further, although there have been amendments made to the statute, none of those change the relevant language at issue in this case.

For all of these reasons, the Court found that the Plaintiffs were successful in demonstrating that there is a genuine threat of prosecution. The consequence of the threat is a chilling of the Plaintiffs’ Frist Amendment right of free speech. The rescinding of the letter by the AG, without revising or rejecting the legal analysis contained in the letter does nothing to ameliorate this threat or to render the Plaintiffs’ lawsuit moot.

As Judge Winmill stated in his opinion: “…It would not have been particularly difficult for the State to definitively establish that no case or controversy exists (“case or controversy” has a special legal meaning derived from the U.S. Constitution in conferring jurisdiction upon a court. If there is no case or controversy, then the court has no legal power to hear and decide the case. For example, if someone owes you $10, and refuses to pay you, but over time you reach an agreement that you will accept $5 as payment in full, endorse the check with the statement “Paid in Full,” and deposit the check, but then later decide to sue the person for the $5 balance, there would be no case or controversy since there was a mutual agreement and satisfaction of the debt.). That is, all it would have taken is for Attorney General Labrador to denounce the Crane Letter’s interpretation or make an affirmative statement that he, or his office, will not enforce Idaho’s criminal abortion statute in such a manner. Instead, the Attorney General has strained at every juncture possible to distance himself from his previous statement without committing to a new interpretation or providing any assurances to this Court or the Medical Providers. Attorney General Labrador’s targeted silence is deafening.”

Based upon all of the above, the Court then proceeded to issue a preliminary injunction that prevents Attorney General Labrador from enforcing Idaho’s criminal abortion statute as interpreted in his letter.

Readers are going to hear about a number of important cases that are based upon the First Amendment’s right to free speech. Unlike this case, some very high-profile cases pending before courts currently are using this First Amendment right as a defense to conduct for which they have been charged. Therefore, in future blog posts, we will review the First Amendment right to free speech, how courts have decided these issues in the past, and whether doctors have a First Amendment right to spread disinformation.

I have written many times previously on my blog about Long COVID or PASC (post-acute sequelae of COVID-19 infection), its manifestations and potential pathogenesis. Now, a new paper looks at the immunology of Long COVID: https://www.nature.com/articles/s41577-023-00904-7. In my discussion below, I will include parts of this paper, as well as some other recent information about Long COVID.

Although post-viral syndromes have been known to occur for many decades now, it was surprising early on in the pandemic to see the large number of people who continued to be plagued by persistent symptoms following the apparent recovery from the acute SARS-CoV-2 infection, including those with mild illness, and even including some children.

There is no diagnostic test for Long COVID, and for a long time, there was no widely accepted case definition for the condition. Therefore, there were widely varying estimates of the disease burden, ranging from a low end of around 10% of COVID-19 patients to a high of around 30%.

The World Health Organization definition of Long COVID is:

A condition that occurs in individuals with a history of probable or confirmed SARS-CoV-2 infection, usually 3 months from the onset of COVID-19, with symptoms that last for at least 2 months and cannot be explained by an alternative diagnosis. Common symptoms include fatigue, shortness of breath, cognitive dysfunction and others, which generally have an impact on everyday functioning. Symptoms may be new onset, following initial recovery from an acute COVID-19 episode, or persist from the initial illness. Symptoms may also fluctuate or relapse over time. A separate definition may be applicable to children.

The CDC provides the following additional information about Long COVID:

• Long COVID can include a wide range of ongoing health problems; these conditions can last weeks, months, or years.
• Long COVID occurs more often in people who had severe COVID-19 illness, but anyone who has been infected with the virus that causes COVID-19 can experience it.
• People who are not vaccinated against COVID-19 and become infected may have a higher risk of developing Long COVID compared to people who have been vaccinated.
• People can be reinfected with SARS-CoV-2, the virus that causes COVID-19, multiple times. Each time a person is infected or reinfected with SARS-CoV-2, they have a risk of developing Long COVID.

We did see some differences relative to Long COVID with different variants. For example, comparing long COVID cases from the first wave to those from the Alpha wave, a change in symptomology was observed, with increased muscle aches, brain fog and anxiety, but decreased frequency in loss of smell and altered sense of taste. Despite these minor variations, the fact that a set of common symptoms endures across the different variants and even in vaccinated populations and, thus, across patients with differing viral loads, points to the presence of determinants of pathology that are intrinsic to the SARS-CoV-2 virus.

There are varying hypotheses as to the pathogenesis of Long COVID: (again, I have written about most of these in prior blog posts if you want to dig deeper into these)

• tissue and organ damage caused directly by the viral infection,
  • heart
  • lungs
  • brain
  • kidneys
• persistence or lack of clearance of SARS-CoV-2 and ongoing antigenic stimulation,
  • gastrointestinal tract,
  • testis,
  • a space between the skull and the brain
• an abnormal immune response to acute COVID-19,
  • an overactive immune response resulting in organ damage either in response to a very high viral load or a dysregulated immune response,
  • an inadequate immune response that allows the virus to wreak more havoc or may result in failure to clear the virus
• reactivation of other viruses,
  • Epstein–Barr virus (EBV) reactivation has been the leading candidate (most people have been infected with this virus that causes infectious mononucleosis or sometimes colloquially referred to as the kissing disease), though human herpes virus – 6 has been implicated.
• altered systemic immune responses,
  • We know that we can see various abnormal or exaggerated immune responses during acute infection and in the several months following (e.g., MIS-C, MIS-A – see prior blog posts where I have discussed these if interested).
  • There is intense debate surrounding whether there is potential longer term immune dysfunction and if so, whether it is relevant to the development of Long COVID or apparent susceptibility to other infections following COVID-19 (e.g., RSV, invasive group A strep, etc.). There are other viruses known to cause either temporary (e.g., a temporary loss of humoral immune memory following measles) or permanent immune dysfunction following infection (e.g., HIV). And, of course, there is the confounding factor that not all of the immune disturbance may be the direct effect of SARS-CoV-2 infection, but rather may be in part related to the indirect effect of reactivation of other viruses, such as Epstein-Barr virus, in those patients in which this occurs. One area of intense disagreement is whether COVID-19 results in significant and persistent T-cell exhaustion in some persons. (You can also read about T-cell exhaustion in some of my posts from last year).
• auto-immunity,
  • Many studies have demonstrated that acute SARS-CoV-2 infection can result in the production of a diverse population of autoantibodies, likely a result of viral mimicry (in other words, the virus contains antigens to which the body produces antibodies that are sufficiently similar to other self-antigens that the antibodies not only attack the virus, but the person’s own cells with that similar antigen on their cell surface.
  • Recent studies have identified increasing accounts of antibodies produced against interferon, which is a critical part of the body’s innate immune response in that interferon serves as a cellular warning system that an invading virus has been identified, which in turn, allows nearby cells to take some precautions that make viral entry more difficult.
  • Just a year ago, we concluded that Epstein-Barr virus (EBV) infection can cause multiple sclerosis decades later following infection, likely through an autoimmune mechanism. It is not yet clear whether EBV reactivation during COVID-19 might also contribute to the development of autoimmunity.
  • Of particular concern are autoantibodies that may target various cells of the brain potentially causing or contributing to the wide array of neurological complications seen during and following COVID-19.
• micro-blood clots, and
  • Some autoantibodies are of the type seen in a syndrome characterized by abnormal clotting.
  • Some antibodies may stimulate endothelial cell (the cells that line the inner walls of blood vessels) activation, which itself can promote clotting.
  • There have also been reports of an amyloid-like protein within these micro-clots that may make them more resistant to the body’s normal mechanisms for dissolving clots.
• microbiome dysbiosis (disruption of the normal gut microbiome).

Now we examine what evidence we have at this point in time to correlate immune responses with Long COVID.

As I mentioned, as of yet, we do not have a diagnostic test for Long COVID (in contrast to other diseases such as blood pressure measures for the diagnosis of hypertension or blood sugars for the diagnosis of diabetes). On the other hand, there have been studies that have found biomarkers (these are not diagnostic of Long COVID, but rather predictive of higher risk for the development of Long COVID such as the persistence of abnormal levels of certain cytokines and chemokines (these are chemical messengers of the immune system that may boost or calm the immune response) such as certain interferons or interleukins. One of the chemokines found to be persistently increased in some patients with Long COVID is CCL11, which interestingly and concerningly, has been identified as a mediator of the neurocognitive decline seen with aging.

Recall from my earlier blog posts that the spike protein is referred to as “S” or the S protein, and people will develop antibodies to the S protein with either vaccination or infection. There are other important proteins in the SARS-CoV-2 virus, and one of those is the nucleocapsid protein, which is referred to as N. Antibodies against the N protein are referred to as anti-N antibodies, and we generally only see anti-N antibodies in the case of infection, because U.S. vaccines only include the S protein and not the N protein.

A study looking at the initial anti-N antibody response during acute infection found an inverse correlation between antibody level and likelihood of symptoms at 3 months or beyond, supporting the view that an inadequate initial antibody response may predispose to Long COVID. [If you are having trouble following that, think about high antibody levels as a vigorous immune response and low antibody levels as a potentially inadequate immune response, but only use this framework early on in an infection, as antibody levels normally decline over time.]

An analysis of a cohort of hospitalized patients of whom roughly 20% would go on to experience Long COVID symptoms at 1-year post-infection found that the Long COVID group showed significantly lower antibody levels to S, with no difference in T cell response. [In this case, the lower antibody levels are to the Spike protein]. Together with the study mentioned directly above, with an association of low anti-N and low anti-S antibody levels with Long COVID, this would naturally cause us to query whether an underwhelming humoral immune response might predispose to the development of Long COVID.

Recall that there are three main parts of the immune response – the innate, the humoral and the cellular immune responses. I liken these to three branches of our military response, e.g., ground troop responses with the Army, a sea response with the Navy and an air response with the Air Force. In the case of immunology, the innate immune response is non-specific and not targeted – continuing with my military analogy, it is like lobbing grenades or dropping bombs from B-52 airplanes like we did decades ago and hoping they get close enough to take out enemy soldiers or tanks, but also realizing there will be a lot of potential collateral damage. The innate immune response is the most immediate immune response.

The humoral and cellular immune responses take days to a week or more longer to develop than the innate immune response. The humoral immune response is your antibody response – these are like laser-guided or heat-seeking missiles that are specifically targeted to the invading enemy. The cellular immune response is incredibly complicated, but in simple terms, antibodies can only capture enemy virus before they enter and infect cells. Once inside cells, we need specialized immune cells that can recognize that a cell is harboring fugitive virus inside and then have orders to take the entire cell out and kill everything in it. [If you are totally geeking out on this and must know what these specialized cells are, these are the cytotoxic T-cells or CD8+ cells].

So far in COVID-19, our limited understanding is that neutralizing antibody levels (a subset of all antibodies, these antibodies are capable of preventing the virus from entering and infecting cells, as opposed to other antibodies that bind to the virus, but do not block cell entry, which we broadly refer to as binding antibodies) correlate with protection from infection and cellular immune responses protect against severe disease. The reason that the COVID vaccines help prevent severe disease is that they provide you with a supply of neutralizing antibodies and stimulation of the cellular immune capability prior to getting infected so that your immune system is already primed and ready, as opposed to infection in unvaccinated persons where the virus gets a 3 – 7-day head start before the immune response can catch up to the virus. Unfortunately, as we have allowed uncontrolled transmission of the virus with subsequent development of progressively more transmissible and immune evasive variants, the neutralizing antibody response from either prior infection or vaccination is less effective and shorter lasting, but fortunately, we have seen the cellular immune response be much more durable lasting in most people at least 8 months and perhaps even longer.

However, a study looking at SARS-CoV-2-specific antibodies and T cell responses at 1–2 months post-infection and 4 months post-infection showed minimal differences between individuals with persistent symptoms and those without. When I see conflicting results from studies, we either have to consider other explanations such as perhaps not all persons with Long COVID have the same immune profiles, but as of now, we cannot conclude a unifying explanation for the development of the disease such as the hypothesis that perhaps those with inadequate humoral immune responses are those that are at risk for developing Long COVID.

Still, in other patients with Long COVID, there is evidence for an enhanced immune response, which may lend support for persistent antigenic stimulation from uncleared virus or virus particles.

Frankly, while this may frustrate readers that results seem to be all over the board, this just suggests to me that Long COVID may very well be a spectrum of disease, manifesting in different ways related to a number of potential pathogenic mechanisms by which Long COVID may result (e.g., perhaps in some patients Long COVID is related to latent Epstein-Barr virus reactivation, but in others it is related to auto-immune responses).

Results of studies that might support this hypothesis include those that show that individuals who went on to report persistent respiratory symptoms showed low serum cortisol, whereas those going on to develop neurological symptoms had an elevation of proteins involved in circadian regulation of the sleep cycle. Also, evidence of Epstein-Barr virus reactivation during acute COVID-19 was a predictor for the development of persistent fatigue.

We have yet to find a unifying immune profile that can be attributed to the development of Long COVID. That could be because Long COVID is not a result of immunopathology or is only such a result in some patients, or there are various profiles involved that account for the variation in how Long COVID manifests. This requires more research because we do have a range of targeted therapies that can treat specific aspects of the immune response. We can remain hopeful that as we better understand Long COVID, we will be able to offer more options to patients.

Crimean-Congo hemorrhagic fever (CCHF) is a vector-borne disease (recall that this means transmission by an insect rather than human-to-human transmission or animal-to-human transmission (zoonotic transmission). However, unlike the several diseases I discussed in the last three posts that are transmitted by mosquitoes, this disease is transmitted by a tick. The virus responsible for this disease is called CCHF virus, a Nairovirus, a member of the Bunyavirus family. The CCHF virus causes severe viral hemorrhagic fever outbreaks with a case fatality rate (CFR – recall that this is determined by dividing the number of people who die with the disease by the number of diagnosed cases of the disease and then expressed as a percentage as opposed to the infection fatality rate or IFR, which is the number of deaths due to the disease divided by the estimated number of people infected when there are cases that may be missed due to mild or asymptomatic cases that may never be diagnosed as cases) of 10–40%.

[Note: We still refer to the disease as vector-borne even when the tick or mosquito feeds on an animal, acquires the virus and then transmits it to a human through a bite (in other words, we would not refer to that as a zoonotic transmission). Similarly, we still refer to the disease as vector-borne when the tick transmits the virus to a human and then the virus is then passed on to a fetus by a pregnant mom or to another human through sexual contact, a blood transmission or an organ or tissue donation. In this case, we would still refer to the main transmission as being vector-borne, but acknowledge that there can be limited subsequent human-to-human transmission.]

CCHF is endemic in Africa, the Balkans, the Middle East and Asian countries south of the 50th parallel north – the geographical limit of the principal tick vector.

Unfortunately, there are a wide range of potential hosts of the virus, including cattle, sheep and goats. And, while the virus does not appear to infect most birds, it does infect ostriches, and ostriches have been reported to be the source of infection for humans even though ostriches generally show no evidence of being ill.

While the primary transmission route is via tick bites, CCHF can also be transmitted by close contact with the blood, secretions, organs or other bodily fluids of infected animals when humans slaughter the animals or those of a human in a household or healthcare setting. The majority of cases have occurred in people involved in the livestock industry, such as agricultural workers, slaughterhouse workers and veterinarians.

A tick may transmit the virus to animal, in which the virus may circulate in the animal’s blood for as long as a week. During that time, another tick may feed on the animal’s blood, which may result in the tick carrying the virus to yet another animal or a human and transmitting the virus as it feeds on the animal or human.

Following infection by a tick bite, the incubation period is usually one to three days, with a maximum of nine days. The incubation period following contact with infected blood or tissues is usually five to six days, with a documented maximum of 13 days.

The onset of symptoms is often sudden, with fever, muscle aches, dizziness, neck pain and stiffness, backache, headache, sore eyes and sensitivity to light. Patients can develop a fast heart rate, swollen lymph nodes and a rash that first may be dominated by small, bright, red dots that may then evolve to areas of bruising. In some cases, patients develop swelling and tenderness in the right upper part of their abdomen due to swelling of the liver.

Severely ill patients may experience rapid kidney deterioration, sudden liver failure or respiratory failure after the fifth day of illness.

Patients who recover from this infection generally show improvement by day 9 or 10 of the illness, whereas those who die from the disease most often die during the second week of illness.

The World Health Organization has identified its top 9 list of “priority diseases,” which in the assessment of the WHO present the greatest public health risks. CCHF is on this list. [That list contains Crimean-Congo hemorrhagic fever, Ebola virus disease and Marburg virus disease, Lassa fever, Middle East Respiratory Syndrome (MERS) and Severe Acute Respiratory Syndrome (SARS), Nipah and henipaviral diseases, Rift Valley fever, and Zika.]

A virologist at the well-respected Karolinska Institute in Sweden, said that the ticks carrying the CCHF virus were “moving up through Europe due to climate change, with longer and drier summers.” In fact, Spain reported a case of CCHF last year. Iraq has been experiencing a prolonged outbreak of CCHF since last year. Already this year, 100 cases and 13 deaths have been reported. There have also been outbreaks in Namibia and Pakistan. Just this month, Turkey is reporting at least two cases.

Again, the point of this blog piece is:

1. There are many outbreaks occurring other than just the SARS-CoV-2 pandemic.
2. Many of these outbreaks are occurring in countries where these diseases have not been endemic, nor seen other than in international travelers who traveled to the south of the 50^th parallel north.
3. We need to commit to more research of these diseases, the development of therapies and the development of safe and effective vaccines.

This is part IV of a blog series that examines recent U.S. outbreaks of diseases that are not yet endemic to the U.S. and for which we usually do not see cases in the continental U.S. other than in international travelers.

In part I, I reviewed the history of some of these outbreaks. In part II, I discussed dengue fever and in part III, I wrote about Zika virus disease. The common denominator was that dengue and Zika are both flaviviruses; the diseases they cause are both vector-borne meaning that these viruses are transmitted to humans primarily through an insect – in the cases of these viruses, a specific species of mosquitoes – rather than human-to-human transmission or zoonotic transmission (animal à human) as are so many of the diseases that I have previously written about; the outbreaks have occurred in the southern U.S.; and given the fact that these viruses generally are endemic in tropical and subtropical areas of the world, these recent outbreaks may be, at least in part, related to climate change making previously less favorable environments in the northern hemisphere more hospitable for the mosquitoes that transmit these diseases.

In this part IV blog piece, I will discuss chikungunya. No doubt you are already wondering where this strange name came from and what it means. I’ll explain below.

The chikungunya virus is an alphavirus in the Togavirus family (this is a different group of viruses than that to which dengue virus and Zika virus belong). It was first identified in Tanzania in 1952, however, it received little attention, research interest or efforts at containment until it did two concerning things – (1) adapted to be able to be transmitted by an additional species of mosquito, allowing for greater spread of the disease and (2) relatedly, began causing disease in the northern hemisphere. [I know you are wondering, so here you go. There are about 3,000 different species of mosquitoes and approximately 200 species can be found in the U.S.]

Since its emergence in Tanzania, the virus has been detected in other countries of Africa and Asia. The first recorded outbreaks in urban areas were in Thailand in 1967 and in India in the 1970s.

Prior to 2006, we rarely identified chikungunya infection in U.S. travelers who travelled abroad.

Between 2006 and 2013, we would detect evidence of recent chikungunya in about 28 Americans on average per year who travelled to Africa, Asia or areas surrounded by the Indian Ocean.

In 2013, chikungunya virus was detected in Central and South America, the Caribbean islands and some U.S. territories.

Beginning in 2014, we began receiving reports of chikungunya virus disease among U.S. travelers returning from Central and South America, but more concerningly, we began seeing local transmission (this means the mosquitoes and virus were circulating in these areas) in Florida and Texas as well as Puerto Rico and the U.S. Virgin Islands.

Given the fact that we did not conduct much research into this virus and the disease it causes until relatively recently, unfortunately, it is now a public health threat for which we have many knowledge gaps, no known effective treatments and no vaccine available.

Chikungunya virus is transmitted by the same mosquitoes that transmit the dengue virus and the Zika virus.

Chikungunya infection causes high fever and disabling joint pains of varying duration. This is where the name of chikungunya comes from. Kimakonde is the language spoken by the Makonde, an ethnic group in the southeastern part of Tanzania. You will recall that Tanzania was where chikungunya was first identified. Also recall from part II of this blog series that people called dengue fever – breakbone fever – a reference to the intensity of bone, joint and muscle pains. The Makonde named this virus chikungunya – the Kimakonde word that means “to become contorted,” another reference to the intensity of the musculoskeletal pain associated with infection.

The onset of symptoms with chikungunya infection is usually 4 – 8 days, but can be as short as 2 or as long as 12 following the mosquito bite. Fortunately, not everyone develops severe symptoms. The most severe cases tend to be in the very young and the elderly. Most often, when patients are symptomatic, the first symptoms are fever and joint pain, usually with a rather abrupt onset. The joint pain is generally so disabling that people are largely bed-ridden in their homes or a hospital. These pains may last only a couple or few days, but unfortunately, in some, the pains may last weeks, months, or even years. Patients also often experience muscle pains and headache. Some will develop swelling of their joints. As with dengue fever, some will develop a rash.

Most patients fully recover, though eye, heart and neurological complications have been reported. Fortunately, at this time, the evidence supports lasting immunity against repeat infection.

Fortunately, and for not entirely clear reasons, cases of locally-contracted chikungunya have declined rapidly in the continental U.S. with no cases reported since 2015, but slower in the U.S. territories, with the last reported cases in 2019.

As with our discussion of these other vector-borne outbreaks, there are no specific precautions for Americans to undertake unless travel is planned to areas where these infections are endemic. My purpose in writing about these disease outbreaks is to raise the level of concern as I believe that these are warning signs that should promote more preparedness, testing capabilities, and research into treatments and vaccines for all of these vector-borne diseases.

In my last two blog pieces, I began a blog series addressing the fact that we have seen a number of diseases that are not endemic to the U.S. pop up and cause outbreaks. Some of these are infections that we have not previously seen people acquire in the continental U.S., but rather were involving international travelers who acquired the infection elsewhere, then traveled to the U.S., became ill, and were diagnosed with the illness here.

In part I, I reviewed a short history of a number of these outbreaks focusing on those that have occurred since 2020 to illustrate that this is not just one or two diseases, nor ancient history.

In part II, I discussed the dengue virus that caused an outbreak in Florida in 2020 that was of note because we rarely see locally contracted infections in the continental U.S.

In this blog piece, I will discuss the Zika virus. Zika virus belongs to the same family of viruses as the dengue virus – flaviviruses. As I mentioned in my last blog piece, flaviviruses are vector-borne diseases, meaning that instead of human à human transmission or animal à human zoonotic transmission, these viruses are transmitted through the bites of mosquitoes (although there is some evidence that Zika can be transmitted through sexual contact, blood transfusions, and perhaps even tissue or organ donation, though these are all less common routes of transmission. Nevertheless, WHO recommends that men returning from an area with active Zika transmission use protection or abstain from sex for a period of 3 months after their return to protect their sexual partners and that women engage only in protected intercourse or abstain from sex for a period of two months following their return from an endemic area). The same type of mosquito that transmits dengue virus and the Chikungunya virus also transmits Zika virus, and thus we tend to see Zika infections in tropical and subtropical regions of the world.

Zika virus was first identified in Uganda in 1947 in a Rhesus macaque monkey followed by evidence of infection and disease in humans in other African countries in the 1950s. During the 1960s through the 1980s, Zika disease predominantly occurred in Asian and African countries. since 2007, outbreaks of Zika virus disease have been recorded in Africa, South and Central America, Asia and the Pacific rim countries that are in the southern hemisphere, where the Aedes mosquitos abound.

In 2015 and 2016, large outbreaks of Zika virus occurred in Central and South American countries, resulting in an increase in travel-associated cases detected in US states, and widespread transmission in Puerto Rico and the US Virgin Islands. In July of 2016, the first outbreak in the continental United States was identified in the Wynwood area of Miami-Dade County, Florida.

While like dengue fever, most cases of Zika virus disease are mild, in early outbreaks we observed an increased frequency of Guillain-Barre’ syndrome (GBS), a disorder that can range from a brief duration of mild weakness and abnormal sensation, to an ascending paralysis that can be severe and progressive enough to require a ventilator for respiratory support until the condition resolves, which it does in most cases. GBS can evolve rapidly over hours, or more slowly over days or even weeks.

When Zika emerged in the Americas with a large outbreak in Brazil in 2015, we noticed an alarming association between Zika virus infection in pregnant women and congenital microcephaly (an abnormally small head) of the infants delivered from these mothers. Infants with complications from their mothers’ Zika infection during pregnancy are said to have congenital Zika syndrome. This appears to occur in 5 – 15% of pregnancies during which the pregnant mom becomes infected (some reports are as high as one-third of infants born to mothers with Zika infection during pregnancy will develop microcephaly), even when the mother is completely asymptomatic and unaware that she was infected. Besides the microcephaly that is generally quite obvious and devastating on its own, this syndrome can include limb contractures (where the arms or legs are unable to move the full normal range of motion), abnormal muscle tone, eye abnormalities and hearing loss. Also tragically, some babies will become non-viable and the mother will experience fetal loss or the baby may be a stillbirth. Zika infection during pregnancy can also result in premature birth.

There is a study following the infants born with congenital Zika syndrome in Brazil following the large outbreak in 2015 that shows these infants have an 11-fold higher mortality risk during the first year of life.

Like with dengue fever, most persons who are infected with Zika virus do not develop symptoms or develop only mild symptoms. Those that do become symptomatic generally do so between days 3 and 14 following infection. Many of the symptoms are similar to those of dengue fever – headache, fever, muscle and joint pain and rash. The symptoms generally last 2 – 7 days.

Other complications of Zika virus disease tend to occur in older children and adults and include Guillain-Barre’ Syndrome (discussed above), peripheral neuropathies (loss of proper nerve functioning of one or more nerves to the extremities), or myelitis (an inflammation of the spinal cord).

Like dengue fever, there are no specific treatments or therapies for Zika virus disease; but unlike dengue fever, there is no vaccine against Zika.

Again, there is nothing in particular that Americans need to do in regard to Zika unless you are planning to travel to an endemic area, however, our public health planning needs to take into account these increasing occurrences of outbreaks of vector-borne diseases occurring in the southern U.S. that we have not previously dealt with in terms of locally acquired infections.

We have had outbreaks in 2016 (Zika), 2020 (dengue fever) and 2023 (malaria). We must consider these as warning signs. In my next blog post, we will discuss Chikungunya.

In my last blog piece, I wrote that we have seen a number of diseases that are not endemic to the U.S. pop up and cause outbreaks. Some of these are infections that we have not previously seen people acquire in the continental U.S., but rather were involving international travelers who acquired the infection elsewhere, then traveled to the U.S., became ill, and were diagnosed with the illness here.

Dengue virus is endemic to over 100 countries in the southern hemisphere, predominantly those in tropical and subtropical regions of the world. While we do occasionally see outbreaks of dengue fever in the U.S. territories of American Samoa, Puerto Rico, and the U.S. Virgin Islands, and the freely associated states, including the Federated States of Micronesia, the Republic of Marshall Islands, and the Republic of Palau, cases in the continental U.S. have historically been in international travelers or travelers from these territories.

In 2020, there was an outbreak of locally-acquired dengue fever in Florida (72 cases), which might be less of a concern if it were not for the pattern of emerging outbreaks of other diseases for which we generally have not seen locally acquired infections in the past, but now have resulted in local outbreaks, especially in Florida – e.g., zika, chikungunya prior to the dengue fever outbreak and most recently malaria (while we have historically had local transmission of malaria, we had eliminated malaria from the U.S. back in 1951). It is interesting to note that the common denominator for these four infections is that they are all transmitted through mosquito bites.

Dengue virus is a flavivirus and flaviviruses cause vector-borne diseases in humans. Vector-borne means that the virus is transmitted to humans through the bite of an insect – typically a mosquito, flea or tick. Dengue virus is transmitted by mosquitoes. Other mosquito-transmitted flaviviruses include the yellow fever virus, Japanese encephalitis virus, the West Nile viruses, and Zika virus.

The mosquitoes that are capable of transmitting dengue virus are of the Aedes species. Modelling studies show that Aedes aegypti and Aedes albopictus mosquitoes could potentially extend their natural habitats in the southern hemisphere up to some areas of the U.S., particularly the southeastern parts of the country.

We may miss cases of dengue fever in the U.S., because in some people (estimated to be about 75% of cases), the illness is mild or even asymptomatic. Those with mild symptoms may attribute them to a cold or the flu, or be seen, but not tested for dengue fever given that this is not something most U.S. doctors have seen before.

Dengue fever can manifest as a severe disease, in fact, it is estimated that 22,000 people die from dengue annually across the globe. Classic dengue fever is characterized by high fever and intense muscle, joint and bone aching, and even muscle spasms, giving rise to its colloquial name, “breakbone fever.”

In classic dengue fever, the first phase of the illness lasts 2 – 7 days. In addition to fever and the muscle, joint and bone pain, some patients will complain of headache, nausea and vomiting and some may experience bruising, bloody nose, or bleeding from their gums. On or about the third day of the illness, most people who are symptomatic with dengue will develop a red rash, that may be smooth, may have tiny bumps, or both. In most cases, the rash does not itch. Some patients will get a rash all over their body, while others will have patchy rashes. When the rash is generalized, it generally begins over the tops of the feet and the back of the hands and then spreads to the arms, legs, abdomen and chest. There is much variation in the possible rashes and in some cases, the particular manifestation of rash tells us what the major underlying pathological process is (e.g., immune reaction versus disruption to the proper functioning of the blood and blood clotting system).

While most people recover within about a week, some people do deteriorate and require hospitalization (about 1 out of every 20 cases). Those at highest risk for severe disease are infants, pregnant moms and those with a reinfection of the virus. They can experience profound fluid losses or maldistribution of these bodily fluids, internal bleeding (sometimes called dengue hemorrhagic fever) and potentially can develop shock (sometimes referred to as dengue shock syndrome).

While many lay people are under the false impression that the initial infection of any illness is the worst, and that subsequent infections will always be milder, this is not always the case, and dengue fever is the classic exception. In the case of dengue reinfections, a phenomenon called antibody-dependent enhancement (ADE) can occur. In essence, what takes place is that the initial infection triggers an immune response. Part of that response is the production of antibodies against the virus. When non-neutralizing antibodies are produced (e.g., antibodies that attach or bind to the virus, but do not interfere with or prevent the virus from entering and infecting cells), there are some cases in which these weak antibodies can actually promote the viral cell entry and infection, often also stimulating an intense inflammatory process, a condition we refer to as ADE.

There is no specific treatment available for treating dengue fever. The efforts to develop a vaccine against this infection has been hampered by the potential for ADE. However, there is a vaccine, though it is not licensed in all countries where dengue virus is endemic.

For now, Americans need not take any specific precautions unless you are planning travel to countries where dengue is endemic. However, we need to be mindful of our own changing and evolving public health situation in the U.S.

With climate change, we may see more and more diseases that are not endemic in the U.S. migrating northward. Further, if we continue to exercise a great deal of complacency against other disease outbreaks in the U.S. such as SARS-CoV-2 and monkeypox, we risk allowing these diseases to become endemic, especially, as we allow new variants to emerge and allow infections to transmit among our wildlife and domesticated animals. We often have an opportunity to eliminate infectious diseases, but that window does not stay open for indefinite periods of time. Further concerning is the fact that after going to the efforts to eliminate a number of vaccine-preventable illnesses in the U.S., we have allowed these diseases to reemerge in outbreaks due to the uncontrolled misinformation, disinformation and anti-vax campaigns that are undermining vaccine confidence in the U.S. and globally.

It should be concerning to everyone that is paying attention that we are experiencing disease outbreaks in the US of diseases that we generally shouldn’t see outside of international travel. In some cases, these are the emergence of diseases that are endemic to other countries of the world, but not the US, and frustratingly, others are the resurgence of diseases that we previously eliminated from the U.S. Consider the list of these diseases in just in the past three years (if we went back further, we could add other infectious diseases to the list such as zika and chikungunya):

2020 – SARS-CoV-2 (novel virus)

              Dengue fever (endemic in the southern hemisphere)

2022 – Monkeypox (previously endemic to only African countries)

              Polio (eliminated from the US in 1979)

              Candida auris

              Measles (eliminated in the US in 2000)

2023 –   Malaria (eliminated from the U.S. in 1951)

The reasons are many, including:

1. The world is failing to appreciate that infectious diseases that appear limited to poor and developing countries are a threat to all countries given international travel and trade (including wildlife).
2. The world is not investing enough in research of novel viruses, antiviral development and better vaccines (durability and the induction of mucosal immunity) with broader coverage against families of viruses that pose epidemic and pandemic threats.
3. The world is not doing enough to minimize the risks of zoonotic (animal à human) transmission of novel viruses. It is estimated that roughly 75% of all newly recognized infectious agents are the result of these spillover events to humans.
4. Climate change and the resulting geographic changes in habitats of animals and vectors (e.g., mosquitos and ticks) that transmit infections to humans.
5. The rampant spread of medical misinformation and disinformation, including the well-organized, well-coordinated and well-funded antivax campaign, that has undermined vaccine confidence, and as a result, vaccination rates, is leading to a resurgence in vaccine-preventable diseases.

I have already written extensively about SARS-CoV-2 previously, so in my next blog post, I will cover Dengue fever and subsequently, the other diseases on this list.