KEVIN KAVANAGH, MD, is the founder of the patient advocacy group Health Watch USAsm and a frequent contributor to 

Kevin Kavanagh, MD

Medicine appears to have largely bought into the SARS-CoV-2 seasonal influenza analogy. Everything appears to be focused on pulmonary disease. Fringe coronavirus deniers started the narrative that COVID-19 was like the flu. This disinformation narrative has taken hold and has even affected decision making of prominent scientific committees, where disease severity is increasingly defined as a hospitalization (most commonly due to pulmonary distress), rather than the potential chronic and long-term disabling sequelae. This unfortunately, appeared to be the focus of some of the members on the Center for Disease Control and Prevention’s Advisory Committee on Immunization Practices (ACIP) which failed to approve boosters for those at high risk of occupational exposure, a decision which the CDC’s director 

COVID-19 has a number of presentations and pulmonary is just one. More than anything else, the receptor used for attachment determines the behavior of any virus, along with what organs and even species it can infect.

Human rhinoviruses, the most common cause of a cold, uses the ICAM-1 (intercellular adhesion molecule-1) receptor to 

. This receptor allows the virus to replicate in sinus tissues but not to a variety of other tissues. The influenza virus attaches to cells via sialic acid receptors, which are sugar-protein and 

. There are a number of modifications of this receptor across species, which require differing viral mutations to enable cellular attachment 

. The influenza virus primarily targets a patient’s lungs, but then the patient’s immune response can also produce a myriad of system symptoms from loss of appetite and 

. HIV uses the CD4 receptor residing on Lymphocytes. HIV is initially asymptomatic, and the initial stages of disease can easily be classified as “mild”, a disease which, if left untreated, almost uniformly turns aggressive and fatal over the course of 

In the case of SARS-CoV-2, the virus which causes COVID-19, the ACE2 receptor is used for viral entry into the cells. The ACE2 receptor is entirely different to that used by the rhinovirus and seasonal flu. It is composed of amino acids along with a 

. This receptor is present throughout the body, not just the lungs.

Clinically, SARS-CoV-2 combines some of the properties of the seasonal flu plus HIV. Similar to the seasonal flu, SARS-CoV-2 can primarily attack the lungs. But ACE2 receptors are everywhere. Similar to HIV, the virus can also enter a stealth mode, silently spreading throughout the host’s body and attacking almost every organ, especially those with a high ACE2 receptor concentration. And similar to HIV, SARS-CoV-2 also frequently causes asymptomatic spread. In full stealth mode, SARS-CoV-2 can asymptomatically attack the vasculature and 

. Myocarditis can occur and the patient is totally unaware of the damage, until an arrhythmia or symptomatic myocarditis develops. In young asymptomatic patients, this is not an uncommon sequela.

SARS-CoV-2 targeting the cardiovascular system of the body should be a given. It has been known for a long time that ACE receptors are involved in cardiovascular regulation. ACE inhibitors and ACE II blockers have long been used to treat high blood pressure. This is the same pathway the virus infects.

Thus, there are multiple presentations of SARS-CoV-2 including pulmonary, cardiac, gastrointestinal (GI), and central nervous system (CNS).

Recently, there has been mounting evidence regarding the CNS effects of SARS-CoV-2. As early as July 2020, scientists were sounding the alarm regarding COVID-19 brain damage: Including temporary brain dysfunction, strokes, nerve damage and 

. At that time, these conditions were still considered relatively uncommon. An article published in 

 found 1 in 3 COVID-19 survivors were diagnosed with brain or mental health disorders, but separating out what is due to the stressors of the illness versus direct effects of the virus was problematic.

Sandra Lopez-Leon, et al. performed a system review and meta-analysis of long COVID-19 and found the 3 most common long COVID symptoms were “fatigue (58%), headache (44%), and attention disorder (27%)”, all of which can 

Ritchie, et al, noted that cognitive dysfunction has been commonly reported with COVID-19, but the true incidence is unknown, and notes that: “The hippocampus appears to be particularly vulnerable to coronavirus infections, thus increasing the probability of post-infection memory impairment…” and that the virus may enter the CNS through the 

. Finally, in August of 2021, research by Gwenaëlle Douaud, et al. documented with brain imaging “abnormalities in limbic cortical areas with direct neuronal connectivity to the primary 

.” In addition, there was “a marked reduction of grey matter thickness in fronto-parietal and temporal regions.” “The 401 SARS-CoV-2 infected participants also showed larger cognitive decline between the two timepoints in the Trail Making Test (visual attention and task switching) compared with the controls…”

Again, none of this should come as a surprise, since anosmia or lack of smell, is one of the most common presenting symptoms of COVID-19. The olfactory nerve is not actually a nerve but a projection of the brain itself.

Thus, COVID-19 has a myriad of different presentations, all of which can result in severe and long-term sequelae.Just because COVID-19 is asymptomatic or does not produce “severe” pulmonary disease does not mean the patient does not have a serious infection.It is of utmost importance for public health officials to implement strategies to prevent the occurrence of long-term COVID-19 related disabilities and not just focus on acute pulmonary symptoms.

Articles

Unlike influenza, SARS-CoV-2 uses ACE2 receptors to infiltrate cells. Similar to HIV, SARS-CoV-2 can silently spread throughout the host’s body and attack almost every organ.

Viewpoint: Here’s Why COVID-19 Is Much Worse Than Flu

This week’s meeting of the Center for Disease Control and Prevention’s Advisory Committee on Immunization Practices (ACIP) focused on approval of the Pfizer/BioNTech vaccine boosters. I was keenly interested in this meeting. For me it was personal. For almost 2 years I have written articles for 

, I have also developed a significant medical issue. This was diagnosed during the pandemic and is a testament to not putting off medical evaluations because of the virus. Initially, I chose to follow conservatively, but because of progression, I elected to have surgery. Surgery that was cancelled because of filled medical centers due to a near collapse of our health care system from unvaccinated COVID-19 patients filling Kentucky and Tennessee hospitals. In addition, there is also a critical shortage of health care personnel.

Thus, I am very biased, and watched with horror as the committee declined to approve boosters for our frontline workers, including health care personnel. This happened even after CDC Director Rochelle Walensky, MD, advised the committee to not be swayed by influences other than science. It did not appear the committee heeded this advice. Instead, it appeared to fall prey to political talking points and what I feel was sub-par research to bolster its position.

At the beginning of the meeting there was time for public comment, and I gave a 3-minute commentary stressing the importance of having to act now and that the United States does not have the luxury of waiting for randomized 

. Non-action is also an action. I stressed the importance of long COVID-19 and pointed out even those with mild or moderate infections were at risk. I advocated for the expansion of the Food and Drug Administration’s recommendations for boosters for those at high risk of occupational SARS-CoV-2 exposure. And finally, that the degree of exposure should not be a consideration, since being exposed is like being pregnant: You either are exposed, or you are not.

A major political talking point, which many committee members appeared to have fallen for, is that if you are not hospitalized you are fine, and prevention of COVID-19 not requiring hospitalization is not a priority. Many refer to this as “mild” or “moderate” disease. Throughout the FDA and CDC approval process I heard that the goal which they were trying to accomplish was to keep patients out of the hospital and ICU. I do not know who set this goal. Certainly not the White House. Their goal appears to be the prevention of morbidity and mortality along with keeping the supply chain open by protecting frontline workers. Already in Kentucky we are seeing signs of collapse with our schools having difficulty in obtaining food supplies for 

The problem with this is that hospitalizations and severe infections are often based upon a patient’s pulmonary symptoms and SARS-CoV-2 is not like the flu, it affects almost every organ of the body. Patients may not have a primary pulmonary presentation, some may have primarily gastrointestinal, cardiovascular or central nervous system symptoms. Cardiovascular involvement is common and can occur in those with no or 

. Myocarditis often is asymptomatic. Thus, the virus damages many organs of the body, resulting in long COVID-19 which afflicts 10% to 30% of patients with mild to moderate symptoms.

In other words, even if not hospitalized, COVID-19 often produces the most severe infection individuals will experience in their lifetimes and can produce lasting symptoms of fatigue, weakness, brain fog and cardiovascular damage. It is unbelievable to me how the loss of smell is just shrugged off as a minor symptom. As a retired ear, nose, and throat doctor, if I would have performed a surgery which resulted in the loss of smell I could have been sued for hundreds of thousands of dollars.

Another political talking point is the assertion that health care workers have been provided adequate protection and are not at high occupational risk for SARS-CoV-2 acquisition. We heard this assertion during the committee meeting. In addition, it was stated there was research to support this position.

However, the main research I could find is one published by Jacobs, et al. in 

 which compared the seropositivity in health care workers with the 

, ScD, one of the overriding problems of this study is that the conclusion that “these findings provide reassurance that current infection prevention practices in diverse health care settings are effective in preventing transmission of SARS-CoV-2 from patients to HCP.” Is not supported by the data. In addition, Brosseau points out that “the investigators fail to note that health care personnel had an overall infection incidence rate of 440/10,000 (4.4%), 6 times higher than the average community infection rate of 72.4/10,000 (0.7%)” And that “a recent study found SARS-CoV-2 transmission between asymptomatic patients and health care personnel despite the use of medical masks and 

. It is time to stop pointing fingers at community transmission and recognize and address the importance of work-related exposure.” Finally, this study used serology and not PCR testing of actual infections. The health care worker participants volunteered for serology testing. I feel the control group needed better description to rule out any biases which may have been present due to differences in these 2 groups.

With the high viral load that health care workers are exposed to, along with the many reports I am hearing of breakthrough infections in these workers, they definitely need to be prioritized for boosters. Health care workers were among the first to be vaccinated and, thus, would be expected to be among the first to have waning vaccine immunity.

Even if community exposure was true, as stated by Helen Keipp Talbot, MD, of Vanderbilt University, who also voted yes, “…vaccinating health care workers, who are being exposed in the community, would help to maintain staffing levels at already 

This is an argument which I wholeheartedly support, since I would not want to have my treatment prevented again due to health care workers afflicted with COVID-19.

Walensky swiftly acted and in the evening 

 the committee’s decision. The following was added to the CDC recommendations for individuals eligible for boosters: “People aged 18-64 years who are at increased risk for COVID-19 exposure and transmission because of occupational or institutional setting may receive a booster shot of Pfizer-BioNTech’s COVID-19 vaccine at least 6 months after their Pfizer-BioNTech primary series, based on their individual benefits and risks.”

I feel this was a very wise decision which demonstrated proactive action and the ability to separate political rhetoric from science. I feel APIC needs to have a paradigm shift in thinking. These are not normal times; we need swift decisions which will often have to be based upon experience and the preponderance of evidence. As stated by John F. Kennedy “There are risks and costs to action. But they are far less than the long-range risks of comfortable inaction.”

Even if not hospitalized, COVID-19 often produces the most severe infection individuals will experience in their lifetimes and can produce lasting symptoms of fatigue, weakness, brain fog and cardiovascular damage.

Viewpoint: Politics, Bad Science Taints Decisions About COVID-19

 of the Food and Drug Administration’s Vaccines and Related Biological Products 

(VRBPAC)regarding boosters for the Pfizer/BioNTech vaccine as indecisive. After hearing a plethora of leading experts regarding waning immunity of the Pfizer vaccine, the FDA initially voted to turn down the proposal to offer a third dose to anyone 16 years of age and older.

VRBPAC essentially threw up its hands on this question and indicated that it might be decided at a meeting of the Advisory Committee on Immunization Practices (ACIP), an advisory committee of the Centers for Disease Control and Prevention, scheduled for 

VRBPAC’s move surprised me, since the Israeli presentation clearly indicated the need for proactive action in a wide range of age groups, and health care providers need maximum flexibility in their recommendation of boosters to patients. In addition, we should all be aware of the dangers of taking a reactive stance, especially during a raging pandemic where action is needed 

 and the immunity elicited by boosters may take weeks to kick in. We do not have the luxury of waiting 6 months for the results of randomized controlled trials.

Sharon Alroy-Preis MD, MPH, MBA, Israel’s Director of Public Health Services, pointed out that Pfizer vaccine boosters not only augmented immunity in the elderly, but also created a 10-fold increase in protection in 40- to 60-year-olds. With the disease profile of delta markedly shifting to younger age groups, not providing boosters to a wide range of individuals would appear to not be good public health policy.

The committee then took a temporary recess and afterwards authorized the Pfizer booster for those individuals 65 years of age and old, and to individuals at high risk for severe COVID-19.

The emphasis appeared to be on the prevention of “severe” disease in those at high biological risk, including those individuals who are 65 years and older and at least 5 months post full vaccination. In this age group, Israeli data found breakthrough infections to be associated with an 8.6% chance of hospitalization and a 2% 

Many or our national authorities and at least one FDA committee member appeared to be mitigating the severity of COVID-19 infections which are not hospitalized, giving the impression that these are “mild” cases and intervention is not urgent. I have friends who have developed mild to moderate cases with resultant loss of smell, chronic fatigue, and brain fog. After many weeks they are still not yet able to return to normal activity These cases represent the severest infections many will experience in their lifetime, and these infections need to be prevented.

There was also concern regarding myocarditis in the young, and if in this age group the risks versus benefits would warrant boosters. However, even in the young, cases of myocarditis are rare (1 in 5,000 to 1 in 6,000). As emphasized Alroy-Preis, 95% of these cases are not severe, and even young individuals can and do develop long COVID.

Finally, concern was expressed regarding availability of vaccines in Third World countries. However, the ultra-cold storage and distribution in Third World nations is problematic at the very least, and as stated on 

 by Francis Collins, MD, this is largely a 

. In addition, the United States has discarded millions of doses of mRNA vaccines which need to be 

After the second vote, it was asked, “What about health care workers?” Suddenly, I could feel an urgency in the committee and the emphasis appeared to shift. Health care workers know all too well the lasting and debilitating effects of long COVID-19. They were one of the first to become vaccinated and are some of the first experiencing breakthrough infections. They are tired, burned out, and many are on the brink of collapse. They do not need to be told: “Tough it out. You are not going to be getting a booster.”

It was proposed to take an informal poll regarding the need to extend the interpretation of the approved FDA recommendation to health care workers. It was then mentioned that other workers with high occupational exposure should also be included. Someone then asked what about those at high risk for COVID-19 who are not employed? But the committee did not include these individuals. One committee member mentioned this would be too difficult to interpret.

From my point of view this was unwise, since the proposal now may exclude caregivers of unvaccinated school age children, and places these caregivers at an unnecessary risk.

The final poll question which passed unanimously was: “Should health care workers or others at high risk for occupational exposure be included in this EUA”? It was clearly stated that this would include health care workers, other frontline workers (such as teachers) and potentially essential infrastructure workers.

I feel this was a 180-degree change in thinking. Initially, the concern appeared to be centered on having solid data which showed severe breakthrough infections were developing, especially in those who are biologically at high risk for disease. Now the concern was focusing on having a high risk of exposure to COVID-19, regardless of the biological susceptibility of the individual.

However, not to include those with non-occupational exposure was not being consistent and would place many at unnecessary risk.

It should be remembered that vaccine complications are exceedingly rare. Even myocarditis does not occur frequently and is usually seen in males under the age of 30. In addition, Alroy-Preis reported boosters provided a 10-fold in protection down to the age of 40.

In view of the above, I feel ACIP should provide further clarification and interpretation of the FDA recommendations. It would be more reasonable to either reconsider the initial proposal of offering boosters to all who are 16 years of age or older, or at least offering boosters to those who are 30 years of age or older, plus individuals who are at high risk for severe long COVID.

Although the latter proposal will exclude many individuals who could benefit from a booster, one needs to remember, it will take some time to roll out boosters and the group below 30 was the last to receive vaccinations, thus, would be expected to be the last to have waning protection. This will give time for more consideration and additional data to emerge regarding optimization of boosters in this cohort.

Health care workers know all too well the lasting and debilitating effects of long COVID-19. They were one of the first to become vaccinated and are some of the first experiencing breakthrough infections. They are tired, burned out, and many are on the brink of collapse.

Viewpoint: On COVID Boosters, CDC Panel Must Recover Ball That FDA Panel Fumbled

Those who had hoped for a full course meal of an endorsement of COVID-19 booster shot availability in the United States resulting from a 

 by an advisory committee to the Food and Drug Administration (FDA) were instead handed a small snack.

The FDA’s Vaccines and Related Biologic Products Advisory Committee (VRBPAC) yesterday declined to approve Pfizer boosters for those 16 years of age or older—despite a preponderance of testimony backing that move—but did approve Pfizer boosters 6 months after full vaccination for those who are 65 years of age or older, along with other individuals who are at risk for severe COVID-19 under the FDA’s emergency use authorization (EAU).

But then at the end of the meeting some committee members expressed second thoughts about their highly restrictive recommendation. There was a discussion regarding health care workers, and agreement that they should be included in the recommendation. There was then agreement that other frontline workers should also be included. But those who were at significant risk of COVID-19 exposure in a non-occupational setting were not to be included. An informal poll was then taken regarding the support for boosters in health care and other frontline workers for the Pfizer vaccine. The poll passed unanimously.

It wasn't clear why that decision was made. In addition, if exposure indeed is a major variable to obtaining a booster—some would argue that the initial question about far-reaching availability of booster shots should perhaps be readdressed.

The bottom line: The committee discussion provided valuable information, but the panel decided against a sweeping strategy. It instead settled on recommending the boosters for those 65 and older and others at risk for severe COVID-19.  In the end, the committee punted to next week’s meeting of the Advisory Committee on Immunization Practices (ACIP), an advisory committee of the Centers for Disease Control and Prevention (CDC).

The meeting occurred as the delta variant has reignited the pandemic with a vengeance. There are 145,000 cases per day and the death rate from COVID-19 has a 7-day moving average of 1,300 deaths per day. At the same time, there are reports out of Israel on the waning of the Pfizer vaccine. Some medical experts say that action is needed. In this case, inaction is also an action—either the United States gives boosters or does not. Many medical experts say that that decision needs to be based on the best available evidence. Instead, there seems to be a desire to wait another 6 months for pristine randomized controlled studies.

COVID-19 vaccines have had a tremendous effect on the prevention of hospitalizations and deaths as illustrated in the below graph on hospitalizations in unvaccinated and vaccinated individuals. 

Source: Centers for Disease Control and Prevention

 was one of the first to publish the Israeli data on severe breakthrough infections in the elderly who are more than 5 months post full vaccination with the 

. In this cohort there was an 8.6% incidence of hospitalizations and 2% incidence of death with delta variant breakthrough infections. Data from Qatar also showed a decline in vaccine effectiveness in those who are over age 60 and after 25 weeks post 

During the FDA meeting the data from Israel was center stage. On July 30, 2021, Israel started to administer Pfizer vaccine boosters to those over the age of 60 and who have received their second vaccine dosage more than 5 months earlier. Recent data published from Israel in the 

 demonstrated that a Pfizer booster administered to those greater than 60 years of age and at least 5 months post full vaccination, lowered reinfections by 11.3% and severe 

 Preliminary results presented at the FDA meeting reported that boosters also created a 10-fold protection from infections in 

Sharon Alroy-Preis, MD, MPH, MBA, Israel’s Director of Public Health Services, reported that in July and early August there was a greater than 10-fold increase in severe cases, and 60% of these were in fully vaccinated individuals. She stressed that the trend in vaccine waning was also seen in the 40 to 60 year-old age groups who were fully vaccinated and that the problem of 

 in young people supports the vaccination of the entire population. 

Donna Boyce from Pfizer presented confirmatory data which showed vaccine efficacy waning 6 to 8 months after the second dose, and a study from Kaiser Permanente suggested the decrease in efficacy is from waning of the immunological response and not from the immune-escape properties of the delta variant.

Some questioned the results because the United States is not currently seeing a high hospitalization rate from breakthrough infections that Israel is seeing. In the Q&A period, 

, of Princeton University, stressed that this may be because Israel vaccinated the elderly very early, and patients were 5 to 6 months out from full vaccination. The elderly is the cohort most impacted with breakthrough cases resulting in severe infections and deaths. In addition, Israel solely used the Pfizer/BioNTech vaccine which may have less durability than the 

During deliberations it was pointed out by several committee members that ideally a booster could be tailored to the Delta variant using mRNA technology. In addition, there was concern that the increase in immune response, which was greater than the second dose, may also increase the risk of myocarditis in young males. Alroy-Preis stated that risks of myocarditis from COVID-19 was greater than that from vaccination, and that 95% of cases were not severe.

Several public commenters, focused on the need for Third World countries to receive the vaccine which would help prevent the emergence of variants in Third World countries. It should be remembered that the distribution requirements for mRNA vaccines require ultra-cold storage and may require three doses; will be formidable in Third World countries. In addition, partially vaccinated individuals in the United States may be even a higher risk for the production of mutations if they become infected with the virus.

In the Q&A, it was pointed out by a researcher from Germany that they were not able to determine an antibody titer which denotes adequate protection from SARS-CoV-2 illness. This revelation is of utmost importance in the current debate in the United States regarding “natural immunity.” The wide range of infection severity produced by SARS-CoV-2 will cause a wide-spectrum of immune responses and it is not yet possible to test and determine who has adequate protection and who does not.

The committee expressed support for a booster for those who are over the age of 60 who are 6 to 8 months post vaccination, but there were concerns over myocarditis and other risks in young patients. The post vaccination risk of myocarditis which most commonly occurs in males less than 30 years of age (peak 16 to 17 years) is between 1 in 5,000 to 1 in 6,000. It was felt that even larger studies would not detect this rare occurrence, only diligent vaccine follow-up.

The recommendation to vaccinate all individuals, not just the elderly, was not only driven by the desire to prevent disease but also by the desire to eliminate transmission, along with long COVID and resultant chronic disability.

Another issue was that it may be more beneficial to focus on efforts on administering vaccine doses to those who have not received the vaccine rather than on giving boosters. However, since March of 2021, 15 million doses of the vaccine have been discarded in the 

. Most agree this is a huge waste and these doses need to be placed in arms, even if boosters are given over primary vaccinations. Some leaders in the United States are already taking action. On September 8, 2021, Governor Larry Hogan of Maryland declared anyone over the age of 65 as being immunocompromised, and are now 

Moderna vaccine boosters were not addressed. The Moderna vaccine contains over three times the amount of mRNA as the 

 and the data from Mayo Clinic has shown less degradation in 

. From January to July, the Pfizer vaccine was observed to decrease its effectiveness in preventing infections by 42%, the Moderna by only 72%. There are little data available on waning efficacy for the Johnson and Johnson vaccine.

Some medical experts say that in this case, inaction is also an action—either the US gives boosters or does not. That decision needs to be based on the best available evidence. Instead, there seems to be a desire to wait another 6 months for pristine randomized controlled studies.

Kevin Kavanagh, MD

Articles

Viewpoint: Here’s Why COVID-19 Is Much Worse Than Flu

Viewpoint: Politics, Bad Science Taints Decisions About COVID-19

Viewpoint: On COVID Boosters, CDC Panel Must Recover Ball That FDA Panel Fumbled

FDA Panel Sidesteps Decision for Broad Distribution of Booster Shots