Categories
Epidemiology Outpatient Practice

Is It Dangerous To Vaccinate Pregnant Women And Children Against COVID?

Last fall, I was hiking and birdwatching in a nature preserve in coastal North Carolina. A woman walked by talking on her cell phone loudly enough for me to overhear her conversation 50 feet away. She spoke about her outrage that children were being vaccinated against COVID and that her internet research from the Children’s Health Defense organization indicated to her that COVID was a hoax propagated by Bill Gates and that COVID vaccines cause autism. I rolled my eyes, kept my mouth shut, and went back to watching egrets.

It reminded me of another conversation that I had with one of our family medicine physicians about 15 years ago. It was October and she was pregnant. I had arranged an influenza vaccination station in the hospital physician lounge and told her about it so that she could get vaccinated. She said that she wasn’t going to get a flu shot because she believed that flu shots in pregnant women cause autism in their children. I tried to convince her otherwise but she was firm in her beliefs. That winter, when she delivered her baby, she had active influenza. Her newborn ended up in the neonatal ICU at Nationwide Children’s Hospital with an intracranial hemorrhage.

The lesson is that misinformation abounds, even among intelligent and educated people. The main defense against misinformation is scientific research. In the short-run, misinformation can persist but in the long-run, science eventually prevails. Beliefs such as the sun revolves around the earth, the earth is flat, and smoking cigarettes is beneficial to your health were all held as incontrovertible truths in the past but eventually were dispelled by science to all except the most gullible. This week, two new scientific studies were published that will help to dispel misinformation about COVID vaccines and children.

The first was a study in JAMA that looked at all newborns in Sweden and Norway between June 2021 and January 2023; in total, 196,470 infants. 48% of the infants were born of mothers who were vaccinated against COVID during pregnancy and 52% were born of unvaccinated mothers. The results are striking. The babies born from unvaccinated mothers were twice as likely to have intracranial hemorrhage compared to babies born from mothers who were vaccinated during pregnancy. In addition, compared to babies whose mothers got vaccinated, the babies of unvaccinated mothers were twice as likely to die and 50% more likely to have hypoxic encephalopathy. The benefits of maternal vaccination did not stop there. Newborns of unvaccinated mothers were also more likely to have anemia, bleeding, thombosis, lower birth weight, septicemia, seizures, heart failure, feeding problems, and necrotizing enterocolitis. This was a study that involved a huge number of subjects and made all the stronger because all children born in the two countries for a year and a half were included in the analysis.

The second study was also published in JAMA and looked at 2,959 children between ages 5-17 at 6 U.S. study sites in Texas, Arizona, Oregon, Michigan, Utah, and Washington. 25% of the children received a bivalent COVID vaccine and 75% were not vaccinated with a bivalent COVID vaccine. The results were not surprising – the unvaccinated children were more likely to get both asymptomatic COVID infections and symptomatic COVID infections compared to the vaccinated children.

These two studies will not convince all anti-vaxxers but they will hopefully loosen the hold of misinformation on some of them. For some people, beliefs are just too hard to break – there are still those among us who believe that there are bands of bigfoot roaming rural Ohio, stealing chickens and throwing rocks at passing cars. Similarly, like the woman at the North Carolina nature preserve, there are those who are ardent believers of Robert F. Kennedy, Jr. (the founder of the Children’s Health Defense organization) who publicly stated about COVID vaccines: “It is criminal medical malpractice to give a child one of these vaccines”. In 1887, Abraham Lincoln famously said “You can fool all of the people some of time; you can fool some of the people all of the time, but you can’t fool all the people all the time.” Kennedy has made millions of dollars for himself by fooling some of the people all of the time.

But physicians can now tell their pregnant patients with confidence that getting a COVID vaccination will improve their chances of having a healthy baby and improve the chances that their baby will live through its first month after birth. COVID vaccines do not provide 100% protection against the infection. But then neither do kevlar vests provide 100% protection in a mass shooting. However, wearing a kevlar vest will improve your chances of surviving and improve your chances of avoiding major injury. COVID vaccines are like wearing a kevlar vest against the virus for pregnant women and for children.

February 7, 2024

Categories
Epidemiology Outpatient Practice

Why Your Practice Needs An Outpatient Antibiotic Stewardship Program

When physicians hear the words “antibiotic stewardship”, they think of inpatient programs to control antibiotic use. However, more than 80% of antibiotics are prescribed in the outpatient setting. The Joint Commission mandates that hospitals have an inpatient antibiotic stewardship program but there is no national requirement in the outpatient setting and consequently, better stewardship of outpatient antibiotic use is essential to control multi-drug resistant bacteria.

Emergence of drug-resistant bacteria

Charles Darwin

The story of drug-resistant bacteria is the story of evolutionary biology and that story dates back more than 2 centuries ago.

It was the fall of 1827 and Charles Darwin was bored. He was in his second year of medical school at the University of Edinburgh but was neglecting his medical studies as he was more interested in studying the biology of oysters than of humans. So, his father sent him to Cambridge to study to become a county parson instead. There, he was more interested in studying entomology than religion. However, he did manage to graduate in 1831. But with no employment opportunities that interested him, he decided to sign on as a naturalist on a 5-year expedition to chart the coast of South America on the HMS Beagle. His observations of during the voyage served as the foundation for his theory of natural selection that later became the central tenet of evolutionary biology.

Alexander Fleming

Perhaps nowhere has natural selection been more easily observed than in the emergence of antibiotic resistant bacteria over the past 80 years. In 1928, Alexander Fleming discovered penicillin, purely by accident. In 1941, police constable Albert Alexander became the first person treated with penicillin when he scratched his face with a rose thorn and developed a flesh-consuming infection caused by Staph aureus. After 5 days of treatment with the new drug, his infection was under control but he then relapsed when his doctors exhausted their supply of penicillin. When penicillin was initially rolled out, it killed essentially all Staph aureus bacteria. But by 1942, penicillin-resistant Staph were identified and by 1946, 12.5% of all Staph aureus isolates were resistant to penicillin. One year later, the incidence of penicillin resistant staph had tripled even further.

Methicillin-resistant Staph aureus

To fight the rapidly emerging resistance of Staph aureus to penicillin, a new semi-synthetic penicillin derivative was created in 1959 called methicillin. It was first marketed in September 1960 but only one month later, a public health lab in London identified isolates of Staph that were resistant to the new antibiotic and these were called methicillin resistant Staph aureus, or MRSA. Thirty years ago, 2% of all Staph infections were due to MRSA. Today, in the United States, most staph infections are caused by MRSA and one-third of all healthy Americans are colonized with MRSA in their noses. To treat MRSA infections, the medical community turned to vancomycin. But in 2002, the first case of vancomycin-resistant Staph aureus was identified in a diabetic patient in Michigan. Today, vancomycin-resistant Staph aureus has replaced MRSA as the bacterial bogyman in our nation’s hospitals.

Currently in the United States, there are 2.8 million infections caused by drug-resistant infections and 35,000 deaths due to antibiotic resistance every year. There are additionally 12,800 deaths each year due to Clostridium difficile that arises as a complication of antibiotic use. Antibiotic overuse and misuse is fertilizer for antimicrobial resistance. To slow the emergence of drug-resistant pathogens, it is necessary to more judiciously prescribe antibiotics, especially in the outpatient setting.

The problem of outpatient antibiotic use

In the U.S., three are 211 million outpatient antibiotic prescriptions written every year. The CDC estimates that 72% of these are necessary but 28% are unnecessary. Even when antibiotic prescriptions are necessary, we have opportunities to improve drug selection, improve drug dosing, and shorten the duration of administration. Taking all of this into consideration, about half of all outpatient antibiotics are either unnecessary or prescribed incorrectly.

All of us who practice outpatient medicine have been guilty of antibiotic misuse at one time or another. A patient comes to the office with a viral upper respiratory infection and the doctor prescribes an antibiotic that was never needed in the first place. Maybe the doctor was not aware of clinical practice guidelines for managing upper respiratory infections. Maybe the doctor wanted to make the patient happy by prescribing an antibiotic. Maybe the doctor was afraid of complications of the URI. Maybe the doctor figured he or she could bill a higher level of service for the office visit by prescribing an antibiotic. Maybe the doctor thought that it would be faster to prescribe an antibiotic than to explain why an antibiotic was not necessary. Regardless of the reason, the next time that the patient has a cold, that patient will believe that an antibiotic is necessary and expect the physician to prescribe one. This results in a vicious cycle of antibiotic misuse.

The 4 components of outpatient antibiotic stewardship

The Centers for Disease Control has an excellent on-line resource for outpatient antibiotic stewardship. This resource identifies four key components that can be incorporated into any outpatient practice: commitment, action, tracking, and education.

Commitment

Not only must the physician be committed to appropriate antibiotic use but the entire office staff must be committed. This implies that a consistent message will be given to patients, from the nurses, from the schedulers, from the medical assistants, and from the physicians. For example, when a patient calls in with a sore throat, the nurses can set the stage for antibiotic stewardship by saying “The doctor needs to evaluate you in person to determine if an antibiotic is necessary” rather than simply calling in an antibiotic prescription. The schedulers can help by telling the patient that the office has the ability to do on-site rapid strep screens during the patient’s office visit. The medical assistants can reinforce the message by telling the patient that a negative rapid strep test means that the sore throat is not caused by a bacteria.

Ideally, each medical practice should have a leader for the practice’s antibiotic stewardship program. This could be a pharmacist, nurse or medical assistant. This individual would be responsible for ensuring that all of the office staff know their roles in antibiotic stewardship and that the office’s commitment to antibiotic stewardship is communicated to patients. A simple way of doing this is with posters in the waiting room or in the examination rooms stating the practice’s commitment. The CDC has a down-loadable poster that can be used by any medical office. A 2014 study found that inappropriate antibiotic prescriptions were reduced by 19.7% simply by hanging commitment posters in exam rooms.

Action

Incorporation of evidence-based guidelines for management of common outpatient infections can help ensure that the right antibiotic is prescribed for the right duration of time for any given bacterial infection. Guidelines can also help ensure that antibacterial antibiotics are not prescribed for viral infections. One of the challenges with use of evidence-based guidelines is that many national organizations publish their own guidelines for any given infection and these guidelines can differ depending on the decisions of different guideline writing committees and how long in the past the guidelines were written. Large medical centers can develop their own practice guidelines based on distillation of available literature. In smaller outpatient practices, it is best for all of the providers to agree on the use of one guideline or another – it can be confusing to staff and patients if different providers in the practice utilize different clinical guidelines. When possible, the power of the electronic medical record should be harnessed to prompt clinicians regarding test ordering or antibiotic prescriptions for any given infection based on the ICD-10 diagnoses.

A useful action plan is the use of the “over-the-counter prescription pad” to use for common viral infections – essentially a printed checklist of non-antibiotic recommendations by the provider for such items as acetaminophen, NSAIDs, decongestant nose sprays, guaifenesin, dextromethorphan, etc. Often, a printed paper to given to the patient that is customized to include the patient’s name, date, and diagnosis can be a powerful way to reinforce that antibiotics are not necessary and that the physician is invested in treating the patient (just not with an antibiotic).

Tracking

For hospital-employed physicians, most compensation plans incorporate some kind of quality metric into each physician’s annual bonus. In our medical center, over the years these have included metrics such as percent of patients getting mammograms or colonoscopies, percent of patients getting influenza vaccinations, and patient satisfaction scores. Antibiotic stewardship is in many ways an ideal quality metric for outpatient and ER practices. This is because appropriate antibiotic prescription is a physician behavior whereas when a patient refuses a flu shot, is a no-show for their scheduled colonoscopy, or writes a bad patient satisfaction survey, it is a patient behavior. As a result, using these latter types of metrics for physician bonuses tends to financially reward physicians who have a “desirable” patient panel as opposed to those physicians who care for a lot of uninsured, lower income, or lower education level patients. By using a physician behavior in the bonus equation, the practice can avoid penalizing physicians for patient behaviors that are beyond the physicians’ control.

The electronic medical record can be utilized to track and report antibiotic stewardship quality metrics such as use of order sets derived from the organization’s clinical practice guidelines, use of rapid strep testing in patients given antibiotics for pharyngitis, and appropriate duration of antibiotics for uncomplicated urinary tract infections.

Education

This requires both education of physicians and education of patients. Physician education can take the form of grand rounds and other CME events about antibiotic stewardship. But on a smaller scale, can include distribution of the organization’s clinical practice guidelines for common infections. Successful distribution can be a challenge, however – many hospitals that maintain a “clinical practice guideline” website on the hospital’s intranet find that physicians rarely access the website. Successful adoption of guidelines usually is most effectively done on a local basis, such as at medical staff meetings, at department meetings, or by incorporation of the guideline into the electronic medical record.

Patients need to be educated about the difference between viral and bacterial infections and why viral infections do not require an antibacterial antibiotic. They also need to be educated about the risks of antibiotics, including costs, side effects, development of drug-resistant bacteria, and C. difficile. Patient education materials can again include posters for the examination rooms but can also include text pasted into the patient’s after visit summary. Whenever possible, after visit summaries should be printed and handed to the patient at the end of their office visit rather than simply loaded onto the patient portal in the electronic medical record – few patient actually open up their patient portal after they leave the office but a piece of paper will tend to stick around until the patient actually reads it.

The Centers for Disease control has several excellent patient education handouts that can be printed as posters for the office’s exam rooms or as paper handouts to be given to patients. These are available in both English and Spanish language versions. These can be downloaded from the CDC’s website or you can click on the images below for the English language handouts.

 

 

 

 

 

 

Penicillin allergy deserves a special mention. Fully 10% of patients report having an allergy to penicillin but only 1% of the population actually has penicillin allergy when tested for IgE-mediated reactions. In other words, 9 out of 10 patients who think they have a penicillin allergy do not actually have an allergy.  One of the reasons for this is that 80% of patients who truly have a penicillin allergy lose their IgE responsiveness after 10 years. But presumption of penicillin allergy drives the use of more broad-spectrum antibiotics and the development of drug-resistant bacteria. Patients reporting penicillin allergy should be asked about the specific symptoms they had when taking penicillin in the past. When uncertainty exists, patients should undergo penicillin skin testing. In the past, this required consulting an allergist but now there are easy-to-perform penicillin allergy skin tests that can be done in the primary care office. Importantly, if the test is negative, then not only does the patient need to be informed that they are not allergic, but penicillin allergy should be removed from their electronic medical record.

The special case of dentistry

Dentists account for 10% of all outpatient antibiotic prescriptions. But dental practices generally fall outside of the purview of our nation’s hospitals. As a consequence, dental practices are largely on their own when it comes to antibiotic stewardship support. Physicians can help by participating in dental continuing education programs and by sharing effective programs and practices with local dentistry colleagues. One of the important changes over the past 20 years has been a move away from indiscriminate use of prophylactic antibiotics prior to dental procedures in patients with heart murmurs and limiting prophylactic antibiotics to only those cardiac patients that truly benefit from them. There are also CDC guidelines for when to prescribe antibiotics for common oral infections such as pulpitis, periodontitis, and pulp necrosis.

An ounce of prevention

The most effective way to reduce antibiotic misuse and development of drug-resistant pathogens is to never get infected in the first place. Keeping patients up to date with vaccinations is essential. Chief among these for bacterial infections is pneumococcal pneumonia – the new PCV20 vaccine should be given to all adults over age 65. Similarly, viral infection can mimic bacterial infections or lead to secondary bacterial infections that can result in antibiotic prescriptions. Preventing these common viral infections can thus reduce antibiotic use. All Americans should receive an annual influenza vaccine and COVID update vaccine. All people over age 60 and all pregnant women should be vaccinated against RSV.

We are fortunate to be living in an era when we have more effective vaccines for deadly diseases than ever before. Vaccine recommendations change frequently as new vaccines are developed. The CDC lists the current vaccination recommendations on their website. You can also click on the images below for the 2024 child and adult vaccine schedules.

 

 

 

We don’t have to lose the war…

I have watched patients die of bacterial infections that were untreatable with any known antibiotic. I have taken care of patients with such extensive drug allergies that there was only one or two antibiotics that I could use for any infection they came down with. I have taken care of patients who were admitted to our ICU with overwhelming Clostridium difficile due to taking an unnecessary antibiotic or due to taking a necessary antibiotic for longer than indicated. In all of these cases, antibiotic misuse and drug-resistant bacteria were the root causes.

The good news is that initiatives to reduce antibiotic misuse are effective. Since 2013, the CDC reports that there has been  a decrease in hospital-acquired infections caused by vancomycin-resistant enterococcal, multi-drug-resistant Pseudomonas, methicillin-resistant Staph aureus, carbapenem-resistant acinetobacter, and drug-resistant Candida. However, other outpatient-acquired drug-resistant pathogens are now on the rise including erythromycin-resistant group A Strep, drug-resistant Neisseria gonorrhoeae, and ESBL-producing Enterobacteriaceae. Outpatient stewardship efforts in our physician offices, urgent care centers, and emergency departments can and will make a difference. To view an OSU MedNet-21 webcast for more information on outpatient antibiotic stewardship, click on this link.

November 22, 2023

Categories
Epidemiology

The Solution To A Better COVID Vaccine Is IgA

One of the concerning observations from the COVID pandemic is that immunity from infection (“natural” immunity) appears to be better than immunity from vaccination. This is often attributed to the fact that when a person is infected with COVID, their adaptive immune system creates antibodies against many different parts of the COVID virus whereas an mRNA vaccine produces antibodies only against one specific site on the exterior of the virus. However, the reason for this difference in immunity may be due to something altogether different – infection results in the immune system producing lots of anti-COVID IgA but mRNA vaccines produce relatively little anti-COVID IgA. To understand why this is important, let’s take a look at the function of the different classes of antibodies (also known as immunoglobulins), including IgA

Summary Points:

  • Current intramuscular COVID vaccines provide good protection against severe COVID infection but offer less protection against mild COVID infection
  • Secretory IgA antibodies in respiratory mucus is the main antibody that prevents inhaled viruses from getting into our bodies
  • Intramuscular COVID mRNA vaccines create a lot of IgG antibodies in the blood but create relatively little secretory IgA antibodies in respiratory mucus
  • Inhaled COVID vaccines offer the potential to create larger amounts of secretory IgA in respiratory mucus and thus provide greater immunity against COVID infection

 

The basics of immunoglobulins

There are five types of immunoglobulins: IgG, IgM, IgA, IgE, and IgD. Each of them plays a different role in the immune system. All are produced by plasma cells. There is a constant amount of many, many different immunoglobulins in the body but in response to an infection, B-lymphocytes are converted into plasma cells that then make antibodies that uniquely target that particular infection. After the infection is cleared, the number of these plasma cells fall with the result that the level of those antibodies targeting a specific infection also fall.

  • IgG is the most abundant immunoglobulin in the blood, accounting for 75% of blood immunoglobulins, and is the main workhorse antibody in the blood to fight bacteria and viruses that have entered the body. New IgG is produced about 1 – 3 weeks after the start of an infection. It is the only type of immunoglobulin that crosses the placenta. It has a half-life of 23 days.f-
  • IgM is also produced by B-lymphocytes and released into the blood. It accounts for 10% of blood immunoglobulins. It is produced faster than IgG after an infection, generally in 5 – 10 days. It is also used to combat bacteria and viruses. It has a hallife of 7 days.
  • IgA is the second most abundant immunoglobulin in the blood, accounting for 15% of blood immunoglobulins. However, secretory IgA is also produced in the mucosal lining that forms the surface of the airways and the gastrointestinal tract. Because of this, IgA is overwhelmingly the most abundant immunoglobulin in the mucus of the lungs and nose. As a result, IgA is the most abundant immunoglobulin in the body, when considering both the amount found in the blood as wells the amount found in other parts of the body. IgA is used to fight bacteria and viruses and secretory IgA in mucus can fight these pathogens before they enter the body. It has a half life of 5.5 days. There are two types of IgA – IgA1 is found in the respiratory tract and IgA2 is found in the gastrointestinal tract.
  • IgE is used by the immune system to fight parasites, such as the worm Strongyloides. It is also involved in allergies. It is not involved in the defense against viruses. It has a half life of 2 days.
  • IgD is only present in very tiny amounts in the blood and its function is not well understood.

Viruses usually enter the body either through the respiratory tract or the gastrointestinal tract. In these tracts, viruses first have to pass through epithelial membranes layered with mucus. The main class of antibodies in mucus is IgA and thus IgA is the more important antibody in the initial protection against respiratory viruses. Mucosal IgA can stop some infections altogether if there is enough IgA to bind all of the individual viruses that are inhaled. Even if a few viruses evade mucosal IgA and get into epithelial cells and into the bloodstream, the numbers of individual viruses are low, giving the adaptive immune system a chance to rev-up blood antibody production and defeat the infection before the virus can replicate into large numbers inside of the body.

IgA levels protect against COVID

One of the ways scientists learn about the roles of different immunoglobulins is by studying people who are born with deficiencies of different immunoglobulins. Selective IgA deficiency is the most common of these immunoglobulin deficiencies and occurs in somewhere between 1 in 200 and 1 in 1,000 Americans. The curious thing about IgA deficiency, however, is that two-thirds of patients are asymptomatic. In about one-third, IgA deficiency confers a greater risk of sinusitis and pulmonary infections. IgA deficiency can also cause increased susceptibility to allergies. However, there is evidence that IgA deficiency plays a role in defending the body against COVID infection. The COVID virus enters the body through the nose and then first infects the epithelial cells lining the respiratory tract by crossing through the airway mucus layer. Because IgA is the most important anti-viral defense in mucus, it follows that lower levels of IgA could increase the risk for COVID.

  • A 2022 study in the Japanese Journal of Infectious Disease found that patients with selective IgA deficiency were 7.7-times more likely to have severe COVID infection than patients with normal IgA levels.
  • A 2022 study in the Journal of Clinical Immunology found that patients with severe COVID infection had lower serum levels of IgA than those with less severe COVID infection and healthy persons.
  • A 2023 study in The Lancet Infectious Disease found that healthcare workers who had detectable anti-COVID IgA in nasal mucus samples after vaccination had a lower risk of later getting a COVID infection than those healthcare workers who did not have detectable anti-COVID IgA in nasal mucus after vaccination.
  • A 2023 study in the Journal of Allergy and Clinical Immunology Practice found that patients with selective IgA deficiency were more likely to get initial COVID infections and were more likely to have recurrent COVID infections than persons with normal IgA levels.
  • IgA levels in respiratory secretions falls as people get older. A 2021 study in the Journal of Pharmacy & Bioallied Sciences found that salivary IgA levels fall after age 60. One possible explanation for the greater risk of severe COVID in the elderly could be from low mucosal IgA levels compared to younger persons.

Current mRNA vaccines have less effect on IgA

Given that secretory IgA in mucus appears to be an important component of the immune system’s defense against COVID, it follows that the effectiveness of vaccines against COVID depends in part on the ability of those vaccines to produce anti-COVID secretory IgA in the airways. Although current intramuscular mRNA vaccines are very good at stimulating anti-COVID IgG antibodies in the blood, they are not as effective in producing anti-COVID IgA antibodies in respiratory secretions.

  • A 2022 study in in the journal Frontiers in Microbiology found that anti-COVID IgA was detectable in throat swabs 4 days after infection with COVID and in the blood 10 days after infection. However, after an intramuscular mRNA COVID vaccine, throat swabs were negative for anti-COVID IgA indicating that COVID infection causes the body to make IgA in respiratory secretions more effectively than COVID vaccination.
  • A 2022 study in the journal Nature found that anti-COVID IgG and IgA was detectable in the saliva after the first dose of an mRNA COVID vaccine. After the second dose IgG antibody levels were boosted but IgA levels were not boosted. In fact, only 30% of subjects had detectable anti-COVID IgA in the sputum after the second dose of vaccine.
  • A 2023 study in The Lancet eBioMedicine found that patients with COVID infection had high levels of anti-COVID IgA in both blood and nasal secretions for 12 months after infection. Subsequent vaccination caused an increase in blood IgA but did not cause an increase in nasal secretion IgA.
  • A 2023 study in The Journal of Allergy and Clinical Immunology: Global found that after intramuscular mRNA vaccination, there was a significant increase in anti-COVID IgA and IgG in the blood but only a minimal increase in anti-COVID IgA in nasal secretions.
  • A 2023 study in The Lancet Microbe found that anti-COVID IgA levels in nasal secretions did not increase substantially after booster mRNA vaccinations whereas IgG levels did increase.

How can we improve COVID vaccines? 

For decades, physicians have written off IgA deficiency as having minimal, if any, clinical significance. But evolutionary science demonstrates that proteins that are unnecessary for the survival of a species eventually go away. It takes a lot of energy and nutrients to produce these proteins and individuals who do not need to expend energy and nutrients for unnecessary proteins can use that energy and nutrients for other functions, giving that individual a survival advantage. Taking into account both blood and secretory amounts, IgA is the most abundant immunoglobulin in the body. Even if we do not fully understand its functions, for the human body to expend so much energy and nutrients on IgA production, it must be important. Given the enormous amount of IgA found in respiratory mucus, it follows that its importance is in defense of inhaled viruses and bacteria.

The lungs have a huge surface area. If you were to lay out the surface of all of the bronchi, bronchioles, and alveoli in a person’s lungs, it would cover an area the size of a half of a tennis court. That surface area is exposed to the outside environment with every breath we take. COVID vaccines that result in a high level of anti-COVID IgA antibodies in the respiratory mucus should give the best protection against COVID infection. These IgA antibodies would be able to bind and destroy COVID viruses before those viruses enter the respiratory epithelial cells and cause infection. Vaccines that only increase antibodies in the blood but not in the respiratory mucus will not reduce the chances of getting infected but only reduce the severity of infection once it occurs.

To use an analogy, if you are trying to defend your country against an invading army, you are better off posting your defensive troops at your border, rather than trying to fight your battles in the interior of the country after the invaders have already crossed your borders.

So, how can we engineer vaccines to cause a robust secretory anti-COVID IgA response? The answer may be to give inhaled vaccines. This would potentially stimulate production of secretory IgA in the airways, where it is needed for the initial defense against COVID. Indeed, it may be that we need both inhaled vaccines to produce secretory IgA to protect against initial infection and intramuscular vaccines to produce blood IgG antibodies to protect against severe infection. The COVID virus enters our bodies in droplets and aerosols – it only makes sense that we should create vaccines that are also administered by droplets and aerosols.

Research is now being done to create inhaled COVID vaccines. At the Ohio State University College of Veterinary Medicine, researchers recently published their work in hamsters using an intranasal live-attenuated mumps virus containing the COVID spike protein. They found that this vaccine was highly effective in generating anti-COVID mucosal IgA and completely protected these hamsters from COVID infection. Subcutaneous administration of this live-virus vaccine was also effective. The MMR vaccine currently in use in pediatrics uses this same attenuated live-virus approach. There are currently phase 1 and phase 2 clinical trials underway in the U.S. and abroad using intranasal COVID vaccines.

The current generation of intramuscular mRNA vaccines have done what was most needed in the first years of the pandemic – they prevented people who were infected with COVID from dying of COVID. The next generation of vaccines should be designed to keep people from getting infected altogether. The key to this goal may be secretory IgA.

October 6, 2023

Categories
Epidemiology

Why “Should You Get A COVID Booster?” Is The Wrong Question

Two weeks ago, the new COVID booster vaccines were released and the internet is full of articles titled “Should you get a COVID booster?“. This is the wrong question – the real question is “When should you get a COVID booster?”. We so want the COVID pandemic to be over and gone. Americans are returning to theaters and restaurants, houses of worship are full again, sporting events are sold out, and mask-wearers are a tiny minority at the grocery stores. But COVID is not going away.

For the past 3 years, there have been two peaks of case numbers every year – a large peak in January and a smaller peak in the summer. Data from the CDC this week indicates that the current 2023 summer peak is cresting and cases should begin to fall over the next few weeks (reported case numbers are unreliable but COVID hospitalizations, COVID deaths, and the percent of ER visits due to COVID are accurate measures). If history repeats itself, then we should have a break in cases for the next couple of months until they begin to rise again in the winter.

COVID is a moderately lethal infection – less lethal than Ebola but more lethal than influenza. Immunity is very effective in protecting you from dying of COVID but less effective from protecting you from catching a non-fatal COVID infection. There are two ways to get immunity – either by having a previous COVID infection or by getting a COVID vaccine (or both). On the whole, immunity from past infection is probably more effective than immunity from a vaccine. However, to get immunity from a past infection, you have to first survive the infection. There are a number of advantages to getting immunity from a vaccination compared to getting immunity from an actual COVID infection:

So far, 1,144,539 Americans have died from COVID and most of these were people who had no immunity to the virus and died from their first infection. To understand how our immune system fights COVID, let’s first take a look at the basics of the immune response to viruses.

How the immune system works

Viruses cannot reproduce on their own – they have to get inside of our cells and then hijack those cells’ RNA to produce new viruses. Our defense against viruses takes two forms: the innate immune system and the adaptive immune system. Innate immunity uses parts of the immune system that we are born with to fight any new infection. The innate immune system consists of interferons, natural killer lymphocytes, and macrophages. When a cell gets infected with a virus, that cell releases interferons that then signal natural killer cells to kill any other infected cell before it can produce more viruses. In addition to stopping the infection by killing infected cells, the innate immune system has macrophages that can eat and kill extracellular viruses before those viruses can infect other cells in the body. The innate immune system works whether or not a person has been previously infected with the same virus or has received a vaccine against that virus. Think of the innate immune system working on instinct. The adaptive immune system, on the other hand, can be thought of as working by learning. Of the two, the adaptive immune system is the more powerful.

The adaptive immune system learns from previous infection or vaccination so that when a person is exposed to a future infection, the adaptive immune system can be immediately activated against that virus. The adaptive immune system consists of T-lymphocytes, B-lymphocytes, and antibodies. When a person is first infected with a virus, T-lymphocytes become activated and then in turn activate B-lymphocytes to produce antibodies that are specifically directed against that particular virus. These antibodies are our immune system’s most important weapon against viruses and can defeat viral infections in four ways. First, antibodies can bind to the virus so that the virus cannot get into cells and thus prevent the virus from infecting cells. Second, when antibodies bind to a virus, it signals macrophages to eat and kill that virus. Third, when antibodies bind to an infected cell, they mark that cell for natural killer lymphocytes to kill that infected cell, thus preventing further viral replication. Fourth, when antibodies bind to infected cells, they activate the complement system to punch holes in that cell, thus killing it and preventing further viral replication. Antibodies last for about a month in the bloodstream and after an infection is resolved, the adaptive immune system cuts way back on new antibody production.

The innate immune system works immediately after an infection but it takes the adaptive immune system 1 – 3 weeks to ramp up antibody production after a new infection. However, the second time a person is infected with the same virus, that adaptive immune system can ramp up antibody production much faster, in a matter of days rather than weeks. This is because of memory T-lymphocytes and memory B-lymphocytes that have learned how to make antibodies against that particular virus. These memory cells cause antibodies to be produced much faster than during the first, initial infection with a virus.

Antibodies and COVID

Many people who are now getting infected with COVID are on their second or third infection. For most people, the second infection is not as severe as the first and the third infection is not as severe as the second. This is because the memory T-lymphocytes and memory B-lymphocytes allow the immune system to respond faster and more effectively against repeat infections. Multiple doses of vaccines do the same thing – with each vaccine dose, your body makes new antibodies against COVID variants covered by that vaccine booster and also trains your memory lymphocytes to ramp-up antibody production quickly if you are exposed to the virus in the future.

Because antibodies only have a lifespan of about a month, antibody levels fall after either an infection or a vaccination as the B-lymphocytes start to slow down antibody production. As a result, after vaccination, COVID antibody levels begin to fall after about 3 months. So, you are best protected against a future infection in the first 3 months after a COVID vaccine as well as in the first 3 months after a COVID infection. But what most people do not realize is that it is not just the antibody levels in the blood that protect against COVID infection but it is also the training of the memory T-lymphocytes and memory B-lymphocytes that protect against infection Those memory cells last many years and can sometimes last for a lifetime. We have blood tests that can measure antibody levels but we do not have blood tests that measure memory lymphocyte levels and consequently, this important effect of vaccination is often overlooked.

When you get a COVID mRNA vaccine, you produce antibodies against one small part of the COVID virus. On the other hand, when you get a COVID infection, you produce antibodies against many different parts of the COVID virus. For that reason, a COVID infection will stimulate stronger immunity against another future infection than vaccination does. But because the memory T-lymphocytes and memory B-lymphocytes learn from each exposure to a virus or to a vaccination, the more you stimulate those memory cells, the better they become at fighting infection. Also, because antibody levels eventually fall after a COVID infection, those antibody levels can be replenished if a person gets vaccinated several months after that infection. For these reasons, a COVID vaccination gives you good immunity, a COVID infection gives you better immunity, and a COVID infection plus a vaccination gives you the best immunity.

So, when should you get a COVID vaccine?

Early in the pandemic, the answer to this question was easy – everyone should get a COVID vaccine as soon as possible. However, now that most Americans have at least some degree of immunity from either previous vaccination, previous COVID infection, or both, the answer to the question is a bit more complicated. In order to get the maximum benefit from vaccination, the timing has to be individualized. And the key to individualization is the fact that antibody levels persist for about 3 months after infection or vaccination before those levels begin to drop off. So, here are my recommendations:

  • No previous vaccination or infection. These are people who are most likely to become severely ill or die if they get a COVID infection. They should get vaccinated immediately. Even if COVID case numbers in their community are low, it is not worth gambling with one’s life that they won’t be exposed to an asymptomatic person at the grocery store, at church, or at work.
  • Received an older COVID vaccine within the past 3 months. These people should wait until at least 3 months after their last vaccination. Their antibody levels are already high and it is better to wait until their antibody levels begin to fall before re-stimulating their adaptive immune system. However, given the anticipated January surge in COVID numbers, they should not wait long after that 3-month period.
  • Had a COVID infection in the past 3 months. These people should similarly wait until at least 3 months after their COVID infection. However, they should also get vaccinated before the anticipated winter surge in cases.
  • Previous vaccination more than 3 months ago and no previous infection. These people should time their vaccine to when they are most likely to be exposed to COVID. For the last 3 years, the winter peak of COVID cases has been in the first week of January. Assuming this year is similar, then get a new COVID vaccine now and by mid-November at the latest.
  • Previous vaccination more than 3 months ago and had a previous infection. Congratulations – these people already have the strongest immunity. But their immunity will be even stronger with a new COVID vaccine now or by mid-November at the latest.
  • Moderately or severely immunocompromised. Here is where things get a bit complicated. These people need more vaccine doses in order to be protected. If they have never been vaccinated, they should receive 3 doses of either the new Pfizer or the new Moderna COVID vaccine. If they have previously received 1 dose of either Pfizer or Moderna, then they should receive 2 doses of either of the new COVID vaccines. And if they have received 2 or more Pfizer or Moderna vaccinations in the past, they should receive 1 dose of either of the new COVID vaccines. If you are uncertain, it is better to err on the side of too many rather than too few doses for immunocompromised people.
  • Planning travel or large family get togethers over Thanksgiving or Christmas. Get a COVID vaccine now (or by the end of October at the latest) in order to ensure that you have protective antibody levels over the holidays. First, because it will protect you from getting infected while traveling and second, because you don’t want to get an infection just before your travel date and have to cancel your trip.

There are three COVID vaccines currently on the market. The Novovax protein subunit vaccine is based on the original strain of COVID and is only approved for primary vaccination in people who have never received any COVID vaccines; it is not available as a booster. Anyone who received the Novovax (or the no-longer available J&J vaccine) still needs to get one of the new mRNA vaccines since neither Novovax nor J&J covers the newly circulating COVID variant. The new Moderna and Pfizer mRNA vaccines are available for anyone for either primary vaccination or as a booster. The new Pfizer and Moderna vaccines are interchangeable so if you have previously received a Moderna vaccine, you can get either a Moderna or Pfizer booster and vice-versa.

The bottom line is that everyone should get a new COVID vaccination

Your body’s immune system is like your muscles – the more you train it the stronger it becomes. Vaccinations both keep your antibody levels high and train your immune system to make new antibodies rapidly and in large quantities. There are really no good reasons to not get vaccinated. Everyone should get vaccinated in the next 6 weeks to optimally protect themselves during the upcoming holidays and the anticipated upcoming winter surge in COVID numbers. The Moderna vaccine or the Pfizer vaccine – either one is fine, no matter what brand of vaccine you have received in the past.

And, oh by the way… get your other protective vaccinations, too. I got my influenza and pneumococcal vaccines together on September 1st and my RSV and new COVID vaccines together on September 18th. This was my 6th dose of a COVID vaccine since December 15, 2020. My immune system will be ready for whatever gets thrown at it this winter.

October 2, 2023

Categories
Epidemiology

COVID Cases Are Surging… Again

Since the beginning of the COVID pandemic, there have been two surges in COVID cases and deaths every year, one in the winter and one in the summer. Because of this, it was predicted that the U.S. would seen a new surge this summer and epidemiology data indicates that it is now starting. The graph below shows the COVID death winter surges in red and summer surges in black.

However, the peaks in COVID deaths lag about 3 weeks behind the peaks in cases. The typical timeline for a person who dies of COVID is to develop initial symptoms one week before hospitalization and then have a 2-week hospitalization before death. COVID hospitalizations in the United States are now beginning to rise. In the graph below, the weekly new hospital admission number has been increasing for the past two weeks and currently number weekly hospitalizations are 8,035, up 12% from the week before.

An even earlier indicator of COVID surges is the COVID test percent positivity. The percentage of COVID tests that are positive starts to rise before the number of hospitalizations and even before the total number of cases. The graph below shows The test percent positivity in yellow and the deaths in blue.

In the graph above, we can see that the test percent positivity began to increase in early July 2023, suggesting that a COVID surge is eminent. But the COVID percent positivity data can be inaccurate because it is dependent on COVID tests that are reported to health departments. Since many people do home tests that are not reported to health departments, many positive (and negative) tests will be missed.

Another harbinger of COVID surges is the percentage of emergency department visits that are due to COVID infections. Because initial symptoms precede hospitalizations by a week or two, people infected with COVID will often present to the ER before getting sick enough to require admission to the hospital. The graph below shows that surges in the percentage of ED visits that are due to COVID (yellow) precede surges in COVID deaths (blue) by several weeks. Once again, we see that the percentage of ED visits due to COVID began to rise in early July.

Another predictor of COVID surges is COVID sewage wastewater sampling. People infected with COVID will shed virus into household wastewater very soon after becoming infected – often before developing symptoms or getting tested. By testing municipal wastewater for COVID viruses, we can detect surges in COVID early. The graph below shows changes in virus levels from more than 1,200 wastewater testing sites throughout the U.S. The red shade indicates the percentage of samples that show a greater than 100% increase in virus levels and is now the highest it has been since January 2023.

So, what should physicians be doing now?

In the past 3 years, the summer COVID surges have been smaller than the winter surges so if history is any indicator, then the current COVID surge should not overwhelm our hospitals. However, medically vulnerable people are at risk of severe infection or death, including those who are older, obese, or have chronic medical conditions. In addition, with schools opening this month, there is the potential for rapid spread of COVID among children. Here are some practical steps physicians should be taking now:

  • Step up vaccinations. Fewer than 50% of Americans have received an updated bivalent COVID vaccine. Physicians should especially target at-risk individuals for vaccination counseling. This includes pregnant women, the obese, diabetics, the immunocompromised, and those over age 65. The CDC recommends that all people older than 6 months get 1 dose of a bivalent vaccine and those over age 65 or immunocompromised get a second dose of a bivalent vaccine.  New monovalent vaccines directed against the XBB.1.5 variant are expected in October but patients should be told to not wait until then to get vaccinated with a current bivalent vaccine.
  • Have a low threshold for testing. Your patient’s sinusitis or common cold is now more likely to be a COVID infection than it was a couple of months ago. Encourage any patient with possible COVID symptoms to be tested. Even if a person’s COVID infection is too mild to warrant treatment, all infected persons need to be in isolation to prevent transmission to more vulnerable people.
  • Be familiar with isolation guidelines. The CDC recommends that all people who test positive be isolated for 5 days and after at least 24 hours have passed since a fever. After the isolation period, infected persons should wear a face mask for an additional 5 days when in public. People with more severe infection should remain in isolation for 10 days, rather than 5 days.
  • Review current treatment recommendations. The COVID treatment guidelines by the National Institutes of Health are regularly updated. For outpatients, be familiar with the indications for Paxlovid. For inpatients, be familiar with the indications for remdesivir, dexamethasone, heparin, baricitinib, and tocilizumab.
  • Advise patients about COVID trends in your community. Our patients are constantly subjected to conflicting and often misleading information about COVID from the media and from on-line sources. Physicians are often the most trusted source of reliable information for patients. Educate patients when they come into the office and harness group messaging through the electronic medical record system.
  • Normalize masking in high risk settings. High population density indoor settings pose the greatest risk of COVID transmission. This includes churches, airports, aircraft, trains, buses, and stores during busy times of the day. Encourage patients to carry masks with them and then wear them if crowded indoor settings cannot be avoided.

COVID will be with us for the long-term. Inevitably, there will be periodic surges in cases and it appear that one of these surges is underway this month.

August 8, 2023

Categories
Epidemiology

Predictions For The 2023-2024 Influenza Season: Lessons From Australia

After two and a half years of the COVID pandemic, influenza has become an after thought for many Americans. But influenza can still kill vulnerable people and even in otherwise healthy individuals, it can cause unpleasant illness, require time off of work, and cause school absences. One of the best predictors of the next U.S. influenza season is the current Australia winter influenza season that occurs during the U.S. summer.

When will the U.S. influenza season start?

The Australian Government Department of Health and Aged Care publishes an influenza epidemiology report every 2 weeks. The most recent report is from July 23, 2023.

Australia

The current influenza data is depicted in the red line in the graph above. Last year’s influenza data is in the taller orange line and the 5-year average is in the black line. In this graph, week 1 corresponds to the week of January 1, 2023. Cases of influenza began to be reported early in Australia this year and most closely matched the 2019 influenza season. Cases started to increase in number in week 8 (late February), had an initial plateau from weeks 13 – 17 (late March to late April), then rose to a peak in week 26 (last week of June).

The Centers for Disease Control publishes a weekly influenza report on the FluView website. The United States influenza season is about 6 months later than the Australian influenza season, owing to the seasonal difference between the northern and southern hemispheres. The graph below shows U.S. influenza data for the last several years with the 2022-2023 data in red. Similar to last year in Australia, influenza was seen earlier and peaked earlier in the U.S. last year.

United States

Based on the current year data from Australia, cases of influenza would be expected to begin to rise in late August or early September in the U.S. and then peak in approximately late December or early January. This would be a much earlier influenza season than is typical in the U.S. and would resemble last year’s influenza season.

What influenza subtypes are likely?

Influenza A and influenza B are the most common varieties of influenza in humans. Each of these can be further divided into common subtypes. The most common subtypes of influenza A are H1N1 and H3N2. The most common subtypes of influenza B are the Victoria lineage and the Yamagata lineage. Each of these subtypes can be further divided into clades and each clade can be divided into subclades. Because influenza can and does mutate regularly, the dominant subclades causing human infection change from year to year. Additionally, the relative percentage of influenza cases caused by influenza A & B varies each year and the relative percentage of each influenza subtype also varies each year. The graph below shows the strains of influenza in the U.S. last year. Most cases were influenza A and most of the influenza A was H3N2 (71%, red bars); H1N1 was much less frequent (29%, orange bars). Influenza B cases were relatively uncommon and mostly seen late in the season (green bars). Notably, all of the influenza B cases were caused by the Victoria lineage (100%) and none were caused by the Yamagata lineage.

United States

This year in Australia, influenza A (63%) was more common than influenza B (35%). The vast majority of influenza A was caused by the H3N2 subtype (82%; dark green bars) as opposed to the H1N1 subtype (18%; purple bars). For influenza B, 100% were caused by the Victoria lineage and none were caused by the Yamagata lineage.

Australia

Influenza A H3N2 clades and subclades.  The two clades of H3N2 which are currently in circulation are clade 1 (limited to China) and clade 2 (the dominant clade in the U.S.). In the figure below, clade 1 is shown in purple and clade 2 is shown in green. Each clade is divided into subclades based on mutations in the influenza hemagglutinin gene. The hemagglutinin protein is located on the surface of influenza and helps the virus bind to human cells. Hemagglutinin is also the target for influenza vaccines.

Influenza A H1N1 clades and subclades.  The two clades of H1N1 which are currently in circulation are 5a.1 and 5a.2. The H1N1 5a.1 influenza clade mostly made up of the subclade A/Hawaii/70/2019. This subclade is decreasing in frequency and is rarely seen in the United States.

Most H1N1 influenza in the United States is from clade 5a.2. H1N1 5a.2 subclades A/Victoria/4897/2022 and A/Wisconsin/67/2022 are dominant in the U.S. whereas H1N1 5a.2 subclade A/Sydney/5/2021is dominant in Australia.

Influenza B subtypes. Of the two influenza B lineages, only the Victoria lineage is currently circulating on Earth and the Yamagata lineage has not been detected in the U.S. or Australia in the past year. As with influenza A, mutations in the hemagglutinin gene creates clade diversity in influenza B. Currently, the 1A.3a.2 strain accounts for 99% of influenza B worldwide.

The 2023 – 2024 influenza vaccine

Every year, the FDA’s Vaccines and Related Biological Products Advisory Committee (VRBPAC) meets in the spring to project which influenza clades and subclades are likely to circulate during the next influenza season and then selects representative virus strains to use to manufacture the next seasonal influenza vaccines. Because the committee meets in early March, data from the Australia influenza season are not yet available when the U.S. selects influenza strains for vaccines. This year, the strains selected for the quadrivalent vaccines are similar to last year’s vaccine with the exception of the influenza A H1N1 strains; the Victoria/4897/2022 strain replaces last year’s Victoria/2570/2019 and the Wisconsin/67/2022 strain replaces last year’s Wisconsin/588/2019 strain:

The 2023-2024 trivalent influenza vaccines will be similar to the 2023 – 2024 quadrivalent cell-based and egg-based vaccines except that they will not include the Phuket/3073/2013 influenza B strain against the Yamagata lineage. Because there have been no Yamagata lineage influenza B infections in the U.S. last year or in Australia this year, it is likely that the trivalent vaccine will be equally effective as the quadrivalent vaccine this year since coverage for the influenza B Yamagata lineage is unnecessary.

Recommendations

When to get vaccinated. Because the Australia influenza season started early, it is likely that the U.S. influenza season will also start early. Physicians should start vaccinating patients in mid-August and aim to get all patients vaccinated by late October.

Quadrivalent versus trivalent. Because there has not been any recent influenza B Yamagata lineage virus circulating recently, the trivalent vaccine should be just as effective as the quadrivalent vaccine. Therefore, patients can get either vaccine and they can be used interchangeably.

When will hospitalizations peak? This year in Australia, hospitalizations peaked between weeks 19 and 28. This would correspond with early November through early January in the United States. This is normally a busy time for elective inpatient surgeries (such as knee and hip replacements) so hospitals should be prepared accordingly.

The holiday travel effect. Because influenza may be peaking during the U.S. Thanksgiving and Christmas holidays, there is the potential that travel for these holidays could fuel a surge in influenza cases.

Universal flu vaccines in the future?

Because the influenza hemagglutinin gene mutates so readily, the antigen targets on the hemagglutinin surface protein change. This requires new vaccines to be made to generate antibodies against these altered hemagglutinin antigens. The mRNA vaccines that were so successful against COVID offer the hope that mRNA technology could be applied to other anti-viral vaccines, including influenza. A study published November 2022 in the journal Science found that an mRNA vaccine that covered 20 strains of influenza was effective in mice and ferrets. However, recent human trials with mRNA influenza vaccines by Sanofi and Moderna were unsuccessful, mainly due to inadequate immune protection against influenza B strains. Another influenza mRNA vaccine created by Pfizer is currently undergoing phase III clinical trials.

In all likelihood, it will be several years before a universal influenza vaccine is commercially available. Until then, we will have to continue our current process of tracking the dominant circulating influenza clades and subclades in order to produce annual influenza vaccines. Based in Australia’s current influenza season, I recommend getting this year’s flu shots as soon as they are available.

August 2, 2023

Categories
Emergency Department Epidemiology

July Is The Peak Of Mass Shooting Season In The United States

What do you call a 4th of July when there are five mass shootings? …Yesterday …and just another July day in America. If it seems like there are a lot of mass shootings in July, that’s because there are. There is a seasonality to mass shootings in the U.S. and summer is the busiest season of the year. A mass shooting is defined as four or more persons shot in one incident, at one location, at roughly the same time.

America loves guns. We have a higher ownership of guns than any other country in the world. There are 120 firearms for every 100 American citizens; the next closest country is Yemen with 53 guns per 100 citizens. One out of three American adults own a gun and 42% of households have a gun. Interestingly, the percentage of Americans who own guns has been falling over the past several decades, even as the total number of guns has increased dramatically. This has been attributed to a rising number of “super owners” who posses 10 or more guns. We have 4% of the world’s population but U.S. civilians own 40% of the world’s firearms. Thus, it is not surprising that guns are our method of choice for both homicides and suicides. However, despite the fall in the percentage of Americans who own guns, the annual number of mass shootings continues to increase.

The Gun Violence Archive keeps a list of all mass shootings in the past 3 years and by analyzing their data, we can determine when mass shootings are most likely to occur and where they are most likely to occur. For the past 3 years, July has been the peak month for mass shootings with a total of 264. December had the lowest number of mass shootings at 95.

The number of people injured during mass shootings follows a similar trend. Over the three year period, there were 1,169 mass shooting injuries in July and only 349 injuries in December.

July was not the peak month for mass shooting deaths, however. That honor went to May with 228 deaths; July came in second with 215 deaths. However, the unusually high number of deaths in May is due to the large number of fatalities from shootings in Buffalo, NY (May 14, 2022; 10 deaths) and Uvalde, TX (May 24, 2022; 21 deaths). 

Certain states are more dangerous than others when it comes to mass shootings. Over the past three years, Illinois has led the country with 199 mass shootings, followed by Texas with 152, California with 139, Pennsylvania with 108, and Florida with 100. Several states had no mass shootings in the past three years including Montana, Wyoming, Vermont, and North Dakota,

Mass Shootings by State July 2020 – July 2023

Mass shootings get a lot of public attention and are the focal point for calls for gun control. However, mass shootings are actually a relatively uncommon way to die from a gun. In 2022, there were a total of 44,357 deaths in the U.S. caused by guns. Of those, 24,090 (54%) were suicides and 20,267 (46%) were homicides. Only 1.5% of gun deaths were from mass shootings or mass murder. Indeed, there were more than twice as many unintentional shootings (accidental shootings) than mass shooting deaths.

CDC data from 2021 shows that the states with the most gun deaths from all causes are Texas (4,613), California (3,576), Florida (3,142), Georgia (2,200), and Illinois (1,195). On the other hand, three states had fewer than 100 gun deaths in 2021: Rhode Island (64), Hawaii (71), and Vermont (83). But total numbers alone can be misleading since states with larger populations would be expected to have more deaths from any cause, including guns. So, the rate of gun deaths per 100,000 population is more meaningful and is shown in the map below.

Firearm Death Rates by State 2021

States with the highest rates of gun deaths per 100,000 are Mississippi (33.9), Louisiana (29.1), New Mexico (27.8), Alabama (26.4), and Wyoming (26.1). At the other end of the spectrum, states with the lowest rates of gun deaths in 2021 were Massachusetts (3.4), Hawaii (4.6), New Jersey (5.2), New York (5.4), and Rhode Island (5.6).

What should hospitals do to prepare?

For our country’s emergency departments and trauma surgeons, gunshot injuries and deaths are all too routine. But large numbers of gun casualties from mass shootings are infrequent. Nevertheless, they can occur anywhere at anytime. Mass shootings have been steadily increasing over the past 50 years and so it is incumbent on our hospitals to be prepared to manage mass casualties from gun violence.

Rockefeller Institute of Government

Hospitals are required to do two disaster drills every year. Each disaster drill encompasses different scenarios, such as a bus crash, an infection outbreak, or a tornado. Several years ago, our community also did a mass shooting disaster drill. This was incredibly helpful to make us think about how we get enough units of blood, how we would triage a large number of patients with penetrating trauma, emergent expansion of the operating rooms, and which physicians can supplement the emergency medicine physicians and trauma surgeons. Every hospital should include a mass shooting drill every 4-5 years. Considerations should include:

  • How quickly can off-duty emergency room doctors be brought in and how will you contact them? This requires having a list of phone numbers of all ER physicians in a readily accessible location.
  • How can you increase the number of nurses in the ER on short notice? This may require calling in off-duty nurses and re-deploying nurses from other hospital locations.
  • How many trauma surgeons and general surgeons can you mobilize? This requires having a plan in place for calling in off-duty surgeons. In an emergency, other surgeons may be able to operate on trauma patients or at least assist, including plastic surgeons, orthopedic surgeons, vascular surgeons, and surgical residents.
  • How will you clear out the operating rooms to accommodate a large number of emergency trauma cases? Elective cases may need to be canceled or delayed.
  • How will you mobilize additional anesthesiologists and OR nurses? Tactics can include calling off-duty staff in from home, using anesthesia residents, and CRNAs.
  • How can you re-deploy other physicians to supplement the emergency room physicians on short notice? Hospitalists can often be used to care for the non-trauma patients in the ER.
  • How quickly can your blood bank acquire additional units of blood? In the 2017 Las Vegas shooting, more than 500 units of blood were used.
  • How will you track patients? Victims may not have identification or be alert enough to provide identifying information.
  • How will your medical records department manage a large number of unidentified patients? This requires a system to provide multiple temporary patient medical record numbers until patient identification can be confirmed.
  • How will your hospital disaster command center operate and who will fill each command center role? It is best to rotate who will fill each role during different disaster drills because when a disaster actually happens, not every hospital leader will be in town or otherwise available.
  • How will you manage press communication, family reunification, and morgue demands? All of these can contribute to the chaos attendant to a true disaster. By having plans in place, chaos can be minimized.
  • How will you transport patients to other hospitals once you reach trauma capacity? A disaster, such as a mass shooting, requires a community-wide response. All regional hospitals need to coordinate in order to take optimal advantage of each hospital’s available resources.
  • How can the community be better prepared to provide pre-hospital care? The Stop The Bleed program is a great resource for community education and can result in a higher percentage of casualties arriving in the emergency department alive.

Situational awareness and preparation

The keys to surviving a mass shooting are situational awareness and preparation. It is up to every American to maintain situational awareness and to teach it to our children. Sometimes, there are warning signs before mass shootings take place: someone carrying a gun where a gun is not necessary; someone making verbal or physical threats; drug deals; or the presence of rival gang members. It is unfortunate but necessary that we always know where exits are and be willing to leave an area when warning signs occur.

For the average citizen, being prepared means familiarity with the Run, Hide, Fight strategy recommended by the Federal Bureau of Investigation. For hospitals, being prepared means rehearsing how a large number of shooting victims would be managed in an emergent situation. Once rare, mass shootings are now a way of everyday life in the United States. Our hospitals can do their part to minimize the number of fatalities when mass shootings do occur.

July 5, 2023

Categories
Emergency Department Epidemiology Outpatient Practice

It’s Back! Malaria In The United States

Last week, I was hiking and birdwatching in Fort Macon State Park in North Carolina. I got a few good bird photos but I got a lot of mosquito bites. In North Carolina, they are a nuisance but in Florida or Texas, they can be deadly. Locally transmitted malaria is now present for the first time in 20 years in the U.S. Many physicians are unfamiliar with its presentation and many hospitals are not prepared to perform diagnostic testing.

Worldwide, malaria affects 241 million people each year and and causes over a half a million deaths per year. It is caused by five species of the protozoan parasite Plasmodium (P. falciparum, P. vivax, P. malariae, P. ovale, and P. knowlesi) which are transmitted by the bite of a female Anopheles mosquito. It primarily occurs in equatorial regions, particularly in central African nations.

In the past, it was also endemic in the United States but was largely eradicated by public health efforts at mosquito control. In 2018, there were 1,823 cases of malaria diagnosed in the U.S., all in foreign travelers who became infected elsewhere. Until this year, the last cases of endemic malaria in the U.S. were in Palm Beach, Florida in 2003 when 8 persons were infected with Plasmodium vivax. 

The recent outbreaks occurred in Sarasota County, Florida (4 cases on May 26, 2023) and Cameron County, Texas (1 case on June 23, 2023). In both areas, the species was Plasmodium vivax. Because of rising temperatures from climate change, southern areas of the United States may see more cases of endemic malaria in the future. Because these are locations that many Americans travel to for vacations, physicians in all states need to include malaria not only in the differential diagnosis of patients presenting with fever who have traveled to endemic countries but also in patients traveling to south Texas or south Florida. It has been nearly 3 decades since I last encountered a case of malaria and much has changed in the diagnosis and management since that time. So, this post is to update practitioners and hospitals on what they need to know.

Clinical presentation

After the initial mosquito bite, patients are asymptomatic during the incubation period and symptom onset is generally 1 – 5 weeks after the initial infection. Symptoms are non-specific and most commonly include fever, chills, headache, myalgias, and fatigue. Less commonly, patients can present with GI symptoms such as nausea, vomiting, and diarrhea. If not diagnosed and treated early, patients can become critically ill with mental status changes, seizures, renal failure, acute respiratory distress syndrome, liver failure, and coma. Pregnant women are at particularly high risk for developing severe disease and death. Others at high risk include immunocompromised patients, those with splenectomy, and children less than 5 years of age. Different Plasmodium species cause different severities of infection: P. falciparum and P. knowlesi infections can cause rapidly progressive severe illness or death, whereas P. vivax (the species causing the recent Florida and Texas cases) is less likely to cause severe disease.

Routine laboratory findings are also non-specific and can include anemia, thrombocytopenia, and elevated liver function tests. Patients presenting with thrombocytopenia are more likely to develop severe disease. Because malaria can progress extremely rapidly, it is essential that diagnosis be made immediately. The clinical suspicion of malaria should be considered a medical emergency – this is not a disease that you discharge patients with from the emergency room to follow-up with their PCP the next day.

Diagnosis and treatment

P. vivax on thin blood smear

Malaria should be considered in any patient with fever and recent travel to endemic areas (now including the southern most areas of the United States). The diagnosis is confirmed by thin and thick blood smears for visual identification of the Plasmodium parasite. A new rapid diagnostic test for malaria has also been developed. The BinaxNOW Malaria test is approved by the FDA and has a sensitivity of 94% and specificity of 84%. The BinaxNOW Malaria test can be used to make a quick presumptive diagnosis but because both false positive and false negative results can occur, it should always be followed by thin and thick blood smear evaluation. PCR tests for malaria are very sensitive and are available through the CDC but the time required for specimen transport and test completion makes PCR impractical for clinical decision making.

The treatment of malaria depends on the specific species involved, the geographic location of travel, and the severity of infection. A summary table is available on the CDC’s malaria diagnosis and treatment for U.S. clinicians website. Uncomplicated infections with P. vivax, P. ovale, P. malariae, and P. knowlesi are generally treated with either chloroquine or artemisinin combination therapy. Uncomplicated infection with P. falciparum is generally treated with artemisinin combination therapy. Severe malaria infections are treated with intravenous artesunate. Most hospital pharmacies do not stock arteunate but it can be obtained in an emergency by having the pharmacist call 1-855-526-4827 to identify the closest distributor.

What hospitals should do now

With international travel picking up post-COVID and now that P. vivax malaria has been identified in the United States, hospitals should evaluate their malaria preparation. Specific steps include:

  • Consider stocking the BinaxNOW Malaria rapid diagnostic test.
  • Ensure that laboratory technicians are educated and competent in performing thin and thick blood smears. The CDC has on-line guidelines.
  • Ensure that laboratory technicians and pathologists are educated and competent in the microscopic identification of malaria trophozoites. The CDC has an on-line resource for identification of malaria and other parasites that includes photomicrographs of trophozoites of the various Plasmodium species on both thick and thin blood smears.
  • Educate medical staff about malaria presentation and diagnosis with particular attention to emergency department providers, hospitalists, critical care practitioners, and primary care providers. Patients with suspected or newly diagnosed malaria should either be admitted or kept overnight in observation status.
  • Ensure that the pharmacy has a process in place for obtaining intravenous artesunate in an emergency.
  • Educate primary care providers and travel clinics about current malaria prophylaxis measures for patients traveling to high-risk areas.

Mosquito bites can be more than just an itch

A mosquito is like a flying syringe that goes from animal to animal and person to person. Like a contaminated syringe, mosquitos can transmit a wide variety of blood-borne diseases including malaria, yellow fever, dengue fever, chikungunya, filariasis, West Nile virus, various forms of encephalitis, and Zika virus. The best way to prevent these infections is to prevent mosquito bites in the first place. This is particularly true for people traveling to locations where any of these various infections are endemic. Here are recommendations we can give to all of our patients:

  • Wear loose-fitting long sleeve clothing. As I learned from my recent outing last week, when shirts get soaked with sweat and stick to the skin, they offer no protection from mosquitos.
  • Use effective insect repellant. The most effective is DEET in 25 – 30% concentrations. OLE (oil of lemon eucalyptus) and picaridin are less-effective alternatives to DEET.
  • For those who work outside or spend a lot of time outside, treat clothing with permethrin. Some outdoor gear can be purchased already treated with permethrin but you can also buy permethrin spray and treat clothing yourself. Just be sure to follow clothing washing instructions to prevent the permethrin from being washed away.
  • Skip the citronella candles, sonic repellant devices, and wearable repellant devices. These are nowhere near as effective as DEET.
  • Inspect window screens. Although keeping doors and windows closed is the best way to keep mosquitos from getting into the house, this is not always an option, especially for homes without air conditioning. Be sure that screens fit tightly into window frames and that there are no holes in the screens.
  • Eliminate stagnant water. For property owners, eliminating places where water accumulates can prevent mosquitos from laying eggs and prevent eggs from hatching. These can include bird baths, gutters, old tires, toys, and other open containers.
  • Where stagnant water cannot be drained, encourage community mosquito control spraying programs.
  • When traveling to areas where sleeping outdoors or in unscreened buildings is necessary, mosquito nets can be effective.

It is too early to say whether or not malaria will become regularly transmitted in the United States in the future. But the recent Florida and Texas cases are a reminder that malaria is still with us. International travel makes the world an increasingly small place with endemic areas just a few hours away from every city in the U.S.

June 30, 2023

Categories
Epidemiology

The COVID Pandemic Is Winding Down… Unless You Are Overweight

This week represented a landmark event in the COVID-19 pandemic: the major epidemiological metrics together were at their lowest points in the U.S. since the pandemic began three years ago. The weekly total cases fell to 77,294, weekly deaths were 1,109, death rate was 0.33 per 100,000, and weekly new hospital admissions were down to 8,060 (note, however, that Florida and Iowa no longer report COVID case numbers and deaths). The CDC announced that it will stop reporting COVID case numbers, vaccine mandates are disappearing, people are shedding their masks, and it almost seems like life is getting back to normal again. But just because the numbers are improving does not mean that everyone is equally safe.

The epidemiological impact of an infection depends on two factors: (1) its incidence and (2) its fatality rate. Take an infection that has a high incidence but low fatality rate, such as rhinovirus. Prior to the COVID pandemic, the average American adult had 2-3 upper respiratory infections per year and the average child had 8-10 URIs per year. Rhinovirus infections account for about one-third of common colds. The net result is that most Americans have at least one rhinovirus infection every year. Rhinovirus causes rather mild symptoms but rarely causes death. On the other end of the epidemiological impact spectrum is ebola, a viral infection that has a low incidence but has a very high case fatality rate. Ebola is rare outside of Western Africa but if someone gets infected, there is a fifty-fifty chance that they will die and a 100% chance that they will at least get very, very sick. Despite its frequency, we really don’t worry too much about rhinovirus infections but even just one case of ebola in the community can induce widespread panic.

The incidence and fatality rate of COVID-19 falls in-between rhinovirus and ebola. Data from the Nationwide Antibody Seroprevalence Survey indicate that by February 2022, approximately 57% of Americans had been infected by COVID-19, a very high incidence but not as high as rhinovirus. The case fatality rate of COVID-19 is somewhere between 0.5% and 1.0% (the exact number is uncertain due to many infections being asymptomatic). This fatality rate is much higher than rhinovirus but much lower than ebola. Consequently, the degree that we worry when COVID-19 cases are in the community is more than rhinovirus but less than ebola.

The UK Biobank Registry study

However, COVID-19 does not affect all people the same. Since the beginning of the pandemic, it has been clear that age has a huge impact on the mortality rate and the older a person is, the more likely they are to die from an infection. A study from this week’s JAMA confirmed the importance of another risk factor for COVID mortality, namely obesity. The study involved 500,000 people from the general population of the United Kingdom who were enrolled in the UK Biobank registry between 2006 – 2010. People with underlying chronic respiratory disease were excluded from the study. Investigators interrogated the UK national electronic health records for data involving COVID infections, lower respiratory infections, and upper respiratory infections in people in the registry between initial enrollment and February 2021. Subjects were divided into four groups based on body mass index (BMI):

  • BMI 14 – 24.9 (normal)
  • BMI 25 – 29.9 (overweight)
  • BMI 30 – 34.9 (obese)
  • BMI 35 – 60 (morbidly obese)

The results showed that in the first year of the pandemic (February 2020 – February 2021), overweight individuals were twice as likely to be hospitalized or die of COVID-19 than those with a normal body mass index. Obese individual were three times more likely to be hospitalized or die and morbidly obese individuals were 4 times more likely to be hospitalized or die. When adjusted for subjects’ age, the increased risks for each BMI category were similar.

The study also looked at non-COVID lower respiratory infections (eg, pneumonia and influenza) and upper respiratory tract infections (eg, common colds) over the entire duration of the registry (average = 11.8 years). The results showed that weight was also a risk for severe infection from colds and pneumonia. During the study period, 2.6% of normal weight individuals were hospitalized or died of lower respiratory infection whereas 3.0% of overweight, 4.1% of obese, and 5.6% of morbidly obese individuals were hospitalized or died. The numbers were similar for upper respiratory infections: 0.22% of normal weight, 0.28% of overweight, 0.32% of obese, and 0.44% of morbidly obese individuals were hospitalized or died of upper respiratory infections.

What does all of this mean for healthcare providers?

The implications of the UK Biobank study is that the degree that we relax COVID precautions depends on how likely you are to become severely ill or die if you get a COVID infection. If you are young, healthy, and have a BMI less than 25, then for all practical purposes, the COVID pandemic is over for you and it is reasonably safe to return to life as usual. However, if you have risk factors such as being overweight or obese, then you should still take precautions because even though the incidence of COVID-19 is dropping, if you are unlucky enough to become infected, then you have a higher chance of dying from it. And the higher the BMI, the greater the risk of dying. In the epidemiological impact spectrum with rhinovirus at one extreme and ebola at the other extreme, being overweight or obese pushes COVID-19 more toward the ebola end of the spectrum than being of normal weight.

So, what should we be telling our overweight and obese patients to do? First, vaccinate. Strongly advise unvaccinated overweight persons to get their initial 2-dose COVID series and be sure that those who are vaccinated are advised to get an updated booster. People who live in the same household as an overweight person should similarly be vaccinated to help prevent transmission to those who are overweight. Given the UK Biobank study results for upper and lower respiratory tract infections, overweight and obese patients should also be strongly advised to get pneumococcal vaccines, influenza vaccines (in the fall), and the new RSV vaccine (for those over age 60). Second, advise obese patients to continue to wear masks in crowded indoor areas. Third, continue to make telemedicine available to those patients who are worried about coming into our offices and clinics.

In 1973, Yogi Berra said of the National League pennant race: “It ain’t over ’til it’s over”. For overweight and obese people, the COVID-19 pandemic is not yet over. There are other people for whom the pandemic is also not over. Those who are over age 65 are 97-times more likely to die of a COVID infection than young adults in their 20’s. Chronic diseases that increase the risk of death from COVID include diabetes, heart disease, COPD, immune suppression, kidney failure, cirrhosis, and HIV. Pregnant people are also at increased risk of serious COVID infection. For these people, masks in high-risk settings are still appropriate.

One of the biggest barriers to mask-wearing is the social pressure to stop wearing them. The awkwardness of wearing a mask when no one else around you is wearing one poses a barrier to those people with obesity and other risks for severe COVID who feel self-conscious wearing masks. As physicians, we can normalize mask wearing by our at-risk patients by wearing a mask ourselves in healthcare settings. Most U.S. hospitals have relaxed mask requirements for healthcare workers, patients, and visitors. Because of this, many physicians and nurses have altogether stopped wearing masks in hospitals or outpatient clinics because they are no longer required to. But the reason we should continue to wear masks in these areas is not because of a lower risk that we will get infected ourselves, it is to signal that it is OK to still wear a mask for our patients with COVID risks such as obesity.

Pandemics don’t just all of a sudden stop one day. Instead, they slowly wind down and then fade away. There will come a time when the COVID pandemic is finally over for all of us but we are not there quite yet. Even though the U.S. hospitalization and death rate is now the lowest in three years, we still had more than 8,000 new COVID hospital admissions and more than 1,000 COVID deaths last week in our country. Just because the pandemic seems over for us individually doesn’t mean that it is over for our patients with risk factors such as obesity.

May 6, 2023

Categories
Epidemiology

Predicting COVID In The Future

Last week, a little-noticed milestone in the U.S. COVID pandemic occurred – it is the first week that the number of new cases of COVID exceeded the number of vaccine doses administered since the vaccines became available to the general public. It seems that America is ready to be done with COVID and move on. The good news is that both the number of cases and the number of deaths is falling. The bad news is that they are still very high – it’s just that we have developed a national desensitization to the COVID numbers. Last week, 226,618 Americans were diagnosed with COVID, that is enough people to fill Yankee Stadium five times over. In addition, 22,422 people were hospitalized with COVID and 2,290 people died of COVID. To put that in perspective, last week, 4 times more people were admitted with COVID and 10 times more people died of COVID than were admitted and died of H1N1 influenza during the peak week of the 2009 H1N1 influenza outbreak in the U.S. In other words, the best days of COVID are still worse than the worst days of H1N1 influenza. So, what will the COVID picture look like in the next year? We can learn a lot from the epidemiology of other viruses.

Summary Points:

  • COVID is likely to assume seasonal variation in the future, similar to other coronaviruses
  • The current mortality rate of 0.5 – 1.5% can be reduced by vaccination and new drug development
  • Hospitals should prepare for a modest increase in COVID hospital admissions and ICU utilization next winter
  • COVID is not going to go away anytime soon

 

What we can learn from non-COVID seasonal coronaviruses

Coronaviruses have been infecting humans for as long as there have been humans. There are dozens of different coronavirus species that each have a preferred animal it infects. For humans, there are four seasonal coronavirus strains cause cold symptoms: 229E, NL63, OC43, and HKU1. These coronaviruses are common and cause 15-30% of all common colds. These viruses recur predictably every year as reported by the Public Health Agency of Canada:

There is a striking seasonality to coronavirus infections with most infections occurring in the winter. The graph below shows the average number of coronavirus infections reported by the Public Health Agency of Canada over a 10-year period:

Future COVID seasonality

For the purpose of simplicity, I will use “COVID” (the name of the disease) as synonymous with “SARS-CoV2” (the name of the virus) in this post. At some point in the future, COVID will most likely go the way of other coronaviruses and assume the same seasonal variation with a baseline year-round rate and a rate surge in the winter. We have already seen signs that COVID has a predilection for the winter months in the case rates during the first 3 years of the pandemic. The graph below shows the number of COVID deaths per 100,000 per week in orange and the number of cases per week in blue.

This graph demonstrates that the death rate for COVID peaks about three weeks after the case rate peaks, consistent with the finding that most people who die from the infection do so about 3 weeks after initial diagnosis. There has been a peak in deaths every January (red dashed lines)  followed by a second, smaller peak in deaths every summer (black dashed lines).

Assuming that COVID becomes a seasonal infection, how long will it take to become primarily seasonal? Any answer to this question is speculative but it will likely be several more years before the seasonal epidemiology of COVID resembles that of other coronavirus infections. Until then, it is likely that there will be a moderate or low baseline level of COVID year-round with case numbers increasing in the winter. The main determinant to becoming seasonal is population immunity.

By now, most Americans have either been vaccinated against COVID or have had a COVID infection or both. The result is that most Americans have some degree of immunity. But what we know from the usual seasonal coronaviruses is that immunity fades and it is common for people to get reinfected with the same coronavirus strain. One study found that up to 21% of people get reinfected with the same strain of non-COVID coronavirus within 6 months of the initial infection. Going forward, having immunity from a previous COVID infection or a previous COVID vaccine will not entirely protect a person from getting a future COVID infection. But immunity can reduce the severity of infection, reduce death rates, and reduce transmission. For the population as a whole, compared to people vaccinated with a bivalent booster, unvaccinated people are 3 times more likely to be diagnosed with COVID, 16 times more likely to be hospitalized with COVID, and 10 times more likely to die from COVID. These numbers likely underestimate the protectiveness of vaccines since people most vulnerable to COVID have been the most likely to get the bivalent booster. As an example, people age 65-79 who are are unvaccinated are 14 times more likely to die of COVID than people age 65-79 who are vaccinated with a bivalent booster.

Unfortunately, we seem to have developed a national aversion (or at last indifference) to vaccination. Currently, 92% of adults have received at least one dose of a COVID vaccine but only 79% received a full primary series. Worse, only 20% of adults have received a bivalent booster. The sooner we can overcome our culture of vaccine hesitancy, the sooner we can overcome the consistent high number of non-seasonal COVID cases.

Future COVID mortality rates

Over the past 3 years, one out of every 300 Americans have died of COVID. It is difficult to know the exact mortality rate of COVID infections because we do not know exactly how many Americans have been infected with COVID. Using case numbers reported to the CDC, the average mortality rate since the beginning of the pandemic is 1.63%. This likely overestimates the true mortality rate because many people who get infected either do not get tested at all or do home tests that are not reported to the CDC.  The mortality rate has varied considerably over the past 3 years. In the graph below, the case numbers reported to the CDC are in blue and the mortality rate of infection is in red.

It is quite striking that when the case numbers are high, the mortality rate is low and vice versa. On possible explanation for this curious finding is that when new, more infectious COVID variants emerge, many non-vulnerable people (children and young adults) get infected with these variants at school and in workplaces causing a surge in case numbers. Because these people are often younger or have some degree of immunity from previous infection, they are less likely to die. Over the following several weeks, they then infect vulnerable people who are more likely to die: the elderly, the nursing home residents, and those with chronic diseases. This possible explanation is purely conjecture, however.

Another way of estimating the mortality rate of COVID in the U.S. is to use data from the Commercial Laboratory Seroprevalence Survey. This survey estimated the number of Americans who have had COVID based on COVID antibody tests performed on left-over blood from commercial lab tests. Notably, the antibodies tested for would be produced by COVID infection but not by COVID vaccination. An advantage of using data from this survey is that it picks up those people who either did not get tested for COVID because they had mild or asymptomatic infections and those who did home COVID tests that were not reported to the CDC. As of February 2022, 57.7% of samples contained antibodies against COVID. If we assume that this is reflective of the U.S. population as a whole, then as of February 2022, 57.7% of Americans had been infected by COVID – that translates to 192,306,920 people. At that time, the total number of people reported to have died of COVID was 939,875. Using these numbers, the mortality rate of COVID infection calculates to be 0.5%

From these analyses, it appears that the COVID mortality rate has most likely been somewhere between 0.5% and 1.5% over the course of the pandemic. In the future, the COVID mortality rate will hopefully be lower as more Americans have immunity from repeated infections and from booster vaccinations. However, it is a near certainty that some number of people will continue to die of COVID infections in future years. Decades of experience with influenza has shown us that neither natural immunity (from past infections) nor vaccination immunity prevents all deaths from influenza. There will always be deaths in vulnerable populations such as the elderly, the immunocompromised, the obese, and the diabetic. In these individuals, immunity can reduce but not eliminate the chance of dying from infection.

COVID is a new infection for the human race. A useful lesson from history about new infections is from the European settlement of North and South America in the 15th and 16th centuries. The indigenous peoples of the Americas had never been exposed to infections such as smallpox, a disease that is highly contagious but preferentially kills adults. When the first Europeans arrived, they brought with them these diseases that then rapidly spread throughout the continents. It is estimated that within a few decades of Columbus’s first landing, about 90% of indigenous people had died of infections such as smallpox. After burning through native populations, the smallpox mortality among these populations settled into a lower baseline number. If COVID behaves like smallpox, then it is likely that once COVID burns through the world’s human population that it will settle into a lower steady state mortality rate.

Future COVID hospitalizations

Early in the pandemic, U.S. hospitals were overrun by COVID patients. With no effective treatments, many patients died rapidly and survivors often required prolonged ICU care, lingering in the hospital for weeks. With better treatments and better population immunity, more patients are surviving their COVID hospitalization and they are improving faster, resulting in shorter hospital stays. However, COVID is still resulting in a relatively large number of hospital admissions. The graph below shows new COVID hospitalizations in orange and COVID deaths in blue as reported by the CDC. During the January 2021 surge, 1 person died for every 3 COVID hospital admissions. That ratio has improved so currently, 1 person dies for every 10 COVID hospital admissions.

During the January 2021 COVID surge, the CDC reported that 19% of all U.S adult hospital beds were occupied by COVID patients and 31% of all U.S. adult ICU beds were occupied by COVID patients. A year later, during the January 2022 surge, COVID patients accounted for 23% of adult hospital beds and 31% of adult ICU beds. These two surges put an enormous strain on our country’s hospital resources, particularly our intensive care units. Last week, 3.4% of both adult inpatient and ICU beds as well as 1.5% of both pediatric inpatient and ICU beds are occupied by COVID patients.

Although it is unlikely that we will see the overwhelming spikes in COVID hospitalizations such as we saw in January 2021 and January 2022, it is likely that we will continue to see seasonal fluctuations in hospital utilization as COVID assumes a more seasonal pattern. Because of this, hospitals should start planning now to ensure sufficient hospital beds and staffing for an anticipated spike in COVID admissions next winter. During the most recent COVID surge in January 2023, COVID patients occupied 6.5% of both adult hospital beds and adult ICU beds. Children with COVID occupied 2.4% of pediatric hospital beds and 2.3% of pediatric ICU beds. To be conservative, hospitals should plan on a similar increase in hospital bed and ICU demand next winter.

Future COVID treatments

Experience with other human infections has shown us that science makes incremental advances in treatment resulting in incremental improvement in mortality rates. Examples include tuberculosis, hepatitis C, and HIV. In each of these infections, the earliest treatments were marginally effective but as pharmacologic research advanced, subsequent treatments were better and better. The result is that now, most people infected with these pathogens can either be cured or kept in indefinite remission with current medications.

Over the past three years, we have also seen steady improvement in COVID treatments ranging from the ineffective (azithromycin) to the ludicrous (ivermectin) to the somewhat effective (Molnupiravir) to the highly effective (Paxlovid). If advances in COVID treatment is anything like hepatitis C, HIV, and TB, then we will likely have even better COVID treatments in the future.

Wild cards

Evolution shows that all living things mutate as they reproduce. COVID has been no exception with new variants emerging that are more infectious than the previous variants. The greater the total number of viruses present on earth at any given time, the greater the likelihood of a new variant developing. As worldwide natural and vaccine immunity increases, it is likely that the rate of new variant emergence will slow. This should give vaccine producers more time to create vaccines effective against those new variants, thus improving our ability to stay one step ahead of COVID. Nevertheless, that other variants will arise in the future is a certainty.

One of the reasons that we cannot eliminate COVID from the planet is that it can infect other animals. So far, COVID has been demonstrated to infect more than 30 different kinds of animals. The disease is not as severe or life-threatening as it is in humans but now other animals can serve as viral reservoirs. Even if we could eliminate all human infections today, humans would just get reinfected from deer, pigs, and dogs tomorrow.

Not only will the human race face new COVID variants but we will also likely see new coronaviruses make the jump from other species to ours. This has already happened recently with the coronaviruses that cause MERS (camels) and SARS (bats). There are many, many different coronavirus species with each species affecting different animals. Thus there are different coronavirus species that have been found in cats, dogs, pigs, camels, bats, cows, and chickens. Mutations in any of these coronavirus species can allow them to become infectious to other animals, including humans. The new mRNA vaccine technology now gives us the ability to rapidly develop and distribute vaccines against new coronavirus species that do cross from animals to humans. One challenge is that new vaccines against new viruses require clinical trials to determine vaccine effectiveness and safety. These trials take time and require a large number of subjects. Ideally, we need ways to rapidly predict efficacy and safety without the months required to perform clinical trials.

A future with COVID

It seems clear by now that COVID is not going to go away in the future. It is unrealistic to think that COVID case numbers will steadily go down until COVID drops off the face of the Earth. It will more likely just become one of the many respiratory viruses that humans regularly get infected with. It is likely that there will be a year-round baseline rate and seasonal rate surges. However, we have the ability to control COVID case numbers and case severity by optimizing immunity and by continued research into new medications.

March 6, 2023