CMG COVID-19 Weekly Update 10.10.21

New or Updated this week:
Revisiting the Risk of Myocarditis After mRNA Vaccination and Possible Mechanisms for Its Occurrence (new)
Updated Timeline for Pfizer Vaccine for Children Age 5-11; Logistics Uncertain (new)
Moderna/CMG Pediatric Vaccine Trial Status (updated)
CMG Flu Vaccine Information (updated)
Status of the Pandemic in the United States and the World (updated)
Status of the Pandemic in the Washington Area (updated)
Statistics – CMG Tests for Active Disease (updated)

Hello again everyone. This is the 78th in a series of COVID-19 updates from Capitol Medical Group. These notices are meant to provide an update on the pandemic, explain procedures we have put in place to best serve you, and provide guidance about protecting yourselves and your families. New and updated sections are so indicated.

Revisiting the Risk of Myocarditis After mRNA Vaccination and Possible Mechanisms for Its Occurrence (new)

Two studies conducted in Israel and published in the New England Journal of Medicine this week quantify the risk of myocarditis (inflammation of the heart tissue) after receiving the Pfizer vaccine. Though the two studies used slightly different methods and generated slightly different numbers, their conclusions are the same: myocarditis does occur in a very small number of people after receiving an mRNA vaccine (in this case Pfizer). The vast majority of cases are mild and resolve fully with time and conservative treatment. Myocarditis after vaccination occurs more often after the second dose, is more common in males than females, and is more common in teen and young adult males than older males.

In the first study, a group of cardiologists reviewed every case of myocarditis diagnosed in Israel from December 20, 2020 through May 31, 2021. During this time, roughly 5.1 million people in Israel became fully vaccinated. All received the Pfizer vaccine. During the study time period, 283 total cases of myocarditis were identified, 136 of which were temporally associated with vaccination. The great majority of these (117) occurred following dose 2, while 19 occurred after dose 1. The authors calculated that myocarditis occurred after dose 2 in roughly 4 of every 100,000 males. Rates were higher among males age 16-19: roughly 15 per 100,000. Females had much lower rates: roughly 1 in 100,000 among those age 16-19 and roughly 1 in 220,000 among all ages. 95% of cases occurring after vaccination (129 of 136) were mild and resolved with rest and anti-inflammatory medication. One patient had a severe case and later died.

The rate of myocarditis among the unvaccinated was roughly 9 per 100,000. This is higher than the historical average because myocarditis occurs frequently in those who contract Covid. As compared to cases following vaccination, myocarditis cases among Covid patients tend to be much more severe and are often accompanied by other cardiac issues that can be acutely dangerous and persist over time. A pre-print study in Research Square this week suggests Covid patients who survive their initial infection remain at significantly elevated risk for a variety of cardiovascular issues a year later. These include myocarditis, abnormal heart rhythm, coronary artery disease, blood clots, and heart failure.

The second New England Journal study looking at myocarditis addressed 2.5 million patients in the largest health care organization in Israel who had received at least one dose of the Pfizer vaccine between December and May. 54 cases were identified and reviewed by cardiologists. Again, the highest incidence was found among young males: 10.7 cases per 100,000 age 16-29. The rate among all patients regardless of age or gender was 2.13 per 100,000. 76% of cases were considered mild and 22% moderate. Again, the vast majority resolved with rest and anti-inflammatory medication.

It is not yet clear why a small number of people develop myocarditis following vaccination. One hypothesis is that testosterone plays a role in some way. The higher rates of myocarditis among males in general and adolescent and young adult males in particular supports this line of thinking. This theory will be put to the test shortly if vaccine is approved for younger children – if increased testosterone is partly to blame, we would expect to see significantly lower rates of myocarditis among pre-adolescent children when they start to receive vaccine.

Another intriguing hypothesis has to do with accidental administration of the vaccine into a vein rather than muscle. As you know, Covid vaccine is injected into the deltoid muscle of the upper arm just below the shoulder. It is intended to be deposited into the muscle fibers themselves, at which point it is taken up by individual muscle cells. The internal machinery of these cells is commandeered to produce spike protein, which is then displayed in the outer membrane of the muscle cells. Immune system cells then identify the spike protein as a foreign protein to be eradicated and start to marshal an immune response against the “infected” muscle cells. Part of that response is to generate antibodies and memory cells which recognize the spike protein and can be called into action should it be detected in an actual future infection. Another part of the response is to generate inflammation in and around the “infected” muscle cells themselves, some of which are attacked and destroyed. This is one reason people experience soreness at the injection site after vaccination. This reaction usually resolves within a few days and rarely causes any problem with the muscle itself.

If the vaccine were inadvertently deposited into the blood supply of the muscle rather than the muscle tissue itself, however, some of the vaccine could then travel through the circulatory system to the heart. A portion of the vaccine might be taken up by heart muscle cells, which would then produce spike protein and present it in the cell membrane just like the deltoid muscle cells. The immune system would then marshal an inflammatory response toward the heart muscle cells, causing inflammation of the heart tissue, or myocarditis. This would occur rarely, as it would require the tip of the needle to be located just inside a vein within the muscle as the vaccine was injected, a very unlikely event.

An impressive recent study in Clinical Infectious Diseases tested this theory in mouse subjects (warning: this paper contains graphic photographs of dissected mice). In this elaborate study, one group of mice was given Pfizer vaccine via the normal intramuscular injection route, a second group was given vaccine intravenously through a tail vein, and a third group received a placebo salt water injection into a muscle. The groups were then monitored for pathological changes of various tissues at the microscopic and macroscopic level, spike protein production in various tissues, and serum markers of inflammation at various time points after injection. The results were quite striking.

The hearts of mice receiving placebo or intramuscular vaccine injection appeared normal on gross pathology review in the days following injection. 37% of the mice receiving vaccine into a vein, however, developed readily apparent plaques on the heart tissue in the two days after injection. Microscopic evaluation of these plaques revealed tissue level pathological changes consistent with myocarditis and pericarditis. These changes included degeneration of some of the individual heart muscle cells, apoptosis of other heart cells (a type of programmed cell death that can occur at an accelerated rate when a “foreign” protein is detected inside the cell), and necrosis with adjacent inflammatory cell infiltration in portions of the heart tissue. These are all signs of myocarditis, suggesting that vaccine injected into a vein can travel to the heart, get taken up by heart muscle cells, and prompt an immune system reaction toward those cells that results in myocarditis. Only the mice receiving the intravenous vaccine developed these changes. The pathological changes were notable after the first dose of vaccine and persisted for two weeks. Interestingly, they were markedly aggravated by the second dose of vaccine regardless of whether that second dose was delivered intramuscularly or intravenously. This suggests that if heart cells take up vaccine administered intravenously in the first dose, the immune system response to the second dose can trigger myocarditis even if that second dose is administered intramuscularly. This could conceivably account for the increased rate of myocarditis in humans following the second dose of vaccine.

This study does not constitute proof that inadvertent administration of vaccine into a vein rather than a muscle is to blame for the rare cases of myocarditis seen after vaccination in humans, but the possibility should be taken seriously because it can easily be prevented by a simple vaccination technique. This involves gently pulling back on the plunger once the needle is inserted to confirm the needle tip is resting in a muscle fiber rather than a vein. On the rare occasion when the needle is in a vein, momentary traction on the plunger will result in blood flow back into the syringe, which can easily be seen by the administrator. The needle can then be removed prior to injection and the process repeated to ensure the vaccine is deposited into the muscle rather than the vein. This is how nurses and physicians are trained to administer vaccines, but this step is omitted by some in an effort to speed the procedure and thus spare the patient a moment of discomfort. The technique adds a fraction of a second to the process, but if it can prevent cases of myocarditis after Covid vaccination (the only known complication of note stemming from the mRNA vaccines), in our view it is absolutely worth it. CMG nurses administering Covid vaccine use this technique; we hope it will be universally adopted at other locations as well.

Updated Timeline for Pfizer Vaccine for Children Age 5-11; Logistics Uncertain (new)

It now appears likely a decision on Pfizer vaccine for children age 5-11 will come in early November. How the pediatric formulation of the vaccine will be distributed and administered, however, is not yet clear. It is possible vaccine may not be immediately available upon approval.

The FDA is currently reviewing data from Pfizer’s vaccine trial in this age group. Its panel of independent advisors is scheduled to meet October 26th. If FDA issues an Emergency Use Authorization for the Pfizer vaccine in this age group, the CDC’s advisory panel will then meet November 2nd and 3rd to perform its own review. The official CDC go-ahead for vaccinating children age 5-11 could come immediately thereafter.

Where the shots will first be available, however, is not yet clear. Like many pediatrics practices, CMG currently has a supply of Pfizer’s vaccine for age 12 and up, but a different formulation will be used for the younger children. This formulation has not been distributed and cannot yet be ordered by pediatricians. We do not yet know whether the initial shipments of pediatric vaccine will go to pediatrics practices, pharmacies, mass vaccination sites, or some combination of the three. We will update you here when a decision is made and the logistics become clear. We hope to be able to offer vaccine quickly to as many of our patients as possible.

Moderna/CMG Pediatric Vaccine Trial Status (updated)

Moderna’s KidCOVE vaccine trial in children will be moving to its two youngest age cohorts, 6 months to less than 2 years and 2 years to less than 6 years, in mid-October. For the time being, CMG has been awarded 25 slots in the 6 months to age 2 group and 90 slots in the age 2 to age 5 group. We will surely have more interest than we have slots, and apologize in advance if your child is not selected for participation in the trial. We are hoping to receive additional slots as time goes on.

It appears that CMG’s participation in this portion of the trial will commence October 18th with the younger age cohort, to be followed soon thereafter by the slightly older cohort. Study staff will begin reaching out to families that have expressed interest this week for the younger cohort and in the coming weeks for the 2-5 year olds. If you would like to indicate interest in enrolling your child(ren) in the study and have not previously done so, please fill out an interest form. Only one interest form is needed per family – multiple children can be registered on the same form.

Children who enroll will receive 2 doses of either vaccine or placebo one month apart. ¾ of the children will receive vaccine, the other ¼ placebo. This is a double blind study, so neither the families nor the doctors will know which children receive vaccine. If during the course of the study either Pfizer or Moderna receives an Emergency Use Authroization for their vaccine in this age group, the study will become unblinded. In this event parents would learn whether their children received vaccine or placebo so a decision can be made about the need for subsequent vaccination.

CMG Flu Vaccine Information (updated)

We are happy to report CMG flu vaccine has arrived and clinics have begun for our patients and their families. We are using an online vaccine scheduling system this year. To book an appointment, please follow this link. Please note that although the link leads to a landing page that says “Capitol Medical Group Pediatrics,” it can and should be used for both pediatric and adult patients and their families. There is not a separate scheduling modality for adults. Please also note that each person being vaccinated must have their own appointment – we will not be able to vaccinate those who arrive without an appointment. Appointments are currently available to be booked through Saturday, November 6th. We will be adding additional days to the schedule as more vaccine arrives in the coming weeks. We anticipate conducting flu clinics through mid-November.

We are using a drive-up vaccine strategy this year, utilizing the building’s parking lots. Flu clinics will occur Tuesdays through Fridays in the first of the two underground parking levels, and Saturdays in the second of the two underground levels. Signs on the street will direct you which garage to enter. Families will be directed where to park, have their appointments checked off, fill out a simple form, receive their vaccines at the car, and drive away. Administering flu vaccine will be the sole activity of these drive-up clinics. The nurses will not have other vaccines available to administer, nor will they be equipped to perform testing of any kind.

Patients who are coming into the office for an appointment with a provider, such as a well visit, will be able to receive flu vaccine at that time if they wish. The exception is during our early morning “Before Hours” walk-in hour for sick children – we do not have enough nursing staff during Before Hours to administer flu vaccine.

Flu vaccine is recommended for everyone age 6 months and up. The efficacy of the flu vaccine varies from year to year and is not knowable in advance. In a good year the vaccine is 60-70% effective; in a bad year the number is more like 30-40%. Though the vaccine does not always prevent contraction of the flu, cases tend to be less severe among the vaccinated. The vaccine cannot give you the flu, though like any vaccine it can generate reactogenic effects as your immune system responds. These might include a sore arm, fever, fatigue, or achiness for a day or two.

Status of the Pandemic in the United States and the World (updated)

The situation in the United States improved again this week. The 7-day average of new cases, test positivity, number of hospitalizations, and deaths per day all decreased.

The 7-day cumulative number of Covid-19 cases per 100,000 people in the United States currently stands at 210, down from 231 last week and 259, 315, 308, and 343 the four weeks prior.

The 7-day average number of new cases per day in the United States is currently 98,000, down from 109,000 last week and 123,000, 148,000, 145,000, and 164,000 the four weeks prior. The United States recorded roughly 685,000 total new cases in the last week. This represents 23.6% of all new cases worldwide. The United States has 4.25% of the world’s population.

The national test positivity rate currently stands at 5.9%, down from 6.8% last week and 7.9%, 8.7%, 10.1%, 10.5%, 11.1%, and 11.4% the six weeks prior.

The number of people currently hospitalized with Covid stands at 68,000, down from 75,000 last week and 85,000, 95,000 and 102,000 the three weeks prior.

An average of roughly 1,770 deaths per day were recorded in the United States this week, down from 1,880, 2,060 and 2,000 the last three weeks. As of Saturday morning, the pandemic had killed roughly 713,000 people in the United States.

39 states saw a decrease in average caseload this week. The current top 10 states (cumulative 7-day case rate per 100,000 population): Alaska 770, Montana 623, North Dakota 567, Wyoming 539, West Virginia 483, Idaho 476, Minnesota 371, Wisconsin 357, Kentucky 350, and Ohio 315. Again, the national number is currently 210 cases per week per 100,000 people.

The per capita numbers in our region improved this week. Cumulative 7-day case rate per 100,000 population: Maryland 126 (down from 147 last week and compared to 140, 147, 112, and 140 the four weeks prior), DC 133 (down from 161, 189, and 266 the last three weeks), and Virginia 224 (down from 231, 266, and 294 the last three weeks). Virginia, DC, and Maryland rank 29th, 45th and 46th out of the 51 states plus DC on the list this week.

15 populous nations have higher per capita rates of disease than the United States at the moment. The top 10: West Bank/Gaza (784 cases per 100,000 population this week), Serbia 651, Lithuania 497, Mongolia 469, Latvia 462, Romania 455, Georgia 378, Singapore 371, UK 357, and Moldova 336.

Status of the Pandemic in the Washington Area (updated)

New cases reported in DC averaged 134 per day this week, down from 161, 193, and 269 the last three weeks. To this point DC has documented roughly 62,270 total cases and 1,182 deaths. New cases in Montgomery County averaged 106 per day this week, down from 122, 116, and 146 the last three weeks. Montgomery County has now recorded roughly 80,430 total cases and approximately 1,632 deaths.

Statistics – CMG Tests for Active Disease (updated)

CMG conducted 542 tests for active disease this week, 8 of which were positive. This translates to a positivity rate of 1.5%, up from 0.8% last week and compared to 4.6%, 1.7%, 1.8%, and 2.5% the four weeks prior. CMG’s average positivity rate for the duration of the pandemic is 2.0%.

Group Virtual Visit Offerings – On Hiatus

CMG’s Group Virtual Visit sessions will remain on hiatus this week. We hope to bring these back in the coming weeks.