COVID-19, Vaccinations and Myocarditis

The world is currently experiencing its third wave of COVID-19, driven by the Delta variant. There is good evidence that vaccinations are effective in the reduction of serious illness and death as a result of COVID-19.

Figures from the COVID-19-Associated Hospitalization Surveillance Network (COVID-NET) in the United States show that unvaccinated adults are 17 times more likely to be hospitalised compared with fully vaccinated adults. (DOI: https://doi.org/10.1101/2021.08.27.21262356)

Similarly, data from countries like the United Kingdom and Israel, where vaccination uptake has been good, shows that recent surges in COVID-19 cases is driven by the section of the population who remain unvaccinated.

The vaccination should no longer be considered ‘experimental'.

The Pfizer vaccine has a good safety record. The end points that were required to authorise the vaccine for use – that’s the safety and efficacy required through phase 3 clinical trials – were met last year. It was double peer reviewed and published in the New England Journal of Medicine 31 Dec 2020. (DOI: 10.1056/NEJMoa2034577).

Why are mRNA vaccines so safe?

The vaccine doesn’t persist in the body. It is injected into muscle, cells are recruited to the area and take up the vaccine. The spike protein is produced and then the mRNA degrades in a matter of hours to days.

What are the side effects of the Pfizer vaccine?

The majority of side effects are mild. Data from the NZ Centre for Adverse Reactions Monitoring (CARM) shows the top 10 most reported symptoms in NZ are:

Myocarditis and pericarditis are rare but serious side effects of the Pfizer vaccination. A study from Israel published in the NEJM shows no increase in any other kind of adverse cardiovascular outcome following the Pfizer vaccination. In comparison, the risk of myocarditis, pericarditis, myocardial infarction and arrhythmia are all increased as a result of having the COVID-19 virus. (DOI: 10.1056/NEJMoa2110475)

How likely is myocarditis following an mRNA COVID-19 vaccination?

Figures from the US Centre for Disease Control and Prevention (CDC) to June 2021, show there were 636 cases of myocarditis reported in 133 million second doses administered. That’s about six cases per million second dose.

The rate is higher in young males, with figures as follows

• 12-17 years old males: 63 cases per million
• 18-24 years old males: 50 cases per million
• 25-29 year old males: 16 cases per million second doses

In females the risk is about eight times lower than in males.

Source: https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2021-06/05-COVID-Wallace-508.pdf

A recent study of 2,000,000 patients published in JAMA Cardiology showed a rate of 1 in 100,000 cases.

Source: https://jamanetwork.com/journals/jama/fullarticle/2782900

doi:10.1001/jama.2021.13443

Risk vs benefit of the vaccination

In short, the risk of getting seriously ill from COVID-19 is greater than the risk of getting seriously ill after the vaccination – even in patient groups who are at higher risk of an adverse event post vaccination.

People are also more likely to develop myocarditis as a result of COVID-19, than they are as a result of the vaccination.

Even in younger cohorts, early research suggests the risk of myocarditis from COVID-19 is still higher than the risk of myocarditis from the vaccination.

Source:Singer ME et al, Risk of Myocarditis from COVID-19 Infection in People Under Age 20: A Population-Based Analysis DOI: https://doi.org/10.1101/2021.07.23.21260998

Source: https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2021-08-30/06-COVID-Rosenblum-508.pdf

Younger people

Although the risk of myocarditis as a result of the COVID-19 vaccination is higher in young men, current evidence suggests having the vaccination, is on balance, less risky than catching the virus.

A benefit risk analysis published in Circulation in July concluded that despite the increased risk of myocarditis, having the vaccination remained favourable for all age groups.

“Given the known potential risk of complications with COVID-19 infection, including hospitalizations and death even in younger adults (mortality remains 0.1–1 per 100 000 for persons 12–29 years of age), the risk-benefit decision remains overwhelmingly favorable for vaccination. COVID-19 vaccination not only prevents COVID-19–related hospitalizations and death, but also COVID-19–related complications such as myocarditis, multisystem inflammatory syndrome, and post–acute sequelae of SARS-CoV-2 infection or long COVID-1.”

Source: https://www.ahajournals.org/doi/full/10.1161/CIRCULATIONAHA.121.056135

Multisystem Inflammatory Syndrome in children (MIS-C) is a rare complication of the COVID-19 virus, occurring two to six weeks after a COVID infection that can cause life-threatening inflammation involving the heart, lungs and blood vessels in children and young adults.

Source: Starship guideline: COVID-19 associated multi-system inflammatory conditions (PIMS-TS, MIS-C

Source: Multisystem Inflammatory Syndrome in US children and adolescents. Feldstein LR, Rose EB, Horwitz SM, Collins JP, Newhams MM, Son MBF et al. N Eng J Med 2020; 383(4):334-46

A study due to be published in Pediatrics looking at post vaccination myocarditis in children and young people aged 12-20 found the course of the condition was mild, with an average length of three days in hospital.

In the under 12s, trial results are expected this month from the United States, looking at use of the vaccine in the 5-11 year old age group, and in six months to four-year-olds, with possibility of fractional doses for younger age groups. New Zealand has not approved the use of vaccine in this age group yet.

Pregnancy

Pregnant women with COVID-19 are at increased risk for severe illness and death compared to nonpregnant women of reproductive age. The vaccine is very safe in pregnancy as the vaccine doesn’t cross the placenta.

Preliminary findings of the v-safe registry and Vaccine Adverse Event Reporting System in the US, published in the NEJM, showed no increase in side effects in pregnant women, and no higher rate of pregnancy loss or adverse neo-natal outcomes.

Source: Preliminary Findings of mRNA COVID-19 Vaccine Safety in Pregnant Persons (DOI: 10.1056/NEJMoa2104983)

People with a cardiac condition

There is no evidence that patients with cardiac disease are more at risk of developing myocarditis after the vaccination than anybody else. Cardiac patients however have a considerably higher risk of adverse outcomes following a COVID-19 infection. Vaccination is highly effective at reducing the rate of mortality and hospitalisation.

The European Society of Cardiology has recommended that all patients with cardiovascular disease should receive the COVID-19 vaccination.

https://www.escardio.org/Education/COVID-19-and-Cardiology/COVID-19-and-vaccinations

People with previous myocarditis or a recent acute cardiac event

Australian guidelines recommend waiting 6 months following a diagnosis of myocarditis before administering the vaccination.

The risk of developing COVID-19 needs to be balanced with the risk from the vaccine. If a patient has fully recovered from the myocarditis, earlier vaccination could be considered.

Patients who develop myocarditis or pericarditis from the first dose of the vaccine should consider delaying the second dose. If the Astra Zeneca or another adenovirus vector vaccine becomes available in NZ this vaccine would be preferred.

There is no evidence of harm from early vaccination following an acute coronary syndrome. Experts suggest waiting four days for recovery until a patient is stable.

People who’ve had the COVID-19 virus

As yet, there’s no New Zealand policy on whether people who’ve had COVID-19 need to be vaccinated as well.

Looking overseas, some countries are not vaccinating, some are giving one dose, and some are giving two.

There is some evidence to suggest that people who’ve had the virus and are given one dose of an mRNA vaccine develop excellent protection.

Vaccine hesitancy in patients

Unvaccinated patients are increasingly likely to be vaccine hesitant, so it’s important to encourage uptake where possible. They are likely to fall into three groups:

Refusal – this group are strongly opposed to the vaccine. They’re probably a relatively small group, but very vocal.

Apathy – this is a much larger group, who aren’t strongly anti-vax but are apathetic or cautious about taking action for various reasons – eg they feel the virus isn’t an immediate threat or they’re worried about the recent case of myocarditis.

Mistrust of the system – especially people from underserved groups. The health system has not always treated them and their whānau well and they know the vaccine is provided by this system, so therefore have reservations.

Individual practitioners can reach out to patients who are vaccine hesitant. The following tips maybe helpful.

• Do not judge your patient for their point of view, even if you don’t agree. If they trust you enough to share their views, do not judge them for a different perspective.
• Gauge where patient is at and open communication avenues.
• Engender trust.
• Communicate clearly.
• Tell them the truth, without judgement. If you don’t know the answer to something, find out.
• Ensure your message is consistent with public health messaging.
• Practice good medicine. Even if you can’t encourage them to get a vaccine, take the opportunity to engage with them on other health issues so the patient feels like you’re taking an interest. For example, helping to manage diabetes, blood pressure, cholesterol etc.
• If you’re on social media, use it to share information from reliable sources.

Remind patients that unvaccinated people are not going to be protected by herd immunity, as we’re unlikely to reach that rate of vaccination.

Timing of vaccinations

How much protection is given by one dose?

The first dose of the Pfizer jab gives 77% protection against severe disease. This protection is likely to be higher in younger people.

What’s the ideal gap between first and second doses?

Three to four weeks. In times of limited vaccination capacity, there is an argument that the population as a whole is better served by having a larger percentage of the population partly vaccinated that a smaller percentage fully vaccinated.

Are there particular patient groups for whom this gap is different?

No.

Does increasing the gap between the doses reduce the risk of post vaccine myocarditis?

There is currently no evidence to support this theory, although it is likely to be investigated in future research.

Boosters

There is no evidence to support the wide use of boosters at this time.

They may be useful for border workers who are at higher risk of infection, and for the elderly and frail, whose immune response to the primary course may not have been as good.

Should someone who has had significant side-effects from the first dose, receive a second?

This decision would need to be made on a case-by-case basis, taking into account a patient’s age, gender, co-morbidities, the type and severity of side-effects, and their risk of getting seriously ill from the virus.

What if I suspect post-vaccination myocarditis?

What are the common symptoms of sign and symptoms of myocarditis?

• New onset chest pain
• Shortness of breath
• Palpitations
• Abnormal heartbeat

Onset is likely to occur within seven days, with average onset three days post vaccination.

What tests should I order if I suspect myocarditis?

Troponin is a very simple and effective test for diagnosing myocardial injury. If it comes back normal then it’s unlikely to be myocarditis. Be aware that for children, troponin is a less sensitive test. The key things to look for are:

• Elevated troponin
• Abnormal ECG

It’s important to enter the patient’s age correctly, as ECG machine adjusts accordingly.

Features of myocarditis will usually be reported on the ECG.

Most common findings in myocarditis are:

• • Widespread ST Elevation with a concave appearance.
  • Significant conduction defects
  • QRS complex in limb leads may be small

• Elevated CRP

Research is showing very elevated CRP in post-vaccine myocarditis.

The CDC indications for diagnosing a case of myocarditis are as follows:

CDC WORKING CASE DEFINITIONS

https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.121.056135

What to do next?

If the patient is seriously unwell, irrespective of the troponin level, admit to hospital. If not, examine the patient listening for a pericardial rub and looking for signs of heart failure.

Check an ECG and blood test including troponin level. If the troponin is elevated admit to hospital.

If not, plan to review the patient again in a couple of days’ time or sooner if they deteriorate.

Significant adverse events should be reported to CARM.