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Dr. Marty Makary on New Lancet Study Showing 1/6 Kids Did Not Recover from Myocarditis 90 Days Post-Jab
Summary
Background
Methods
Findings
Interpretation
Funding
Introduction
Evidence from the USA and multiple international vaccine safety monitoring systems support a small but increased risk of myocarditis after mRNA COVID-19 vaccination.
In 2021, data from the Vaccine Adverse Event Reporting System (VAERS) indicated that in US individuals aged 12 years or older, approximately 4·8 cases of myocarditis per million doses of mRNA COVID-19 vaccines administered were reported, with the highest reporting rates in those aged 12–29 years.
Despite the higher than expected occurrence of myocarditis after COVID-19 vaccination, the benefits of mRNA COVID-19 vaccines have been shown to outweigh the risk of myocarditis.
Research in context
Cardiac assessment of patients diagnosed with myocarditis after mRNA COVID-19 vaccination often shows increased cardiac biomarkers (eg, troponin concentrations) and atypical cardiac imaging (eg, echocardiograms), which are similar findings to those shown for viral or acute myocarditis.
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Viral myocarditis unrelated to mRNA COVID-19 vaccination can lead to heart failure, cardiac transplantation, or death.
Conversely, case descriptions suggest that clinical outcomes following a diagnosis of myocarditis after mRNA COVID-19 vaccination are more favourable than those associated with viral myocarditis, with resolution of symptoms often described at or soon after discharge from a short hospital stay for myocarditis after mRNA COVID-19 vaccination.
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However, data on follow-up prognoses for adolescents and young adults diagnosed with myocarditis after mRNA COVID-19 vaccination are scarce.
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To conduct surveillance, the US Centers for Disease Control and Prevention (CDC) developed a working myocarditis case definition with a team of subspecialists that has been used in several studies.
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Methods
Study design and population
In this follow-up surveillance study, we included US patients who were aged 12–29 years at the time of mRNA COVID-19 vaccination and for whom the time to myocarditis symptom onset was more than 90 days since vaccination and a VAERS report was filed between Jan 12, to Nov 5, 2021. VAERS is a national passive surveillance system coadministered by the CDC and the US Food and Drug Administration (FDA).
Any vaccine recipients, health-care providers, and vaccine providers can submit a report to VAERS. Under emergency use authorisations, vaccination providers are subject to mandatory reporting requirements for certain adverse events after COVID-19 vaccination, including hospitalisation.
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The CDC encourages both vaccination providers and recipients report any clinically significant adverse event, regardless of the plausibility of the vaccine causing the event. Signs and symptoms of adverse events are coded using the Medical Dictionary for Regulatory Activities.
Physicians at the CDC reviewed all identified VAERS reports and available medical records to determine if the case met CDC case definition criteria
for confirmed or probable myocarditis or myopericarditis (henceforth referred to as myocarditis; appendix 1 p 6).
Procedures
To assess patient quality of life and overall health after myocarditis diagnosis, we administered the EuroQol 5-dimension, 5-level (EQ-5D-5L) questionnaire that characterises health across five dimensions: mobility, self-care, pain or discomfort, perform usual activities, and anxiety or depression.
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The EQ-5D-5L instrument has been validated for use in people aged 12–29 years
and was used in this surveillance activity to describe the overall wellbeing of the patient group, not as an indicator of myocarditis recovery. For the quality of life questionnaire, five levels of response, from no problems to extreme problems, were dichotomised as no problems (severity level 1) or any problems (severity levels 2–5).
Weighted analysis converted patient responses to a numerical scale ranging from 0 (equivalent to death) to 1 (full health; appendix 1 p 7).
Overall health was self-rated by patients using the EuroQol visual analog scale (EQ-VAS), with scores ranging from 0 to 100 (100 representing the best possible health and 0 representing the worst possible health). We compared the patients’ EQ-5D-5L survey responses with published EQ-5D-5L survey results of 18–24-year-old US population respondents before and during the COVID-19 pandemic.
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In both parts of the survey, health-care providers and patients were asked about any previous SARS-CoV-2 infection in the patient before the diagnosis of myocarditis, as determined by a positive laboratory-confirmed test; however, we did not ask about the severity of infection. To assess myocarditis recovery, health-care providers were asked the following: based on your clinical assessment and any testing information, please describe the patient’s cardiac recovery status as of the date of your last visit or consultation (compared with the time of initial myocarditis diagnosis; appendix 2 p 4). Survey options were fully recovered, probably fully recovered, improved but not fully recovered, same cardiac status as at the initial diagnosis (ie, no worse or no better), worse cardiac status, unsure, or declined to answer. For this evaluation, patients determined to be fully or probably fully recovered by the health-care provider were designated recovered and patients deemed to be improved but not fully recovered or with the same cardiac status at initial diagnosis were designated not recovered. CDC’s Clinical Immunization Safety Assessment (CISA) Project provided technical input for survey development.
Statistical analysis
Role of the funding source
Results
Between Jan 12 and Nov 5, 2021, 989 cases of myocarditis after mRNA COVID-19 vaccination in patients aged 12–29 years were reported to VAERS and met the CDC’s case definition for myocarditis. Of these, 836 (85%) patients were at least 90 days post-myocarditis onset (figure 1). Of the 836 patients, 204 (24%) patients had no telephone number available for contact and 257 (31%) patients were unreachable. Of the remaining 375 patients, 357 (95%) patients consented to the survey and 18 (5%) patients declined. Between Aug 24, 2021, and Jan 12, 2022, we contacted and collected data for 519 (62%) of the 836 eligible patients: 126 patients via patient survey only, 162 patients via health-care provider survey only, and 231 patients via both the patient and health-care provider survey (figure 1). Median interval from myocarditis onset to survey completion was 143 days (IQR 131–162) for patients and 191 days (170–216) for health-care providers. We found no significant differences in VAERS reporter type (health-care provider or patient), geographical census region, age, sex, initial echocardiogram findings, or race or ethnicity in patients surveyed compared with patients who were not surveyed (appendix 1 p 8). In a subset of patients with abnormal echocardiograms, the abnormality identified was a left ventricular ejection fraction (LVEF) of less than 50%. Of the 100 survey respondents with LVEF values recorded at their initial diagnosis, 33 (33%) had LVEF values less than 50%, which was not statistically different from the results in non-respondents (27 [42%] of 65 non-respondents; χ2=1·24, p=0·265).
Most patients were male (457 [88%] of 519 patients) and White non-Hispanic (274 [53%]), and the median age of all patients was 17 years (IQR 15–22; table 1). 98 (19%) of 519 patients were Hispanic of any race. There was no notable difference between recovered individuals compared with individuals who were not recovered across any ethnic or racial groups. Overall, patients considered to be recovered and not recovered from myocarditis were similar with respect to age (median age 17 years [IQR 15–21] for patients considered recovered vs 17 years [15–21] for those considered not recovered) and sex (290 [91%] male individuals who were considered recovered vs 56 [86%] of male individuals who were considered not to be recovered, and 30 [9%] female individuals who were considered recovered vs 9 [14%] of female individuals who were not considered recovered). The median time from illness onset to health-care provider interview for the 320 (81%) of 393 individuals who were considered recovered was 189 days (IQR 167–214), and for the 61 (16%) of 393 patients who were considered improved but not fully recovered the median time was 195 days (179–195).
| Patients fully or probably fully recovered (n=320) | Patients not recovered (n=65) | All patients (n=519) | p value | ||
|---|---|---|---|---|---|
| Median age, years (IQR) | 17 (15–21) | 17 (15–21) | 17 (15–22) | .. | |
| Age group, years | |||||
| 12–14 | 58 (18%) | 9 (14%) | 92 (18%) | 0·84 | |
| 15–19 | 160 (50%) | 35 (54%) | 245 (47%) | .. | |
| 20–24 | 69 (22%) | 15 (23%) | 120 (23%) | .. | |
| 25–29 | 33 (10%) | 6 (%9) | 62 (12%) | .. | |
| Sex | |||||
| Male | 290 (91%) | 56 (86%) | 457 (88%) | 0·39 | |
| Female | 30 (9%) | 9 (14%) | 61 (12) | .. | |
| Unknown | 0 | 0 | 1 (<1%) | .. | |
| Race, ethnicity | |||||
| White, non-Hispanic | 182 (57%) | 32 (49%) | 274 (53%) | 0·32 | |
| Asian, non-Hispanic | 16 (5%) | 1 (2%) | 25 (5%) | 0·33 | |
| Black, non-Hispanic | 10 (3%) | 2 (3%) | 16 (3%) | 0·71 | |
| Other race, non-Hispanic | 11 (3%) | 0 | 12 (2%) | 0·22 | |
| Multiple races, non-Hispanic | 10 (3%) | 1 (2%) | 12 (2%) | 0·69 | |
| American Indian or Alaskan native, non-Hispanic | 1 (<1%) | 0 | 1 (<1%) | .. | |
| Hispanic | 53 (17%) | 14 (22%) | 98 (19%) | 0·33 | |
| Unknown | 37 (12%) | 13 (20%) | 81 (16%) | .. | |
| Previous SARS-CoV-2 infection | 28 (9%) | 4 (6%) | 48 (9%) | 0·61 | |
| Received two COVID-19 vaccine doses | 278 (87%) | 58 (89%) | 448 (86%) | 0·75 | |
| Underlying medical condition | |||||
| At least one condition, excluding obesity | 63 (20%) | 16 (25%) | 99 (19%) | 0·46 | |
| Asthma | 29 (9%) | 4 (6%) | 41 (8%) | 0·60 | |
| Autoimmune disease | 10 (3%) | 1 (2%) | 13 (3%) | 0·69 | |
| Arrhythmia | 9 (3%) | 1 (2%) | 16 (3%) | 0·86 | |
| Congenital heart disease | 8 (2%) | 2 (3%) | 10 (2%) | 0·68 | |
| Genetic or chromosomal | 7 (2%) | 8 (12%) | 15 (3%) | 0·0005 | |
| Previous heart failure | 1 (<1%) | 1 (2%) | 2 (<1%) | 0·31 | |
| Kawasaki disease | 1 (<1%) | 0 | 2 (<1%) | .. | |
| Myocarditis | 4 (1%) | 1 (2%) | 7 (1%) | .. | |
| Type 1 diabetes | 1 (<1%) | 1 (2%) | 3 (1%) | 0·31 | |
| BMI-based obesity | 80/291 (27%) | 16/63 (25%) | 99/359 (28%) | 0·86 | |
| Patient-reported symptoms in the patient survey | n=195 | n=28 | n=357 | .. | |
| At least one symptom | 94 (48%) | 18 (64%) | 178 (50%) | 0·16 | |
| Chest pain or discomfort | 55 (28%) | 13 (46%) | 113 (32%) | 0·082 | |
| Chest pain or discomfort while resting | 45 (23%) | 11 (39%) | 92 (26%) | 0·011 | |
| Fatigue | 40 (21%) | 12 (43%) | 89 (25%) | 0·018 | |
| Fatigue while resting | 28 (14%) | 10 (36%) | 63 (18%) | 0·012 | |
| Shortness of breath | 38 (19%) | 9 (32%) | 80 (22%) | 0·28 | |
| Shortness of breath while resting | 15 (8%) | 4 (14%) | 38 (11%) | 0·42 | |
| Heart palpitations | 36 (18%) | 6 (21%) | 77 (22%) | 0·71 | |
| Heart palpitations while resting | 28 (14%) | 5 (18%) | 59 (17%) | 0·84 | |
Of 357 patients surveyed, 249 (71%) consented to completing both the EQ-5D-5L and EQ-VAS components of the patient survey. Of 249 patients, four (2%) reported problems with self-care, 13 (5%) with mobility, 49 (21%) with performing usual activities, 74 (30%) with pain, and 114 (46%) with anxiousness or depression (figure 2A). Overall, patients reported having good health, reflected by the high median weighted index score (0·94; IQR 0·88–1·00) and median overall health status (EQ-VAS) score (90; 80–95; figure 2B, C).
The mean EQ-5D-5L weighted utility score in our group (0·91 [SD 0·13]) was significantly higher than that for US respondents aged 18–24 years who completed a EQ-5D-5L questionnaire during the pandemic, as reported by Hay and colleagues
(0·75 [0·28]; p<0·0001). Mean EQ-5D-5L weighted utility scores from the pre-pandemic timepoint among US respondents aged 18–24 years have also been reported by Jiang and colleagues, from face-to-face surveys and online surveys.
The weighted score from our survey was not significantly different to that obtained in the face-to-face surveys (0·92 [0·13]), but our score was significantly higher than that from the online surveys (0·84 [0·18]; p<0·0001).
Most patients were admitted to hospital after an initial diagnosis of myocarditis (484 [93%] of 519 patients). Of these 484 patients, 393 (81%) patients had information on level of care, according to the health-care provider surveys; 99 (25%) of these 393 patients were treated in an intensive care unit and one (<1%) patient required extracorporeal membrane oxygenation (table 2). To our knowledge, no deaths occurred during follow-up among the patients eligible for the survey. Six (2%) of 357 patients who self-reported re-admission to hospital had a hospital admission because of an adverse event after myocarditis treatment (n=3; adverse reactions to intravenous immune globulin) or had any cardiac abnormality identified (n=3; appendix 1 p 6); all patients were discharged within 1 week.
| Patients fully or probably fully recovered (n=320) | Patients not recovered (n=65) | Patient recovery unknown (n=8) | p value | ||
|---|---|---|---|---|---|
| Highest level of care | |||||
| Hospitalised with no intensive care | 210 (66%) | 40 (62%) | 4 (50%) | 0·66 | |
| Hospitalised with intensive care | 85 (27%) | 12 (18%) | 2 (25%) | 0·22 | |
| Not hospitalised, managed as outpatient | 14 (4%) | 9 (14%) | 2 (25%) | 0·0074 | |
| Intensive care with ECMO | 0 | 1 (2%) | 0 | .. | |
| Unknown | 11 (3%) | 3 (5%) | 0 | .. | |
| Patient restrictions on physical activity | |||||
| At time of initial myocarditis hospitalisation or diagnosis | 267 (83%) | 53 (82%) | 6 (75%) | 0·84 | |
| At time of last health-care provider follow-up | 91 (28%) | 31 (48%) | 3 (38%) | 0·0038 | |
| Cleared for physical activity and date of clearance known | 160/267 (60%) | 16/53 (30%) | 2/6 (33%) | 0·026 | |
| Median days from myocarditis onset to physical activity clearance (IQR) | 104 (63–135) | 114 (73–156) | 80 | 0·12 | |
| Patient cardiac MRI | |||||
| At time of initial myocarditis hospitalisation or diagnosis | 137 (43%) | 32 (49%) | 0 | 0·56 | |
| At time of healthcare provider follow-up | 114 (36%) | 36 (55%) | 1 (13%) | 0·0023 | |
| Patient echocardiogram | |||||
| At time of initial myocarditis hospitalisation or diagnosis | 257 (80%) | 55 (85%) | 7 (88%) | 0·53 | |
| At time of health care provider follow-up | 230 (72%) | 51 (78%) | 3 (38%) | 0·35 | |
| Patient troponin | |||||
| At time of initial myocarditis hospitalisation or diagnosis | 318 (99%) | 65 (100%) | 7 (88%) | 0·76 | |
| At time of healthcare provider follow-up | 166 (52%) | 33 (51%) | 1 (13%) | 0·86 | |
| Patient electrocardiogram | |||||
| At time of initial myocarditis hospitalisation or diagnosis | 210 (66%) | 34 (52%) | 6 (75%) | 0·059 | |
| At time of health-care provider follow-up | 251 (78%) | 55 (85%) | 5 (63%) | 0·34 | |
| Patient exercise stress test | |||||
| At time of health-care provider follow-up | 91 (28%) | 16 (25%) | 2 (25%) | 0·63 | |
| Patient ambulatory rhythm monitoring | |||||
| At time of health-care provider follow-up | 86 (27%) | 18 (28%) | 1 (13%) | 0·89 | |
| Prescribed medication at last provider follow-up | 68 (21%) | 33 (51%) | 3 (38%) | <0·0001 | |
| Daily medication types prescribed | |||||
| Colchicine | 31 (10%) | 17 (26%) | 0 | 0·0005 | |
| β-blocker | 29 (9%) | 12 (18%) | 1 (13%) | 0·043 | |
| Non-steroidal anti-inflammatory | 21 (7%) | 9 (14%) | 1 (13%) | 0·081 | |
| Aspirin | 9 (3%) | 5 (8%) | 1 (13%) | 0·069 | |
| Angiotensin-converting enzyme inhibitor | 8 (3%) | 6 (9%) | 0 | 0·018 | |
| Diuretic | 3 (1%) | 3 (5%) | 0 | 0·063 | |
| Corticosteroid | 1 (<1%) | 3 (5%) | 0 | 0·016 | |
| Angiotensin II receptor blocker | 2 (1%) | 7 (11%) | 0 | <0·0001 | |
| Other medication | 3 (1%) | 2 (3%) | 1 (13%) | ||
was uncommon (20 [13%] of 151 patients; appendix 1 p 9). Median interval from symptom onset to evidence of ongoing myocarditis was 26 days (IQR, 9–94) and from symptom onset to evidence of late gadolinium enhancement was 109 days (58–163; appendix 1 p 10). Of the 67 patients with late gadolinium enhancement or evidence of ongoing myocarditis, additional follow-up testing indicated abnormal echocardiograms in five (7%) patients, abnormal troponin concentrations in five (7%) patients, and abnormal electrocardiograms in 14 (21%) patients (appendix 1 p 13).
In the subset of patients with abnormal findings at the time of myocarditis diagnosis, abnormal diagnostic markers or abnormal imaging were also observed at follow-up in seven (12%) of 60 with initial abnormal echocardiograms, 19 (5%) of 387 with initial elevated troponin levels, and 47 (32%) of 146 with initial abnormal cardiac MRIs (figure 4). There was substantial heterogeneity in cardiac biomarkers, imaging, and patient functional status between patients considered recovered or not recovered from myocarditis (appendix 1 p 16). All cardiac test results (ie, echocardiogram, electrocardiogram, cardiac MRI, and troponin) were available for follow-up review in only 199 (62%) of 320 patients considered recovered, 44 (68%) of 65 considered not recovered, and three (38%) of eight with an unknown recovery status.
