Sex: M
Vaccine: COVID19
Symptoms: Activated partial thromboplastin time prolonged, Antinuclear antibody, Blood glucose, Blood pressure measurement, Body temperature
Clinical narrative: This approximately 42-year-old Male subject was participating in Study to Evaluate the Efficacy, Safety, and Immunogenicity of mRNA-1273 SARS-CoV-2 Vaccine in Adults Aged 18 Years and Older (mRNA-1273-P301) and experienced the medically significant serious adverse event of special interest of myocarditis. The subject's medical history, as provided by the investigator and the medical record, included dislocated left knee, environmental allergies, torn cartilage right shoulder, lactose intolerant, vasectomy, left eye amblyopia, allergy to cat and dog dander, allergy to walnuts, asthma, eczema - bilateral upper arms, nephrolithiasis right side, Lyme disease, left knee arthroscopic surgery, right shoulder arthroscopic surgery, spastic gait, and mild obstructive sleep apnea. Concomitant medications included salbutamol, tilactase, ibuprofen, prednisone, sertraline, colecalciferol, fish oil, and ascorbic acid. Prior to event onset, the subject received intramuscular mRNA-1273 (booster, dose 3) SARS-CoV-2 vaccination on 12 Oct 2021 approximately 1 day before onset of the event. On 12 Oct 2021, the subject experienced myocarditis. The subject reported developing a low-grade fever, myalgias, and chest pain that awoke him from sleep. The chest pain was sharp, constant, non-exertional and worse when lying down on left side. On 14 Oct 2021, the subject presented to the emergency room (ER) complaining of worsening of symptoms. Pain described as having an exertional and positional component. It was noted that the subject had no history of coronary artery disease. Vital signs at triage were blood pressure 126/86, body temperature 36 degrees Celsius, heart rate 89, respirations 16, and oxygen saturation 99 percent (%) on room air. A chest X-ray showed clear lungs and no pleural effusion or pneumothorax. An electrocardiogram (ECG) on arrival showed no changes. High sensitivity troponin levels were 159.4 pg/mL at 19:56 (normal 0.0-19.8 pg/mL) and 129.3 pg/mL at 23:22. Additional vital signs were blood pressure 122/84, body temperature 36 degrees C, heart rate 72, and respiratory rate 18. Cardiology was consulted, the subject was admitted to the hospital, and treatment was initiated with intravenous heparin, transdermal nitroglycerin, oral acetylsalicylic acid, and oral metoprolol. Laboratory value of note was glucose 147 milligram per deciliter (mg/dL) (normal 70-109 mg/dL). Other labs within normal limits. On 15 Oct 2021, a high sensitivity troponin was 76.4 pg/mL at 04:11. The subject experienced an episode of nausea and headache during the night and a repeat ECG showed normal sinus rhythm with non-specific T-wave abnormality. Laboratory values of note activated partial thromboplastin time of 44 seconds, antinuclear antibody positive, glucose 158 mg/dL, C-reactive protein 24.5 milligrams per liter (mg/L) (normal 0.00-5.0 mg/L), and hemoglobin A1c 6.3 % (normal 4.5-6.2%). A left heart catheterization with fluoroscopy using low osmolar contrast was performed with the subject receiving fentanyl and midazolam for sedation. Results showed normal coronary arteries, normal left-sided filling pressure, and no gradient across the aortic valve. A transthoracic echocardiogram with left ventriculogram was normal and showed left ventricular end diastolic pressure 9 millimeters of Mercury (mmHg), no significant gradient across the aortic valve on pullback, no reginal wall motion abnormalities, and a calculated ejection fraction of 65%. The subject was determined to have myocarditis after normal echocardiogram and cardiac catheterization. Heparin and acetylsalicylic acid were discontinued. Vital signs were blood pressure 116/77, body temperature 36.6 degrees C, heart rate 68, respiratory rate 18, and oxygen saturation 96% on room air. On 16 Oct 2021, vital signs were blood pressure 120/78, body temperature 36.6 degrees C, heart rate 71, respiratory rate 18, and oxygen saturation 97% on room air. A SARS-Cov-2 test (nares) was performed with a result of not detected. On 17 Oct 2021, the subject reported some slight upper lip swelling suspected to be secondary to metoprolol. No rash, tongue swelling, or stridor noted. Metoprolol was discontinued and treatment with oral carvedilol was started. Laboratory value of note was glucose of 110 mg/dL. Vital signs blood pressure 128/82, body temperature 36.7 degrees C, heart rate 62, respiratory rate 18, and oxygen saturation 97% on room air. The subject reported feeling better with minimal mild, intermittent chest pressure and was discharged from the hospital. Prior to discharge there was no worsening of the lip swelling after initiation of carvedilol and swelling was assessed as having improved slightly at time of discharge. The subject was scheduled to follow-up with his primary care provider and cardiology. A cardiac magnetic resonance imaging scan was scheduled for the end of November. On 29 Nov 2021, the subject underwent magnetic resonance imaging of the heart which revealed normal systolic function and mildly limited delayed enhancement images demonstrating no evidence of myocarditis. The subject received all scheduled doses of study drug prior to the event; therefore, action taken with study drug in response to the event was not applicable. The event, myocarditis, was reported as resolved on 22 Dec 2021. The investigator assessed the event, myocarditis, as related to study drug (per the investigator, as symptoms started the same day the booster dose was administered) and not related to study procedure. Follow-up received on 26 Oct 2021 and 02 Nov 2021 included updated event outcome, event term (previously chest pain), and concomitant medication details. Follow-up received on 24 Nov 2021 included updated event verbatim (previously cardiac chest pain). Follow-up received on 09 Dec 2021 included updated event outcome (sequelae removed) and treatment details. Follow-up received on 17 Dec 2021 included no new information. Follow-up received on 25 Jan 2021 and 26 Jan 2021 included updated event outcome and event end date and medical records with additional medical history, vital signs, laboratory data, COVID-19 testing, diagnostic testing, and treatment details. Follow up received on 17 Feb 2022, included updated event onset date. Follow-up received on 22 Feb 2022 included no new information. Follow-up received on 04 Aug 2022 included diagnostic test result. On 26 Oct 2021, the safety database was searched for events similar to Chest Pain using the following search criteria: PT: Chest pain cardiac, Myocarditis and Troponin increased. 1257 cases were retrieved from PM and CT settings, excluding the index case; out of 1257, one was a CT case. 1208 cases were retrieved with PT: Myocarditis and 48 cases were retrieved with PT: Troponin increased. The CT case (MOD-2021-273925) reported an event with PT: Troponin increased. As of 26 Oct 2021, under ID PRIVATE for mRNA-1273, 2 similar events were retrieved, including the current index case. One case reporting event Troponin increased was previously submitted as IND Safety Reports. There were 0 of subtotal cases unrelated cases were non-IND Safety Reports (expected and related or unexpected and unrelated or expected and unrelated to the IMP) reporting the following events: Chest pain cardiac (0), Myocarditis (0), Troponin increased (0). The case previously reported as IND concerns a 70-year-old female subject with relevant medical history of dyslipidemia, hypertension, type II diabetes, cardiac stress test positive about 20 years ago, overweight, and sinus bradycardia who experienced dizziness and elevated troponin. The events occurred 29 days after receiving single booster shot dose of mRNA-1273. At the time of the events ECG revealed known sinus bradycardia and echocardiogram revealed borderline concentric left ventricular hypertrophy. Both events resolved within two days. The event elevated troponin was assessed as related to mRNA-1273 in agreement with the Investigator. The event dizziness was assessed as unrelated to mRNA-1273 in agreement with the Investigator. The index case concerns a 42-year-old, male subject with a medical history relevant for asthma and Lyme disease, and NO history of CAD. Other medical history included dislocated left knee, environmental allergies, torn cartilage right shoulder, lactose intolerance, vasectomy, left eye amblyopia, eczema, and nephrolithiasis. The subject experienced chest pain on the day following the booster dose; the subject had received the first dose of mRNA-1273 1 year 1 month prior to the event and the second dose, 1 year prior to the event. The event chest pain developed in the context low-grade fever and myalgia. The chest pain was sharp, constant, non-exertional, and worsened lying down on the left side. The subject went to the ER and his troponin was noted to be elevated, echocardiogram and coronary catheterization were unremarkable. The subject was treated with carvedilol, and his troponin levels decreased. A final diagnosis was not provided but per the subject's recollection it was unknown versus myocarditis or pericarditis; medical records are pending. The outcome of the event chest pain was unknown. The event was considered related to the study vaccine in agreement with the Investigator based on close temporal association. In the index case the chest pain happened one day following the booster injection, which favors causal association. There was no history of CAD and no SOB, and the subject had accompanying symptoms of fever and myalgia. No final diagnosis was provided but differential diagnoses included vs myocarditis/pericarditis. In all 3 conditions, troponin could be elevated, accompanying symptoms of fever and myalgia as well as subject's age and lack of history of CAD with unremarkable coronary catheterization, are more in favor of possible myocarditis/pericarditis. Final diagnosis is to be confirmed once medical records are received. Based on review of available data, and temporal association, the Sponsor cannot rule out a possible cause and effect relationship between administration of mRNA-1273 and the occurrence of Chest pain. After review of the clinical details and investigator comments pertaining to this adverse event, and based upon experience to date, the Sponsor does not believe that changes to the conduct of this clinical trial are warranted. The Company will continue to monitor these and other serious adverse events reported and will communicate any relevant changes to the protocol, Informed Consent Form, Investigator's Brochure, and/or Core Safety Information. Company Comment: This case concerns a 42 -year-old male subject with a medical history of dislocated left knee, environmental allergies, torn cartilage right shoulder, lactose intolerant, vasectomy, left eye amblyopia, allergy to cat and dog dander, allergy to walnuts, asthma, eczema - bilateral upper arms, nephrolithiasis right side, Lyme disease, left knee arthroscopic surgery, right shoulder arthroscopic surgery, spastic gait, and mild obstructive sleep apnea, who experienced the expected event of special interest of myocarditis. The event occurred 1 year 27 days after the first dose of mRNA-1273, and the following day of the booster dose. The event was reported as resolved. The event was considered related to the study vaccine in agreement with the Investigator based on close temporal association and known adverse drug reactions for the vaccine. Further information will be requested. Reporter's Comments: Company Comment: This case concerns a 42 -year-old male subject with a medical history of dislocated left knee, environmental allergies, torn cartilage right shoulder, lactose intolerant, vasectomy, left eye amblyopia, allergy to cat and dog dander, allergy to walnuts, asthma, eczema - bilateral upper arms, nephrolithiasis right side, Lyme disease, left knee arthroscopic surgery, right shoulder arthroscopic surgery, spastic gait, and mild obstructive sleep apnea,  who experienced the expected event of special interest of myocarditis. The event occurred 1 year 27 days after the first dose of mRNA-1273, and the following day of the booster dose. The event was reported as resolved. The event was considered related to the study vaccine in agreement with the Investigator based on close temporal association and known adverse drug reactions for the vaccine. Further information will be requested.