Sex: F
Vaccine: COVID19
Symptoms: Electrocardiogram, Heart rate, Myocardial necrosis marker, Physical examination, SARS-CoV-2 test
Clinical narrative: ELEVATED TROPONIN; DIZZINESS; This 70-year-old, White, female subject (US0070109) was participating in "A Phase 2/3 Study to Evaluate the Immunogenicity and Safety of mRNA Vaccine Boosters for SARS-CoV-2 Variants (mRNA-1273-P205)" and experienced dizziness and elevated troponin.   The subject's medical history, as provided by the investigator, included complete hysterectomy, bilateral oophorectomy, suspected ovarian cancer, benign abdominal mass, excision benign abdominal mass, sinus bradycardia, chronic diarrhea, dyslipidemia, hypertension, type II diabetes, sensory diabetic neuropathy of bilateral feet, sulfa drugs allergy, erythromycin allergy, mild venous insufficiency, postmenopausal, smoker, minocycline allergy, and tetracycline allergy. Concomitant medications reported included potassium chloride, hydralazine, rosuvastatin, lisinopril, pregabalin, tramadol, metformin hydrochloride/sitagliptin phosphate monohydrate, acetylsalicylic acid/caffeine/paracetamol, calcium chloride/potassium chloride/sodium lactate, and magnesium.  The subject previously experienced the serious adverse event of symptomatic bradycardia (MOD-2021-258186) while participating in this study.   On 02 Jul 2021, approximately 29 days prior to the onset of the events, the subject received the single booster shot dose of mRNA-1273.211 intramuscularly, 100 micrograms (one-time dose) in the left arm in Part A of the study for prophylaxis of COVID-19 infection.  On 30 Jul 2021, the subject experienced dizziness and elevated troponin. Subject presented to the emergency department with dizziness, diaphoresis, and nausea that morning. She denied chest pain. She reported feeling off balance. Two weeks ago, she woke up with similar symptoms but more severe. At that time, she went to the hospital and was found to be bradycardic (heart rate 32-34). She was referred to outpatient cardiology but has not followed up. The subject reported she did not drink a lot of the water the day before and that dehydration usually causes these types of symptoms. Vitals revealed pulse was 46-58 beats per minute (bpm). She was admitted because of sinus bradycardia. She was given intravenous fluids and heart rate went back to normal. Subject also endorsed a positive stress test about 20 years ago but never followed up with further evaluation. Physical exam of cardiovascular revealed regular rate. Regular rhythm. No murmurs, rubs, or gallops. Distal pulses were 2+ and symmetric. Labs revealed cardiac enzymes were elevated upon initial admission; troponin was 0.01 ng/mL (<0.01 ng/mL). The subject had a negative SARS-CoV-2 real-time reverse transcription polymerase chain reaction nasopharyngeal swab. Chest x-ray revealed normal heart size. No infiltrates were seen. Normal appearance to the pulmonary vasculature. No pleural effusion was apparent. No acute bony abnormality seen. Electrocardiogram (ECG) showed sinus bradycardia and low voltage QRS. No significant change when compared to ECG of 23 Jun 2006. Treatment included intravenous calcium chloride/ potassium chloride/ sodium lactate for dizziness and oral acetylsalicylic acid and subcutaneous enoxaparin for elevated cardiac enzymes.  On 31 Jul 2021, the subject's troponin was <0.01 ng/mL, and she remained hospitalized for further evaluation. Computerized tomogram of head and brain was normal. ECG showed sinus bradycardia and low voltage QRS. No significant change when compared to ECG from previous day. Transthoracic echocardiogram revealed left ventricular estimated ejection fraction 70%. Left ventricular size was normal. Borderline concentric left ventricular hypertrophy. No regional wall motion abnormalities. Hyperdynamic left ventricular systolic function. Benign diastolic inflow patter. No significant valve pathology. Doppler suggested normal pulmonary artery pressures.   On 01 Aug 2021, repeat troponin was within normal limits at <0.01 ng/mL. Vitals include heart rate of 52 bpm. Physical exam of cardiovascular revealed S1 and S2 normal, bradycardic no murmurs, rubs, or gallops. The subject was hemodynamically stable and cardiology cleared the subject. She was discharged from the hospital and advised to follow-up with cardiology soon after discharge for cardiac monitor placement.   On 02 Aug 2021, repeat troponin was within normal limits. Per the investigator, there was no underlying cause known to date. Dizziness can be in the setting of bradycardia and dehydration. Subject had risk factors, hypertension, and diabetes.   The subject received the single booster shot dose of study drug prior to the events; therefore, action taken with the drug in response to the events was not applicable.  The event, dizziness, was reported as resolved on 30 Jul 2021. The event, elevated troponin, was reported as resolved on 31 Jul 2021.   The investigator assessed the events, dizziness and elevated troponin, as not related to the study drug.  Follow-up received on 11 Aug 2021 included updated event term to dizziness (previously reported symptomatic bradycardia), medical history, treatment, concomitant medication details, additional AESI of elevated cardiac enzyme, and confirmation of discharge date.  Follow-up received on 14 Sep 2021 included updated event term (previously elevated cardiac enzyme), updated severity for event elevated troponin (previously mild), concomitant medications, COVID-19 test results, troponin results, medical history, and information that elevated troponin is not an AESI.  Follow-up received on 21 Sep 2021 and 22 Sep 2021 included updated event term to elevated cardiac enzymes (previous elevated troponin) and discharge summary with additional medical history, diagnostic tests, laboratory results, symptoms, and other clinical details of hospitalization.   Follow-up received on 04 Oct 2021 included updated event term (previously elevated cardiac enzymes) and confirmation of study drug arm.  Follow-up received on 15 Oct 2021 included no new information.  Follow-up received on 29 Oct 2021 included an update to the causality of the study drug for event of elevated troponin (previously reported as related) and downgrade to serious adverse event.  Follow-up received on 08 Nov 2021 included confirmation of study drug.  On 28 Sep 2021, the safety database was searched for events similar to Myocardial necrosis marker increased using the following search criteria: PT: Myocardial necrosis marker increased  As of 28 Sep 2021, under IND 019745 for mRNA-1273.211, two similar events were retrieved, including the current index case.  None of these cases reporting the following event were previously submitted as IND Safety Reports: Myocardial necrosis marker increased.  One case was a non-IND Safety Report (expected and related or unexpected and unrelated or expected and unrelated to the IMP) reporting the following event: Myocardial necrosis marker increased (1) MCN# MOD-2021-199200.  Case MOD-2021-199200: Unexpected events of elevated cardiac enzymes and chronic obstructive pulmonary disease (COPD) exacerbation was experienced by a 68 year old male subject with medical history of diabetes mellitus type 2, supraventricular tachycardia, chronic obstruction pulmonary disease, hypertension, and hyperlipidemia. The events occurred 9 months 10 days after the first dose of mRNA-1273.211 vaccine and 8 months 13 days after the last dose. The events were considered unrelated to the study medication in agreement with the Investigator's assessment, noting the multiple comorbidities may remain as risk factors.  Based on review of available data, the Sponsor does not believe a cause and effect relationship has been established between administration of mRNA-1273 study vaccine and the occurrence of dizziness.  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 in association with the IMP and will communicate any relevant changes to the protocol, Informed Consent Form, Investigator's Brochure, and/or Core Safety Information.; Reporter's Comments: This case concerns a 70-year-old, White, female subject with a medical history of dyslipidemia, hypertension, type II diabetes, sensory diabetic neuropathy, complete hysterectomy, bilateral oophorectomy, suspected ovarian cancer, benign abdominal mass, excision benign abdominal mass, sinus bradycardia and chronic diarrhea who experienced dizziness and elevated troponin. The events happened 29 days after receiving single booster shot dose of mRNA-1273.211, and both events resolved within two days. The event elevated troponin was initially assessed as related to mRNA-1273.211 by the sponsor and the investigator and finally it was reassessed as not related to IP in agreement with the Investigator. The event dizziness was assessed as unrelated to mRNA-1273.211 in agreement with the Investigator. The event dizziness might be explained by the subject's medical history of sinus bradycardia and type II diabetes.