Sex: M
Vaccine: COVID19
Symptoms: Echocardiogram, High density lipoprotein, Low density lipoprotein, Pericardial effusion, SARS-CoV-2 antibody test
Clinical narrative: PERICARDIAL EFFUSION; This 23-year-old, male subject was participating in a Study.  The subject's medical history, as provided by medical records, included allergy to minocycline (muscle aches). The subject had no prior history of heart disease. No concomitant medications were reported.  The subject was randomized to receive blinded intramuscular Placebo (dosed on 14 Aug 2020 and 11 Sep 2020) and was unblinded on 12 Jan 2021. The subject consented to receive mRNA-1273 for SARS-CoV-2 vaccination after being unblinded and received his first dose of mRNA-1273 on 12 Jan 2021. The subject's last dose of mRNA-1273 prior to event onset was on 11 Feb 2021.  In Nov 2020, the subject tested positive for COVID-19 with episodes of fatigue and loss of smell. His parents also had COVID-19 at the same time.   On 01 Mar 2021, the subject experienced pericardial effusion. The subject had been experiencing bradycardia relative to baseline but did not seek medical attention until the symptoms had persisted for over a month. Bradycardia was not considered a serious adverse event as it was asymptomatic and not interfering with subject's daily activities.  On 17 Mar 2021, transthoracic echocardiogram showed small pericardial effusion mostly localized anteriorly without evidence of tamponade physiology. Posterior pericardium appeared somewhat bright in multiple views.  On 26 Mar 2021, the subject sought treatment from a cardiologist and was diagnosed with bradycardia and pericardial effusion. His heart rate (HR) was 36 beats per minute (bpm) and physical exam was normal. The subject had been an athlete all his life with base HR in 50s to 60s bpm since 2015. Post COVID-19, he continued to be very active and exercise maintaining good fitness and was noted to have HR in 30s bpm after donating blood. The subject had no symptoms of shortness of breath, palpitation, chest pain, episodes of syncope, near syncope, lower extremity edema, paroxysmal nocturnal dyspnea (PND), orthopnea, or positional chest pain. Laboratory results included hematocrit 40.5 (low), blood urea nitrogen 28 (high), cholesterol 230 (high), high-density lipoprotein 107 (high), and low-density lipoprotein 104 (high). An electrocardiogram showed sinus bradycardia with right axis deviation. The cardiologist recommended evaluation for Lyme's antibody, thyroid disorder, antinuclear antibody for any autoimmune condition, Holter monitor to assess for HR variability and a limited echocardiogram to evaluate for resolution of pericardial effusion. The subject was started on oral colchicine twice daily for ten days and was encouraged to increase hydration liberal salt and use compression garments.  On 12 Apr 2021, a limited transthoracic echocardiogram showed a small pericardial effusion was present without hemodynamic impact. Grossly normal left ventricular chamber size wall thickness and systolic function, ejection fraction 69%.  On 07 May 2021, the subject presented for a follow-up cardiology visit. The subject stated he was doing better since adding electrolytes. Exercise tolerance was unchanged, and he participated in aerobic conditioning most days. He denied complaints of chest pain, pressure, heaviness, or shortness of breath at rest or with exertion. There was no orthopnea, PND, lower extremity edema, lightheadedness, dizziness, syncope, presyncope, or palpitations noted. His HR was 65 bpm and physical exam was normal. Holter monitor demonstrated adequate HR response to exercise with a maximum HR of 171 bpm, minimum HR 31 bpm at 2 am during presumed sleep, average HR of 54 bpm, and predominant underlying rhythm was sinus rhythm. The subject and parent requested electrophysiology consult for reassurance of his underlying asymptomatic bradycardia. It was recommended the subject to continue with increase hydration added electrolytes and exercise as previously.   As of 28 Oct 2021, the subject had not had updated scans since the initial contact with the cardiologist. He was still being followed by his cardiologist and the next appointment was scheduled for December.  Action taken with study drug in response to the event was not applicable, as the subject had already received both scheduled doses.  The event, pericardial effusion, was reported as resolving.  The investigator assessed the event, pericardial effusion, as related to study drug and not related to study procedure. The event was considered immune-mediated event.  Follow-up received on 10 Jun 2021 included updated action taken, confirmation of no concomitant medications, and confirmation of no history of substance abuse.   Follow-up received on 16 Jun 2021 included cardiology visit records which included medical history, event details, laboratory and diagnostic results and treatment.  Follow-up received on 28 Oct 2021 included updated status of event.   Analysis of Similar Events: On 14 May 2021, the safety database was searched for events similar to Pericardial Effusion using the following search criteria: PT: Pericardial Effusion.   As of 14 May 2021, under IND 019745 for mRNA-1273, 2 similar events were retrieved, including the current index case MOD-2021-016798.  One case of pericardial effusion was previously submitted as IND Safety Reports: MOD-2020-000916. Pericardial effusion was reported in a 59-year-old, White, female subject with a medical history of mild asthma, who also experienced the unlisted events of pericarditis, pleural effusion, and episodic atrial flutter. The events of pericardial effusion, pericarditis, and pleural effusion were diagnosed two months and one week after the second dose of mRNA-1273 SARS-CoV-2 Vaccine, and the event of episodic atrial flutter was diagnosed 2 months 17 days after the second dose of mRNA-1273. The events of pericardial effusion, pericarditis, and pleural effusion were considered related to mRNA-1273 SARS-CoV-2 Vaccine in agreement with the Investigator. Acute shortness of breath, along with chest discomfort, five days following the second dose of study drug might have been the earliest manifestations of the reported events; however, no effusion was noted on CT at that time. Thus, the actual date of onset of the events remains unclear, as it is unknown whether the episode of shortness of breath with chest discomfort, five days after the second dose of mRNA-1273 SARS-CoV-2 Vaccine is representing the first signs of onset of the events versus a later date. Concomitant Flublok RIV4 vaccination and sinus congestion indicating viral infection, which both occurred a month before diagnosis of the events, and history of dilatation of the ascending aorta remain confounders. The event of episodic atrial flutter was considered unrelated to mRNA-1273 SARS-CoV-2 Vaccine in agreement with the Investigator.  Based on review of available data, the Sponsor cannot rule out a possible cause and effect relationship between administration of mRNA-1273 SARS-CoV-2 Vaccine and the occurrence of and the occurrence of Pericardial effusion.  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: Company Comment: This case concerns a 23-year-old, male subject with prior medical history of COVID-19 infection two months before receiving the first dose of the mRNA-1273 vaccine. Patient experience an unexpected event of pericardial effusion 1 month 16 days after the first dose of mRNA-1273 study vaccine administration and 18 days after the second dose administration. Action taken with study drug in response to the event was not applicable, as the subject had already received both scheduled doses. The event, pericardial effusion, was reported as resolving. Based on patient's risk factors (including patient's medical history of  COVID-19 infection) this report is confounded. However, given the temporal association between the use of the product and the start date of the events, a causal relationship cannot be excluded. The event was considered related to the mRNA-1273 study vaccine in agreement with the Investigator.