Sex: M
Vaccine: COVID19
Symptoms: Echocardiogram, Electrocardiogram, Face and mouth X-ray, Heart rate, Orthostatic hypotension
Clinical narrative: SYNCOPE; ORTHOSTATIC HYPOTENSION; This approximately 59-year-old Male subject.  The subject's medical history, as provided by the investigator, included mild asthma, male hair loss, pruritus ani, benign prostatic hyperplasia, hemorrhoidectomy, and squid allergy. It was also noted by the investigator that the subject had no prior episodes of syncope, nor orthostatic hypotension. Concomitant medications included minoxidil, finasteride, hydrocortisone cream 0.1%, amoxicillin sodium/ clavulanate potassium, ciprofloxacin hydrochloride/ dexamethasone, and tadalafil.  The subject was randomized to receive blinded intramuscular Placebo (dosed on 14 Aug 2020 and 16 Sep 2020) and was unblinded on 13 Jan 2021. The subject consented to receive mRNA-1273 for SARS-CoV-2 vaccination after being unblinded and received their first dose of mRNA-1273 on 13 Jan 2021 and second dose on 12 Feb 2021. The subject received a booster dose of mRNA-1273 on 02 Oct 2021.  On 02 Oct 2021, after the subject received his Covid-19 booster shot at about 14h16, he went home and went to bed with no issues.   On 03 Oct 2021, the subject experienced syncope and orthostatic hypotension and was hospitalized. The subject reported that he woke up to use the bathroom at about 05h00. He was standing up, in front of the toilet when he suddenly felt lightheaded, dizzy and felt himself passing out. He also felt himself falling and crashing into something. When he came to, a few minutes later, there was blood in his nose, forehead and mouth. Subject was able to get up and feed and walk his dogs before ordering a car service to take him to the emergency room for evaluation. Upon arrival, he denied any chest pain, shortness of breath, palpitation, numbness, focal weakness, recent nausea, vomiting, diarrhea, or abdominal discomfort. Vitals at 06:10 revealed pulse 92 beats per minute (BPM), respiratory rate 18 breaths per minute (BPM), and blood pressure 106/68 mmHg. Glasgow coma scale revealed eye response: 4/4; verbal response 5/5, motor response 6/6  total score 15. Physical exam revealed a 4.0 cm laceration to forehead, 1.5 cm laceration to right upper inner lip, 1.5 cm laceration to bridge of nose and 0.5 cm laceration to left side of nose. Subject was neurologically alert and oriented to person, place, time, and situation. No focal neurological deficit observed and normal sensory, motor, speech, and coordination observed. The investigator reported that there were no additional signs or symptoms noted at the physical examination. A facial x-ray was performed and confirmed nasal fracture/ displacement. Initially, blood pressure readings were 60's sitting/lying and 50's standing. Following treatment with intravenous (IV) sodium chloride hydration, blood pressure became normal with 110's systolic and 70's diastolic sitting/lying and 100's systolic standing. Despite the resolution of syncope and orthostatic hypotension, the subject was kept in the hospital for further monitoring and diagnostics. An electrocardiogram (ECG) revealed normal sinus rhythm. A chest x-ray revealed lungs clear, no pleural abnormalities, normal cardio-mediastinal silhouette. A computerized tomogram (CT) of head confirmed nasal bone fracture, with no intracranial abnormalities. A CT of maxillofacial revealed bilateral nasal bone fracture and nasal septum fracture. A CT of spine revealed no fracture or misalignment. Serial troponin laboratories levels, taken throughout the day, were normal at: 3pg/mL, 3 pg/mL, 3 pg/mL and 4 pg/mL (normal, reference range: <86 pg/mL). A COVID-19 nasopharyngeal swab test was negative. Treatment included sutures to the forehead, IV hydration (normal saline), IV ceftriaxone, oral cephalexin, intraperitoneal lidocaine, and intramuscular tetanus toxoid vaccine.   On 04 Oct 2021, subject was reevaluated and stated he felt better than when he came in except for some facial soreness. He was able to ambulate down the hallway and denied any dizziness or lightheadedness during ambulation. Vitals revealed heart rate 69 bpm, respiratory rate 18 bpm, blood pressure 99/65 mmHg (sitting) and 98/61 mmHg (standing). The investigator noted that lacerations to the forehead, right upper inner lip, bridge of nose and left side of nose were resolved. The subject also underwent a 2D echocardiogram, which was normal. The subject was discharged from the hospital on the same day.   On 08 Oct 2021 the subject received post outpatient corrective surgery for bilateral nasal nose fracture and nasal septum fracture. The investigator noted that both nasal nose fractures and nasal septum fracture were resolved on this day. Treatment medications included oral cephalexin for post procedure infection prophylaxis and oral oxycodone/paracetamol for post-procedure pain.  Action taken with study drug in response to the events was not applicable, as the subject had already received both scheduled doses and the scheduled booster dose.   The events, syncope and orthostatic hypotension, were reported as resolved on 03 Oct 2021.  The investigator assessed the events, syncope and orthostatic hypotension, as related to study drug and not related to study procedure.  Follow-up received on 19 Oct 2021 included updated event (syncope) outcome, as well as updates to the events details, diagnostic tests (including Covid-19 test), procedures performed, and treatment medications. Additional updates included action taken with study drug, and confirmation that subject had no prior history of the events.  Follow-up received on 22 Oct 2021 included medical records with additional medical history, vitals, diagnostic tests, and course of event details.   On 12-Oct-2021, the safety database was searched for events similar to Syncope and Orthostatic hypotension using the following search criteria: PT: Syncope and HLT: Vascular Hypotensive Disorders.  As of 12-Ot-2021 under IND 019745 for mRNA-1273 39 similar events were retrieved in 36 cases including the current index case (see table below). 23 cases were retrieved with PT Syncope; 10 cases were retrieved under HLT: Vascular Hypotensive Disorders (PT: Orthostatic hypotension (2) and Hypotension (8)) and 3 cases had 2 events: MOD-2020-000832 (PT: Hypotension (2 episodes); MOD-2021-008627 (PT: Hypotension and PT: Syncope) and MOD- 2021-343429 (Index case: PT: Syncope and PT: Orthostatic hypotension).  Zero cases reporting the following events were previously submitted: Syncope, Orthostatic hypotension and Hypotension  There were 35 cases (expected and related or unexpected and unrelated or expected and unrelated to the RA) reporting the following events: Syncope, Orthostatic hypotension and Hypotension.  Based on review of available data, the Sponsor cannot rule out a possible cause and effect relationship between administration of mRNA-1273 and the occurrence of Syncope and Orthostatic hypotension in this case as the events occurred the following day of a booster dose; cardiologic evaluations including ECG, Echocardiogram and troponin values were reported as normal and no alternative etiologies were provided. Additional information was requested.  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 study vaccine 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 59-year-old, White, Male subject with a medical history of mild asthma, benign prostatic hyperplasia, and hemorrhoidectomy who experienced events of syncope and orthostatic hypotension. The subject also experienced nasal fracture, and lacerations on the face because of the syncope. The subject had no prior episodes of syncope, nor orthostatic hypotension. The events occurred 8 months, 20 days after first dose of IP, 7 months, 20 days after second dose and the following day of a booster dose. ECG, Echocardiogram, CT of the head and troponin values were reported as normal. Action taken with study drug in response to the events was not applicable, as the subject had already received both scheduled doses and the scheduled booster dose. The events syncope and orthostatic hypotension were reported as resolved. The events were considered related to the study vaccine in agreement with the Investigator based on temporal association as the events occurred within 24 hours of the vaccine administration with no other clear etiology observed.