Sex: F
Vaccine: COVID19
Symptoms: Body temperature, Disease risk factor, Febrile convulsion, Heart rate, Oxygen saturation
Clinical narrative: FEBRILE SEIZURE; FEVER; This 17-month-old, female subject was participating in a study.  The subject's medical history, as provided by medical records, included Salmon patch nevus - left eyelid and glabellum; and umbilical hernia  small. Family history was notable for early onset senile dementia (maternal living grandfather). No concomitant medications were reported.   Prior to event onset, the subject received blinded mRNA-1273 or Placebo (Dose 1) on 18 Feb 2022, approximately 6 hours and 3 minutes before onset of the event, fever, and 2 days before onset of the event, febrile seizure.  On 18 Feb 2022 at 18:00, the subject experienced fever with a temperature of 103.1. Treatment for the event fever included oral paracetamol.   On 19 Feb 2022, the fever continued throughout the day and the subject experienced a febrile seizure. Around 23:00, the subject was heard crying (she usually sleeps through the night). The mother went into child's bedroom. The subject was lying down (usually stands when parents are in room) and had stooled in her diaper. Mother picked her up to change her diaper and noticed that the subject was floppy, also felt hot, with temperature of 104 Fahrenheit, she was not making any purposeful movement, and was alert but not tracking.  Parent called their pediatric infectious disease physician, who advised the parents to take their child to the emergency room (ER) for evaluation. Her parents immediately took her to the local ER. After arrival to the ER around midnight, the subject was irritable but oriented and asking for water. Vitals revealed heart rate 170 beats per minute, temperature 39.1 degrees Celsius, respiratory rate 32 breaths per minute, and oxygen saturation 97%. The subject had face/legs/activity/cry/consolablity (FLACC) score of 3. FLACC score noted the following: Face revealed occasional grimace or frown, withdrawn, disinterested; Legs revealed normal position or relaxed; Activity noted lying quietly, normal position, moved easily; Cry was described as moaned or whimpered, with occasional complaint; Consolability revealed reassured by occasional touching, hugging or being talked to. Review of systems noted skin with maculopapular non-specific rash on chest, abdomen and back; did not appear petechial. Otherwise, the remainder of systems review was noted was appropriate. Her differential diagnosis was noted as: confusion. Medical record noted that the subject presented with altered mental status. Of note on medical record, the subject's father, who was a local family practice physician, provided most of the history and he stated that they took the subject, on the day prior, for trial vaccine, double-blinded, so they did not know if she was given placebo or study drug.. It was also noted in the medical record that prior to the vaccine, the subject was well-appearing and had no ill symptoms and no recent infectious symptoms. The ED physician reported that, given the description presented by the subject's parent, the physician suspected that the subject had had a febrile seizure while in her bed. It was not a witnessed seizure, but she cried and when mother arrived to find her, she sounded to have been postictal. The ED physician noted that the fever would the account for afebrile seizure. The ED physician and the subject's father discussed about potential options. The ED physician offered labs and even looking for a further infectious source other than her vaccine, as it was unclear if she was given placebo or the vaccine. The parents requested that the ED physician discuss her care with infectious disease physician. Based on her risk factors in the past, the ED physician thought that it was reasonable to just observe her. The subject had been monitored for four hours without further reoccurrence, and no seizure activity was witnessed by the parents, or ER physicians. The subject's temperature was down, and she had been resting comfortably.  The subject had been drinking without vomiting. The ED physician discussed fever control at home, in the future.The plan was to have the infectious disease pediatricians (from university and study) to contact the parents that night and the next day.  On 20 Feb 2022 at 03:56 the subject was discharged to home. Her condition was noted as improved and stable. Educational materials were provided on febrile seizure; follow-up was scheduled. No laboratories were drawn. Treatment for fever included oral ibuprofen. No other treatments were needed.   On 23 Feb 2022, the subject visited the pediatric clinic. Per mother report, the subject seemed back to usual on this day. She had no fever since 20 Feb 2022 and no previous febrile seizures. The physician's notes, signed on this day, reported that the subject's risk of recurrent febrile seizure was around 3 %, although with no risk factors (negative family history of febrile seizures, age over 1-year, documented fever in ER). Her pain was noted as 0/10. The subject was to follow up with as needed concerns.   On 30 Mar 2022, it was reported that there was no clinical finding of viral infection or any close contact.  No action was taken with the study drug in response to the events.   The events, febrile seizure and fever, were reported as resolved on 20 Feb 2022.    The investigator assessed the events, febrile seizure and fever, as related to study drug and as not related to study procedure.  Follow-up received on 28 Feb 2022 included no new information.  Follow-up received on 08 Mar 2022 included no new information.  Follow-up received on 15 Mar 2022 included no new information.  Follow-up received on 30 Mar 2022 included event details.  Follow-up received on 31 May 2022 included no new information.  Follow-up received on 07 Jun 2022 included medical records which provided updated medical history, family history, event details, laboratories, and diagnostics.   Company Comment: This case concerns a 17-month-old female subject with medical history of Salmon patch nevus - left eyelid and glabellum and small umbilical hernia, and family history of early onset senile dementia (maternal living grandfather),  who experienced the unlisted solicited adverse event of special interest (AESI) of fever and AESI of febrile seizure. The event fever occurred 6 hours after the first dose of mRNA-1273 or Placebo (Dose 1), and the event febrile seizure occurred the following day after the vaccine administration. As per the report, the subject was limp, not making any purposeful movement, and alert but not tracking, in the context of fever, and at after arrival to the ER, around midnight, the subject was irritable but oriented and asking for water. Based on the clinical picture of the subject and the history of fever the emergency room physician was able to make the diagnosis of febrile seizure even though neither the parents nor the physician witnessed the actual seizure. The outcome of the events was reported as resolved and considered related to IP in agreement with the Investigator based on the nature of the events and close temporal association between the study vaccine administration and the events, providing that no clinical finding for viral infection or close contact was observed. The principal investigator safety unblinded the subject.     On 24 Feb 2022, the safety database was searched for events similar to Febrile convulsion and Pyrexia using the following search criteria: PT: Febrile convulsion and PT: Pyrexia  As of 24 Feb 2022, under IND for mRNA-1273, 7 similar events were retrieved in 6 cases, including the current index case (see table below). Four cases were retrieved with PT: Pyrexia and 3 cases were retrieved with PT: Febrile convulsion.  Zero cases reporting the following events were previously submitted as Safety Reports: Febrile convulsion and Pyrexia.  There were 5 cases that were non-Safety Reports (expected and related or unexpected and unrelated or expected and unrelated to the IMP) reporting the following events: Febrile convulsion (2) MCN# MOD-2021-261464 and MOD-2021-393204 and Pyrexia (3) MCN# MOD-2021-208296, MOD-2021-362859, and MOD-2021-406376.  In the index case, a 1-year-old female subject, with no reported medical history, experienced fever and a febrile seizure within 24 hours of the study vaccine administration; the subject was limp, not making any purposeful movement, and alert but not tracking, in the context of fever. At the local emergency room, she was found febrile, irritable but oriented. No neurological abnormality was reported, and it is unclear from available information if there was any witnessed seizure activity. The subject stayed in ER for four hours for observation, was treated with antipyretics, and the events resolved. Risk factors for febrile seizures include viral illnesses, certain vaccinations, and genetic predisposition. Based on review of available data, the Sponsor believes there is a reasonable possibility of a cause-and-effect relationship between administration of IMP and the occurrence of Pyrexia and Febrile convulsion.  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 17-month-old female subject with medical history of Salmon patch nevus - left eyelid and glabellum and small umbilical hernia, and family history of early onset senile dementia (maternal living grandfather),  who experienced the unlisted solicited adverse event of special interest (AESI) of fever and AESI of febrile seizure. The event fever occurred 6 hours after the first dose of mRNA-1273 or Placebo (Dose 1), and the event febrile seizure occurred the following day after the vaccine administration. As per the report, the subject was limp, not making any purposeful movement, and alert but not tracking, in the context of fever, and at after arrival to the ER, around midnight, the subject was irritable but oriented and asking for water. Based on the clinical picture of the subject and the history of fever the emergency room physician was able to make the diagnosis of febrile seizure even though neither the parents nor the physician witnessed the actual seizure. The outcome of the events was reported as resolved and considered related to IP in agreement with the Investigator based on the nature of the events and close temporal association between the study vaccine administration and the events, providing that no clinical finding for viral infection or close contact was observed. The principal investigator safety unblinded the subject.