Sex: M
Vaccine: COVID19
Symptoms: Body temperature, Muscular weakness
Clinical narrative: MUSCLE WEAKNESS LOWER EXTREMITIES; This 74 -year-old male subject (experienced muscle weakness lower extremities.  The subject's medical history, as provided by the investigator, included right knee arthroplasty, hyperlipidemia, vasectomy, obesity, bilateral upper extremity dermatoses, peripheral neuropathy, gastroesophageal reflux disease, generalized osteoarthritis, cervical spine herniated disc, cervical fusion, osteoarthritis right shoulder, right shoulder arthroscopic debridement and right knee torn cartilage. Concomitant medications included simvastatin, gabapentin, paracetamol, omeprazole and hydrocortisone.  The subject was randomized to receive blinded intramuscular Placebo (dosed on 11 Aug 2020 and 09 Sep 2020) and was unblinded on 18 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 18 Jan 2021. The subject's last dose of mRNA-1273 prior to event onset was on 15 Feb 2021.  On 15 Feb 2021, in the evening, the subject experienced fever, generalized fatigue and sustained a minor fall because of extremity weakness.  On 16 Feb 2021 at 02:50, the subject experienced muscle weakness in lower extremities. He experienced fever of greater than 102 degrees Fahrenheit and urinary retention starting in the middle of the night. The subject went to the emergency room (ER) due to severe muscle weakness of the lower extremities as he was unable to stand. The investigator contacted the ER physician attending to the subject. The subject was afebrile in ER, urinary retention resolved but still had weakness in both lower extremities and difficulty walking. The subject denied experiencing chest pain, shortness of breath, loss of consciousness, cough or any other symptoms other than generalized weakness and fevers. The subject also denied experiencing any side effects with his first dose. He was admitted for observation only and overnight monitoring. Testing for the event and COVID-19 testing were not performed. Treatment included oral paracetamol for fever.  On 17 Feb 2021, the subject was discharged in stable condition with recommendation to follow-up as an outpatient. The subject was recommended to visit ER if symptoms worsened.    Action taken with study drug in response to the event was not applicable, as the subject had already received both scheduled doses.   The event, muscle weakness lower extremities, was resolved on 17 Feb 2021.    The investigator assessed the event, muscle weakness lower extremities, as related to study drug and related to study procedure. There were no underlying or pre-disposing risk factors associated with the event.  Follow-up received on 24 Feb 2021 included updated event outcome and stop date; added hospital discharge date and other event details.   Follow-up received on 16 Mar 2021 included updated causality and event details.   Follow-up received on 25 Mar 2021 included confirmation from the site that the hospitalization was short-lived for any tests to be conducted for the event. Information received did not contain new/significant information.  Analysis of Similar Events: On 05 Mar 2021, the safety database was searched for events similar to Muscle weakness lower extremities using the following search criteria: PT: Muscle weakness.  As of 05 Mar 2021 for mRNA-1273, 40 similar events using the term muscle weakness were retrieved, including the current index case. Of those, 15 are new cases. 1 was subcategorized as diffuse muscle weakness, 1 as arm and hand muscle weakness, 1 as weakness of right side of body, 1 as bilateral weakness in legs, and 1 as left lower extremity weakness.   15 of these cases reporting the following events were previously submitted: Muscular weakness (41) MCN# MOD-2020-001248, MOD-2021-002312, MOD-2021-010645, MOD-2021-011078, MOD-2021-011684, MOD-2021-012735, MOD-2021-021409, MOD-2021-024544, MOD-2021-028395, MOD-2021-011327, MOD-2021-011592, MOD-2021-011535, MOD-2021-012851, MOD-2021-014796, MOD-2021-016858, MOD-2021-029697, MOD-2021-011754, MOD-2021-012398, MOD-2021-016100, MOD-2021-029750, MOD-2021-029703, MOD-2020-001248, MOD-2021-012083, MOD-2021-011801, MOD-2021-023659, MOD-2021-023551, MOD-2021-012801, MOD-2021-012747, MOD-2021-014739, MOD-2021-016085, MOD-2021-030130, MOD-2021-003188, MOD-2021-010932, MOD-2021-028407, MOD-2021-011298, MOD-2021-012411, MOD-2021-023061, MOD-2021-029697, MOD-2021-030480.   There were two cases reported the following events: Muscular weakness (2) MCN# MOD-2020-001248 and MOD-2021-014642.  In the 15 new cases reported, ages ranged between 49 and 95 years-old with half of those patients being older than 70 years old. The event of weakness happened by itself only in 3 patients, and in the others, it was associated with either a viral syndrome or as a part of a neurologic deficit disorder such as stroke. The events were experienced mostly after the first dose and, in a less cases, after the second dose of the vaccine. The latency time ranged between hours and up to 10 days after vaccination. More than half of the patients had a reported medical history with comorbidities that could have contributed to the events and 3 patients had a history of prior COVID infection.   In the index case, the subject is a 74-year-old male who developed muscle weakness approximately 1 month after the first dose and 1 day after second dose of mRNA-1273. The subject also experienced fever and urinary retention. He had a history of peripheral neuropathy among other comorbidities.  Based on temporal association and available data, the Sponsor cannot rule out a possible cause and effect relationship between administration of RA and the occurrence of muscle weakness. However, the patient's underlying condition of peripheral neuropathy as well as accompanying symptoms of fever and urinary retention could suggest an alternative etiology.   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 RA 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 74-year-old male subject with medical history of hyperlipidemia, obesity, bilateral upper extremity dermatoses, peripheral neuropathy, herniated cervical disc, torn cartilage right knee, and generalize osteoarthritis, among others, who experienced an unexpected event of muscular weakness lower extremities. The subject was randomized to receive blinded intramuscular Placebo (dosed on 11 Aug 2020 and 09 Sep 2020). He was subsequently unblinded on 18 Jan 2021 and consented to receive mRNA-1273 for SARS-CoV-2 vaccination. He received the first dose of vaccine on 18 Jan 2021 and 2nd dose of mRNA-1273 on 15 Feb 2021. The event occurred 1 day after the second dose of mRNA-1273. The investigator considered the event was related to mRNA-1273 and related to study procedure. However, the sponsor assessed the event, muscle weakness lower extremities, as related to mRNA-1273 and not related to study procedure.