ERCP INDUCED ACUTE PANCREATITIS; SEPTIC SHOCK; ACUTE RESPIRATORY FAILURE; CHOLELITHIASIS; This 70-year-old, male subject was participating in A Phase 3, Randomized, Stratified, Observer-Blind, Placebo-Controlled Study and experienced ERCP induced acute pancreatitis, acute respiratory failure, septic shock, and cholelithiasis.  The subject's medical history, as provided by the investigator, included seasonal allergies, benign prostatic hyperplasia, acid reflux, smoker, elevated cholesterol, kidney stones, and allergic rhinitis. Concomitant medications included montelukast, tamsulosin, fluticasone, probiotic, ascorbic acid/calcium/ minerals nos/retinol/tocopheryl acetate/vitamin b/vitamins/zinc, famotidine, acetylsalicylic acid, and loratadine/pseudoephedrine sulfate.  Prior to event onset, the subject received intramuscular mRNA-1273 (Booster, Dose 3) for SARS-CoV-2 vaccination on 01 Nov 2021, approximately 29 days before onset of the events.  On 29 Nov 2021, the subject experienced cholelithiasis and was admitted to the hospital. He presented to the emergency room at 02:00 with increasing right upper quadrant pain. Upon further exam with labs and imaging, it was determined that the subject had cholecystitis and gallstones. Laboratories performed included total bilirubin of 1.5 mg/dl high (0.20 - 1.30 mg/dl), aspartate transaminase (AST) of 97 U/L high (17 - 59 U/L), alanine aminotransferase (ALT) of 59 U/L high (1 - 50 U/L), lipase of 216 U/L (23 - 300 U/L) and urinalysis was negative. The subject underwent a emergency laparoscopic cholecystectomy with intraoperative cholangiogram.  Gallstones were noted in the bile duct during the surgery. It was reported that surgeon was not comfortable going further to get what he thought was a stone lodged, so it was decided to transfer subject to another medical center to have an endoscopic retrograde cholangiopancreatography (ERCP). Treatment of gallstones included intravenous (IV) ketorolac, IV sodium chloride/sodium lactate/potassium chloride/calcium chloride, IV iohexol, IV hydromorphone hydrochloride, IV cefoxitin, IV indocyanine, IV midazolam, IV dexamethasone, IV rocuronium, IV propofol, IV sevoflurane, IV glucagon, IV sugammadex, IV propofol, IV bupivacaine/epinephrine, and IV ondansetron. For post-operative pain, treatment included oral oxycodone / paracetamol.   On 30 Nov 2021, the subject was transferred to another hospital and endoscopic retrograde cholangiopancreatography (ERCP) was performed and no lodged gallstones were identified. Pathology for gallbladder showed acute hemorrhagic cholecystitis with focal epithelial necrosis, reactive to epithelial atypia. No dysplasia or neoplasm identified. On the same day, the subject was discharged home from the hospital in stable condition.  On 01 Dec 2021, the subject experienced ERCP induced pancreatitis. Risk factors associated with the event included elevated body mass index, being a smoker, and elevated cholesterol. The subject presented to the emergency room with complaints of difficulty breathing. Upon examination the subject had an oxygen saturation of 87%, tachycardia, and tachypnea and experienced acute respiratory failure.  Treatment with 2L (liters) of oxygen via nasal cannula was initiated and eventually titrated up to 15L with worsening respiratory effort. A chest computed tomography (CT) angiogram revealed no pulmonary embolus, bilateral lower lobe atelectasis, aspirations, or pneumonia. There was a small left effusion. CT of the abdomen and pelvis showed diffuse inflammation in the left retroperitoneal space and along the left paracolic gutter suggestive of acute pancreatitis. Laboratory values of note included total bilirubin of 3.2 mg/dl (high), AST of 108 U/L, ALT of 101 U/L, lipase of 6901, lactate 4.2, lactate dehydrogenase of 956 U/L (normal 313-618 U/L), calcium 7.4 mg/dL (normal 8.4-10.2 mg/dL), creatinine 1.9 mg/dL (normal 0.8-1.5 mg/dL), glucose 136 mg/dL (normal 75-110 mg/dL), sodium 130 milliequivalents per liter (mEq/L) (normal 136-146 mEq/L), blood urea nitrogen (BUN) 28 mg/dL (normal 9-20 mg/dL), influenza test negative, blood cultures x2 showed no growth after five days, COVID-19 virus test was negative, troponin levels were 0.050 nanogram per milliliter (ng/mL) at 10:49 and 0.027 ng/mL at 20:43 (normal 0.0-0.12 ng/mL), and white blood cell count (WBC) 12.9 T/MM3 (normal 4.5-11.0 T/MM3). An ultrasound-guided right internal jugular triple lumen central venous catheter was placed. A chest X-Ray showed right internal jugular line tip projects over the mid superior vena cava and also revealed left lower lobe atelectasis or pneumonia with small effusion. The subject was admitted to the hospital to the intensive care unit (ICU) with ERCO induced acute pancreatitis, septic shock, and acute respiratory failure. Additional treatment included bilevel positive air way pressure (BIPAP) due to continued worsening respiratory effort. Subject was initially in normal sinus rhythm which converted to atrial fibrillation. Treatment for atrial fibrillation included IV amiodarone hydrochloride, oral apixaban, oral sotalol, IV heparin, and subcutaneous enoxaparin sodium. Treatment for ERCP induced acute pancreatitis included IV sodium chloride/sodium lactate/potassium chloride/calcium chloride, IV piperacillin, IV hydromorphone hydrochloride, IV vancomycin hydrochloride, oral pancrelipase, and oral colestipol.  Treatment for septic shock included IV sodium chloride, IV sodium chloride/sodium lactate/potassium chloride/calcium chloride, and oral amoxicillin/clavulanic acid.  For postoperative pain, treatment included IV morphine sulfate, IV ondansetron hydrochloride, IV prochlorperazine edisylate,  IV fentanyl, IV metoclopramide hydrochloride,  oral paracetamol, and oral hydrocodone/paracetamol.   For respiratory failure, treatment included respiratory albuterol.  Additional treatment included IV dexmedetomidine hydrochloride, IV lorazepam and intramuscular haloperidol lactate for delirium; oral metoprolol for hypotension; IV pantoprazole sodium for gastroesophageal reflux disorder; IV furosemide and IV bumetanide for fluid overload; IV calcium gluconate for hypocalemia; oral quetiapine and oral melatonin for insomnia, and oral potassium chloride. Subject was in the intensive care unit for 4 days.  On 03 Dec 2021, laboratory values of note were activated partial thromboplastin time (APTT) 43.7 seconds (normal 24-36 seconds), calcium 6.0 mg/dL, creatinine 1.0 mg/dL, glucose 167 mg/dL, potassium 3.0 mEq/L (normal 3.6-5.5 mEq/L), sodium 134 mEq/L, BUN 21 mg/dL, hematocrit (Hct) 39.5 % (normal 41-52%), red blood cell count of 4.31 M/MM3 (normal 4.5-5.9 M/MM3), and WBC 10.8 T/MM3. Vital signs were body temperature 98.5 degrees Fahrenheit (F), blood pressure 138/63, pulse 101, respiratory rate 38, and oxygen saturation 92%. An echocardiogram showed normal left ventricular function with ejection fraction of 75%, a trace of mitral regurgitation, and a trace of tricuspid regurgitation with estimated pulmonary artery systolic pressure of 31. Chest X-Ray showed stable chest. The subject continued 15L of supplemental oxygen. Physical and occupational therapy were initiated.   On 04 Dec 2021, laboratory values of note were APTT 39.6 seconds, ALT 69 U/L, AST 103 U/L, albumin 2.7 gram per deciliter (g/dL) (normal 3.5-5.0 g/dL), calcium 5.8 mg/dL, glucose 137 mg/dL, potassium 3.1 mEq/L, sodium 136 mEq/L, BUN 18 mg/dL, Hct 36.2%, hemoglobin (Hgb) 12.1 g/dL (normal 13.5-17.5 g/dL), total protein 5.7 g/dL (normal 6.3-8.2 g/dL), RBC 3.88 M/MM3, WBC 10.7 T/MM3.  A chest X-Ray showed a worsening of the effusions.   On 05 Dec 2021, laboratory values of note included lipase of 677, LDH of 1042, and APTT 53.2 seconds. The subject was continued on 5-6L supplemental oxygen and reportedly began to make slow gains and was feeling better.  On 06 Dec 2021, subject was transferred out of the ICU to a regular room. Laboratory values of note were APTT 54.7 secondsALT 54 U/L, AST 81 U/L, albumin 2.7 g/dL, calcium 6.8 mg/dL, creatinine 0.7 mg/dL, glucose 111 mg/dL, potassium 3.1 mEq/L, sodium 139 mEq/L, BUN 13 mg/dL, Hct 37.6%, Hgb 12.6 g/dL, total protein 6.0 g/dL, RBC 4.08 M/MM3, and WBC 13.9 T/MM3. Vital signs were body temperature 97.9 F, blood pressure 147/80, pulse 88, respiratory rate 27, and oxygen saturation 92%.  On 07 Dec 2021, laboratory values of note were APTT 42.5 seconds, albumin 2.7 g/dL, calcium 7.3 mg/dL, creatinine 0.7 mg/dL, glucose 113 mg/dL, potassium 3.6 mEq/L, sodium 134 mEq/L, Hct 39.0%, Hgb 13.0 g/dL, RBC 4.2 M/MM3, and WBC 16.0 T/MM3. A chest X-Ray revealed increasing moderate left effusion, a small right effusion, no pneumothorax, and compressive atelectasis of the left lower lobe.  On 08 Dec 2021, laboratory values of note ALT 45 U/L, AST 65 U/L, albumin 2.8 g/dL, calcium 7.7 mg/dL, creatinine 0.8 mg/dL, glucose 148 mg/dL, sodium 134 mEq/L, Hct 39.4%, Hgb 13.0 g/dL, total protein 6.7 g/dL, RBC 4.2 M/MM3, and WBC 19.0 T/MM3. A chest ultrasound was performed that showed a small pleural effusion with a pocket depth of 1.6 cm. Respiratory failure resolved and the subject was now on room air.  On 09 Dec 2021, the subject was discharged home from the hospital in stable condition. Chest X-Ray showed a slight decrease in left effusion. Laboratory values of note included total bilirubin of 1.9 mg/dl, AST of 67 U/L, ALT of 39 U/L, albumin 3.0 g/dL, calcium 7.9 mg/dL, glucose 90 mg/dL, potassium 3.5 mEq/L, sodium 134 mEq/L, Hct 39%, Hgb 12.9 g/dL, RBC 4.18 M/MM3, and WBC17.9 T/MM3. Vital signs were body temperature 98.2 F, blood pressure 132/63 pulse 71, respiratory rate 18, and oxygen saturation 93%. Discharge diagnosis included septic shock, acute pancreatitis status post laparoscopic cholecystectomy and ERCP, acute respiratory failure bilateral lower lobe atelectasis, aspiration or pneumonia with likely component of 3rd spacing fluid, atrial fibrillation, acute kidney injury, metabolic acidosis, sinus tachycardia, transaminitis and hyperbilirubinemia, hyponatremia, hypocalcemia, asymptomatic bacteruria, hypokalemia, and hypophosphatemia. Discharge medications included oral sotalol, oral bumetanide, oral apixaban, oral melatonin, and oral potassium chloride.  The subject received all scheduled doses of study drug prior to the events; therefore, action taken with study drug in response to the events was not applicable.  The event, cholelithiasis, was reported as resolved on 30 Nov 2021.   The event, ERCP induced acute pancreatitis, was reported as resolved on 07 Dec 2021.  The events, septic shock and acute respiratory failure, were reported as resolved on 08 Dec 2021.  The investigator assessed the event, cholelithiasis, as related to study drug and related to study procedure.  The investigator assessed the events, ERCP induced acute pancreatitis, septic shock, and acute respiratory failure, as not related to study drug and not related to study procedure.  Follow-up received on 21 Dec 2021 and 29 Dec 2021 included booster dose location, and laboratory test. Updated severity, outcome, hospital admission date, and investigator's causality with study drug updated for the event pancreatitis.  Follow-up received on 05 Jan 2022, included new event septic shock and acute respiratory failure, updated event term (previously pancreatitis), updated clinical course, laboratory results, treatment, updated causality assessment to study procedure for pancreatitis, discharge date for the event pancreatitis, and updated days in the ICU for the event pancreatitis.  Follow-up received on 11 Jan 2021 and 13 Jan 2021 included updated event term (previously gallstones), treatment medications, and discharge summary with laboratory testing, diagnostic testing, medical history, and narrative details.   Follow-up received on 19 Jan 2022 included additional medical records with vital signs, laboratory and diagnostic testing with results, and additional treatment specifics.   Follow-up received on 11 Feb 2022 included updated start and stop dates for the event, ERCP induced acute pancreatitis. Additional updates included an updated severity grade (previously reported as Grade 4) for the event, ERCP induced acute pancreatitis.  Company Comment: This case concerns a 70-year-old, male subject with a history of seasonal allergies, benign prostatic hyperplasia, acid reflux, smoker, elevated cholesterol, kidney stones, and allergic rhinitis, who experienced the unexpected events of ERCP induced acute pancreatitis, acute respiratory failure, septic shock and cholelithiasis. The event cholelithiasis occurred approximately 1 year 3 months 23 days after the first dose of mRNA-1273 and 28 days after the third and most recent dose, the event pancreatitis occurred 1 year 3 months 25 days after the first dose of mRNA-1273 and 1 month after the third and most recent dose and the events acute respiratory failure and septic shock occurred 1 year 3 months 26 days after the first dose of mRNA-1273 and 1 month 1 day after the third and most recent dose. The event pancreatitis developed the following day after the endoscopic retrograde cholangiopancreatography (ERCP) to remove gallstones identified during cholecystectomy. The events were reported as resolved. Action taken with the study vaccine, dechallenge and rechallenge, were not applicable as the subject had already received all scheduled doses. The event cholelithiasis was considered related to the study vaccine by the investigator. The event cholelithiasis was considered not related to the study vaccine by the sponsor due to lack of biological plausibility. The events ERCP induced acute pancreatitis, acute respiratory failure and septic shock were considered not related to the study vaccine in agreement with the investigator; the events ERCP induced acute pancreatitis, acute respiratory failure and septic shock might be explained as complications post ERCP based on close temporal association and nature of the events. The event cholelithiasis might be explained by the subject´s medical history of elevated cholesterol. The benefit-risk relationship of drug mRNA-1273 is not affected by this report.; Reporter's Comments: Company Comment: This case concerns a 70-year-old, male subject with a history of seasonal allergies, benign prostatic hyperplasia, acid reflux, smoker, elevated cholesterol, kidney stones, and allergic rhinitis, who experienced the unexpected events of ERCP induced acute pancreatitis, acute respiratory failure, septic shock and cholelithiasis. The event cholelithiasis occurred approximately 1 year 3 months 23 days after the first dose of mRNA-1273 and 28 days after the third and most recent dose, the event pancreatitis occurred 1 year 3 months 25 days after the first dose of mRNA-1273 and 1 month after the third and most recent dose and the events acute respiratory failure and septic shock occurred 1 year 3 months 26 days after the first dose of mRNA-1273 and 1 month 1 day after the third and most recent dose. The event pancreatitis developed the following day after the endoscopic retrograde cholangiopancreatography (ERCP) to remove gallstones identified during cholecystectomy. The events were reported as resolved. Action taken with the study vaccine, dechallenge and rechallenge, were not applicable as the subject had already received all scheduled doses. The event cholelithiasis was considered related to the study vaccine by the investigator. The event cholelithiasis was considered not related to the study vaccine by the sponsor due to lack of biological plausibility. The events ERCP induced acute pancreatitis, acute respiratory failure and septic shock were considered not related to the study vaccine in agreement with the investigator; the events ERCP induced acute pancreatitis, acute respiratory failure and septic shock might be explained as complications post ERCP based on close temporal association and nature of the events. The event cholelithiasis might be explained by the subject´s medical history of elevated cholesterol. The benefit-risk relationship of drug mRNA-1273 is not affected by this report.