Sex: M
Vaccine: FLUA4
Symptoms: Mean cell haemoglobin concentration decreased, Mean cell haemoglobin decreased, Mean cell volume decreased, Monocyte count increased, Neutrophil count increased
Clinical narrative: Acute pneumonia; Atrial fibrillation with RVR; Acute severe COPD exacerbation; Acute hypoxic respiratory failure; Sepsis; This clinical trial case, initially received on 19-Jan-2024, with additional information received on 24-Jan-2024 and 25-Jan-2024, was reported by a health professional and concerns an elderly male subject. Weight: 75.1 kg; Height: 167.6 cm  The subject was enrolled in the study  Past medical history included Irritable bowl syndrome, Pneumonia. At the time of the event the subject had Shell fish allergy, Ezcema, COPD, Benign prostatic hyperplasia (BPH), Asthma, Falls, Gastrooesophageal reflux disease (GERD).Concomitant medication: over 50 multivitamin (unspecified vitamins), used for unreported indication, tamsulosin for BPH, ProAir RespiClick (salbutamol sulfate), Spiriva (tiotropium bromide), ipratropium bromide, Trelegy ellipta (fluticasone furoate, umeclidinium bromide, vilanterol trifenatate) for COPD, and acetaminophen, Alka seltzer plus (chlorphenamine maleate, paracetamol, phenylephrine hydrochloride), and Mucinex dm (dextromethorphan hydrobromide, guaifenesin), all three used for four fractured ribs, fentanyl and sodium chloride for 4 fractured ribs, laceration by left eye-4 stitches, and lacarations on L-knee, oxycodone and acetaminophen for 4 fractured ribs, laceration by left eye-4 stitches, lacarations on L-knee, and chest wall contusion (L-sided chest wall pain), ibuprofen and Lidoderm (lidocaine) for chest wall contusion (L-sided chest wall pain), pantoprazole for gastroesophageal reflux disease (GERD), oxygen for four fractured ribs, chest wall contusion (L-sided chest wall pain), acute severe COPD exacerbation, and atorvastatin for hypercholesterolemia. The subject's historical vaccine included a flu shot (brand not specified) received on 16-Feb-2023 and Daptacel (diphtheria vaccine toxoid, pertussis vaccine acellular, tetanus vaccine toxoid) for prophylaxis received on 13-Dec-2023. Concomitant medication: Refer to the appropriate section.  Administration of company suspect drug: On 28-Nov-2023, at 11:05, the subject was vaccinated with the blinded study vaccine aQIVc HD vs QIVr vs aQIV (dose: 0.5 ml; route of administration: intramuscular, anatomical location: left deltoid) for prophylaxis of influenza. The study vaccine was administered as per the protocol.  No additional suspect drugs.  Adverse reactions/events and outcomes: On 07-Jan-2024, the subject experienced Acute pneumonia (Hospitalized, outcome: Recovered / Resolved, stop date: 11-Jan-2024), Acute severe COPD exacerbation (Hospitalized, outcome: Recovered / Resolved, stop date: 11-Jan-2024), Acute hypoxic respiratory failure (Hospitalized, outcome: Recovered / Resolved, stop date: 11-Jan-2024), Sepsis (Hospitalized, outcome: Recovered / Resolved, stop date: 11-Jan-2024), Atrial fibrillation with RVR (Hospitalized, outcome: Not recovered / Not resolved however, stop date provided as 13-Nov-2024).  On 07-Jan-2024, one month and 11 days after receiving blinded study vaccine aQIVc HD vs QIVr vs aQIV, the subject presented to the emergency department (ED) because of worsening dyspnea on exertion for the past three days. 'Yesterday', as reported, he started wheezing. He had productive cough with phlegm. No associated fever but had intermittent chills. The subject reported that back on 13-Dec-2023 he had a car versus pedestrian accident and was ran over and sustained left rib and back injuries. The subject was actively wheezing and desaturated to 80% on room air. He received several doses off nebulization. The subject developed atrial fibrillation (A-fib) with rapid ventricular response (RVR). Cardizem bolus (diltiazem) and oxygen were given. Then, telemetry showed heart rate of 109. The subject denied chest pain or palpitations. The labs were remarkable for leukocytosis, creatinine was 1.4. Chest x-ray at 08:41 revealed mild infiltrate in the right lung base, which was discussed with ED. Medical doctor (MD) recommended admission for pneumonia and A-fib RVR. The subject started with doxycycline and Rocephin (ceftriaxone sodium), intravenously, daily, for acute pneumonia. On the same day, the subject had acute severe COPD exacerbation, acute hypoxic respiratory failure and sepsis.  On the same date at 09:18, the subject's white blood cell (WBC) count was 16.3 (High (H)), red blood cell (RBC) count was 4.40 (Low (L)), haemoglobin (HGB) was 10.4 (L), haematocrit (HCT) was 33.1 (L), mean cell volume (MCV) was 75.2 (L), mean cell haemoglobin (MCH) was 23.6 (L), neutrophil percentage was 84.7 (H), lymphocyte percentage was 8.1 (L), neutrophil count was 13.8 (H), monocyte count was 1.1 (H), creatinine was 1.40 (H), estimated glomerular filtration rate (GFR) was 52 (L), random glucose was 117 (H), calcium was 8.4 (L), aspartate transferase (AST) was 8 (L), and POC B-natriuretic peptide was 106 (H). The normal ranges for laboratory tests performed were not reported.  On 08-Jan-2024 at 04:45, the subject's WBC count was 12.1 (H), RBC count was 3.93 (L), HGB was 9.2 (L), HCT was 29.8 (L), MCV was 75.8 (L), MCH was 23.4 (L), neutrophil percentage was 93.5 (H), lymphocyte percentage was 4.0 (L), neutrophil count was 11.3 (H), lymphocyte count was 0.5 (L), chloride was 109 (H), BUN was 20 (H), estimated GFR was 62 (L), random glucose was 188 (H), calcium was 8.4 (L), and procalcitonin was 0.09 (H). The normal ranges for laboratory tests performed were not reported.  On 09-Jan-2024 at 07:29, the subject's WBC count was 17.6 (H), RBC count was 3.80 (L), HGB was 8.9 (L), HVT was 28.5 (L), MCV was 75.0 (L), MCH was 23.4 (L), neutrophil percentage was 91.8 (H), lymphocyte percentage was 3.8 (L), neutrophil count was 16.2 (H), lymphocyte count was 0.7 (L), chloride was 111 (H), BUN was 20 (H), estimated GFR was 69 (L), random glucose was 154 (H), and calcium was 8.4 (L). The hospital did not provide reference ranges.   On 10-Jan-2024, the subject stopped with doxycycline and Rocephin (ceftriaxone sodium). On the same date at 06:03, the subject's white blood cell (WBC) count was 13.3, RBC count was 3.88 (L), haemoglobin (HGB) was 9.0, haematocrit (HCT) was 29.7, mean cell volume (MCV) was 76.5, mean cell haemoglobin (MCH) was 23.2, mean corpuscular haemoglobin (MCHC) was 30.3, neutrophil percentage was 79.9, neutrophil count was 10.6, monocyte count was 1.1, chloride was 110, blood urea nitrogen (BUN) was 23, and estimated glomerular filtration rate (GFR) was 69. The normal ranges for laboratory tests performed were not reported.   On an unspecified date in Jan-2024, during the hospitalization, the subject's skin had normal temperature, turgor and texture. Neurological examination revealed the subject was alert, oriented (reported as 'x3'), normal sensory, no focal defects, cranial nerves II-XII were grossly intact. Psychological examination revealed normal mood and affect.  On 11-Jan-2024, the subject was discharged from the hospital. The discharge diagnoses were acute severe COPD exacerbation, acute hypoxic respiratory failure, acute pneumonia, sepsis and new onset A-Fib with RVR. Preliminary micro results at discharge included aerobic and anaerobic blood culture (peripheral blood) that showed no growth in four days. The subject started with doxycycline and cefdinir intravenously, once, for acute pneumonia.  On the same date, the subject recovered from the events of 'COPD exacerbation', 'acute hypoxic respiratory failure', sepsis, and acute pneumonia.  On 12-Jan-2024, the subject started with aspirin at a dose of 325 mg, daily, orally, metoprolol tartrate at a dose of 50 mg, twice a day, orally, nitroglycerin at a dose of 0.4 mg, occasionally, sublingually, all three for atrial fibrillation with rapid ventricular response (RVR),  Symbicort (budesonide, formoterol fumarate) at a dose of 2 puffs, daily, via respiratory route, prednisone at a dose of 40 mg, orally, daily, both for acute severe COPD exacerbation, acute hypoxic respiratory failure, and acute pneumonia.  On 16-Jan-2024, the subject stopped with prednisone.  At the time of follow up reporting, on 08-Apr-2024, the subject had not recovered from the event of atrial fibrillation.  No additional suspect drugs.  Non-drug treatment/Other action taken:  aQIVc HD  vs QIVr vs aQIV action taken: Not Applicable Treatment medication: Aspirin 325 mg Every day/daily, Cardizem   Single, Cefdinir   Single, Doxycycline   Single, 1  Every day/daily, Metoprolol tartrate 50 mg Twice a day, Nitroglycerin .4 mg As needed, Prednisone 40 mg Every day/daily, Rocephin   Every day/daily, Symbicort   Twice a day  Reporter's assessment: The Investigator considered the events Acute hypoxic respiratory failure, Acute pneumonia, Acute severe COPD exacerbation, Atrial fibrillation with RVR, Sepsis as serious due to seriousness criterion of hospitalization, not related to the administration of the investigational drug. The alternative cause for the events of acute pneumonia,atrial fibrillation with RVR, acute severe COPD exacerbation, acute hypoxic respiratory failure and sepsis was reported as other. It was unknown if sepsis was attributable to pneumonia   The subject remained blinded in the study.  Follow-up (27-Jan-2024) with additional information, one received on 29-Jan-2024, two received on 30-Jan-2024 and one received on 04-Feb-2024 (being processed together) from Investigator: Ethnicity added on patient tab. 'Intramuscular' route of administration and 'left deltoid' anatomical location added for suspect vaccine. 'Severe' intensity added for the event of pneumonia. Start date for concomitant tamsulosin amended to '01-Jan-2020'. Hospital name added. 'COPD exacerbation', 'acute hypoxic respiratory failure' and sepsis added. Description as reported and description to be coded changed from 'V. FIB' to 'atrial fibrillation with RVR' and event recoded. Treatment medications Cardizem, aspirin, metoprolol tartrate, prednisone, Budesonide and Formoterol and nitroglycerin added. Lab data of oxygen saturation, heart rate, creatinine, chest x-ray, and leucocyte count added. Alternative cause for the events amended to 'other'. Narrative amended accordingly.   Follow-up (06-Feb-2024), with additional information received on 07-Feb-2024 (being process together) from Investigator: Start date for benign prostatic hyperplasia (BPH) updated from '01-Jan-2023' to '01-Jan-2022'. Dose updated for multivitamin. Historical vaccine of daptacel added. The event of 'Pneumonia' recoded to 'Acute pneumonia'. Outcome updated from 'Recovering / Resolving' to 'Recovered / Resolved' and stop date added as '11-Jan-2024' for the event of 'Acute pneumonia'. Concomitant medications of fentanyl, oxycodone and acetaminophen, sodium chloride ibuprofen, Lidoderm added. Treatment medications of doxycycline, Rocephin and Cefdinir were added. Start date of aspirin, metoprolol tartrate, nitroglycerin changed from 11-Jan-2024 to 12-Jan-2024. Atrial fibrillation with RVR added as indication for aspirin, metoprolol tartrate, nitroglycerin. Start and stop date for prednisone changed and indications added. Budesonide and Formoterol recoded to Symbicort and indications added. Alternative cause for the events was added. Narrative was amended accordingly.  Follow-up (23-Feb-2024) with additional information received on 28-Feb-2024 (being processed together) from Investigator: Pantoprazole, Spiriva, ipratropium bromide, oxygen, atorvastatin and Trelegy ellipta added as concomitant medications. Start date for Symbicort amended to 07-Jan-2024, and stop date added. Dose description updated for oxycodone and acetaminophen from '3/325' mg to '5/325' mg. Stop date and indication added for Cardizem. Narrative amended accordingly.  Follow-up (06-Mar-2024) from Investigator: Indication changed from '4 cracked ribs' to '4 fractured ribs' for acetaminophen, Alka Seltzer Plus (chlorphenamine maleate, paracetamol, phenylephrine hydrochloride), and Mucinex dm (dextromethorphan hydrobromide, guaifenesin). Indication for sodium chloride changed from 'Bruises and lacarations on left knee' to 'Lacerations on L-knee'. Laboratory data performed on an unspecified date in 2024 was added (WBC, RBC, HGB, HCT, MCV, MCH, lymphocyte count, neutrophil count chloride, BUN, GFR, and random glucose calcium. The narrative was updated accordingly.  Follow-up (20-Mar-2024) with additional information received on 22-Mar-2024 (being processed together) from Investigator: Indication for fentanyl and oxycodone and acetaminophen updated from 'Bruised and lacarations on left knee' to 'Lacarations on L-knee'. Dose updated from '200 mg' to '1 tablet', and formulation added for Mucinex dm. Gastrooesophageal reflux disease added as a current condition. Outcome for the event of 'Atrial fibrillation with rapid ventricular response' updated from 'Recovered / Resolved' to 'Not recovered / Not resolved', and stop date removed. Alternative cause for the event of acute pneumonia was changed. Narrative and case comment were amended accordingly.  Follow-up (08-Apr-2024) received from Investigator: It was unknown if sepsis was attributable to pneumonia and if there were any laboratory investigations (cultures etc).  Follow-up (17-Apr-2024) received from Investigator: Results for laboratory tests performed on 07-Jan-2024, 08-Jan-2024, 09-Jan-2024, and 10-Jan-2024, as well as preliminary micro results, were reported. The narrative was updated accordingly.  Follow-up (02-May-2024) received from Investigator: It was confirmed that additional information regarding reference ranges were not provided. The narrative was updated accordingly.  Follow up (08-Jul-2024) received from Investigator: In the lab data provided by email on 16-Apr-2024 some lab values are highlited in yellow to access clinical progress. No changes in the narrative.   Follow up (16-Jul-2024) received from the Investigator: It was stated that there was no additional lab data available regarding the event, except for data from January, which was provided via email. No changes in the narrative.  Follow-up (19-Nov-2024) received from investigator: stop date provided for the event atrial fibrillation with rapid ventricular response). Narrative updated accordantly.   Linked Case ID(s): US-BEH-202401133, US-BEH-2024176616 (same patient) 04-OCT-2024 (System Update): Linked Case ID(s):202401133 (Patient Link); 2024176616 (Patient Link); Reporter's Comments: A 77-year-old subject was vaccinated with the blinded study vaccine aQIVc HD vs QIVr vs aQIV. On 07-Jan-2024, one month and 11 days after receiving blinded study vaccine, the subject was presented to the emergency department due to worsening dyspnea on exertion for the past three days. The subject also had had intermittent chills. The subject reported that back on 13-Dec-2023 he had a car versus pedestrian accident and was ran over and sustained left rib and back injuries. The subject was actively wheezing and desaturated to 80% on room air. The subject received several doses off nebulization. The subject developed atrial fibrillation with rapid ventricular response and was given Cardizem bolus (diltiazem) and oxygen. Medical doctor recommended admission for pneumonia and atrial fibrillation with rapid ventricular response. The subject started with doxycycline and Rocephin (ceftriaxone sodium), intravenously, daily, for acute pneumonia. On the same day, the subject had acute severe COPD exacerbation, acute hypoxic respiratory failure and sepsis. Four days later, on 11-Jan-2024, the subject was discharged from the hospital. The discharge diagnoses were acute severe COPD exacerbation, acute hypoxic respiratory failure, acute pneumonia, sepsis, and new onset A-Fib with RVR. In line with investigator's causality assessment, Sponsor assessed the events as not related to the study vaccine, due to biological and chronological implausibility. The subject's significant medical history included pneumonia, chronic obstructive pulmonary disease and asthma which are risk factors for the events including his elderly age. Of note, the subject sustained significant traumatic injuries to chest (4 broken ribs and contusions) due to a car accident 25 days earlier which may have further increased the subject's susceptibility to the events. Listedness was assessed using version.