Age: 59.0
Sex: M
Vaccine: COVID19-2, FLU4, COVID19-2, FLUC3
Symptoms: Cough, Creatinine renal clearance normal, Depression, Diuretic therapy, Drug-induced liver injury
Clinical narrative: Sepsis; HAP (hospital-acquired pneumonia) / Left upper lobe pneumonia; Decompensated hepatic cirrhosis; Pleural effusion on the right; Elevated troponin / Initial high sensitivity troponin 42 up trending to 55; Elevated d-dimer / D-Dimer Pl QN: 2018 ng/mL DDU High; Elevated brain natriuretic peptide (BNP) level / BNP very slightly elevated at 117; Degenerative changes of cervical spine; Episode of hepatic encephalopathy; This spontaneous case was retrieved on 11-Dec-2023 from Vaccine Adverse Event Reporting System (VAERS) (reference number: 2716783-1) reported by other health professional with additional information received on 18-Dec-2023 form Seqirus' manufacturing quality assurance department (being processed together), and concerned a 59-year-old, male patient.  The patient's concurrent conditions included Alzheimer's disease, schizophrenia, cognitive impairment, hypothyroidism, hypertension, hyperlipidemia, chronic anemia, anxiety disorder, type 2 diabetes, seizure disorder, cirrhosis, depression, diabetic neuropathy, hearing deficit, hyperammonemia, hypotension, pre-ulcerative calluses, tachycardia, elevated liver function test (LFTs), unstable gait, mood disorder, change in mental status, hallux abductovagus, onychogryphosis due to dermatophyte and the patient was positive to purified protein derivative (PPD). The patient's historical conditions included closed non-displaced fracture of greater tuberosity of right humerus with routine healing, proximal humerus fracture and scalp laceration. The patient's past procedures included retinal eye exam and colonoscopy. The patient's allergies included allergy to Depakote (valproate). The patient's concomitant medications included lisinopril for blood pressure, Aldactone (spironolactone), Abreva (docosanol), aspirin, Biotene Mouthwash (glucose oxidase; lactoferrin; lactoperoxidase; lysozyme; sodium fluorophosphate), buspirone, ciclopirox, clozapine, diazepam, divalproex sodium, fenofibrate, Ferosul (ferrous sulfate), fluoxetine, lactulose, Lasix (furosemide), latanoprost, milk of magnesia, Mintox Maximum Strength (aluminium hydroxide, magnesium hydroxide, simeticone), rifaximin, Silvadene (sulfadiazine silver), oxybutynin, simvastatin, Synthroid (levothyroxine sodium), Tylenol (paracetamol), and Namzaric (donepezil hydrochloride; memantine hydrochloride), all used for unreported indications. The patient was well nourished and denied alcohol and substance abuse and electronic cigarettes use.  It was reported that on 18-Oct-2023, the patient was vaccinated with Afluria Quadrivalent (Influenza vaccine inact split 4v; dose: not reported, route of administration: injection (reported as 'SYR'), anatomical location, and indication: not reported). The batch number reported was A51594B (reported batch number was identified by Seqirus to be most likely batch: AS1594B). The reported batch number was identified by Seqirus to be linked to suspect product Flucelvax Quadrivalent (influenza vaccine inact sag 4v) instead of reported suspect product Afluria Quadrivalent. Based on the reported batch number, the suspect product was changed to Flucelvax Quadrivalent.  On the same date, the patient was vaccinated with non-company, co-suspect Moderna COVID-19 Vaccine, Bivalent (Original and Omicron BA.4/BA.5) (davesomeran, elasomeran; dose: reported as '4', route of administration: injection (reported as 'SYR'), anatomical location, and indication: not reported). The batch number reported was 017H22A.  On 09-Nov-2023, the patient was recently admitted with Hepatic encephalopathy (HE) and had last therapeutic paracentesis on 11/9 removing 3.2L of ascitic fluid.  On 11-Nov-2023, 24 days after receiving Flucelvax Quadrivalent and non-company, co-suspect Moderna COVID-19 Vaccine, Bivalent, the patient experienced episode of hepatic encephalopathy and was admitted to hospital.   On 16-Nov-2023, the patient was discharged from hospital.  On 19-Nov-2023 at 06:45, the patient was admitted to hospital again with his caregiver at his bedside due to shortness of breath, and reproductive cough. Reportedly, the patient has been short of breath since his prior discharge on the 16-Nov-2023. The patient abdomen has stayed tense, his bilateral lower extremities have been very edematous, he was a little more confused and sometimes did not respond appropriately to questions. Earlier that day the patient fell. It was uncertain if he hit his head, but he was complaining of some although pain. The patient also experienced pitting edema, moderate cognitive impairment, ecchymosis was present on left elbow, mild asterixis, moderate pleural effusion on the right and large tense abdomen due to ascites, sepsis, decreased volume lungs, and hepatic hydrothorax. The patient met sepsis criteria most likely due to hospital-acquired pneumonia. Could possibly also be abdominal source but patient was without any abdominal pain which was concerning for spontaneous bacterial peritonitis (SBP). The patient had a left upper lobe pneumonia and was treated with antibiotic treatment.   Review of systems constitutional showed no fevers, no chills, no sweats. Eye examination showed no changes in vision. Examination of ears, nose, mouth, and throat showed no ear pain, no nasal congestion, and no sore throat. Respiratory examination showed no wheeze. Cardiovascular examination showed no chest pain, no palpitations, and no edema. Gastrointestinal examination showed no abdominal pain, no nausea, no vomiting, no diarrhea, and no constipation. The patient had at least three non-bloody bowel movements per day. Genitourinary examination showed no frequency, no urgency, no dysuria, and no hematuria. Hematologic/lymphatic examination showed no bruising, and no enlarged lymph nodes. Allergic/immunologic examination showed no hives. Endocrine examination showed no cold intolerance, no heat intolerance, no polyuria, no polydipsia. Musculoskeletal examination showed no arthralgia and no myalgia. Skin examination showed no rash, no pruritus. Neurological examination showed slight confusion, anxiety and depression, no headache, no focal weakness, no numbness. Psychiatric examination revealed anxiety and depression. A physical exam revealed mild distress. The oral mucosa was moist. Neck was supple, non-tender, with intact range of motion (ROM). Respiratory examination showed poor air movement bilaterally. Cardiovascular examination showed regular rate and rhythm. Gastrointestinal examination showed soft, non-tender, normoactive bowel sounds, and a distended, tense abdomen. Musculoskeletal examination showed no joint swelling, no deformity, intact bilateral ROM, and pitting edema. Neurologic examination showed moderate cognitive impairment, no focal deficits, and mild asterixis present. Psychiatric examination showed that the patient was cooperative, appropriate mood and affect.   On the same date, a hematology test revealed following: white blood cell (WBC) count was high (12.8 k/cumm), red blood cell (RBC) count was 3.78 million/cumm, hemoglobin (Hgb) was 11.7 GM/dL (low), Hct was 35.1 %  MCV: 93 fL, MCH: 31 pg, MCHC was 33.3 GM/dL, RDW: 15.3 %, platelet count was 175 k/cummm MPV was 9.1 fL, neutrophils % was 89 %, lymphocytes % was 5%, monocytes % was 5 %, eosinophils % was 1 %, basophils % was 0 % absolute neutrophil was 11.4 k/cumm (high), absolute lymphocyte was 0.6 k/cumm (low) absolute monocyte was 0.7 k/cumm, absolute eosinophil was 0.1 k/cumm, absolute basophil was 0.1 k/cumm. Chemistry analysis showed: Sodium was 131 mmol/L (low), potassium SerPl was 3.8 mmol/L, chloride was 100 mmol/L, carbon dioxide was 26 mmol/L, anion gap was 5 mmol/L, blood urea nitrogen (BUN) was 18 mg/dL, creatinine was 0.75 mg/dL (low), estimated glomerular filtration rate (GFR) (CKD-EPI, no race) was >90, estimated creatinine clearance (CRCL) was 107 mL/min, glucose was 175 mg/dL (high), calcium total was 8.8 mg/dL, alkaline phosphatase was 254 Units/L (high), alanine transaminase (ALT) was 75 Units/L (high) , aspartate aminotransferase (AST) was 173 Units/L (high), bilirubin total was 1.1 mg/dL (high), total protein was 6.9 GM/dL,  albumin was 2.8 GM/dL (low) troponin-I high sensitivity was 55 ng/L (high), brain natriuretic peptide (BNP) was 117 pg/mL (high), ammonia was50 mCmol/L (high), lactate venous was 1.5 mmol/L, pH of venous blood was 7.44 , pCO2 of venous blood was 41 mmHg, pO2 of venous blood was <34 (low), base excess of  venous blood was 3 mmol/L (high), venous blood bicarbonate was 28 mmol/L,  oxygen saturation in venous blood was 66%. Body temperature: 37 degrees Celsius (C). Coagulation tests showed prothrombin time (PT) was 19 seconds (high)international normalised ratio (INR) was 1.7 (high), D-Dimer was 2018 ng/mL DDU (high). Urine studies revealed: yellow colour, slightly cloud urine, specific gravity was 1.031 (high), pH was 6, protein was 50 (abnormal), glucose was normal, ketones, bilirubin, urine haemoglobin, nitrite, and urine leukocyte esterase were negative, urobilinogen was normal; WBC, RBC, bacteria and squamous epithelial were none seen, mucous was present. Nasopharyngeal coronavirus rapid SARS-CoV2 test was negative. Rapid influenza A PCR test was negative. Rapid Influenza B PCR test was negative. Chest X-ray showed low lung volumes, subtle bibasilar airspace opacities, likely related to atelectasis or pneumonia in the right clinical setting. No pleural effusion or pneumothorax. A computerized tomogram (CT) of chest showed no obvious pulmonary embolism, moderate right layering pleural effusion with an estimated volume of 200-300 mL, ascites, right basilar compressive atelectasis, parenchymal scarring and/or early pneumonia in the correct clinical setting, ll-defined nodular infiltrate in the left upper lobe., early pneumonia in the correct clinical setting. X-ray of elbow was negative for any acute fractures. Ther were no acute bony findings. CT of head without (w/o) the need of intravenous (IV) contrast showed no acute intracranial abnormality. CT of cervical spine w/o IV contrast showed mild to moderate degenerative changes of cervical spine and no acute findings. Electrocardiogram (EKG) showed no acute ST or T wave change. Pupillary light reflex tests (PERRLA) showed normal conjunctiva, no scleral icterus, and extraocular muscles intact (EOMI). Legionella strep urine antigen test was performed, however, no further information was provided. Liver biopy showed decompesated liver cirrhosis with Childs-Pugh class C.  On the same day, the patient was treated with Lasix (furosemide), lactulose, rifaximin, and Aldactone (spironolactone). It was reported that the patient will need diagnostic and therapeutic paracentesis and possibly paracentesis and thoracentesis.  Dyspnea was most likely multifunctional, patient had pneumonia in addition to a moderate pleural effusion on the right and large tense abdomen due to ascites causing decreased lung volumes. The patient did not require oxygen. For decompensated hepatic cirrhosis, a further evaluation was required, the home diuretic regime was increased to Lasix 40mg, Aldactone 100 mg and low salt diet with strict input/outputs (I/Os). For pleural effusion on the right, most likely due to hepatic hydrothorax, the diuresis was continued and the patient may have needed thoracentesis with Interventional radiology (IR). For Hepatic encephalopathy the patient was to continue with lactulose 45ml TID, titrate 2-4 BM per day, with rifaximin at home. The chronic anemia was stable, normoxytix, no active signs of bleeding, an the patient was to continue to trend. For Alzheimer's disease, anxiety disorder, depression, the patient was to continue with home medications. For diabetes, the patient was to follow the protocol in place. For hyperlipemia the patient was to continue with statin therapy. For hypertension, the patient was to hold home antihypertensive, as aggressive diuresis was pusherd, restarting as appropriate was considered. For hypothyroid, the patient was to continue with levothyroxine. For seizure disorder, it was discussed with caregiver that the patient does not have a seizure disorder (discrepant information) and was put on Depakote in the past for mood disorder.  On an unspecified date in Nov-2023, the patient was treated with doxycycline.  The outcome of the events was not reported.  The reporter did not provide a causality assessment.  All the events were considered to be serious due to seriousness criteria of hospitalization. Additionally, the events of sepsis, hospital acquired pneumonia, hepatic cirrhosis, hepatic encephalopathy were considered to be medically significant by a Physician within Seqirus' Pharmacovigilance Department.  Company comment: A 59-year-old patient was vaccinated with Afluria Quadrivalent and non-company, co-suspect Moderna COVID-19 Vaccine on 18-Oct-2023. On 09-Nov-2023, the patient had last therapeutic paracentesis on 11/9 removing 3.2L of ascitic fluid. On 11-Nov-2023, 24 days after receiving Flucelvax Quadrivalent and non-company, co-suspect Moderna COVID-19 Vaccine, Bivalent, the patient experienced episode of hepatic encephalopathy and was admitted to hospital. On 19-Nov-2023, the patient was admitted to hospital due to shortness of breath, and reproductive cough. The patient also experienced pitting edema, moderate cognitive impairment, ecchymosis was present on left elbow, mild asterixis, moderate pleural effusion on the right and large tense abdomen due to ascites, sepsis, decreased volume lungs, and hepatic hydrothorax. The patient met sepsis criteria most likely due to hospital-acquired pneumonia. The patient had a left upper lobe pneumonia and was treated with antibiotics. Neurological examination showed slight confusion, anxiety and depression. Diagnostic and laboratory investigations revealed among others degenerative changes of cervical spine, elevated brain natriuretic peptide (BNP) level, troponin increased and fibrin D dimer increased. The patient's concurrent conditions included Alzheimer's disease, schizophrenia, cognitive impairment, hypothyroidism, hypertension, hyperlipidemia, chronic anemia, anxiety disorder, type 2 diabetes, seizure disorder, cirrhosis, depression, diabetic neuropathy, hearing deficit, hyperammonemia, hypotension, pre-ulcerative calluses, tachycardia, elevated liver function test (LFTs), unstable gait, mood disorder, change in mental status. All events (pneumonia, sepsis, decompensated liver cirrhosis, hepatic encephalopathy, pleural effusion, cervical spine degeneration, elevated brain natriuretic peptide (BNP) level, troponin increased and fibrin D dimer increased) are assessed as not related to the suspect vaccines, based on biological implausibility and strong alternative aetiology (medical history).; Sender's Comments: Company comment: A 59-year-old patient was vaccinated with Afluria Quadrivalent and non-company, co-suspect Moderna COVID-19 Vaccine on 18-Oct-2023. On 09-Nov-2023, the patient had last therapeutic paracentesis on 11/9 removing 3.2L of ascitic fluid. On 11-Nov-2023, 24 days after receiving Flucelvax Quadrivalent and non-company, co-suspect Moderna COVID-19 Vaccine, Bivalent, the patient experienced episode of hepatic encephalopathy and was admitted to hospital. On 19-Nov-2023, the patient was admitted to hospital due to shortness of breath, and reproductive cough. The patient also experienced pitting edema, moderate cognitive impairment, ecchymosis was present on left elbow, mild asterixis, moderate pleural effusion on the right and large tense abdomen due to ascites, sepsis, decreased volume lungs, and hepatic hydrothorax. The patient met sepsis criteria most likely due to hospital-acquired pneumonia. The patient had a left upper lobe pneumonia and was treated with antibiotics. Neurological examination showed slight confusion, anxiety and depression. Diagnostic and laboratory investigations revealed among others degenerative changes of cervical spine, elevated brain natriuretic peptide (BNP) level, troponin increased and fibrin D dimer increased. The patient's concurrent conditions included Alzheimer's disease, schizophrenia, cognitive impairment, hypothyroidism, hypertension, hyperlipidemia, chronic anemia, anxiety disorder, type 2 diabetes, seizure disorder, cirrhosis, depression, diabetic neuropathy, hearing deficit, hyperammonemia, hypotension, pre-ulcerative calluses, tachycardia, elevated liver function test (LFTs), unstable gait, mood disorder, change in mental status. All events (pneumonia, sepsis, decompensated liver cirrhosis, hepatic encephalopathy, pleural effusion, cervical spine degeneration, elevated brain natriuretic peptide (BNP) level, troponin increased and fibrin D dimer increased) are assessed as not related to the suspect vaccines, based on biological implausibility and strong alternative aetiology (medical history).