Age: 74.0
Sex: F
Vaccine: COVID19
Symptoms: Activated partial thromboplastin time, Alanine aminotransferase, Aspartate aminotransferase, Autopsy, C-reactive protein
Clinical narrative: COVID-19 pneumonia/acute to organizing diffuse alveolar damage; Encephalopathy/Mild hypoxic ischemic injury; This literature-non-study case was reported in a literature article and describes the occurrence of COVID-19 PNEUMONIA (COVID-19 pneumonia/acute to organizing diffuse alveolar damage) and HYPOXIC-ISCHAEMIC ENCEPHALOPATHY (Encephalopathy/Mild hypoxic ischemic injury) in a 74-year-old female patient who received mRNA-1273 (Moderna COVID-19 Vaccine) for COVID-19 prophylaxis.        The patient's past medical history included GERD and Pulmonary embolism. Concurrent medical conditions included Diabetes mellitus, Hypertension, Hyperlipidemia, Depression and Cholangiocarcinoma metastatic.   On an unknown date, the patient received second dose of mRNA-1273 (Moderna COVID-19 Vaccine) (unknown route) 1 dosage form. On an unknown date, received first dose of mRNA-1273 (Moderna COVID-19 Vaccine) (unknown route) dosage was changed to 1 dosage form. On an unknown date, the patient experienced COVID-19 PNEUMONIA (COVID-19 pneumonia/acute to organizing diffuse alveolar damage) (seriousness criteria death and medically significant) and HYPOXIC-ISCHAEMIC ENCEPHALOPATHY (Encephalopathy/Mild hypoxic ischemic injury) (seriousness criterion medically significant). The patient was treated with DEXAMETHASONE for COVID-19 treatment, at an unspecified dose and frequency. The patient died on an unknown date. The reported cause of death was COVID-19 pneumonia. An autopsy was performed. The autopsy-determined cause of death was COVID-19 pneumonia. At the time of death, HYPOXIC-ISCHAEMIC ENCEPHALOPATHY (Encephalopathy/Mild hypoxic ischemic injury) outcome was unknown.      DIAGNOSTIC RESULTS (normal ranges are provided in parenthesis if available): On an unknown date, Activated partial thromboplastin time: 29.3 secs. On an unknown date, Alanine aminotransferase (10-50): 7 U/L. On an unknown date, Aspartate aminotransferase (10-50): 28 U/L. On an unknown date, Autopsy: 1180 gram and N1 RT-qPCR from autopsy lung FFPE mean Ct was 27.1 and mean corrected quantification was 9.2 E plus 02 copies/microlitre. On an unknown date, C-reactive protein (0.0-10.0): 120.1 milligram per litre. On an unknown date, Fibrin D dimer (Unknown-500): 3214 ng/mL. On an unknown date, Fluorescent in situ hybridisation: Spike RNA in situ hybridization was negative for frontal, thalamus and medulla regions of brain-IN SITU HYBRIDISATION. On an unknown date, Glomerular filtration rate (59-Unknown): 93 millilitre per minute per 1.73 square metre. On an unknown date, Immunohistochemistry: CD61 immunohistochemistry showed intravascular aggregates of platelets and no thrombi were identified by H&E or CD61 IHC in any of the sections and fibrinogen immunohistochemistry showed qualitatively similar degrees of perivascular fibrinogen staining. Nucleocapsid and spike immunohistochemistry was negative for frontal, thalamus and medulla regions of brain.. On an unknown date, International normalised ratio (0.9-1.1): 1.0. On an unknown date, Lymphocyte count (1.00-4.80): 0.75 thousand per microlitre. On an unknown date, Neurological examination: COVID-19 associated neuropathological findings showed mild hypoxic ischemic injury. On an unknown date, Neutrophil count (2.50-6.00): 10.20 thousand per microlitre. On an unknown date, SARS-CoV-2 test: (Positive) positive for SARS-CoV-2 RT-PCR by premortem nasopharyngeal swab nucleic acid amplification tests. On an unknown date, Serum ferritin (13-150): 293 microgram per litre. On an unknown date, Viral test: Viral staining was negative in neurons, glia, endothelium, and immune cells in the frontal lobe with olfactory nerve, thalamus, and medulla.. On an unknown date, White blood cell count (4.00-10.00): 11.34 thousand per microlitre. On an unknown date, Whole-genome sequencing: SARS-CoV-2 genotyping(Pango lineage) of pre/peri-mortem nasopharyngeal swab showed BA.1 (Omicron). Amplicon sequencing of autopsy lung tissue confirmed BA.1 (Omicron)..     For mRNA-1273 (Moderna COVID-19 Vaccine) (Unknown), the reporter did not provide any causality assessments.   Patients with positive nasopharyngeal swab SARS-CoV-2 RT-PCR testing with postmortem brain examination at Hospital from 1-Apr-2020 to 15-Feb-2022 were screened for inclusion in this study. Omicron variant cases with first reported symptoms from 16-Dec-2021 to 15-Feb-2022 were also identified. Water and pre-COVID-19-era autopsy brain tissue samples were used as negative controls for the extraction.  Patient's Neuro symptoms were reported as Encephalopathy. Autopsy lung FFPE and neuroimaging  were not done. Patient did not received mechanical ventilation.  Patient died 6 days after onset of symptoms and postmortem was done in the interval of 65 hours.  Concomitant medications were not reported. It was reported that patient died with COVID-19 pneumonia in the setting of widely metastatic cholangiocarcinoma.  Five Omicron variant autopsies were performed between 30-Dec-2021 and 4-Feb-2022. Evidence of COVID-19 pneumonia, including acute to organizing diffuse alveolar damage was observed.  Median age at death was slightly higher for Omicron variant patients at 67 (interquartile range [IQR] 5068) years compared to Delta variant (56 [IQR 4865] years) and non-Delta/non-Omicron variant (53 [IQR 5063] years) patients.  In this study, neither viral RNA nor protein was identified in brain tissue of the Delta or Omicron variant patients despite evidence of microvascular injury and microglial infiltration, supporting a non-neuroinvasive mechanism of neuropathogenesis.   This case was linked to US-MODERNATX, INC.-MOD-2023-714401 (Linked Report).  Company comment: This is a literature non-study case concerning a 74-year-old female patient, with relevant medical history of pulmonary embolism and underlying conditions of diabetes mellitus, hypertension, hyperlipidemia and cholangiocarcinoma metastatic, who experienced the serious fatal event of COVID-19 pneumonia and the unexpected and serious (due to medically significant) AESI of Hypoxic-ischaemic encephalopathy, which occurred on an unknown date after the second dose of mRNA-1273 vaccine. Laboratory tests were performed and showed C-reactive protein of 120.1 mg/l, fibrin D dimer of 3214 ng/mL, ferritin of 293 mg/L, glomerular filtration rate of 93 ml/minute, among others. SARS-CoV-2 test was positive by premortem nasopharyngeal swab and whole-genome sequencing showed Omicron variant (BA.1). Neurological examination revealed mild hypoxic ischemic injury. Patient received treatment with dexamethasone (unknown dose and frequency). Patient died 6 days after the symptom onset. The reported cause of death was COVID-19 pneumonia. An autopsy was performed and showed amplicon sequencing of lung tissue with Omicron variant. CD61 immunohistochemistry showed intravascular aggregates of platelets and no thrombi were identified by H&E or CD61 IHC in any of the sections and fibrinogen immunohistochemistry showed qualitatively similar degrees of perivascular fibrinogen staining. Nucleocapsid and spike immunohistochemistry was negative for frontal, thalamus and medulla regions of brain. Patient´s medical history and underlying conditions remain confounding factors for the case. The benefit-risk relationship of mRNA-1273 vaccine is not affected by this report.; Sender's Comments: This is a literature non-study case concerning a 74-year-old female patient, with relevant medical history of pulmonary embolism and underlying conditions of diabetes mellitus, hypertension, hyperlipidemia and cholangiocarcinoma metastatic, who experienced the serious fatal event of COVID-19 pneumonia and the unexpected and serious (due to medically significant) AESI of Hypoxic-ischaemic encephalopathy, which occurred on an unknown date after the second dose of mRNA-1273 vaccine. Laboratory tests were performed and showed C-reactive protein of 120.1 mg/l, fibrin D dimer of 3214 ng/mL, ferritin of 293 mg/L, glomerular filtration rate of 93 ml/minute, among others. SARS-CoV-2 test was positive by premortem nasopharyngeal swab and whole-genome sequencing showed Omicron variant (BA.1). Neurological examination revealed mild hypoxic ischemic injury. Patient received treatment with dexamethasone (unknown dose and frequency). Patient died 6 days after the symptom onset. The reported cause of death was COVID-19 pneumonia. An autopsy was performed and showed amplicon sequencing of lung tissue with Omicron variant. CD61 immunohistochemistry showed intravascular aggregates of platelets and no thrombi were identified by H&E or CD61 IHC in any of the sections and fibrinogen immunohistochemistry showed qualitatively similar degrees of perivascular fibrinogen staining. Nucleocapsid and spike immunohistochemistry was negative for frontal, thalamus and medulla regions of brain. Patient´s medical history and underlying conditions remain confounding factors for the case. The benefit-risk relationship of mRNA-1273 vaccine is not affected by this report. US-MODERNATX, INC.-MOD-2023-714401:(Patient 10); Reported Cause(s) of Death: COVID-19 pneumonia; Autopsy-determined Cause(s) of Death: COVID-19 pneumonia