Sex: F
Vaccine: UNK
Symptoms: Computerised tomogram head abnormal, Death, Disseminated intravascular coagulation, Haemorrhagic cerebellar infarction, Headache
Clinical narrative: pharmacodynamic interaction between methotrexate, rituximab and tozinameran was considered; Brain death; COVID-19 pneumonia; systemic lupus erythematosus, had been receiving treatment with rituximab, methotrexate 25mg per week; This is a literature report.  A 60-year-old woman developed brain death secondary to COVID-19 pneumonia following concomitant administration of methotrexate, rituximab and tozinameran [routes not stated; not all dosages and outcomes stated]. The woman, who had a medical history of hypertension, type II diabetes mellitus and systemic lupus erythematosus, had been receiving treatment with rituximab, methotrexate 25mg per week and unspecified steroids. She had also been receiving apixaban for atrial fibrillation. On 02May2021, she presented to the hospital with fever (maximum temperature 104 degree F) and productive cough for a duration of one week. She had been vaccinated with tozinameran [Pfizer] for prevention of COVID-19 disease and received the second dose of vaccination on 18February2021. On 01April2021, she underwent routine COVID testing. At that time, she was tested positive; however, she was asymptomatic. On 24April2021, she developed productive cough and fever. Therefore, she was presented to the hospital. On day of hospital presentation, the polymerase chain reaction (PCR) testing for COVID-19 was found to be positive. Based on the clinical presentation and laboratory findings, COVID-19 pneumonia was considered. Therefore, the woman was admitted to the hospital on 03May2021. On hospital admission, her therapy with methotrexate was stopped and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies were found to be negative. On 09May2021, she was admitted to the ICU due to acute hypoxic respiratory failure. Therefore, she received a complex course of treatment including unspecified broad spectrum antibacterial antibiotics, remdesivir and high-dose unspecified steroids for prevention of lupus flair. During the initial 5 days of hospitalisation, she continued receiving apixaban therapy, which was subsequently stopped due to the development of disseminated intravascular coagulation. On admission day 13, an altered mental status was observed, and she also reported headache. Subsequent head CT revealed a new acute to subacute infarct involving the right frontal operculum and insular region, new parenchymal haemorrhage versus haemorrhagic infarct involving the left parietal lobe and left cerebellar hemisphere and multifocal acute subarachnoid haemorrhage. The CT angiogram of the head and neck showed no definite evidence of an acute large vessel intracranial arterial occlusion or substantial arterial stenosis; however, multifocal irregularity within the superior sagittal sinus with sinus venous thrombosis were noted. The brain MRI performed on the following day showed acute left middle cerebral artery territory infarct and evolution of right frontal lobe infarcts on diffusion weight imaging. The contrast-enhanced venogram showed non-occlusive superior sagittal sinus thrombosis. After interdisciplinary discussion with haematology, neurosurgery and neurology, the woman was treated with heparin drip. On admission day 19, head CT showed continued expected evolution of infarcts with sulcal effacement surrounding the dominant left sided infarcts and trace rightward midline shift. On admission day 35, final head CT revealed cessation of contrast opacification of the anterior and posterior intracranial arterial circulation as well as new cerebral oedema with effacement of the gray-white matter borders, sulci, ventricles and cisterns, haemorrhage in the right frontal and left frontoparietal lobes at the site of previous infarctions, and new hyperdensity in the sylvian fissures consistent with subarachnoid haemorrhage. Based on the clinical presentation and laboratory findings, brain death secondary to COVID-19 pneumonia following pharmacodynamic interaction between methotrexate, rituximab and tozinameran was considered. Additionally, acute cerebrovascular disease was considered. Subsequently, she died due to COVID-19 pneumonia.  Pfizer is a marketing authorization holder of Rituximab and Methotrexate Sodium in the country of incidence or the country where the product was purchased (if different). This may be a duplicate report if another marketing authorization holder of Rituximab and Methotrexate Sodium has submitted the same report to the regulatory authorities.; Sender's Comments: Based on a temporal association and known product safety profile, a causal relationship between the reported events and suspect drugs were  assessed as possible. The impact of this report on the benefit/risk profile of the Pfizer product is evaluated as part of Pfizer procedures for safety evaluation, including the review and analysis of aggregate data for adverse events. Any safety concern identified as part of this review, as well as any appropriate action in response, will be promptly notified to RAs, Ethics Committees, and Investigators, as appropriate.; Reported Cause(s) of Death: Brain death; COVID-19 pneumonia; pharmacodynamic interaction between methotrexate, rituximab and tozinameran was considered