Sex: F
Vaccine: COVID19
Symptoms: Interleukin-2 receptor assay, International normalised ratio, Laboratory test, Lymphocyte count, Multisystem inflammatory syndrome in children
Clinical narrative: This is a literature report for the following literature source(s): Multisystem inflammatory syndrome in children (MIS-C) possibly secondary to COVID-19 mRNA vaccination, Case Reports, 2022; Vol:15(3), DOI:10.1136/bcr-2021-247176. An adult female patient received BNT162b2 (BNT162B2), as dose 1, single (Batch/Lot number: unknown) and as dose 2, single (Batch/Lot number: unknown) for Covid-19 immunisation. The patient's relevant medical history included: "dysmenorrhea" (unspecified if ongoing); "appendectomy" (unspecified if ongoing), notes: 6 months prior. The patient's concomitant medications were not reported. Past drug history included: Ethinyl estradiol for dysmenorrhea; Norgestimate for dysmenorrhea; Nitrofurantoin for urinary tract infection. The following information was reported: MULTISYSTEM INFLAMMATORY SYNDROME IN CHILDREN (hospitalization, medically significant), 12 weeks after the suspect product(s) administration, outcome "recovered". The patient underwent the following laboratory tests and procedures: Activated partial thromboplastin time (23-32): 31.2 seconds; Antithrombin III (80-135): 86 %; Blood creatine phosphokinase MB (normal high range 4.4): 0.7 ng/ml; Blood fibrinogen (150-440): 810 mg/dl; Blood lactate dehydrogenase (110-240): 208 uL; Blood lactic acid (0.3-1.9): 0.9 mmol/L; Blood pressure measurement: 122/70 mmHg; Body mass index: 28.3 kg/m3; Body temperature: 39.6 Centigrade; Brain natriuretic peptide (normal high range 100): 75 pg/mL; Chest X-ray: normal; C-reactive protein (normal high range 10): 235.3 mg/l; less than 1.0; Echocardiogram: showed normal biventricular function, notes: valvular function and coronary artery dimensions; Electrocardiogram: showed normal sinus rhythm, notes: with RS pattern which was considered a likely normal variant in the setting of normal QRS duration and no significant increase in voltages; normal, notes: Follow-up; Heart rate: 121, notes: units: beats/min; Interleukin-2 receptor assay (175.3-858.2): 1499.5 pg/mL; International normalised ratio (2-3.5): 1.0; D-dimer (normal high range 0.5): 1.92 mg/l; Lymphocyte count (0.9-3.4): 0.5 10*6/uL; Neutrophil count: 8.99 10*9/mL, notes: neutrophilia; Oxygen saturation: 100 %, notes: in room air; Prothrombin time (9.6-12.4): 11.3 seconds; Red blood cell sedimentation rate (normal high range 20): 120, notes: units: mm/hour; SARS-CoV-2 test: negative; Serum ferritin (11-306): 237 ng/ml; Troponin I (0.01-0.04): 0.23 ng/ml; Urine analysis: Notable for: slightly cloudy, notes: 3 protein, 2 ketones, 1 blood, rare bacteria; White blood cell count (4.3-10.8): 7.7 10*9/mL; 11 10*9/mL. Therapeutic measures were taken as a result of multisystem inflammatory syndrome in children. Clinical information: A woman in her late teens presented to our hospital emergency department with fevers up to 40°C for 4 days, chills, sweats, tachycardia, shortness of breath, fatigue and a throbbing headache. Fevers were only briefly responsive to antipyretics. At the time of presentation, she also described mid-sternal chest pressure resolving with ambulation, diffuse myalgias, nausea, one episode of vomiting and four episodes of watery non-bloody diarrhoea. The patient had a history of dysmenorrhea managed by oral contraceptives (ethinyl estradiol and norgestimate). Her prior surgical history included an appendectomy 6 months prior. SARS-CoV-2 PCR testing done both 3 and 2 days prior to admission were negative. She had received weekly to biweekly PCR testing in the 3-month period prior to presentation, given her employment at a long-term care facility. All PCR tests were negative. The patient received her first dose of the Pfizer BioNTech COVID-19 vaccine approximately 12 weeks prior to her presentation, with her second dose 20 days later. Six weeks prior to her presentation, with her second dose 20 days later. Six weeks prior to her presentation, the patient's two younger siblings developed febrile illnesses of unclear aetiology that lasted 36 hours and self-resolved. They were seen at an urgent care facility at that time and had negative SARS-CoV-2 PCR testing. They did not have COVID-19 antibody testing performed at that time or subsequently. No one else in the home was sick and the final diagnosis of the siblings at the urgent care facility was an unspecified viral illness. At that time, the patient developed dysuria and haematuria without vaginal discharge, spotting or abdominal pain and was prescribed nitrofurantoin at an urgent care facility for treatment of a urinary tract infection. She had no fever or other symptoms at that time and her symptoms resolved shortly thereafter with antibiotics. The patient had no known contact with COVID-19 positive individuals and no travel, animal or other environmental exposures. Vital signs in the emergency department were notable for: temperature 39.6°C, heart rate 121 beats/min, blood pressure 122/70 mm Hg and oxygen saturation 100% in room air. Anthropometrics included: weight 77 kg, height 165.1 cm and body mass index 28.3 kg/m². The patient was ill appearing with persistent tachycardia despite normal saline boluses (2 L in total) and maintenance fluids. Her blood pressure remained normal. Her initial examination was otherwise unremarkable apart from bilateral non-exudative conjunctivitis. The patient fulfilled clinical and laboratory criteria for MIS-C including =24 hours of fever, evidence of systemic inflammation with at least two organ systems involved (gastrointestinal, haematological, dermatological/mucocutaneous, neurocognitive and cardiac) and illness requiring hospitalisation. She had a positive COVID-19 IgG (Beckman Coulter Access SARS-CoV-2 IgG), although this could certainly have been secondary to receipt of vaccine. Stool studies were not performed as her diarrhoea resolved. The patient did not fulfil criteria for KD, acute COVID-19, bacterial sepsis or toxic shock syndrome. As above, viral aetiologies were explored but molecular testing for additional viruses (such as enterovirus/rhinovirus, adenovirus and parainfluenza) was not sent as extended viral testing at our centre has a multiday turnaround time. Given expanded viral testing was not sent, it remains possible that another viral aetiology, not specified, could have caused this patient's presentation. Viral aetiologies known to cause multisystem involvement are listed in box 1. This patient was immunocompetent and was not expected to present with serious illness secondary to these other viruses, however, it remains possible that another viral illness was present. She had no evidence of excessive immune activation (such as haemophagocytic lymphohistiocytosis or macrophage activation syndrome) or rheumatological disease such as systemic lupus erythematosus or vasculitis. In the absence of an alternative plausible diagnosis, the decision was made to treat her for MIS-C. Treatment for MIS-C was initiated with intravenous immune globulin 2 g/kg ×1 dose, as well as medium dose aspirin 650 mg every 6 hours for anti-inflammatory effect,15 and methylprednisolone 1 mg/kg every 12 hours. She was also given enoxaparin secondary to concern for risk of coagulopathy as she was taking combined oral contraceptives. By 24 hours after treatment initiation, the patient defervesced and reported that all of her symptoms had resolved. Her physical examination was normal including resolution of conjunctivitis. She was discharged 48 hours from admission in good condition on aspirin 81 mg daily and oral prednisone taper over 3 weeks. At the time of outpatient follow-up 2 weeks from hospital discharge, the patient reported she was back to her baseline. slight increase in white cell count to 11×109/L and neutrophilia (absolute neutrophil count 8.99×109/L), likely secondary to neutrophil demargination related to corticosteroid therapy. C reactive protein (CRP) had normalised to <1.0 mg/L. Given the previously noted IgG titre may have been from vaccination, ant nucleocapsid IgG testing (Abbott ARCHITECT SARS-CoV- 2 IgG) was performed (this testing was not available at the time of hospitalisation). Testing was negative, suggesting she had not had prior COVID-19 disease. No follow-up attempts are possible; information about lot/batch number cannot be obtained. No further information is expected. Sender's Comments: Based on the information available a possible contributory role of the suspect BNT162B2 cannot be excluded for the reported events of Multisystem inflammatory syndrome. 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 regulatory authorities, Ethics Committees, and Investigators, as appropriate