Sex: M
Vaccine: COVID19
Symptoms: International normalised ratio, Investigation, Myocarditis, Platelet count, Polymerase chain reaction
Clinical narrative: fulminant myocarditis; recurrent cardiac arrest; refractory shock; This is a literature report associated with BNT162b2 mRNA COVID-19 vaccination in two patients. This author reported similar events for two patients. This is first of two reports.   A 27-year-old male with trisomy 21 complicated by speech impairment without history of cardiovascular disease presented in cardiogenic shock 2 days after his second vaccine dose. He had received the first dose without adverse effects. Approximately 36 h after the second dose, he developed nausea and vomiting. He presented to another hospital in shock (blood pressure 77/54 mmHg and heart rate 133/min) and found to have diffuse ST segment elevation in electrocardiogram (Fig. 1). Cardiac catheterization showed no coronary obstructions. Initially, creatine kinase myocardial band level (CK-MB) was 252 ng/mL (normal value [NV] < 5). Transthoracic echocardiogram showed severe left ventricular systolic dysfunction (LVEF 20%) and a small circumferential pericardial effusion without tamponade. A diagnosis of presumed fulminant pericarditis was made and methylprednisolone 1000 mg and human immunoglobulin (IVIG) 60 g were given. The course was complicated by hemodynamically unstable ventricular tachycardia refractory to electrical cardioversion followed by pulseless electrical activity. He was resuscitated with veno-arterial extracorporeal mechanical oxygenation (VA-ECMO). After return of circulation, he was supported by multiple vasopressors, mechanical ventilation, and renal replacement therapy (RRT). Despite these interventions, multiorgan failure and refractory shock persisted. Lactic acid increased from 6 to 28 mmol/L (NV less than 2), D-dimer increased from 4.21 to greater than 20 ug/mL (critically high >5.0), INR increased from 2.0 to 10.0, and fibrinogen dropped to 100 mg/dL. C-reactive protein (CRP) and ferritin were highly elevated on admission at 13.1 mg/dL (NV less than 0.5) and 23,000 ng/mL, respectively, leading to a decision to administer anakinra (Kineret). Interleukin-6 level eventually came back highly elevated at 333 pg/mL (NV less than 13). thrombocytopenia developed progressively from 223x10 9 /L to 21x10 9 /L, while hemoglobin decreased from 11.5 to 8.7 g/dL. The patient demonstrated acute liver injury (ALI) with alanine transferase (ALT) and aspartate transferase (AST) at 7995 and 9003 u/L. Polymerase chain reaction (PCR) for SARS-CoV2 and other common respiratory viruses more frequently associated with myocarditis was negative. SARS-CoV2 spike protein IgG antibody was positive (62.8 arbitrary units/ml [NV less than 15), and anti-nucleocapsid IgG was negative, consistent with immunization status. Approximately 21 h after admission, patient died due to recurrent cardiac arrest and refractory shock. Family declined request for autopsy. In summary, both cases presented features of fulminant myocarditis with a temporal association with the BNT162b2 mRNA Covid-19 vaccination, in absence of other apparent causes and with unique features of systemic hyperinflammation associated with refractory shock. These cases identify the need for awareness of a potential, albeit extremely rare, link of BNT162b2 mRNA Covid-19 vaccination associated with fulminant myocarditis as part of a severe systemic hyperinflammatory syndrome, requiring mechanical cardiac support and, most importantly, immunosuppressive therapy. The degree of the inflammatory biomarkers and multiorgan dysfunction seen in the two cases described, as in some patients with Covid-19, is indeed out of proportion to with hemodynamic failure and shock and it is not rapidly resolved by cardiac mechanical support, reflecting a significant degree of vasoplegia. The optimal immunosuppressive treatment for systemic hyperinflammation associated with fulminant myocarditis is unknown. They chose a combination of high dose methylprednisolone, IVIG and anakinra (Table 1) as a strategy used across a variety of immunologic and rheumatologic diseases characterized with inappropriate macrophage activation. Table 1 Key biomarkers at admission and immunomodulating therapy: Patient #1: Presentation included Symptoms: Nausea and vomiting. Vaccine type was BNT162b2 mRNA Covid-19. Timing was 2 days after second dose. Hemodynamics included Hypotension and tachycardia. ECG: ST segment elevation. Echocardiogram: LVEF 20%. Biomarkers included: CRP: 13.1 mg/dl; Interleukin-6 : 333 pg/ml; Ferritin : 23,000 ng/ml; INR : 2.0; D-dimer : 4.21 ug/ml; Lactic acid : 6 mmol/l; CK-MB : 252 ng/ml; SARS-CoV2 spike IgG : 62.8 a.u./ml; SARS-CoV2 NC IgG : negative. Immunosuppressive Therapy included: Methylprednisolone : 1000 mg; Immunoglobulins : 60 mg; Anakinra : 100 mg (2 doses). Outcome was Deceased 21 h after admission.  No follow-up attempts are possible; information about lot/batch number cannot be obtained. No further information is expected.; Sender's Comments: Based on temporal association and known drug profile, a contributory role of the suspect drug cannot be excluded in the development of events myocarditis, cardiac arrest, and shock. This case will be reassessed upon receipt of additional information.,Linked Report(s) :PFIZER INC-202101116531 Same article/ drug/event and different patient; Reported Cause(s) of Death: recurrent cardiac arrest; refractory shock; fulminant myocarditis