fulminant myocarditis; This is a literature report associated with BNT162b2 mRNA COVID-19 vaccination in two patients. This author reported similar event for two patients. This is second of two reports.   A 34-year-old female without prior medical history presented 9 days after her first vaccine dose. On day 4 after vaccine, she developed fevers, cough, chest pain, nausea, and vomiting. She presented to another institution with hypotension and sinus tachycardia, an echocardiogram showed severely reduced LVEF of 15%. Cardiac catheterization showed no obstructive coronary artery disease. She was transferred for initiation of VA-ECMO. On admission, she was in severe shock requiring multiple vasopressors. CRP, ferritin and CK-MB were elevated at 5.6 mg/dL, >30,000 ng/mL, and 42.4 ng/mL, respectively. VA-ECMO and RRT were initiated. Treatment was initiated with methylprednisolone 1000 mg daily and continued for 3 days followed by a slow taper over, with IVIG 30 mg daily for 4 days, and anakinra 100 mg daily. Lactic acid 13 mmol/ L on admission normalized within 24 h of ECMO onset, INR improved from 4.5 to 1.7. Interleukin-6 level was mildly elevated at 17 pg/mL and interleukin-2 soluble receptor alpha was 1067 U/mL (NV less than 710). Thrombocytopenia was noted at 106x10 9 /L which persisted for several days. ALI was noted with ALT and AST at 14,477 and 6086 u/L which steadily improved thereafter. PCR for SARS-CoV2 and other common respiratory viruses was negative. SARS-CoV2 spike protein IgG antibody was positive (64 arbitrary units/ml), and IgG anti-nucleocapsid was negative, consistent with immunization due to vaccine without prior infection. Vasopressors were weaned off, LVEF was documented at 50% by transthoracic echocardiography, VA-ECMO was discontinued. She was treated with prednisone 1 mg/kg and anakinra with prednisone tapered first (by reducing 0.1 mg every week) and tapering anakinra planned after prednisone is discontinued. An endomyocardial biopsy performed on day 13 of hospital admission, after recovery of cardiac function and near resolution of the systemic hyperinflammation, showed cardiomyocytes with minute foci of cytoplasmic vacuolization and rare interstitial lymphocytic infiltrate, which is consistent with healing myocarditis, but did not meet conventional diagnostic criteria for acute myocarditis. A cardiac catheterization at the same time showed preservation of cardiac output and normal filling pressures. A cardiac magnetic resonance, performed 45 days after the initial presentation, showed LVEF of 35%, diffuse elevation of native T1 values, small pericardial effusion with enhancement of the pericardium anterior and anterolaterally and small patchy areas of enhancement following delayed imaging after gadolinium in the mid-wall of the anterior wall, consistent with myopericarditis. Genetic testing for 121 genes showed no variants associated with genetic disorders. Guideline-directed heart failure treatment was also initiated. She was discharged from the hospital after 73 days. 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 #2: Presentation included: Symptoms: Fever, cough, chest pain, nausea and vomiting. Vaccine type was BNT162b2 mRNA Covid-19. Timing was 9 days after 1st dose. Hemodynamics included Hypotension and tachycardia. ECG : Non-specific changes. Echocardiogram: LVEF 15%. Biomarkers included: CRP : 5.6 mg/dl; Interleukin: 17.2 pg/ml [12 h after therapy]; Ferritin : greater than 30,000 ng/ml; INR : 4.5; D-dimer : greater than 20 ug/ml; Lactic acid : 13 mmol/l; CK-MB : 42 ng/ml; SARS-CoV2 spike IgG : 64 a.u./ml; SARS-CoV2 NC IgG : negative. Immunosuppressive therapy included: Methylprednisolone : 1000 mg daily for 3 days, followed by a slow prednisone taper over several weeks; Immunoglobulins : 30 mg daily for 4 days; Anakinra : 100 mg daily. Outcome was Recovering, minimal symptoms, LVEF 35%, delayed enhancement after gadolinium at cardiac magnetic resonance; discharged from the hospital after 73 days.  No follow-up attempts are possible; information about lot/batch number cannot be obtained. No further information is expected.; Sender's Comments: The event myocarditis is considered possibly related to suspect BNT162b2 mRNA COVID-19 vaccination, based on temporal association and in absence of other apparent causes, and with unique features of systemic hyperinflammation associated with refractory shock.  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.,Linked Report(s) : US-PFIZER INC-202101116136 Same article/ drug/event and different patient