key: cord-0843157-katbupcy authors: Trpkov, Cvetan; MacMullan, Paul; Feuchter, Patricia; Kachra, Rahim; Heydari, Bobak; Merchant, Naeem; Bristow, Michael S.; White, James A. title: Rapid Response to Cytokine Storm Inhibition using Anakinra in a Patient with COVID-19 Myocarditis date: 2020-10-12 journal: CJC Open DOI: 10.1016/j.cjco.2020.10.003 sha: 22b2fb139c046bbf988810d0c96a68331363d6d6 doc_id: 843157 cord_uid: katbupcy A 62-year-old female with COVID-19 developed acute respiratory failure and cardiogenic shock in the setting of a systemic hyper-inflammatory state and apparent ST-elevation myocardial infarction. Cardiac magnetic resonance (CMR) imaging showed fulminant acute myocarditis with severe left ventricular dysfunction. Treatment with the recombinant interleukin-1 (IL-1) receptor antagonist anakinra and dexamethasone resulted in rapid clinical improvement, reduction in serum inflammatory markers and a marked recovery in CMR-based markers of inflammation and contractile dysfunction. The patient was subsequently discharged from hospital. Emerging evidence supports use of anti-inflammatory therapies, including anakinra and dexamethasone, in severe COVID-19. Since the onset of the COVID-19 pandemic in late December 2019 in Wuhan, China, over 35 million cases have been described worldwide, leading to more than 1 million deaths. 1 Observational data have shown myocardial injury, as detected by serum marker elevation, to be a strong independent predictor of adverse outcomes. While several mechanisms of myocardial injury are postulated, acute myocarditis due to cytokine storm-like syndrome is of interest given the potential for it to be mitigated by therapies directly targeting the inflammasome. 2 We report a case of fulminant myocarditis in a patient with severe COVID-19 complicated by hyperinflammation successfully treated with the recombinant human interleukin-1 (IL-1) receptor antagonist anakinra and dexamethasone. A 62-year-old female with a prior medical history of primary progressive multiple sclerosis (MS) presented with acute altered level of consciousness, hypoxemia and shock. One week earlier she had tested positive by nasopharyngeal swab polymerase chain reaction for SARS-CoV-2. Initial blood pressure was 55/32 mmHg with a heart rate of 120 beats/minute, respiratory rate of 32 breaths/minute and oxygen saturation of 95% on 100% oxygen by a nonrebreather face mask. A chest X-ray revealed dense airspace opacities in the right lung with ground-glass opacity in the left lung, and a 12-lead ECG showed sinus tachycardia with diffuse The patient experienced rapid clinical improvement during the following 72 hours with reduced oxygen requirements, improved blood pressure and a reduction in heart rate. Anakinra treatment was continued for five days in total. Renal function improved and a progressive reduction in inflammatory markers was observed (Supplementary table S1). At this time, the J o u r n a l P r e -p r o o f patient was alert, hemodynamically stable, and required only 1 liter of supplemental oxygen. On day 14 (12 days following the initiation of anakinra), a repeat CMR demonstrated marked improvement in LVEF from 24% to 54% with a reduction in LGE signal intensity and global reductions in myocardial T1and T2 values and ECV (Figure 1, Figure 2 ). While no baseline pericardial changes were observed, convalescent imaging demonstrated a small pericardial effusion with enhancement of the parietal pericardium along the basal to mid inferolateral wall (Figure 1) , consistent with pericarditis. Resolution of pulmonary consolidation and pleural effusions was observed. The patient was discharged from hospital several days later. Myocardial injury is commonly observed in cases of severe COVID-19 and is strongly predictive of adverse outcomes. 3 The incidence of myocarditis is unknown, and exceptional cases where CMR was performed have shown varying degrees of inflammatory myocardial injury. 4 A cytokine-storm syndrome, resembling secondary haemophagocytic lymphohistiocytosis/macrophage activation syndrome, is increasingly recognized in patients with severe COVID-19. 2 We describe the first case of fulminant COVID-19 myocarditis successfully treated by off-label use of anakinra, a recombinant IL-1 receptor antagonist, and dexamethasone. This treatment was associated with rapid and marked improvement in inflammatory markers, improvement in CMR-based markers of tissue injury, and marked improvement in LV systolic function. • COVID-19 myocarditis may present as acute ST segment elevation myocardial infarction. • COVID-19 myocarditis can be associated with systemic hyperinflammation An interactive web-based dashboard to track COVID-19 in real time COVID-19: consider cytokine storm syndromes and immunosuppression Cardiovascular Implications of Fatal Outcomes of Patients with Coronavirus Disease 2019 (COVID-19) COVID-19 and myocarditis: What do we know so far? CJC Open Interleukin-1 receptor blockade rescues myocarditis-associated end-stage heart failure Treating lifethreatening myocarditis by blocking interleukin-1 Anakinra for severe forms of COVID-19: a cohort study Interleukin-1 blockade with high-dose anakinra in patients with COVID-19, acute respiratory distress syndrome, and hyperinflammation: a retrospective cohort study Figure S1 . A) Chest X-ray demonstrating prominent right-sided patchy consolidation consistent with pneumonia. B) 12-lead ECG demonstrating marked ST-segment elevation in the anterolateral leads.