key: cord-0903282-tuhxso4k
authors: Jean-Marie, Elizabeth M.; Tabbalat, Aya; Raymond, Chad; Moghbelli, Meisam; Armitage, Keith; Neeland, Ian J.
title: Cardiogenic shock temporally associated with COVID-19 vaccination after prior COVID-19 infection: A case report
date: 2022-03-05
journal: Am Heart J Plus
DOI: 10.1016/j.ahjo.2022.100113
sha: 51fd375a47418706947e1d5dc22f23a9befe4649
doc_id: 903282
cord_uid: tuhxso4k

The introduction of coronavirus 2019 (COVID-19) vaccination has been an integral force in stopping the spread of COVID-19 across the globe. While reported side effects of vaccination have predominantly been mild, in the last year reports have emerged of myocarditis following the BNT162b2 (Pfizer-BioNtech) and mRNA-1273 (Moderna) vaccinations. The adolescent and young adult population have been the population most reported, with over 1000 cases under review by the Centers for Disease Control (CDC) since April 2021. Here we report a case of a previously healthy 21-year-old male who developed Multisystem Inflammatory Syndrome in Adults (MIS-A) and following the second dose of the Pfizer-BioNtech vaccine. The young male initially presented with fever, leukocytosis with high neutrophil-lymphocyte ratio, severe cardiac illness, and positive COVID-19 nucleocapsid serology, consistent with MIS-A diagnosis. His case was complicated by cardiogenic shock, requiring brief venoarterial extracorporeal membrane oxygenation (VA-ECMO) support. While this report does not detract from the overwhelming benefit of vaccination from COVID-19, clinicians should be aware of this possible relationship in the future.

syndrome caused by COVID-19 has had devastating effects, with over 5 million deaths reported [1] . The disease burden has predominantly been in adults, with children and adolescents typically experiencing mild illness without hospital admission [2] . During early May 2020 however, reports emerged from the United Kingdom of children requiring admission to intensive care units due to an unexplained Kawasaki-like disease syndrome now known as Multisystem Inflammatory Syndrome in Children (MIS-C) [2, 3] . A similar condition has also been reported as a rare complication of COVID-19 in adults, named Multisystem Inflammatory Syndrome in Adults (MIS-A) [2, [22] [23] . While the incidence of MIS-C/A remains low, the severity of the disease can be significant, with many patients requiring inotropic and ventilatory support [2] . 

A 21-year-old previously healthy African American male presented to the emergency department with intractable nausea and vomiting. He received his Pfizer-BioNtech vaccine on 05/11/2021, and developed fatigue, subjective fever, night sweats and myalgias the day after.

Within three days, he developed a non-pruritic confluent red macular rash on his hands bilaterally that spread to his arms, legs then to his torso. He also reported nausea, with nonbilious, non-bloody emesis, and diarrhea. He had poor appetite, and minimal oral intake, and was reportedly unable to keep anything down, so he was brought to the emergency room by his family seven days after the onset of symptoms.

In the emergency room, the patient was found to be hypotensive (95/56 mmHg) and tachycardic (139 bpm) and developed fever with temperature of 38 °C. The patient's laboratory findings were notable for leukocytosis (white blood cell count 35,000) with neutrophilia (absolute neutrophil count 30.92) and lymphopenia (lymphocyte count 0.99), and thrombocytopenia (platelet count 118,000). Multiple inflammatory markers were elevated including C-reactive protein (28 mg/dL), erythrocyte sedimentation rate (85 mm/h), D-dimer (2053 ng/mL) and lactate dehydrogenase (528 U/L). Blood cultures were drawn, and the patient was started on empiric antibiotics and fluid resuscitation for presumed sepsis.

An electrocardiogram (ECG) showed sinus tachycardia with ST segment elevation in anterior leads V2, V3 and reciprocal depressions in the inferior leads II, III, and aVF ( Figure 1 ).

Troponin I was elevated at 1.94, and BNP was elevated at 785. Given the patient's young age, and clinical presentation of viral prodrome, at this time it was suspected that the elevated troponins were attributable to demand ischemia, as opposed to coronary arterial disease. A J o u r n a l P r e -p r o o f bedside echocardiogram was performed revealing a reduced left ventricular (LV) ejection fraction at 35-40% as well as reduced right ventricular systolic function. Despite fluid resuscitation, the patient remained hemodynamically unstable and was transferred to the intensive care unit (ICU) for further management.

An expedited cardiac workup was completed within 24 hours of ICU admission with a cardiac MRI revealing severe biventricular systolic dysfunction with global hypokinesis (LV ejection fraction 11%, RV ejection fraction 12%) and normal ventricular size. Cardiac MRI did not show elevation of myocardial T2 signal or hyperenhancement to suggest myocardial edema, inflammation, or fibrosis ( Figure 2 ). Cardiac MRI was also significant for no evidence of myocardial infarction, and left heart catheterization revealed normal coronary arteries. Right heart catheterization was done with evidence of severe biventricular failure, with right atrial and right end diastolic pressure of 13 mmHg, pulmonary capillary wedge pressure of 25 mmHg, and cardiac index 1.6 L/min/m2. During the right heart catheterization procedure, the patient had an episode of sustained ventricular tachycardia, requiring termination with synchronized cardioversion. Given severe cardiac dysfunction and continued hemodynamic instability evidenced by sinus tachycardia and elevated lactate despite appropriate fluid resuscitation, the patient was initiated on VA-ECMO for management of cardiogenic shock.

After initiation of VA-ECMO, the patient continued to require blood pressure support with epinephrine and inotropic support with milrinone for several days. He was continued on J o u r n a l P r e -p r o o f broad spectrum antibiotics (meropenem 1g q8 hr and vancomycin 1.5g q12 hr) and started on methylprednisolone. Diagnostic workup was extensive for the patient's presentation including infectious, autoimmune, and toxicology studies (Table 1) . Stool PCR resulted positive for Campylobacter and serum studies resulted positive for Coxsackie A IgG. As there was concern for MIS-C/A, the patient was tested for COVID-19 with a PCR test twice, each time resulting negative. He was then tested for SARS-CoV-2 Nucleocapsid IgG which resulted positive.

While on ECMO, the patient required pulmonary arterial catheter guided diuresis with IV loop diuretics. The patient had multiple episodes of atrial fibrillation with rapid ventricular response that converted to normal sinus rhythm after a brief amiodarone infusion. An echocardiogram was performed six days after initiation of ECMO, which revealed a LVEF of 40% and a normal right ventricular function. ECMO decannulation was successfully performed three days later, and patient was weaned off all vasopressor medications. A cardiac MRI was performed the day after transferring out of the ICU, which showed further improvement in cardiac function with a LVEF of 60% with normal left ventricular size. As before, there was no evidence of myocarditis on repeat cardiac MRI. After seven days total, meropenem, vancomycin, and high dose steroids were discontinued. The patient was discharged home the next day with scheduled follow up with outpatient Cardiology.

Here, we present a case of cardiogenic shock temporally related to BNT162b2 vaccination in a patient with prior asymptomatic COVID-19 infection. Interestingly, the clinical syndrome on presentation for this patient resembles the presentation of MIS-C/A. The six criteria in the preliminary case definition for MIS-A include adult age (≥ 21 years), fever, laboratory J o u r n a l P r e -p r o o f markers of inflammation, shock/hypotension, severe cardiac illness, and lack of alternative diagnosis. The MIS-A criteria by the CDC is currently the only definition for MIS-A (Table 2) .

Our patient presented with fever, thrombocytopenia, diffuse rash, hypotension, severe cardiac illness, elevated C-reactive protein level and erythrocyte sedimentation rate, and positive COVID-19 serology meeting criteria for a MIS-A diagnosis ( Table 3) While the case we report here had clear evidence of cardiac dysfunction (LVEF 11% on CMRI) and injury (troponin 1.94), there was no evidence of myocardial edema on imaging, failing to meet a myocarditis diagnosis by Lake Louise consensus criteria (Table 4 ). In the reported cases of MIS-C and MIS-A, the role of myocardial enhancement varies-with one case series reporting myocardial edema on CMRI in only 50% of cases [25] . This again distinguishes our case from previous reports of vaccine associated myocarditis, as the clinical picture for our patient was closer to that of MIS-A.

Fortunately, our patient had recovery of cardiac function, with his LV ejection fraction returning to normal within ten days of presentation to the hospital. It appears that prompt initiation of VA-ECMO, and inotropic support, as well the anti-inflammatory effect of J o u r n a l P r e -p r o o f Journal Pre-proof corticosteroids, were key to this patient's recovery, as has been seen with MIS-C/A in the literature [2] [3] [4] .

Several limitations to this report merit comment. Since MIS-A is a clinical diagnosis based on a constellation of symptoms, rather than a specific diagnostic marker, we cannot definitively confirm the proposed diagnosis here. Additionally, without an endomyocardial biopsy, we were unable to definitively rule out myocarditis given the positive serology for Coxsackie A and Campylobacter [18] . It is important to note however, in comparison to Coxsackie B viral myocarditis-which contributes to nearly 25% cases of myocarditis yearly-Coxsackie A and Campylobacter are rarely reported to cause myocarditis [26, 27] . Furthermore, with lack of inflammatory myocardial findings in two cardiac MRIs days apart, it appears to be more likely that the patient had a diagnosis of MIS-A, and not multiple concomitant infections leading to myocarditis. Considering the clinical history, the short interval between the administration of vaccination and the presentation of cardiogenic shock, and the exclusion of other common causes, BNT162b2 vaccine-induced MIS-A is the proposed diagnosis in our patient.

As the global effort for COVID-19 vaccination continues, further surveillance will be needed as to whether MIS-C/A could be an adverse effect of mRNA-COVID-19 immunization. 

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Patient provided written informed consent. New-onset neurologic signs and symptoms Includes encephalopathy in a patient without prior cognitive impairment, seizures, meningeal signs, or peripheral neuropathy (including Guillain-Barré syndrome)

The presence of laboratory evidence of inflammation AND SARS-CoV-2 infection.

Elevated levels of at least TWO of the following: C-reactive protein, ferritin, IL-6, erythrocyte sedimentation rate, procalcitonin  A positive SARS-CoV-2 test for current or recent infection by RT-PCR, serology, or antigen detection 

In the setting of clinically suspected myocarditis, CMR findings are consistent with myocardial inflammation, if at least two of the following criteria are present: 1. Regional or global myocardial SI increase in T2-weighted images 2. Increased global myocardial early gadolinium enhancement ratio between myocardium and skeletal muscle in gadolinium-enhanced T1-weighted images 3. There is at least one focal lesion with non-ischemic regional distribution in IRprepared gadolinium-enhanced T1-weighted images ("late gadolinium enhancement") d A CMR study is consistent with myocyte injury and/or scar caused by myocardial inflammation, if -criterion 3 is present. A repeat CMR study between 1 and 2 weeks after the initial CMR study is recommended, if -none of the criteria are present, but the onset of symptoms has been very recent and there is strong clinical evidence for myocardial inflammation.

-one of the criteria is present. The presence of LV dysfunction or pericardial effusion provides additional, supportive evidence for myocarditis.

World Health Organization, World Health Organization, covid19.who

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