key: cord-0951124-8pad9j4c
authors: Halil Özdemir, İbrahim; Özlek, Bülent; Burak Özen, Mehmet; Gündüz, Ramazan; Bayturan, Özgür
title: Type 1 Kounis syndrome induced by inactivated SARS-CoV-2 vaccine
date: 2021-05-07
journal: J Emerg Med
DOI: 10.1016/j.jemermed.2021.04.018
sha: 26a03e6ae2d457a999c63ff28cc2ab1496055dbb
doc_id: 951124
cord_uid: 8pad9j4c

BACKGROUND: : Vaccination is the most important way to out of the novel coronavirus disease (COVID-19). Vaccination practices have started in different countries for community immunity. In this process, health authorities in different countries have preferred different type of COVID-19 vaccines. Inactivated COVID-19 vaccine is one of these options and has been administered to more than 7 million people in Turkey. Inactivated vaccines are generally considered safe. Kounis syndrome (KS) is a rare clinical condition which defined as the co-existence of acute coronary syndromes and allergic reactions. CASE REPORT: : We present the case of a 41-year-old female who with no cardiovascular risk factors admitted at our emergency department with flushing, palpitation, dyspnea and chest pain 15 minutes after the first dose of inactivated coronavirus vaccine (CoronaVac). Electrocardiogram (ECG) showed V4-6 T wave inversion, and echocardiography revealed left ventricular wall motion abnormalities. Troponin-I level on arrival was elevated. Coronary angiography showed no sign of coronary atherosclerosis. She was diagnosed with type 1 KS. The patient's symptoms resolved and she discharged from hospital in a good condition. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS? : To the best of our knowledge, this is the first case of allergic myocardial infarction secondary to inactivated coronavirus vaccine. This case demonstrates that KS may occur after inactivated virus vaccine against COVID-19. Although the risk of severe allergic reaction after CoronaVac administration seems to be very low, persons who developed chest pain after vaccine administration should be followed by ECG and troponin measurements.

Vaccines appear to be the greatest hope to eradicate Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection which caused novel coronavirus disease (COVID- 19) pandemic. Nowadays, different COVID-19 vaccines are being to used for immunity around the world. Some of these are inactive-attenuated virus vaccines, protein subunit-based vaccines, non-replicating viral vector vaccines, and DNA-based or RNA-based vaccines [1] .

RNA-based COVID-19 vaccines (such as Pfizer-BioNTech, Moderna, Oxford-AstraZeneca) are administered in European Union countries and United States. So far, approximately 7.7 million people have been vaccinated with inactivated coronavirus vaccine (CoronaVac) in Turkey [2] . Based on the available data, although there are important differences in effectiveness rates, no major safety concern was reported for these vaccines [3] [4] [5] [6] .

Kounis syndrome (KS) is defined as the co-incidental occurrence of acute coronary events and hypersensitivity reactions caused by vasospastic mediators following an allergic reaction [7] . This syndrome has been associated with several diseases, a variety of drugs or environmental exposures [8] . Although vaccine ingredients may be considered potential inducers of allergic events [9] , KS induced by vaccines is a very rare clinical condition. Only few cases of allergic myocardial infarction due to tetanus and influenza vaccines have been previously reported [10, 11] . However, KS precipitated by inactivated coronavirus vaccine has not been reported before. In this report, we describe a 41-year-old woman who developed type 1 KS induced by the first dose of inactivated coronavirus vaccine. With this case presentation, we aimed to keep in mind that KS may occur after inactivated virus vaccine against COVID-19.

A 41-year-old female who with no cardiovascular risk factors or any chronic disease admitted at Manisa City Hospital Emergency Department (ED) with flushing, palpitation, lip and tongue swelling, shortness of breath and chest pain 15 minutes after the first dose of inactivated coronavirus vaccine (CoronaVac, Sinovac Life Sciences, Beijing, China). The patient denied any history of asthma or allergic reaction. The patient also stated that she did not have any cardiac or non-cardiac complaints or history before vaccination. Upon ED arrival, physical examination demonstrated the following vital signs: respiratory rate 22 breaths/min, heart rate 108 beats/min, temperature 36.1 °C, pulse oximetry 96% on room air, and blood pressure 110/75 mmHg. Cardiac examination showed regular rate with normal S1 and S2 without murmurs, rubs, or gallops. She had bronchospasm findings in lung auscultation. She had erythematous appearance in face and there was an edema in her lips and uvula. She reported typical chest pain. On admission, her electrocardiogram (ECG) showed poor R wave progression in precordial leads, V4-6 T wave inversion, and fragmented QRS in aVL (Figure 1 ). Transthoracic echocardiography (TTE) performed in the ED showed posterior and apicolateral wall hypokinesia with a left ventricular ejection fraction (LVEF) of 55% (Figure 2) . Troponin-I estimated on arrival was 0.068 ng/mL (reference: <0.023 ng/mL), creatine kinase-MB fraction was 5.01 ng/mL (reference: <4.88 ng/mL). Complete blood count was consistent with eosinophilia (620 µl, reference range <400 µl). Blood glucose, urea, creatinine, alanine aminotransferase, aspartate aminotransferase, electrolyte parameters, C-reactive protein, procalcitonin, and hemoglobin levels were within normal ranges. N-terminal pro-brain natriuretic peptid (NT-proBNP) was 323 pg/mL (reference range <125 pg/mL). Intravenous pheniramine maleate 4.5 mg, dexamethasone 8 mg, oxygen treatment, continuous salbutamol by nebulizer and epinephrine 0.5 mg intramuscular were administered in ED. Coronary angiography (CAG) was performed to exclude coronary artery disease, and showed no sign of coronary atherosclerosis ( Figure 3A-B) . However, ventriculography revealed apical and apicolateral wall hypokinesia ( Figure 3C-D) . Troponin-I estimated 6 hours after admission was 0.034 ng/mL and decreased to 0.025 ng/mL on the next day. The patient was diagnosed to have KS type I variant, secondary to the first dose of inactivated coronavirus vaccine. She was treated with aspirin, oral antihistamines, diltiazem and corticosteroid for 4 days. Two days later, the repeated cardiac markers were within normal limits, with resolution of electrocardiographic abnormalities and echocardiographic changes with a LVEF of 65%. The patient was discharged from hospital in a good condition, and after 7 days, at a follow-up visit, she was doing well.

To the best of our knowledge, this is the first case of allergic myocardial infarction secondary to inactivated coronavirus vaccine. KS was defined by Kounis and Zafras in 1991 [7] . KS is defined as the co-existence of acute coronary syndromes, including coronary spasm, and allergic reactions associated with mast cell and platelet activation. This syndrome is caused by inflammatory mediators such as histamine, platelet activating factor, arachidonic acid products, and various cytokines and chemokines released during the allergic activation process [12] . It is also defined as allergic angina due to development after an allergic reaction.

Various allergens such as foods, environmental exposures and drugs have been described in the literature that may cause this syndrome [13] [14] [15] . Three variants of the syndrome have been identified (Table-1 ) [16] [17] [18] . The type 1 variant includes patients with normal coronary arteries without predisposing factors for coronary artery disease. The release of inflammatory mediators may cause an increase in cardiac enzymes due to coronary artery spasm progressing to acute myocardial infarction. Type 2 is defined as the presence of coronary spasm due to inflammatory mediators together with the erosion or rupture of the pre-existing atherosclerotic plaque. Normal cardiac enzymes and troponin are observed in Type 2. Type III includes patients with coronary stent thrombosis as a result of an allergic reaction [17, 18] . In patients with allergic myocardial infarction, ECG may be normal or some nonspecific ST-T wave changes, ST segment elevation, ST segment depression may be seen. Cardiac biomarkers, complete blood count, D-dimer, NT-proBNP, serum tryptase and eosinophil levels could be helpful to identify this syndrome. TTE may also show regional wall motion abnormalities in the distribution of the affected artery, which usually resolve in a few days or weeks without any complication after the acute phase of the disease. CAG is usually needed for patients with suspected KS to assess the coronary anatomy and to make a differential diagnosis [18] . The type 1 variant has a better prognosis [19] . The therapeutic management of KS is a procedure that requires treating both cardiac and allergic symptoms at the same time. In patients with type I variant, treatment of the allergic event can relieve symptoms. Corticosteroids and antihistamines are recommended to be used for the treatment of allergic reactions.

Vasodilators such as calcium channel blockers may treat hypersensitivity induced vasospasm [19] . In type 2 and 3 variants, the acute coronary syndrome protocol should be applied [18] .

Vaccines represent the most powerful weapons against viral epidemic diseases.

However, as with any medication, allergic events may occur during vaccination. Fortunately, allergic events triggered by the vaccine are neither serious nor frequent. Nevertheless, it is important to report major adverse events such as allergic myocardial infarction, even though it is very rare. All COVID-19 vaccines currently in use are generally considered safe [3] [4] [5] [6] .

Since these vaccines have just started to be administered, they are closely monitored for possible serious adverse events. In a recently published paper [20] , it has been showed that the risk of serious allergic reaction or anaphylaxis of the RNA-based COVID-19 vaccine is very low. According to this report, 1,893,360 first doses of Pfizer-BioNTech COVID-19 vaccine had been administered in the United States. Among these, anaphylaxis occurred in 21 cases, including 17 in patients with a documented history of allergic events, seven of whom had a history of anaphylaxis. On the other hand, no allergic myocardial infarction was reported in this analysis [20] . CoronaVac is an inactivated SARS-CoV-2 vaccine. The phase-1 and 2 results of the CoronaVac have been published [21] , but the phase-3 results have not yet been presented. Pain at the injection site has been reported as the most common adverse reaction in phase-1 and 2 study. Only one case of acute hypersensitivity with manifestation of urticaria 48 hours after the first dose was reported in phase-1 study. No serious adverse reaction or allergic myocardial infarction was reported in the phase-2 study [21] . With the publication of phase-3 results, we will understand more clearly the safety profile of this vaccine in a real-life practice.

Since inactivated vaccines have been used to prevent different infectious diseases for many years, their safety profile is generally known to be good. According to the data in current literature, the risk of serious allergic reaction after CoronaVac administration seems to be very low. However, this case shows that type 1 KS is among these rare serious adverse events.

Physicians should be aware that KS induced by inactivated coronavirus vaccine is a rare but important reaction. Persons who developed post-vaccination chest pain or serious allergic reaction should be followed by ECG, echocardiography, troponin measurements and should be observed for a sufficient period of time or hospitalized if necessary. 

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Informed consent: The patient has given informed consent to the publication of this case report.