Fever-induced asymptomatic brugada syndrome in patient with COVID-19: a case report

M.A. Ansori1, R. Fadhilah1, H. Hernawan2, 1General Practitioner, Dinda General Hospital, Tangerang, Banten,

Indonesia; 2Cardiologist, Dinda General Hospital, Tangerang, Banten, Indonesia

INTRODUCTION

At the end of 2019 the world was shocked by a new model of pneumonia pandemic that started in Wuhan,
China, SARS Cov 2 Coronavirus (COVID-19). COVID-19 has a wide spectrum of symptoms, ranging from
asymptomatic, mild symptoms, pneumonia, to ARDS and not infrequently other manifestations outside the
respiratory system. Fever is one of the most common symptoms of COVID-19. Brugada syndrome is a familial
arrhythmic syndrome and is a disease that increases the risk of ventricular fibrillation and sudden death.
Brugada syndrome can be asymptomatic and can be triggered by various factors, one of which is fever.

CASE
A male patient, 42 years old, came to the ED with complaints of recurrent fever accompanied by chills and dry
cough and heavy breathing for 7 days before being admitted to the hospital. The patient also complains of
nausea and weakness. Chest pain and palpitations were denied. He denied history of hypertension and diabetes.
History of previous drug use was denied. The patient works in a car repair shop. The patient said that about 5
years ago he had come to the ER with complaints of palpitations but when examined by a doctor it was said to
be normal. Both the patient and his family denied any history of heart disease, fainting, or sudden death. On
examination in the ER, the patient's consciousness was compos mentis with GCS E4M6V5 blood pressure
130/80, HR 92x/minute, RR 23x/minute, temperature 38.6º C and oxygen saturation 96% with room air.
Physical examination only found minimal rales in both lungs. Laboratory results were within normal range as
follow.

Laboratory results
Parameters Value Reference
Hemoglobin (g/dL) 15.1 15-17.4
Total WBC (cell/µl) 7200 5,000-10,000
Platelets (x10 cell/µl)
3
167,000 150,000-450,000
Hematocrits (%) 45
Basophil count (%) 0 0-1
Eosinophil count (%) 0 1-4
Neutrophil count (%) 75 40-60
Lymphocyte count (%) 20 20-40
Monocyte count (%) 3 2-8
Erythrocyte count (million//µl) 5.0
ESR (mm/hour) 30
Random blood sugar (mg/dL) 92 <200
 Sodium level (mEq/L) 137 135-145
Chloride level (mEq/L) 3.7 3.5-5.5
Potassium level (mEq/L) 99 94-111

His chest X-ray revealed a thin heterogeneous infiltrate on the periphery of both lower lung fields and the
middle layer of the left lung.

Chest X-Ray at Admission

On ECG examination in the ER, ST elevation was found to be sharply dipped in leads V2 and V3 (Brugada type
1 pattern).

Brugada Type 1 ECG Pattern on Examination in the ER (Temperature 38.6 C)

The patient was diagnosed with fever on day 7 with suspected COVID-19 and Brugada Syndrome. The therapy
given was Ringer Lactate, ondansetron injection, ranitidine injection, levofloxacin injection, paracetamol, N-
acetylcysteine, and zinc.

On the third day of treatment, the patient had no complaints. The results of the COVID-19 diagnostic PCR swab
obtained a CT value of 31.34. Fever, shortness of breath, nausea, chest pain and palpitations were denied. The
patient's vital signs were 120/70, HR 96x/minute, RR 22x/minute, temperature 37.2ºC and oxygen saturation
97% with room air. The patient underwent a repeat ECG examination and a normal sinus rhythm was obtained.

ECG of Normal Sinus Rhythm on Day 3 of Treatment (Temperature 37.2 C)

DISCUSSION

 The Brugada pattern type 1, which is the diagnostic criterion for Brugada syndrome, is characterized by
a sharply dipping ST elevation of 2 mm in 1 of the right precordial leads (V1, V2, and V3), J-point
elevation, gradual descent of the ST segment ending in a negative T wave without evidence of
ischemia, electrolyte imbalance, or other structural heart disease.
 Patients with a Brugada type 1 pattern, both spontaneous and induced, have a 300-fold increased risk of
cardiac arrest compared with the general population.
 The prevalence of Brugada Syndrome is highest in Southeast Asia (3.7:1000), and the incidence in men
is 8 times more often than women.
 The occurrence of the Brugada type 1 pattern was 20 times more common in febrile patients than in
afebrile patients. Fever is also a predictor of cardiac arrest in 18% of symptomatic Brugada patients.
 As many as 38% of patients with fever-induced Brugada syndrome experience arrhythmias during
fever which include VT, VF, syncope, cardiac arrest and atrial arrhythmias.
 COVID-19 is the cause of fever in this case. The cytokine storm in COVID-19 infection can also
manifest as viral myocarditis causing ischemia or inflammation of the heart.
 In the cohort study by Misuzawa et al., there were differences in the number of cases of fever-induced
Brugada type 1 cardiac arrest depending on the clinical manifestations. In patients with a history of VF
it was 3.0%/year, in patients with a history of syncope it was 1.3%/year, and only 0.9%/year in
 asymptomatic patients. Thus, implantation of a defibrillator in patients with Brugada syndrome with
history of cardiac arrest, VF, or syncope may be beneficial.
 In this patient, a Brugada type 1 pattern was found with no other clinical signs or a history of
malignant arrhythmias, so implantation of a defibrillator was not required.

CONCLUSION
 Fever as a marker of the inflammatory response in COVID-19 may reveal Brugada type 1 patterns in
asymptomatic patients.
 With the high incidence of cardiac arrest caused by Brugada Syndrome, it is recommended that an
ECG be routinely performed in COVID-19 patients with fever, especially in Asian male patients.
 In COVID-19 patients with fever-induced Brugada Syndrome, antipyretic therapy should be
administered as quickly and as aggressively as possible.

REFERENCE

1. Manohar S, Dahal BR, Gitler B. Fever-induced Brugada syndrome. J Investig Med High Impact Case
Rep. 2015 Jan-Mar; 3(1): 2324709615577414.
2. Kawada S, Morita H, Antzelevitch C, Morimoto Y, Nakagawa K, Watanabe A. Shanghai score system
for diagnosis of Brugada syndrome. JACC Clin. Electrophysiol. 2018 Jun; 4(6): 724–30
3. Li Q, Guan X, Wu P, Wang X, Zhou L et al. (2020) Early transmission dynamics in Wuhan, China, of
novel coronavirus–infected pneumonia. N Engl J Med 382: 1199–1207.
4. Vidovich MI. Transient Brugada-like ECG pattern in a patient with Coronavirus Disease 2019
(COVID-19). JACC Case Rep. 2020 Jul 15; 2(9): 1245–1249.
5. Mizusawa Y, Morita H, Adler A, Havakuk O, Thollet A, Maury P, Wang DW, Hong K, Gandjbakhch
E, Sacher F, Hu D, Amin AS, Lahrouchi N, Tan HL, Antzelevitch C, Probst V, Viskin S, Wilde AA.
Prognostic significance of fever-induced Brugada syndrome. Heart Rhythm. 2016 Jul;13(7):1515-20.