Allergic Angina with QTc Prolongation and Wellens Type-A Syndrome Post-ceftriaxone Parallel to COVID-pneumonia-A New Causation and Treatment

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CASE REPORT
Allergic Angina with QTc Prolongation and Wellens Type-A Syndrome
Post-ceftriaxone Parallel to COVID-pneumonia-A New Causation and Treatment
Yasser Mohammed Hassanain Elsayed
Critical Care Unit, Kafr El-Bateekh Central Hospital, Egyptian Ministry of Health, Kafr Al Battikh, Egypt
Received: 19 April 2025; Revised: 01-05-2025; Accepted: 03-06-2025
ABSTRACT
Rationale: Antibiotics may cause serious adverse effects. Allergic acute coronary syndrome (ACS) or
Kounis Zafras (KZ) syndrome is a newly described syndrome relevant to allergen exposure. Coronavirus
disease 2019 (COVID-19) infection may have lethal cardiovascular and respiratory complications. Wellens
syndrome is particular for critical stenosis of the left anterior descending artery. However, there is a strong
relationship between coronary artery disease and COVID-19 infection. Patient Concerns: A 28-year-old
married homemaker Egyptian female patient was admitted to the intensive care unit with angina, QTc
prolongation, and Wellens type-A syndrome after ceftriaxone injection post-COVID-pneumonia.
Diagnosis: Allergic angina with QTc prolongation and Wellens type-A syndrome post-ceftriaxone
Parallel to COVID-pneumonia. Interventions: Oxygenation, arterial blood gas, electrocardiography,
and echocardiography. Outcomes: Gradual dramatic clinical, and electrocardiographic improvement
had occurred. Lessons: Ceftriaxone-inducing allergic ACS or KZ syndrome with QTc prolongation and
Wellens type-A syndrome post-COVID-pneumonia is a distinctive new adverse effect. The widespread
non-ST-segment elevation myocardial infarction with ST-segment elevation in aVR lead and T-wave
inversion in anterolateral leads or Wellens syndrome type A may be interpreted as accompanied
by multi-vessels disease. An associated COVID-19 infection may be an exacerbated factor for the
ceftriaxone-inducing allergic ACS.
Keywords: Allergic coronary syndrome, ceftriaxone, coronary artery disease, coronavirus, coronavirus
disease 2019, Kounis Zafras syndrome, long QT syndrome, pneumonia, QT/QTc interval
INTRODUCTION
Allergic acute coronary syndrome (ACS) or
Kounis Zafras (KZ) syndrome is hallmarked as
the co-association of an ACS with hypersensitivity
reactions following an allergenic exposure.[1]
KS
wasinitiallyidentifiedbyKounisandZavrasin1991
as an “allergic angina syndrome”, “allergic angina”
or “allergic myocardial infarction”.[1,2]
There is
ACS-associated mast cell activation from allergic,
hypersensitivity, or anaphylactoid reactions.[2]
The
essential pathogenesis of KS is the inflammatory
*Corresponding Author:
Yasser Mohammed Hassanain Elsayed,
E-mail: dryaser24@yahoo.com
cytokines mediators released through mast cell
activation during a hypersensitivity reaction
triggered by food, insect bites, or drugs. There is
a subsequent coronary artery spasm (CAS) with
possible atheromatous plaque erosion or rupture.[2]
The allergic angina commonly starts within 1 h
of exposure to the offending allergen. Longer
onset ACS also have been reported.[3]
Variant
presentations of KS have been reported.[2]
Three
different variants of KS have been described:
Type I occurs in structurally normal coronary
arteries with no cardiovascular risk factors. The
coronary spasm was suggested. With or with no
associated acute myocardial infarction (AMI).
Type II KS occurs in patients with pre-existing
ischemic heart disease, in whom the acute release
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Elsayed: Allergic angina with QTc prolongation and wellens type-a syndrome post-ceftriaxone parallel to COVID-
pneumonia-A new causation and treatment
IJPBA/Apr-Jun-2025/Vol 16/Issue 2 2
of inflammatory mediators induces CAS that may
lead to plaque rupture and myocardial infarction.
Type III KS occurs in patients with coronary artery
stent-associated thrombosis.[1,3-5]
Ceftriaxone is a
third-generation semisynthetic cephalosporin that
has a long half-life.[6]
It was approved for use in
the US in 1984.[7]
It is administered intravenously
or intramuscularly and has a broad spectrum
of activity against Gram-positive and Gram-
negative aerobic, and some anaerobic, bacteria.
Ceftriaxone has generally been well tolerated by
adults and children following intravenous (IV)
and intramuscular injection. The commonest
adverse effects were diarrhea, rash, and reactions
at the injection site such as phlebitis and pain on
intramuscular injection.[6]
Ceftriaxone’s adverse
effects are usually well-tolerated. It includes
diarrhea, nausea, abdominal pain, dyspepsia,
headache, rash, and rarely; clostridium difficile-
associated diarrhea, hypersensitivity, angioedema,
anaphylaxis, and Stevens–Johnson syndrome/
toxic epidermal necrolysis.[7]
The QT-interval is
an electrocardiography (ECG) phase measured in
milliseconds (ms) from the beginning of the QRS
complex until the end of the T-wave. It represents
the ventricular depolarization followed by the
ventricular repolarization. It is used as a hallmark
for a prolongation of the ventricular repolarization
time. A prolonged QTc-interval is considered
if higher than 450 ms in adult males and higher
than 470 ms in adult females.[8]
QT prolongation
is an imperfect biomarker for proarrhythmic
risk.[9]
A prolonged QTc interval can lead to
ventricular arrhythmias (torsades de pointes) and
sudden cardiac death (SCD).[8]
For the risk of
SCD, “borderline QTc” in males is 431–450 ms;
and, in females, 451–470 ms. An “abnormal”
QTc in males is a QTc above 450 ms; and, in
females, above 470 ms.[10]
All patients with
long QT syndrome (LQTS) should avoid drugs
that prolong the QT interval or that reduce their
serum potassium or magnesium levels.[11]
Beta-
blockers are the drugs of choice for patients with
LQTS.[12,13]
An inverted T-wave is described as
a T-wave 1 mm below the isoelectric line in
two or more adjacent leads. However, a biphasic
T-wave is defined as an inverted T-wave if the
T-wave is 1 mm below the isoelectric line in the
terminal part of the T-wave.[14]
There are two main
causes of biphasic T waves: Myocardial ischemia
and hypokalemia. The two waves go in opposite
directions. Biphasic T-wave due to ischemia goes
up and then down.[15]
Wellens syndrome is a pattern
of inverted or biphasic T-wave in V2-3 (in patients
presenting with/following ischemic-sounding chest
pain) that is highly specific for critical stenosis
of the left anterior descending artery. There are
two patterns of T-wave abnormality in Wellens
syndrome: (1) Type A is a biphasic T-wave with
the initial deflection positive and the terminal
deflection negative (25% of cases). (2) Type B is
a T-wave that is deeply and symmetrically inverted
(75% of cases).[15]
The systemic inflammatory
response in severe coronavirus disease 2019
(COVID-19) is the output of raised levels of
cytokines causing cytokine-release syndrome that
can destroy multiple tissues, including vascular
endothelium and cardiac myocytes. Plaque
rupture AMI due to the systemic inflammation
and catecholamine surge in this disease. Coronary
thrombosis also has been recognized as a cause of
AMI in COVID-19 patients.[16,17]
CASE PRESENTATION
A 28-year-old married homemaker Egyptian
female patient was referred to the intensive care
unit (ICU) with angina and palpitations. Dizziness,
circumorally numbness, extremities paresthesia,
fatigue, loss of appetite, loss of smell, and
generalized body aches were associated symptoms.
She gave a recent history of IV injection of 2 g
ceftriaxone for a recent chest infection 2 h ago.
She gave a history of fever 4 days ago. Currently,
she has a history of contact with his relative who
confirmed a COVID-19 patient in the past 11 days.
Upon general physical examination; generally,
the patient was tachypneic, and distressed, with
a regular pulse rate (ventricular rate [VR] of 70),
blood pressure of 120/70 mmHg, respiratory rate
of 20 bpm, a temperature of 37.5°C, pulse oximeter
of oxygen (O2) saturation of 95%, and Glasgow
coma scale of 15/15. Tests for provocative latent
tetany were positive. No more relevant clinical
data were noted during the clinical examination.

The patient was admitted to ICU with ceftriaxone-
inducing angina. Initially, the patient was treated
with O2
inhalation by O2
inhalation central system
(100%, by simple mask, 5L/min). The patient was
maintained and treated with aspirin; 4 oral tablets
(75 mg, then OD), clopidogrel; 4 oral tablets
(75 mg, then OD), diltiazem tablets (60 mg, OD),
enoxaparin SC (60 mg, BID), oral nitroglycerine
capsule (2.5 mg, BID), and atorvastatin (20 mg,
OD). Hydrocortisone sodium succinate (100 mg
IV BID), azithromycin tablets (500 mg, OD),
oseltamivir capsules (75 mg, BID only for 5 days),
and paracetamol (500 mg IV every 8 h as needed)
were added. The patient was hourly monitored
for vital signs and O2 saturation. The initial ECG
was done on the initial ECG on presentation in the
point-of-care (POC) showing normal sinus rhythm
(NSR) (VR of 72) with ST-segment depression in
high lateral leads, anterolateral leads, and inferior
leads. There is ST-segment elevation in aVR lead
[Figure 1a]. The second ECG tracing was taken
on the initial ECG on presentation within 30 min
after ICU admission showing NSR with ST-
segment depression in lead I, anterolateral leads,
and inferior leads. There is ST-segment elevation
in aVR lead [Figure 1b]. The initial complete
blood count (CBC); hemoglobin was 11.7 g/dL,
RBCs; 4.38 × 103
/mm3
, white blood cells; 18.9 ×
103
/mm3
(neutrophils; 88.4%, lymphocytes: 9.8%,
monocytes; 1.1%, eosinophils; 0.7% and basophils
0%), platelets; 481 × 103
/mm3
. arterial blood
gas was (PH; 7.469 mmHg, PCO2
; 23.4 mmHg,
HCO3
; 16.6 mmHg, SO2
; 99.4%, and PaO2
;
217.2 mmHg). C-reactive protein was (12 mg/L).
Serum glutamic-pyruvic transaminase was (57 U/L)
and serum glutamic-oxaloacetic transaminase was
(30 U/L). Serum albumen was (4.8 mg/dL). Serum
creatinine was (0.7 mg/dL). Random blood sugar
was (127 mg/dL). Total calcium was (8.11 mg/d).
Ionized calcium was (3.81 mg/d). The troponin
I test was (9.62 U/L). The Creatine Kinase-MB
was (37 U/L). Echocardiography was done on the
4th
day of the presentation showing a mild thickened
tip of anterior mitral valve leaflet prolapse and
mild mitral regurgitation with an eccentric jet of
an ejection fraction of 62% [Figure 2]. Serial ECG
tracings were done. The third ECG tracing was
taken within 7 h of the ICU management showing
NSR (VR of 74) with ST-segment depression in
lead II and anterolateral leads. There is a T-wave
inversion in anterior leads and QTc prolongation
of 471 ms [Figure 3a]. The fourth ECG tracing was
taken within 3 days after ICU discharge showing
NSR with normalization of the above ST-segment
depression and QTc prolongation. There is a Wavy
triplesign(Yasser’ssign)intheV2lead[Figure 3b].
Allergic angina with QTc prolongation and
Wellens type-A syndrome post-ceftriaxone parallel
Figure 1: Serial ECG tracings; (a) tracing was done on the initial electrocardiography (ECG) on presentation in the point-
of-care showing normal sinus rhythm (NSR) (ventricular rate [VR] of 72) with ST-segment depression in high lateral leads
(I and aVL; green arrows) anterolateral leads (V3-6; golden arrows) and inferior leads (II, III, and aVF; red arrows). There
is ST-segment elevation in aVR lead (lime arrow). (b) Tracing was done on the initial ECG on presentation within 30 min
after intensive care unit admission showing NSR (VR of 62) with ST-segment depression in lead I (green arrow) anterolateral
leads (V3-6; golden arrows), and inferior leads (II, III, and aVF; red arrows). There is ST-segment elevation in aVR lead
(lime arrow)
b
a

to COVID-pneumonia was the most probable
diagnosis. Within 3 days of the above management,
the patient finally showed nearly complete clinical
and ECG improvement. The patient was continued
on aspirin tablets (75 mg, OD), diltiazem tablets
(60 mg, OD), oral nitroglycerine capsules (2.5 mg,
BID), oral calcium, and Vitamin-D preparations
for 30 days with further recommended cardiac and
immunological follow-up.
DISCUSSION
Overview
• A young married female patient was referred
to the critical care unit with angina, QTc
prolongation, and Wellens type-A syndrome
post-ceftriaxone parallel to COVID-19
pneumonia
• The primary objective for my case study was
the presence of a young married female patient
who was referred to the critical care unit with
angina, with QTc prolongation and Wellens
type-A syndrome post-ceftriaxone parallel to
COVID-19 pneumonia in ICU.
The secondary objective for my case study was the
question of; how did you manage the case?
• There was a history of direct contact with a
confirmed COVID-19 case
• The presence of direct contact with a confirmed
COVID-19 case, clinical manifestations (fever,
generalized body aches, loss of appetite, and
loss of smell), and CBC evidence (leukocytosis,
lymphopenia, and neutrophilia) of suspected
COVID-pneumonia on top of acute tachypnea
will strengthen the COVID-19 diagnosis
• There are initial high lateral leads, anterolateral
leads, and inferior leads ST-segment depression
Figure 2: (a-c) Echocardiography was done on the 4th
day of the presentation showing a mild thickened tip of anterior
mitral valve leaflet prolapse (light blue arrows) and mild mitral regurgitation with eccentric jet (yellow arrow) of an ejection
fraction of 62% (lime arrow)
c
b
a
Figure 3: Serial electrocardiography tracings; (a) Tracing was done within 7 h of the intensive care unit (ICU) management
showing normal sinus rhythm (NSR) (ventricular rate [VR] of 74) with ST-segment depression in anterolateral leads
(V3-6; golden arrows) and lead II (red arrow). There is a T-wave inversion in anterior leads (V1-6; golden arrows) and QTc
prolongation of 471 ms (purple rectangle). (b) Tracing was done within 3 days after ICU discharge showing NSR (VR of 71)
with normalization of the above ST-segment depression and QTc prolongation. There is a Wavy triple sign (Yasser’s sign) in
V2 lead (red, dark blue, and green arrow)
b
a

with elevated troponin I and subsequent
T-wave inversion. This indicates the presence
of extensive non-ST-segment elevation
myocardial infarction (non-STEMI)
• QTc of 471 ms indicates the presence of LQTS
• There is ST-segment elevation in aVR lead.
This has a different prognostic value
• The presence of extensive Non-STEMI with
ST-segment elevation in aVR lead and T-wave
inversion in anterolateral leads
• An existence of biphasic T-wave with the initial
deflection positive and the terminal deflection
negative is a hallmark ofWellens syndrome type A
• The presence of extensive non-STEMI
with ST-segment elevation in aVR lead and
T-wave inversion in anterolateral leads or
Wellens syndrome type A may be interpreted
as accompanied by severe specific ischemic
myocardial insult
• Normalization of the above ST-segment
depression may be evidence of CAS
• The later disappearance of the above ECG
changes after management strengthens the role
of included treatment
• The dramatic reversal of ST-segment
depressions in ECG may be interpreted as a
CAS
• Occurrence of angina after injection of
ceftriaxone indicates its possible causation.
Naranjo’s probability scale in the current case
study was +11. This means that there was a
definite relationship between these adverse
drug effects and ceftriaxone injection [Table 1].
KZ syndrome probably will be implicated in
pathogenesis.
• I can’t compare the current case with similar
conditions. There are no similar or known
cases with the same management for near
comparison
• The only limitation of the current study was the
unavailability of coronary angiography.
CONCLUSION AND
RECOMMENDATIONS
• Ceftriaxone-inducing allergic ACS or KZ
syndrome with QTc prolongation and Wellens
type-A syndrome post-COVID-pneumonia is a
distinctive new adverse effect
• The widespread non-STEMI with ST-segment
elevation in aVR lead and T-wave inversion in
anterolateral leads or Wellens syndrome type A
may be interpreted as accompanied by multi-
vessels disease.
• An associated COVID-19 infection may be an
exacerbated factor for the ceftriaxone-inducing
allergic ACS.
CONFLICT OF INTEREST
There are no conflicts of interest.
ACKNOWLEDGMENT
I wish to thank my wife for saving time and
improving the conditions for helping me.
REFERENCES
1. Fassio F, Losappio L, Antolin-Amerigo D, Peveri S,
Pala G, Preziosi D, et al. Kounis syndrome: A concise
Table 1: Naranjo algorithm‑adverse drug reaction
probability scale in the case report
Question Yes No Do not
know
Score
1.
Are there previous conclusive
reports on this reaction?
+1 0 0 +1
2.
Did the adverse event appear after the
suspected drug was administered?
+2 −1 0 +2
3.
Did the adverse event improve
when the drug was discontinued or a
specific antagonist was administered?
+1 0 0 +1
4.
Did the adverse event reappear when
the drug was readministered?
+2 −1 0 +2
5.
Are there alternative causes that could
on their own have caused the reaction?
−1 +2 0 +2
6.
Did the reaction reappear when a
placebo was given?
−1 +1 0 0
7.
Was the drug detected in blood or
other fluids in concentrations known
to be toxic?
+1 0 0 0
8.
Was the reaction more severe when
the dose was increased or less severe
when the dose was decreased?
+1 0 0 +1
9.
Did the patient have a similar
reaction to the same or similar drugs
in any previous exposure?
+1 0 0 +1
10.
Was the adverse event confirmed
by any objective evidence?
+1 0 0 +1
Total score: +11

review with focus on management. Eur J Intern Med
2016;30:7-10.
2. Memon S, Chhabra L, Masrur S, Parker MW. Allergic
acute coronary syndrome (Kounis syndrome). Proc
(Bayl Univ Med Cent) 2015;28:358-62.
3. Abdelghany M, Subedi R, Shah S, Kozman H. Kounis
syndrome: A review article on epidemiology, diagnostic
findings, management and complications of allergic
acute coronary syndrome. Int J Cardiol 2017;232:1-4.
4. Kounis NG. Kounis syndrome: An update on
epidemiology, pathogenesis, diagnosis and therapeutic
management. Clin Chem Lab Med 2016;54:1545-59.
5. Hermans M, Van Lennep JR, Van Daele P, Bot I. Mast
cells in cardiovascular disease: From bench to bedside.
Int J Mol Sci 2019;20:3395.
6. Richards DM, Heel RC, Brogden RN, Speight TM,
Avery GS. Ceftriaxone. A review of its antibacterial
activity, pharmacological properties and therapeutic use.
Drugs 1984;27:469-527.
7. Bethesda. LiverTox: Clinical and Research Information
on Drug-Induced Liver Injury. National Institute of
Diabetes and Digestive and Kidney Diseases; 2012.
Available from: https://www.ncbi.nlm.nih.gov/books/
nbk548258/[Last accessed on 2021 Dec 20].
8. Vandael E, Foulon V. Drug-induced QTc-prolongation:
Risk management in a community pharmacy. J Malta
College Pharm Pract 2017;23:7-12.
9. Giorgi MA, Bolaños R, Gonzalez CD, Di Girolamo G.
QT interval prolongation: Preclinical and clinical testing
arrhythmogenesis in drugs and regulatory implications.
Curr Drug Saf 2010;5:54-7.
10. Medscape CRM News. QTc Prolongation and Risk
of Sudden Cardiac Death: Is the Debate Over?
Medscape. Available from: https://www.medscape.com/
viewarticle/522879 [Last accessed on 2006 Feb 03].
11. Heemskerk CP, Pereboom M, Van Stralen K, Berger FA,
Van Den Bemt PM, Kuijper AF, et al. Risk factors
for QTc interval prolongation. Eur J Clin Pharmacol
2018;74:183-91.
12. Duncan G, Firth K, George V, Hoang MD, Staniforth A,
Smith G, et al. Drug-mediated shortening of action
potentials in LQTS2 human induced pluripotent
stem cell-derived cardiomyocytes. Stem Cells Dev
2017;26:1695-705.
13. Hassanain Elsayed YM. The dramatic reversal of acute
pulmonary embolism-induced corrected Qt-interval
prolongation with bisoprolol; a case report. J Clin Case
Rep Stud 2020;1:1-5.
14. Ranjbar A, Sohrabi B, Sadat-Ebrahimi SR, Ghaffari S,
Kazemi B, Aslanabadi N, et al. The association
between T wave inversion in leads with ST-elevation and
patency of the infarct-related artery. BMC Cardiovasc
Disord 2021;21:27.
15. Burns ED, Buttner RT. Wave.Available from: https://litfl.
com/t-wave-ecg-library [Last accessed on 2021 Mar 11].
16. Elsayed YM. Covid-19 inducing acute myocardial
infarction with mitral regurgitation and pneumonia;
the risks and poor outcome: Acase report in cardiology,
infectious diseases, and critical care medicine. J Anest
Inten Care 2021;2:56-9.
17. Elsayed YM. Acute myocardial infarction with
transient LBBB, AF with pre-excitation, high lateral
coronary spasm, and wavy triple sign (Yasser’s sign)
post-COVID-19 pneumonia in a senile female patient;
complex dilemma and management. J Med Clin Stud
2023;6:198.

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