Postanginal septicemia, another term for Lemierre syndrome (LS), is a rare, life-threatening condition characterized by septic thrombophlebitis of the internal jugular vein (IJV), anaerobic sepsis, and metastatic infection secondary to oropharyngeal infection [1]. This condition is especially critical when combined with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection [2]. Herein, we describe the case of a 71-year-old man with COVID-19, throat swelling, and pharyngitis, which resulted in septic thrombophlebitis of the IJV and a pseudoaneurysm of the internal carotid artery (ICA). The therapeutic approach included continuous antibiotic administration, endovascular treatment of the pseudoaneurysm with stent grafting, and maxillofacial surgery to drain the cervical effusion.

The concomitant presence of LS, COVID-19, and a pseudoaneurysm of the ICA is a very rare combination of coexisting diseases that threaten the patient’s life and require active and immediate treatment by a multidisciplinary team.

The study is exempt from ethical approval. Patient consent was obtained for the publication of this paper.

A 71-year-old male patient was admitted to the emergency department of Nicosia General Hospital with fever, pharyngalgia, and odynophagia, accompanied by a gradual increase in right-sided neck swelling. At the same time, the patient tested positive for COVID-19. His medical history included chronic obstructive pulmonary disease, arterial hypertension, dyslipidemia, sleep apnea, heart failure, and obesity. The patient had undergone dental surgery for tooth extraction in the right maxillary area 10 days prior.

Contrast-enhanced computed tomography (CT) of the neck revealed an air-containing mass in the right sternocleidomastoid muscle in contact with the right IJV, indicating septic thrombophlebitis, and a saccular aneurysm of the right ICA without rupture (Fig. 1). Based on the symptoms, laboratory, and imaging findings, the suspicion of LS was almost inevitable.

Figure 1. Contrast-enhanced CT of the neck showed the increase in the diameter of the ICA pseudoaneurysm 6 hours after (orange arrows) the admission (red arrows) of the patient. (A) Sagittal image, (B) coronal image, (C) axial image. CT, computed tomography; ICA, internal carotid artery.

The patient was immediately administered intravenous antibiotics with tazobactam-piperacillin and vancomycin, and blood cultures were sent. Gradually, within a few hours, the patient’s condition worsened with an increase in neck swelling, and a new CT showed a greater peri-inflammatory reaction around the carotid artery and an increase in the diameter of the ICA pseudoaneurysm (Fig. 1). The patient was urgently treated with endovascular exclusion of the right ICA pseudoaneurysm, using a Gore Viabahn VBX Balloon Expandable Endoprosthesis (VBX 7-59), which was placed and deployed across the lesion (Fig. 2). Persistent neck swelling warranted an exploration by a maxillofacial surgeon; however, no abscess was drained from the area. Blood culture results indicated the presence of Staphylococcus aureus, and the patient was treated with piperacillin-tazobactam, vancomycin, and rifampicin. Subsequently, the patient developed hoarseness. According to the otolaryngologist’s assessment, swelling of the laryngeal muscles and hemiparesis of the left vocal cord were observed; therefore, the patient was treated with cortisone.

Figure 2. (A) DSA showed the ICA pseudoaneurysm. (B) The endovascular exclusion of the right ICA pseudoaneurysm with a Gore Viabahn VBX Balloon Expandable Endoprosthesis (VBX 7-59). DSA, digital subtraction angiography; ICA, internal carotid artery.

One month later, the patient underwent magnetic resonance imaging of the brain and neck, which showed a reduction in the mass around the carotid artery with a patent VBX stent graft. The patient was hospitalized for 1 month and was discharged with antibiotics and corticosteroids. At the 3- and 6-month follow-ups, his condition was stable and carotid Doppler ultrasonography showed patent VBX stent graft without stenosis in right carotid artery (Fig. 3). The patient was continuously administered oxygen for chronic obstructive pulmonary disease. He underwent regular laboratory check-ups with infectious disease specialists who regulated his antibiotic treatment with trimethoprim and sulfamethoxazole, which was continued due to the infected cervical area and the presence of the stent graft.

Figure 3. At a 6-month follow-up, the carotid Doppler ultrasound showed good stent graft patency without carotid stenosis. (A) Arterial flow of right ICA with a satisfactory level of peak systolic velocity. (B) Stent graft in the right ICA. ICA, internal carotid artery.

Lemierre syndrome (LS) was first described by Andre Lemierre in 1936, who identified Fusobacterium necrophorum (F. necrophorum) as the causative organism, leading to septic emboli in the lungs, bones, and brain [1]. It mostly affects young, healthy adolescents [1]. There is no universally accepted definition of LS. However, a Danish epidemiological study defined it as a septic case of F. necrophorum infection, confirmed by blood cultures, originating in the oropharynx and primary located in the head and neck, with potential extension to nearby and distant regions [3].

In the last century, the introduction of antibiotics has limited the outbreak and progression of LS to a point where it can be characterized as a forgotten disease. However, the presence of microorganisms such as Klebsiella pneumoniae, Bacteroides spp., Group B and C streptococci, Streptococcus oralis, Enterococcus spp., Proteus mirabilis, Eubacterium spp., and Eikenellacorrodens has allowed the disease to resurface in recent decades. Its incidence has increased in the last four years, with the appearance of the COVID-19 pandemic due to SARS-CoV-2 infection [1]. In our case, Staphylococcus aureus was the responsible microorganism, demonstrating that even rarer microbial strains can trigger LS.

The disease is sporadic, with a reported incidence of 0.6-2.3 per million [4], and carries a high mortality rate of 32%-90% without antibiotics, compared to 5%-18% with antibiotic treatment. IJV thrombosis is its main characteristic, whereas septic thrombophlebitis is associated with gram-negative septicemia, most commonly caused by F. necrophorum. Common signs and symptoms of septic thrombophlebitis of IJV include pain, induration, or swelling at the ipsilateral angle of mandible extending along the sternocleidomastoid muscle, together with high fever and trismus [2,3], as seen in our patient.

The origin of the primary infection is usually the head and neck, such as pharyngitis and sinusitis, with a high percentage of patients (up to 92%) being affected in the respiratory tract, including septic pulmonary embolism. Cavernous sinus thrombosis is considered a rare complication affecting the central nervous system through the metastatic spread of inflammation to nearby anatomical structures, which can cause severe ophthalmic symptoms, including loss of vision. Considering the vessels, the venous structures are more often affected, causing mainly IJV thrombosis and septic thrombophlebitis. Extension to the carotid artery is extremely rare and causes thrombosis, stenosis, and aneurysm formation [3].

The management of IJV thrombosis in patients with LS has evolved over the years. Currently, systemic antibiotic therapy is the primary treatment method, replacing common interventions such as ligation or resection of the IJV. However, these methods are still indicated in cases of uncontrolled sepsis or ongoing septic emboli despite the use of antibiotics [2].

Anticoagulation therapy is not routinely used in LS, but if extensive thrombosis exists and thrombosis progresses retrogradely to the cavernous sinus, anticoagulation therapy is recommended [5]. In our patient, the patient was required to take aspirin and clopidogrel for at least one month due to stent graft placement. The patient was hospitalized for more than a month, and was discharged on aspirin monotheray. The anticoagulant and antiplatelet treatments could be individualized according to each patient’s comorbidity.

Herein, we describe a patient who developed an ICA pseudoaneurysm in the setting of LS and COVID-19 infection. To our knowledge, this is the second reported case of a similar situation in the literature. Similarly, Chamseddin and Kirkwood [6] described a case of ICA thrombosis and a mycotic aneurysm of the external carotid artery in a healthy 18-year-old patient. Gupta et al. [7] described a case of bilateral mycotic aneurysms of the vertebral arteries, while Bordet et al. [8] reported a case of a mycotic pseudoaneurysm of the carotid bulb as a complication of LS.

The therapeutic approach includes conservative or surgical treatment with open or endovascular techniques such as ICA ligation, bypass graft, coil embolization, and stent grafting. Chamseddin and Kirkwood [6] performed an open ligation of the ECA. Benedetto et al. [9] treated the ICA pseudoaneurysm using vein graft bypass, while Bordet et al. [8] ligated ECA and IJV, and performed bypass using cryopreserved arterial allograft. Dai et al. [3] described and reported the first case of a rare combination of COVID-19, LS, and carotid aneurysm in an 18-year-old male who underwent ICA embolization and cervical ICA sacrifice.

Our patient underwent endovascular exclusion of an ICA pseudoaneurysm with stent graft placement. In the acute phase, where the pseudoaneurysm increases in diameter with severe edema of the inflamed cervical area, the endovascular approach seemed to be the best and fastest option relative to the open approach, even though we knew that the stent graft could become infected. The comorbidities of the patient and the presence of air in the cervical mass with deterioration of his clinical picture imposed the need for rapid repair of the pseudoaneurysm and avoidance of extensive surgical incisions in the cervix to prevent further complications and reduce the chances of the spread of inflammation. Therefore, the endovascular approach was decided according to all involved specialities - infectious disease specialists, vascular surgeons, and maxillofacial surgeons - to achieve the best result.

Undoubtedly, the COVID-19 pandemic has triggered a resurgence of LS, a disease many thought relegated to the past. In recent years, many cases of LS have been described, but only four have been associated with aneurysms in the carotid vessels, and only one of these patients simultaneously had a SARS-CoV-2 infection (Table 1) [3,6,8,9].

Table 1 . Reported cases of Lemierre syndrome combined with carotid aneurysm.

	Author	Age (y)/sex	Symptom	Microbe	Vascular involvement	COVID-19	Treatment
1	Dai et al. [3]	18/M	Fever, chills, headache, 6th nerve palsy, left-sided ophthalmoplegia, vision decline	Haemophilus influenzae, Fusobacterium necrophorum	Left-sided intracavernous mycotic aneurysm, and cavernous sinus thrombosis	Yes	Left ICA embolization and cervical ICA sacrifice
2	Chamseddin et al. [6]	18/F	Pseudomonas sepsis	Pseudomonas	ICA occlusion and ipsilateral ECA mycotic aneurysm	No	Open ligation of the ECA
3	Bordet et al. [8]	74/M	Fever, neck swelling, dysphonia	Fusobacterium necrophorum	IJV thrombophlebitis, right carotid bulb pseudoaneurysm	No	Cryopreserved arterial allograft bypass after ligation of the ECA and the IJV
4	Benedetto et al. [9]	75/M	Sore throat, odynophagia, left visions lost, fever, hypotension, dyspnea	Streptococcus	ICA pseudoaneurysm	No	Cormier carotid vein graft bypass
5	Christoforou et al.	71/M	Fever, pharyngalgia, odynophagia, gradual increase in right-sided neck swelling	MRSA	ICA pseudoaneurysm	Yes	Stenting right ICA

M, Male; F, Female; ICA, internal carotid artery; ECA, external carotid artery; IJV, internal jugular vein; MRSA, methicillin-resistant Staphylococcus aureus..

LS is a pathological entity that makes early diagnosis and treatment difficult, especially when complicated by COVID-19, as described here. This rare but serious disease can have an insidious onset, rapidly progressing into a life-threatening complication. Clinicians should be cautious and suspect LS when there are symptoms of pharyngitis that do not improve, accompanied by the development of systemic signs of infection. The situation is undoubtedly complicated when COVID-19 is present, which also causes systemic inflammatory manifestations masking life-threatening LS [10]. A multidisciplinary team was essential to achieving excellent clinical outcomes by combining antimicrobial therapy, pseudoaneurysm exclusion, abscess drainage, and risk factor modulation, which proved lifesaving for the patient described. This case report highlights the co-infection of LS and SARS-CoV-2, and also emphasizes the involvement of Staphylococcus aureus as an unusual pathogen in LS. This diagnosis requires a high index of suspicion, especially in the current era of COVID-19.

None.

The authors have nothing to disclose.

Concept and design: all authors. Analysis and interpretation: PC. Data collection: PC, CC, LH. Writing the article: PC. Critical revision of the article: PC, CC, LH. Final approval of the article: PC, CC, LH. Statistical analysis: none. Obtained funding: none. Overall responsibility: PC.