Supraclavicular Lymphadenitis Following COVID-19

Cervical lymphadenopathy in is a common in Many cases of cervical lymphadenopathy after the vaccine were reported. there is yet reporting a case of supraclavicular cervical lymphadenopathy as a result of COVID-19. A 12-years-old girl presented with fever, cough, fatigue, anosmia, and ageusia. COVID-19 was conrmed by real-time PCR. The symptoms were resolved within 10 days. After 7 days, she complained of supraclavicular swelling. Physical examination revealed painless, multiple, and mobile supraclavicular lymph nodes. Ultrasound and ne-needle aspiration cytology were suspicious. Therefore, an excisional biopsy of the largest node was performed. The specimen was sent for histopathology and immunohistochemistry evaluation which conrmed the benign nature of the lymph node. To

The neck is the joining part between the head and body. There are various causes of neck masses, these are broadly divided into three groups congenital or developmental, in ammatory (infectious or noninfectious), and tumors [(benign or malignant (primary or secondary)].
Many viruses, particularly in the pediatric population, may cause cervical lymphadenopathies like adenovirus, Epstein bar virus, herpes virus, coxsackievirus, and cytomegalovirus. Moreover, cervical lymphadenopathy following COVID-19 vaccines was reported [4] [5]. Distinguin et al. reported three COVID-19 patients with cervical lymphadenopathy in level II (upper jugular group) [6]. However, there is no reported case of supraclavicular cervical lymphadenopathy as a result of COVID-19. We reported the rst case of supraclavicular lymph node enlargement in a 12-years-old girl following the COVID-19 disease.

Case Presentation
A 12-years-old female presented with a neck mass in the right supraclavicular area of one-month duration. The patient had a history of contact with her infected grandmother with COVID-19. She complained of fever (38.5℃), dry cough, fatigue, and loss of smell and taste. She consulted a doctor and gave her advice on bed rest and home quarantine from her family members after sending her for a realtime PCR test of the nasopharyngeal swab. The test was positive for SARS-CoV-2. Chest X-ray revealed a right-sided upper zone pneumonic patch. Supportive treatment in form of antipyretic and tonic as well as antibiotics was given. The patient became well and all presenting symptoms disappeared completely at the 10 days follow-up period. After one week, there was an appearance of a right supraclavicular lump which was painless and gradually increase in size Fig. 1. Physical examination revealed a non-tender neck mass in the right supraclavicular region, oval in shape, 2 x 1.5 cm, freely mobile, no scar, and no skin changes over the swelling or surrounding areas. There were no focal infective areas or masses or other lymph node enlargement in the body. The patient took a 5 days antibiotic course but without bene t. Ultrasound examination revealed multiple cervical lymph nodes in the right supraclavicular area, the largest one of 19x14 mm in diameter. These nodes showed abnormal fatty hilum and abnormal round index as well as exaggerated hypo-echoic texture as shown in Fig

Discussion
The head and neck contain around 2/3rd of the lymph nodes in the body. Besides, the in ammatory or malignant process in any area can reach the neck through the lymphatic system. Therefore, there is a huge list of causes of cervical lymphadenopathy (enlargement of a node > 1 cm in diameter). Cervical lymphadenopathy is common in the pediatric population, and most of the cases are benign. The rst systematic review about the causes of cervical lymphadenopathy in children of Deosthali et al. [7] reported that 67.8% of the 2687 cases are due to nonspeci c benign causes, followed by Epstein-Barr virus (8.86%), malignancy (4.69%), and granulomatous disease (4.06%). In the presenting case, the histopathology and immunohistochemistry evaluations revealed the reactive benign nature of the supraclavicular lymph node. The high possible cause of this cervical lymphadenopathy was COVID-19 because the patient was diagnosed as COVID-19 by real-time PCR of the nasopharyngeal swab and high IgM as well as an absence of indicators of other pathologies in the history, examination, and investigations. Accordingly, COVID-19 can lead to reactive cervical lymph node enlargement. Involvement of the axillary and/or supraclavicular lymph nodes on the same side is a frequent adverse effect of the vaccines against COVID-19. This is due to local activation of the immune response [8] [9][10].

Moreover, Distinguin et al. reported 3 cases of cervical lymphadenopathy in group II (upper jugular group)
on magnetic resonance imaging (MRI) in patients with COVID-19. All those patients have complained of otorhinological symptoms (anosmia, aguesia, nasal obstruction, rhinorrhea, and sore throat). These symptoms due to in ammation of the nose, nasopharynx, and oropharynx that caused by SARS-CoV-2.
As a result of this in ammation, a local immune reaction occurs, resulting in lymph node enlargement of the Waldeyer's ring, neck, and parotid regions [6]. Interestingly, we presented the rst case in the world of unilateral supraclavicular enlargement in a patient with COVID-19. Although the mechanism of supraclavicular lymphadenopathy is obscure, it is of utmost importance to put the COVID-19 in the differential diagnosis of supraclavicular lymphadenopathy.
Identi cation of the possible ways of the transmission of the SARS-CoV-2 has a major role in understanding the mechanism of the infection with its further treatment options. The speci c coronavirus receptor (ACE-2 receptor) is distributed in all body tissues, including the lymph nodes [11], therefore, it is possible to nd the virus in the lymph node as in the presenting case, leading to in ammation and enlargement of the node. Another possible mechanism of getting enlargement of the supraclavicular lymph node is a local immune response in the lung.
According to the American College of Radiology (ACR) recommendations, chest X-ray and computerized tomography (CT) should not be used as a screening or rst diagnostic tool of the COVID-19 owing to the similarity of the radiological signs among various lung conditions. However, radiological investigation in the pediatric population plays an essential tool for moderate and severe forms of COVID-19 (as a baseline, assessment of complications, and assessment of treatment response or progression of the disease). Moreover, chest X-ray is considered the rst radiological investigation in children, and CT scan is reserved for suspicious cases of pulmonary embolism or worsening clinical condition [12]. Pulmonary abnormalities in children are unilateral in 55% and bilateral in 45% of affected children [13] and about 8% are affected the right upper lobe of the lung [14] which was a similar nding of our patient.
Cervical lymphadenopathy following COVID-19 is extremely rare. However, it can put on the long list of differential diagnoses which include infections and primary tumor (lymphoma) or secondary malignant lymph node. Radiological investigations in the form of sonography or MRI as a diagnostic tool should be performed when there are suspicious ndings on physical examination.
As reported in the literature, supraclavicular lymphadenopathy after taking the COVID-19 vaccine affects mostly females and occurs in up to 24 days (mostly in the rst 10-15 days). It gradually subsides within 4-6 weeks [15]. Our case presented with features of COVID-19 (fever, fatigue, cough, and loss of smell and taste) for 10 days, and the disease was con rmed by a real-time PCR test of the nasopharyngeal swab. Seven days following the resolution of the symptoms, there was an appearance of right-sided supraclavicular lymphadenopathy. Supraclavicular lymphadenopathy in children, particularly if persists for more than two weeks, carries a sinister pathology [16], therefore we subjected the child to an excisional biopsy which revealed a benign nature of the lesion on the histopathological and immunohistochemical evaluation. Accordingly, the supraclavicular lymphadenopathy in the presenting case was highly suspicious that the COVID-19 was a cause.

Conclusion
Supraclavicular lymphadenopathy due to COVID-19 was never reported in the literature. However, it might be a side effect of the COVID-19 vaccine. Besides, cervical lymphadenopathy in level II was reported. This is the rst case in the world of supraclavicular lymphadenopathy due to COVID-19 in a child. Therefore, it is necessary to ask the patients with cervical lymphadenopathy whether they have gotten COVID-19 recently. Figure 2 Grayscale ultrasound of the neck shows abnormal-looking lymph nodes evident by exaggerated hypoechoic echotexture and lost fatty hilum. The largest one 18 x10 mm in diameter.