The PubMed and Embase databases were searched for articles published between 2019 and 2022. KoreaMed was explored between 2010 and 2022 due to the relative shortage of products in the pilot search. The searched keywords included “nasopharyngeal swab,” “nasopharynx swab,” “nasal swab,” “pernasal swab,” “rhinopharyngeal swab,” “pharyngeal swab,” “nasopharyngeal test,” “swab stick,” “swabbing test,” “complications,” “safe,” “safety,” “COVID,” “severe acute respiratory syndrome,” “coronavirus,” “2019nCoV,” “nCoV2019” or “HCoV-19,” and “NCOVID-19”. The literature search focused on human studies and excluded animal experiments. Articles written in English or Korean were included in the database.

A total of 314, 774, and 29 articles were extracted from the initial search through PubMed, Embase, and KoreaMed databases, respectively. After removing duplicate cases, 842 articles remained. The first author fully screened all abstracts and titles of the results to identify articles related to complications due to nasopharyngeal COVID-19 testing. Finally, 27 articles were selected for review.31112151617181920212223242526272829303132333435364041

All the researched complications due to nasopharyngeal COVID-19 testing were classified, and the related information is shown (Table 1). Retained swabs31216171820212426273235 due to swab fracture during the examination and epistaxis31217242832 were the frequently reported complications. Cerebrospinal fluid (CSF) leakage31112152223282930333436 was a frequently documented serious adverse event requiring prompt attention and evaluation. Nasal septal abscess,312171925 and ethmoidal silent syndrome31 were also reported as related complications after nasopharyngeal swabbing.

Retained swabs after nasopharyngeal COVID-19 testing have been frequently reported in the literature.31216171820212426273235 Swabs for COVID-19 examination are intrinsically vulnerable to accidental fragmentation due to an inherent breakpoint mechanism for effective transfer to the transport vial, especially in uncooperative or sedated patients.12 Moreover, accidental hard contact with nasal anatomical structures, including septal spurs and inferior and middle turbinates, are other risk factors for swab fracture.12 Therefore, clinicians should remember related anatomical structures and check for the presence of structural anomalies including severe septal deviation before testing. Many cases of the retained swab could be managed with nasal endoscopic removal17202427 or sometimes retrieved with a bronchoscope.21 In addition, the swab fragments could be found in the gastrointestinal (GI) tract such as the stomach1626 and duodenum,1835 which requires GI endoscopy for retrieval. In one case, a fractured swab was found in the upper part of the nose behind the underlying severe septal deviation and was extracted after mini-septoplasty and septal spur removal.32 The possibility of foreign body ingestion or aspiration should be carefully inspected if the retained swab is not found in the endoscopic evaluation.12

Epistaxis is one of the most common adverse events associated with nasopharyngeal COVID-19 testing. A total of sixteen cases of epistaxis were reported as a result of nasopharyngeal swab.31217242832 Highly vascular nasal mucosa is prone to mechanical trauma by the swab and bleeding, especially in the circumstances of an inflamed upper respiratory tract in COVID-19 patients, an elderly person who takes anticoagulation medications, or a person with intranasal anatomical variations including septal deviations.312 Most of the cases were self-limiting or could be managed with nasal packing.31217 However, potentially life threatening bleeds were also reported and additional procedures including bipolar coagulation, artery ligation, and embolization were required for proper hemostasis.24 The anatomical area of epistaxis often determines the progress because most cases of anterior bleed could be easily managed with firm external nasal pressure; however, posterior bleeds frequently require endoscopic cauterization and packing.31724 Clinicians should remember to screen risk factors, check the more comfortable side during nasal breathing prior to the procedure, and avoid forceful insertion in the presence of any resistance.317 In the presence of high-risk factors for bleeding, less invasive evaluation should be considered instead of performing a nasopharyngeal swab.12

The CSF leakage resulting from iatrogenic skull base damage is a potentially fatal adverse event. It is commonly thought to be rare, but severe cases have been reportedly related to nasopharyngeal COVID-19 testing.11152223282930333436 Traumatic CSF leakage after nasopharyngeal COVID-19 testing is usually manifested as unilateral clear rhinorrhea, persistent headache, or salty or metallic taste postnasal drip within 48 hours after the procedure.11222930333436 The amount of rhinorrhea tends to increase with bending forward and Valsalva maneuver.11222930 The majority of CSF leakage originated from damage in the cribriform plate (Fig. 1A),1522232829333436 and sometimes the sphenoid area.1130 A beta-2-transferrin assay with the sample of rhinorrhea can confirm the diagnosis of CSF leakage.11152228303334 A beta-2-transferrin assay is a sensitive and specific diagnostic tool for CSF leakage because it is only found in CSF, perilymph, and vitreous humor.22 Computed tomography and/or magnetic resonance imaging are required to locate traumatic damage or sometimes pre-existing skull base defects with encephalocele293034 or meningocele.22 Patients who show CSF leakage should remain on strict bed rest, maintain head elevation to 30 degrees, and avoid blowing their nose, coughing, and performing strenuous exercise.22 CSF leakage can be treated with endoscopic surgical repair in most cases, but further management, including systemic antibiotics and corticosteroids, is required when meningitis is complicated.3121522 Clinicians should check for a history of septal deviations, pre-existing skull base defects, previous sinus or trans-sphenoidal pituitary surgery, and other possible concerns for a skull base injury before testing.31134 After confirmation of the high-risk factors, alternative examinations such as modified nasopharyngeal swab through the trans-oral way or saliva swab should be considered to prevent potentially lethal complications.3344243 Clinicians should be educated about appropriate angles and depths of swab insertion before nasopharyngeal COVID-19 testing for safe procedures.

The nasal septal or pharyngeal abscess could be due to nasopharyngeal COVID-19 testing.312181925 The infectious state could comorbid with cellulitis,19 mastoiditis, osteitis, and even aggravate to sepsis.25 The treatment methods were incision and drainage17 and administration of systemic antibiotics.1925 A single case of ethmoidal silent sinus syndrome was also documented after nasopharyngeal swab.31 Silent sinus syndrome is manifested as orbital floor depression, enophthalmos, hypoglobus, enlargement of middle nasal meatus, and facial asymmetry due to maxillary sinus atelectasis as a result of chronic obstruction of the sinus drainage.31 The traumatic etiology of silent sinus has been rarely documented.3144

Sufficient orientation or simple reminders of the anatomical background related to the procedure is expected to lower the possibility of adverse events demonstrated in the previous section. The important anatomical landmarks to remember are cribriform plate, anterior wall of the sphenoid sinus, anterior nasal spine, and nasal floor (Fig. 1A).45 The angle of nasopharyngeal swab insertion into the nasal passage should be within 30°, a safe angle, from the nasal floor for safe testing (Fig. 1A). Upward swab insertion with angles greater than 30° not only results in inadequate sample collection but also can damage the skull base, including the cribriform plate and sphenoid, which can lead to CSF leakage.31245 Clinicians could predict the horizontal plane of the nasal floor and full depth of insertion by the line and length between the nostril and the external ear canal, respectively.45 Clinicians need to hold the swab in an appropriate way for safe insertion just above the nasal floor, which requires delicate pressing in the lower direction (Fig. 1B and C).

Past or current medical history should be thoroughly investigated to avoid a preventable high-risk adverse event. The cautious medical history includes recent nasal trauma, surgery, significant septal deviation, chronic obstruction of the nasal passage, known skull base defects with or without encephalocele or meningocele, idiopathic intracranial hypertension, and severe coagulopathy.3124546

Strict adherence to the respiratory and contact precautions, recommended by the Centers for Disease Control and Prevention (CDC), during the wearing of personal protective equipment (PPE) including a gown, gloves, a qualified respirator, and a face shield is essential.46 All personal items and jewelry should be removed before testing.47 First, clinicians should wear a protective gown and wash their hands. The next steps are putting on non-sterile gloves and a respirator with a grading of N95 or higher. Finally, the equipment of a face shield is followed for face and eye protection.4647

Clinicians are recommended to ask their patients to take off their face masks and blow their nose to clear possible secretions that hinder effective swab insertion.46 Tilting the head slightly backward has been recommended in some studies for a more accessible nasal passage3046 but a safe and effective approach of nasopharyngeal swab does not seem to be significantly related to head extension.45 Moreover, a head extension exposes the skull base to trauma if the clinician incorrectly performs the procedure.45 Therefore, the recommended procedural steps start from requesting patients to gaze forward with the head positioned on a horizontal plane parallel to the floor.47 Clinicians can predict the full depth of swab insertion by measuring the length between the nostril and the external ear canal (Fig. 2A). It is more ideal if the patient is comfortably seated with the back of their head against the headrest.4748 Second, the swab is appropriately held (Fig. 1B and C) and inserted into the nostril 2 to 3 cm parallel to the nasal bridge until it reaches the anterior nasal spine (Fig. 2B). Raise the hand that holds the swab approximately 70° upward at the same position and gently insert the swab along the nasal septum just above the nasal floor to the target area, nasopharynx, considering the anatomical structures of the nasal cavity and its surroundings (Fig. 2C).2445464748 The swab should be kept on the nasopharynx for several seconds and gently pulled back while rotating it within fingers (Fig. 2D).464748 Forceful movement should be attempted, especially in patients at a high risk of possible complications.24

Samples collected on nasopharyngeal swabs were moved to collection tubes by breaking the swab at the groove. Sealed state and labeling should be checked, and surface disinfection should be performed.4648 Taking off PPE is recommended to be observed by other personnel, if possible, to lower the possible risk of contamination.46 The first step is to remove the gown and gloves, followed by cleansing hands with decontaminating agents, including alcohol-based solutions. Second, new gloves are worn, and the face shield is removed. Third, we put on another pair of new gloves and remove the respirator. Finally, the gloves are removed, and hands are re-washed using decontaminating agents.46