RT-PCR testing is the standard for COVID-19 confirmation, but there have been reports of painful complications arising from incorrect testing methods. A recent study published in JAMA sought to understand the frequency of possibility of these complications and also provided precautionary pointers while performing the sampling.

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The study

Specialists have accepted that timely and reliable testing plays an important role in controlling the COVID-19 pandemic. Nasopharyngeal swab RT-PCR testing is often used as the main diagnostic method because it yields early results with moderate sensitivity and excellent specificity. Researchers Dr Anni Koskinen and co-workers retrospectively screened all patients presenting to the dedicated otorhinolaryngology emergency department (ED) of Helsinki University Hospital Department of Otorhinolaryngology-Head and Neck Surgery between March 1 and September 30, 2020, for complications after SARS-CoV-2 nasopharyngeal swab sampling. They reported the study in JAMA Otolaryngology-Head & Neck Surgery, published online on April 29, 2021. The frequency of complications was found to be extremely low in this study.

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Sampling

During the COVID-19 pandemic, researchers took numerous swab samples for SARS-CoV-2 reverse transcription-polymerase chain reaction (RT-PCR) testing. Nasopharyngeal sampling for the study is considered safe in spite of having many adjacent vital structures such as orbit, skull base, rich vasculature etc. However, a single report consisting of a few cases and clinical observations indicate the possibility of severe complications. This case series investigated the frequency and type of SARS-CoV-2 nasopharyngeal test complications. The researchers reviewed the medical records of those experiencing sampling complications. They collected the data on the number of SARS-CoV-2 tests performed in the catchment population (1.6 million people) of the Helsinki University Hospital during the same time period from the Finnish Institute for Health and Welfare.

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Results

During the 7-month study period, the hospital performed 6,43,284 SARSCoV-2 RT-PCR tests. The researchers identified eight complication-related visits (7 females, 1 male; age range, 14.0-78.6 years; mean age 39.5 years in 2899 otorhinolaryngology Emergency Department (ED) patients—4 nasal bleeds and 4 broken swabs, all occurring immediately after sampling.

None of these 8 patients tested positive for COVID-19. The researchers estimated that the frequency of complications requiring treatment in the ED was 1.24 per 100,000 SARS-CoV-2 tests. Physicians removed the broken swabs via nasal endoscopy under local anaesthesia, whereas the nasal bleeds needed medication, numerous nasal packings, and surgical and endovascular procedures and led to sepsis, and blood transfusions.

Half of the bleeds were potentially life-threatening (haemoglobin level fell below 6.5 g/dL). Massive bleeding complicated localisation of the bleeds. The researchers stated that infections, as well as intranasal adhesions and septal perforations, likely resulted from repetitive nasal packings.

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Discussion

The frequency of complications was extremely low in this study. All complications appeared to involve an incorrect sampling technique: excess use of force or an overly cranial direction of the swab. While the patients who experienced broken swabs fared well, the patients with nose bleed had unsteady recuperations.

The complications also exposed personnel to the risk of an aerosol-generating procedure. Literature regarding SARS-CoV-2 sampling complications is scarce. Breaking of the swab tip led to a foreign body in the nasal cavity, the oesophagus and, after sampling through a tracheostomy, the bronchus. There was also one instance of a test-related cerebrospinal fluid leak, probably owing to pre-existing encephalocele. (Wikipedia describes encephalocele as a neural tube defect characterised by sac-like protrusions of the brain and the membranes that cover it through openings in the skull. These defects are caused by failure of the neural tube to close completely during foetal development.)

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Precautionary steps

1. Those carrying out the sampling should always keep in mind the anatomical structures of the nasal cavity and its surroundings to ensure safe sampling and correct results.
2. They should never use force especially in patients with known prior operations of the nose or skull base.
3. They should direct the sampling swab along the nasal floor, not too laterally nor too cranially until resistance is encountered.

The researchers conceded that retrospective setting is a limitation of this study. Finland has a national public health service. Of the Helsinki University Hospital’s catchment population (1.6 million), physicians treated all severe acute otorhinolaryngology problems solely in the emergency department. Patients presenting with minor complications may have been treated at other facilities. However, the researchers did not have access to this information. Furthermore, no private otorhinolaryngologist offices have been open for patients with suspected COVID-19. The researchers concluded that in spite of these conditions, this study aptly represented patients with SARS-CoV-2 nasopharyngeal swab test complications in a large tertiary care referral centre.

The researchers found that the risk for a severe complication requiring specialist-level care after SARS-CoV-2 nasopharyngeal swab testing is extremely low. Nonetheless, complications that involve anatomically challenging locations and adjacent vital structures (e.g., orbit, skull base, rich vasculature) may be life-threatening. The researchers say that to avoid complications, correct sampling techniques are crucial.

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NP swab testing and false-negative results

In an earlier paper in the JAMA Otolaryngology- Head-Neck Surgery (SARS-CoV-2 Nasopharyngeal Swab Testing—False-Negative Results, September 17, 2020), Dr Thomas S. Higgins, Department of Otolaryngology-Head and Neck Surgery and Communicative Disorders, University of Louisville School of Medicine, Louisville, Kentucky and others highlighted the concerns raised regarding the rates of false-negative results in community testing locations. These researchers noted that an early retrospective review of community hospital testing in China reported a sensitivity of only 71 per cent.

The researchers found that laboratory errors, patient misidentification, and inadequate collection of secretions are among the sources of false-negative results. They also suggested that improper technique resulting in swabs not reaching the target site of the nasopharynx is a pervasive but modifiable error. The researchers realised that the trajectory from the nostril to the nasopharynx is often presumed to be along the dorsum of the nose, possibly because of the visual appearance of the external nose. Actually, the correct trajectory is along the floor of the nose in the direction back toward the ear.

“As otolaryngologists, we have long provided education to patients, nurses, and doctors about this false anatomical presumption in treating epistaxis*. There is a tendency to place packing “up” the nose where it may not only fail to reach the intended location but also be uncomfortable for the patient because the packing is wedged against the middle turbinate," the researchers added. [* nose bleeding]

The researchers illustrated the nasal anatomy showing correct and incorrect trajectory for a swab directed into the nasopharynx (NP). “As NPS is widely used to test for other respiratory viral infections and has supplanted nasopharyngeal aspiration for its accuracy and convenience in this setting. However, poor technique in NPS testing may convert this test to a simple nasal swab”, the researchers cautioned.

“The NPS is inherently uncomfortable even with good technique, and a patient or the NPS operator may retract prematurely before the swab reaches the correct location and is saturated with mucus. Limited attention has been paid to the effect of the proper technique on the accuracy of results in NPS testing even with regard to testing for influenza or other respiratory viruses”, they clarified. According to them, the frontline health care workers performing NPS must consider three points: trajectory angle, depth, and patient expectations.

“The swab should be angled to follow the floor of the nose, and the depth required to reach the nasopharynx is often surprising to non-otolaryngologists: approximately 9 to 10 cm in adults. For many swabs, this means that almost the entire length is inserted into the nasal cavity, with only a small portion left to be held outside the nose. Both the patient and the operator should have proper expectations for the procedure: the NPS is uncomfortable but should not cause severe pain. Such discomfort should indicate to the operator that an anatomical obstruction, such as a deviated septum, is occluding the pathway, and a modified trajectory or contralateral approach should be attempted”, they added.

“Given our subspecialty focus on nasal anatomy, we have been involved in training personnel at our respective institutions on the proper techniques for NPS collection for SARS-CoV-2 testing, and we have noticed pervasive misperception about the location of the nasopharynx. Although many sites around the world are likely providing proper training, we are concerned that inadequate NPS collection may continue to lead to false-negative results. The rate of false-negative results in reverse transcriptase-polymerase chain reaction testing is a great concern because it underestimates the prevalence of SARS-CoV-2 infection, gives a false sense of security to patients and the health care workers caring for them, and limits public health efforts in identifying and tracing the spread of the virus. We hope to highlight that the nasopharynx is back, not up, can help limit false-negative results in testing for SARS-CoV-2 and other respiratory viruses”. They said while addressing the causes of false-negatives.

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Useful guide for non-specialist physicians and others

The researchers referred to the use of Interim Guidelines for Collecting and Handling of Clinical Specimens for COVID-19 Testing published by the US Centers for Disease Control and Prevention for training purposes.

Disclaimer- The views and opinions expressed in this article are those of the author's and do not necessarily reflect the official policy or position of M3 India.

Dr K S Parthasarathy is a former Secretary of the Atomic Energy Regulatory Board and a former Raja Ramanna Fellow, Department of Atomic Energy. A Ph. D. from the University of Leeds, UK, he is a medical physicist with a specialisation in radiation safety and regulatory matters. He was a Research Associate at the University of Virginia Medical Centre, Charlottesville, USA. He served the International Atomic Energy Agency as an expert and member in its Technical and Advisory Committees.