key: cord-0682443-r7tvt0m5 authors: Bleier, Benjamin S.; Welch, Kevin C. title: Pre‐procedural COVID‐19 Screening: Do Rhinologic Patients Carry a Unique Risk Burden for False Negative Results? date: 2020-06-18 journal: Int Forum Allergy Rhinol DOI: 10.1002/alr.22645 sha: d0449447fae588a525bb69bd7ea464b71d2bbe5d doc_id: 682443 cord_uid: r7tvt0m5 nan metrics. The results from the fact that failure to identify a COVID-19 positive patient could result in inadvertent spread to both the healthcare team as well as other vulnerable patients [1] . From the perspective of proper timing, a recent meta-analysis [2] confirmed that the highest risk of a false negative result occurs in the pre-symptomatic period up to 4 days prior to symptom onset. With regard to proper site, several studies, including one of 353 patients, confirmed that the nasopharynx is the optimal sampling location relative to the nasal cavity and oropharynx [3] [4] . This is consistent with earlier data demonstrating high viral loads within the nasopharynx among both symptomatic and asymptomatic patients [5] . Finally, with respect to proper sample, adequate viral material must be obtained in order to be amplified and subsequently detected by RT-PCR. Consequently, the CDC recommends the use of flocked swabs over calcium alginate swabs [6] as, among other advantages, they improve sample yield through increased surface area within the multi-length (e.g. "flocked") swab fibers. In light of recent evidence regarding the aerosolization risk during both clinical and surgical rhinologic procedures [7] [8] multiple societal guidelines [9] [10] [11] have endorsed various degrees of high level PPE use (e.g N95 respirators, gown and eye protection), source control, and environmental controls such as adequate room air changes per hour (ACHs) following these potential aerosol generating procedures (AGPs). Given the ongoing scarcity of PPE and the potential for subsequent infectious waves, some institutions have explored a strategy of pre-procedural COVID-19 screening tests with the presumption that a negative test would enable preservation of provider PPE and ameliorate the burden of source/environmental controls. However, this tactic may be hazardous as the rhinologic patient population poses unique challenges to all three tenets of effective RT-PCR based testing. These patients may therefore assume a distinct excess false negative risk as a consequence of the very sinonasal disorders they are seeking care for. Assuming that pre-procedural testing was coupled with symptom screening, we may assume that the patients proceeding to sampling would largely be asymptomatic. According to the Kucirka et al meta-analysis [2] this would therefore a priori bias the population towards sampling during the worst performing timing window where the pre-symptomatic median false negative rate is at least 3 times higher than in the symptomatic population. Rhinologic patients further carry an array of diagnoses which have the potential to obstruct access to the optimal sampling site within the nasopharynx. These include baseline structural issues such as a deviated septum, turbinate hypertrophy, and concha bullosa; inflammatory conditions including nasal polyps and antro/spheno-choanal polyps; and neoplastic disease such as sinonasal and skull base tumors. As screening testing could occur prior to endoscopy and/or imaging in many cases, these factors may not be known at the time of testing and could not be accounted for by sampling technique. This limitation of access to the proper sampling site may have contributed to a recent experience by the authors of a false negative result in a patient with severe chronic rhinosinusitis with nasal polyps. In this case, the patient presented with large nasal polyps obstructing the nasopharynx (See Figure 1A) and underwent preoperative RT-PCR based testing 48 hours prior to the operation. After the polyps were resected, it became clear that the nasopharynx could not have been sampled correctly and a thorough swab of the nasopharynx was obtained during the operation. Prior to the termination of the case, the staff was notified by the lab that the swab was positive for SARS-CoV-2 prompting closure of the OR room. Since the use of N95 respirators was not required in the setting of a negative preoperative screen, all healthcare workers who were wearing traditional surgical masks had to report to Corporate Health, undergo a 2-week period of symptom questionnaires, and were required to undergo RT-PCR testing 5-7 days after the exposure. Of note, these rhinology related pathologies may not only obstruct the nasopharynx but also increase the risk to the patient during sampling. For example, patients with vascular lesions (See Figure 1B ) may be at higher risk for postsampling epistaxis. Furthermore blind nasopharyngeal swabbing of post-operative patients with a patent sphenoid sinus and/or dissected skull base could risk injury to these exposed structures and at least one post-swab CSF leak has been anecdotally reported in an ENT related blog post though not verified. Even with optimized timing and site of collection, sample acquisition faces additional challenges in this patient population. As previously noted, sample yields are facilitated by swab designs which improve absorption and eventual release of viral material. Relative to patients without sinonasal disease, rhinologic patients are more likely to have an increased volume and viscosity of mucus within the nasal cavity resulting from an array of possible conditions including allergy, eosinophilic inflammation, and neutrophilic infection [12] . Regardless of the primary etiology, these secretions have the potential to saturate the swab as it is advanced towards the nasopharynx effectively displacing the intended sample with more proximal material. These common issues faced by patients with rhinologic disease conspire to increase the potential false negative rate at all three points of failure related to RT-PCR testing. This phenomenon is a function of the idiosyncratic challenges to proper sample timing, site, and acquisition associated with sinonasal disease. These latter two concepts have been specifically validated in the sinonasal cavity as endoscopic guidance and guarding of flocked swabs has become the preferred method of obtaining site specific rRNA samples for microbiome sequencing [13] . At the current time, nasopharyngeal RT-PCR testing for SARS-CoV-2 may be helpful to exclude positive patients however a negative result should be viewed with caution when making decisions to supplant source/environmental controls and provider PPE. Figure 1 . Examples of rhinologic patients at risk for false negative RT-PCR testing. A. Sagittal CT scan of patient with false negative pre-procedural COVID-19 testing due to severe Chronic Rhinosinusitis with Nasal Polyps and positive intra-operative positive testing after endoscopic guided nasopharyngeal swab. B. T1 contrast enhanced sagittal MRI scan of patient with juvenile nasopharyngeal angiofibroma and nasopharyngeal obstruction who experienced epistaxis following COVID-19 screening. Interpreting a covid-19 test result Variation in False-Negative Rate of Reverse Transcriptase Polymerase Chain Reaction-Based SARS-CoV-2 Tests by Time Since Exposure Comparison of nasopharyngeal and oropharyngeal swabs for SARS-CoV-2 detection in 353 patients received tests with both specimens simultaneously Swabs Collected by Patients or Health Care Workers for SARS-CoV-2 Testing SARS-CoV-2 Viral Load in Upper Respiratory Specimens of Infected Patients Endonasal instrumentation and aerosolization risk in the era of COVID-19: simulation, literature review, and proposed mitigation strategies Airborne Aerosol Generation During Endonasal Procedures in the Era of COVID-19: Risks and Recommendations Nasal endoscopy and laryngoscopy examination of ENT patients COVID-19 Educational Videos for Rhinologists Guidance for Return to Practice for Otolaryngology-Head and Neck Surgery The international sinonasal microbiome study: A multicentre, multinational characterization of sinonasal bacterial ecology