key: cord-0766643-ab9t31ih authors: Salvatore, Phillip P.; Bhattacharyya, Sanjib; Christensen, Kim; Tate, Jacqueline E.; Kirking, Hannah L. title: Reduced Sensitivity of SARS-CoV-2 PCR Testing with Single-Nostril Nasal Swabs date: 2021-05-09 journal: J Clin Virol DOI: 10.1016/j.jcv.2021.104852 sha: 3f6f108e1a81f2104569e09bad0ce5775d3fc120 doc_id: 766643 cord_uid: ab9t31ih nan To the Editors, Nasopharyngeal (NP) specimens collected by clinicians are used as the "gold standard" for diagnostic real-time reverse transcriptase polymerase chain reaction (rRT-PCR) testing for SARS-CoV-2. Previous reports indicate that two-nostril nasal swabs offer a sensitive (94%) alternative to NP specimens and are better tolerated by patients (1) . Importantly, Food and Drug Administration (FDA) authorization of nasal swab protocols require sampling of both nostrils. Prior to FDA authorization of two-nostril nasal swabs, we evaluated the diagnostic accuracy of singlenostril nasal swabs (used for sampling other respiratory viruses (2) We collected 452 paired NP and nasal swab specimens from 226 participants. When compared with NP specimens, single-nostril nasal swabs demonstrated a PPA of 47% (95% confidence interval [CI]:38%-57%; Figure 1 ) and a NPA of 99% (95% CI: 98%-100%). Measured PPAs of single-nostril nasal swabs were similarly low at study sites in Utah (43%; 95% CI: 33%-55%) and Wisconsin (57%; 95% CI: 42%-78%). The PPA of single-nostril nasal swabs was significantly associated with rRT-PCR cycle threshold (Ct) values of the viral target in the paired NP specimens (Cochran-Armitage p<0.001 for the N1 target; p=0.001 for the N2 target). PPA of single-nostril nasal swabs was higher (78%; 95% CI: 61%-100%) among children (age range among cases: 3-17 years), lower among participants who reported no symptoms at collection (32%; 95% CI: 19%-55%), and was negatively associated with days between onset and collection (Cochran-Armitage p<0.001); the negative association with days between onset and collection remained significant when stratified by Ct value category. These trends Two-nostril nasal swabs produce less discomfort than NP swabs. While two-nostril nasal swabs demonstrate a sensitivity of 94% (1), our analysis indicates that single-nostril nasal swabs demonstrate a low PPA of 47% and that the PPA of single-nostril swabs is lowest (32%) among persons with Ct values over 30 (low levels of viral RNA, suggesting low viral burden). This discrepancy might be related to sampling variability between nostrils, as has been observed for influenza A virus (5) . As a result, single-nostril nasal swabs are likely to result in a high proportion of false-negative results leading to missed cases and, potentially, increased transmission. The distinction between single-nostril and two-nostril swabs is critical as many clinicians, familiar with single-nostril nasal swab sampling protocols for other respiratory viruses (2), might perform single-nostril nasal swabs when sampling for SARS-CoV-2. Additionally, it is critical to ensure patients are reminded and understand the importance of swabbing both nostrils when conducting self-collected nasal swabs. Our results reinforce the importance of proper specimen collection technique and sampling of both nostrils to ensure accurate testing results. ☒ The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. confidence intervals. Results for each subgroup, as well as N2 target cycle thresholds, are presented in Supplementary Table S2 . Swabs collected by patients or health care workers for SARS-CoV-2 testing Equivalence of self-and staff-collected nasal swabs for the detection of viral respiratory pathogens Household transmission of SARS-CoV-2 in the United States Epidemiological correlates of PCR cycle threshold values in the detection of SARS-CoV-2 Sampling variability between two mid-turbinate swabs of the same patient has implications for influenza viral load monitoring