Where is Omicron? Comparison of SARS-CoV-2 RT-PCR and Antigen Test Sensitivity at Commonly Sampled Anatomic Sites Over the Course of Disease

Abstract

Background: Upper respiratory samples for SARS-CoV-2 detection include the gold standard nasopharyngeal (NP) swab, and mid-turbinate (MT) nasal swabs, oropharyngeal (OP) swabs, and saliva. Following the emergence of the omicron (B.1.1.529) variant, limited preliminary data suggest that saliva may be more sensitive than nasal swab, highlighting the need to understand differences in viral load across different sites. Methods: MT, OP, and saliva samples were collected from symptomatic individuals presenting for evaluation in Atlanta, GA, in January 2022. Longitudinal samples were collected from a family cohort following COVID-19 exposure to describe detection of viral targets over the course of infection. Results: SARS-CoV-2 RNA and nucleocapsid antigen measurements demonstrated a nares-predominant phenotype in a familial cohort. A dominant location for SARS-CoV-2 was not found among cohort of 54 individuals. Positive percent agreement for virus detection in MT, OP and saliva specimens were 66.7 [54.1-79.2], 82.2 [71.1-93.4], and 72.5 [60.3-84.8] by RT-PCR, respectively, and 46.2 [32.6-59.7], 51.2 [36.2-66.1], and 72.0 [59.6-84.4] by ultrasensitive antigen assay. The composite of positive MT or OP assay was not significantly different than either alone for both RT-PCR and antigen assay (PPA 86.7 [76.7-96.6] and 59.5 [44.7-74.4], respectively). Conclusions: Our data suggest that SARS-CoV-2 nucleocapsid and RNA exhibited similar kinetics and diagnostic yield in three upper respiratory sample types across the duration of symptomatic disease. Collection of OP or combined nasal and OP samples does not appear to increase sensitivity versus validated nasal sampling for rapid detection of viral antigen

Evaluation of the Panbio™ COVID-19 Antigen Rapid Diagnostic Test in subjects infected with Omicron using different specimens

“…Our data is in contrast with those reported by Marais 2021 [17], but support previous observations using the Panbio™ COVID-19 Ag RDT for other VOCs detection [29]. On the other hand, Lin 2022 reported no difference between nasal and saliva specimens for Omicron diagnosis [30]. The discrepancy could potentially reflect our patient cohort, where most individuals were fully vaccinated with two doses of COVID-19 vaccine, and a large number of patients having completed the third vaccine dose.…”

Evaluation of the Panbio COVID-19 Antigen Rapid Diagnostic Test in Subjects Infected with Omicron Using Different Specimens

“…Our data are in contrast with those reported by Marais et al in 2021 ( 17 ), but support previous observations using the Panbio COVID-19 Ag RDT for other VOC detection ( 28 ). On the other hand, Lin et al in 2022 reported no difference between nasal and oropharyngeal specimens for Omicron diagnosis when RT-PCR or Ag-RDT was tested ( 29 ). This discrepancy could potentially reflect our patient cohort, where most individuals were fully vaccinated with two doses of COVID-19 vaccine and a large number of patients had completed the third vaccine dose.…”

“…Indeed, the poor performance of oral swabs in Ag-RDT in our samples could also be related to the fact that we only used oral and not oropharyngeal swabs and the nonoptimization of the sample buffer used for collection. Given saliva’s complex contents, optimization of the sample collection buffer would be crucial to increase Ag-RDT sensitivity ( 29 ).…”

Extreme differences in SARS-CoV-2 viral loads among respiratory specimen types during presumed pre-infectious and infectious periods

“…However, participants in both studies were infected with pre-Omicron variants, and neither used OPS, which have been speculated to be superior at detecting early Omicron infections. 20 Only one longitudinal study 18 analyzed viral loads in all three major specimen types (SA, ANS and OPS) over time in Omicron. Unfortunately, daily measurements in all three sample types were captured for only two individuals, both of whom were already positive upon enrollment.…”

“…16 Viral variant plays a role too; one study 15 suggested that healthcare-worker-acquired mid-turbinate (MT) swabs had significantly better performance than self-collected oral swabs for Beta and Delta variants but not Omicron. 14 Several studies, 18,19 news media, 20 and social media posts have speculated that in Omicron infections viral load accumulates in oral specimens before the nasal cavity, but findings from single timepoints are contradictory and rigorous comparisons starting from the incidence of infection are needed. Thus, despite compelling anecdotal evidence that oral specimens might be superior for detection of Omicron infections, nasal swabs (including those in rapid antigen tests) continue to be the dominant specimen type used in the U.S., including for workplace screenings and at-home testing.…”