Viral load may impact the diagnostic performance of nasal swabs in nucleic acid amplification test and quantitative antigen test for SARS-CoV-2 detection

Abstract

Introduction: Compared to nasopharyngeal swabs (NPS), there has been insufficient evaluation of the diagnostic performance of nasal swabs (NS) for the detection of severe acute respiratory coronavirus 2 (SARS-CoV-2) in the nucleic acid amplification test (NAAT) and quantitative SARS-CoV-2 antigen test (QAT).

Methods: We prospectively compared healthcare worker-collected and flocked NS within nine days after symptom onset to paired NPS to detect SARS-CoV-2 in NAAT and QAT on the fully automated Lumipulse system. The agreement between sample types was evaluated, and cycle threshold (Ct) values and antigen levels were used as surrogate viral load measures.

Results: Sixty sets of NPS and NS samples were collected from 40 patients with COVID-19. The overall agreements between NAAT and QAT samples were 76.7% and 65.0%, respectively. In NAAT, the Ct value of NS was significantly higher, 5.9, than that of NPS. Thirty-nine (95.1%) NS tested positive in 41 positive-paired NPS with Ct ≤ 30. The negative correlation was observed between antigen levels of NS in QAT and Ct values of NS in NAAT (r = -0.88). In QAT, the antigen level of NS was significantly lower than that of NPS. Thirty-six (90.0%) NS tested positive in 40 positive-paired NPS with antigen levels >100 pg/mL, which were collected significantly earlier than those with antigen levels ≤100 pg/mL.

Conclusions: In NAAT and QAT, NS had limited performance in detecting SARS-CoV-2 compared to NPS. However, NS may be helpful for patients with COVID-19 with high viral loads or those in the early stages of the illness.

Keywords: Nasal swabs; Nasopharyngeal swabs; Nucleic acid amplification test; Quantitative SARS-CoV-2 antigen test; SARS-CoV-2; Viral load.

Fig. 1

a. The difference of Ct values in paired NPS-NAAT between positive and negative NS-NAAT b. The difference of Ct values in positive NAAT between nasopharyngeal swabs and nasal swabs (n = 44) NAAT, nucleic acid amplification test NS-NAAT, nucleic acid amplification test using nasal swabs NPS-NAAT, nucleic acid amplification test using nasopharyngeal swabs * Mann–Whitney U test was performed. ** Paired t-test was performed.

Fig. 2

a. Correlation between antigen levels of NS-QAT and Ct values of NS-NAAT (n = 45) b. The difference of antigen levels in paired NPS-QAT between positive and negative NS-QAT c. The difference in antigen levels in positive QAT between nasopharyngeal swabs and nasal swabs (n = 39) QAT, quantitative antigen test NS-QAT, quantitative antigen test using nasal swabs NPS-QAT, quantitative antigen test using nasopharyngeal swabs NS-NAAT, nucleic acid amplification test using nasal swabs * Mann–Whitney U test was performed.