SARS-CoV-2 detection in different respiratory sites: A systematic review and meta-analysis

Abstract

Background: The accurate detection of SARS-CoV-2 through respiratory sampling is critical for the prevention of further transmission and the timely initiation of treatment for COVID-19. There is a diverse range of SARS-CoV-2 detection rates in reported studies, with uncertainty as to the optimal sampling strategy for COVID-19 diagnosis and monitoring.

Methods: We performed a systematic review and meta-analysis of studies comparing respiratory sampling strategies for the detection of SARS-CoV-2 RNA. The inclusion criteria were studies that assessed at least two respiratory sampling sites (oropharyngeal swab, nasopharyngeal swab, and sputum) in participants with COVID-19. The percentage positive tests were compared between sampling modalities by constructing a Z-test assuming independence and using the standard errors obtained from the random effects meta-analysis.

Findings: From 1039 total studies, we identified 11 studies that met our inclusion criteria, with SARS-CoV-2 testing results from a total of 3442 respiratory tract specimens. Compared to nasopharyngeal swab sampling, sputum testing resulted in significantly higher rates of SARS-CoV-2 RNA detection while oropharyngeal swab testing had lower rates of viral RNA detection. Earlier sampling after symptom onset was associated with improved detection rates, but the differences in SARS-CoV-2 RNA detection by sampling method was consistent regardless of the duration of symptoms.

Interpretation: The results support sputum sampling as a valuable method of COVID-19 diagnosis and monitoring, and highlight the importance of early testing after symptom onset to increase the rates of COVID-19 diagnosis.

Funding: This study was funded in part by the NIH grants U01AI106701 and by the Harvard University for AIDS Research (NIAID 5P30AI060354).

Keywords: COVID-19; Diagnosis; Nasopharyngeal; Oropharyngeal; SARS-CoV-2; Sputum.

Fig. 1

Study profile.

Fig. 2

Rates of SARS-CoV-2 detection by three methods of sampling. Forest plots of detection rates for oropharyngeal swabs (a), nasopharyngeal swabs (b), and sputum (c) and in a pooled analysis (d). The error bars in (d) are 95% confidence intervals (95% CIs). P-values were calculated by the Z-test.

Fig. 3

Rates of SARS-CoV-2 detection by three methods of sampling and time since symptom onset. Forest plots of detection rates for oropharyngeal swabs (a), nasopharyngeal swabs (b), and sputum (c) are categorized by days since symptom onset (0–7, 8–14, >14 days) and in a pooled analysis (d). The error bars in (d) are 95% confidence intervals (95% CIs). P-values were calculated by the Z-test.