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Evaluating the accuracy of different respiratory specimens in the laboratory diagnosis and monitoring the viral shedding of 2019-nCoV infections

Our take —

This study followed hospitalized COVID-19 patients prospectively, collecting multiple samples and sample types for testing. While there were very few samples collected early after symptom onset and many individuals were administered antiviral medications, this study does provide insight into the sensitivity of RNA testing at different timepoints post-symptom onset, and suggests that nasal swabs are preferable to throat swabs when sputum samples are not available.

Study design

Prospective Cohort Study

Study population and setting

213 patients with Guangdong CDC-confirmed SARS-CoV-2 associated pneumonia hospitalized in Shenzhen Third People’s Hospital between January 11 and February 3, 2020 were enrolled in this study. These patients provided 866 clinical respiratory samples at admission and during follow up, including: nasal and throat swabs, sputum, and bronchoalveolar lavage fluid.

Summary of Main Findings

This study demonstrated variability in molecular testing sensitivity by both sample type, and by time since symptom onset. The study generally showed that sputum samples were most likely to test positive for viral RNA compared to other sample types throughout the duration of infection, and this remained true regardless of the clinical severity of disease, with a few notable exceptions. For instance, after ≥15 days post-symptom-onset in mild or moderate cases, a slightly higher proportion of samples were positive in nasal swabs than sputum, and after ≥8 days post symptom onset in severe cases, a slightly higher proportion of bronchoalveolar lavage fluid samples were positive compared to sputum samples. Overall, throat swabbing consistently yielded the lowest proportion of positive samples compared to other upper respiratory tract samples.

Study Strengths

This study followed patients prospectively and collected multiple sample types, including from both upper and lower respiratory tract, from individuals over time. The authors repeated testing on low viral RNA samples to confirm results.

Limitations

The patients enrolled in this study are all CDC-confirmed cases with clinical disease and therefore may not represent all infected individuals, particularly asymptomatic individuals. The authors note that most of their samples were collected after patients had been administered antiviral medications, and so viral shedding, or the lack thereof, should be interpreted with caution. The number of patients contributing serial samples from both upper and lower respiratory tract was very limited, and samples from the lower respiratory tract in general were much more limited than upper respiratory tract specimens. Finally, the study does not have samples from most individuals collected early after onset of symptoms (<4 days), so it remains unclear what the diagnostic utility of RNA detection is in this early symptomatic time period.

Value added

This study shows that testing sputum samples will likely result in more true positive RNA test results than other upper respiratory tract sample types. However, given the difficulty of obtaining sputum samples from all patients, nasal swabs would be preferable to throat swabs for upper respiratory tract sample testing throughout the duration of infection post-symptom onset.