Laboratory Diagnosis and Monitoring the Viral Shedding of SARS-CoV-2 Infection

Abstract

The worldwide epidemic of coronavirus disease 2019 (COVID-19) is ongoing. Rapid and accurate detection of the causative virus SARS-CoV-2 is vital for the treatment and control of COVID-19. In this study, the comparative sensitivity of different respiratory specimen types were retrospectively analyzed using 3,552 clinical samples from 410 COVID-19 patients confirmed by Guangdong CDC (Center for Disease Control and Prevention). Except for bronchoalveolar lavage fluid (BALF), the sputum possessed the highest positive rate (73.4%-87.5%), followed by nasal swabs (53.1%-85.3%) for both severe and mild cases during the first 14 days after illness onset (d.a.o.). Viral RNA could be detected in all BALF samples collected from the severe group within 14 d.a.o. and lasted up to 46 d.a.o. Moreover, although viral RNA was negative in the upper respiratory samples, it was also positive in BALF samples in most cases from the severe group during treatment. Notably, no viral RNA was detected in BALF samples from the mild group. Despite typical ground-glass opacity observed via computed tomographic scans, no viral RNA was detected in the first three or all upper respiratory tract specimens from some COVID-19 patients. In conclusion, sputum is most sensitive for routine laboratory diagnosis of COVID-19, followed by nasal swabs. Detection of viral RNA in BALF improves diagnostic accuracy in severe COVID-19 patients.

Keywords: COVID-19; SARS-CoV-2; molecular diagnosis; respiratory specimens; viral shedding.

Graphical abstract

Figure 1

Detection of SARS-CoV-2 RNA in Respiratory Specimens of COVID-19 Cases Respiratory specimens, including BALF, sputum, nasopharyngeal swabs, and oropharyngeal swabs were collected from 410 COVID-19 patients at different time points after onset of illness. The positive rates of different sample types and the Ct values are shown in (A) and (B). Mean and minimum to maximum Ct values are shown. p values between 0.01–0.05, 0.001–0.01, and 0.0001–0.001 were considered statistically significant (∗), very significant (∗∗), and extremely significant (∗∗∗), respectively.

Figure 2

Serial Detection of Viral RNA in Different Sites of the Respiratory Tract from 21 COVID-19 Cases Numbers of cases from severe and mild groups are marked in red and black, respectively. The detection results of samples from the upper respiratory tract are in green, and from the lower respiratory tract (BALF) in black. Lower cycle threshold (Ct) values indicate higher viral loads. The black and red arrows indicate hospital admission and the start of antiviral treatment, respectively.

Figure 3

CT Scan of 11 Cases from Whom SARS-CoV-2 RNA Was Not Detected in the Upper Respiratory Specimens for at Least the First 3 Tests