Patterns of viral clearance in the natural course of asymptomatic COVID-19: Comparison with symptomatic non-severe COVID-19

Abstract

Objectives: The aim of this study was to elucidate patterns of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) clearance in the natural course of asymptomatic coronavirus disease 2019 (COVID-19).

Methods: Consecutive patients with non-severe COVID-19 were included retrospectively. Asymptomatic patients with a normal body temperature and no evidence of pneumonia throughout the disease course were assigned to the asymptomatic group. The reverse transcription PCR (RT-PCR) assay was repeated every two to five days after the first follow-up RT-PCR assay. Negative conversion was defined as two consecutive negative RT-PCR assay results within a 24-h interval. Rebound of the cycle threshold (Ct) value was defined as negative from the single RT-PCR assay and positive from the following assay.

Results: Among a total of 396 patients identified (median age 42.5 years (interquartile range (IQR) 25.0-55.0 years), 35.6% male), 68 (17.2%) were assigned to the asymptomatic group and 328 (82.8%) to the symptomatic group. The time until negative conversion was significantly shorter in the asymptomatic group than in the symptomatic group: median 14.5 days (IQR 11.0-21.0 days) and 18.0 days (IQR 15.0-22.0 days), respectively (p = 0.001). Rebound of Ct values was observed in 78 patients (19.7%).

Conclusions: Time until negative conversion is shorter in asymptomatic COVID-19 than in symptomatic COVID-19. Rebound of Ct values is not uncommon.

Keywords: Asymptomatic; COVID-19; Coronavirus disease 2019; Negative conversion; SARS-CoV-2; Viral clearance.

Figure 1

The proportion of patients with negative conversion according to time until negative conversion in the asymptomatic (A) and symptomatic (B) groups.

Figure 2

Changes in the proportion of patients without negative conversion relative to hospitalization day.

Figure 3

Changes in Ct value from RT-PCR assays for the E gene of SARS-CoV-2 in the asymptomatic (A) and symptomatic (B) groups, RdRP gene of SARS-CoV-2 in the asymptomatic (C) and symptomatic (D) groups, and N gene^a of SARS-CoV-2 in the asymptomatic (E) and symptomatic (F) groups. Each line represents one patient. ^aThe RT-PCR assay for the N gene was performed in 23 patients in the asymptomatic group and 84 patients in the symptomatic group. Ct, cycle threshold; E, envelop protein; N, nucleocapsid protein; RdRP, RNA-dependent RNA polymerase; RT-PCR, reverse transcription polymerase chain reaction; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.