Viral load dynamics in asymptomatic and symptomatic patients during Omicron BA.2 outbreak in Shanghai, China, 2022: A longitudinal cohort study

Abstract

The SARS-CoV-2 virus, particularly the Omicron BA.2 variant, led to a significant surge in Shanghai, 2022. However, the viral load dynamic in Omicron infections with varying clinical severities remain unclear. This prospective cohort included 48,830 hospitalized coronavirus disease 2019 (COVID-19) patients across three hospitals in Shanghai, China, between 23 March and 15 May, 2022. Systematic nucleic acid testing was performed using RT-PCR Cycle threshold (Ct) value as a proxy of viral load. We analyzed the kinetic characteristics of viral shedding by clinical severity and identified associated risk factors. The study comprised 31.06% asymptomatic cases, 67.66% mild-moderate cases, 1.00% severe cases, 0.29% critical and fatal cases. Upon admission, 57% of patients tested positive, with peak viral load observed at 4 days (median Ct value 27.5), followed by a decrease and an average viral shedding time (VST) of 6.1 days (Interquartile range, 4.0-8.8 days). Although viral load exhibited variation by age and clinical severity, peak Ct values occurred at similar times. Unvaccinated status, age exceeding 60, and comorbidities including hypertension, renal issues kidney dialysis and kidney transplantation, neurological disorders, rheumatism, and psychotic conditions were found to correlate with elevated peak viral load and extended VST. Asymptomatic cases demonstrated a 40% likelihood of contagiousness within 6 days of detection, while mild-moderate and severe cases exhibited post-symptom resolution infectious probabilities of 27% and over 50%, respectively. These findings revealed that the initial Ct values serve as a predictive indicator of severe outcomes. Unvaccinated elderly individuals with particular comorbidities are at high-risk for elevated viral load and prolonged VST.

Keywords: BA.2; COVID-19; Omicron; Viral load dynamics; Viral shedding time.

Fig. 1

Characteristics of viral shedding of total participants. A Ct value and negative proportion at each time point since initial detection. Solid and dashed lines indicate average Ct value and proportion, respectively. Grey shadow indicates 95% CI. B Time distribution of viral shedding duration. Vertical dashed line indicates median of viral shedding time. C Correlation between peak Ct value and the time to reach peak since initial detection. Blue dashed lines indicate median of time at peak and the median of peak Ct value.

Fig. 2

Clinical severity-specific characteristics of viral shedding. A Ct value at each time point since initial detection. Solid line indicates average Ct value, shadow indicates 95% CI. B Time distribution of viral shedding duration. Vertical dashed line indicates median of viral shedding time. C Correlation between peak Ct value and time to reach peak since first positive PCR test. Vertical dashed line indicates median of time at peak and the median of peak Ct value.

Fig. 3

Age group-specific characteristics of viral shedding. A Ct value at each time point since first positive PCR test. Solid line indicates average Ct value, shadow indicates 95% CI. B Time distribution of viral shedding duration. Vertical dashed line indicates median of viral shedding time. C Correlation between peak Ct value and time to reach peak since first positive PCR test. Vertical dashed line indicates median of time at peak and the median of peak Ct value.

Fig. 4

Risk factors associated with viral load dynamics. Risk factors related to peak viral load (A) and viral shedding duration (B). The coefficients (dots) and 95% CIs (line segments) were estimated from a multivariable regression analysis with an adjustment for gender, age, and comorbidities, and vaccination-infection status. Regression coefficients along with 95% CIs are reported as solid dots and horizontal lines relative to the value of the regression intercept. ∗P ​< ​0.05; ∗∗P ​< ​0.01; ∗∗∗P ​< ​0.001.

Fig. 5

Clinical severity-specific progression of positive proportion from initial detection along with symptom statues. A: asymptomatic group; B: mild-moderate group; C: severe group; D: clinical or death group. The above margined figure is the density of time intervals between symptom onset since initial PCR detection (red) and the symptom resolution since initial PCR detection (blue). The vertical dashed lines represented the median of time of onset and symptom resolution date since initial detection. ∗: aggregated 20–30 days into a group, other time points were not treated.