Variant-Specific Viral Kinetics in Acute COVID-19

Abstract

Understanding variant-specific differences in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral kinetics may explain differences in transmission efficiency and provide insights on pathogenesis and prevention. We evaluated SARS-CoV-2 kinetics from nasal swabs across multiple variants (Alpha, Delta, Epsilon, Gamma) in placebo recipients of the ACTIV-2/A5401 trial. Delta variant infection led to the highest maximum viral load and shortest time from symptom onset to viral load peak. There were no significant differences in time to viral clearance across the variants. Viral decline was biphasic with first- and second-phase decays having half-lives of 11 hours and 2.5 days, respectively, with differences among variants, especially in the second phase. These results suggest that while variant-specific differences in viral kinetics exist, post-peak viral load all variants appeared to be efficiently cleared by the host. Clinical Trials Registration. NCT04518410.

Keywords: COVID-19; variant; viral kinetics.

Figure 1.

A, Maximum viral load during study follow-up by variant. B, Days post–symptom onset to maximum viral load by variant. The boxplots represent the 25th and 75th percentiles (bottom and top edge of the box), the circle in the box represents the median, and whiskers extending from the edges of the box represent the smallest (bottom) or largest (top) value no further than 1.5 times the interquartile range. Outliers are represented as open circles. The P values shown correspond to analyses after adjusting for baseline covariates. Abbreviations: ANOVA, analysis of variance; DPO, days post–symptom onset.

Figure 2.

Kaplan-Meier plot of duration of viral shedding by variant (N = 299). The y-axis denotes the probability of continuing to shed virus at different times and the x-axis denotes time post–symptom onset. The vertical tick marks correspond to 26 individuals lost to follow-up.

Figure 3.

Spaghetti plot of the decay in viral load (light gray lines and symbols) for each participant (n = 204), with the best population fit represented as a thick black line. The decay dynamics estimated from the model for each variant is shown as thick lines in the following order from top to bottom at time 0: Delta, Alpha, Overall, Others, Epsilon (note that the line for Gamma is barely visible under the Overall/Others lines). The y-axis denotes log₁₀ severe acute respiratory syndrome coronavirus 2 RNA copies/mL and the x-axis denotes time in days since maximum viral load.