SARS-CoV-2 nasopharyngeal viral load in individuals infected with BA.2, compared to Alpha, Gamma, Delta and BA.1 variants: A single-center comparative analysis

Abstract

Background: SARS-CoV-2 has evolved, leading to the emergence of new Variants Of Concern (VOCs) with significant impact on transmissibility. Although the transmission process is complex, higher nasopharyngeal viral load (NP-VL) can be considered as a proxy for greater transmissibility.

Objectives: The aim of this analysis was to compare NP-VL across a set of representative VOCs observed in mildly symptomatic patients.

Study design: Observational single-center comparative analysis of patients with early mild-to-moderate COVID-19, enrolled within the early treatment access program of Lazzaro Spallanzani Institute (March 2021-March 2022). NP-VL before drug administration was estimated through RT-PCR, based on cycle threshold values (CTs); VOCs were identified by Sanger sequencing. VOCs' average treatment effect (ATE) was estimated on the CTs fitted in the log2 scale, controlling for potential confounders.

Results: A total of 707 patients were included. VOCs were: 10% Alpha, 3% Gamma, 34% Delta, 34% BA.1, 19% BA.2. Mean CTs for BA.1 and BA.2 were lower than Delta and BA.1, respectively. After adjusting for calendar time, age, immunodeficiency and vaccination, CTs for Gamma were lower than those seen for Alpha and higher than Delta, for Delta were similar to BA.1, for BA.2 were lower than Delta and BA.1.

Conclusions: Our analysis shows higher NP-VL of BA.2 compared to previously circulating VOCs, even after controlling for factors potentially contributing to the amount of nasopharyngeal viral RNA, included vaccination, supporting the increased transmissibility of BA.2. Further studies are necessary to clarify this mechanism and to provide guidance for public health measures.

Keywords: Cycle threshold (CT) values; Increased transmissibility; Nasopharyngeal viral load; Omicron BA.2; SARS-CoV-2; Variants of concern (VOCs).

Fig. 1

Key assumptions regarding the underlying causal link between measured factors. According to our assumptions, age, vaccination status, calendar time of study entry and immunodeficiency at time of drug administration were identified as main confounders of our comparison of interest. VOC, variant of concern; CT, cycle threshold values.

Fig. 2

Dot-plots showing means and Standard Deviation (SD) of nasopharyngeal viral RNA levels detected in (a) patients with Alpha, Gamma and Delta (DiaSorin assay) variants infection; in (b) patients with Delta (Abbott Alinity assay), Omicron BA.1 and Omicron BA.2 variants infection. Viral RNA levels are expressed as log2 Cycle Threshold (CT) values. Means in log2 CT values and SD are shown. Statistical analysis of the comparisons between variants of concern (VOCs) was performed by Kruskal-Wallis test and specific contrasts PValue corrected by Dunn's method for multiple comparisons. Horizontal dashed line represents the limit of detection (CT=40.0), CT values ≥40 are considered negative. n, number of participants in group.

Fig. 3

Dot-plots showing means and Standard Deviation (SD) of nasopharyngeal viral RNA levels, stratified by vaccination categories (unvaccinated, partially vaccinated, recent fully vaccinated or boosted, waned fully vaccinated or unboosted). Viral RNA levels are expressed as log2 Cycle Threshold (CT) values. Means in log2 CT values and SD are shown. Statistical analysis of the comparison between stratification groups was performed by means of analysis of variance (ANOVA, with global Fisher F test and specific contrasts PValues corrected by Holm-Šídák's method for multiple comparisons). Horizontal dashed line represents the limit of detection (CT=40.0), CT values ≥40 are considered negative. n, number of participants in group.