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[Preprint]. 2021 Aug 20:2021.08.15.21262077.
doi: 10.1101/2021.08.15.21262077.

Infection with the SARS-CoV-2 Delta Variant is Associated with Higher Infectious Virus Loads Compared to the Alpha Variant in both Unvaccinated and Vaccinated Individuals

Chun Huai Luo  1 , C Paul Morris  1   2 , Jaiprasath Sachithanandham  3 , Adannaya Amadi  1 , David Gaston  1 , Maggie Li  3 , Nicholas J Swanson  3 , Matthew Schwartz  1 , Eili Y Klein  4   5 , Andrew Pekosz  3   4 , Heba H Mostafa  1
Affiliations

Infection with the SARS-CoV-2 Delta Variant is Associated with Higher Infectious Virus Loads Compared to the Alpha Variant in both Unvaccinated and Vaccinated Individuals

Chun Huai Luo et al. medRxiv. .

Update in

Abstract

Background: The emerging SARS-CoV-2 variant of concern (VOC) B.1.6.17.2 (Delta) quickly displaced the B.1.1.7 (Alpha) and is associated with increases in COVID-19 cases nationally. The Delta variant has been associated with greater transmissibility and higher viral RNA loads in both unvaccinated and fully vaccinated individuals. Data is lacking regarding the infectious virus load in Delta infected individuals and how that compares to individuals infected with other SARS-CoV-2 lineages.

Methods: Whole genome sequencing of 2,785 clinical isolates was used to characterize the prevalence of SARS-CoV-2 lineages circulating in the National Capital Region between January and July 2021. Clinical chart reviews were performed for the Delta, Alpha, and B.1.2 (a control predominant lineage prior to both VOCs) variants to evaluate disease severity and outcome and Cycle threshold values (Cts) were compared. The presence of infectious virus was determined using Vero-TMPRSS2 cells and anti-SARS-CoV-2 IgG levels were determined from upper respiratory specimen. An analysis of infection in unvaccinated and fully vaccinated populations was performed.

Results: The Delta variant displaced the Alpha variant to constitute 88.2% of the circulating lineages in the National Capital Region by July, 2021. The Delta variant associated with increased breakthrough infections in fully vaccinated individuals that were mostly symptomatic when compared to the Alpha breakthrough infections, though it is important to note there was a significantly longer period of time between vaccination and infection with Delta infections. The recovery of infectious virus on cell culture was significantly higher with the Delta variant compared to Alpha in both vaccinated and unvaccinated groups. The impact of vaccination on reducing the recovery of infectious virus from clinical samples was only observed with Alpha variant infections but was strongly associated with low localized SARS-CoV-2 IgG for both variants. A comparison of Ct values showed a significant decrease in the Delta compared to Alpha with no significant differences between unvaccinated and vaccinated groups.

Conclusions: Our data indicate that the Delta variant is associated with increased infectious virus loads when compared to the Alpha variant and decreased upper respiratory antiviral IgG levels. Measures to reduce transmission in addition to increasing vaccinations rates have to be implemented to reduce Delta variant spread.

Funding: NIH/NIAID Center of Excellence in Influenza Research and Surveillance contract HHS N2772201400007C, Johns Hopkins University, Maryland department of health, Centers for Disease Control and Prevention contract 75D30121C11061.

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Conflict of interest statement

Declaration of interests

We declare no relevant competing interests

Figures

Figure 1.
Figure 1.
A) SARS-CoV-2 molecular testing at Johns Hopkins Laboratory showing total tested, total positives, and % positivity from January to July 2021 B) Circulating SARS-CoV-2 clades including VOC and VOI from January to July 2021.
Figure 2.
Figure 2.
Cycle threshold (Ct) values of Alpha, Delta, and control variants. A) Ct values of B.1.2 (N = 254), Alpha (N = 562), and Delta (N = 98) variants from all samples with available Ct values. B and C) Correlation of Ct values and ranges of days after the onset of symptoms B) 0 to 5 days, C) >5 days. For this analysis, samples from asymptomatic patients were not included (N: B.1.2 = 214, Alpha = 511, Delta = 75). D) Ct values of Alpha and Delta variants broken down by vaccination status. Alpha (unvacccinated, N = 442, fully vaccinated N = 42), Delta (unvaccinated, N = 47, fully vaccinated N = 23). For this analysis, samples from partially vaccinated patients were not included. E and F) Correlation of Ct values and ranges of days after the onset of symptoms of the Alpha and Delta variants divided by the vaccination status. E) 0 to 5 days, F) >5 days. One-way ANOVA * p < 0.05, ** p < 0.001, ***, p < 0.0001.
Figure 3.
Figure 3.. Recovery of infectious SARS-CoV-2 on Vero-TMPRSS2 cells for Alpha and Delta variants.
A) Percent CPE positives and negatives for Alpha and Delta total, unvaccinated, and vaccinated groups (Alpha unvaccinated, N = 95, vaccinated N = 46, Delta unvaccinated, N = 63, vaccinated, N = 27). Chi-squared test *** p < 0.0001. B) Ct range of CPE positive and negative Alpha and Delta variants. One-way ANOVA *** p < 0.0001 C) Correlation of Ct values and days to the first appearance of CPE (cytopathic effect) for the Alpha and Delta groups.
Figure 4.
Figure 4.. Local SARS-CoV-2 IgG in upper respiratory samples.
A) IgG levels by ELISA in the upper respiratory samples collected from patients with Alpha or Delta variants (unvaccinated: Alpha, N = 30, Delta, N = 17, vaccinated: Alpha, N = 43, Delta, N = 24). One-way ANOVA *** p < 0.0001 B) SARS-CoV-2 IgG correlation to days to the first appearance of cytopathic effect (CPE) for Alpha and Delta true breakthrough specimens on Vero-TMPRSS2 cells. C) Correlation between local IgG levels, Ct values, and recovery of infectious virus. Dashed line demarcates the limit of borderline and negative ELISA results as specified per assay’s package insert. Define the p value and state the statistical tests used.
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