An Update on Severe Acute Respiratory Syndrome Coronavirus 2 Diversity in the US National Capital Region: Evolution of Novel and Variants of Concern

Morris, C. Paul; Luo, Chun; Amadi, Adannaya; Schwartz, Matthew C.; Gallagher, Nicholas; Ray, Stuart C.; Pekosz, Andrew; Mostafa, Heba H.

doi:10.1093/cid/ciab636

Cited by 29 publications

(34 citation statements)

References 42 publications

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“…300 µL of sample was extracted and eluted in 60 µL elution buffer. Sequencing and data analysis were performed as previously described (4,22).…”

Section: Amplicon Based Sequencingmentioning

confidence: 99%

“…Lineage B.1.1.7 (Alpha) was classified as a variant of concern (VOC) by the United States Center for Disease Control and Prevention (CDC) due to evidence of higher transmissibility and concern for more severe disease (1). The Alpha variant, which was first detected in Southeast England in September 2020 (2), became the predominant in new SARS-CoV-2 infections in the UK by December 2020, spread globally, and rapidly became the major lineage in the US by April 2021 (3,4).…”

Section: Introductionmentioning

confidence: 99%

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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

Luo¹,

Morris

Sachithanandham

et al. 2021

Preprint

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154

144

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BackgroundThe 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.MethodsWhole 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.ResultsThe 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.ConclusionsOur 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.FundingNIH/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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“…300 µL of sample was extracted and eluted in 60 µL elution buffer. Sequencing and data analysis were performed as previously described (4,22).…”

Section: Amplicon Based Sequencingmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Luo¹,

Morris

Sachithanandham

et al. 2021

Preprint

Self Cite

154

144

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“…SARS-CoV-2 genome data were taken from NCBI virus database on 14 April 2021. After removing short sequence snippets, the original data set consisted of 65,359 SARS-CoV-2 genomes assigned to different labeling schemes (Table A1) [6][7][8][9][10]17], namely those (i) of the World Health Organization (WHO) using Greek letters for Variants of Concern (VOCs) and Variants of Interest (VOIs); (ii) clades proposed by the GISAID (Global Initiative on Sharing All Influenza Data) [9], (iii) lineages suggested by the PANGOLIN (Phylogenetic Assignment of Named Global Outbreak LINeages) tool [19], (iv) the years-and-letter nomenclature code introduced by Nextstrain, all combined with information about date and geographic location, when and where the respective samples were collected. Sequences were downloaded as FASTA files and mapped to the reference genome (NC_045512.2m WIV04, [20]) using BLAST to obtain the mutated positions in terms of SNVs (Single Nucleotide Variants) for each variant of the genome.…”

Section: Sars-cov-2 Genome Data and Preprocessingmentioning

confidence: 99%

“…Variants of concern (VOCs) became dominating since late 2020 where alpha, beta, gamma arising in parallel all becoming presently replaced by the 'Indian' delta variant. Often appearance of VOCs is associated with increased incidence reflecting the evolution of the virus towards increased infectivity (transmissibility) and/or better adaption to hosts physiology and virulence [10,[32][33][34][35].…”

Section: Covid-19 In Time and Spacementioning

confidence: 99%

“…Virus sequences are now being generated and shared at an unprecedented rate and opened a new age of virus genomic studies. More than two million SARS-CoV2 sequences are available in total and thousands of new sequences coming in each day via GISAID (the Global Initiative on Sharing All Influenza Data) to permit a near real-time surveillance of the pandemic [8,9] for a better understanding of the dynamics of viral spread and evolution [10]. Sequencing provided a detailed picture of the changing virus, presumably the best documented virus evolutionary process so far.…”

Section: Introductionmentioning

confidence: 99%

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The Evolving Faces of the SARS-CoV-2 Genome

Schmidt

Arshad

Bernhart

et al. 2021

Viruses

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Surveillance of the evolving SARS-COV-2 genome combined with epidemiological monitoring and emerging vaccination became paramount tasks to control the pandemic which is rapidly changing in time and space. Genomic surveillance must combine generation and sharing sequence data with appropriate bioinformatics monitoring and analysis methods. We applied molecular portrayal using self-organizing maps machine learning (SOM portrayal) to characterize the diversity of the virus genomes, their mutual relatedness and development since the beginning of the pandemic. The genetic landscape obtained visualizes the relevant mutations in a lineage-specific fashion and provides developmental paths in genetic state space from early lineages towards the variants of concern alpha, beta, gamma and delta. The different genes of the virus have specific footprints in the landscape reflecting their biological impact. SOM portrayal provides a novel option for ‘bioinformatics surveillance’ of the pandemic, with strong odds regarding visualization, intuitive perception and ‘personalization’ of the mutational patterns of the virus genomes.

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