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

Abstract

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants concerning for enhanced transmission, evasion of immune responses, or associated with severe disease have motivated the global increase in genomic surveillance. In the current study, large-scale whole-genome sequencing was performed between November 2020 and the end of March 2021 to provide a phylodynamic analysis of circulating variants over time. In addition, we compared the viral genomic features of March 2020 and March 2021.

Methods: A total of 1600 complete SARS-CoV-2 genomes were analyzed. Genomic analysis was associated with laboratory diagnostic volumes and positivity rates, in addition to an analysis of the association of selected variants of concern/variants of interest with disease severity and outcomes. Our real-time surveillance features a cohort of specimens from patients who tested positive for SARS-CoV-2 after completion of vaccination.

Results: Our data showed genomic diversity over time that was not limited to the spike sequence. A significant increase in the B.1.1.7 lineage (alpha variant) in March 2021 as well as a transient circulation of regional variants that carried both the concerning S: E484K and S: P681H substitutions were noted. Lineage B.1.243 was significantly associated with intensive care unit admission and mortality. Genomes recovered from fully vaccinated individuals represented the predominant lineages circulating at specimen collection time, and people with those infections recovered with no hospitalizations.

Conclusions: Our results emphasize the importance of genomic surveillance coupled with laboratory, clinical, and metadata analysis for a better understanding of the dynamics of viral spread and evolution.

Keywords: COVD-19; SARS-CoV-2; sequencing; variant of concern.

Figure 1.

Severe acute respiratory syndrome coronavirus 2 positivity and genotypes at Johns Hopkins Hospital. A, Percentage positivity among total molecular tests. B, Percentage clade distribution between November 2020 and March 2021. C, Stack plot of estimated number of cases per clade based on total number of cases per day and percentage sequenced within each clade. Data shown as 15-day rolling average.

Figure 2.

Patient demographics in all patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) diagnosed at Johns Hopkins Hospital (A, C, E) and SARS-CoV-2–positive results characterized by whole-genome sequencing (B, D, F), from November 2020 to the end of March 2021. A, B, Patient race by percentage (white [blue line], black [orange line], Asian [green line], or other/unknown [dark red line]) and 15-day rolling mean age (purple line). C, D, Age of symptomatic and asymptomatic patients, by race. E, F, Cycle threshold (Ct) for positive results in symptomatic and asymptomatic patients, by race.

Figure 3.

Phylogenetic relatedness of severe acute respiratory syndrome coronavirus 2 genomes sequenced at Johns Hopkins between November 2020 and the end of March 2021. The tree was generated using Nextstrain [26].

Figure 4.

Genomic diversity over time and associated patient demographics. A, Percentage of predominant lineages over time. B, Total numbers of key lineages over the surveillance period. C, Patient ages for predominant and key lineages, colored by clade. D, Cycle threshold (Ct) values in predominant and key lineages, colored by clade. E, Patient race by percentage, in association with predominant and key lineages. *P < .05.

Figure 5.

Genomic changes in the National Capital Region over 1 year. A, Characterized lineages from March 2020 and March 2021. B, Number of unique amino acid substitutions and deletions viral encoded proteins from March 2020 and March 2021. C, Heat map of amino acid substitutions and deletions present in March 2021 and March 2020.

Figure 6.

Association of lineages with severe coronavirus disease 2019. A, Number of samples by lineage with hospital admission status separated by disease severity. Numbers above bars represent percentages of the total for each lineage. *P < .05. Abbreviation: ICU, intensive care unit. B, Heat map of percentages of samples with amino acid changes that showed at ≥5% of samples from hospitalized patients, compared with all samples.