Genomic Surveillance for SARS-CoV-2 Variants: Circulation …

By inergency On Nov 13, 2023

Kevin C. Ma, PhD¹^,2,*; Philip Shirk, PhD^1,*; Anastasia S. Lambrou, PhD¹^,2; Norman Hassell, MS¹; Xiao-yu Zheng, PhD¹; Amanda B. Payne, PhD¹; Akilah R. Ali, MPH¹; Dhwani Batra, MS, MBA³; Jason Caravas, PhD³; Reina Chau, MS¹^,4; Peter W. Cook, PhD¹; Dakota Howard¹^,4; Nicholas A. Kovacs, PhD¹; Kristine A. Lacek, MS¹; Justin S. Lee, DVM, PhD³; Duncan R. MacCannell, PhD³; Lakshmi Malapati¹^,5; Sandra Mathew¹; Neha Mittal, PhD¹^,6; Roopa R. Nagilla, MS¹^,4; Rishika Parikh, MPH¹^,7; Prabasaj Paul, PhD³; Benjamin L. Rambo-Martin, PhD¹; Samuel S. Shepard, PhD¹; Mili Sheth, PhD³; David E. Wentworth, PhD¹; Amber Winn, MPH¹; Aron J. Hall, DVM¹; Benjamin J. Silk, PhD¹; Natalie Thornburg, PhD¹; Rebecca Kondor, PhD¹; Heather M. Scobie, PhD¹; Clinton R. Paden, PhD¹ (View author affiliations)

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CDC has used national genomic surveillance since December 2020 to monitor SARS-CoV-2 variants that have emerged throughout the COVID-19 pandemic, including the Omicron variant. This report summarizes U.S. trends in variant proportions from national genomic surveillance during January 2022–May 2023. During this period, the Omicron variant remained predominant, with various descendant lineages reaching national predominance (>50% prevalence). During the first half of 2022, BA.1.1 reached predominance by the week ending January 8, 2022, followed by BA.2 (March 26), BA.2.12.1 (May 14), and BA.5 (July 2); the predominance of each variant coincided with surges in COVID-19 cases. The latter half of 2022 was characterized by the circulation of sublineages of BA.2, BA.4, and BA.5 (e.g., BQ.1 and BQ.1.1), some of which independently acquired similar spike protein substitutions associated with immune evasion. By the end of January 2023, XBB.1.5 became predominant. As of May 13, 2023, the most common circulating lineages were XBB.1.5 (61.5%), XBB.1.9.1 (10.0%), and XBB.1.16 (9.4%); XBB.1.16 and XBB.1.16.1 (2.4%), containing the K478R substitution, and XBB.2.3 (3.2%), containing the P521S substitution, had the fastest doubling times at that point. Analytic methods for estimating variant proportions have been updated as the availability of sequencing specimens has declined. The continued evolution of Omicron lineages highlights the importance of genomic surveillance to monitor emerging variants and help guide vaccine development and use of therapeutics.

CDC’s national genomic surveillance system integrates SARS-CoV-2 sequences from three sources: 1) the National SARS-CoV-2 Strain Surveillance (NS3) program,^† 2) CDC-contracted commercial laboratories, and 3) public sequence data repositories, including the Global Initiative on Sharing All Influenza Data (GISAID) repository and National Center for Biotechnology Information (NCBI) GenBank.^§ Variant proportions generated by genomic surveillance are regularly updated on CDC’s COVID Data Tracker and guide public health measures to address COVID-19^¶ (1,2).

Weekly SARS-CoV-2 consensus sequences** from the NS3 program, commercial laboratories, and data repositories were quality-filtered,^†† deduplicated, and assigned Pango lineages (3). During January 2022–May 2023, the median interval from specimen collection to data availability was 16 days. Weekly variant proportions were estimated at the national and U.S. Department of Health and Human Services (HHS) regional levels^§§ by specimen collection date for the 11 weeks before the most recent 3 weeks; lineages were included if they constituted ≥1% (unweighted) of sequences nationally and contained spike protein substitutions of potential therapeutic relevance. To estimate variant proportions for the most recent 3 weeks, nowcasts were generated using multinomial regression fit on the previous 21 weeks of data.^¶¶ All methods included weighting to account for the complex survey design and adjust for potential sampling biases.*** Nowcasts were conducted for any lineages with ≥0.5% prevalence beginning October 11, 2022,^††† to improve accuracy by accounting for differential growth rates of grouped sublineages. Weekly numbers of COVID-19 cases attributable to variants were estimated by multiplying counts of positive nucleic acid amplification tests from COVID-19 electronic laboratory reporting (CELR) with variant proportions. Doubling times for proportions of specific lineages were estimated from the coefficients of the multinomial nowcasting model.^§§§ Methodologic changes following the public health emergency expiration (4) were summarized. Biweekly estimates using the updated model were compared with weekly estimates from the previous model to assess consistency. Data were current as of June 1, 2023. This activity was reviewed by CDC and conducted consistent with applicable federal law and CDC policy.^¶¶¶

During January 2, 2022–May 13, 2023, a total of 1,697,197 SARS-CoV-2 surveillance sequences from 56 U.S. jurisdictions**** were generated by or reported to CDC from NS3 (1%), commercial laboratories (60%), and repositories (38%); the percentage of sequences from repositories represented an increase from 10% during June 2021–January 2022 (1). The weekly number of sequenced specimens decreased from approximately 65,000 collected in January 2022 to approximately 4,400 in April 2023, as the number of COVID-19 cases declined (Supplementary Figure 1, https://stacks.cdc.gov/view/cdc/129515).

Omicron remained predominant during January 2, 2022–May 13, 2023, with various descendent lineages emerging and becoming predominant nationwide. The BA.1.1 lineage reached predominance by the week ending January 8, 2022, followed by BA.2 by March 26, BA.2.12.1 by May 14, and BA.5 by July 2 (Figure 1). The prevalence of these lineages peaked at 75.7% (95% CI = 73.8%–77.5%) for BA.1.1 by the week ending February 19, 2022; 73.4% (95% CI = 69.6%–77.0%) for BA.2 by April 16; 62.4% (95% CI = 60.7%–64.0%) for BA.2.12.1 by May 28; and 86.2% (95% CI = 85.2%–87.2%) for BA.5 by August 20. Circulation of these lineages coincided with surges in COVID-19 cases (Figure 1) (Supplementary Figure 2, https://stacks.cdc.gov/view/cdc/129516).

During the latter half of 2022, multiple Omicron descendants of BA.2, BA.4, and BA.5,^†††† including BA.2.75, BA.4.6, BF.7, BQ.1, BQ.1.1, BA.5.2.6, BN.1, BF.11, and CH.1.1 accounted for >1% of circulating variants at different points (Figure 1). Several of these lineages independently acquired spike receptor binding domain (RBD) substitutions, including R346T, K444T, N460K, and F486S/P (Table). None attained predominance individually; however, BQ.1 (which includes K444T and N460K) and BQ.1.1 (which also includes R346T) reached a combined peak prevalence of 59.3% by December 24, 2022 (BQ.1, 22.1%; BQ.1.1, 37.2%), coinciding with a winter surge in cases (Figure 1) (Supplementary Figure 2, https://stacks.cdc.gov/view/cdc/129516).

In late fall 2022, the XBB lineage (recombinant of two BA.2 descendant lineages, BM.1.1.1 and BJ.1, with R346T, G446S, N460K, and F486S RBD substitutions) emerged in the United States, reaching <5% prevalence nationally. XBB.1.5, an XBB descendant (harboring an additional S486P substitution) was initially reported in New York City in October 2022 (5) and first reached predominance in HHS Region 2 (New York, New Jersey, Puerto Rico, and the U.S. Virgin Islands) on December 31, 2022, and Region 1 (Connecticut, Maine, Massachusetts, New Hampshire, Rhode Island, and Vermont) on January 7, 2023 (Figure 2). XBB.1.5 further spread south and west to attain national predominance by January 28, 2023, reaching a peak prevalence of 84.1% (95% CI = 81.4%–86.5%) by April 1 (Figure 1).

As of May 13, 2023, the commonly circulating Omicron lineages were XBB.1.5 (61.5%; 95% CI = 56.4%–66.4%), XBB.1.9.1 (10.0%; 95% CI = 6.8%–14.1%), and XBB.1.16 (9.4%; 95% CI = 6.9%–12.5%), with approximately a 19% combined prevalence of other circulating lineages, including XBB (5.3%), XBB.1.9.2 (4.5%), XBB.2.3 (3.2%), XBB.1.16.1 (2.4%), and XBB.1.5.1 (1.9%). Whereas many circulating XBB lineages share the XBB.1.5 spike sequence, XBB.1.16 and XBB.1.16.1 also contain the K478R RBD substitution and XBB.2.3 also contains the P521S substitution (Table). During the week ending May 13, 2023, the fastest doubling times were observed for XBB.1.16 (15.7 days; 95% CI = 13.9–17.9), XBB.1.16.1 (16.7 days; 95% CI = 14.3–20.2), and XBB.2.3 (20.3 days; 95% CI = 16.6–26.0).

The fastest doubling times among lineages assessed at 1% prevalence during January 2, 2022–May 13, 2023, occurred for BA.2.12.1 (5.4 days; 95% CI = 4.8–6.1), BQ.1.1 (6.3 days; 95% CI = 5.5–7.2), BA.5 (6.8 days; 95% CI = 5.9–8.2), and XBB.1.5 (7.0 days; 95% CI = 5.8–8.6). In comparison, the doubling time for Omicron B.1.1.529 was 3.2 days (1). BA.5, XBB.1.5, and BA.1.1 remained predominant for the longest durations (19, 16, and 10 weeks, respectively). The number of cases attributed to each lineage was highest for BA.1.1 (14 million), B.1.1.529 (9.8 million) and BA.5 (8.0 million) (Figure 1) (Supplementary Figure 2, https://stacks.cdc.gov/view/cdc/129516). As of May 13, 2023, XBB.1.5 was associated with 1.8 million cases, with numbers expected to continue increasing.

Beginning May 13, 2023, after the expiration of the public health emergency declaration (4) and in response to declining numbers of cases and sequenced specimens, methodologic changes were made regarding the analysis of SARS-CoV-2 genomic surveillance data. The reporting cadence and unit of analysis changed from weekly to biweekly, with variant proportions estimated for 2-week periods and nowcast predictions conducted for the most recent 4 weeks,^§§§§ and state-specific estimates were discontinued. For calculating survey weights, the level and source for information on positive test results changed to regional-level data from the National Respiratory and Enteric Virus Surveillance System (NREVSS)^¶¶¶¶ (6). The previous and updated analytic methods using CELR- and NREVSS-derived survey weights, respectively, produced similar variant proportion estimates for all lineages. An example comparison of national and regional proportions of XBB.1.5 demonstrates the consistency between methodologies (Supplementary Figure 3, https://stacks.cdc.gov/view/cdc/129517).