Results
Spatiotemporal Distribution of Omicron Variant in NYC
Since the COVID-19 pandemic started in March 2020, we tested 185,870 specimens for SARS-CoV-2 RNA by diagnostic multiplex RT-PCR. A total of 17,058 (9.18%) specimens were positive. These specimens were collected from 87,616 unique persons who were tested once or multiple times. Of those persons, 12,858 had SARS-CoV-2 infection; average incidence rate was 14.68%.
A total of 9,516 specimens were run through NGS; 7,237 specimens passed our quality control, of which 392 specimens were identified as Omicron (Figure 1, panel A). Those Omicron viruses were collected during November 25–December 11, 2021 (Figure 1, panel B); they were widespread throughout NYC, and densities were higher in the boroughs of Manhattan and Brooklyn.
Figure 1.
Distribution of SARS-CoV-2 viruses in New York, New York, USA. A) Temporal distribution of 7,237 sequenced viruses, March–December 2021. B) Temporal distribution of 392 Omicron viruses, November 25–December 11, 2021.
Epidemiologic and Genomic Evidence for Multiple Introductions of Omicron Subclades
We performed a phylogenetic analysis of these 392 Omicron isolates. We found that these isolates could be divided into 4 main clades based on the genotype network, phylogenetic tree, and nucleotide substitutions (Figures 2–4). Most (n = 262; 67%) of these isolates clustered into clade A; those isolates shared a G5515T nucleotide substitution. A total of 65 isolates clustered into 3 smaller clades: clade B (n = 26; 7%), with clade-defining substitution G5924A; clade C (n = 25; 6%), with 3 clade-defining substitutions T10135C, C25708T, and A29301G; and clade D (n = 14; 4%), with 2 clade-defining substitutions C2470T and G22599A. Of note, clade D was consistent with the Omicron subclade BA.1.1 because of its G22599A nucleotide substitution (spike, R346K).
Figure 2.
Genotype network of 392 Omicron viruses from New York, New York, USA, November 25–December 11, 2021. In this network, nodes represent nucleotide genotypes by clade, and lines between nodes represent pairs of nucleotide genotypes with the highest genetic similarity. Node size is scaled to log2 of the number of viruses with the corresponding genotype. Dashed lines indicate pairs of similar genotypes of different clades.
Figure 3.
Geographic distributions of 4 main clades of SARS-CoV-2 Omicron variant virus from New York, New York, USA, November 25–December 11, 2021. A) Clade A. B) Clade B. C) Clade C. D) Clade D. Map source: New York City Department of Health and Mental Hygiene (https://github.com/nychealth/coronavirus-data/blob/master/Geography-resources/MODZCTA_2010_WGS1984.geo.json).
Figure 4.
Phylogeny of 392 SARS-CoV-2 Omicron variant virus isolates from New York, New York, USA, November 25–December 11, 2021. Colored dots represent isolates from this study by clade. Substitution locations are indicated.
We also noted that some Omicron viruses in regions other than NYC had the same substitutions as those 4 clades (Figure 5). To investigate the origins of these 4 clades, we clustered 14,817 global Omicron viruses downloaded from GISAID[22] into the 4 clades based on their clade-defining substitutions. Among the global Omicron viruses, 861 (6%) clustered into clade A, 3,563 (24%) clustered into clade B, 1,716 (12%) clustered into clade C, and 1,686 (11%) clustered into clade D.
Figure 5.
Distribution of SARS-CoV-2 Omicron variant virus isolates clustered into 4 main clades, including viruses identified in this study from New York, New York, USA, November 25–December 11, 2021, and viruses from various regions as obtained from GISAID (https://www.gisaid.org). A) Clade A. B) Clade B. C) Clade C. D) Clade D. For viruses from GISAID, regions were divided into Africa, Asia, Europe, North America (excluding New York state), Oceania, South America, and New York State. Vertical gray dashed lines are to the left of the time at which viruses within the indicated clade were detected in the city of New York during this study. Light blue shading represents the time before our detection of viruses within the indicated clade; light red shading represents the time after we detected the viruses.
We subsequently investigated the spatiotemporal distribution and phylogenetic relationship of global and NYC viruses within these 4 clades (Figures 5, 6). Clade A and its corresponding substitutions were initially detected in NYC on November 29, 2021; clade B on November 25, clade C on December 6, and clade D on December 1. Of note, we found viruses from other regions clustered into these 4 clades that had been collected earlier than our sequenced viruses in NYC (Figure 5): a total of 12 clade A viruses, 71 clade B viruses, 233 clade C viruses, and 83 clade D viruses. The earlier detection of these viruses in other regions suggests independent introductions into NYC.
Figure 6.
Phylogeny of viruses clustered into 4 main clades, including viruses identified in this study from New York, New York, USA, November 25–December 11, 2021, and contextual viruses in various regions from GISAID (https://www.gisaid.org). For each clade, we designated global viruses detected before the time at which we detected the virus within the clade in New York as contextual viruses for phylogeny construction. Colored dots represent viruses from New York by clade; light blue dots represent global contextual viruses.
To further identify the potential introductions, we constructed a phylogenetic tree using viruses clustered into clades A, B, C, and D, including 327 viruses from NYC and 399 viruses from around the world (Figure 6). We found that the early viruses clustered into clade A were detected in North America, Africa, and Europe. Of note, 3 of them (GISAID accession nos. EPI_ISL_7129868, EPI_ISL_7782594, and EPI_ISL_7908023) were detected in other laboratories in New York state. In the phylogenetic tree, early global clade A viruses were located near the base of clade A, and some viruses in NYC were distributed along main branches. Combining the phylogenetic and spatiotemporal distribution of all clade A viruses, we inferred that this clade was introduced into NYC and then spread through local transmission.
Most clade B early viruses were detected mainly in Africa, with sporadic detection in Europe, North America, and Asia. The viruses in NYC clustered closely with those viruses in the early stage of the wave. Clade B viruses were detected only in Africa before November 21, 2021, suggesting that clade B had spread outside of Africa after early local transmission. Thus, we believe that clade B viruses in NYC were the result of another independent introduction. Similarly, clade C and clade D were distributed in regions including Europe, North America, and Africa before our detections in NYC. The close genetic relationship within these 2 clades suggests 2 additional independent introduction events.
Potential Importation Risk for Omicron Variant From Travelers
Our phylogenetic analysis shows that the Omicron variant outbreak in NYC likely resulted from multiple independent introductions. We found that, among the 392 sequenced Omicron viruses in NYC, 13 of them were obtained from domestic travelers from the following states: California (2), Florida (2), Georgia (1), Maryland (1), Maine (1), North Carolina (2), Oregon (1), Rhode Island (1), Texas (1), and Utah (1) (Figure 7). To investigate the genetic relationship between viruses from travelers and locals, we analyzed the 392 Omicron viruses in a timescaled phylogenetic tree, which we constructed using Nextstrain workflow and visualized as timescaled using Auspice[21] (Figure 7). The viruses from travelers were distributed across the phylogeny: 8 of them fell into clade A and 1 into clade C; the remaining 4 did not fall into any of the 4 main clades being discussed. Considering the collection time and genetic similarity, we did not find irrefutable evidence that the sequenced viruses from domestic travelers were the origin of the Omicron variant in NYC.
Figure 7.
Phylogeny of SARS-CoV-2 Omicron viruses identified from travelers and locals in this study, New York, New York, USA, November 25–December 11, 2021. In the phylogenetic tree, colored dots represent viruses from New York residents by clade. Yellow dots represent viruses from travelers. The inset map shows the states and number of patients with isolated viruses. Yellow circles represent travelers' home states; blue circle represents local New York residents. Map source: Wikimedia Commons (https://commons.wikimedia.org/wiki/File:Blank_US_Map_(states_only).svg).
Community Transmission and Co-circulation of Omicron Subclades in NYC
The Omicron variants were distributed in various areas in NYC (Figure 3). To investigate if introductions from outside NYC led to local transmission, we constructed the genotype network and timescaled phylogenetic tree of these 392 viruses (Figures 2, 4). We constructed this phylogenetic tree using Nextstrain workflow and visualized it as timescaled using Auspice.[21] In addition to clade-defining substitutions, we found many novel heritable substitutions added to the subsequent progenies. The close genetic relationship within different clades showed that multiple clades spread in NYC with a co-circulation pattern after introductions.
We also discovered several instances of Omicron community transmission in NYC. We noted the viral distribution in 2 postal (ZIP) codes that had the highest detected number of viruses (Figure 8). In the 11201 ZIP code, we found the 2 viruses (nyomi222 and nyomi335) shared the G2398A substitution that belonged to 2 patients from the same family (family 1). Two viruses (nyomi200 and nyomi352) from patients living in the same household shared the C16596T substitution (household 4). These viruses with shared genome sequences from patients within the same family or the same household address suggest local household transmission (Figure 8, panel A; Figure 9). In the 11220 ZIP code, 8 viruses were from patients working in the same building (workplace 1), and 4 of them (nyomi198, nyomi228, nyomi337 and nyomi358) shared identical genetic substitutions. This epidemiologic evidence suggests community transmission in the workplace (Figure 8, panel B; Figure 9). We also found that even viruses isolated from patients at the same working address might fall into different clades, implying complex and possibly cryptic transmission.
Figure 8.
Mutational profiles of SARS-CoV-2 Omicron variant viruses in 2 local districts, New York, New York, USA, November 25–December 11, 2021. A) District of postal (ZIP) code 11201. Viruses isolated from patients within the same living address or the same family are labeled on the right. B) District of ZIP code 11220. Viruses isolated from patients working at the same building are labeled on the right. Column labels at top indicate substitution locations; shading indicates substitution from any nucleotide to a nucleic acid: dark blue indicates substitution to adenine; red, substitution to cytosine; green, substitution to thymine; and light blue, substitution to guanine.
Figure 9.
Genotype network mapping of transmission events of SARS-CoV-2 Omicron variant in specific groups, New York, New York, USA, November 25–December 11, 2021. Colored dots indicate genotypes of viruses within each transmission event by clade, if known. A) Household 1. B) Household 2. C) Household 3. D) Household 4. E) Family 1. F) Workplace 1.
Emerging Infectious Diseases. 2023;29(2):371-380. © 2023 Centers for Disease Control and Prevention (CDC)
