New York City (NYC) experienced a large mpox outbreak in 2022, with 3821 cases. Case counts remained low through most of 2023 at only 184 cases, a mean of 3.5 cases per week. However, incidence increased in 2024, with 191 cases as of 4 May 2024, a mean of 10.6 cases per week. To investigate the evolutionary dynamics underlying this increase in case count, we performed phylogenetic and phylodynamic analysis of the 81 mpox virus (MPXV) genomes sampled in 2023 and 2024 in NYC, sequenced by the NYC Public Health Labs (PHL), in the context of the global MPXV diversity published on NCBI and GISAID as of 30 May 2024.
Of the 113 NYC MPXV genomes sampled from people diagnosed with mpox at sexual health clinics between January 2023 through April 2024, 81 are from unique individuals (32 of these genomes are from a second sequenced swab from the same person) representing 21.6% of NYC mpox cases; 38 genomes were sampled in 2023 and 43 in 2024.
Our maximum likelihood phylogenetic tree (IQ-TREE v.2.1.3, GTR+F+I substitution model) revealed that 79% (34/43) of NYC MPXV sampled in 2024 can be attributed to two clusters. The largest of the clusters (Figure 1A) comprises 30 people with MPXV genomes from NYC, sampled between October 2023 through April 2024 (5 in 2023 and 25 in 2024). The remaining MPXV genomes in this cluster were sampled from across the United States: 5 from Los Angeles County, 3 from Connecticut, 1 from Illinois, and 1 from Washington state. Bayesian phylodynamic inference (BEAST v.1.10.4, HKY+F substitution model, SkyGrid coalescent prior) indicates this cluster has a time of most recent common ancestor in August 2023 (95% highest posterior density: May 2023 through October 2023), with repeated exports of MPXV from NYC to other jurisdictions in 2024.
The second MPXV cluster (Figure 1B) includes MPXV genomes sampled from people in NYC, sampled between January through March 2024, had a time of most recent common ancestor in October 2023 (95% highest posterior density: July 2023 through December 2023). This cluster also includes an MPXV genome sampled in Massachusetts in 2024, which lacks a reported month of sampling and was excluded from phylodynamic inference.
In comparison, the remaining NYC MPXVs clusters during the 2023-2024 sampling period contained 3 of fewer MPXV genomes; the largest comprises people sampled in January and February 2023 (NCBI Access Numbers: PP533281, PP533285, PP533286).
Even though these findings are based on a small number of MPXV genomes, they represent a high proportion of sequenced genomes and indicate that MPXV is persisting locally in NYC and has spread to at least five other jurisdictions across the United States in 2024. It remains to be determined if this cluster growth is due to waning vaccine-induced and/or naturally acquired immunity, a realignment of the sexual network along which MPXV spreads, or viral adaptation.
NYCClustersMPXV.pdf (20.4 KB)
Figure 1. Maximum clade credibility trees for two largest MPXV clusters in NYC detected as of May 2024. (A) The largest cluster. (B) The second largest cluster. Colors indicate geographic location of sampling: CT, Connecticut; IL, Illinois; LAC, Los Angeles County; NYC, New York City; WA, Washington.
Contributors:
Joel O. Wertheim — University of California San Diego
Tetyana I. Vasylyeva — University of California, Irvine
Jonathan E. Pekar — University of California San Diego
Jennifer L. Havens — University of California San Diego