The first local mpox outbreak in Guangdong Province, China occurred in June 2023. However, epidemiological data have failed to quickly identify the source and transmission of the outbreak. Here, phylogeny and molecular evolution of 10 monkeypox virus (MPXV) genome sequences from the Guangdong outbreak were characterized, revealing local silent transmissions that may have occurred in Guangdong whose mpox outbreaks suggested a molecular epidemiological correlation with Portugal and several regions of China during the same period. The lineage IIb C.1, which includes all 10 MPXV from Guangdong, shows consistent temporal continuity in both phylogenetic characteristics and unique molecular evolutionary mutation spectrum, reflected in the continuous increase of single nucleotide polymorphisms (SNPs) and shared mutations over time. Compared with the Japan MPXV, the Guangdong MPXV showed higher genomic nucleotide differences and separated 14 shared mutations from the B.1 lineage, comprising 6 non-synonymous mutations in genes linked to host regulation, virus infection, and virus life cycle. The unique mutation spectrum with temporal continuity in IIb C.1, related to apolipoprotein B mRNA-editing catalytic polypeptide-like 3, promotes rapid viral evolution and diversification. The findings contribute to understanding the ongoing mpox outbreak in China and offer insights for developing joint prevention and control strategies.

On April 23, 2022, an international flight KQ880 from Nairobi, Kenya arrived at Guangzhou Baiyun International Airport, Guangzhou City, Guangdong Province. All passengers were transferred to the quarantine hotel for routine 14-day medical observation and regular tested of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid. One of the patients, a 27-year-old Chinese male, reported positive SARS-CoV-2 nucleic acid on April 27, 2022. The patient had a history of full coronavirus disease 2019 (COVID-19) vaccination and denied exposure to other COVID-19 cases in the past 14 days. After diagnosis, he was transferred to Guangzhou Eighth People’s Hospital for treatment. On April 30, 2022, a nasal swab sample from the patient was sequenced using the Illumina MiniSeq platform (Illumina, San Diego, CA, USA), and genotyping results showed that the patient was infected with Omicron subvariant BA.2.12.1. A total of 33 amino acid mutation sites (T19I, A27S, G142D, V213G, G339D, S371F, S373P, S375F, T376A, D405N, R408S, K417N, N440K, L452Q, S477N, T478K, E484A, Q493R, Q498R, N501Y, Y505H, D614G, H655Y, N679K, P681H, S704L, N764K, D796Y, Q954H, N969K and L24del, P25del, P26del) were detected on the spike gene, two of which (L452Q and S704L) were key sites defining the signature of sublineage BA.2.12.1 (1-2) (Figure 1). The sequence has been submitted to the National Genomics Data Center (under the accession number WGS025539). On May 4, 2022, the World Health Organization reminded to closely monitor BA.2.12.1 subvariants (2). Compared to other Omicron variants, BA.2.12.1 subvariants shows stronger immune escape, even after having been vaccinated with booster dose (3). Several studies have shown that the transmissibility of BA.2.12.1 is about 23% to 27% faster than that of BA.2. Omicron BA 2.12.1 subvariants spread very fast, which led to the resurgence of the epidemic in many parts of the United States, and cases have been reported in at least 17 countries (4). Public health officials are focusing on this subvariant and trying to learn more. Author Affiliations

On April 29, 2022, a flight arrived at Baiyun International Airport, Guangzhou City, Guangdong Province, from Amsterdam Schiphol Airport, Netherlands. After the first test of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid at the airport, all passengers were admitted to a quarantine hotel for a routine 14-day medical observation. On April 30, one of the passengers (a 20-year-old Chinese female) was reported positive for coronavirus disease 2019 (COVID-19), and then a nasopharyngeal swab sample was immediately retested on May 1 and reported positive. The patient was fully vaccinated against COVID-19 and completed 14 days of quarantine before flying to China. She denied any history of exposure to COVID-19 cases. After diagnosis, the patient was sent to Foshan Fourth People’s Hospital for treatment. On May 4, 2022, the viral genomic sequence of the patient was obtained using the Illumina MiniSeq platform (Illumina, San Diego, CA, USA), and genotyping results showed that the genome belonged to the Omicron/variant of concern (VOC) sublineage BA.4, with a total of 30 amino acid mutations (V3G, T19I, A27S, G142D, V213G, G339D, S371F, S373P, S375F, T376A, D405N, R408S, K417N, N440K, L452R, S477N, T478K, E484A, F486V, Q498R, N501Y, Y505H, D614G, H655Y, N679K, P681H, N764K, D796Y, Q954H, N969K) and 5 deletions (L24del, P25del, P26del, H69del, V70del) in the Spike protein gene. The phylogenetic tree indicates that the sequenced BA.4 has high similarity to the genome detected in Denmark on May 4, 2022 (GISAID: EPI_ISL_12648960) (Figure 1). The sequence has been deposited in the National Genomics Data Center (under the accession number WGS025540). On May 4, 2022, the World Health Organization reminded to closely monitor Omicron BA.4 subvariants (1). BA.4 is driving the upsurge in South Africa and has rapidly replaced BA.2, with over 50% of sequenced cases since the first week of April 2022 (2). Compared to BA.2, the BA.4 subvariants also showed stronger immune escape to the plasma of 3-dose vaccinees, even vaccinated BA.1 convalescent plasma (3-4). Cases of BA.4 infection have been reported in at least 20 countries, mainly from South Africa (62.39%) (5-6). Researchers are focusing on this subvariant and trying to learn more.