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Review 6: "Clade I Mpox Virus Genomic Diversity in the Democratic Republic of the Congo, 2018 - 2024: Predominance of Zoonotic Transmission"

Overall, the reviewers appreciated the authors' candid acknowledgment of the study's limitations, including potential sampling biases, and recognized the urgent need for enhanced genomic surveillance to mitigate the mpox epidemic in the DRC. 

Published onOct 05, 2024
Review 6: "Clade I Mpox Virus Genomic Diversity in the Democratic Republic of the Congo, 2018 - 2024: Predominance of Zoonotic Transmission"
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Clade I Mpox virus genomic diversity in the Democratic Republic of the Congo, 2018 - 2024: Predominance of Zoonotic Transmission
Clade I Mpox virus genomic diversity in the Democratic Republic of the Congo, 2018 - 2024: Predominance of Zoonotic Transmission
Description

ABSTRACT Background Recent reports raise concerns on the changing epidemiology of mpox in the Democratic Republic of the Congo (DRC), with increasing case counts, sexual contact-mediated clusters, and sustained human-to-human transmission driven by a novel monkeypox virus (MPXV) subclade, clade Ib. However, only a limited number of clade I MPXV genomes have been characterized so far, from a limited number of regions.Methods We conducted whole genome sequencing of 603 mpox-positive samples that were collected from 581 patients between 2018-2024 in 17 of the 26 provinces of the DRC.Results Genome coverage was at least 70% for 429/603 (71.1%) samples and near full-length MPXV genomes (>90% coverage) were obtained for 348/603 (57.7%) samples from 337 patients. All newly generated MPXV sequences belonged to clade I, among which 17 were clade Ib strains, all from patients infected in 2024 in the South-Kivu province. The large majority (>95%) of the new strains fall within previously described clade Ia groups and potential new groups have also been observed. The low number of APOBEC3 mutations found among clade Ia suggests that most human mpox cases are probably linked to zoonotic transmissions. Genetically diverse MPXV lineages co-circulate in small geographic areas during the same outbreak suggesting multiple zoonotic introductions over a short period from one or multiple reservoir species. Recent identification of mpox cases in Kinshasa shows that multiple lineages circulate in a large urban center, indicating separate introduction events.Conclusion The mpox epidemic in the DRC exhibits two distinct patterns. In traditional endemic regions, the epidemic is predominated by zoonotic spill-over events involving clade Ia. Conversely, in the eastern part of the country, the clade Ib outbreak is driven by human-to-human transmission highlighting the need for a coordinated response effort at the national, regional and international levels.

RR\ID Evidence Scale rating by reviewer:

  • Strong. The main study claims are very well-justified by the data and analytic methods used. There is little room for doubt that the study produced has very similar results and conclusions as compared with the hypothetical ideal study. The study’s main claims should be considered conclusive and actionable without reservation.

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Review: In this study, the authors have analyzed 603 mpox genome sequences from Democratic Republic of Congo (DRC) between 2018 to 2024. Two criterion were used for assessing the sequence quality, coverage and quality. This is as per standard norms and acceptable. Based on the sequencing analysis and corroboration with the existing data, the authors show that mpox sequences from DRC though predominantly belonged to previously reported clade 1A, several new strains/variants are also observed. The data also supports local or geographical evolution of mpox genomes which has also been observed in SARS-CoV-2. 

The differential mutational profile of genome for specific regions highlighted the presence of zoonotic transmission in certain regions while human-to-human transmission in other areas. This signifies how the virus is getting introduces to the human population from its animal reservoirs and thereon spreading in the human population, evolving in the process as well. The role of polymorphisms in APOBEC3 in determining zoonic/human transmission is well documented. 

The methodology is well explained. The figures and tables are apt and aid in understanding of the manuscript. However, the data will have more clarity if two things are added. First, in terms of the phylogenetic tree, it would be highly beneficial if the authors summarize the key mutations or defining variations for each clade. This would help comprehend the results better, particularly the phylogenetic analysis with timeline shown in Figure 3. Secondly, the description of novel variations in the dataset should be better discussed in terms of variations present in other regions of the world as well. The mutations reported elsewhere but absent from DRC and vice versa can be catalogued as a part of the study.  

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Arden jake:

The study provides a comprehensive analysis of 603 mpox genome sequences from DRC, highlighting significant findings like new strains and zoonotic transmission. The methodology is solid, but further clarity on phylogenetic tree mutations and novel variations in global contexts would enhance the study. Overall, this work is crucial and actionable. For more details, visit inat-tv.tr.

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