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Since May 2022, Monkeypox, a zoonotic Orthopox DNA virus was reported in more than 102 countries indicating expansion of its geographic range. We analyzed the complete genomes sequences of Monkeypox cases from Kerala (n=5 travelled from UAE) and Delhi (n=5 no travel history), India confirmed during July to August 2022. All the retrieved MPXV sequences from India covering 90 to 99% genome belong to A.2 lineage of clade IIb. The A.2 MPXV lineage divided in three sub clusters; first cluster Kerala n=5, Delhi n=2 aligned with the USA-2022 ON674051.1; while second of Delhi n=3 aligned with USA-2022 ON675438.1 and third consists of the UK, USA and Thailand. Recent update in MPXV lineage designated all the five sequences from Kerala as A.2.1. In addition to known 16 single nucleotide polymorphisms (SNPs) along with 13 APOBEC3 cytosine deaminase activity determined specific lineage defining mutations in A.2 lineage, 25 additional APOBEC3 mutations were found in 10 reported sequences. The study emphasizes need of enhancing genomic surveillance to understand the mutation and its linkage.

Monkeypox deaths have been rarely reported across the globe. A total of 15 fatalities have been reported globally from endemic and non-endemic countries in 2022. The current outbreak of Monkeypox had been largely limited to the community of men who have sex with men primarily with multiple bisexual or homosexual partners. The vast majority of the cases infected with Monkeypox had recovered and the complications like sepsis and encephalitis had been reported in the immunocompromised individuals. The mortality in Brazil and Mexico were primarily in the immunocompromised individuals, while in Spain the fatal cases were immunocompetent with no underlying conditions. To date, India had recorded 11 cases of Monkeypox infection from Kerala (n = 5) and New Delhi (n = 6). Here we report the first fatal case of Monkeypox virus (MPXV) infection imported from UAE to Kerala, India in July 2022. A 22-year-old apparently immunocompetent male with no significant past medical history was admitted in an unconscious state to a private hospital in Kerala following a single episode of acute onset generalized tonic-clonic seizures. The clinical features, MRI findings, CSF picture, and EEG findings of this case suggest encephalitis. Only the case's oropharyngeal/nasopharyngeal swabs (OPS/NPS) were found to be positive for MPXV. The next generation sequencing on OPS/NPS specimen could retrieve 92.76% of the MPXV genome and belonged to A.2 lineage of clade IIb as observed in the other confirmed Monkeypox cases from India.