WHOLE GENOME SEQUENCE OF SARS-COV-2 FROM COVID-19 ACQUIRED HEMOPHILIA PATIENT

Abstract

Intro: Acquired hemophilia is an atypical pathology of SARS-CoV-2 infection, which could be variant associated. Here, we share a sequence of the SARS-CoV-2 genome from patient with COVID-19 acquired haemophilia. We explore its lineage, genomic and novel structural variations. Methods: The genome of SARS-CoV-2 from a rare case of COVID-19 acquired hemophilia was extracted and subjected to whole genome sequencing. Bioinformatics analysis was carried out to investigate the lineage, sequence, and novel structural polymorphism in the virus. Findings: Radiological and laboratory work up positively diagnosed the patient with COVID-19 and acquired hemophilia. The patient was treated with standard protocol for the management COVID-19 and an acquired hemophilia and recovered well. The virus was identified of 21J lineage belongs to SARS-CoV-2 delta variant. The genome sequence showed presence of 43 nonsynonymous mutations/indel with a novel 9 amino acid deletion in NSP3 region flanked by nucleic acid binding domain and replicase domain. Structurally, carbon alpha back bone of NSP3 protein showed noticeable variation with the NSP3 of SARSCoV-2 Wuhan strain. Discussion: NSP3 is a 1945 amino acid-long virus protein with multiple functionally important domains. The mutation lies between the nucleic acid binding domain and coronavirus replicase domain of the protein. NSP3 is profoundly important for viral polyprotein processing as it is involved in the cleavage of several NSPs and self-cleavage by working as a papain-like protease. Moreover, NSP3 interacts with several host proteins, including IRF3, ABHD17A, ZNF410, MKRN3, and MKRN2, which have a role in modulating inflammatory pathways. Hence, it suggests a link between low-grade inflammation and hemophilia among infected individuals. Conclusion: There are few previous reports of COVID-19 related acquired hemophilia, the presence of novel NSP3 mutation in the virus warrants further genome surveillance and functional studies to explore the potential association between acquired hemophilia and SARS-CoV-2 variant specific infection.