Molecular epidemiology of SARS-CoV-2 isolated from COVID-19 family clusters

Gunadi, Wibawa H., Hakim M.S., Marcellus, Trisnawati I., Khair R.E., Triasih R., Irene, Afiahayati, Iskandar K., Siswanto, Anggorowati N., Daniwijaya E.W., Supriyati E., Nugrahaningsih D.A.A., Budiono E., Retnowulan H., Puspadewi Y., Puspitawati I., Sianipar O., Afandy D., Simanjaya S., Widitjiarso W., Puspitarani D.A., Fahri F., Riawan U., Fauzi A.R., Kalim A.S., Ananda N.R., Setyati A., Setyowireni D., Laksanawati I.S., Arguni E., Nuryastuti T., Wibawa T., Herini E.S., Widowati T., Satria C.D., Sumardi, Riyanto B.S., Gani M., Maulana S., Rizki L.P., Intansari U.S., Herningtiyas ‬E.H., Harahap N.I.F., Poermadjaja B., Hutasoit S.H.M.T., Indaryati, Setyawan H., Athollah K., Inggriani M.P., the Yogyakarta-Central Java COVID-19 study group

Pediatric Surgery Division, Department of Surgery/Genetics Working Group, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada/Dr, Sardjito Hospital, Jl. Kesehatan No. 1, Yogyakarta, 55281, Indonesia; Disease Investigation Center Wates, Directorate General of Livestock and Animal Health Services, Ministry of Agriculture, Yogyakarta, Indonesia; Department of Microbiology, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia; Genetics Working Group, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia; Pulmonology Division, Department of Internal Medicine, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada/Dr, Sardjito Hospital, Yogyakarta, Indonesia; Department of Clinical Pathology and Laboratory Medicine, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada/Dr, Sardjito Hospital, Yogyakarta, 55281, Indonesia; Department of Child Health, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada/Dr, Sardjito Hospital, Yogyakarta, Indonesia; Balai Besar Teknik Kesehatan Lingkungan Dan Pengendalian Penyakit, Yogyakarta, Yogyakarta, Indonesia; Department of Computer Science and Electronics Faculty of Mathematics and Natural Sciences, Universitas Gadjah Mada, Yogyakarta, Indonesia; Department of Child Health/Genetics Working Group, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada/UGM Academic Hospital, Yogyakarta, Indonesia; Department of Physiology, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada/UGM Academic Hospital, Yogyakarta, Indonesia; Department of Anatomical Pathology/Genetics Working Group, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia; Department of Microbiology, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, UGM Academic Hospital, Yogyakarta, Indonesia; Centre of Tropical Medicine, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia; Department of Pharmacology and Therapy/Genetics Working Group, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia


Abstract

Background: Transmission within families and multiple spike protein mutations have been associated with the rapid transmission of SARS-CoV-2. We aimed to: (1) describe full genome characterization of SARS-CoV-2 and correlate the sequences with epidemiological data within family clusters, and (2) conduct phylogenetic analysis of all samples from Yogyakarta and Central Java, Indonesia and other countries. Methods: The study involved 17 patients with COVID-19, including two family clusters. We determined the full-genome sequences of SARS-CoV-2 using the Illumina MiSeq next-generation sequencer. Phylogenetic analysis was performed using a dataset of 142 full-genomes of SARS-CoV-2 from different regions. Results: Ninety-four SNPs were detected throughout the open reading frame (ORF) of SARS-CoV-2 samples with 58% (54/94) of the nucleic acid changes resulting in amino acid mutations. About 94% (16/17) of the virus samples showed D614G on spike protein and 56% of these (9/16) showed other various amino acid mutations on this protein, including L5F, V83L, V213A, W258R, Q677H, and N811I. The virus samples from family cluster-1 (n = 3) belong to the same clade GH, in which two were collected from deceased patients, and the other from the survived patient. All samples from this family cluster revealed a combination of spike protein mutations of D614G and V213A. Virus samples from family cluster-2 (n = 3) also belonged to the clade GH and showed other spike protein mutations of L5F alongside the D614G mutation. Conclusions: Our study is the first comprehensive report associating the full-genome sequences of SARS-CoV-2 with the epidemiological data within family clusters. Phylogenetic analysis revealed that the three viruses from family cluster-1 formed a monophyletic group, whereas viruses from family cluster-2 formed a polyphyletic group indicating there is the possibility of different sources of infection. This study highlights how the same spike protein mutations among members of the same family might show different disease outcomes. © 2021, The Author(s).

COVID-19 severity; Family cluster; Multiple spike protein mutations; Phylogenetic analysis; SARS-CoV-2 transmission; Whole genome sequencing


Journal

BMC Medical Genomics

Publisher: BioMed Central Ltd

Volume 14, Issue 1, Art No 144, Page – , Page Count


Journal Link: https://www.scopus.com/inward/record.uri?eid=2-s2.0-85107375854&doi=10.1186%2fs12920-021-00990-3&partnerID=40&md5=c9f3a5745afae5e39b1a294b6afa1fa9

doi: 10.1186/s12920-021-00990-3

Issn: 17558794

Type: All Open Access, Gold, Green


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