Molecular epidemiology of SARS-CoV-2 isolated from COVID-19 family clusters.
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.
['Gunadi|||', 'Wibawa|Hendra|H|', 'Hakim|Mohamad Saifudin|MS|', 'Marcellus|||', 'Trisnawati|Ika|I|', 'Khair|Riat El|RE|', 'Triasih|Rina|R|', 'Irene|||', 'Afiahayati|||', 'Iskandar|Kristy|K|', 'Siswanto|||', 'Anggorowati|Nungki|N|', 'Daniwijaya|Edwin Widyanto|EW|', 'Supriyati|Endah|E|', 'Nugrahaningsih|Dwi Aris Agung|DAA|', 'Budiono|Eko|E|', 'Retnowulan|Heni|H|', 'Puspadewi|Yunika|Y|', 'Puspitawati|Ira|I|', 'Sianipar|Osman|O|', 'Afandy|Dwiki|D|', 'Simanjaya|Susan|S|', 'Widitjiarso|William|W|', 'Puspitarani|Dyah Ayu|DA|', 'Fahri|Fadil|F|', 'Riawan|Untung|U|', 'Fauzi|Aditya Rifqi|AR|', 'Kalim|Alvin Santoso|AS|', 'Ananda|Nur Rahmi|NR|', 'Setyati|Amalia|A|', 'Setyowireni|Dwikisworo|D|', 'Laksanawati|Ida Safitri|IS|', 'Arguni|Eggi|E|', 'Nuryastuti|Titik|T|', 'Wibawa|Tri|T|', '|||']
D000328:Adult D000368:Aged D000369:Aged, 80 and over D000086382:COVID-19 D002648:Child D005190:Family D005260:Female D059014:High-Throughput Nucleotide Sequencing D006801:Humans D007214:Indonesia D008297:Male D008875:Middle Aged D009154:Mutation D010802:Phylogeny D012367:RNA, Viral D000086402:SARS-CoV-2 D012720:Severity of Illness Index D064370:Spike Glycoprotein, Coronavirus D000073336:Whole Genome Sequencing
Family cluster Multiple spike protein mutations Phylogenetic analysis COVID-19 severity SARS-CoV-2 transmission Whole genome sequencing