Analysis of genome characteristics and transmission of SARS-CoV-2 strains in North-East of Romania during the first COVID-19 outbreak

Romania officially declared its first SARS-CoV-2 case on February 26, 2020. The first and largest COVID-19 outbreak in Romania was recorded in Suceava, N/E region of the country, and originated at the Suceava regional county hospital. Following sheltering-in-place measures, infection rates decreased, only to rise again after relaxation of measures. This study describes the incursion of SARS-CoV-2 in Suceava and other parts of Romania and analyzes the mutations and their association with clinical manifestation of the disease during the period of COVID-19 outbreak. Phylogenetic analysis indicated multiple sites of origin for SARS-CoV-2 strains in Suceava, specifically from Spain, Italy and Russia, but also other strains related to those from Czech Republic, Belgium and France. Most Suceava samples contained mutations common to European lineages, such as A20268G, however aproximately 10% of samples were missing such mutations, indicating a possible different origin. While overall genome regions ORF1ab, S and ORF7 were subject to most mutations, several recurring mutations such as C27707T were identified, and these were mainly present in severe forms of the disease. Non-synonymous mutations, such as C3225A (Thr987Asn in NSP3a domain), associated with changes in a protein responsible for decreasing viral tethering in human host were also present. Patients with diabetes and hypertension exhibited eight and three time,s respectively, higher odds ratios of acquiring severe forms of the disease and these were mainly related to C27707T mutation. These results will aid in tracing virus movement throughout Romania and identification of infectivity, virulence and pathogenicity.