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Genomic Epidemiology of the First Wave of SARS-CoV-2 in Italy.

ABSTRACT: Italy was one of the first countries to experience a major epidemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with >1000 cases confirmed by 1 March 2020. However, virus genome sequence data is sparse and there has been only limited investigation of virus transmission across the country. Here, we provide the most extensive study to date of the genomic epidemiology of SARS-CoV-2 in Italy covering the first wave of infection. We generated 191 new full-length genomes, largely sampled from central Italy (Abruzzo), before, during, and after the enforcement of a nationwide "lockdown" (8 March-3 June). These were combined with 460 published SARS-CoV-2 sequences sampled across Italy. Phylogenetic analysis including global sequence data revealed multiple independent introductions into Italy, with at least 124 instances of sequence clusters representing longer chains of transmission. Eighteen of these transmission clusters emerged before the nation-wide lockdown was implemented on 8 March, and an additional 18 had evidence for transmission between different Italian regions. Extended transmission periods between infections of up to 104 days were observed in five clusters. In addition, we found seven clusters that persisted throughout the lockdown period. Overall, we show how importations were an important driver of the first wave of SARS-CoV-2 in Italy.

SUBMITTER: Di Giallonardo F

PROVIDER: S-EPMC7765063 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Genomic Epidemiology of the First Wave of SARS-CoV-2 in Italy.

Di Giallonardo Francesca F Duchene Sebastian S Puglia Ilaria I Curini Valentina V Profeta Francesca F Cammà Cesare C Marcacci Maurilia M Calistri Paolo P Holmes Edward C EC Lorusso Alessio A

Viruses 20201214 12

Italy was one of the first countries to experience a major epidemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with >1000 cases confirmed by 1 March 2020. However, virus genome sequence data is sparse and there has been only limited investigation of virus transmission across the country. Here, we provide the most extensive study to date of the genomic epidemiology of SARS-CoV-2 in Italy covering the first wave of infection. We generated 191 new full-length genomes, largely ...[more]

PMID: 33327566

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Project description:ImportanceUnderstanding of SARS-CoV-2 variants that alter disease outcomes are important for clinical risk stratification and may provide important clues to the complex virus-host relationship.ObjectiveTo examine the association of identified SARS-CoV-2 variants, virus clades, and clade groups with disease severity and patient outcomes.Design, setting, and participantsIn this cross-sectional study, viral genome analysis of clinical specimens obtained from patients at the Cleveland Clinic infected with SARS-CoV-2 during the initial wave of infection (March 11 to April 22, 2020) was performed. Identified variants were matched with clinical outcomes. Data analysis was performed from April to July 2020.Main outcomes and measuresHospitalization, intensive care unit (ICU) admission, mortality, and laboratory outcomes were matched with SARS-CoV-2 variants.ResultsSpecimens sent for viral genome sequencing originated from 302 patients with SARS-CoV-2 infection (median [interquartile range] age, 52.6 [22.8 to 82.5] years), of whom 126 (41.7%) were male, 195 (64.6%) were White, 91 (30.1%) required hospitalization, 35 (11.6%) needed ICU admission, and 17 (5.6%) died. From these specimens, 2531 variants (484 of which were unique) were identified. Six different SARS-CoV-2 clades initially circulated followed by a rapid reduction in clade diversity. Several variants were associated with lower hospitalization rate, and those containing 23403A>G (D614G Spike) were associated with increased survival when the patient was hospitalized (64 of 74 patients [86.5%] vs 10 of 17 patients [58.8%]; χ21 = 6.907; P = .009). Hospitalization and ICU admission were similar regardless of clade. Infection with Clade V variants demonstrated higher creatinine levels (median [interquartile range], 2.6 [-0.4 to 5.5] mg/dL vs 1.0 [0.2 to 2.2] mg/dL; mean creatinine difference, 2.9 mg/dL [95% CI, 0.8 to 5.0 mg/dL]; Kruskal-Wallis P = .005) and higher overall mortality rates (3 of 14 patients [21.4%] vs 17 of 302 patients [5.6%]; χ21 = 5.640; P = .02) compared with other variants. Infection by strains lacking the 23403A>G variant showed higher mortality in multivariable analysis (odds ratio [OR], 22.4; 95% CI, 0.6 to 5.6; P = .01). Increased variants of open reading frame (ORF) 3a were associated with decreased hospitalization frequency (OR, 0.4; 95% CI, 0.2 to 0.96; P = .04), whereas increased variants of Spike (OR, 0.01; 95% CI, <0.01 to 0.3; P = .01) and ORF8 (OR, 0.03; 95% CI, <0.01 to 0.6; P = .03) were associated with increased survival.Conclusions and relevanceWithin weeks of SARS-CoV-2 circulation, a profound shift toward 23403A>G (D614G) specific genotypes occurred. Replaced clades were associated with worse clinical outcomes, including mortality. These findings help explain persistent hospitalization yet decreasing mortality as the pandemic progresses. SARS-CoV-2 clade assignment is an important factor that may aid in estimating patient outcomes.

Dataset Information

Genomic Epidemiology of the First Wave of SARS-CoV-2 in Italy.

Publications

Genomic Epidemiology of the First Wave of SARS-CoV-2 in Italy.

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