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.

Keywords: Italy; SARS-Cov-2; lockdown; phylogeny; transmission.

Figure 1

Number of COVID-19 cases and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomes sequences per region and over time in Italy. (A) Italian regions with virus sequence data are coloured, and name of the geographic region and number of sequences are indicated. (B) The number of cases (top)—extracted from publicly available database [11]—and sequences (bottom) for the North, Central, and South regions is shown over time. The period of lockdown is indicated. Blue = North Italy, yellow = Central Italy, orange = South Italy, black = not specified.

Figure 2

Distribution of SARS-CoV-2 lineages in Italy. (A) Number of sequences from different lineages across time for the three major geographic regions in Italy. The circle colour corresponds to each lineage and their size is proportional to the number of sequences sampled for a day for each lineage. Smallest circle = 1 sequence, largest circle = 15 sequences. (B) Italian sequences were extracted from a time-scaled tree (the global tree is shown in Figure S1). Branch lengths indicate the number of nucleotide substitutions per site and branches are coloured according to region; blue = North Italy, yellow = Central Italy, red = South Italy. Tip circles are coloured according to lineage.

Figure 3

Identification of transmission clusters in Italy. The figures depict time-trees with branch lengths proportional to time in years. Branches are coloured according to geographic territory; blue = North Italy, yellow = Central Italy, red = South Italy. Tip circles are coloured according to clustering type; clusters = pink, singletons = black. Lockdown periods are marked by dotted lines. (A) Global tree, (B) Italian sequences extracted from global tree.