The first wave of the COVID-19 epidemic in Spain was associated with early introductions and fast spread of a dominating genetic variant

Abstract

The coronavirus disease 2019 (COVID-19) pandemic has affected the world radically since 2020. Spain was one of the European countries with the highest incidence during the first wave. As a part of a consortium to monitor and study the evolution of the epidemic, we sequenced 2,170 samples, diagnosed mostly before lockdown measures. Here, we identified at least 500 introductions from multiple international sources and documented the early rise of two dominant Spanish epidemic clades (SECs), probably amplified by superspreading events. Both SECs were related closely to the initial Asian variants of SARS-CoV-2 and spread widely across Spain. We inferred a substantial reduction in the effective reproductive number of both SECs due to public-health interventions ( R e < 1), also reflected in the replacement of SECs by a new variant over the summer of 2020. In summary, we reveal a notable difference in the initial genetic makeup of SARS-CoV-2 in Spain compared with other European countries and show evidence to support the effectiveness of lockdown measures in controlling virus spread, even for the most successful genetic variants.

Evolutionary and Phenotypic Characterization of Two Spike Mutations in European Lineage 20E of SARS-CoV-2

“…S1 in the supplemental material). These mutations continued arising independently of each other and, by the end of June, when the predominant circulating genotypes from the first wave in Spain had already been replaced by other variants ( 30 ), were also observed together ( Fig. S1 ).…”

“…We therefore examined if the presence of D1163Y and G1167V alters the neutralization capacity of convalescent-phase sera using VSV pseudotyped with either the 20E or 1163.7 S genotypes. We tested the sensitivity of these pseudotyped viruses to neutralization by sera from early (April 2020; first wave in Spain) or later (October 2020; second wave in Spain) in the pandemic, when newer variants were dominant ( 5 , 30 ). Overall, the 1163.7 genotype conferred a modest but statistically significant reduction in sensitivity to neutralization by six serum samples tested from the early stage of the pandemic, as measured by the titers required to inhibit viral entry by 80% (ID 80 ; mean = 6.75; range, 1.30 to 17.68; P = 0.008 by paired t test) ( Fig.…”

“…We examined if these two mutations conferred evasion of preexisting immunity, which could compromise vaccine efficacy and/or result in reinfection. For this, we used sera from both the first (April 2020) and second (October 2020) epidemic waves of the infection in Spain, because an almost complete replacement of SARS-CoV-2 S genotypes of different variants occurred between these two time points in Spain ( 30 ). When utilizing sera from donors infected during the first wave of the pandemic in Spain, we found a modest but statistically significant reduction in susceptibility to neutralization of the 1163.7 S genotype compared to the 20E S genotype of approximately 6-fold ( Fig.…”

“…The dominance of a lineage in a geographical region is sometimes determined by the number of introductions and mobility among regions ( 30 ) rather than by a change in a biological trait that confers a selective advantage ( 5 ). Nearly all VOC thus far have spread outside the country where they were initially identified and are estimated to spread faster than other cocirculating genotypes, becoming dominant for a period ( 25 , 31 , 32 ) and eventually being replaced locally by other variants ( 24 ).…”

A Genomic Snapshot of the SARS-CoV-2 Pandemic in the Balearic Islands

“…RNA virus extraction from respiratory samples was performed with the MagMAX Viral/Pathogen II Nucleic Acid Isolation Kit (Thermo Fisher Scientific) which is specifically designed to recover RNA and DNA from viral particles contained in viral transport media. Genomic library preparation was conducted following the SeqCOVID Consortium protocols (López et al, 2021). Briefly, RNA was first retro-transcribed into cDNA and SARS-CoV-2 complete genome amplification was conducted in two parallel multiplex PCR, accordingly to the openly available protocol developed by the ARTIC network (Quick, 2020) and using the V3 multiplex primers scheme (Github, 2019).…”