Friday, October 30, 2020

PrePrint: Emergence and Spread of a SARS-CoV-2 Variant Through Europe in the Summer of 2020



#15,527


All viruses evolve over time, and for the most part, these changes do little or nothing to affect the function or biological fitness of the virus. It's part of the evolutionary process, and despite Hollywood tropes, `mutations' are not necessarily ominous or bad.

Single-stranded RNA viruses (like influenza and coronaviruses) are prone to `duplication errors' during replication (see Mechanisms of Viral Mutation), resulting in random amino acid substitutions. 

Most of these AA substitutions end up being of little consequence, and do nothing to affect the transmissibility, replication, host range, or virulence of the virus. Some even prove detrimental, making the virus less `fit' than its predecessors, or attenuating its virulence.

But we are in a pandemic right now because a (likely) bat-borne coronavirus hit the `right' combination of mutations to allow it to jump species; either to an intermediate host, or directly to humans.

So far, hundreds of variants of SARS-CoV-2 have been identified around the globe, although functional differences between variants are less apparent.

In early May of this year, in More COVID-19 (SARS-CoV-2) Mutation Reportswe looked at a pre-print paper from researchers at the Los Alamos National Laboratory that described a new and increasingly dominant `European' strain of SARS-CoV-2 which they believed had enhanced transmissibility. 

The gist of this report was a new strain (G clade) of SARS-CoV-2 emerged in Europe in February carrying the D614G mutation (among others), and has since overtaken the original Asian strain in many regions of the world due to its enhanced transmissibility. 

The paper was subsequently published in the journal Cell:

Tracking Changes in SARS-CoV-2 Spike: Evidence that D614G Increases Infectivity of the COVID19 Virus

In Brief Korber et al. present evidence that there are now more SARS-CoV-2 viruses circulating in the human population globally that have the G614 form of the Spike protein versus the D614 form that was originally identified from the first human cases in Wuhan, China. Follow-up studies show that patients infected with G614 shed more viral nucleic acid compared with those with D614, and G614-bearing viruses show significantly higher infectious titers in vitro than their D614 counterparts.

Although many researchers cautioned that the pronouncement of a more transmissible `G' clade may be premature, over the summer we've seen several other studies that seem to support the theory that the D614G mutation enhances transmissibility. 

With millions of people actively infected around the globe - each generating millions of new viral copies daily - the emergence of new variants is inevitable. Most will be evolutionary failures or maintain the status quo, but those that gain `fitness' are apt to survive, and even thrive. 

Today we've a new preprint article from researchers at the University of Basel, Switzerland and from Spain which has identified a new, SARS-CoV-2 variant which appears to have emerged in Spain over the summer, and is rapidly gaining traction across parts of Europe. 

Dubbed 20A.EU1, this new variant has increased from very low values prior to mid-July to 40-70% in Switzerland, Ireland, and the United Kingdom by September. 
 
It isn't clear, however, whether this rise to prominence is due to enhanced transmissibility, or was caused by a relaxation of social distancing and travel restrictions in Europe over the summer. 

First a link to, and the abstract from, the study - followed by excerpts from a press release from the University of Basel. Follow the link to read the study in its entirety.


Emma B Hodcroft, Moira Zuber,Sarah Nadeau, Inaki Comas, Fernando Gonzalez Candelas, SeqCOVID-SPAIN consortium, Tanja Stadler, Richard A Neher
 
Abstract 
 
A variant of SARS-CoV-2 emerged in early summer 2020, presumably in Spain, and has since spread to multiple European countries. The variant was first observed in Spain in June and has been at frequencies above 40% since July. Outside of Spain, the frequency of this variant has increased from very low values prior to 15th July to 40-70% in Switzerland, Ireland, and the United Kingdom in September. It is also prevalent in Norway, Latvia, the Netherlands, and France.
 
Little can be said about other European countries because few recent sequences are available. Sequences in this cluster (20A.EU1) differ from ancestral sequences at 6 or more positions, including the mutation A222V in the spike protein and A220V in the nucleoprotein. We show that this variant was exported from Spain to other European countries multiple times and that much of the diversity of this cluster in Spain is observed across Europe. 
 
It is currently unclear whether this variant is spreading because of a transmission advantage of the virus or whether high incidence in Spain followed by dissemination through tourists is sufficient to explain the rapid rise in multiple countries.

(Continue . . . )          



29 October 2020
Spread of a novel SARS-CoV-2 variant across Europe in summer 2020

Researchers from Basel and Spain have identified a novel SARS-CoV-2 variant that has spread widely across Europe in recent months, according to an un-peer-reviewed preprint released this week. While there is no evidence of this variant being more dangerous, its spread may give insights into the efficacy of travel policies adopted by European countries during the summer.

In Europe alone, hundreds of different variants of the new coronavirus SARS-CoV-2 are currently circulating, distinguished by mutations in their genomes. However, only very few of these variants have spread as successfully and become as prevalent as the newly identified variant, named 20A.EU1.

The researchers at the University of Basel, ETH Zürich in Basel and the SeqCOVID-Spain consortium analyzed and compared virus genome sequences collected from Covid-19 patients all across Europe to trace the evolution and spread of the pathogen (see box). Their analysis suggests that the variant originated in Spain during the summer. The earliest evidence of the new variant is linked to a super-spreading event among agricultural workers in the north-east of Spain. The variant moved into the local population, expanding quickly across the country, and now accounts for almost 80% of the sequences from Spain.

“It is important to note that there is currently no evidence the new variant’s spread is due to a mutation that increases transmission or impacts clinical outcome,” stresses Dr. Emma Hodcroft of the University of Basel, lead author of the study. The researchers believe that the variant’s expansion was facilitated by loosening travel restrictions and social distancing measures in summer.
Similar pattern as in spring in Spain

“We see a similar pattern with this variant in Spain as we did in the spring,” advises Professor Iñaki Comas, co-author on the paper and head of the SeqCOVID-Spain consortium. “One variant, aided by an initial super-spreading event, can quickly become prevalent across the country.”

From July, 20A.EU1 moved with travelers as borders opened across Europe, and has now been identified in twelve European countries. It has also been transmitted from Europe to Hong Kong and New Zealand. While initial introductions of the variant were likely from Spain directly, the variant may then have continued to spread onward from secondary countries.

Currently, 20A.EU1 accounts for 90% of sequences from the UK, 60% of sequences from Ireland, and between 30 and 40% of sequences in Switzerland and the Netherlands. This makes this variant currently one of the most prevalent in Europe. It has also been identified in France, Belgium, Germany, Italy, Latvia, Norway, and Sweden.
Travel facilitated the spread

Genetic analysis indicates that the variant travelled at least dozens and possibly hundreds of times between European countries. “We can see the virus has been introduced multiple times in several countries and many of these introductions have gone on to spread through the population,” says Professor Tanja Stadler of ETH Zürich, one of the study’s principal investigators, “This isn’t a case of one intr
oduction just happening to do well.”

Though the rise in prevalence of 20A.EU1 corresponds with the increasing number of cases observed in many European countries this autumn, the study’s authors caution against interpreting the new variant as a cause for the rise in cases. “It is not the only variant circulating in recent weeks and months,” says Professor Richard Neher of the University of Basel, one of the study’s principal investigators. “Indeed, in some countries with significant increases in Covid-19 cases, like Belgium and France, other variants are prevalent.”

(Continue . . . )