Travel-driven emergence and spread of SARS-CoV-2 lineage B.1.620 with multiple VOC-like mutations and deletions in Europe

Abstract

Many high-income countries have met the SARS-CoV-2 pandemic with overwhelming sequencing resources and have identified numerous distinct lineages, including some with notably altered biology. Over a year into the pandemic following unprecedented reductions in worldwide human mobility, distinct introduced lineages of SARS-CoV-2 without sequenced antecedents are increasingly discovered in high-income countries as a result of ongoing SARS-CoV-2 genomic surveillance initiatives. We here describe one such SARS-CoV-2 lineage, carrying many mutations and deletions in the spike protein shared with widespread variants of concern (VOCs), including E484K, S477N and deletions HV69del, Y144del, and LLA241/243del. This lineage - designated B.1.620 - is known to circulate in Lithuania and has now been found in several European states, but also in increasing numbers in central Africa owing to important recent increases in genome sequencing efforts on the continent. We provide evidence of likely ongoing local transmission of B.1.620 in Lithuania, France, Germany, Spain, Belgium and the Central African Republic. We describe the suite of mutations this lineage carries, its potential to be resistant to neutralising antibodies, travel histories for a subset of the European cases, and evidence of local B.1.620 transmission in Europe. We make a case for the likely Central African origin of this lineage by providing travel records as well as the outcomes of carefully crafted phylogenetic and phylogeographic inference methodologies, the latter of which is able to exploit individual travel histories recorded for infected travellers having entered different European countries.

Evidence for increased breakthrough rates of SARS-CoV-2 variants of concern in BNT162b2-mRNA-vaccinated individuals

“…3). This is in line with recent concerns regarding misclassifications of Pangolin 37 , and led us to manually verify the phylogenetic location of all sequences in our study. R v4.0.4, Python v3.7.4, pandas v0.24.2 (ref.…”

Human inhalable antibody fragments neutralizing SARS-CoV-2 variants for COVID-19 therapy

“…Additionally, it is to note that the scFv76-cluster antibody reactivity is not significantly affected by mutations at residues K417, L452, Based on present data, we expect the neutralizing activity of scFv76-cl Abs to be maintained since both mutations were found to be independently recognized. Similarly, the recently described SARS-CoV-2 VUI B.1.620, found in several European states and in central Africa (18), is expected not to escape scFv76-cluster antibody recognition. In fact, this variant carries two spike mutations that are either already shown to be recognized (E484K) or are not among the residues composing the spike antigenic epitope (S477N).…”

Evolutionary trajectory of SARS-CoV-2 and emerging variants

“…Preliminary data show increased ACE2 binding affinity and reduced antibody-mediated neutralization for the P.3 variant from Brazil, which contains the spike mutations E484K, N501Y, and P681H [164]. Data also suggest increased ACE2 binding affinity and reduced neutralization profile for the B.1.620 variant from Central Africa, which contains spike mutations E484K, S477N, D614G, and P681H [226]. Other notable variants include N440K variants from India [227] that have increased transmissibility, and the R.1 variant from Japan which contains potential immune escape mutations W152L and E484K [228] , and L452R, all of which contribute to some degree of resistance to antibody-mediated neutralization [229].…”