Covid-19 – No alarmism about the new English variant: what do we need to know?

by Giuseppe Scarlata, Antonino Napoleone, Domenico Gangemi, | December 27, 2020

On December 14, 2020, British authorities have reported to the World Health Organization (WHO) that a new mutated variant of SARS-CoV-2 had been identified using genomic sequencing techniques, in several Covid-19 positive individuals within the British population. Current nomenclature defines it as SARS-CoV-2 VUI 202012/01 (Variant under investigation, year 2020, month 12, variant 01) although it is most commonly known as the “English variant.” “Variant under investigation” would be the most appropriate definition for it as there are still numerous questions to be answered by scientists around the world: is it really associated with increased transmissibility? Will recently developed and approved vaccines be as effective in counteracting the new variant of the virus?  Experts say that the current vaccines will be effective but that unfortunately the variant is associated with a transmissibility even 70% higher than the viral strain originally identified in Wuhan at the beginning of the pandemic. 

Epidemiological studies

The tripling of cases of COVID-19 in the South-East of England in a few weeks prompted the British researchers to deepen and investigate the situation. On December 13, 2020, sequencing data (viral genome analysis) carried out on virus-positive patients detected in the same period were made official and it was found that there were 1108 cases associated with this new variant in the UK. Retrospective studies have dated the emergence of the new variant to September 20, in the south-east of England, more precisely in Kent; there followed a rapid increase in cases associated with it after few weeks, but above all it was found that the transmissibility affected mainly individuals under 60 years of age. Figure 1 shows epidemiological data from the GISAID EpiCoV database updated to December 20, relating SARS-CoV-2 VUI 202012/01 sequences to total SARS-CoV-2 sequences in the United Kingdom.

Genetic variability of RNA viruses

There are different types of viruses, but among these, RNA viruses (i.e. having a genome made up of RNA) are particularly difficult to fight because of their innate ability to change rapidly and produce mutated viral strains that can adapt more easily to their hosts and to new environments. Many RNA viruses (such as Coronavirus) are able to produce a large number of mutations within weeks, precisely because of their genome, which is particularly unstable and prone to mutations of varying degrees that may involve protein complexes involved in the viral structure or in the system of penetration into target cells. Consequently, an RNA virus usually does not constitute a homogeneous population, but rather a set of similar but not identical viral variants. In fact, when in virology we interface with RNA viruses, we apply the concept defined as “quasi-species” of viruses, to indicate the path that characterizes this type of viruses. This concept applies when from the replication of a single original species characterized by a high rate of mutations, numerous related viral variants originate within the same population. This example applies to numerous RNA viruses, such as Coronaviruses, Influenza viruses, or other RNA viruses.  These mutated variants of the virus are continually undergoing selection and changes, and this means that a single mutation may persist and become stable within the viral species, or it may be replaced by subsequent ones, and this depends on many factors, not always predictable experimentally and mathematically. 

Which mutations are involved?  

The analysis of the viral genome by sequencing analyses has revealed 14 mutations compared to the original strain identified in Wuhan last year, identified as sudden changes in the sequence of the RNA of the virus, which affect mainly the Spike protein of the virus. Only some of them are related to its transmissibility and the most relevant seems to be N501Y (Figure 2), which couses the alteration of an amino acid within six key residues in the receptor binding domain (RBD) of the virus; similarly happens with regard to the additional P681H mutation. 

How does this impact on diagnostics?

Can the new mutations negatively affect the performance of diagnostic tests? (for more details: when to do the swab) In this aspect we have good news: a mutation identified in the English variant (deletion of amino acids at position 69/70) can actually negatively affect the results and the specificity of molecular diagnostic tests by Real-Time PCR that have as target the S gene (encoding for the Spike protein of the virus). This is because in the diagnostic phase these tests are looking for a specific portion of the virus, which if subject to numerous mutations, may be less readable and identifiable. However, given that most of the tests in use in diagnostics aim to search for multiple target genes of the virus, there should be no significant impact on diagnostics.

How does this impact on vaccinations? 

A further doubt is related to the effectiveness of the vaccination against the mutated virus: the neutralizing antibodies produced by our body after the inoculation of the vaccine attack more regions of the Spike protein, on whose model the current vaccines were developed (for more details: Pfizer and Moderna vaccines). This explains why it is unlikely that changing just one region of the Spike protein would render the vaccination ineffective. So basically, the vaccine should train the immune system to recognize and fight the virus from different parts of the Spike protein, so even if individual portions were mutated, it should not drastically affect the effectiveness of the vaccine itself. But this must be investigated and analyzed by scientists, who immediately set to work to better understand this point. However, it is not to be excluded that over time further mutations of SARS-CoV-2 will force pharmaceutical companies to remodel and update the composition of vaccines, similar to what normally happens with the flu vaccine (for more information: difference between vaccine technologies).

The situation in Italy

COVID-19 continues to spread rapidly and to cause numerous victims, as well as having a negative impact on the world economic situation. Clearly, the attention of the mass media has shifted towards the new English variant, which apparently may not be the only one, since there is also the possibility of an “African variant”. This should not cause big concern or alarm, since it is a mechanism related to the tendency and intrinsic ability of this virus to generate mutations. Numerous European countries, including Italy, have been forced to interrupt flights to and from the United Kingdom in order to stem the escalation of contagions that such a mutation could entail. In addition, for those who returned from the UK in these days is mandatory to perform a nasopharyngeal swab and self-isolation of 14 days in order to trace and isolate any positive cases, some of which have already spread this variant in other European countries. The WHO recommendation is always to sanitize hands, keep a safe distance and use the facial mask, simple rules that are necessary against the spread of contagions, even those due to each new variant of the virus. Share and have faith in the medical sciences rather than the media: to cope with the current situation we need the collaboration of everyone, and especially during the Christmas holidays period, we need to respect more the hygiene recommendations.

References:

1. https://www.who.int/csr/don/21-december-2020-sars-cov2-variant-united-kingdom/en/
2. Rapid increase of a SARS-CoV-2 variant with multiple spike protein mutations observed in the United Kingdom – ECDC – 20 December 2020.
3. Jacqui Wise, Covid -19: New coronavirus variant is identified in UK. BMJ 2020; 371. https://doi.org/10.1136/bmj.m4857
4. https://www.huffingtonpost.it/entry/variante-inglese-del-covid-trasmissibilita-vaccini-misure-dei-governi-cosa-sappiamo-finora_it_5fe06543c5b60f828857b884
5. Figlerowicz M, Alejska M, et al. Genetic variability: the key problem in the prevention and therapy of RNA-based virus infections. Med Res Rev. 2003 Jul;23(4):488-518. doi: 10.1002/med.10045. PMID: 12710021; PMCID: PMC7168509.