Used abbreviations

 Variants Detection

Compared to other RNA viruses, coronaviruses have a genetic proofreading mechanism: a complex molecular machinery involved in maintaining the integrity of the SARS-CoV-2 RNA genome, preventing and repairing mutations.

In consequence, the SARS-CoV-2 sequence diversity and overall evolutionary rate appear to be low. Nevertheless, viral mutations occur, and rose in frequency due to natural selection of favourable mutations, random genetic drift, or epidemiological factors.

Newvariants are classified according the potential impact on transmissibility, severity and/or immunity
that is likely to have an impact on the epidemiological situation. ECDC classifies variants as ‘Variants
of Concern’ (VOC) if the impact is known to be significant, ‘Variants of Interest’ (VOI) if preliminary
evidence is indicating a potential impact, and ‘Variants under Monitoring’ 

FACT SHEET

Self test detection of COVID-19 disease (SARS-CoV-2 virus)


D614G variant detection

Till beginning 2021, the main circulating variant of SARS-CoV-2 was the D614G
variant (also referred to as G614), resulting from an D-to-G amino acid change caused by a single
nucleotide mutation at position 1841 of the S-gen in the Wuhan reference strain (D614). Initially
originating in China, this variant emerged in Europe, and went on to become the globally dominant
strain over the course of three months (5): as SARS-CoV-2 is transmitted more rapidly than it evolves,
the viral population is becoming more homogeneous.

Based on CT-value analysis, it had been suggested that the G614 variant is associated with potentially
higher viral loads but not with disease severity (6). Nevertheless, higher viral loads do not prove per
se an increased transmission potential, and there was debate whether G614 was more infectious
than D614, as nicely summarized by Grubaugh et al (7). Later studies demonstrated, however, shifts
over time versus the G614 variant in the same geographic areas, providing more arguments for a
higher transmission rate of this variant (8,9). Both these studies did not find any evidence of a
significant relationship between virus genotypes and altered virulence. A study ex vivo and in vivo in
rodents concluded that the D614G substitution enhanced SARS-CoV-2 infectivity, competitive
fitness, and transmission in primary human cells and animal models (10).

Although the G614 mutation is located in the S protein, it appeared unlikely that it would have a
major impact on vaccines in the pipeline or drastically affect antibody-mediated immunity as the
RBD of the virus is not affected by this locus. An additional study, performing phylogenetic,
population genetics, and structural bioinformatics analyses of 18 514 sequences, also concluded that
a vaccine candidate based on the Wuhan reference strain was likely to be efficacious against all
lineages circulating at that time (11). However, it still remained unknown whether, in the long run,
a gradual accumulation of mutations could result in an ‘antigenic drift’ of SARS-CoV-2 that could
impact vaccine-effectiveness, as seen in analogy with influenza (6).

Alpha variant. In November 2020, a new SARS-CoV-2 variant (VOC202012/01, later named 501Y.V1,
lineage B.1.1.7, initially referred to as the ‘UK variant’, but now referred to as the Alpha variant), was
identified in the United Kingdom (12,13). The variant is defined by 14 mutations resulting in amino
acid changes and three deletions, some of which influence the virus’s transmissibility in humans. In
December 2020, the UK’s New and Emerging Respiratory Virus Threats Advisory Group reported that
the rate of transmission of the variant was 71%, higher than for other variants, and that it may also
have a higher viral load (14). Mathematical modelling showed that an assumed 56% higher
transmissibility is likely to lead to a large increase in incidence, with hospitalizations and deaths
projected to reach higher levels in 2021 than were observed in 2020, even if stringent restrictions
were maintained (15). A later modelling study established that the variant spread during the English
lockdown (from November 5 to December 2) with an average R=1.25, against 0.85 for other variants
(16), and another study that it was 75% more transmissible than other variants (17). A Danish
modelling study from Denmark, on the other hand, estimated an additional transmissibility of 36%
(18). A study in Canada found that the secondary attack rate was 1.31 times higher than for nonVOC cases (19). A rapid scoping review in pre-print found reported increases of risk of transmission ranging from 45% to 71% (20). The consensus is that it is about 50% more transmissible than previous variants.

One of the changes with an impact on the amino acid sequence of the Alpha variant is a deletion at
position 69/70 of the Spike-protein, which has been found to affect the performance of some
diagnostic PCR assays that use an S gene target (TaqPath assay).

By 20 December 2020 more than 97% of PCR tests in England which test negative on the S-gene target and positive on other targets
were due to the 501Y.V1 variant. S gene drop-out has therefore been used as a proxy for 501Y.V1
(21). Analysis of data in the UK, as of January 10, 2021, found that the secondary attack rates for
cases with S gene deletion were 25% to 40% higher than for cases without S-gene deletion (22).

Initial assessment by Public Health England of disease severity through a matched case-control study
reported no significant difference in the risk of hospitalisation or death compared to other variants
(23). Later studies confirmed, however, an increased risk in both hospital admission and death (24).