Viral sequencing uncovers new mutations, guiding effective response

More then 9,641,109 genome sequences already published on GISAID as of end of March 2022.

WHO Coronavirus (COVID-19) Dashboard

As of end of March 2022, 174 countries shared 2,541,971 Omicron genome sequences with unprecedented speed from sample collection to making these data publicly accessible via GISAID EpiCoV.

Viruses mutate constantly and SARS-CoV-2 is not any different. The emergence of mutations leads to new variants that have different characteristics. Next generation sequencing for the SARS-CoV-2 virus was key to identifying the more transmissible variants. CDC has initiated a genome surveillance program for sequencing genes in the SARS-CoV-2 virus for the purpose of detecting variants that:

Can spread more quickly among individuals
Cause milder or more severe symptoms
Evade detection by PCR based diagnostic kits
Decreased responsiveness to monoclonal antibody-based therapy
Evade natural or vaccine induced immunity

Ayass BioScience are sequencing positive COVID-19 cases to find new mutations.

SARS-CoV-2 genome sequencing is a fast and efficient method for research on viral replication, packaging, function of terminase, transcription regulation, and metabolism of host cell. Ayass BioScience, LLC delivers high quality sequencing data for SARS-CoV-2 genome. Sequencing viral RNA can also describe patterns of infection to help make important decisions about where to steer public health orders and to whom the vaccine needs are delivered. We can apply the sequencing data to show where the highest risks lie for health care providers. A coordinated sequencing system in the U.S. could help end not only this pandemic, but also the next ones.

Positive, negative, neutral mutations during the evolution of coronaviruses:

SARS-CoV-2 variants, if considered to have concerning epidemiological, immunological or pathogenic properties, warranting urgent follow-up investigation.

System for genomic surveillance and the effort to expand sequencing of all emerging variants will increase the availability of timely U.S. genomic surveillance data.

The B.1.1.529 variant was first reported to WHO from South Africa on 24 November 2021. The epidemiological situation in South Africa has been characterized by three distinct peaks in reported cases, the latest of which was predominantly the Delta variant. In recent weeks, infections have increased steeply, coinciding with the detection of B.1.1.529 variant. The first known confirmed B.1.1.529 infection was from a specimen collected on 9 November 2021. (WHO).

Lineage: B.1.1.529, Sublineages: BA.1, BA.1.1, BA.2, BA.3.

This variant has a large number of mutations, some of which are concerning. Preliminary evidence suggests an increased risk of reinfection with this variant, as compared to other VOCs. The number of cases of this variant appears to be increasing in almost all provinces in South Africa. Current SARS-CoV-2 PCR diagnostics continue to detect this variant. Several labs have indicated that for one widely used PCR test, one of the three target genes is not detected (called S gene dropout or S g ene target failure) and this test can therefore be used as marker for this variant, pending sequencing confirmation. Using this approach, this variant has been detected at faster rates than previous surges in infection, suggesting that this variant may have a growth advantage. (WHO)

Conserved Spike mutations – A67V, Δ69-70, T95I, G142D/Δ143-145, Δ211/L212I, ins214EPE, G339D, S371L, S373P, S375F, K417N, N440K, G446S, S477N, T478K, E484A, Q493K, G496S, Q498R, N501Y, Y505H, T547K, D614G, H655Y, N679K, P681H, N764K, D796Y, N856K, Q954H, N969K, L981F.

Conserved non-Spike mutations – NSP3 – K38R, V1069I, Δ1265/L1266I, A1892T; NSP4 – T492I; NSP5 – P132H; NSP6 – Δ105-107, A189V; NSP12 – P323L; NSP14 – I42V; E – T9I; M – D3G, Q19E, A63T; N – P13L, Δ31-33, R203K, G204R.

EPI_ISL_6590608 (partial RBD Sanger sequencing from Hong Kong)

Most Omicron sequences also contain a 3 amino acid insertion (EPE) at position 214 in the Spike protein.

Transmissability: Increased risk of reinfection. It is not yet clear whether Omicron is more transmissible (e.g., more easily spread from person to person) compared to other variants, including Delta. The number of people testing positive has risen in areas of South Africa affected by this variant, but epidemiologic studies are underway to understand if it is because of Omicron or other factors. (According to WHO)
Virulence: It is not yet clear whether infection with Omicron causes more severe disease compared to infections with other variants, including Delta. Preliminary data suggests that there are increasing rates of hospitalization in South Africa, but this may be due to increasing overall numbers of people becoming infected, rather than a result of specific infection with Omicron. There is currently no information to suggest that symptoms associated with Omicron are different from those from other variants. Initial reported infections were among university students—younger individuals who tend to have more mild disease—but understanding the level of severity of the Omicron variant will take days to several weeks. All variants of COVID-19, including the Delta variant that is dominant worldwide, can cause severe disease or death, in particular for the most vulnerable people, and thus prevention is always key. (According to WHO)
Antigenicity: Increase in transmissibility or detrimental change in COVID-19 epidemiology; increase in virulence or change in clinical disease presentation; decrease in effectiveness of public health and social measures or available diagnostics, vaccines, therapeutics (monoclonal antibodies).
Effectiveness of current tests: The widely used PCR tests continue to detect infection, including infection with Omicron, as we have seen with other variants as well. Studies are ongoing to determine whether there is any impact on other types of tests, including rapid antigen detection tests.

Global Positive Samples Sequenced9,641,109

Omicron (Combined Lineages) Sequenced: 2,390,289

% of Global Samples Sequenced: 24.79%

Omicron Lineage BA.2 Sequenced: 443,380 with 10,318 in US (United Kingdom 45.0%, Denmark 25.0%, Germany 5.0%, India 5.0%, Sweden 3.0%)

Summary of B.1.1.529 Data

Summary of Lineage BA.2

Summary for Omicron (Combined Lineages) Data

Global Samples Sequencing Data

Updated March 25 2022

Date of designation – VOI – 4 April 2021, VOC –  11 May 2021. In October 2020 B.1.617 emerged in India, causing an rapid increase in COVID-19 cases across the country. The lineage is further divided into three subgroups: B.1.617.1, B.1.617.2, and B.1.617.3; of which the B.1.617.2 variant has been designated as Variant of Concern (VOC) because of significantly increased infectivity.

B.1.617.2 variant contains nine spike mutations, including five mutations in the N-terminal domain (NTD), 2 mutations in the receptor-binding domain (RBD), 1 mutation in the furin-cleavage site, and one mutation in the spike S2 subunit.

Spike Protein Substitutions: T19R, (V70F*), T95I, G142D, E156-, F157-, R158G, (A222V*), (W258L*), (K417N*), L452R, T478K, D614G, P681R, D950N.
(*) = detected in some sequences but not all.

GeneNucleotideAmino acid
22029-22034 delAGTTCA
EF 156-157 deletion
ORF828248-282530 delGATTTCDF 119-120 deletion
Transmissability: Increased.
Virulence: Likely Increased.
Antigenicity: B.1.617.2 variant is resistant to therapeutic monoclonal antibodies, natural infection’s or vaccine-induced antibodies.
Spread: Originally was discovered in India and has now spread to more than 60 countries. Variant is dominant in India & UK now (and many other Asian countries where sequence data is not widely available), but prevalence also growing fast in US, as well as many European countries.

Global Positive Samples Sequenced: 8,599,460

B.1.617.2 Sequenced: 151,284 (169 Countries/56 US States)

% of Global Samples Sequenced: 1.76%

Most common countries for B.1.617.2 Lineage: United States of America 27.0%, India 18.0%, United Kingdom 15.0%, Germany 5.0%, Turkey 4.0% (Predominantly India lineage with several spike mutations, pango-designation issue #49).

Summary of B.1.617.2 data

Global Samples Sequencing Data

Updated February 2022

What will help to make a path to the end of Covid-19 pandemic?

Successful vaccine development and population vaccination within the time frame not considered possible in the past. Two mRNA COVID-19 vaccines produced efficacy of 94–95%. A key issue here is whether COVID-19 vaccines will be able to protect against infection/disease from these concerning NEW SARS-CoV-2 variants. (READ MORE)