Viral sequencing uncovers new mutations, guiding effective response

VOCs are a very real threat to our people and our current progress on combatting mutations

More then 2,167,558 sequences already published on GISAID as of July 2021

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 discovered in the UK, South Africa, Brazil, California and more recently New York and India. 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.

Without more of this kind of surveillance, much of the country will remain blind to changes in the types of virus circulating in their communities.
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.

The COVID-19 pandemic has devastated health-care systems, shut down schools and communities, dipped the world into an economic recession. Understandably the 2020 was tested all of us, but 2021 looks are presenting with the emergence of multiple variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

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.

An unexpected recent rise in reported COVID-19 cases was attributed to the emergence of the new major SARS-CoV-2 variants. 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.

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.

GeneNucleotideAmino acid
ORF1abC14408TP4715L
G15451AG5063S
C16466TP5401L
SpikeC21618GT19R
22029-22034 delAGTTCA
EF 156-157 deletion
G21987AG142D
T22917GL452R
C22995AT478K
A23403GD614G
C23604GP681R
G24410AD950N
ORF3AC25469TS26L
MT26767CI82T
ORF7AT27638CV82A
C27752TT120I
ORF828248-282530 delGATTTCDF 119-120 deletion
NA28461GD63G
G28881TR203M
G29402TD377Y

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: 2,167,558

B.1.617.2 Sequenced: 163,338

% of Global Samples Sequenced: 7.54%

Distribution of B.1.617.2 Sequences Top 5 Countries: United Kingdom 76.0%, India 8.0%, United States of America 5.0%, Germany 2.0%, Singapore 1.0%

(Predominantly India lineage with several spike mutations.)

Updated July 2021

A more highly transmissible variant of SARS-CoV-2, B.1.1.7 (first detected and sequenced in the UK in September 2020), now has been detected in 12 US States. Modeling data indicate that B.1.1.7 has the potential to increase the U.S. pandemic trajectory in the coming months, because B.1.1.7 has tendency to explode rapidly in new countries where it appears.

This variant has a mutation in the receptor binding domain (RBD) of the spike protein at position 501, where the amino acid asparagine (N) has been replaced with tyrosine (Y). There are three mutations of particular interest in the spike region of the B.1.1.7 genome: N501Y, 69–70del, P681H.

GeneNucleotideAmino acid
ORF1abC3267TT1001I
C5388AA1708D
T6954CI2230T
11288–11296 delTCTGGTTTTSGF 3675–3677 deletion
S (S Protein)21765–21770 delTACATGHV 69–70 deletion
21991–21993 delTTAY144 deletion
A23063TN501Y
C23271AA570D
A23403GD614G
C23604AP681H
C23709TT716I
T24506GS982A
G24914CD1118H
ORF8C27972TQ27stop
G28048TR52I
A28111GY73C
N28280 GAT→CTAD3L
C28977TS235F

Transmissability: Increased by 50% (more efficient and rapid transmission)
Virulence: Potentially 30% more lethal and impact on vaccine efficacy
Antigenicity: Indications of ostensible reduced antigenic activity
Spread: Global

Global Positive Samples Sequenced: 2,167,558

B.1.1.7 Sequenced: 938,834

% of Global Samples Sequenced: 43.31%

Distribution of B.1.1.7 Sequences Top 5 Countries: United Kingdom 27.0%, United States of America 20.0%, Germany 11.0%, Denmark 6.0%, Sweden 6.0%

(UK lineage of concern, associated with the N501Y mutation).

Updated July 2021

This variant was first detected in South Africa and was first sequenced in December 2020. B.1.351 has a mutation that makes it more transmissible from one person to another and a separate mutation that might make it less responsive to the antibodies we form when we have COVID or get vaccinated. This variant was first detected in US in January 2021.

There are three mutations of particular interest in the spike region of the B.1.351 genome: K417N, E484K, N501Y.

GeneNucleotideAmino acid
ORF1abC1059TT265I
G5230TK1655N
C8660TH2799Y
C8964TS2900L
A10323GK3353R
G13843TD4527Y
C14408TP4715L
C17999TT5912I
EC26456TP71L
NC28887TT205I
S (S Protein)
C21614TL18F
A21801CD80A
A22206GD215G
G22299TR246I
G22813TK417N
G23012AE484K
A23063TN501Y
A23403GD614G
C23664TA701V
22286-22294 delCTTGCTTTALAL 242-244del

Transmissability: Increased by 50%
Antigenicity: 21% reduction in antigenicity, but effective neutralisation
Spread: Global

Global Positive Samples Sequenced: 1,924,067

B.1.351 Sequenced: 22,658

% of Global Samples Sequenced: 1.18%

Distribution of B.1.351 Sequences Top 5 Countries: South Africa 19.0%, Sweden 10.0%, Germany 9.0%, United States of America 9.0%, France 8.0%

Updated July 2021

P.2 (descendent of B.1.1.28). This variant was first detected in Brazil and was first sequenced in November 2020.
P.1 (descendent of B.1.1.28). This variant was first detected in Japan in travelers from Brazil in January 2021.
Both variants were identified in the United States at the end of January 2021.

There are three mutations of particular interest in the spike region of the P.1/P.2 genome: N501Y, E484K, K417T.

GeneNucleotideAmino acid
ORF1abC3828TS1188L
A5648CK1795Q
11288–11296 delTCTGGTTTTSGF 3675–3677 deletion
G17259TE5665D
SpikeC21614TL18F
C21621AT20N
C21638TP26S
G21974TD138Y
G22132TR190S
A22812CK417T
G23012AE484K
A23063TN501Y
A23403GD614G
C23525TH655Y
C24642TT1027I
ORF8G28167AE92K
ins28269-28273 AAAC
NC28512GP80R

Transmissability: Likely Increased
Virulence: 10–80% more lethal
Antigenicity: Overall reduction in effective neutralisation
Spread: International
Both variants contains a set of additional mutations that may affect its ability to be recognized by antibodies.

Global Positive Samples Sequenced: 2,167,558

P.1 Sequenced: 45,159

P.2 Sequenced: 4,222

% of Global Samples Sequenced (P1): 2.08%

% of Global Samples Sequenced (P2): 0.19%

Distribution of P.1 Sequences Top 5 Countries: United States of America 41.0%, Brazil 29.0%, Canada 10.0%, Belgium 4.0%, Chile 4.0%

(Alias of B.1.1.28.1, Brazilian lineage with a number of spike mutations with likely functional significance E484K, K417T, and N501Y).

Distribution of P.2 Sequences Top 5 Countries: Brazil 53.0%, United States of America 28.0%, Canada 4.0%, Suriname 2.0%, Argentina 2.0%

(Alias of B.1.1.28.2, Brazilian lineage.)

Updated July 2021

This variants first emerged in late spring or summer of 2020 before it was first detected by researchers from the University of California, San Francisco, in December 2020. Now they have been found in at least 45 U.S. states and several countries around the world.
This variant is concerning because scientific data shows that it is more contagious, more likely to be associated with severe illness, and at least partially resistant to neutralizing antibodies.

There are five mutations of particular interest in the spike region of this genomes: 4205V and D1183Y in the ORF1ab-gene, and S13I, W152C, L452R in the spike proteins S-gene.

B.1.427

GeneNucleotideAmino acid
ORF1abC1059TT265I
G9738CS3158T
C16394TP5377L
G17014TD5584Y
SpikeT22917GL452R
A23403GD614G
NC28887TT205I
ORF3aG25563TQ57H

B.1.429

GeneNucleotideAmino acid
ORF1abC1059TT265I
A12878GI4205V
C14408TP4715L
G17014TD5584Y
SpikeG21600TS13I
G22018TW152C
T22917GL452R
A23403GD614G
ORF3aG25563TQ57H
NC28887TT205I

Transmissability: Likely Increased
Virulence: Likely Increased
Antigenicity: Likely Increased
Spread: North America, and in Europe, Asia and Australia

B.1.427

Global Positive Samples Sequenced: 2,167,558

B.1.427 Sequenced: 16,295

% of Global Samples Sequenced: 0.75%

Distribution of B.1.427 Sequences Top 5 Countries: United States of America 97.0%, Mexico 2.0%, Aruba 0.0%, Argentina 0.0%, Canada 0.0%

(USA lineage (CA))

B.1.429

Global Positive Samples Sequenced: 2,167,558

B.1.429 Sequenced: 33,950

% of Global Samples Sequenced: 1.57%

Distribution of B.1.429 Sequences Top 5 Countries: United States of America 98.0%, Canada 1.0%, Mexico 1.0%, South Korea 0.0%, Chile 0.0%

(A lineage predominantly circulating in California but with exports to other countries. Characterized by the spike L452R mutation but also has spike:W152C orf1ab:D5584Y and N:T205I.)

Updated July 2021

The variant first emerged in samples taken in November. By Jan. 2021, the variant represented about 3% of samples analyzed by researchers, rising to 12.3% by mid-February, according to a study by scientists at Columbia University Vagelos College of Physicians and Surgeons that has yet to be peer-reviewed. By mid-February, the Caltech team found that B.1.526 cases had risen to 27 percent of viral sequences in the database.

There are three mutations of particular interest in the spike region of the B.1.526 genome: E484K, S477N, N501Y.
Genetic analysis of B.1.526 variants also revealed several mutations on the spike protein including, L5F, T95I, D253G, D614G, and A701V.
Additional mutations in the S, N, NSP2, NSP3, NSP4, NSP6, NSP8, NSP12 and NSP13 genes.

ProteinNucleotideAmino acid
ORF1abC1059TT265I
T9867CL3201P
11288–11296 delTCTGGTTTTSGF 3675–3677 deletion
C14408TP4715L
A16500CQ5412H
SpikeC21575TL5F
C21846TT95I
A22320GD253G
G23012AE484K
G22992AS477N
A23403GD614G
C23664TA701V
NC28869TP199L
G28975AM234I
ORF3aC25517TP42L
G25563TQ57H
ORF8C27925TT11I

Transmissability: Likely Increased
Virulence: Likely Increased
Antigenicity: Drop in effectiveness of certain monoclonal treatments and some current vaccines. This mutation could evade natural immune responses, causing reinfection in people who were had recovered from earlier variants of the coronavirus.
Spread: Has been reported in some of the most populous areas of New York: Westchester, Bronx, Queens, Manhattan and Brooklyn. When genomic data from public databases was analyzed, approximately 140 genomes was found to be related to the B.1.526 variant spread across the Northeast.

Global Positive Samples Sequenced: 2,167,558

B.1.526 Sequenced: 44,051

% of Global Samples Sequenced: 2.03%

Distribution of B.1.526 Sequences Top 5 Countries: United States of America 98.0%, Spain 0.0%, Aruba 0.0%, Ecuador 0.0%, Colombia 0.0%

(A lineage predominantly circulating in New York but with a few exports to other countries. Characterized by spike mutations T95I and D253G, plus others. The most frequent spike mutation pattern is L5F T95I D253G E484K D614G A701V, with a smaller fraction having S477N instead of E484K. Spike mutation E484K is present in about half of this lineage (as of 2021-02-10) – Very possible not all new additions carry T95I and D253G (someone should check this, e.g. for USA/NY-Wadsworth-21008455-01/2021 and Aruba/AW-RIVM-11403/2021).

Updated July 2021

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.