Updates on VOCs & VOIs
All viruses, including SARS-CoV-2, the virus that causes COVID-19, change over time. Most changes have little to no impact on the virus’ properties. However, some changes may affect the virus’s properties, such as how easily it spreads, the associated disease severity, or the performance of vaccines, therapeutic medicines, diagnostic tools, or other public health and social measures.
WHO, in collaboration with partners, expert networks, national authorities, institutions and researchers have been monitoring and assessing the evolution of SARS-CoV-2 since January 2020. During late 2020, the emergence of variants that posed an increased risk to global public health prompted the characterisation of specific Variants of Interest (VOIs) and Variants of Concern (VOCs), in order to prioritise global monitoring and research, and ultimately to inform the ongoing response to the COVID-19 pandemic.
WHO and its international networks of experts are monitoring changes to the virus so that if significant mutations are identified, we can inform countries and the public about any changes needed to react to the variant, and prevent its spread. Globally, systems have been established and are being strengthened to detect “signals” of potential VOIs or VOCs and assess these based on the risk posed to global public health. National authorities may choose to designate other variants of local interest/concern.
Current strategies and measures recommended by WHO continue to work against virus variants identified since the start of the pandemic.
The established nomenclature systems for naming and tracking SARS-CoV-2 genetic lineages by GISAID, Nextstrain and Pango are currently and will remain in use by scientists and in scientific research. To assist with public discussions of variants, WHO convened a group of scientists from the WHO Virus Evolution Working Group, the WHO COVID-19 reference laboratory network, representatives from GISAID, Nextstrain, Pango and additional experts in virological, microbial nomenclature and communication from several countries and agencies to consider easy-to-pronounce and non-stigmatising labels for VOI and VOC. At the present time, this expert group convened by WHO has recommended using labeled using letters of the Greek Alphabet, i.e., Alpha, Beta, Gamma, which will be easier and more practical to discussed by non-scientific audiences.
A SARS-CoV-2 variant that meets the definition of a VOI (see below) and, through a comparative assessment, has been demonstrated to be associated with one or more of the following changes at a degree of global public health significance:
WHO label | Pango lineage | GISAID clade/lineage | Nextstrain clade | Earliest documented samples | Date of designation |
|---|---|---|---|---|---|
Alpha | B.1.1.7 | GRY (formerly GR/501Y.V1) | 20I (V1) | United Kingdom, | 18-Dec-2020 |
| Beta | B.1.351 | GH/501Y.V2 | 20H (V2) | South Africa, May-2020 | 18-Dec-2020 |
| Gamma | P.1 | GR/501Y.V3 | 20J (V3) | Brazil, Nov-2020 | 11-Jan-2021 |
| Delta | B.1.617.2 | G/478K.V1 | 21A | India, Oct-2020 | VOI: 4-Apr-2021 VOC: 11-May-2021 |
| WHO label | Pango lineage | GISAID clade/lineage | Nextstrain clade | Earliest documented samples | Date of designation |
|---|---|---|---|---|---|
| Epsilon | B.1.427/B.1.429 | GH/452R.V1 | 21C | United States of America, Mar-2020 | 5-Mar-2021 |
| Zeta | P.2 | GR/484K.V2 | 20B/S.484K | Brazil, Apr-2020 | 17-Mar-2021 |
| Eta | B.1.525 | G/484K.V3 | 21D | Multiple countries, Dec-2020 | 17-Mar-2021 |
| Theta | P.3 | GR/1092K.V1 | 21E | Philippines, Jan-2021 | 24-Mar-2021 |
| Iota | B.1.526 | GH/253G.V1 | 21F | United States of America, Nov-2020 | 24-Mar-2021 |
| Kappa | B.1.617.1 | G/452R.V3 | 21B | India, Oct-2020 | 4-Apr-2021 |
Lambda | C.37 | GR/452Q.V1 | 20D | Peru, Dec-2020 | 14-Jun-2021 |
A SARS-CoV-2 isolate is a Variant of Interest (VOI) if, compared to a reference isolate, its genome has mutations with established or suspected phenotypic implications, and either:
KEYS POINTS
( sitaatti tehty 23.6. 2021. https://www.cdc.gov/coronavirus/2019-ncov/variants/variant-info.html
Viruses constantly change through mutation. A variant has one or more mutations that differentiate it from other variants in circulation. As expected, multiple variants of SARS-CoV-2 have been documented in the United States and globally throughout this pandemic. To inform local outbreak investigations and understand national trends, scientists compare genetic differences between viruses to identify variants and how they are related to each other.
The US Department of Health and Human Services (HHS) established a SARS-CoV-2 Interagency Group (SIG) to improve coordination among the Centers for Disease Control and Prevention (CDC), National Institutes of Health (NIH), Food and Drug Administration (FDA), Biomedical Advanced Research and Development Authority (BARDA), and Department of Defense (DoD). This interagency group is focused on the rapid characterization of emerging variants and actively monitors their potential impact on critical SARS-CoV-2 countermeasures, including vaccines, therapeutics, and diagnostics.
A variant with specific genetic markers that have been associated with changes to receptor binding, reduced neutralization by antibodies generated against previous infection or vaccination, reduced efficacy of treatments, potential diagnostic impact, or predicted increase in transmissibility or disease severity.
Possible attributes of a variant of interest:
A variant of interest might require one or more appropriate public health actions, including enhanced sequence surveillance, enhanced laboratory characterization, or epidemiological investigations to assess how easily the virus spreads to others, the severity of disease, the efficacy of therapeutics and whether currently authorized vaccines offer protection.
Current variants of interest in the United States that are being monitored and characterized are listed in the table below. The table will be updated when a new variant of interest is identified.
B.1.525 (Pango lineageexternal icon)a
Spike Protein Substitutions: A67V, 69del, 70del, 144del, E484K, D614G, Q677H, F888L
Name (Nextstrainexternal icon)b: 20A/S:484K
WHO Label: Eta
First Identified: United Kingdom/Nigeria – December 2020
Attributes:
B.1.526 (Pango lineageexternal icon)a
Spike Protein Substitutions: (L5F*), T95I, D253G, (S477N*), (E484K*), D614G, (A701V*)
Name (Nextstrainexternal icon)b: 20C/S:484K
WHO Label: Iota
First Identified: United States (New York) – November 2020
BEI Reference Isolatec: NR-55359external icon
Attributes:
B.1.526.1 (Pango lineageexternal icon)a
Spike Protein Substitutions: D80G, 144del, F157S, L452R, D614G, (T791I*), (T859N*), D950H
Name (Nextstrainexternal icon)b: 20C
First Identified: United States (New York) – October 2020
Attributes:
B.1.617 (Pango lineageexternal icon)a
Spike Protein Substitutions: L452R, E484Q, D614G
Name (Nextstrainexternal icon)b: 20A
First Identified: India – February 2021
Attributes:
B.1.617.1 (Pango lineageexternal icon)a
Spike Protein Substitutions: (T95I), G142D, E154K, L452R, E484Q, D614G, P681R, Q1071H
Name (Nextstrainexternal icon)b: 20A/S:154K
WHO Label: Kappa
First Identified: India – December 2020
Attributes:
B.1.617.3 (Pango lineageexternal icon)a
Spike Protein Substitutions: T19R, G142D, L452R, E484Q, D614G, P681R, D950N
Name (Nextstrainexternal icon)b: 20A
First Identified: India – October 2020
Attributes:
P.2 (Pango lineageexternal icon)a
Spike Protein Substitutions: E484K, (F565L*), D614G, V1176F
Name (Nextstrainexternal icon)b: 20J
WHO Label: Zeta
First Identified: Brazil – April 2020
Attributes:
(*) = detected in some sequences but not all
a – Phylogenetic Assignment of Named Global Outbreak (PANGO) Lineages is software tool developed by members of the Rambaut Lab. The associated web application was developed by the Centre for Genomic Pathogen Surveillance in South Cambridgeshire and is intended to implement the dynamic nomenclature of SARS-CoV-2 lineages, known as the PANGO nomenclature.
b – Nextstrain, a collaboration between researchers in Seattle, USA and Basel, Switzerland, provides open-source tools for visualizing the genetics of outbreaks. The goal is to support public health surveillance by facilitating understanding of the spread and evolution of pathogens.
c – The Biodefense and Emerging Infections Research Resources (BEI Resources) is a NIAID-funded repository to provide reagents, tools, and information to the research community. The reference viruses proposed here facilitate the harmonization of information among all stakeholders in the COVID-19 pandemic research community. Please note that the reference viruses provided in the tables below are based on what is currently available through the BEI Resources.
A variant for which there is evidence of an increase in transmissibility, more severe disease (e.g., increased hospitalizations or deaths), significant reduction in neutralization by antibodies generated during previous infection or vaccination, reduced effectiveness of treatments or vaccines, or diagnostic detection failures.
Possible attributes of a variant of concern:
In addition to the possible attributes of a variant of interest
Variants of concern might require one or more appropriate public health actions, such as notification to WHO under the International Health Regulations, reporting to CDC, local or regional efforts to control spread, increased testing, or research to determine the effectiveness of vaccines and treatments against the variant. Based on the characteristics of the variant, additional considerations may include the development of new diagnostics or the modification of vaccines or treatments.
Current variants of concern in the United States that are being closely monitored and characterized by federal agencies are included in the table below. The table will be updated when a new variant of concern is identified.
B.1.1.7 (Pango lineageexternal icon)a
Spike Protein Substitutions: 69del, 70del, 144del, (E484K*), (S494P*), N501Y, A570D, D614G, P681H, T716I, S982A, D1118H (K1191N*)
Name (Nextstrainexternal icon)b: 20I/501Y.V1
WHO Label: Alpha
First Identified: United Kingdom
BEI Reference Isolatec: NR-54000external icon
Attributes:
B.1.351 (Pango lineageexternal icon)a
Spike Protein Substitutions: D80A, D215G, 241del, 242del, 243del, K417N, E484K, N501Y, D614G, A701V
Name (Nextstrainexternal icon)b: 20H/501.V2
WHO Label: Beta
First Identified: South Africa
BEI Reference Isolatec: NR-55282external icon
Attributes:
B.1.427 (Pango lineageexternal icon)a
Spike Protein Substitutions: L452R, D614G
Name (Nextstrainexternal icon)b: 20C/S:452R
WHO Label: Epsilon
First Identified: United States-(California)
Attributes:
B.1.429 (Pango lineageexternal icon)a
Spike Protein Substitutions: S13I, W152C, L452R, D614G
Name (Nextstrainexternal icon)b: 20C/S:452R
WHO Label: Epsilon
First Identified: United States-(California)
Attributes:
B.1.617.2 (Pango lineageexternal icon)a
Spike Protein Substitutions: T19R, (G142D*), 156del, 157del, R158G, L452R, T478K, D614G, P681R, D950N
Name (Nextstrainexternal icon)b: 20A/S:478K
WHO Label: Delta
First Identified: India
Attributes:
P.1 (Pango lineageexternal icon)a
Spike Protein Substitutions: L18F, T20N, P26S, D138Y, R190S, K417T, E484K, N501Y, D614G, H655Y, T1027I
Name (Nextstrainexternal icon)b: 20J/501Y.V3
WHO Label: Gamma
First Identified: Japan/Brazil
BEI Reference Isolatec: NR-54982external icon
Attributes:
A variant of high consequence has clear evidence that prevention measures or medical countermeasures (MCMs) have significantly reduced effectiveness relative to previously circulating variants.
Possible attributes of a variant of high consequence:
In addition to the possible attributes of a variant of concern
A variant of high consequence would require notification to WHO under the International Health Regulations, reporting to CDC, an announcement of strategies to prevent or contain transmission, and recommendations to update treatments and vaccines.
Currently there are no SARS-CoV-2 variants that rise to the level of high consequence.
Substitutions of Concern for SARS-CoV-2 Monoclonal Antibody Therapies
In the United States, there are three anti-SARS-CoV-2 monoclonal antibody treatments with FDA Emergency Use Authorization (EUA) for the treatment of COVID-19: bamlanivimab plus etesevimabexternal icon, casirivimab plus imdevimab,external icon, and sotrovimabexternal icon.
CDC’s national genomic surveillance program identifies new and emerging SARS-CoV-2 variants to determine implications for COVID-19 diagnostics, treatments, or vaccines authorized for use in the United States. Sequences with similar genetic changes are grouped into lineages, and multiple lineages can have the same substitutions. For example, the E484K substitution is found in lineages B.1.351, P.1, B.1.526, and many others. Genomic surveillance efforts provide the capability to detect viruses that have reduced susceptibility to treatments more quickly.
In laboratory studies, SARS-CoV-2 variants that contain certain substitutions in the spike protein cause a marked reduction in susceptibility to bamlanivimab and may have reduced sensitivity to etesevimab and casirivimab. The L452R substitution found in the B.1.427 and B.1.429 lineages has been shown to cause a significant reduction in susceptibility to bamlanivimab and a modest decrease in susceptibility to the combination of bamlanivimab and etesevimab, although the clinical implications of this modest decrease are not known. 7 The E484K substitution found in the B.1.351, P.1, and B.1.526 lineages also results in a marked reduction in susceptibility to bamlanivimab, as well as the combination of bamlanivimab and etesevimab.7 Laboratory studies also suggest that the K417N and K417T substitutions, which are present in the B.1.351 and P.1 variants, respectively, along with the E484K mutation, reduces virus susceptibility to casirivimab, although the combination of casirivimab and imdevimab appears to retain activity.14 There is no reported reduction in susceptibility of variants to sotrovimab.28
The table below shows the national and regional unweighted proportions of SARS-CoV-2 that contain the L452R or E484K substitution, individually, as well as the unweighted proportions of SARS-CoV-2 that contain the combination of K417N, E484K, and N501Y substitutions or the combination of K417T, E484K, and N501Y substitutions. As new data become available, additional substitutions may be added to the table below. The national and regional proportions provided in the table below will be updated weekly.
Kun tiedot koronavirus Sars-2:n genomista alkoivat tulla, katselin sitä rakeennetta geeni geeniltä 2020 vuoden aikana, mutta kun etsi erilaisiaterapiamuotoja viruksen moninaista työkaluarsenaalia vastaan , huomaa lopulta , että lähtökohta tiedon hankkimiseen pitää sittenkin keskittää rokotuksen kehittelyn ja rokotekohteen etsintään. Tähän taan olennaisesti liittyy ajan mittaan tulevien virusvarianttien tutkiminen ja niitä koskevien artikkeleiden löytäminen. Nyt kun rokotteistakin alkaa seuloutua tehokkaimpia ja relevanteimpia esiin, eri kansat koettavat hankkia kukin mahdollisuuksiensa mukaan rokotesuojaa. Sain oman mRNA- perusteisen rokotteeni Ruotsin puolella viime kuun alkupäivinä ja toisen anoksen tulen saamaan juhannuksen aikoihin. Tämä on sitä Pfizerin rokotetta.
COVAX- ohjelmassa koetetaan saada kaikille valtioille 20%:inen rokotekattavuus. Skandinaviassa lienee nyt rokotettujen määrät ainakin 40% ellei jo ylikin.
Nyt viime päivinä olen katsellut varianttien luokittelua VOC, VOI, VUI, VHC. Very High Concern- ryhmään ei tällä hetkellä lueta mitään nykyvarianteista. Vaikutavimmat VOC- ryhmäläiset on alettu nietä kreikkalaisin krijaimin Alfa,Beta, Gamma ja Delta. Lisäksi on tarkkailtavien variantein joukossa epsilonista Kappaan asti merkattuja linjoja.
thl.fi ja CDC antavat tarkkoja luetteloja näistä varianteista
Varianttien nimityksistä PANGOLIN järjestelmässä on pitkä luettelonsa joista osa on jo hiipuneita variantteja. Tällaisen listan löytin tänään.https://gifhub.com/cov-lineages/pango-designation/blob/master/lineage-notes.txt
https://github.com/cov-lineages/pango-designation/blob/master/lineage_notes.txt
Sitten löysin erään varianttipuun, jossa A = The Root of the pandemic. Etsin yhden variantin merkitystä, ja näin löysin Brasilialaisten VOC varianttien kaavakuvan ja puun. Brasiliassa on ollutkovin suuri kuolemanaalto. Myös Venäällä on nyt menossa paha kuolemanaalto pandemiasta.
www.isbtweb.org/fileadmin/user_upload/Silvano_Wendel_SARS-CoV-2_Variants_in_Brazil_TTID_meeting_SW_Final_Mar_2021.pdf
Monissa maissa on parin kolmen aallon jälkeistä rauhallisempaa vaihetta kuten nyt Skandinaviassa ,jossa eräitä rajoittavia sääntöjä jo voidaan asteittan helpottaa. Yhteiskunnan liikkuvuus ja ekonomiset rattaat alkavat pikku hiljaa normalisoitua.
Olen ollut pitkiä ajanjaksoja näinä pandemian päivinä Tanskan puolellatyttäreni ja tyttärentyttäreni luona.Hil
jaiseloa. Maskin käyttöä ulkona kaupassa käydessä tai tarhaan lasta viedessä. Emme ole olleet missään erityisessä monipäisten joukkojen tilaisuuksissa pandemian aikana. Joulukirkossa käytiin Tanskan suomalaisten kanssa.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2788023/
Ihmisellä geeni tunnetaan nimellä ISYNA1, sijainti19p13.11.
Tämä on inositolia sisältävien yhdisteiden metaboliassa tahtia rajoittava entsyymi. Sen tehtävät on konvertoida glukoosi-6-fosfaattia myoinositoli-1-fosfaatiksi (MIP) , siitä taas impaasi-entsyymit voivat saada aikaan myoinositolia mI. Sanon tätäsokeria "haisokeriksi"!. Hai käyttää tätä sokeria energiansa kehittämiseen. Myös ihmisaivojen harmaissa soluissa on inositolilipidien kehittämää energia järjestelmää . Glukoosin aueella toimii ATP ja GTP, galaktoosin alueella UTP ja tämä inositoli alkaa CTP alueella synteesejään. mutta metabolinen tie yhtyy lopulta jälleen ATP ja GTP teihin, joitten toimintaa tämä vahvistaa.