Pangokoodin nimilista laajenee edelleen. JN.1 varianttien alaryhmät saavat uusia merkintöjään Omikronien joukossa.

 https://github.com/cov-lineages/pango-designation/blob/master/pango_designation/alias_key.json

 

Huomaa myös rekombinaatiot!

 

 

Covid-19 ja Sars-Cov-2 tartunnat vain jatkuvat tosin hiljaiselolla edelleen vuoden 2024 lopulla.

 Rokotuksista on delleen hyötyä. Sairautta aiheuttava omikron varianttien joukko on JN.1  alalinjoista muodostunut ja edelleen ilmentää uusia varianttilinja. Kansanterveysviiraston lähteestä saa kuulla tilanteen ruotsinkielisenä tekstinä.  Suositellaan  ottamaan sekä koronavirusrokote että influenssavirusrokote, varsinkin  yli 65 vuotiaille ja iäkkäimmille   ja riskiryhmille  esitetään suositus.

https://www.folkhalsomyndigheten.se/folkhalsorapportering-statistik/statistik-a-o/sjukdomsstatistik/covid-19-veckorapporter/

Veckorapporter för 2024

• Aktuell veckorapport om covid-19
• Arkiv för covid-19 veckorapporter 2024

Seuraava raportti saadaan viikon 45 lopulla.  

Taulukoitua tietoa: 

Tabellbilaga

Samtliga genetiska grupper i tabell 1 är undergrupper inom omikronvarianten JN.1. Data i tabell 1 är preliminära då sekvenseringsresultat kommer att tillkomma.

Tabell 1. Genetiska grupper enligt pangolin som utgör minst en procent av fall från vecka 38 till och med vecka 41 2024, sekvenserade inom övervakningsprogrammet för SARS-CoV-2.

Genetisk grupp enligt pangolin	Antal sekvenserade fall	Andel av sekvenserade fall (procent)
KP.3.1.1	342	44
XEC	105	14
JN.1.16.5	32	4
MC.1	24	3
MC.13	21	3
MC.16	19	2
LB.1.4	18	2
KP.2.3.6	16	2
KP.1.1.3	13	2
LF.7	13	2
KP.2.3	11	1
KP.3.3	10	1
MC.10	10	1
MC.6	9	1
MC.8	8	1

Uuden influenssapandemian alla... Tärkeää alustavaa tietoa H5N1 lintuviruksesta,joka on lähetnyt liikeklle lämminverisiin eläinlajeiin ja myös hieman ihmiskuntaan jo.

 https://www.buzzsprout.com/1109867/15128389

Euroopan tilanteesta   yllä.

GISAID , OIE /Wahis,  FAO, WHO   tietolähteitä.

Tavalliset Mekan matkakuolemat taas lisääntyneet 2024 - liekö joukossa Covid-19-pandemian jälkitilassa olevia?

 

Nearly 500 confirmed fatalities from Hajj heatwave as hundreds more feared dead. The official death toll from this year's Hajj pilgrimage has soared to almost 500 and the true toll could be more than double that as reports emerged that as many as 600 Egyptian worshipers perished on the route to Mecca amid extreme heat.for 1 dag siden Google News

Lämpöhalvaus ja Covid-19, paha samanaikaisliittymä.

 https://pubmed.ncbi.nlm.nih.gov/38831931

 

. 2024 May 30:17:555-563.

doi: 10.2147/IMCRJ.S461078. eCollection 2024. 

Background: Hyperthermia and multiple organ dysfunction syndrome (MODS) are the main characteristics of heatstroke and COVID-19. Differentiating between these illnesses is crucial during a summer COVID-19 pandemic, but cases of heatstroke comorbid with COVID-19 are rarely reported. 

Case description: We report the first case of heatstroke comorbid with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection in a 52-year-old male. After receiving intravenous antibiotics, organ protection measures, and treatment for coagulation disorders, his fever and coma resolved. However, he developed dyspnea and cerebral hemorrhage after several days. This patient experienced a multi-pathogen pulmonary infection and an intractable coagulopathy that ultimately resulted in MODS and death.  

Heatstroke Comorbid with SARS-CoV-2 Infection:

 A Case Report and Literature Review

inflammation, immune abnormalities, and coagulation disorders. The interaction between inflammation and coagulation disturbances contributed to the underlying mechanism in this case, highlighting the importance of early anti-infection, treatment for coagulopathy, immune regulation, and organ protection as crucial interventions.

Keywords: COVID‐19; cerebral hemorrhage; coagulation disorder; heatstroke; infection.

© 2024 Ni et al.

 

Suomen THL suosittelee iäkkäille ja immuunivajeisille ensi sijassa syksyn 2024 uutta varianttirokotetta (JN.1 antigeeninä).

 

THL suosittelee koronarokotteen tehosteannosta iäkkäille ja tietyille riskiryhmille syksyllä – rokotukset aiempaa aikaisemmin

Julkaisuajankohta 23.5.2024

Terveyden ja hyvinvoinnin laitos (THL) suosittelee tulevana syksynä koronarokotteen tehosteannosta iäkkäille ja tietyille riskiryhmille. Suositus on, että rokotukset toteutetaan aiempaa aikaisemmin ja kahdessa vaiheessa.

Ensi syksynä koronarokotteen tehosteannosta suositellaan hoitokodeissa ja säännöllisessä järjestetyssä kotihoidossa oleville, kaikille yli 80-vuotiaille sekä kaikille voimakkaasti immuunipuutteisille iästä huolimatta. Suositus on, että näiden ryhmien rokotukset aloitetaan syksyllä heti kun rokotteet ovat saapuneet Suomeen. 

Edellä mainittujen ryhmien ohella syksyn tehosterokotetta suositellaan myös kaikille 75–79-vuotiaille. Heillä vakavan taudin riski on kuitenkin yllä mainittuja ryhmiä pienempi. THL suosittelee, että myös nämä rokotukset toteutetaan tulevana syksynä tavanomaista aikaisemmin.

Koronarokotetta on lisäksi syytä tarjota syksyllä viimeistään influenssarokotusten yhteydessä myös muille 65 vuotta täyttäneille sekä 18 vuotta täyttäneille, joilla on jokin vakavan koronavirustaudin riskiä lisäävä perussairaus. 

Hyvinvointialueet vastaavat rokotusten järjestämisestä alueellaan ja kertovat, mistä ja milloin rokotteen voi saada.  

Tavoitteena ehkäistä sairaalahoitoja ja kuolemia

Koronarokotuksilla pyritään ehkäisemään koronasta johtuvia sairaalahoitoja ja kuolemia. Suosituksen pohjaksi THL:ssä on yhdistetty rekisteritietoja koronan aiheuttamista sairaalahoidoista ja kuolemista syksyllä 2023, henkilöiden perussairauksista ja iästä sekä syksyn 2023 koronarokotuksista. 

“Analyysimme perusteella rokottaminen on hyvin vaikuttavaa yli 80-vuotiailla ja voimakkaasti immuunipuutteisilla. Koronakuolemia voidaan estää etenkin rokottamalla hoitokotien asukkaita, sillä suurin osa kuolemista tapahtuu hoitokodeissa“, sanoo THL:n tutkimusprofessori Tuija Leino. Alle 75-vuotiaiden rokottaminen ei olekaan yhtä vaikuttavaa kuin iäkkäämpien.

Iällä on vaikutus rokotusten vaikuttavuuteen

Riski sairastua sairaalahoitoiseen koronatautiin nousee selvästi iän myötä, mutta vakavan koronavirustaudin riskiä lisäävien perussairauksien määrä ja vakavuus vaihtelevat ihmisillä paljon. Tämän vuoksi rokotteita on syytä tarjota myös muille 65 vuotta täyttäneille sekä niille yli 18-vuotiaille, joiden perussairaus lisää koronataudin riskiä. 

Tämänhetkisen tiedon mukaan syksyn koronarokotuksissa käytetään varianttiräätälöityjä rokotteita, jotka on päivitetty Euroopan lääkeviraston suosituksen mukaisesti uutta JN.1-varianttia vastaan.

Suositukset koronarokotuksista perustuvat Kansallisen rokotusasiantuntijaryhmän (KRAR) ja THL:n yhteisiin arvioihin.

Lisätiedot 

Kuka tarvitsee koronarokotuksen syksyllä 2024? Suositus ja sen epidemiologinen tausta. (THL,pdf)Avautuu uudessa välilehdessäLinkki toiselle sivustolle

Koronarokotteet (THL, sivut päivitetään myöhemmin)

ECDE katsaus respiratoristen taudinaiheuttajien tilanteeseen kesäkuun 1. viikolla 2024

 https://www.ecdc.europa.eu/en/publications-data/communicable-disease-threats-report-1-7-june-2024-week-23

 European Centre for Disease Prevention and Control, Solna, Sweden
www.ecdc.europa.eu
ECDC NORMAL
Week 23, 1−7 June 2024
This week’s topics
1. Overview of respiratory virus epidemiology in the EU/EEA - weekly monitoring
2. SARS-CoV-2 variant classification
3. Cholera – Comoros and Mayotte – 2024 – Weekly monitoring
4. Out-of-season increase in norovirus (NoV) activity
5. Seasonal surveillance on West Nile virus infections starts in week 23
6. Middle East respiratory syndrome coronavirus (MERS-CoV) – Multi-country – Monthly update
7. Influenza A(H5N2) - Multi-country (World) - Monitoring human cases
8. Oropouche virus disease - Cuba - 2024

Pikakatsahdus rekombinoitumisten evoluutioon Omikron varianteissa

 Alustava artikkeli  toukokuulta antaa tieteellistä taustaa omikronin  alkuvaiheen rekombinaatioihin: 

https://pubmed.ncbi.nlm.nih.gov/38793756/

Niitähän ilmeni ensin BA.1 ja BA.2 diversiteettien kesken, sittemmin niiden kehityneiden alalinjojen kesken ja sittemmin rekombinaatioon osallistui rekombinntit itse.  tietyt   rekombinantit VOI- viruksista toimivat  ikäänkuin  vaihdeasemina,, joissa päälinjojen  tehokkaasti lisääntyvät  linajt pystyivät parantamaan tehokkuuksiaan, mutta toisaalta  heikkoja sivulinjoja syntyi lukuisasti. 

Tehokkaaksi päälinjaksi on osoitautunut BA.2 omikron päälinjasta  kehittyneet  VOI ja VUM variantit. Varsinkin   delt-aallon jälkeen on BA.2. 75* toiminut monissa  rekombinanteissa  tehon tuottoprosessisa tekijänä. Nytkuitenkin  on vaihtunut  sen sijaan BA.2.86* diversiteetin virukset.  Niiten  viimeaikaisista  rekombinaatioista eikutienkaan vielä saa tieteellisiä artikkeleita PubMed kliinisestä kentästä. Tämä siirtymä BA.2.75  diversiteetistä BA.2.86 diversiteettiin on tapahtunut   aivan tässä viime aikoina ja  siltä ajalta on seuraavia rekombinanteja taulukossa:

XDD, XDK, XDN, XDQ,  XDP, XDR, XDS, XDT, XDU, XDV, XDW, XDY, XDZ, XEA ja viimeisenä  GITHUB listoihin ilmoitettu XEB. 

Erikoista on myös se, että esim XDY on rekombinaatio näiden uusimpien BA.2.86.1 alalinjojen virusten kesken   "LB.1.2.1" ja "KP.3.2."

Lyhennykset LB ja KP osoittavat  alalinjojen alalinjoja BA.2.86.1* diversiteetin kartalla. 

"LB" Alias JN.1.9.2, Alias BA.2.86.1.1.9.2

"KP" Alias  JN.1.11.1  Alias , BA.2.86.1.1.11.1 .

Näm JN ä linjat sinänsä  ovat akkumuloineet immunologiaan vaikuttavia  aminohappomuutoksia askel askeleelta, joten arveltavasti rekombinaatiosta voi sattua  tulemaan vakaviakin  tuloksia, sattumista, Toisaalta  voi  tulokset olla  huonompaakin laatua kuin nämä nykyiset  ilmenevät JN ja KP alalinjat itse.  Evoluutio on sanottu konvergoivaksi laadultaan.  Eri virukset  eri tavoin, eri tietä,  hankkivat tuloksena samankaltaisia  hyötyä antavia  aminohapposubstituutioita tai deleetioita.  Saa vain odotella uutisia, onko  tällä pandemian aiheuttaneella  omikronvariantilla vielä  jotain "mahtavampaa  historiaa" tänä vuonna kirjoitettavanaan. Joka tapauksessa  on valmiustilaa ja rokotteen suunnittelua. Rokoteantigeeni katsotaan JN.1 linjasta  ilmeisesti. 

Huolestuttavaa tietomurtoa on tapahtunut GITHUB näyttöpintaan heijastuvanakin tässä virustutkimuksen kriittisessä vaiheessa

 Nyt olisi pystyttävä näkemään mikä varianteista vaikuttaa  aiheuttavan vielä ehkä pahankin pa ulkopuolelta vaikutettua katoamista. Esim käyriä ja  graafisia karttoja antava ohjelma ei enää tulee esiin, tietysti  näytteiden vähäinen määrakin tekee niiten  luomisen mahdottomaksi. Tiedemiesryhmä on  aurannut tulevan  tietomäärän kahteen  laariin jo aiemmin, vähemmän tärkeät ja pienimääräiset uudet virusnäytteet käsitellään  alustavasti eri kohdassa ja nostetaan tarvittaessa esiin aktuelliksi aiheeksi, mutta tässäkin funktiossa on jotain jarrua nyt 18.6.  etsin jo  netistä selitystä ja löysin GitHUB  tietueita koskevan uutisen:

273GB of data stolen in GitHub repo hack

As BleepingComputer reported over the weekend, a 273GB torrent file containing The New York Times' stolen data was leaked on the 4chan message board on Thursday.

"Basically all source code belonging to The New York Times Company, 270GB," the 4chan forum post said. "There are around 5 thousand repos (out of them less than 30 are additionally encrypted I think), 3.6 million files total, uncompressed tar."

"Around June 6, 2024, a post on another third-party site made this data publicly available, including a file that contained some of your personal information," the Times confirmed in data breach notification letters sent to affected contributors.

The folder names indicate that a wide variety of information was stolen, including IT documentation, infrastructure tools, and source code, allegedly including the viral Wordle game.

A 'readme' file in the archive states that the threat actor used an exposed GitHub token to access the company's repositories and steal the data.

 

 

Pango linjoja . Jotain mainintaa JN ja KP koodeja kantavista varianteista. FLiRT muutokset, "level" arviota antavat muutokset.

 https://cov-lineages.org/lineage_list.html

Tästä linkistä saa tietoja variantin  alkamisesta, sen määrittelyhetken , määrittelyssä olleet  virusmäärät ja  sittemmin  ilmoitetut virusmäärät  tilastojen merkintäpäivään mennessä.

Tällä kertaa en onnistu saamaan esiin sitä Pangotaulukkoa, missä mainitaan kaikki aminohappomutaatiot esim Spike-proteiinista, muta olin kirjoittanut vihkooni  kevättalvella JN.1  Spike- aminohapot.  Mutaatiolistan. Listassa on   66 mutaatiokohtaa mainittu, niistä n  deleetiokohtia kolme. 

Aiemmin ilmoitettiin ns.  level substitutions and deletions., siis mutaatiot, joiden mukaan  viruksen  vaarallisuutta  ja riskejä  arvioitiin 0-7  asteikolla. Näitä muutoksia mainittiin 18  aminohappoaseman suhteen. Nämä aminohapot  olivat ja ehkä ovat edlleen tasoa määräävässä asemassa. Luettelen ne: 

346, 356, 444, 445,  450, 446, 452, 460, 486, 490, 494, 498Q ( reversiomuoto alfaan)

Näisti JN.1 (Alias BA.2.86.1.1 eli Alias B.1.1.529.2.86.1.1,   omikronlinjan  variantti) omaa seuraavia  tasoa määrittäviä minohappomuutoksia:

K356T, V445H,  G446S, N450D, L452W, N460K, F486P,  (Q498R) esiintyvät  JN.1 variantissa ja  jo  "JN"  koodin saaneessa  edeltäjävariantissa (parent)  BA.2.86.1. 

 JN.1 variantin oma erityinen määritelmä on  L455S  substituutiomuutos Spike-proteiinissa.Lisämääritelmänä on ORF1a:R3821K sekä ORF7b . F19L. Nämä erityiset määritelmät näkyvät  internetissä Katso alapuolella oleva kopio  linkistä. .

Kliinisesti vaikuttavia  aminohapposubstituutioita, joita näissä uusissa JN.1*  linjan varianttidivertiteetissä esiintyy  on mm   ns. FLiRT  ryhmän  aminohapot. Näitä tulee sitten JN.1 alaryhmien  variantteihin vähä vähältä useampia  ja  niistä on jo runsaasti  kartoitusta ja määritelmiä olemassa ja GITHUB. uutisissa saa  päivittäin  tietoa uusista  alalinjaehdotuksista. 

 FLiRT  aminohappomutaatiot käsitellään alaryhmädiversiteetteinään  tässä vaiheessa juuri kuten  JN.1 + R346X ryhmänään  tai  JN.1 +F456L ryhmänään   tai JN.1 +T572I sisältävät  ryhmänään, jolloin saadaan paljon tarkkoja  alavarianttilinjoja, mikä helöpottaa  tilastointia , tilanteen arviointia ja lopulta  rokotteisiin sopivan antigeenin täsmennystä. Näillä aminohapoilla on merkitystä  kliinisesti  viruksen  vastustuskyvyssä. 

Linkistä voi seurata  alavariantti alavariantilta, mikä tärkeä aminohappomuutos on lisääntynyt linjaan.  Esimerkiksi JN.1.1 linkki:

Kopio linkistä JN.1

JN.1

United States of America 33.0%, Canada 9.0%, United Kingdom 8.0%, Spain 6.0%, South_Korea 4.0%

2020-01-20

4066,

93025

Alias of B.1.1.529.2.86.1.1, S:L455S, ORF1a:R3821K, ORF7b:F19L, Europe

 Kopio linkistä JN.1.1

Alias of B.1.1.529.2.86.1.1.1, ORF1a:F499L, C11747T, France, from sars-cov-2-variants/lineage-proposals#987

Kopio linkistä JN.1.1.1 osoittaa yhden FLIRT  aminohappolisän edelliseen arsenaaliin. 

Alias of B.1.1.529.2.86.1.1.1.1, S:T572I on C9142T branch, France/Sweden/Poland, from sars-cov-2-variants/lineage-proposals#1097.

 Kopio linkistä JN.1.2  osoittaa taipumusta  Spike proteiinin  C-päädyn uusiin  substituutioihin. Viimeisin aminohapposubstituutio  JN.1  spike-proteiinissa on P1143L .  Sen jälkeisiä  mutaatioitakin alkaa esiintyä C-päädyssä.

Alias of B.1.1.529.2.86.1.1.2, S:M1229I, USA/Canada, from sars-cov-2-variants/lineage-proposals#1087

Kopio linkistä JN.1.11

Alias of B.1.1.529.2.86.1.1.11, S:V1104L, G17334T, India, from #2446   

 

Kopio linkistä  JN.1.11.1   ( tämä on "KP" koodilinjan  parent)   Tässä ilmenee FLIRT aminohappo F456L.

Alias of B.1.1.529.2.86.1.1.11.1, S:F456L, after ORF1a:T2283I, India, from sars-cov-2-variants/lineage-proposals#1253

Tämä aminohappo saa koodin " KP".

 

Kopio linkistä  KP.1 .Alias BA.2.86.1.11.1

Alias of B.1.1.529.2.86.1.1.11.1.1, S:K1086R, from sars-cov-2-variants/lineage-proposals#1364

KP.1 saa uuden aminohapposubstituution, uta se ei ole FLIRT joukkoon kuuluva.  

Kopio linkistä KP.1.1. Tässä jo  nähdään  lisänä FLIRT aminohappomuutos.

 Alias of B.1.1.529.2.86.1.1.11.1.1.1, S:R346T (FLiRT) , from sars-cov-2-variants/lineage-proposals#1089

 

Kopio  Linkistä KP.2 , joka on nykyisen  Covidaallun valtavariantti.

Alias of B.1.1.529.2.86.1.1.11.1.2, S:R346T (FLiRT)  on JN.1.11.1 polytomy, from sars-cov-2-variants/lineage-proposals#1089

 

GITHUB tietoa KP2 linjan rikastumisesta eri  aminohappomutaatioilla. 

KP.2.1  , S:1201K  saa oman  aminohappolisänsä.

KP.2.2 ,  S: F59; S:K1266R. saa kaksi aminohappomutaatiota lisää.

KP.2.3,      S: H146Q, OrF3A: K67N, S:31 deleetio.  

KP.2.3.1,  S:A475V.

KP.2.3.2,    S:G184V.

KP.2.3.3,   S:N185T. 

KP.2.4,  S:T250N.

KP.2.5,   S:N185D.

KP.2.6,   S:W64R.

KP.2.7,    S:31F, (C22795 nt jälkeen).

KP.2.8, S: S 60I

KP.2.9,  S:T572I     (FLiRT muutos lisää rakenteeseen) .

KP.2.10, S:F59S.

KP.2.11, S:S56V,  Orf Ia:T2693I.

KP.2.12,  S:V1176F, G-T nt mutaatio. 

KP.2.13: , S:K478E , N:P6T, Kaksi C-T nt mutaatiota.

KP.2.14: S:G184V, S: S31F. 

KP.2.15: A-G nt mutaatio, S: -31 deletio.

KP.2.16: ORF8:F6S. 

(Jätän tässä  mutaatiot merkkamatta kunnes tulee taas  FLIRT muutos vastaan:

KP.3

KP.3.1

KP.3.1.1

KP.3.1.2

KP.3.1.3

KP.3.1.4

KP.3.2

KP.3.2.1

KP.3.2.3.

KP.3.2.4

KP.3.2.5

KP.3.3

KP.4  , C-T nt mutaatio )

KP.4.1,    S:R346T  (FLiRT muutos)

KP.4.2,   S:R346T /(FLiRT muutos),  S:K187R. 

KP.4.2.1,  S:S31F.

KP.4.2.2,   S:F59I.

KP.5 , S:T572I (FLiRT muutos) 

 

JN.1.12  ALIAS ba.2.88.1.1.12  S:F456V (FLiRT muutos),  Orf7a:A8T

 

 

  ( JN ja KP  koodeja kantavista ryhmistä on tullut maailmaa kiertäviä virulentteja muotoja, jotka ovat voittaneet   rekombinanttien valtakauden)  Kirjoittelen pikkutunneilla,joten voi olla kirjoitusvirheitä.

Netistä löytyvässä taulukossa mainitaan  dominoivista Sars-2 viruksista   taulukko, joka heijastaa  tämän alkukevään  muuttumisia dominanssissa.https://pubmed.ncbi.nlm.nih.gov/38826376/#&gid=article-figures&pid=figure-1-uid-0

Mainitut variantit ovat:

JN.1 jonka ote  alkaa hellittää.

KP.2 sen sijaan vahvistuu.

JN.7

JN.1.16

JN.1.13.1

KP.1.1

JN.1.11.1    ( Koodataan  "KP").

JN.1.8

Muilla  entisillä varianteilla on  vähenevä osuus. 

Listassa mainituilla esiintyvillä varianteilla on  alaryhmiä,joista muutamat ovat saaneet omia koodejaan kuten JN.1.11.1  omaa koodin "KP".

Mainitsen muutamia löytämiäni koodimerkintöjä:_ 

"LT" Alias JN.1.1.3, (FLIRT,S:R346T)

"KR" Alias JN.1.1.5, (FLIRT, S:R346T)

"KZ" alias JN.1.1.6, (FLIRT, S:R346T)

"LC", AliasJN.1.1.7,(FLIRT, S:F456L),

"LL", Alias JN.1.4.2

"KQ", Alias  JN.1.4.3, (FLIRT, S:T572I)

"KV",Alias JN.1.4.5,

"LE",Alias  JN.1.4.7,

"LK", Alias JN.1.7.5,

"KY", Alias JN.1.8.2,

"LB", JN.1.9.2,

("KP" on jo mainittu:JN.1.11.1)

"LP", Alias KP.1.1.3, Alias JN.1.11.1.1.1.3  BA.2.86.1.11.1.1.1.3),

"KS", Alias JN.1.13.1, (FLIRT, S:R346T;  mainitaan dominoivissa linjoissa)

"LU", Alias JN.1.15.1, /(FLIRT , S:F456L)

"LF", Alias JN.1.16.1, (Tämän "Parent" mainitaan  dominoivissa: JN.1.16. )

"LA", Alias JN.1.16.2, 

"LQ",  Alias JN.1.18.1 ,

"LS", Alias JN.1.18.5, /FLIRT, S:R456L)

"LM", AliasJN.1.25.1 (FLIRT S:R346T),

"KW", Alias  JN.1.28,

"LG", Alias KW.1.1.1 Alias  BA.2.86.1.1.28.1.1.1.1.

"KU", Alias JN.1.30.1  (FLIRT , S:R346T).

"LJ", Alias JN.1.51,

"LN", Alias JN.1.53.1.

Jos ei itse Koodin omaavassa  kantalinjassa ole FLIRT substituutioita, niin  näitten koodattujen linjojen alahaaroissa vähitellen kertyy niitä kolmea mainittua  :S-mutaatiota  kronologisesti eri laisessa järjestyksessä ja erilaisista  taustoistakin konvergoivan evoluution periaatteella.  (S taimuita merkittäviä  mutaatioita.  S:R346T, S:F456L, S:T572I. Joskus  muuntunut aminohappo merkataan X, koska evoluutiossa siirtymä kohti   riskialtteinta FLIRT muotoa voi mennä eri aminohappojen teitse. Esim R346X). 

Koodilistaa voi etiä GITHUB  tietueesta.

 

.

Siis on odoteltavissa Covid-19 nykyvarianttien taholta maailmanlaajuisesti ulottuvaa kesäaaltoa

 Kliinisessä kuvassa  ei liene ainakaan pahempaa  mainittu olevan tulossa .  Virus tosin on rekombinanttiajaltaan hankkinut pätevyyksiä  ja uusia mutaatiokombinaatioita, joilla se pystyy voittamaan rekombinanttien valtakauden ja osoittamaan alkuomikronien BA.1 ja BA.2  ominaisuuksien (mm  XAK rekombinanttia  muistuttavia)  yhdistettyjä  parhaita puolia  spike-rakenteensa   nykyrungossaa ja uusia mutaatioita tulee alueille, joissa  aiemmin ei niitä ole esiintynyt mainitavasti   ja myös  sellaisiakin mitä on  aiemmissa valtavariantseissa ennen omikronia esiintynyt. 

Toisaalta ihmiskuntakin on ehättänyt kerrostamaan immuunivastettaan.

WHO Covid-19 tilanteesta Sars-2 viruksen VOI ja VUM variantit kesän alussa 2024

 *(Alkuriskin asettelusta  BA.2. 86 varianttilinjalle WHO:n merkintää:)

 https://www.who.int/docs/default-source/coronaviruse/21112023_ba.2.86_ire.pdf?sfvrsn=8876def1_3

*(Nykytilanteesta kuvaa:)

Currently circulating variants of interest (VOIs) (as of 5 June 2024)

https://www.who.int/activities/tracking-SARS-CoV-2-variants 

^$ Excludes BA.2.86 sublineages listed here as VOIs.

#Excludes JN.1 sublineages listed as VUMs below.

Currently circulating variants under monitoring (VUMs) (as of 3 May 2024)

ango lineage	Next strain clade	Genetic features	Earliest documented samples	Date of designation and risk assessments
EG.5	Not assigned	XBB.1.9.2 + S:F456L Includes EG.5.1 (23F): EG.5 + S:Q52H HK.3 (23H): EG.5 + S:Q52H, S:L455F HV.1: EG.5 + S:Q52H, S:F157L, S:L452R	17-02-2023	09-08-2023 EG.5 Initial Risk Evaluation, 09 August 2023 EG.5 Updated Risk Evaluation, 21 September 2023 EG.5 Updated Risk Evaluation, 21 November 2023
BA.2.86$	23I	Mutations relative to BA.2	24-07-2023	21-11-2023 BA.2.86 Initial Risk Evaluation, 21 November 2023
JN.1#	24A	BA.2.86 + S:L455S	25-08-2023	18-12-2023 JN.1 Initial Risk Evaluation 18 December 2023 JN.1 Updated Risk Evaluation 9 February 2024 JN.1 Updated Risk Evaluation 15 April 2024

 

Currently circulating variants under monitoring (VUMs) (as of 3 May 2024)

Pango lineage	Next strain clade	Genetic features	Earliest documented samples	Date of designation
JN.1.7	Not assigned	JN.1 + S:T572I, S:E1150D	25-09-2023	03-05-2024
KP.2	Not assigned	JN.1 + S:R346T, S:F456L, S:V1104L	02-01-2024	03-05-2024
KP.3	Not assigned	JN.1 + S:F456L, S:Q493E, S:V1104L	11-02-2024	03-05-2024
JN.1.18	Not assigned	JN.1 + S:R346T	02-11-2023	03-05-2024

 

 

Technical Advisory Groups

KP.2 variantti(JN.1.11.1.2) on voittoisaa Sars-2 viruksen jälkikasvua nykyään.

 https://pubmed.ncbi.nlm.nih.gov/38782005/

The JN.1 variant (BA.2.86.1.1), arising from BA.2.86.1 with the S:L455S substitution, showed increased fitness and outcompeted the previous dominant XBB lineage by the beginning of 2024.

¹

JN.1 subsequently diversified, leading to the emergence of descendants with spike (S) protein substitutions such as S:R346T and S:F456L. Particularly, the KP.2 (JN.1.11.1.2) variant, a descendant of JN.1 bearing both S:R346T and S:F456L, is rapidly spreading in multiple regions as of April, 2024. Here, we investigated the virological properties of KP.2. KP.2 has three substitutions in the S protein including the two above and an additional substitution in the non-S protein compared with JN.1 (appendix p 15). We estimated the relative effective reproduction number (R_e) of KP.2 based on the genome surveillance data from the USA, UK, and Canada, where more than 30 sequences of KP.2 have been reported, using a Bayesian multinomial logistic model (appendix pp 8–13, 15).

²

The R_e of KP.2 is 1·22-times, 1·32-times, and 1·26-times higher than that of JN.1 in the USA, UK, and Canada, respectively (appendix p 15). These results suggest that KP.2 has higher viral fitness and potentially becomes the predominant lineage worldwide. Indeed, as of the beginning of April, 2024, the estimated variant frequency of KP.2 has already reached 20% in the UK (appendix p 15).

We then did a neutralisation assay using monovalent XBB.1.5 vaccine sera and breakthrough infection sera with XBB.1.5, EG.5, HK.3, and JN.1 infections. In all cases, the 50% neutralisation titre against KP.2 was significantly lower than that against JN.1 (appendix p 15). Altogether, these results suggest that the increased immune escape ability of KP.2 contributes to its higher R_e compared with JN.1.

Uusimpia Sars-2-koronaviruskirjoja valaiseva taulukko osoittaa KP.2 , JN.1 ja JN.7 dominoivimmiksi touk0kuun alussa.

 https://pubmed.ncbi.nlm.nih.gov/38826376/#&gid=article-figures&pid=figure-1-uid-0

uusin GITHUB asia on variantista JN.1.3

 https://github.com/cov-lineages/pango-designation/issues/2655

JN.1.3+S:F456L with Orf8:Q18* (C27945T branch) (44 seqs) #2655

Open

DailyCovidCases opened this issue Jun 16, 2024 · 2 comments

 

Sars -2- omicron varianttien nykyisestä valtakaudesta JN.1 varianttien lisääntyessä

Characteristics of JN.1-derived SARS-CoV-2 subvariants SLip, FLiRT, and KP.2 in neutralization escape, infectivity and membrane fusion

Pei Li  ^{1   2} , et al. 

Affiliations

• PMID: 38826376
• PMCID: PMC11142104
• DOI: 10.1101/2024.05.20.595020 
•  
  Abstract

  SARS-CoV-2 variants derived from the immune evasive JN.1 are on the rise worldwide. Here, we investigated JN.1-derived subvariants SLip, FLiRT, and KP.2 for their ability to be neutralized by antibodies in bivalent-vaccinated human sera, XBB.1.5 monovalent-vaccinated hamster sera, sera from people infected during the BA.2.86/JN.1 wave, and class III monoclonal antibody (Mab) S309. We found that compared to parental JN.1, SLip and KP.2, and especially FLiRT, exhibit increased resistance to COVID-19 bivalent-vaccinated human sera and BA.2.86/JN.1-wave convalescent sera. Interestingly, antibodies in XBB.1.5 monovalent vaccinated hamster sera robustly neutralized FLiRT and KP.2 but had reduced efficiency for SLip. These JN.1 subvariants were resistant to neutralization by Mab S309. 

  In addition, we investigated aspects of spike protein biology including infectivity, cell-cell fusion and processing, and found that these subvariants, especially SLip, had a decreased infectivity and membrane fusion relative to JN.1, correlating with decreased spike processing. Homology modeling revealed that L455S and F456L mutations in SLip reduced local hydrophobicity in the spike and hence its binding to ACE2. 

  In contrast, the additional R346T mutation in FLiRT and KP.2 strengthened conformational support of the receptor-binding motif, thus counteracting the effects of L455S and F456L. These three mutations, alongside D339H, which is present in all JN.1 sublineages, alter the epitopes targeted by therapeutic Mabs, including class I and class III S309, explaining their reduced sensitivity to neutralization by sera and S309. 

  Together, our findings provide insight into neutralization resistance of newly emerged JN.1 subvariants and suggest that future vaccine formulations should consider JN.1 spike as immunogen, although the current XBB.1.5 monovalent vaccine could still offer adequate protection.

https://pubmed.ncbi.nlm.nih.gov/38826376/

https://pubmed.ncbi.nlm.nih.gov/38826376/#&gid=article-figures&pid=figure-1-uid-0

Mitä tarkoittaa FLiRT variantti? Kaikki ne variantit jotka alkavat KP ja JN rakenteella. F456, R346 ja T572 mutaatiot merkitseviä.

 What are these “FLiRT variants”? This is the term being used to describe a whole family of different variants—including KP.2, JN.1.7, and any other variants starting with KP or JN—that appear to have independently picked up the same set of mutations. This is called convergent evolution.

JN  (alias BA.2.86.1.)

KP  (alias JN.1.11.1) 

 At the end of March, the KP.2 variant was causing about 4% of infections in the U.S., according to the CDC, while its parental strain, JN.1, was causing over 50% of infections at that time. As of early May, KP.2 makes up about 28% of infections, overtaking JN.1 as the dominant variant.

KP.2 is one of several variants being referred to as “FLiRT variants,” named after the technical names for their mutations. The prevalence of these variants comes at a critical time, when experts are deciding how to formulate the fall COVID vaccine.

In this Q&A, Andy Pekosz, PhD, a professor in Molecular Microbiology and Immunology, explains what virologists like him are seeing, whether these variants might cause a summer wave of infections, and how people can protect themselves.

What are these “FLiRT variants”?

This is the term being used to describe a whole family of different variants—including KP.2, JN.1.7, and any other variants starting with KP or JN—that appear to have independently picked up the same set of mutations. This is called convergent evolution. They are all descendants of the JN.1 variant that has been dominant in the U.S. for the past several months.

The particular mutations that people refer to as “FLiRT”s or “FLip”s refer to specific positions in the spike protein—in this case, positions 456, 346, and 572.

Viruses like SARS-CoV-2 mutate frequently, and when they mutate to evade recognition by antibodies, this often weakens their ability to bind to the cells they want to infect. We then see mutations appear that improve that binding ability. This is a cycle we have seen many times with SARS-CoV-2. The fact that these different variants are picking up the same mutations tells virologists that this combination of mutations is helping the virus accomplish these goals most efficiently.

ttps://publichealth.jhu.edu/2024/what-to-know-about-covid-flirt-variants

• 15.6. 2024 kommenttin:  (Wuhan  wt virus , F456, R346 ja  T572).

How do these mutations help the virus bind to cells while evading antibodies?

Two of these mutations—456 and 346—eliminate binding sites for antibodies that neutralize SARS-CoV-2. However, those same antibody binding sites are also important for the virus to bind to and enter cells. So in evading antibodies, these FLiRT variants may have also lost some ability to bind to their receptor. At the same time, the 572 mutation appears to allow the virus to more tightly bind to cells and ultimately cause an infection.

Do people who recently had COVID have any protection against infection from FLiRT variants?

A JN.1 infection should provide pretty strong protection against all the FLiRT variants. The difference between JN.1 and these variants is only one or two amino acid changes, so there are still a lot of other places antibodies can bind to. Infection from a variant older than JN.1 is less likely to offer as much protection.

...

How might these variants impact plans for the COVID vaccine formula that gets updated for the fall?

This is the time of year when governing bodies like the WHO and FDA recommend a formulation for updated COVID vaccines that will roll out in early fall. Last year, the vaccines were based on the XBB.1.5 variant, and only a few months later, the JN.1 variant became the dominant variant in the U.S.

At the end of April, the WHO announced that their COVID vaccine advisory group advises using the JN.1 lineage as the antigen for the upcoming formulations of the vaccine. All of these FLiRT variants are within the JN.1 family of variants.

Here in the U.S., the FDA has postponed its meetingto determine the fall 2024 COVID vaccine from mid-May to early June. That gives them more time to see which of the FLiRT variants is becoming the dominant one so they can fine-tune the WHO recommendation to what they anticipate will be most prominent in the fall.

New COVID variants are likely to crop up after a decision is made—just as it did last summer—but the goal remains to select a formulation that, come fall, will match the circulating variants as closely as possible.

 

 

 

Linkki sars-2 koronaviruksen pangolinjaluetteloihin 15.6. 2024

 https://github.com/cov-lineages/pango-designation/blob/master/lineage_notes.txt

Vilkaisu GITHUB palstan uutisiin 14.6.2024 Erittäin runsaasti erilaisia BA.2.86.1 variantin alalinjoja viime aikoina

 https://github.com/cov-line135 open issues to daages/pango-designation/issues

135 open issues 

https://github.com/cov-lineages/pango-designation/issues

JN.1.18.2 (S:F59S) FLirt lineage emerging fast in Puerto Rico (19) with further S:P217S, S:N1125S (13) #2654 opened 10 hours ago  Jun 14, 2024 by FedeGueli  

JN.1.18.2 (59S) Flirt lineage with Orf10:Q29* (12 seqs 4 continents) #2653 opened  11 houers ago Jun 14, 2024 by FedeGueli 

Ne w DeFLiRT : JN.1.16.1 with S:S31del and Orf8:Q29* emerged recently in France (23 seqs, 8 countries )   #2652 opened  2 days ago Jun 12, 2024 by FedeGueli

 

JN.1.34+S:F456L with C8802T branch (23 seqs, 9 countries) #2651 opened 4 days ago   Jun 10, 2024 by DailyCovidCases

 

KP.1.1+Orf1b:L2213F+S:N185del, F186I(117 seqs, 17 countries)   5 days ago

etc. 

BA.2.86.1 alalinjoissa tarvitaan  useita uusia koodilyhennyksiä

kuten 

KP Alias JN.1.11.1  Alias BA.2.86.1.1.11.1

KQ Alias JN.1.4.3 

KS. Alias JN.1.13.1 

KT  Alias JN.1.1.3 

KU Alias JN.1.30.1 

KV Alias JN.1.4.5 

KW Alias  JN.1.28 

KY Alias JN.1.8.2

KZ Alias JN.1.1.6 

LA Alias JN,1,16.2 

LB Alias JN.1.9.2  

LE Alias  JN.1.4.7 

LF Alias  JN.1.16.1 

LJ Alias JN.1.51

LL Alias JN.1.4.2 

LM Alias JN.1.25.1  

LN Alias  JN.1.53.1

LQ Alias JN.1.18.1 

LS Alias JN.1.18.5 

LT Alias JN.1.1.3 

LU Alias  JN.1.15.1 

....

Siis: Viime vuoden 2023 yllätysvariantti nousi  BA.2 omicron linjasta.BA.2.86.

Sen alalinja BA.2.86.1 merkattiin  alun alkaen koodilla JN.

Sillä on tietysti se pitkä  sars-2Cov  omicron merkintänsäkin Alias. B.1.1.529.2.86.1 

  Se nousi rekombinanttien XBB    valtakauden aikana Käytössä oli koodimerkintään KN  asti.

Myös BA.2. 75 linjasta  tuli  jokusia alalinjoja: JV  alias BA.2.75.3.4.1.1.1.1.1.7.1.2.  merkkasivat 

 KG  Alias BA.2.75.3.4.1.1.1.1.1.7.1.5 Alias  B.1.1.529.2.75.3.4.1.1.1.1.1.7.1.5.

Nämä merkkasin vihkooni 12. helmikuuta 2024. Silloin oli  käytössä KN koodikin jo..

 Nyt  14.6. 2024 havaitsen KP koodi merkintää   monella. K kombinaatiot on käytetty  KZ asti  joten  L kirjainkombinaatiot on otettu jo käyttöön.

Tälle sivulle olen kerännyt niitä koodinimiä, joita tänään  14.6. 2024  olen vihkoihini saanut merkattua viime aikaisista luetteloista. Olen ollut Tanskassa keväällä ja nyt viikko sitten tulin kotitietokoneeni ääreen ja tänään katsoin  viimeisiä uutisia GITHUB listoista.   Kevättalven aikana on ollut paljon hengitystieinfektioita ihmisillä,  Viittä eri virusta mainitaan , alkuvuodesta RSV, loppukeväästä Parvovirustakin joukossa.  tavallista  yskää ja nuhaa on ollut  monilla ilman että virusta tulee tunnistettua.  Harva enää näyttää käyttävän hengityssuojainta tai  käsidesiä kaupoissa tai noudattaa väljyysohjeita. Yleisvaikutelma on että busseissa tai joukoissa ei yskitä tähän aikaan.  Lintuinfluenssa-asia paisuu vähitellen uutisissa.  Punkkeja esiintyy , Tanskassakin sitä  taigapunkkia idästä.  Hyttysistäkin aletaan puhua ja olla huolissa ilmastonmuutoksesta.

 Tunti siten ilmestyi GITHUB särmille uusin designaatio, määritelmä linjalle:Kello  on Ruotsissa 22:20 perjanttai iltana 14.6. 2024. Otan kopion:

Designate JN.1.58.3 (S:S31F)

https://github.com/cov-lineages/pango-designation/commit/91473838d4dba8634e89115c0de227aad2dcacfe

 

WHO:n suhde koronaviruksiin konsolidoitu: CoViNet perustettu tänä vuonna!

 

WHO launches CoViNet: a global network for coronaviruses

27 March 2024

News release

Geneva

Reading time: 1 min (308 words)

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WHO has launched a new network for coronaviruses, CoViNet, to facilitate and coordinate global expertise and capacities for early and accurate detection, monitoring and assessment of SARS-CoV-2, MERS-CoV and novel coronaviruses of public health importance.

CoViNet expands on the WHO COVID-19 reference laboratory network established during the early days of the pandemic.  Initially, the lab network was focused on SARS-CoV-2, the virus that causes COVID-19, but will now address a broader range of coronaviruses, including MERS-CoV and potential new coronaviruses. CoViNet is a network of global laboratories with expertise in human, animal and environmental coronavirus surveillance.

The network currently includes 36 laboratories from 21 countries in all 6 WHO regions.

Representatives of the laboratories met in Geneva on 26 – 27 March to finalize an action plan for 2024-2025 so that WHO Member States are better equipped for early detection, risk assessment, and response to coronavirus-related health challenges.

The CoViNet meeting brings together global experts in human, animal, and environmental health, embracing a comprehensive One Health approach to monitor and assess coronavirus evolution and spread. The collaboration underscores the importance of enhanced surveillance, laboratory capacity, sequencing, and data integration to inform WHO policies and support decision-making.

“Coronaviruses have time and again demonstrated their epidemic and pandemic risk. We thank our partners from around the world who are working to better understand high threat coronaviruses like SARS, MERS and COVID-19 and to detect novel coronaviruses,” said Dr Maria Van Kerkhove, acting Director of WHO’s Department of Epidemic and Pandemic Preparedness and Prevention. “This new global network for coronaviruses will ensure timely detection, monitoring and assessment of coronaviruses of public health importance.”

Data generated through CoViNet's efforts will guide the work of WHO's Technical Advisory Groups on Viral Evolution (TAG-VE) and Vaccine Composition (TAG-CO-VAC) and others, ensuring global health policies and tools are based on the latest scientific information.

 

GITHUB uutisia 8.6. 2024 sars-2 koronaviruksen varianttien kehityksestä

Asia #2646 tullut eilen  särmille:  Siitä muutama kopiokuva tähän: Linkki  esittää

 3prim UTR  rakenteen, mutta sitä en saa kopioitua tähän.  UTR muutokset lienevät   avaintekijää SARS-2 viruksen  tässä valtavassa  rönsyilyssä. 

KP.3.1 + ∆29728-29776 (bigger s2m deletion) [47 seq, 4 continents, June 7] #2646

Open

ryhisner opened this issue Jun 7, 2024 · 0 comments 

Earliest sequence: 2024-4-15, Australia, Victoria — EPI_ISL_19084514
Most recent sequence: 2024-5-6, Spain, Madrid — EPI_ISL_19144199
Continents circulating: Oceania (7), Asia (2), Europe (2)
Countries circulating: Australia (5), New Zealand (2), Spain (2), China (1), Singapore (1)
Number of Sequences: 11
GISAID Nucleotide Query: A1620G, G15372T, -G29734
CovSpectrum Query: Nextcladepangolineage:KP.3* & [2-of: A1620G, G15372T] & [1-of: 29729-, !29735-]
Substitutions/Deletions on top of KP.3:
ORF1a: E452G (NSP2_E282G)
Nucleotide: G15372T, A19722G, A1620G, ∆29728-29733 + ∆29760-29776

Phylogenetic Order of Mutations: G15372T, A19722G → A1620G (ORF1a:E452G), ∆29728-29733 + ∆ 29760-29776

USHER Tree
https://nextstrain.org/fetch/raw.githubusercontent.com/ryhisner/jsons2/main/KP.3_29728-29776.json?c=gt-ORF1ab_452&gmax=21555&gmin=266&label=id:node_2371524

 Evidence
BA.2 was the first global variant to feature a deletion in s2m, a 3' UTR stem-loop that is highly conserved in sarbecoviruses. All Omicron since BA.1 have had ∆29734-29759. This sublineage adds 23 nucleotides to the standard Omicron s2m deletion with ∆29728-29776. When the s2m deletion is enlarged, this is the most common pattern. s2m's function is unknown, and the reason for its deletion in BA.2/4/5 is also a mystery.

 

 

 

Viimeaikaisia (2024) PubMed artikkeleita Sars-Cov-2 vallitsevista varianteista ja rokotetehoista; Tilanteen hahmotusta

 HAKU:  JN.1  variant of Sars-Cov-2 

4 articles found by citation matching

 

Virological characteristics of the SARS-CoV-2 JN.1 variant.

Kaku Y, et al. Lancet Infect Dis. 2024. PMID: 38184005 No abstract available.

The SARS-CoV-2 BA.2.86 lineage, first identified in August 2023, is phylogenetically distinct from the current circulating SARS-CoV-2 omicron XBB lineages, including EG.5.1 and HK.3. Compared with XBB and BA.2, BA.2.86 carries more than 30 mutations in the spike protein, indicating a high potential for immune evasion.

BA.2.86 has evolved and its descendant, JN.1 (BA.2.86.1.1), emerged in late 2023. JN.1 harbours Leu455Ser and three mutations in non-spike proteins (appendix pp 17–18). Spike protein mutation Leu455Ser is a hallmark mutation of JN.1: we have recently shown that HK.3 and other flip variants carry Leu455Phe, which contributes to increased transmissibility and immune escape ability compared with the parental EG.5.1 variant.⁵

Here, we investigated the virological properties of JN.1. We estimated the relative effective reproductive number of JN.1 using genomic surveillance data from France, the UK, and Spain, where more than 25 sequences of JN.1 have been reported, using a Bayesian multinomial logistic model (appendix pp 10–15, 17–18). ⁶ The reproductive number of JN.1 in these three countries was higher than that of BA.2.86.1 and HK.3, one of the XBB lineages with the highest growth advantage at the end of November, 2023 (appendix pp 17–18). ⁵ These results suggest that JN.1 might soon become the dominant lineage worldwide. Indeed, by the end of November 2023, JN.1 had already overtaken HK.3 in France and Spain (appendix pp 17–18).

The in vitro ACE2 binding assay ⁷ showed that the dissociation constant value of the JN.1 receptor-binding domain (RBD) was significantly higher than that of the BA.2.86 RBD (appendix pp 17–18), suggesting that Leu455Ser decreases binding affinity to the human ACE2 receptor. In contrast, the pseudovirus assay showed that the infectivity of JN.1 was significantly higher than that of BA.2.86 (appendix pp 17–18). This discrepancy could be due to the difference between monomeric RBD and trimerised whole spike protein (appendix pp 2, 17–18). We then performed a neutralisation assay using rodent sera infected with BA.2.86 or immunised with BA.2.86 spike protein. In both cases, the 50% neutralisation titre (NT₅₀) against JN.1 was similar to that against BA.2.86 (appendix 17–18), suggesting that Leu455Ser does not affect the antigenicity of BA.2.86. On the other hand, the NT₅₀ of breakthrough infection sera with XBB.1.5 and EG.5.1 against JN.1 was significantly lower than that of HK.3 (2·6-fold to 3·1-fold) and BA.2.86 (3·8-fold; appendix pp 17–18). Furthermore, JN.1 shows robust resistance to monovalent XBB.1.5 vaccine sera compared with BA.2.86 (appendix 17–18). Taken together, these results suggest that JN.1 is one of the most immune-evading variants to date. Our results suggest that Leu455Ser contributes to increased immune evasion, which partly explains the increased reproductive number of JN.1.

KJI and KS are supported in part by AMED SCARDA Japan Initiative for World-leading Vaccine Research and Development Centers UTOPIA and by AMED SCARDA Program on R&D of new generation vaccine including new modality application. The G2P-Japan Consortium and KS are supported by AMED Research Program on Emerging and Re-emerging Infectious Diseases and by the JSPS KAKENHI Fund for the Promotion of Joint International Research (International Leading Research). KS received funding from the AMED Research Program on HIV/AIDS, JST CREST, JSPS Core-to-Core Program, The Tokyo Biochemical Research Foundation, and The Mitsubishi Foundation; received consulting fees from Moderna Japan and Takeda Pharmaceutical; and honoraria for lectures from Gilead Sciences, Moderna Japan, and Shionogi & Co. JI received funding from JST PRESTO and JSPS KAKENHI Grant-in-Aid for Early-Career Scientists; and received consulting fees and honoraria for lectures from Takeda Pharmaceutical. KU is a JSPS Research Fellow DC2. YKo is a JSPS Research Fellow DC1. JZ is funded by the International Joint Research Project of the Institute of Medical Science, the University of Tokyo and the project of National Institute of Virology and Bacteriology, Programme EXCELES, that is funded by the European Union, Next Generation EU. The other authors declare no competing interests. We thank CEU Universities and Santander Bank (Ayudas a la movilidad internacional de los investigadores en formación de la CEINDO) and to the Federation of European Biochemical Societies for their financial support to MP-B during the first and second part of his internship period at BIOCEV.

 

 

Evolving immune evasion and transmissibility of SARS-CoV-2: The emergence of JN.1 variant and its global impact. Ou G, et al. Drug Discov Ther. 2024. PMID: 38382991 Abstract (20.3. 2024)

The continuous evolution of SARS-CoV-2 variants constitutes a significant impediment to the public health. The World Health Organization (WHO) has designated the SARS-CoV-2 variant JN.1, which has evolved from its progenitor BA.2.86, as a Variant of Interest (VOI) in light of its enhanced immune evasion and transmissibility. The proliferating dissemination of JN.1 globally accentuates its competitive superiority and the potential to instigate fresh surges of infection, notably among cohorts previously infected by antecedent variants. Notably, prevailing evidence does not corroborate an increase in pathogenicity associated with JN.1, and antiviral agents retain their antiviral activity against both BA.2.86 and JN.1. The sustained effectiveness of antiviral agents offers a beacon of hope. Nonetheless, the variant's adeptness at eluding the immunoprotective effects conferred by extant vaccines highlights the imperative for the development of more effective vaccines and therapeutic approaches. Overall, the distinct evolutionary trajectories of BA.2.86 and JN.1 underscore the necessity for ongoing surveillance and scholarly inquiry to elucidate their implications for the pandemic's evolution, which requires the international communities to foster collaboration through the sharing of data, exchange of insights, and collective scientific endeavors.

 

As COVID-19 Cases Surge, Here's What to Know About JN.1, the Latest SARS-CoV-2 "Variant of Interest".  Rubin R. JAMA. 2024. PMID: 38214935

Parents often bask in the glow of their children’s accomplishments, so if SARS-CoV-2 variants were like people, BA.2.86 would be busting its buttons right about now. BA.2.86’s spawn, JN.1, has become the dominant SARS-CoV-2 variant in the US, status its parent variant never achieved. Fortunately, although COVID-19 cases have surged, hospitalizations and deaths from the disease are still considerably lower than they were the same time a year earlier. When BA.2.86 joined the SARS-CoV-2 Omicron family last summer, it grabbed pandemic trackers’ attention because it was so different from its progenitor, BA.2. Compared with BA.2, BA.2.86’s spike protein carries more than 30 mutations, suggesting that it might spread more easily than its predecessors

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1

Ongoing evolution of SARS-CoV-2 drives escape from mRNA vaccine-induced humoral immunity.

Roederer AL, Cao Y, St Denis K, Sheehan ML, Li CJ, Lam EC, Gregory DJ, Poznansky MC, Iafrate AJ, Canaday DH, Gravenstein S, Garcia-Beltran WF, Balazs AB. medRxiv [Preprint]. 2024 Mar 7:2024.03.05.24303815. doi: 10.1101/2024.03.05.24303815. PMID: 38496628 Free PMC article. Preprint.Since the COVID-19 pandemic began in 2020, viral sequencing has documented 131 individual mutations in the viral spike protein across 48 named variants. To determine the ability of vaccine-mediated humoral immunity to keep pace with continued SARS-CoV-2 evolution, we assessed the neutralization potency of sera from 76 vaccine recipients collected after 2 to 6 immunizations against a comprehensive panel of mutations observed during the pandemic. Remarkably, while many individual mutations that emerged between 2020 and 2022 exhibit escape from sera following primary vaccination, few escape boosted sera. However, progressive loss of neutralization was observed across newer variants, irrespective of vaccine doses. Importantly, an updated XBB.1.5 booster significantly increased titers against newer variants but not JN.1. These findings demonstrate that seasonal boosters improve titers against contemporaneous strains, but novel variants continue to evade updated mRNA vaccines, demonstrating the need for novel approaches to adequately control SARS-CoV-2 transmission.

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Distinct evolution of SARS-CoV-2 Omicron XBB and BA.2.86/JN.1 lineages combining increased fitness and antibody evasion.

Planas D, Staropoli I, Michel V, Lemoine F, Donati F, Prot M, Porrot F, Guivel-Benhassine F, Jeyarajah B, Brisebarre A, Dehan O, Avon L, Bolland WH, Hubert M, Buchrieser J, Vanhoucke T, Rosenbaum P, Veyer D, Péré H, Lina B, Trouillet-Assant S, Hocqueloux L, Prazuck T, Simon-Loriere E, Schwartz O. Nat Commun. 2024 Mar 13;15(1):2254. doi: 10.1038/s41467-024-46490-7. PMID: 38480689 Free PMC article. The unceasing circulation of SARS-CoV-2 leads to the continuous emergence of novel viral sublineages. Here, we isolate and characterize XBB.1, XBB.1.5, XBB.1.9.1, XBB.1.16.1, EG.5.1.1, EG.5.1.3, XBF, BA.2.86.1 and JN.1 variants, representing >80% of circulating variants in January 2024. The XBB subvariants carry few but recurrent mutations in the spike, whereas BA.2.86.1 and JN.1 harbor >30 additional changes. These variants replicate in IGROV-1 but no longer in Vero E6 and are not markedly fusogenic. They potently infect nasal epithelial cells, with EG.5.1.3 exhibiting the highest fitness. Antivirals remain active. Neutralizing antibody (NAb) responses from vaccinees and BA.1/BA.2-infected individuals are markedly lower compared to BA.1, without major differences between variants. An XBB breakthrough infection enhances NAb responses against both XBB and BA.2.86 variants. JN.1 displays lower affinity to ACE2 and higher immune evasion properties compared to BA.2.86.1. Thus, while distinct, the evolutionary trajectory of these variants combines increased fitness and antibody evasion.

3

Key mechanistic features of the trade-off between antibody escape and host cell binding in the SARS-CoV-2 Omicron variant spike proteins.

Li W, Xu Z, Niu T, Xie Y, Zhao Z, Li D, He Q, Sun W, Shi K, Guo W, Chang Z, Liu K, Fan Z, Qi J, Gao GF. EMBO J. 2024 Mar 11. doi: 10.1038/s44318-024-00062-z. Online ahead of print. PMID: 38467833

 Since SARS-CoV-2 Omicron variant emerged, it is constantly evolving into multiple sub-variants, including BF.7, BQ.1, BQ.1.1, XBB, XBB.1.5 and the recently emerged BA.2.86 and JN.1. Receptor binding and immune evasion are recognized as two major drivers for evolution of the receptor binding domain (RBD) of the SARS-CoV-2 spike (S) protein. However, the underlying mechanism of interplay between two factors remains incompletely understood. Herein, we determined the structures of human ACE2 complexed with BF.7, BQ.1, BQ.1.1, XBB and XBB.1.5 RBDs. Based on the ACE2/RBD structures of these sub-variants and a comparison with the known complex structures, we found that R346T substitution in the RBD enhanced ACE2 binding upon an interaction with the residue R493, but not Q493, via a mechanism involving long-range conformation changes. Furthermore, we found that R493Q and F486V exert a balanced impact, through which immune evasion capability was somewhat compromised to achieve an optimal receptor binding. We propose a "two-steps-forward and one-step-backward" model to describe such a compromise between receptor binding affinity and immune evasion during RBD evolution of Omicron sub-variants.

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Neutralization of SARS-CoV-2 Omicron subvariant BA.2.87.1.

Lasrado N, Rössler A, Rowe M, Collier AY, Barouch DH. Vaccine. 2024 Mar 7:S0264-410X(24)00292-5. doi: 10.1016/j.vaccine.2024.03.007. Online ahead of print. PMID: 38458874 Free article.

A new highly mutated Omicron subvariant BA.2.87.1 has recently been identified with over 30 amino acid mutations in the Spike protein compared with BA.2, BA.5, XBB.1.5, and JN.1 variants. Multiple mutations in BA.2.87.1 are located in the N-terminal domain (NTD) rather than in the receptor binding domain (RBD) of the Spike protein. We evaluated neutralizing antibody (NAb) responses to BA.2.87.1 because of its highly mutated sequence and its unique NTD region. Our data show that NAb responses to BA.2.87.1 were lower than to BA.2 but higher than to JN.1, suggesting that BA.2.87.1 is not a further antibody escape variant compared with other currently circulating variants. Moreover, XBB.1.5 mRNA boosting increased NAb titers to all variants tested including BA.2.87.1. 

 

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Effectiveness of Omicron XBB.1.5 vaccine against infection with SARS-CoV-2 Omicron XBB and JN.1 variants, prospective cohort study, the Netherlands, October 2023 to January 2024.

Huiberts AJ et al. 2024 Mar;29(10). doi: 10.2807/1560-7917.ES.2024.29.10.2400109. PMID: 38456217 Free article. We estimated vaccine effectiveness (VE) of SARS-CoV-2 Omicron XBB.1.5 vaccination against self-reported infection between 9 October 2023 and 9 January 2024 in 23,895 XBB.1.5 vaccine-eligible adults who had previously received at least one booster. ...Sequenci … 

 

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Wastewater-based epidemiological surveillance of SARS-CoV-2 new variants BA.2.86 and offspring JN.1 in south and Southeast Asia.

Wannigama DL, Amarasiri M et al.  Travel Med. 2024 Mar 4:taae040. doi: 10.1093/jtm/taae040. Online ahead of print. PMID: 38438141 No abstract available.

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Next-generation treatments: Immunotherapy and advanced therapies for COVID-19.

Arevalo-Romero JA et al.  2024 Feb 19;10(5):e26423. doi: 10.1016/j.heliyon.2024.e26423. eCollection 2024 Mar 15. PMID: 38434363 Free PMC article. Review.

The emergence of new SARS-CoV-2 lineages, shaped by mutation and recombination processes, has led to successive waves of infections. ...Moreover, the detrimental consequences of the novel emergence of SARS-CoV-2 lineages bear a particular …

8

Evolving immune evasion and transmissibility of SARS-CoV-2: The emergence of JN.1 variant and its global impact.

Ou G, Yang Y, Zhang S, Niu S, Cai Q, Liu Y, Lu H. Drug Discov Ther. 2024 Mar 20;18(1):67-70. doi: 10.5582/ddt.2024.01008. Epub 2024 Feb 22. PMID: 38382991 Free article.

The continuous evolution of SARS-CoV-2 variants constitutes a significant impediment to the public health. The World Health Organization (WHO) has designated the SARS-CoV-2 variant JN.1, which has evolved from …

9

XBB.1.5 monovalent mRNA vaccine booster elicits robust neutralizing antibodies against XBB subvariants and JN.1.

Wang Q, Guo Y, Bowen A, Mellis IA, Valdez R, Gherasim C, Gordon A, Liu L, Ho DD. Cell Host Microbe. 2024 Mar 13;32(3):315-321.e3. doi: 10.1016/j.chom.2024.01.014. Epub 2024 Feb 19. PMID: 38377995 Free article. COVID-19 vaccines have recently been updated to specifically encode or contain the spike protein of the SARS-CoV-2 XBB.1.5 subvariant, but their immunogenicity in humans has yet to be fully evaluated and reported, particularly against emergent viruses that are rapidly expanding. We now report that administration of an updated monovalent mRNA vaccine booster (XBB.1.5 MV) to previously uninfected individuals boosted serum virus-neutralizing antibodies significantly against not only XBB.1.5 (27.0-fold increase) and EG.5.1 (27.6-fold increase) but also key emerging viruses such as HV.1, HK.3, JD.1.1, and JN.1 (13.3- to 27.4-fold increase). Individuals previously infected by an Omicron subvariant had the highest overall serum neutralizing titers (ID₅₀ 1,504-22,978) against all viral variants tested. While immunological imprinting was still evident with the updated vaccines, it was not nearly as severe as observed with the previously authorized bivalent BA.5 vaccine. Our findings strongly support the official recommendation to widely apply the updated COVID-19 vaccines. 

 

 

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XBB.1.5 monovalent booster improves antibody binding and neutralization against emerging SARS-CoV-2 Omicron variants. Jain S, Kumar S et al. . bioRxiv [Preprint]. 2024 Feb 5:2024.02.03.578771. doi: 10.1101/2024.02.03.578771. PMID: 38370837 Free PMC article. Preprint.The rapid emergence of divergent SARS-CoV-2 variants has led to an update of the COVID-19 booster vaccine to a monovalent version containing the XBB.1.5 spike. To determine the neutralization breadth following booster immunization, we collected blood samples from 24 individuals pre- and post-XBB.1.5 mRNA booster vaccination (∼1 month). The XBB.1.5 booster improved both neutralizing activity against the ancestral SARS-CoV-2 strain (WA1) and the circulating Omicron variants, including EG.5.1, HK.3, HV.1, XBB.1.5 and JN.1. Relative to the pre-boost titers, the XBB.1.5 monovalent booster induced greater total IgG and IgG subclass binding, particular IgG4, to the XBB.1.5 spike as compared to the WA1 spike. We evaluated antigen-specific memory B cells (MBCs) using either spike or receptor binding domain (RBD) probes and found that the monovalent booster largely increases non-RBD cross-reactive MBCs. These data suggest that the XBB.1.5 monovalent booster induces cross-reactive antibodies that neutralize XBB.1.5 and related Omicron variants.