Daniele Focosi, MD PhD MSc @dfocosi Twitter profile

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Daniele Focosi, MD PhD MSc

3 months

‼️JUL 18 UPDATE FLiRTTI & FLiRT31 on the rise. Epistasis again at work: on a R346T background, F456L seems required before getting T572I. @yunlong_cao @RajlabN @BenjMurrell @SystemsVirology @EricTopol @tylernstarr @JPWeiland @LongDesertTrain @siamosolocani @CorneliusRoemer

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Daniele Focosi, MD PhD MSc

@dfocosi

2 years

If you got infected with Omicron at any time, a third vaccine dose actually doubles your risk of reinfection compared to 2 doses only. Amazing immune imprinting at work.

Eric Topol

@EricTopol

2 years

Some further potential evidence for immune imprinting from a nationwide Qatar study on vaccination, with or without a booster, for protection from Omicron -raddadreinfection @HChemaitelly @Laith_AbuRaddad and colleagues

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Daniele Focosi, MD PhD MSc

@dfocosi

2 years

The clearest evidence that without containment we are increasing the chances for SARS-CoV-2 to mutate further. Mutation rate increased by 30% in just 1 year. @TRyanGregory @denise_dewald @K_G_Andersen @EricTopol @kakape @ewencallaway

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Daniele Focosi, MD PhD MSc

@dfocosi

2 years

Convergent evolution UPDATE 11/04. New entries: BA.4.6.5, BA.5.11, BA.5.2.39, BE.5/6/7/8, BF.33, BQ.1.24, CA.3.1, CM.7, DB.1, DD.1. But this time PLEASE read the 🧵below: amazing findings on RBD immune escape and ACE2 affinity. @EricTopol @ewencallaway @SolidEvidence @firefoxx66

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Daniele Focosi, MD PhD MSc

@dfocosi

1 year

‼️Bad news. EG.5.1 escapes both XBB.1.5 and BA.5+XBB.1.5 breakthrough infection sera at unprecedented levels. Expect a big wave, and let’s hope cell-mediated immunity is not as bad. @EricTopol @kakape @florian_krammer @MarionKoopmans @ACasadevall1 @manuelenicastri

The Sato Lab (Kei Sato)

@SystemsVirology

1 year

BREAKING🔔 A new preprint from G2P-Japan🇯🇵 is out at bioRxiv @biorxivpreprint . We evaluated the antiviral humoral immunity induced by breakthrough infection (BTI) of XBB subvariants and its effect against a new one, EG.5. Please RT. 1/

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Daniele Focosi, MD PhD MSc

@dfocosi

2 years

“With MERS-CoV being endemic in camels in Qatar, the simultaneous hosting of the FIFA World Cup 2022, and the camel beauty pageant, poses an enhanced risk of transmission and globalisation of MERS-CoV.”

The Qatar FIFA World Cup 2022 and camel pageant championships increase risk of MERS-CoV transmiss...

Mass gatherings, such as sporting events and festivals, create ideal conditions for human-to-human transmission of a range of infectious diseases, which can rapidly spread globally due to ease of...

www.thelancet.com

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Daniele Focosi, MD PhD MSc

@dfocosi

2 years

CONVERGENT EVOLUTION UPDATE 14/10. New hypermutated lineages to watch (and test in vitro @yunlong_cao 😉): BE.4.2, CS.1, CH.1.1, CR.1, BA.4.6.3, and BQ.1.17. @EricTopol @SolidEvidence @CorneliusRoemer @DrEricDing @TRyanGregory @siamosolocani @JosetteSchoenma @LongDesertTrain

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Daniele Focosi, MD PhD MSc

@dfocosi

2 years

Getting a lower respiratory tract infection during early childhood almost doubled the risk of dying from respiratory disease by age 73 years. Stop kidding with “immunological debt” theories. Etymology sounds obvious: pathogens are never good for health.

Early childhood lower respiratory tract infection and premature adult death from respiratory...

In this prospective, life-spanning, nationally representative cohort study, LRTI during early childhood was associated with almost a two times increased risk of premature adult death from respiratory...

www.thelancet.com

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Daniele Focosi, MD PhD MSc

@dfocosi

2 years

SARS-CoV-2 Spike protein convergent evolution chart UPDATE 01/09. New entries: XBB.1.9.1, XBB.6.1, BA.2.3.22, CK.1.2, CM.11, BL.6, DS.1, and XBL (recombinant of a recombinant 😱) Please note XBB.* is also resistant to bebtelovimab @EricTopol @TRyanGregory @DrEricDing @yunlong_cao

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Daniele Focosi, MD PhD MSc

@dfocosi

2 years

Convergent evolution chart UPDATE 11/14. New entries: BQ.1.25, DE.2, DF.1, BF.34, XBB.1.5, CM.8.1, BA.5.2.41, and expecially BE.9 from Amazonas @EricTopol @TRyanGregory @ewencallaway @kakape @rquiroga777 @K_G_Andersen @RajlabN @mildanalyst @DrEricDing @ilariacapua @denise_dewald

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Daniele Focosi, MD PhD MSc

@dfocosi

2 years

Right now, out of 2199 PANGOLIN-designated SARS-CoV-2 sublineages, 480 (including recombinants) go under the WHO name “Omicron”. At current pace, Omicron will have more than 1000 sublineages within end of next Spring, and people will think nothing is moving. @CorneliusRoemer

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Daniele Focosi, MD PhD MSc

@dfocosi

2 years

Omicron Spike convergent evolution chart UPDATE 11/03. New entries: XAY.1.1 (deltacron recombinant), CP.3 and CZ.1. With the ongoing wave, we already have 48 BQ.* sublineages designated (many with del144). @ewencallaway @SolidEvidence @EricTopol @rquiroga777 @mildanalyst

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Daniele Focosi, MD PhD MSc

@dfocosi

2 years

‼️REAL data from China ⚠️ 1) 55 sequences from Italy ✈️ surveillance ~ 708 released by China 👍 2) 2 “new” variants dominant: BF.7.14 (North) and BA.5.2.48 (South) @DrEricDing @EricTopol @TRyanGregory @RobertoBurioni @ilariacapua H/T @siamosolocani

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Daniele Focosi, MD PhD MSc

@dfocosi

2 years

My greatest concern about a coming bird flu pandemic is exactly “pandemic fatigue” by the masses. At the very beginning many (most?) people would not take claims and mandates seriously. But a flu pandemic leaves no room for negotiations.

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Daniele Focosi, MD PhD MSc

@dfocosi

2 years

Convergent evolution UPDATE 10/19. More converging BQ.1.* sublineages and an interesting pipeline (CA.4, BN.4, BN.3.1, BL.1.*) @EricTopol @TRyanGregory @DrEricDing @ewencallaway @CorneliusRoemer @siamosolocani @florian_krammer @kakape @denise_dewald @mildanalyst @RobertoBurioni

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Daniele Focosi, MD PhD MSc

@dfocosi

2 years

SARS-CoV-2 Spike convergent evolution map UPDATE 12/31 (last of the year😉). Housekeeping & new entries: BF.5.1, BA.5.2.46, XBB.1.5 nickname “Kraken”. @EricTopol @DrEricDing @TRyanGregory @Tuliodna @PeterHotez @RobiVil @kakape @ewencallaway @ilariacapua . Stay safe&tuned in 2023!

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Daniele Focosi, MD PhD MSc

@dfocosi

2 years

UPDATE. Convergent evolution under selective pressure facilitating immune escape. @ACasadevall1 @bjarijn @MarionKoopmans @EricTopol @JosetteSchoenma @yunlong_cao @florian_krammer @Tuliodna @CorneliusRoemer @GuptaR_lab @firefoxx66 @PeacockFlu (thx @SolidEvidence & @siamosolocani )

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Daniele Focosi, MD PhD MSc

@dfocosi

2 years

Update 3/20 SARS-CoV-2 Spike convergent evolution chart. 1) 486P convergence in growing XBB.* family goes on; 2) more BA.2.*xBA.5.* recombinants; 3) 3 more 2nd generation recombinants (XBW, XBY, XBV) after XBL 4) ‼️XBB.1.16 “Arcturus” @EricTopol @TRyanGregory @RobertoBurioni

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Daniele Focosi, MD PhD MSc

@dfocosi

2 years

Convergent evolution UPDATE 11/24. Splitted BA.1-2 and BA.4/5 charts, with red lineages representing contact points. New entries: BW.1.1, DJ.1.*, BA.5.2.42, CM.2.1, and BQ.1.1.25. @TRyanGregory @CorneliusRoemer @yunlong_cao @SolidEvidence @ewencallaway @kakape @EricTopol

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Daniele Focosi, MD PhD MSc

@dfocosi

2 years

Travellers surveillance confirms ~ half of China COVID-19 wave is driven by BF.7+ORF7a:H47Y+S:C1342F. S2 mutations are unlikely to confer Ab escape, but the close ORF7a:F59 downregulates to HLA class I… 🧐 @TRyanGregory @EricTopol @yunlong_cao @PeacockFlu

The SARS-CoV-2 accessory factor ORF7a downregulates MHC class I surface expression

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in over 500 million infections and more than six million deaths worldwide. Although the viral genomes...

www.biorxiv.org

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Daniele Focosi, MD PhD MSc

@dfocosi

2 years

Antigenic chartographies show that the distance from SARS-CoV-2 to XBB is the same as to SARS-CoV(-1). Time to nominate SARS-CoV-3? @TRyanGregory @EricTopol @PeacockFlu @DrEricDing @kallmemeg @ewencallaway @kakape

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Daniele Focosi, MD PhD MSc

@dfocosi

2 years

Convergent evolution UPDATE 5/10. Bubbles reconciled, mAb resistance legend, and a novel #Baseline4 category: BE.4.1.1. Seems BA.5 has a preference for K444X, while BA.2 and BA.4 do not @CorneliusRoemer @PeacockFlu @SolidEvidence @ewencallaway @EricTopol @RobertoBurioni

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Daniele Focosi, MD PhD MSc

@dfocosi

2 years

Convergent evolution chart UPDATE 12/5. Bugfixing after split. New entries: BA.5.2.43, BA.5.2.45, DL.1, CH.3, and the recombinant XBJ. @TRyanGregory @CorneliusRoemer @yunlong_cao @SolidEvidence @ewencallaway @kakape @EricTopol @K_G_Andersen @LongDesertTrain @DrEricDing

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Daniele Focosi, MD PhD MSc

@dfocosi

9 months

‼️As expected, wild circulation leads to wild evolution First signs of JN.* convergence at old-fashioned R346T, L455S again (preferred to L455F), S:T572I (4 branches designated out of 28 identified) and A475X. L452W is no longer Pirola-specific since found in HV.1.10. @EricTopol

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Daniele Focosi, MD PhD MSc

@dfocosi

1 year

It is amazing to see how much interest there is at understanding the origins of SARS-CoV-2 compared to how little interest is at developing newer effective antivirals and vaccines.

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Daniele Focosi, MD PhD MSc

@dfocosi

2 years

🔔🔔 after DN.1.1.1 in UK (BQ.1.1 descendant), another sublineage harboring the mink adaptation signature Y453F is out : XBB.1.12 in Spain/Germany/Sweden. Definitely a mutation to monitor. @Asinickle1 @LongDesertTrain @RajlabN @TRyanGregory @PeacockFlu @Fabrizi66265683

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Daniele Focosi, MD PhD MSc

@dfocosi

2 years

Convergent evolution chart UPDATE 12/15. New entries: CV.2, CH.3.1, BE.10, CN.2 and the XBK recombinant (BA.2.3.20xCJ.1) @EricTopol @TRyanGregory @PeterHotez @DrEricDing @SolidEvidence @ewencallaway @kakape @siamosolocani @CorneliusRoemer @LongDesertTrain

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Daniele Focosi, MD PhD MSc

@dfocosi

2 years

Are Chinese authorities aware they have just approved a drug which does nothing other than creating more mutants ? ⁦ @yunlong_cao ⁩ ⁦ @LongDesertTrain ⁩ ⁦ @WmHaseltine ⁩ ⁦ @EricTopol ⁩

China Approves Merck’s Covid Therapy Amid Shortage of Drugs

China approved Merck & Co.’s Covid-19 antiviral molnupiravir for emergency use as Beijing seeks to expand access to treatments amid a massive wave of infections following its abrupt pivot away from...

www.bloomberg.com

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Daniele Focosi, MD PhD MSc

@dfocosi

2 years

UPDATE 9/30. Convergent evolution in Omicron sublineages, 10 more sublineages added. Please report bugs. @TRyanGregory . @EricTopol @florian_krammer @Tuliodna @CorneliusRoemer @PeacockFlu @DrEricDing @kakape @SolidEvidence @ewencallaway @RobertoBurioni @mlipsitch @JeremyKonyndyk

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Daniele Focosi, MD PhD MSc

@dfocosi

10 months

‼️🚨 #IDTwitter : SARS-CoV-2 in wastewater analysis by country showing impact of #Pirola descendant JN.1 (much better than NPS) . A graph 🧵 @EricTopol @SolidEvidence @LongDesertTrain @SystemsVirology @trvrb @jbloom_lab @ACasadevall1 @yunlong_cao @kakape @ewencallaway @JPWeiland

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Daniele Focosi, MD PhD MSc

@dfocosi

4 months

‼️MAY 29 UPDATE The FLiRT31 family is growing. PLEASE keep JN.1+346T+456L+del31 as next boost! @yunlong_cao @RajlabN @BenjMurrell @SystemsVirology @BenjMurrell @SimonLoriereLab @EricTopol @LongDesertTrain h/t @siamosolocani for proposals & @CorneliusRoemer for designations

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Daniele Focosi, MD PhD MSc

@dfocosi

1 year

SARS-CoV-2 Arcturus descendants are the first “level-3” within the XBB family, harboring all of the 3 major 2023 convergent Spike mutations . GY.2 (aka XBB.1.16.2.2) has F486P+K478R+T883I. XBB.1.16.1 and XBB.1.16.9 have F486P+K478R+F456L . We should pay attention at them.

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Daniele Focosi, MD PhD MSc

@dfocosi

2 years

Interesting paper showing how Spike protein from different SARS-CoV-2 VOCs induce red blood cell agglutination and eventually facilitate blood clots….

SARS-CoV-2 Spike Protein Induces Hemagglutination: Implications for COVID-19 Morbidities and...

Experimental findings for SARS-CoV-2 related to the glycan biochemistry of coronaviruses indicate that attachments from spike protein to glycoconjugates on the surfaces of red blood cells (RBCs),...

www.biorxiv.org

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Daniele Focosi, MD PhD MSc

@dfocosi

2 years

Convergent evolution in recent Omicron sublineages, UPDATE 9/27. Bugfixing and mythology nomenclature by @TRyanGregory . @EricTopol @florian_krammer @Tuliodna @CorneliusRoemer @PeacockFlu @DrEricDing @kakape @SolidEvidence @ewencallaway @RobertoBurioni @mlipsitch @JeremyKonyndyk

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Daniele Focosi, MD PhD MSc

@dfocosi

2 years

Transmissible SARS-CoV-2 variants with resistance to Paxlovid. Who could have predicted this? ⁦ @ACasadevall1 ⁩ ⁦ @manuelenicastri ⁩ ⁦ @andreaantinori ⁩ ⁦ @LongDesertTrain ⁩ ⁦ @PeacockFlu ⁩ ⁦ @theosanderson ⁩

Transmissible SARS-CoV-2 variants with resistance to clinical protease inhibitors

Circulating SARS-CoV-2 variants show resistance to viral protease drugs, nirmatrelvir (Paxlovid) and ensitrelvir (Xocova).

www.science.org

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Daniele Focosi, MD PhD MSc

@dfocosi

2 years

SARS-CoV-2 Spike convergent evolution UPDATE 10/21 (animated GIF). XBB.4 joins CH.1 in the yellow bubble; CK.1 and CK.2.1 join the BQ.1/BW.1/BE.4.2 light blue bubble. @DGBassani @DrEricDing @mildanalyst @TRyanGregory @_b_meyer @denise_dewald @ewencallaway @EricTopol

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Daniele Focosi, MD PhD MSc

@dfocosi

2 years

SARS-CoV-2 Spike convergent evolution UPDATE 2/3. It’s impressive how many independent instances of the 2-nucleotide mutation S486P occurred in XBB.* (clear immune pressure at work). And how tight DN.1.1.1 (a BQ.1.1 descendant) binds to ACE2… @TRyanGregory @RajlabN @PeacockFlu

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Daniele Focosi, MD PhD MSc

@dfocosi

11 months

JN.1 is skyrocketing worldwide and it is going to put an end to the XBB era. A pain that seasonal vaccines are not updated. I feel time has come to nickname JN.1 as “Juno” @TRyanGregory

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Daniele Focosi, MD PhD MSc

@dfocosi

9 months

It has never been the @WHO to alert the world about new SARS-CoV-2 variants. It has been guys like @siamosolocani @PeacockFlu @CorneliusRoemer and many other who created the infrastructure and run it. WHO has lived on their shoulders and it’s a shame you don’t acknowledge them.

Maria Van Kerkhove

@mvankerkhove

9 months

🙏Appreciate the chance to talk to you @ErinMPrater I disagree with your headline though. It’s @WHO with our TAG-VE that continues to track globally, risk assesses & warn the world that this virus- & all its variants- continues to evolve, infect & kill- when it doesn’t have to.

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Daniele Focosi, MD PhD MSc

@dfocosi

2 years

#China SARS-CoV-2 lineages by province (based on GISAID entries, non-imported cases). LIVE GOOGLE CHART. BA.5.2.48 vs BF.7.14 . H/T @siamosolocani for data gathering. @RobertoBurioni @EricTopol @TRyanGregory @DrEricDing @RajlabN @PeacockFlu #IDTwitter

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Daniele Focosi, MD PhD MSc

@dfocosi

1 year

An amazing finding of SARS-CoV-2 evolution in China (both BA.5.* and XBB.* waves) is that almost no RBD mutation has occurred there in one year yet… maybe whole-virus vaccines? @RajlabN @florian_krammer @siamosolocani @LongDesertTrain @yunlong_cao @jbloom_lab @DrEricDing

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Daniele Focosi, MD PhD MSc

@dfocosi

3 months

‼️JUN 29 UPDATE More FLIRT31’s. Convergent evolution and simplified chart @yunlong_cao @RajlabN @BenjMurrell @SystemsVirology @SimonLoriereLab @EricTopol @TRyanGregory @tylernstarr @JPWeiland @LongDesertTrain h/t @siamosolocani for proposals & @CorneliusRoemer for designations

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Daniele Focosi, MD PhD MSc

@dfocosi

2 years

UPDATE 10/26. Amazing findings. BQ.1 and BU.1 only differ at residue 444: T escapes immunity better than M BA.2.75.5 evolution shows F490S alone is detrimental unless “rescued” by R346T @SolidEvidence @siamosolocani @CorneliusRoemer @yunlong_cao @EricTopol @ewencallaway @kakape

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Daniele Focosi, MD PhD MSc

@dfocosi

2 years

A tribute to the SARS-CoV-2 variant seekers, either employed or “simple” citizen scientists. @siamosolocani @RajlabN @JosetteSchoenma @LongDesertTrain @PriscillaFalzi1 @PeacockFlu @theosanderson @SolidEvidence @rquiroga777 @TWenseleers @DoropFan @nzm8qs @AngieSHinrichs @OliasDave

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Daniele Focosi, MD PhD MSc

@dfocosi

2 years

@JosetteSchoenma Likely vaccinated with all 3 doses before the first Omicron infection. Definitely false safety feeling could have overexposed them. But to me the most disturbing point here is that reinfection rate in unvaccinated is similar to the rate in triple vaccinated…

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Daniele Focosi, MD PhD MSc

@dfocosi

5 months

‼️The FLiRTTI family is growing, while waiting for FLIRT+31 family… SLuQE KP.3 remains an outlier @yunlong_cao @RajlabN @BenjMurrell @SystemsVirology @BenjMurrell @SimonLoriereLab @EricTopol @LongDesertTrain h/t @siamosolocani for proposals & @CorneliusRoemer for designations

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Daniele Focosi, MD PhD MSc

@dfocosi

1 year

Let me understand. Since 2 years a team of volunteers regularly identifies variants that @WHO regularly labels as VOI/VOC’s only months later, and you say (“with all of due respect”) they should stop since they are not WHO officials? What a strange way to say “thank you!”.

Tulio de Oliveira

@Tuliodna

1 year

With all of due respect, there is absolute NO CONCERN of Omicron EG.5 in South Africa or most of the world. It would be a good idea if people STOP to spread alarm when a lineage of Omicron emerge or giving SILLY NAMES, this one is called 'Eris' by a single scientist, that has no

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Daniele Focosi, MD PhD MSc

@dfocosi

10 months

Only 2 explanations left here: either JN.1 has transformed into a gastrointestinal virus, or there is more SARS-CoV-2 around now than ever…

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Daniele Focosi, MD PhD MSc

@dfocosi

1 year

‼️AUG 7 UPDATE Convergent evolution of Spike in XBB.* family. Welcome the “FLip” (L455F+F456L): XBB.1.5.70 and HK.3 @RajlabN @florian_krammer @LongDesertTrain @yunlong_cao @jbloom_lab @DrEricDing @SystemsVirology @TRyanGregory @PeacockFlu @EricTopol @SolidEvidence @BarouchLab

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Daniele Focosi, MD PhD MSc

@dfocosi

1 year

‼️SEP 3 UPDATE Spike convergent evolution in XBB.* New FLip members: HK.8, HK.10, JJ.1. HS.1.1 joins 456L+478R family FL.1.5.1 recombined w/ “last of Cerberus” BQ.1.2.2 🧵 @RajlabN @LongDesertTrain @yunlong_cao @jbloom_lab @SystemsVirology @EricTopol @SolidEvidence @BarouchLab

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Daniele Focosi, MD PhD MSc

@dfocosi

9 months

‼️🚨 #IDTwitter : Dec 30 UPDATE (last of 2023🍾) of the tour of #SARSCoV2 loads the world #wastewaters , showing impact of #Pirola descendant JN.1 🧵 @EricTopol @SolidEvidence @LongDesertTrain @trvrb @jbloom_lab @ACasadevall1 @kakape @ewencallaway @angie_rasmussen @TRyanGregory

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Daniele Focosi, MD PhD MSc

@dfocosi

10 months

‼️🚨 #IDTwitter : Dec 13 UPDATE of the tour of the world wastewaters, showing impact of #Pirola descendant JN.1 🧵 @EricTopol @SolidEvidence @LongDesertTrain @trvrb @jbloom_lab @ACasadevall1 @yunlong_cao @sigallab @kakape @ewencallaway @JPWeiland

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Daniele Focosi, MD PhD MSc

@dfocosi

2 years

The BF.7 sublineage dominant in China has just been designated as BF.7.14. ⁦ @yunlong_cao ⁩ ⁦ @TRyanGregory ⁩ ⁦ @DrEricDing ⁩ ⁦ @EricTopol ⁩ ⁦ @siamosolocani ⁩ ⁦ @Asinickle1 ⁩ ⁦ @PeacockFlu ⁩

BF.7 sublineage with S:C1243F circulating in China (292 seq as of 2023-01-06) · Issue #1470 ·...

Proposal for a sublineage of BF.7 Earliest seq: 2022-09-27 (Inner Mongolia, China) Countries detected: China (15 seq, from Beijing and Inner Mongolia), Singapore (8, including 4 travellers from Chi...

github.com

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Daniele Focosi, MD PhD MSc

@dfocosi

1 year

‼️JUN 30 UPDATE Convergent evolution of Spike in the XBB.* family (395 members 😬): bugfixing and plenty of new entries. @RajlabN @florian_krammer @siamosolocani @LongDesertTrain @yunlong_cao @jbloom_lab @DrEricDing @kakape @SystemsVirology @TRyanGregory @PeacockFlu @EricTopol

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Daniele Focosi, MD PhD MSc

@dfocosi

1 year

Good news. Moderna’s updated XBB.1.5-based monovalent vaccine (mRNA-1273.815) increased neutralizing antibody levels against Eg.5.1/Eris and FL.1.5.1/Fornax. It is now fundamental to test vaccine-elicited sera against BA.2.86/Pirula asap.

Moderna Clinical Trial Data Confirm Its Updated COVID-19 Vaccine Generates Robust Immune Response...

Updated COVID-19 vaccine effectively targets EG.5, a dominant variant of concern, as well as the rapidly spreading FL 1.5.1 variant Updated vaccine expected to be available, pending approval, in...

investors.modernatx.com

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Daniele Focosi, MD PhD MSc

@dfocosi

9 months

Sounds like #Paxlovid has dosing issues. And this would be even more worrying for immunocompromised patients. @ACasadevall1 @jhDavidSullivan @ShohamTxID @bjarijn @manuelenicastri

Persistence of an infectious form of SARS-CoV-2 post protease inhibitor treatment of permissive...

Reports have described SARS-CoV-2 rebound in COVID-19 patients treated with nirmatrelvir, a 3CL protease inhibitor. The cause remains a mystery, although drug resistance, re-infection, and lack of...

www.biorxiv.org

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Daniele Focosi, MD PhD MSc

@dfocosi

2 years

@Renmarkable1 @EricTopol @ewencallaway @SolidEvidence @firefoxx66 That the virus is escaping our immune system any possible way.

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Daniele Focosi, MD PhD MSc

@dfocosi

1 year

Oops . And what if CaLu-3 cells are a more relevant model of human infectiousnesss than 293T-ACE2 cells? @yunlong_cao @BarouchLab @BenjMurrell @sigallab @SystemsVirology @PeacockFlu

Shan-Lu Liu

@ShanLuLiu1

1 year

We find that BA.2.86 has low infectivity in 293T-ACE2 cells, similar to @yunlong_cao results, but high infectivity in CaLu-3 cells - actually the highest among all Omicron variants tested.

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Daniele Focosi, MD PhD MSc

@dfocosi

8 months

Bad news for #LongCovid : #Paxlovid treatment doesn’t reduce incidence. Vaccination remains the most effective option. @EricTopol

Effect of Paxlovid Treatment on Long COVID Onset: An EHR-Based Target Trial Emulation from N3C

Preventing and treating post-acute sequelae of SARS-CoV-2 infection (PASC), commonly known as Long COVID, has become a public health priority. In this study, we examined whether treatment with...

www.medrxiv.org

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Daniele Focosi, MD PhD MSc

@dfocosi

4 months

‼️JUN 5 UPDATE 266 JN.1* sublineages. Convergent evolution and simplified charts @yunlong_cao @RajlabN @BenjMurrell @SystemsVirology @BenjMurrell @SimonLoriereLab @EricTopol @TRyanGregory @LongDesertTrain h/t @siamosolocani for proposals & @CorneliusRoemer for designations

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Daniele Focosi, MD PhD MSc

@dfocosi

1 year

‼️AUG 22 UPDATE Convergent evolution of Spike in XBB.* family. Many more converging, including 1 new FLip member (JD.1) @RajlabN @florian_krammer @LongDesertTrain @yunlong_cao @jbloom_lab @DrEricDing @SystemsVirology @TRyanGregory @PeacockFlu @EricTopol @SolidEvidence @BarouchLab

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Daniele Focosi, MD PhD MSc

@dfocosi

1 year

One limitation of COVID-19 mRNA vaccines so far has been they are Spike-centric: BioNTech is testing a BNT162b2 (Spike only) complementary vaccine (BNT162b4) targeting non-Spike region, which works well in animal models.

The T-cell-directed vaccine BNT162b4 encoding conserved non-spike antigens protects animals from...

Adding non-spike targeting components to mRNA vaccination elicits promising T cell responses against SARS-CoV-2 variant strains in rodent models of COVID-19.

www.cell.com

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Daniele Focosi, MD PhD MSc

@dfocosi

2 years

This is definitely not good. Dec 2022 surveillance is -80% compared to Jan 2022. We are approaching a blind flight in the middle of a pandemic. @EricTopol @ewencallaway @kakape @RobertoBurioni @RobiVil

Raj Rajnarayanan

@RajlabN

2 years

Status of Global #SARSCoV2 #Genomic #Surveillance Source: GISAID

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Daniele Focosi, MD PhD MSc

@dfocosi

6 months

APR 4 UPDATE: convergent evolution of JN.* Spike hits “level 4” (346+455+456+572I) with KW.1.1 and KZ.1.1.1 @yunlong_cao @RajlabN @SystemsVirology @BenjMurrell @SimonLoriereLab @EricTopol @TRyanGregory @LongDesertTrain @SolidEvidence @CorneliusRoemer @siamosolocani @BenjMurrell

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Daniele Focosi, MD PhD MSc

@dfocosi

2 years

@EricTopol @NCBI @GISAID @ScienceTM Paxlovid resistance just reviewed here : Delivering it to immunocompromised patients as a monotherapy sounds risky.

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Daniele Focosi, MD PhD MSc

@dfocosi

9 months

‼️ JAN 22 UPDATE of JN.1* evolution. Convergent muts: T95I, R346T, L455S (“SLip”), F456V (“SVip”), A475V/S, T572I, V1004L. See 🧵 below for genetic evolution. @LongDesertTrain @SolidEvidence @jbloom_lab @siamosolocani @JosetteSchoenma @SystemsVirology @yunlong_cao @EricTopol

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Daniele Focosi, MD PhD MSc

@dfocosi

2 months

Good news from @Novavax on their upcoming #COVID19 vaccine boost. Despite not being targeted on currently circulating lineages, it provides good cross-protection

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Daniele Focosi, MD PhD MSc

@dfocosi

10 months

DEC 18 UPDATE ‼️Spike convergent evolution in the skyrocketing #Pirola descendant JN.1* (including XDD and XDK recombinant) + 🧵 @yunlong_cao @RajlabN @PeacockFlu @MarionKoopmans @jbloom_lab @SystemsVirology @SolidEvidence @BarouchLab @sigallab @GuptaR_lab @BenjMurrell @EricTopol

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Daniele Focosi, MD PhD MSc

@dfocosi

2 years

You now Nextclade has this great chart where you can filter variants according to RBD immune escape and ACE2 binding affinity. Then I tried to move the convergent evolution chart with arrows. Amazing how each mutation added invariably increases immune escape . Here is CZ.1 chart

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Daniele Focosi, MD PhD MSc

@dfocosi

1 year

With 4 great studies out so far in #Pirola and it’s 1st sublineage designated, it’s time to summarize findings, crosscheck predictions, solve discrepancies, & exhibit more tools. A🧵 @EricTopol @DrEricDing @TRyanGregory @ewencallaway @kakape @MarionKoopmans @florian_krammer

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Daniele Focosi, MD PhD MSc

@dfocosi

1 year

Good news : in 3 weeks BA.2.86 is almost stuck at 2% (same share found in Swiss wastewater) and seems unable to compete. Bad news: low-level circulation is enough for evolution(>5 branches so far). Without genomic surveillance we can’t really timely predict anything.

Nick Rose

@Asinickle1

1 year

Denmark uploaded new sequences today, 2 of which are BA.2.86. My model shows that the upload lowered the best guess for growth rate advantage, and improved the confidence. Best guess: 35% advantage 80% as likely: [20%, 55%] 50% as likely: [10%, 75%]

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Daniele Focosi, MD PhD MSc

@dfocosi

11 months

First signs of the fitness of #Pirola . Not only 9 different descendants (JN.1 to JN.9), but also a JN.1 recombinant with EG.5.1.1 (named XDD) … @yunlong_cao @RajlabN @MarionKoopmans @jbloom_lab @SystemsVirology @SolidEvidence @BarouchLab @sigallab @GuptaR_lab

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Daniele Focosi, MD PhD MSc

@dfocosi

1 year

‼️JUL 19 UPDATE Convergent evolution of Spike in the XBB.* family: more & different level-3 families. @RajlabN @florian_krammer @siamosolocani @LongDesertTrain @yunlong_cao @jbloom_lab @DrEricDing @kakape @SystemsVirology @TRyanGregory @PeacockFlu @EricTopol @SolidEvidence

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Daniele Focosi, MD PhD MSc

@dfocosi

11 months

‼️New charts of Spike convergent evolution, with a focus on FLip’s + S:A475V and the #Pirola descendant JN.1 @yunlong_cao @RajlabN @PeacockFlu @MarionKoopmans @jbloom_lab @SystemsVirology @SolidEvidence @BarouchLab @sigallab @GuptaR_lab @ACasadevall1 @siamosolocani @EricTopol

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Daniele Focosi, MD PhD MSc

@dfocosi

2 years

Furthermore, there are at least 5 examples here (please report if you know more) where a convergent RBD mutated residue further mutated during evolution (enough to designate a sublineage). Amazingly, this invariably translated into increased ACE2 affinity (rightward arrows)

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Daniele Focosi, MD PhD MSc

@dfocosi

2 years

Here is the XBB.* and CH.1.1.1 chart. Same upward progression in RBD immune escape . No single downward arrow.

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Daniele Focosi, MD PhD MSc

@dfocosi

1 year

SARS-CoV-2 genome is changing. After truncated N, deleted ORF8, and loss of ORF7a, now ORF7b stop codons are leading to massive epitope changes in 2 non-XBB competitive lineages (XBC.1 and FR.1). Immune escape in action. @EricTopol @TRyanGregory @SystemsVirology @jbloom_lab

Ryan Hisner

@LongDesertTrain

1 year

What's going on with ORF7b? Something unusual has occurred in ORF7b in two unrelated variants—two of the only non-XBB variants that remain competitive. They took entirely different routes to reach the same end point: a new ORF7b protein. But first a short primer on ORF7b. 1/

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Daniele Focosi, MD PhD MSc

@dfocosi

2 years

Italy is reporting a unique SARS-CoV-2 Cerberus sublineage, a die hard against the XBB wave, with an intriguing Spike deletion. H/t @siamosolocani for proposing the lineage. @Fabrizi66265683 @RobertoBurioni @RobiVil @AurelianoStingi

Rise of the BQ.1.1.37 SARS-CoV-2 Sublineage, Italy

BQ.1.1 has dominated the Europe and Americas COVID-19 wave across the 2022–2023 winter, and further viral evolution is expected to escape the consolidating immune responses. We report here the...

www.mdpi.com

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Daniele Focosi, MD PhD MSc

@dfocosi

2 years

What’s going with SARS-CoV-2 in China? Local evolution, as expected, but at residues ≠ those converging in the rest of the world. More DY.* expected soon, I guess. Here’s a graphical summary. @siamosolocani @DrEricDing @EricTopol @PeacockFlu @TRyanGregory @RajlabN @ilariacapua

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Daniele Focosi, MD PhD MSc

@dfocosi

1 year

Wait a little more before saying Pirola is not transmissible enough. Mutated descendants and clusters emerging:

Andrew Urquhart

@wolfeagle1989

1 year

BA.2.86’s first sublineage BA.2.86.1 has been designated. It is defined by 2 additional mutations: ORF1a:K1973R (NSP3:K1155R) and synonymous nucleotide mutation C12815T. It debuts in 2nd place on #Collection42 sorted by CI (low).

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Daniele Focosi, MD PhD MSc

@dfocosi

9 months

‼️Does the updated XBB.1.5 vaccine protects against the SARS-CoV-2 variant JN.1 ? A short🧵 @EricTopol @kakape @ewencallaway @DrEricDing @PeterHotez @jbloom_lab @BenjMurrell @RajlabN @LongDesertTrain @PeacockFlu @siamosolocani @ACasadevall1 @MarionKoopmans @RobiVil

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Daniele Focosi, MD PhD MSc

@dfocosi

1 year

⁦⁦ @ewencallaway ⁩ : it’d have been nice to acknowledge the contribution of variant seekers such as ⁦ @shay_fleishon ⁩ ⁦ @LongDesertTrain ⁩ ⁦ @OliasDave . Without them ⁦ @WHO ⁩ and we all wouldn’t be aware of BA.2.86 at this point.

Why a highly mutated coronavirus variant has scientists on alert

Nature - Research is under way to determine whether the mutation-laden lineage BA.2.86 has the potential for global spread — or whether it is nothing to worry about.

www.nature.com

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Daniele Focosi, MD PhD MSc

@dfocosi

8 months

‼️ FEB 2 UPDATE of JN.1* evolution. Convergent muts: T95I, R346S/T, L455S (“SLip”), F456V (“SVip”), A475V/S, T572I. MAT and bubble views. @LongDesertTrain @SolidEvidence @jbloom_lab @siamosolocani @JosetteSchoenma @SystemsVirology @yunlong_cao @EricTopol

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Daniele Focosi, MD PhD MSc

@dfocosi

2 years

SARS-CoV-2 evolution in China moves as fast as expected @yunlong_cao @DrEricDing @TRyanGregory @EricTopol

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Daniele Focosi, MD PhD MSc

@dfocosi

1 year

Molnupiravir is mutagenic (and EMA has deauthorized it since it’s ineffective). Shifting stockpiles for treating a different coronavirus (FIPV) in a species which can be easily co-infected with SARS-CoV-2, is NOT a good idea ⁦⁦⁦ @PeacockFlu ⁩

Cyprus to begin treating island’s sick cats with anti-Covid pills

Vets receive medication originally meant for people amid virulent feline coronavirus that has killed thousands of cats

www.theguardian.com

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Daniele Focosi, MD PhD MSc

@dfocosi

1 year

‼️SEP 18 UPDATE of the Spike convergent evolution in XBB.* More “FLip” nodes: JG.3 and EG.5.1.8 @RajlabN @LongDesertTrain @yunlong_cao @jbloom_lab @SystemsVirology @EricTopol @SolidEvidence @BarouchLab @sigallab @siamosolocani @GuptaR_lab @tylernstarr @BenjMurrell @ShanLuLiu1

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Daniele Focosi, MD PhD MSc

@dfocosi

2 years

XBB.1.5 (Kraken) has both “increase in transmissibility” AND “decrease in effectiveness of […] available […] therapeutics”: then its a VOC, not a VOI, per @who “criteria”. ⁦ @TRyanGregory ⁩

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Daniele Focosi, MD PhD MSc

@dfocosi

1 year

BA.2.86 variant under monitoring (VUM) (formerly BA.X) is now at 5 (totally unrelated) cases since July 24 across 4 countries with high sequencing rates (2 in Denmark and 1 each in Israel, Michigan, & today UK). Higher prevalence is reasonable. 🧵 @kakape @ewencallaway @EricTopol

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Daniele Focosi, MD PhD MSc

@dfocosi

6 months

MAR 27 UPDATE : convergent evolution of Spike in JN.* reaches “level 3” (346+455+456). @yunlong_cao @RajlabN @SystemsVirology @BenjMurrell @SimonLoriereLab @EricTopol @TRyanGregory @LongDesertTrain @SolidEvidence @CorneliusRoemer @siamosolocani @BenjMurrell @SimonLoriereLab

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Daniele Focosi, MD PhD MSc

@dfocosi

2 years

Somebody forecasted this: Merck’s mutagenic antiviral pill #molnupiravir creates a quasispecies swarm in immunocompromised patients. ⁦ @WmHaseltine ⁩ ⁦ @LongDesertTrain ⁩ ⁦ @FabrizioChiodo ⁩ ⁦ @siamosolocani ⁩ ⁦ @ACasadevall1 ⁩

Antiviral treatments lead to the rapid accrual of hundreds of SARS-CoV-2 mutations in immunocompr...

The antiviral Molnupiravir (Lageviro) is widely used across the world to treat SARS-CoV-2 infection. Molnupiravir reduces viral replication by inducing mutations throughout the genome, yet in...

www.medrxiv.org

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Daniele Focosi, MD PhD MSc

@dfocosi

1 year

WHO escalated EG.5.1.* to VOI because it is now 24% of cases, in < 2 months (right part of the chart is deleted bc time from sampling to sequence deposition in GISAID is >2 weeks in most of the world + the time CoV-Spectrum takes for updates). No slowing.

Daniele Focosi, MD PhD MSc

@dfocosi

1 year

‼️Bad news. EG.5.1 escapes both XBB.1.5 and BA.5+XBB.1.5 breakthrough infection sera at unprecedented levels. Expect a big wave, and let’s hope cell-mediated immunity is not as bad. @EricTopol @kakape @florian_krammer @MarionKoopmans @ACasadevall1 @manuelenicastri

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Daniele Focosi, MD PhD MSc

@dfocosi

1 year

‼️JUN 17 UPDATE Convergent evolution of Spike in XBB.* : plenty of updates. @US_FDA @WHO_Europe : XBB.1.5, but seriously? @RajlabN @florian_krammer @siamosolocani @LongDesertTrain @yunlong_cao @jbloom_lab @DrEricDing @kakape @SystemsVirology @TRyanGregory @PeacockFlu @EricTopol

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Daniele Focosi, MD PhD MSc

@dfocosi

1 year

This biologist is reporting #Pirola symptoms as “mimicking those of severe flu with 38’C fever for several days, strong rhinitis and headache. It is no longer characterized by the asymptomatic pattern typical of many Omicron variants”.Raw data source, plz?

Nuova variante Covid 'Pirola' ha 40 mutazioni e 2 da monitorare - Medicina - Ansa.it

La nuova variante Covid BA.2.86, soprannominata 'Pirola' presenta "un numero significativo di 40 mutazioni che potrebbero aiutare il virus a eludere la risposta immunitaria" ma "due sono in partico...

www.ansa.it

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Daniele Focosi, MD PhD MSc

@dfocosi

6 months

APR 16 UPDATE. Here’s the answer: they converge. At 3 positions which could largely inform the next vaccine boost. @yunlong_cao @RajlabN @SystemsVirology @BenjMurrell @SimonLoriereLab @EricTopol @LongDesertTrain @SolidEvidence @CorneliusRoemer @siamosolocani @BenjMurrell

Elon Musk

@elonmusk

6 months

🤔

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Daniele Focosi, MD PhD MSc

@dfocosi

10 months

NOV 29 UPDATE ‼️Spike convergent evolution, with a focus on FLip’s + S:A475V and the skyrocketing #Pirola descendant JN.1 @yunlong_cao @RajlabN @PeacockFlu @MarionKoopmans @jbloom_lab @SystemsVirology @SolidEvidence @BarouchLab @sigallab @GuptaR_lab @BenjMurrell @EricTopol

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Daniele Focosi, MD PhD MSc

@dfocosi

1 year

While still waiting for the 6th #BA286 / #Pirola sequence from Denmark, it is becoming increasingly clear how different this lineage is from BA.2 and XBB.1.5. (h/t @CorneliusRoemer )

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Daniele Focosi, MD PhD MSc

@dfocosi

2 years

After the failure of molnupiravir, more shadows on #Paxlovid from studies in ferrets and mice (does not prevent transmission but prevents an adaptive immune response: hint for explaining rebounds?) @LongDesertTrain @WmHaseltine

Nirmatrelvir treatment blunts the development of antiviral adaptive immune responses in SARS-CoV-2...

Alongside vaccines, antiviral drugs are becoming an integral part of our response to the SARS-CoV-2 pandemic. Nirmatrelvir – an orally available inhibitor of the 3-chymotrypsin-like cysteine protease...

www.biorxiv.org

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Daniele Focosi, MD PhD MSc

@dfocosi

1 year

This is not a 🧵: this is the most clear and updated review on SARS-CoV-2 cell entry I have ever read.

Ryan Hisner

@LongDesertTrain

1 year

I think this preprint, by @Stuartturville , is potentially one of the more important recent SARS-CoV-2 papers. It promises to unwrap some of the most mystifying aspects of Omicron surrounding cell entry, TMPRSS2 use, & reduced lung invasion/pneumonia. 1/48

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Daniele Focosi, MD PhD MSc

@dfocosi

2 years

Synchronous respiratory viral infections have never been rare, but in this triple-pandemic season (SARS-CoV-2, influenzavirus and RSV) they will be exceedingly common: now we know that hybrid viruses can develop. ⁦ @TRyanGregory ⁩

Coinfection by influenza A virus and respiratory syncytial virus produces hybrid virus particles

Nature Microbiology - Chimeric particles are formed when influenza A virus and respiratory syncytial virus coinfect lung cells in vitro.

www.nature.com

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Daniele Focosi, MD PhD MSc

@dfocosi

1 year

‼️🆕Time to track convergent evolution of Spike in XBB.* : please report bugs and consider there is much more than Spike. @RajlabN @florian_krammer @siamosolocani @LongDesertTrain @yunlong_cao @jbloom_lab @DrEricDing @kakape @SystemsVirology @TRyanGregory @PeacockFlu @EricTopol

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