BGBIO: FORSKNING OG MEDISINER RELATERT TIL BerGenBio


Her er en samling forskningsrelaterte artikler som samlet sett indikerer at de vaksinene som er under utvikling i fase III i dag, kanskje ikke kommer til å virke mer enn noen måneder, eller at de kanskje til og med kun kommer til å virke mot den opprinnelige virusvarianten D614 (Original Wuhan strain), mens det i dag finnes veldig mange andre varianter, der D614G er den som øker mest og er den mest vanlige.
Det finnes mange andre sars-cov-2 varianter, blant annet V483G* som har vist seg langt mer smittsom, uten å være mindre dødelig (så langt). Denne finnes nå i Brasil, Midt-Østen, UK og i USA.
(Her er en god artikkel som viser virusvarianter som nå er mest utbredt i ulike verdensdeler https://www.news-medical.net/news/20200925/D614G-mutation-now-the-dominant-variant-in-the-global-COVID-19-pandemic.aspx)

Årsaken til at vaksinene kanskje ikke kommer til å være effektive skyldes blant annet at antistoffer ser ut til å forsvinne relativt raskt, samt at vaksinene som nå er i fase III ble ferdigstilt rundt mars måned 2020, og har derfor ikke inkludert mutasjoner som har kommet til senere, eller som ikke var vanlige på det tidspunktet.


En kanadisk studie ledet av forskere ved Temerty Faculty of Medicine ved Universtitetet i Toronto viser at antistoffer kun er effektive i 3 måneder fra man får covid-19 symptomer. IgA og IgM antistoffer falt kraftig, og forsvant etter 3 måneder. IgG antistoffer var stabile opp til 105 dager etter virussykdommen inntraff. Studien vurderte til og med dag 115 (studien stoppet der). De siste dagene fra dag 105 til dag 115 ble det observert signifikant reduksjon i IgG, men siden studien ikke pågikk lengre er det vanskelig å dra konklusjoner ut av dette.
IgA antistoffer er antagelig de viktigste antistoffene mot covid-19, og kan være såkalte "neutralizing antibodies".
Flere studier har funnet at antistoffer mot sars-cov-2 i seg selv ikke beskytter mot covid-19. Det er "neutralizing antibodies" som beskytter best.
"Indeed, IgA is an important mediator of protection against gastrointestinal viruses (38), is essential in achieving immunity against avian viruses (39), has been shown to contribute to the neutralizing antibody (nAb) response to SARS-CoV-2 (28)".
https://www.thailandmedical.news/news/covid-19-antibodies-university-of-toronto-study-shows-that-sars-cov-2-coronavirus-antibodies-last-for-only-about-three-months-after-infection
https://immunology.sciencemag.org/content/5/52/eabe5511

En studie viste at barn kan ha IgG antistoffer mot SARS-COV-2, samtidig som de er smittet med SARS-COV-2.
https://www.thailandmedical.news/news/breaking-covid-19-pediatrics-study-shows-that-kids-can-have-the-sars-cov-2-coronavirus-and-the-antibodies-simultaneously
https://www.medrxiv.org/content/10.1101/2020.08.06.20162446v1

"SARS-CoV-2 reinfection in two patients who have recovered from COVID-19"
"During the second admission, both patients showed increases in their IgG anti-SARS-CoV-2 titers, and one patient also showed renewed reactivity for IgM anti-SARS-CoV-2. As both had recovered clinically and had negative throat swab viral RNA for 43–58 days before they became sick again with positive throat swab viral RNA together with an increase in IgG antibody (with one also showing IgM again), they were considered as having SARS-CoV-2 reinfection."
https://academic.oup.com/pcm/advance-article/doi/10.1093/pcmedi/pbaa031/5901533

ANTISTOFFER TILSVARENDE DET NIVÅ FORSØKSPERSONER FÅR ETTER BOOSTING DOSE (dose nr 2) MED COVID-19 VAKSINE HINDRET IKKE REINFEKSJON HOS PASIENT MED D614G strain.
https://www.thailandmedical.news/news/must-read-study-involving-case-of-reinfection-questions-efficacy-of-covid-19-vaccines-under-development-or-trials-against-em

"Covid-19 Immunity short-lived for those who are asymtpomatic or had mild symptoms. Doubts raised about ability of vaccines to really work".
https://www.thailandmedical.news/news/covid-19-immunity-short-lived-for-those-who-are-asymptomatic-or-had-mild-symptoms-doubts-raised-about-ability-of-vaccines-to-really-work
https://www.medrxiv.org/content/10.1101/2020.09.05.20187435v1.full.pdf

"Antibodies COVID-19: Another study shows that antibodies not effective in treating COVID-19 and warns of vaccines focusing only on spike proteins"
https://www.thailandmedical.news/news/antibodies-covid-19-another-study-shows-that-antibodies-not-effective-in-treating-covid-19-and-warns-of-vaccines-focusing-only-on-spike-proteins
https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1008796

En artikkel som beskriver hvordan sars-cov-2 smitten spres i land av asymptomatiske pasienter.
https://www.thailandmedical.news/news/the-frightening-tale-of-a-hypothetical-south-east-asian-country-where-4-percent-of-its-population-might-already-been-affected-by-milder-strains-of-sar

"COVID-19 Immunity: Study shows that protective immunity to current seasonal coronaviruses are short-lasting, SARS-COV-2 could be the same".
Studien går tilbake til data fra 1980-tallet til i dag, og ser på infeksjoner med coronavirus. Pasientene hadde 3-17 reinfeksjoner med coronavisu, og reinfeksjon skjedde fra 6-105 måneder. Reinfeksjoner ble hyppig observert etter 12 måneder.
https://www.thailandmedical.news/news/covid-19-immunity-study-shows-that-protective-immunity-to-current-seasonal-coronaviruses-are-short-lasting,-sars-cov-2-could-be-the-same
https://www.nature.com/articles/s41591-020-1083-1

"COVID-19 herd immunity is impractical and disastrous according to new study plus emerging studies indicate immunity is short lived".
https://www.thailandmedical.news/news/covid-19-herd-immunity-is-impractical-and-disastrous-according-to-new-study-plus-emerging-studies-indicate-immunity-is-short-lived
https://www.pnas.org/content/early/2020/09/21/2008087117

"Coronavirus latest: Experts concerned as reinfections occuring in shorter intervals, also new study shows antibodies in infected diminish in about 60 days".
https://www.thailandmedical.news/news/coronavirus-latest-experts-concerned-as-reinfections-occurring-in-shorter-intervals,-also-new-study-shows-antibodies-in-infected-diminish-in-about-60-
https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciaa1436/5908892

"MUST READ! Study involving case of reinfection questions efficacy of covid-19 vaccines under development or trials against emerging mutated strains".
https://www.thailandmedical.news/news/must-read-study-involving-case-of-reinfection-questions-efficacy-of-covid-19-vaccines-under-development-or-trials-against-emerging-mutated-strains

"BREAKING!! Covid-19 immunity: New study that is yet to be peer-reviewed says humans may never develop immunity against covid-19".
https://www.thailandmedical.news/news/breaking-covid-19-immunity-new-study-that-is-yet-to-be-peer-reviewed-says-humans-may-never-develop-immunity-against-covid-19
https://www.medrxiv.org/content/10.1101/2020.06.13.20130252v1.full.pdf+html


Missed the cut:
https://www.thailandmedical.news/news/covid-19-antibodies-new-york-university-scientist-discover-that-up-to-75-percent-of-recovered-covid-19-patients-have-low-neutralizing-antibody-titers
https://www.thailandmedical.news/news/breaking-covid-19-re-infections-more-cases-of-documented-covid-19-re-infected-cases-emerging-first-hong-kong,-now-belgium-and-netherlands
https://www.thailandmedical.news/news/covid-19-vaccine-researchers-identify-t-cell-epitopes-for-effective-vaccine-development
https://www.thailandmedical.news/news/thailand-covid-19-news-6-new-imported-cases-of-which-3-are-reinfections-opening-of-phuket-to-foreigners-delayed,-phangnga-imposes-strict-measures-
https://www.thailandmedical.news/news/rare-covid-19-antibody-development-in-cancer-patients-observed-in-german-study (Kun 6 av 77 smittede i en tysk studie hadde antistoffer).
https://www.thailandmedical.news/news/india-covid-19-coronavirus-news-documented-reinfections-emerging-in-india,-vaccines-and-antibodies-being-questioned,-record-94,000-cases-in-24-hours
https://www.thailandmedical.news/news/breaking-covid-19-research-mutated-sars-cov-2-spike-protein-variants-evade-neutralizing-antibodies-warning-of-emergence-of-antibody-resistant-variants
https://www.biorxiv.org/content/10.1101/2020.07.21.214759v1.full.pdf
https://www.thailandmedical.news/news/breaking-covid-19-reinfections-israeli-doctor-reinfected-with-sars-cov-2-just-12-weeks-after-recovering,-more-reinfections-appearing-globally
https://www.timesofisrael.com/israeli-doctor-diagnosed-with-virus-after-apparently-recovering-from-covid-19
https://www.publichealth.columbia.edu/public-health-now/news/risk-coronavirus-reinfection-remains-after-recovery
https://www.medrxiv.org/content/10.1101/2020.04.27.20082032v1

"Reinfections" i nyhetene:
https://www.sciencealert.com/35-year-study-of-coronavirus-reinfections-suggests-human-immunity-is-short-lived
https://news.harvard.edu/gazette/story/2020/10/covid-survivors-may-have-four-months-of-protection/
LES DENNE: https://www.scientificamerican.com/article/what-covid-19-reinfection-means-for-vaccines/
"The Kenya study on endemic human coronaviruses, however, offers evidence to the contrary that may turn out to be applicable to SARS-CoV-2. In some patients, it was found that high antibody levels actually potentiated infection rather than preventing or mitigating it"
https://bgr.com/2020/10/06/coronavirus-immunity-reinfection-cases-mount-second-wave/
https://www.theguardian.com/world/2020/oct/06/flurry-of-coronavirus-reinfections-leaves-scientists-puzzled
https://www.mlive.com/news/muskegon/2020/10/rise-of-coronavirus-in-nursing-homes-has-muskegon-county-probing-possible-reinfections.html


*V483G mutasjonen er motstandsdyktig mot antistoffer.
https://www.thailandmedical.news/news/v483g-mutation-warning-about-growing-prevalence-of-new-sars-cov-2-mutant-strain-v483g-that-is-antibody-resistant-and-even-more-infectious
Forøvrig spekuleres det i at dersom monoclonal antibodies fungerer (det Trump fikk), så kan prisen på hver behandling bli 6-8000 dollar.
Redigert 21.01.2021 kl 09:40 Du må logge inn for å svare
BioBull
26.01.2021 kl 21:38 8134

Regner med at ditt sitat er «gått ut på dato», hvis ikke ville ikke Merck ha informert om at det ikke finnes medisiner mot sykdommen.

Jeg siterer fra Merck web side - se nederste avsnitt !

https://www.merck.com/stories/hpv-awareness/

« A common virus that can cause certain cancers in both men and women
HPV is a common virus that can have potentially serious consequences. In fact, HPV is so common that a majority of sexually active people will become infected in their lifetime. For most people, HPV clears on its own. But, for others who don’t clear the virus, it can cause certain cancers and other diseases. And there’s no way to predict who will or won’t clear the virus.

HPV doesn’t discriminate. Both men and women are at risk for the certain cancers and diseases it can cause. In women, HPV can cause cervical, vaginal and vulvar cancer. It can also cause anal cancer and genital warts in both women and men.

The impact of HPV
icon
~14M
The estimated number of people in the U.S. infected with HPV each year.
icon
~23,230
2015 estimated U.S. incidence of cervical, vulvar, vaginal and anal cancers.
icon
~80%
The probability of being infected with HPV by age 45 among sexually active people in the U.S.


0 - ZERO - NULL - INGEN - NADA
The number of treatment options for HPV infection.

While there may be treatments available for certain HPV-related cancers and diseases, there is no treatment available for HPV infection.»
Redigert 26.01.2021 kl 21:55 Du må logge inn for å svare
Carrera
26.01.2021 kl 21:43 8135

Statens legemiddelverk.
Det er mangel på Gardasil 9 «MSD Vaccins». Årsak til mangelen er økt etterspørsel internasjonalt. Forventet leveringstid er 1. kvartal 2021
Gardasil 9 inneholder rekombinant Humant Papillomavirus (HPV) og brukes til aktiv immunisering mot HPV-relaterte premaligne lesjoner, kjønnsvorter og kreft.

Legemiddelverket har frem til 31. juli 2020 mottatt til sammen 1165 bivirkningsmeldinger etter at nesten 540 000 personer har blitt vaksinert med minst en dose HPV-vaksine i Norge. I all hovedsak betegnes bivirkningene som lite alvorlige.

https://www.felleskatalogen.no/medisin/gardasil-9-msd-vaccins-633598
BioBull
26.01.2021 kl 21:58 8107



Ta imot gode råd fra Merck - ikke mer fra meg :

« For more information about HPV, certain related cancers and preventative measures, speak with your doctor»
Carrera
26.01.2021 kl 22:34 8012

Gardasil 9 is an HPV vaccine approved by the U.S. Food and Drug Administration and can be used for both girls and boys. This vaccine can prevent most cases of cervical cancer if given before a girl or woman is exposed to the virus.

Hør gjennom siste presentasjoner.
NSCLC dataene som er presentert tidligere, er såkalte "umodne" data. Dvs det tar tid før man kan se hva den faktiske forskjellen i bedring og overlevelse blir.
For å være godt forberedt til presentasjonen kan det nok være lurt å se gjennom siste NSCLC ppt /pdf presentasjon.
AML studiene viste svært gode resultat, så der kan vi nok forvente at BGBIO lykkes med å finne en partner i løpet av 2021.
De umodne NSCLC dataene har ikke vert like overbevisende. Og det er NSCLC som det er mest penger i. Det blir derfor spennende å se hva de kommer med.
Carrera
26.01.2021 kl 22:41 8026

Legislation[edit]
Shortly after the first HPV vaccine was approved, bills to make the vaccine mandatory for school attendance were introduced in many states.[171] Only two such bills passed (in Virginia and Washington DC) during the first four years after vaccine introduction.[171] Mandates have been effective at increasing uptake of other vaccines, such as mumps, measles, rubella, and hepatitis B (which is also sexually transmitted).[165] However most such efforts developed for five or more years after vaccine release, while financing and supply were arranged, further safety data was gathered, and education efforts increased understanding, before mandates were considered.[171] Most public policies including school mandates have not been effective in promoting HPV vaccination while receiving a recommendation from a physician increased the probability of vaccination.[172] The FDA approved Gardasil 9 for women and men ages 27 to 45 in October 2018.[1
BioBull
26.01.2021 kl 23:12 7988

Full fokus på Fredagens presentasjon:

https://library.iaslc.org/conference-program?product_id=20&author=&category=&date=&session_type=&session=&presentation=&keyword=bemcentinib&cme=undefined&;

For dere som ikke har registrert dere eller har fått tilgang :

OA01 - Established Drugs in Special Populations and New Drugs in Established Populations
09:15 - 10:15 ( Singapore time)
1/29/2021
Location: Scientific Program Auditorium
IASLC CME Accredited
Type: Oral
Track: Immunotherapy (Phase II/III Trials)
-
OA01.07 - A Phase II Study of the Oral Selective AXL Inhibitor Bemcentinib with Pembrolizumab in Patients with Advanced NSCLC
09:50 - 10:00 | Presenting Author(s): Matthew G. Krebs

Abstract
Introduction
AXL is a mediator of resistance to immunotherapy and a negative prognostic factor for NSCLC. Bemcentinib (BGB324), a first-in-class, oral, selective and potent AXL kinase inhibitor, enhances checkpoint inhibitor (CPI) efficacy in pre-clinical models through tumor-immune mechanisms. Increasingly, the combination of doublet chemotherapy with checkpoint inhibitors (Chemo-CPI) is a commonly used option for advanced NSCLC, and recurrence following such first line therapy represents an area of great unmet need. BGBC008 addresses the unmet need for NSCLC patients who fail 1L SOC.
Methods
BGBC008 is a PhII single-arm, 2-stage study with bemcentinib (200mg/d) and pembrolizumab (200 mg/q3wk) for previously-treated Stage IV lung adenocarcinoma comprising 3 cohorts: chemotherapy-failed IO-naïve patients (post-Chemo), patients progressing on prior CPI therapy (post-CPI monotherapy) and platinum-doublet chemotherapy in combination with pembrolizumab (post-Chemo-CPI). Primary endpoint was ORR according to RECIST1.1 with pre-defined criteria to proceed from the first to second stage in each cohort. Secondary endpoints included DCR, PFS, OS and safety. Exploratory endpoints include biomarker analysis and correlation with clinical endpoints, including composite (tumor and immune cell) cAXL score, PD-L1 TPS, and genome-wide mutational and transcriptome analyses.
Results
As of August 2020, enrollment in the post-Chemo cohort and stage 1 of the post-CPI monotherapy cohort is completed. Results of the post-Chemo cohort (n=50) and post-CPI monotherapy stage 1 cohort (n=16) were previously presented. Stage 2 of the post-CPI monotherapy cohort and stage 1 of the post-Chemo-CPI cohort are currently recruiting into the study.
In patients treated to date, common TEAEs (>25% of patients) for NSCLC patients receiving the bemcentinib + pembrolizumab combination were: increased ALT (29%; 10% G3+), AST (29%; 5% G3+), and diarrhoea (29%; 1% G3+). All cases of treatment-related transaminase increase were reversible and managed with concomitant administration of steroids and treatment interruption.
Having previously demonstrated a very high clinical benefit rate in post-Chemo and post-CPI monotherapy (stage 1) in cAXL-positive patients (73% and 85%, respectively), and low probability of clinical benefit in cAXL-negative patients (40% and 0%, respectively) further focus on the predictive value of cAXL in second line patients following either CPI monotherapy or Chemo-CPI relapse will be reported, together with transcriptional analysis to identify gene based predictive signatures.
Conclusion
Overall, bemcentinib in combination with pembrolizumab was well-tolerated and shows promising clinical activity in relapsed lung cancer. The key unmet need population of second line patients refractory to CPI monotherapy or Chemo-CPI will be presented together with translational data. Clinical Trial Registration: NCT03184571

BioBull
27.01.2021 kl 07:59 7834

Flott tilbud for alle som ønsker å leve «det gode liv» på Barbados under COVID-19.

“Working remotely from Barbados 🇧🇧 is seem less”
Manhattan Investment Banker working from the Beach


https://open.spotify.com/episode/5q06ivFOkeDkshZJEl2yBR?si=Q8OWUr8fRgu9YBYVmoUMrQ
Nobilis
28.01.2021 kl 11:36 7484

Mulig denne studien som er publisert i Nature er kommentert tidligere. Det er tydeligvis mange kompetente her på forum. Hva er deres kommentar til konklusjonen neders og relevans for Bergen Bio?
Abstract
The current coronavirus disease 2019 (COVID-19) pandemic presents a global public health challenge. The viral pathogen responsible, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), binds to the host receptor ACE2 through its spike (S) glycoprotein, which mediates membrane fusion and viral entry. Although the role of ACE2 as a receptor for SARS-CoV-2 is clear, studies have shown that ACE2 expression is extremely low in various human tissues, especially in the respiratory tract. Thus, other host receptors and/or co-receptors that promote the entry of SARS-CoV-2 into cells of the respiratory system may exist. In this study, we found that the tyrosine-protein kinase receptor UFO (AXL) specifically interacts with the N-terminal domain of SARS-CoV-2 S. Using both a SARS-CoV-2 virus pseudotype and authentic SARS-CoV-2, we found that overexpression of AXL in HEK293T cells promotes SARS-CoV-2 entry as efficiently as overexpression of ACE2, while knocking out AXL significantly reduces SARS-CoV-2 infection in H1299 pulmonary cells and in human primary lung epithelial cells. Soluble human recombinant AXL blocks SARS-CoV-2 infection in cells expressing high levels of AXL. The AXL expression level is well correlated with SARS-CoV-2 S level in bronchoalveolar lavage fluid cells from COVID-19 patients. Taken together, our findings suggest that AXL is a novel candidate receptor for SARS-CoV-2 which may play an important role in promoting viral infection of the human respiratory system and indicate that it is a potential target for future clinical intervention strategies.
klaesp
28.01.2021 kl 12:12 7489

Trekker ut essensen.
while knocking out AXL significantly reduces SARS-CoV-2 infection in H1299 pulmonary cells and in human primary lung epithelial cells. Soluble human recombinant AXL blocks SARS-CoV-2 infection in cells expressing high levels of AXL. The AXL expression level is well correlated with SARS-CoV-2 S level in bronchoalveolar lavage fluid cells from COVID-19 patients. Taken together, our findings suggest that AXL is a novel candidate receptor for SARS-CoV-2 which may play an important role..

Noen som tviler på kommende Covid oppdatering?
long41
28.01.2021 kl 12:19 7583

Selv om lenken er postet tidligere, er det fint å få den med når dere siterer artikkelen på nytt. Så jeg legger den ved her: https://www.nature.com/articles/s41422-020-00460-y

Det er en veldig positiv artikkel for bemcentinib mot covid, da den sier at AXL er mer relevant enn ACE2. :)
klaesp
28.01.2021 kl 15:19 7391

Jepp, forventer solid oppgang i morgen og neste uke i påvente av melding (er) starter allerede i morgen.

Ligger godt ann til rally siden timen i påvente av morgendagens nyheter 👍
Redigert 28.01.2021 kl 15:25 Du må logge inn for å svare

Presentasjonen er vel i natt? Det er vel ikke særlig trolig med store nyheter da? De vil vel evt komme senere i en ordinær melding? Men kursen går vel sikkert noe før stengetid i dag, men ikke voldsomt mye. Kanskje 34-35 om man tar i skikkelig? Så litt ned igjen i morgen pga skuffede håpefulle i forhold til presentasjonen? Så kommer det en melding eller fem en gang i løpet av vinteren som gjør susen!
klaesp
28.01.2021 kl 15:47 7443

Jeg har trua på andre nyheter neste uke .

Personlig tror jeg fase3 er nært forestående , ref melding fra i 20

Videre opplyses det at styret er stadig mer overbevist om at fortsatt lovende data fra studier av bemcentinib i AML, MDS og NSCLC representerer klinisk "proof of concept" for AXL-hemming i kreftterapi, noe som garanterer ytterligere undersøkelser i avgjørende forsøk.
Redigert 28.01.2021 kl 15:58 Du må logge inn for å svare

Det blir spennende nå fremover - Vi kommer jo nærmere for hver dag som går. Vi får håpe de kommer med kursdrivende meldinger slik at stemningen blir på topp. 👍

Ny studie indikerer at asymptomatisk smitte er vanligere enn vi har trodd.

"The corrections due to the serological test sensitivity (in particular those ones depending on the symptoms onset) make the comparison between data and models less accurate. conclusions: The predictions of the model confirm a relevant presence of asymptomatic individuals also during the second pandemic wave in Italy. The ratio of reported to unreported cases is predicted to be roughly 1:4..."
https://www.medrxiv.org/content/10.1101/2021.01.27.21250597v1

Hvordan viruset har utviklet seg, og alvorlighetsgraden til de ulike variantene:
https://www.bbc.com/future/article/20210127-covid-19-variants-how-mutations-are-changing-the-pandemic

"Will Covid-19 evolve resistance to vaccines?"
https://www.bbc.com/future/article/20210119-covid-19-variants-how-the-virus-will-mutate-in-the-future

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COVID-19

Will Covid-19 evolve resistance to vaccines?

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(Image credit: Oscar Del Pozo/Getty Images)

By Richard Gray

20th January 2021

Every time the coronavirus passes from person to person it picks up tiny changes to its genetic code, but scientists are starting to notice patterns in how the virus is mutating.

Article continues below

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For more than three months the patient struggled against Covid-19. His immune system was already in a bad way when he caught the virus – he had been receiving a drug treatment for lymphoma, a type of blood cancer, that depleted some of his immune cells. With fewer of the usual defences against infection, the virus was able to spread in his body relatively unchecked.

As doctors tried to help the elderly patient fight the virus, they gave him blood plasma collected from people who had already recovered from Covid-19. Contained within this milky-brown liquid – also known as convalescent plasma – were antibodies against the virus that might help to neutralise it.

Over the course of 101 days as they treated the man, clinicians at Addenbrookes Hospital in Cambridge, UK, took 23 swab samples as he fought against the disease. Each swab was sent off to a nearby laboratory to be analysed. But when virologists looked at the virus’s genetic material in the samples, they noticed something astonishing – Covid-19 was evolving before their eyes.

"We saw some remarkable changes in the virus over that time," says Ravinda Gupta, an infectious diseases consultant at the hospital and a clinical microbiologist at the University of Cambridge who analysed the patient’s samples. "We saw mutations that seemed to suggest the virus was showing signs of adaptation to avoid the antibodies in the convalescent plasma treatment. It was the first time we had seen something like this happening in a person in real time."

Nearly a year after the global Covid-19 pandemic started, the issue of mutations looms large. New variants capable of spreading faster are emerging and leading to inevitable questions about whether they will make the newly approved vaccines less effective. To date, there is little evidence they are, but scientists are already starting to explore how the Covid-19 virus will mutate in the future and whether they might be able to head it off. In the first of a two part series looking at Covid-19 mutations, we look at what they have learned so far.

Story continues below

The worldwide effort to test and sequence samples of Covid-19 is helping to reveal new variants as they emerge (Credit: Jeff Pachoud/Getty Images)

Among the mutations Gupta and his colleagues identified was a deletion of two amino acids – known as H69 and V70 – in the spike protein sitting on the outside of the Covid-19 virus. This protein plays a key role in the ability of the coronavirus to infect cells.

The oily capsule that surrounds most of the virus is studded with these spikes sticking outwards, making it look like a crown when viewed through an electron microscope. It is this appearance that gives the coronavirus family its name – corona is Latin for crown. The spikes are also the main way Covid-19 recognises the cells it can infect and helps the virus penetrate them.

When Gupta and his team looked closer at the spike protein deletion they had spotted, it produced worrying results. "We did some infection experiments using artificial viruses and they showed that the H69/V70 deletion mutation increases the infectivity by twofold," says Gupta. This prompted the researchers to scour the international genetic databases of Covid-19. There they found that something more alarming was taking place.

"We wanted to see what was happening worldwide and we stumbled upon this big expanding group of [H69/V70 deletion] sequences in the UK," says Gupta. "When we looked more closely, we found that there was a new variant causing a big outbreak."

Even as they made this discovery in early December last year, infectious disease experts elsewhere in England were struggling to understand rapidly rising case numbers in London and the south-east of England despite a national lockdown. They started to notice something strange in the results of Covid-19 tests being carried out on samples.

To me these seem like a glimpse into the future where we are going to be in an arms race with this virus – Michael Worobey

The main diagnostic tool for Covid-19 has been polymerase chain reaction (PCR) tests, which search for traces of the virus's genetic material in samples. Usually, it targets three parts of the virus to confirm the presence of an infection. But one of these targets was increasingly coming back negative in samples from the areas of England with rapidly rising case numbers, while the other two targets in the tests continued to work.

"We were not missing cases but it is unusual to see two of the tests working but a third not," Wendy Barclay, a virologist at Imperial College London and a member of the UK’s New and Emerging Respiratory Virus Threats Advisory Group, told the BBC’s Today programme on 22 December.

The part of the virus that this part of the PCR test targeted was a sequence on the spike protein. When the scientists delved deeper, they found that the virus in these samples had picked up a mutation – a deletion at the same H69 and V70 positions in the protein seen by Gupta – that meant the PCR test was failing to pick it up sometimes.

Alongside this genetic change, they also found 16 other mutations that had altered the viral proteins they coded for, including several on the spike protein. What they had discovered was a new lineage of the Covid-19 virus that had picked up multiple mutations over a relatively short period of time. They designated it B117 – the new British Covid-19 variant, also known as VOC 202012/01 in the messy world of coronavirus nomenclature. It has cut a swathe across the UK and had spread to 50 other countries by mid-January.

The spike proteins (red) that stud the surface of the Covid-19 virus help it to get inside cells, but are also targetted antibodies (Credit: CDC/Getty Images)

The emergence of this new variant – which is estimated to be 50-75% more transmissible than the original Covid-19 virus – along with others now being detected such as the South African and Brazilian variants, has shone a spotlight on how the coronavirus is mutating as the pandemic rumbles on. It has also raised concerns about how it might continue to change in the future as we try to fight it with vaccines.

"To me these seem like a glimpse into the future where we are going to be in an arms race with this virus, just like we are with flu," says Michael Worobey, a viral evolutionary biologist at the University of Arizona. Each year the flu vaccine has to be updated as the influenza virus mutates and adapts to escape the immunity already present in the population, says Worobey. If the coronavirus shows similar capabilities, it could mean we will have to adopt similar tactics to keep it at bay, by regularly updating vaccines.

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Many believe that drug companies should already be updating their vaccines to target mutated versions of the Covid-19 spike protein. But can the patterns of mutations scientists are seeing popping up in Covid-19 around the world offer any clues about how the virus will continue to evolve?

"It is hard to speculate, but it is interesting that all of a sudden there does seem to be a lot of mutations appearing that could be associated with immune escape or immune recognition," says Brendan Larsen, a PhD student working with Worobey in Arizona. He recently identified a new variant of Covid-19 circulating in Arizona that has the H69/V70 deletion seen in several other versions of the virus. While still only spreading at a relatively low level there and in other states of the US, it suggests that this particular mutation is recurring independently around the world, says Larsen.

This repeated occurrence of the same mutations in different variants provides some clues as to what is going on – as the virus has spread through millions of people, it may be facing similar evolutionary pressures that are causing it to change in particular ways.

In most viruses and disease-causing bacteria, the use of treatments and vaccines causes them to evolve ways of escaping them so they can continue to spread

"By themselves they are likely to have a minor impact overall," says Larson. "But together all of these different mutations might make it more difficult for the immune system to recognise the virus." This could then lead to more patients catching the disease twice and perhaps also mean the vaccines may need to be altered.

"Even a relatively small amount of immune escape could make it harder to achieve herd immunity," adds Worobey.

Researchers in Illinois have also recently identified another new variant, called 20C-US, which has a number of unique and specific mutations that may alter the virus’s ability to replicate itself once inside human cells. It also features a mutation close to a site on the Covid-19 spike protein that is thought to have been crucial in allowng the virus to jump species to humans towards the end of 2019..."

"Our findings suggest that vaccines that do not prevent infection will allow extensive endemic SARS-CoV-2 spread upon a return to pre-pandemic social and economic conditions. Vaccines that only reduce symptomatic COVID-19 or mortality will fail to mitigate serious COVID-19 mortality risks, particularly in the over-65 population, likely resulting in hundreds of thousands of US deaths on a yearly basis."
https://www.medrxiv.org/content/10.1101/2021.01.27.20240309v1
BioBull
01.02.2021 kl 22:36 6294

Accord oppdatering - like før nyheter fra BGBIO ?

https://www.pharmaceutical-journal.com/news-and-analysis/features/everything-you-need-to-know-about-the-covid-19-therapy-trials/20208126.article?firstPass=false

Everything you need to know about the COVID-19 therapy trials

The Pharmaceutical Journal26 JAN 2021By Julia Robinson
There are thousands of clinical trials investigating treatments and preventative measures for COVID-19.

Bemcentinib

Selectively inhibits AXL kinase, which blocks viral entry and enhances the antiviral type I IFN response;
Investigational treatment for COVID-19;
Reported to exhibit potent anti-viral activity in pre-clinical models against several enveloped viruses, including Ebola and Zika virus.
Ongoing trials

A Multicentre, Seamless, Phase 2 Adaptive Randomisation Platform Study to Assess the Efficacy and Safety of Multiple Candidate Agents for the Treatment of COVID 19 in Hospitalised Patients (ACCORD-2-001).


https://www.clinicaltrialsregister.eu/ctr-search/trial/2020-001736-95/GB#E



Kan noen forklare dette ?
Nederst på web siden leser vi :

«The status of studies in GB is no longer updated from 1.1.2021
For the UK, as from 1.1.2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI
EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
European Medicines Agency © 1995-Mon Feb 01 22:30:09 CET 2021 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands».
DeWired
02.02.2021 kl 00:19 6121

Antar det har noe med at GB ikke lenger er en del av EU, og at det derfor ikke kommer flere oppdateringer på sidene til clinicaltrialsregister.eu .

Det kan kanskje få konsekvenser at UK ikke lengre er med i EU, men det er litt vanskelig å lese seg opp på dette for menigmann, som meg.
Jeg håper selskapet etter hvert kan dele noen tanker om dette. Det jeg leser meg frem til er at samarbeidet innen godkjennelser av medisin og medisinsk forskning skal fortsette med samme standarder etc, men at det kanskje oppstår noe mer formaliteter og byråkrati for selskap som ønsker medisiner godkjent.

Here we show functionalized nanoparticles, termed "Nanotraps", completely inhibited SARS-CoV-2 infection by blocking the interaction between the spike protein of SARS-CoV-2 and the ACE2 of host cells.
https://www.biorxiv.org/content/10.1101/2021.02.01.428871v1

"British scientists say the next dangerous Covid variant is likely already out there. We just don't know it yet"
https://edition.cnn.com/2021/02/03/europe/tracing-uk-variant-origins-gbr-intl/index.html


A new paper released this week suggested that a vaccine developed by AstraZeneca and Oxford University not only protected clinical trial participants from developing disease, but also may significantly reduce transmission of the virus that causes the disease.

In the recent burst of data on Covid-19 vaccines, that suggestion stood out. The question of whether Covid-19 vaccines reduce transmission has been a critical and unanswered one, creating uncertainty over whether people who have been vaccinated will still be able to be infected by and transmit onward SARS-Cov-2, the virus that causes Covid, to those who have not yet been vaccinated. 

Media reports seized on a reference in the paper from Oxford researchers that a single dose of the vaccine cut positive test results by 67%, pointing to it as the first evidence that a vaccine could prevent transmission of the virus. But the paper, which has not yet been peer-reviewed, does not prove or even claim that — although it hints at the possibility.
.... mer i artikkelen...
https://www.statnews.com/2021/02/03/with-a-seductive-number-astrazeneca-study-fueled-hopes-that-eclipsed-its-data/
Redigert 04.02.2021 kl 04:06 Du må logge inn for å svare

Kommende konkurrent?

"Increasing data suggests UK variant may be deadlier, says CDC director"
https://edition.cnn.com/world/live-news/coronavirus-pandemic-vaccine-updates-02-04-21/h_3d96e0765677dcf6617fd51dbfa8efce

Det at et virus muterer slik at det blir mer dødelig er i strid med det virologer uttalte tidlig i pandemien, der de hevdet at viruset ville bli mindre farlig etter hvert som det muterte.

CONCLUSIONS: In COVID-19 patients requiring mechanical ventilation, sufficiently dosed methylprednisolone can lead to a further decreased mortality as compared to dexamethasone.
https://www.medrxiv.org/content/10.1101/2021.02.03.21251088v1

Oxford/AstraZeneca Covid jab far less effective against S African strain, study shows

https://www.ft.com/content/e9bbd4fe-e6bf-4383-bfd3-be64140a3f36

Se følgende studie:
https://pubmed.ncbi.nlm.nih.gov/29474201/

Betyr dette at kraftig hosting øker Axl? ... og at kraftig hosting hos covid pasienter dermed forverrer lungesykdommen? ... men at bemxentinib hemmer Axl - shedding.
Kanskje en (lavdose) calcium channel blocker burde prøves ut i kombinasjon med bemcentinib?
Redigert 07.02.2021 kl 00:17 Du må logge inn for å svare

Oppdatert vaksine mot Sør-Afrika varianten er først klar til høsten en gang.
Nanoq
07.02.2021 kl 21:27 4056

Syd-Afrika har nettopp meldt ut at de ikke vil bruke (har suspendert) Astra Zeneca-vaksinen p.g.a. dårlig effekt mot Covid-19 mutasjonen i S-A. (nyhet via BBC i kveld).

Twittermelding:
"⚠️SURGING #B117 WITHIN US—growing 7% per day, doubling every 9.8 days nationally, & expected to become dominant by March 23rd. It is surging fastest in Florida—doubling every 9.1 days. Scientists are extremely worried: 35-45% more transmissible.🧵#COVID19
https://t.co/T3GV8anzYz https://t.co/RFyifNq4QS"
Ser ut som det er Washington Post som er kilde. Har brukt opp mine gratisartikler der for lengst.
BioBull
08.02.2021 kl 08:11 3868

Fant denne studien som viser at Bemcentinib er blant de ledene kandidater innen medisin mot Ebola og COVID-19 :

Krever innlogging :

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7302206/

( uviss dato , men oppdatert i 2021 )
Redigert 08.02.2021 kl 10:45 Du må logge inn for å svare
Gullit
08.02.2021 kl 08:26 3895

Det hadde vert helt fantastisk. I henhold til dagens situasjon synes eg det går alt for lang tid. Må da kunne se resultater som e gode eller dårlig nok. Vi er midt i en krise!!