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Dr. Ali Nouri Profile picture
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5 Jan, 5 tweets, 2 min read
1/📌BREAKING on #SARS_CoV_2 variants: the emerging variants in South Africa and Brazil that harbor the E484K mutation have "greatly reduced susceptibility" to neutralization by polyclonal serum antibodies derived from some individuals. This may have consequences for vaccines🧵
2/The "Receptor Binding Domain" on the Spike protein of the virus is a critical site for antibodies to bind to because those antibodies can block the virus from binding the ACE2 receptor on our cells. Mutations at that site are allowing the virus to escape antibodies.
3/Report shows neutralizing activity of convalescent sera (rich in polyclonal antibodies) was reduced >10-fold because of single mutation in RBD domain. They also found some sera samples that still neutralized, perhaps through antibodies binding other critical regions of spike.
4/This is worrying but the fact that neutralizing function was diminished, not eliminated, suggests a strong vaccine response will protect against the variant. However, failure to control the pandemic gives the virus more opportunities to evade vaccines. biorxiv.org/content/10.110…
5/Thread from the lab that conducted this research:

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More from @AliNouriPhD

Dr. Ali Nouri Profile picture
7 Jan
1/📌Concerning case of reinfection: healthy 45 year old was reinfected with the genetically distinct SARS-CoV-2 variant that harbors the E484K mutation - this is the variant that was recently reported to escape neutralizing antibodies 1/6🧵 Image
2/Second infection was more severe. Given the infections were 5 months apart its hard to know whether the immune response against the 1st infection simply waned, or, alternatively, if the variant virus managed to evade the immune response 2/6
preprints.org/manuscript/202… Image
3/Mutation is in RBD region of virus - the part that grabs human cell surface receptor, ACE2. Antibodies that bind RBD can block virus from entering our cells. But an earlier report this week showed that the E484K mutation in RBD is reducing the ability of antibodies to bind. 3/6 Image
Read 6 tweets
Dr. Ali Nouri Profile picture
30 Dec 20
1/The #oxfordvaccine just approved in the UK is a version of an adenovirus (common cold virus) that instructs our cells to make the Spike protein of coronavirus. This trains our immune system so when we encounter #SARSCoV2, we can mount a defense. Here's how the vaccine works🧵
2/#SARSCoV2 is covered w/Spike proteins that help the virus grab human cells. To make the vaccine, researchers first isolated the gene that is responsible for making the Spike protein. They 'snipped' it from the rest of the genetic material of the coronavirus.
3/They then needed a delivery vehicle to get the Spike gene into our cells. So they took an adenovirus that normally infects chimpanzees, and genetically altered it so it can no longer replicate or cause disease. They then added the Spike gene to the adenovirus vector.
Read 5 tweets
Dr. Ali Nouri Profile picture
29 Dec 20
1/📌NIH Study: COVID-19 severity could depend on route of infection: Infection through inhaling #Airborne virus could lead to more severe disease than infection from fomites (contact w/ contaminated objects.) To test it, hamsters were infected via the different routes. 1/7🧵
2/Intranasal (I.N) and aerosol inoculation caused more severe respiratory pathology, higher viral loads and increased weight loss. Fomite exposure led to milder disease. Here's weight loss👇Black lines are control animals in each group. 2/7
3/Also, compared to intranasal exposure, aerosol exposed
hamsters had higher viral load in trachea and lung "suggesting aerosol exposure more efficiently deposits viral droplet nuclei in the lower respiratory system" Preprint: 3/7
biorxiv.org/content/10.110…
Read 7 tweets
Dr. Ali Nouri Profile picture
28 Dec 20
1/📌In order to limit the importation of the variant coronavirus from the UK, CDC now requires travelers to be tested before boarding a flight. The strategy is insufficient because it's overly reliant on diagnostic tests that can't detect the virus in early stages of infection🧵
2/CDC requires a negative test up to 3 days prior to flight. One problem is you can test negative but catch the virus in intervening days. Another is that tests, even the gold standard PCR test, misses the virus in the early stages of infection & provides a false sense of safety.
3/This study, for instance, shows that on the day of the infection, the PCR test misses 100% of the cases. Each day after that the detection rate improves, but even by Day 5, when viral load tends to be high, these tests miss over a third of infections: bit.ly/2Hykuzk
Read 5 tweets
Dr. Ali Nouri Profile picture
28 Dec 20
1/📌Next US Vaccine💉:@Novavax began Phase 3 Trial. KEY difference: While Moderna/Pfizer deliver genetic material (mRNA) that our cells subsequently turn into Spike protein, #Novavax delivers the Spike protein directly. To do that, they first have to make Spike protein in a lab🧵
2/That's done by taking the Spike DNA🧬and splicing it into a larger piece of DNA that is used to deliver genes into cells that are growing in a lab. Those cells "read" the DNA, turn it into RNA, and then into proteins. The Spike proteins are then harvested and purified.
3/Next, Spike proteins are mixed with the delivery vehicle: synthetic particles, or "nanoparticles" that are about the size of the virus. Nanoparticles get studded with a bunch of Spike proteins. Those Spike proteins train and boost our immune system. rb.gy/i1lnb9
Read 6 tweets
Dr. Ali Nouri Profile picture
24 Dec 20
1/📌Evidence of #Airborne #SARSCoV2 traveling 12 floors of an apt building through the drainage system: 200+ residents in a wing of a high-rise were tested, revealing 9 infections. Those families lived in 3 vertically aligned flats connected by drainage pipes in the bathrooms🧵 Image
2/To confirm apt units are indeed connected, tracer gas was released into drainage system of one unit and shown to come out of the other. Evidence for alternative mechanisms of transmission (e.g. use of public spaces, elevators, etc..) could not be found. Image
3/Plausible scenario is infection through drainage system. While U-traps typically act as water seals in each bathroom's drainage system, if unused, they can dry out, allowing aerosols from one unit to travel to another.
Report: ncbi.nlm.nih.gov/pmc/articles/P… ImageImage
Read 4 tweets

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