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
4/They found that the neutralizing activity of convalescent sera (rich in polyclonal antibodies) was reduced >10-fold against this variant. But they also found some sera samples that still neutralized it, perhaps because antibodies could still bind to other critical regions. 4/6 Image
5/The fact that neutralizing function was diminished, not eliminated, suggested a strong vaccine response will still protect against the 484 variant. This reinfection case with that variant is discouraging, but it's still just one case and not enough to draw conclusions from. 5/6
6/However, our failure to control the pandemic gives the virus more opportunities to accrue more mutations and potentially evade vaccines. H/T @adamhamdy 6/6 biorxiv.org/content/10.110…
7/The images and data above that relate to the research that uncovered the diminished ability of polyclonal antibodies to neutralize E484K variant made possible by the hard work of @jbloom_lab, @AllieGreaney and @tylernstarr.

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More from @AliNouriPhD

16 Jan
📌1/Infectious #SARSCoV2 in the air of a car 2 hrs after unmasked driver w/mild #COVID exited vehicle. Researchers found the virus in tiny air samples (0.25-0.5 um) and showed the virus retained ability to infect cells in a lab. H/T @UniversalMaski2 1/8🧵
rb.gy/odlbap
2/In July study found the virus to be stable in air. Mechanically generated aerosols/airborne #SARSCoV2 retained ability to infect cells for at least 16 hrs. Hardier in aerosols than SARS-1 or MERS. Helps explain why #airborne route is a major culprit: rb.gy/jxh0oh 2/8
3/#Airborne transmission has been observed in a restaurant from 20 ft away. How do they know? Video footage showed patient had no direct contact w/those who were infected far away. The restaurant lacked windows & ventilation system: rb.gy/5lh973 3/8
Read 8 tweets
5 Jan
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.
Read 5 tweets
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
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
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
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

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