Hi All from a fellow Durhamite!
Autoimmune disorders are often discussed as a risk factor, but what about over reactive immune systems? I have a mast cell activation disorder, which leads to mast cells overreacting and causing allergic type reactions frequently. Normally, the silver lining is I rarely get sick, and when I do it’s often a shorter course and milder illness. There are questions around whether or not we would be considered high risk because the most damaging repercussions of SARS COV 2 seem to be from inflammation caused by the immune system. What role do you see mast cells playing in the current pandemic and how would you expect those with mast cells that do not function properly to react?
Thank you for the wealth of information you’ve been providing during this time. On an era where Plandemic is circulating wildly, it is much appreciated!
My name is Olivia, and I just accepted a spot in the M&I PhD program at CUMC for the fall of 2020. Hopefully we will actually be able to start in the fall, and I will get to see the famous Wall of Polio!
Here is my question regarding SARS-CoV2 and immunology:
Recently, there was a Cell Pre-proof (http://doi.org/ds9j) that came out demonstrating IFN signaling induces expression of ACE2 in upper airway of humans infected with influenza virus. Do you think IFN expression in SARS-CoV2 infection could be creating a vicious positive feedback loop of infection in the upper airway, contributing to the severity of disease? Is this seen in other infections?
I’ve been listening to both TWiV and Immune for some time now and love what you guys do!
Dear Immune Team,
Thank you for your podcasts – I follow all of the microbe.tv podcasts. I live in the Bangkok area and continue to be puzzled why the number of cases as well as the per-million population mortality rate are so low. Thailand reported the first case outside of China, the hospital and medical surveillance system here is extensive and advanced. Everyone started wearing masks in March and the government took strong steps to contain the spread, but during December-January there were millions of Chinese tourists, including a reported forty thousand visitors from Wuhan.
I read the Chumakov/Voroshilova paper and it occurred to me that perhaps the widespread lifetime exposure to enteroviruses has conferred some measure of resistance to serious outcomes of Covid-19? Hot and humid weather may play a role as well, especially in reducing fomites and droplet viability. But do you see hot weather possibly increasing immunity among the majority of people who are routinely outside?
Dear Vincent, Stephanie and Cynthia,
Thank you for your highly informative and educative series of podcasts – these have been a revelation to me in helping to make sense of what’s going on with this pandemic. I don’t have a background in microbiology or immunology but I have been trying to get up to speed on certain things using textbooks and online resources – Vincent’s lectures on virology have also been a great guide.
I had a question regarding you mentioning a neutralizing antibody immunoassay as being the “holy grail” on one of your podcasts. I wonder why is that so hard to achieve? And with respect to SARS-CoV-2, do you think what these researchers from UNC-Chapel Hill, UCSD and Emory point to (ie using the RBD as an antigen) can be used as the basis of such an assay?:
Thank you and please keep up the good work!
Hello Immune Team!
My questions concern vaccine development for Sars-CoV-2. I’m looking at the “DRAFT landscape of COVID-19 candidate vaccines” published by the WHO (May 11). It’s reassuring to see that many vaccine candidates are being developed and will be tested, but it seems as though the vast majority involve using the spike protein as immunogen. This looks great on paper, but…given the high failure rate of experiments in general, and the even higher possibility of failure of clinical trials, do you think that current vaccine efforts are putting too many eggs in the spike protein basket? In my Utopian world of cooperative science, academic researchers and pharmaceutical companies and government agencies would work together to cast a wide net (in terms of potential immunogens). What do you all think about this? Other than the live-attenuated vaccine and inactivated vaccine candidates listed in the WHO table, are you aware of other possible polyvalent vaccine candidates that can or should be explored?
Thanks for sharing your thoughts. Maybe you would consider doing an episode or two on vaccinology: theory and practice? Listeners like me would enjoy learning more about this fascinating field, especially in the context of SARS.
I really love your podcast: very informative, great explanations, and a refreshing ability to say “I don’t know”. I started listening just before the pandemic started, and I appreciate how well you shifted gears so quickly to focus on topics relevant to Sars-CoV-2. I’m looking forward to the day when you can return to other topics.
I am also a longtime listener to TWiM and TWiV and now TWiN and TWiEvo. Because of this pandemic and because of Vincent’s energetic efforts, there is an excellent synergy among these shows. Thank you!
I have also enjoyed hearing listeners comment on Vincent’s occasional ‘grumpiness’. To my ears, in his different podcasts he exhibits quite a range on the Grump-O-Meter and it correlates roughly with his level of expertise: nonexistent when he is the interested novice (TWiN), very low when there is another designated curmudgeon (TWiM), slightly higher when he knows a bit more and there is no other curmudgeon in sight (Immune), and highest when he knows quite a lot even in the presence of other curmudgeons (TWiV), but only when provoked.
Thanks for a great series of podcasts,
Rick from Maryland (10 miles from NIH Bethesda campus)
SARS-CoV-2 ORF3b is a potent IFN antagonist
I’m sure you’ve seen this preprint detailing a case study of placental infection in SARS-CoV-2. The fact that exclusively the syncytiotrophoblast of the placenta jumped out to me, given that SARS-CoV-2 also forms syncytial layers and that the proteins driving the formation of the syncytiotrophoblast are derived from viral proteins.
IFITM seems like a plausible candidate here. I went digging for papers and found that both “replication of infectious SARS-CoV and entry mediated by the SARS-CoV spike protein are restricted by IFITM proteins” and “IFITM proteins inhibit placental syncytiotrophoblast formation and promote fetal demise.” The story here would be that other placental tissues would appropriately upregulate IFITM to prevent viral entry in response to immunological signaling, but the synctiotrophoblast has some mechanism downregulating IFITM, preventing it from fighting off the infection.
Interested to hear what you think,