We met in the hallway in DC last week. Sorry it took me so long to find this site. I have one comment and one question.
Comment: As a retired physician, I think that you give doctors too much credit for understanding how the vaccine and someone's personal health problems might interact. Doctors have far less time to read articles and mostly will know less than you will about the vaccine side effects. They at this point are making decisions based on their own experiences which will be, at best, anecdotal. I have more time to read scientific literature now that I'm retired, and I have found almost nothing that would allow me to make a fully informed recommendation on which vaccine to use for any specific patient.
Question: I may have missed earlier posts covering this, but I have been wondering if my early information about the mechanism of infection is still valid. I understand that the virus spike protein binds to ACER2 receptors, after being cleaved by the enzyme(?) furin. These ACER2 receptors are, I thought, deep in the sinuses and lung mucosa. If so, that would make the initial viral invasion possible only through deeply inhaled aerosol particles. Is that true? Have other binding sites been identified?
Also, I've been wondering how the circulating antibodies produced by the vaccines can be of any help at all in preventing this initial surface invasion. Is this why the vaccine seems best at preventing severe disease (which would require some form of viremia) and not at preventing mild URIs or, sadly, transmission?
Thanks for reaching out. It was nice to meet you at Worldcon. In retrospect I am also glad that our interaction was relatively distanced and we were both wearing masks, since I later tested positive.
Regarding your comment...the power that I give physicians credit for is the legal licensure to practice medicine. I lack that, so I always have to refer people to their personal physicians. I am not a valid source of specific medical advice, and for both legal and practical reasons I have to make this clear to readers.
To your first question: ACE2 receptor is expressed ubiquitously in the respiratory system, including in lung tissue and also upper respiratory mucosa. The levels of expression differ in different cell types throughout, but clearly we have cells throughout the respiratory system that are permissive to infection, both upper respiratory and lower. At this time I know of no other receptor for SARS-CoV-2.
Re: antibodies and the initial infection, there is evidence that vaccination induces both IgG (blood-circulating antibodies) and IgA (mucosal antibodies). The IgA response from mRNA vaccines drops pretty quickly (about three weeks), but it is there, and it is probably boosted by infection. IgG is probably more relevant in preventing severe disease deep in the lung. Viremia is not common with SARS-CoV-2, but deep in the lung tissues are accessible for IgG. Yes, this is part of why I think the mRNA vaccines are better at preventing severe disease than infection. In fact this is part of why I think practically all injected vaccines for respiratory illnesses are better at preventing disease than preventing infection. T cells also probably play a role in the severe disease prevention as well.
PF4 antibodies are also implicated in HITT (heparin induced thrombocytopenia and thrombosis, a particular rare adverse reaction to heparin), so that's interesting. Also fully agreed that boosters should be incorporated into the definition of "fully vaccinated".
The big question with HITT is...what's activating the T cell partner that lets the B cells proliferate? There must be some immune insult. Is it, perhaps in some cases, infection with a circulating adenovirus? There is some interesting science to be done here, and impactful too.
Happy that you are recovering nicely from the plague. I would like to plan some travel for when the risk level fades again. My sense of omicron is that it is spreading so fast that we are seeing a huge spike that will burn itself out fairly quickly once a critical mass is infected. In the current state of the world, what models would you turn to for guessing what the covid situation will be in Country X in Month Y? https://covid19.healthdata.org/united-states-of-america seems pretty easy to use, but I wonder how good their models are.
Nice question! These mutations are in reference to a "canonical" sequence isolated in Wuhan, originally called "Wuhan seafood market pneumonia virus" but now called "hCoV-19/Wuhan/Hu-1/2019". The overall lineage this is a part of is called 19A.
Maybe over a year ago my friend’s teenage son came home from school with Covid. He infected his brother, mother and father. No one was hospitalized and they all recovered. Later they all got the first two vaccine shots. Then the mother got the third. The other day I had a social lunch planned with my friend. He called to tell me that maybe we should cancel it. One of the sons came home with Covid and infected his brother and mother. My friend the dad had not been infected yet. As I have not been vaccinated and don’t intend to be I agreed that we should cancel our lunch. The vaccines seen useless to me.
Hello John,
We met in the hallway in DC last week. Sorry it took me so long to find this site. I have one comment and one question.
Comment: As a retired physician, I think that you give doctors too much credit for understanding how the vaccine and someone's personal health problems might interact. Doctors have far less time to read articles and mostly will know less than you will about the vaccine side effects. They at this point are making decisions based on their own experiences which will be, at best, anecdotal. I have more time to read scientific literature now that I'm retired, and I have found almost nothing that would allow me to make a fully informed recommendation on which vaccine to use for any specific patient.
Question: I may have missed earlier posts covering this, but I have been wondering if my early information about the mechanism of infection is still valid. I understand that the virus spike protein binds to ACER2 receptors, after being cleaved by the enzyme(?) furin. These ACER2 receptors are, I thought, deep in the sinuses and lung mucosa. If so, that would make the initial viral invasion possible only through deeply inhaled aerosol particles. Is that true? Have other binding sites been identified?
Also, I've been wondering how the circulating antibodies produced by the vaccines can be of any help at all in preventing this initial surface invasion. Is this why the vaccine seems best at preventing severe disease (which would require some form of viremia) and not at preventing mild URIs or, sadly, transmission?
Lisa Freitag, MD
Hi Lisa!
Thanks for reaching out. It was nice to meet you at Worldcon. In retrospect I am also glad that our interaction was relatively distanced and we were both wearing masks, since I later tested positive.
Regarding your comment...the power that I give physicians credit for is the legal licensure to practice medicine. I lack that, so I always have to refer people to their personal physicians. I am not a valid source of specific medical advice, and for both legal and practical reasons I have to make this clear to readers.
To your first question: ACE2 receptor is expressed ubiquitously in the respiratory system, including in lung tissue and also upper respiratory mucosa. The levels of expression differ in different cell types throughout, but clearly we have cells throughout the respiratory system that are permissive to infection, both upper respiratory and lower. At this time I know of no other receptor for SARS-CoV-2.
Re: antibodies and the initial infection, there is evidence that vaccination induces both IgG (blood-circulating antibodies) and IgA (mucosal antibodies). The IgA response from mRNA vaccines drops pretty quickly (about three weeks), but it is there, and it is probably boosted by infection. IgG is probably more relevant in preventing severe disease deep in the lung. Viremia is not common with SARS-CoV-2, but deep in the lung tissues are accessible for IgG. Yes, this is part of why I think the mRNA vaccines are better at preventing severe disease than infection. In fact this is part of why I think practically all injected vaccines for respiratory illnesses are better at preventing disease than preventing infection. T cells also probably play a role in the severe disease prevention as well.
PF4 antibodies are also implicated in HITT (heparin induced thrombocytopenia and thrombosis, a particular rare adverse reaction to heparin), so that's interesting. Also fully agreed that boosters should be incorporated into the definition of "fully vaccinated".
The big question with HITT is...what's activating the T cell partner that lets the B cells proliferate? There must be some immune insult. Is it, perhaps in some cases, infection with a circulating adenovirus? There is some interesting science to be done here, and impactful too.
Hi John,
Happy that you are recovering nicely from the plague. I would like to plan some travel for when the risk level fades again. My sense of omicron is that it is spreading so fast that we are seeing a huge spike that will burn itself out fairly quickly once a critical mass is infected. In the current state of the world, what models would you turn to for guessing what the covid situation will be in Country X in Month Y? https://covid19.healthdata.org/united-states-of-america seems pretty easy to use, but I wonder how good their models are.
Thanks again for your great service.
Question: each variant is described in terms of a series of mutations, but what’s the reference sequence the mutations are relative to?
Nice question! These mutations are in reference to a "canonical" sequence isolated in Wuhan, originally called "Wuhan seafood market pneumonia virus" but now called "hCoV-19/Wuhan/Hu-1/2019". The overall lineage this is a part of is called 19A.
Here is the NCBI reference sequence: https://www.ncbi.nlm.nih.gov/nuccore/1798174254
And here is the same sequence on Nextstrain, an excellent resource for evolutionary virology: https://nextstrain.org/ncov/gisaid/global?s=hCoV-19/Wuhan/Hu-1/2019
Maybe over a year ago my friend’s teenage son came home from school with Covid. He infected his brother, mother and father. No one was hospitalized and they all recovered. Later they all got the first two vaccine shots. Then the mother got the third. The other day I had a social lunch planned with my friend. He called to tell me that maybe we should cancel it. One of the sons came home with Covid and infected his brother and mother. My friend the dad had not been infected yet. As I have not been vaccinated and don’t intend to be I agreed that we should cancel our lunch. The vaccines seen useless to me.
It sounds like everyone in this family is alive despite multiple exposures to and infections with COVID-19.
People who are unvaccinated die at approximately 10 times the rate as people who are vaccinated. Source: https://ourworldindata.org/grapher/united-states-rates-of-covid-19-deaths-by-vaccination-status?country=~All+ages
I would not call a product that reduces the chance of death by 90% "useless," unless I didn't particularly value my life.