"It's the Infectivity, Stooopid."
Having listened assiduously to every "This Week In Virology" (TWiV) podcast since February, the Phantom has noticed that he has become, to his surprise, to some degree more educated than even his colleagues who are specialized and board certified in Infectious Disease (ID), in this one small niche of virology.
At a Journal Club, where a very learned ID doctor spoke, the Phantom was surprised to hear this specialist embrace the idea that SARS CO-v-2 (the virus that causes COVID 19) is a blood borne virus--i.e. it has a significant viremic phase. The Phantom had heard the virologists of TWiV discuss this point on many occasions, the studies of trying to culture (with plaque assays) the virus from blood so he "knew the literature" as the ID doc did not.
The fact is, you could, too, if you had the time, because we are all learning it together now.
The thing about whether SARS COv-2 is blood borne is important because, typically, blood borne viruses elicit long term immunity if you survive them--measles being the classic example. But viruses which are not blood borne, like corona viruses, typically do not elicit long term immunity.
A small point but one which makes a larger point: Even the doctors who normally are up to date about infections are not up to date on COVID 19 because the news and concepts are changing too fast, and ID doctors are too busy to be listening to 4 hours of TWiV every week. But the Phantom can listen to every minute, because he has a smart phone and a bicycle and he goes for 2 hour bicycle rides four times a week and listens.
This does not make the Phantom an expert in virology, or immunology (although he does listen to the "Immune" podcast by the same crew.) But it does mean he has kept up with the shifting sands of what we know more than most doctors who are busier than the Phantom is right now.
So where are we now?
The latest TWiV episode (#645) begins with an update by the physician who sees lots of COVID 19 patients, Daniel Griffin.
Dr. Griffin is important for the very reason he himself has disparaged in other doctors: He has seen a lot of patients with the disease and so his experience, his anecdotes are illuminating.
Griffin managed to annoy a lot of docs by saying that he is purer than they are because he will not act based on "experience" but only on the basis of controlled, prospective, double blind studies--the gold standard of medical care or "evidence based medicine," as Griffin calls it.
But as Dr. Siddhartha Murhurjee (author of "The Emperor of Disease") observed, there are never enough of these elegant, rigorous studies to guide thinking on the ward where daily a myriad of problems arise for which there are no studies yet published. You are always learning as you go along, as Griffin did when he "proned" his patients whose blood oxygen levels fell--rumor had it that if you turned them on their abdomens or sides, lung blood flow improved, and, it worked, so Griffin recommended it, despite the lack of rigorous studies.
So we are all feeling our way along, gathering data not always systematically and what is true today may be disproved tomorrow. But from his broad and intense experience with COVID patients, Griffin has described a disease which looks very different in different people but usually begins with a short phase, just after the virus finds its way into the naso pharynx. The fate of the patient and the course of the illness, likely depends on how many virions get in--the dose--and the host's defenses, which depend on his immune system, his age, his general state of health, other diseases he may harbor which make him more vulnerable.
This "pre-symptomatic" phase, before the patient develops fatigue, headache, cough or fever, may last 3-7 days, our best guess.
And at some point during this phase--when the patient is either not feeling sick at all or just mildly off his game--the virus is stoking up its takeover of host cells and pumping out billions of replicas of itself--infectious virus. This is the "infectious stage" and even the more insensitive (saliva/ monoclonal antibody/instant ) tests will be positive and turn colors and ring bells.
The more sensitive PCR tests from nasal swabs which detect virus particles in the thousands will, of course, not miss the disease incubating at this point, but they take days to weeks to come back from the lab.
The idea that you're only infectious and a risk to others during this brief window when you're making millions to billions of virions, is one pushed by Michael Mina, MD, PhD at the Harvard School of Public Health. And it is or should be central to our response to this pandemic, because if this is true, it means we can reopen schools, factories and much more.
The test Dr. Mina prefers misses virus levels below the level of infectivity, but catches the infectious patient, who is the only patient a public health official cares about, the only person who places the public at risk: You want to test everyone daily, catch these guys and keep them isolated until they are no longer infectious.
Once they are infected, the patients may not get seriously ill, but if they do they become the problem of the hospital doctors, not the public health folks.
So there is a way to prevent the virus from spreading, to stop it in its tracks, with daily home testing with little cardboard strips available now, and only awaiting ramp up of manufacturing and distribution. (Assuming the anti science/anti-vax/anti-think crowed at 1600 PA Ave in WDC allow.)
If the patient gets really ill, that is usually not because the virus kills his cells--although it can do that--but because the virus elicits an explosion from the patient's immune system, like an ammo dump getting hit by a grenade, so called cytokine storm, usually 7-21 days after the virus has established a beach head and pushed inland. During this time, glucocorticoids (dexamethasone, prednisone) can douse this explosion and save the patient. Anti-virals, like remdesevir are of no use during this cytokine storm--the virus is long gone. It's the immune rampage that's killing the patient.
Antivirals only really help when the patient is incubating, pumping out millions of viral replicants from inside the cells it has infected.
Then there are the much feared sequelae. Weeks to months later, profound fatigue and breathlessness with exertion may linger. (The "long haulers.) But worst of all, clots in arteries in the brain or the fingers, legs or toes may cost patients their digits and limbs or parts of their brains.
Anti body tests were once promoted as identifying immune people who could be issued passports to go back to normal life, but the antibody tests may be of little value owing to certain new concepts: Antibodies (made by B cells) rise during the initial illness 3-7 days (IgM) but then, after a couple of weeks, the next phase of antibodies (IgG) may peak and then fall to low levels, making tests go negative.
That has been typical of other coronaviruses, the ones that cause the common cold. This may mean the patient is no longer protected against reinfection. Or it may simply mean the immune system realizes there is not much virus to fight and it brings its troops back into the barracks and awaits a second attack.
It may be the T cells are now programmed and they will be the cells roused from the forts and barracks to meet the next attack.
This is all what's called the "correlate of protection" by Brianne Barker, an immunologist from Drew University. It may be antibody (B cell products) testing is irrelevant to the question of who is immune. We might be better informed with T cell tests, but these are less widely available.
As for vaccines: The big worries here are:
1/ Most vaccines are assessed in two basic ways for efficacy:
--Measurement of antibody levels in response to the vaccine doses.
If we are measuring antibodies but antibodies are not actually what's protecting us, this may be misleading. (Antibody titers at best tell if the vaccine is likely to work.)
--Assessment of how many people who received the vaccine get the disease they were vaccinated against, vs how many in the control group (not vaccinated) get it.
(This tells us if the vaccine actually does work.)
2/ Coronaviruses have been notoriously unfazed by vaccines or prior explosure to the native virus--people get re infected with the same coronaviruses over and over in the case of the common cold and even when some immunity is attained through vaccine or infection, it wanes rapidly.
3/ Most vaccines under development have been made against the spike protein on the virus, which is the hook which attaches to the normal cells--but if that does not work, then all the scores of vaccine candidates under trial will fail for the same reason. Vincent Raccaniello, of Columbia, has complained that we have put all our eggs in one basket with the spike protein as our target. We ought to be making vaccines which target other parts of the virus as well.
In order to know whether the vaccine protects, you have 2 options:
1/ challenge the patient with the virus or
2/ vaccinate a large number (30,000) of people and let them go out into the COVID infected world and see how many of them get the disease and how many are protected compared to those who did not get the vaccine.
The problem with the "challenge" is you are giving patients disease which might kill them and there is no such thing as truly informed consent here.
The problem with the double blind prospective controlled study is that it can take months to years to get the data.
So that's where the Phantom thinks we are now with COVID 19.
Here's a link to TWiV #645
https://www.microbe.tv/twiv/twiv-645/
Next month, some of what has just been said will be proved wrong and there may be new concepts.
Having listened assiduously to every "This Week In Virology" (TWiV) podcast since February, the Phantom has noticed that he has become, to his surprise, to some degree more educated than even his colleagues who are specialized and board certified in Infectious Disease (ID), in this one small niche of virology.
At a Journal Club, where a very learned ID doctor spoke, the Phantom was surprised to hear this specialist embrace the idea that SARS CO-v-2 (the virus that causes COVID 19) is a blood borne virus--i.e. it has a significant viremic phase. The Phantom had heard the virologists of TWiV discuss this point on many occasions, the studies of trying to culture (with plaque assays) the virus from blood so he "knew the literature" as the ID doc did not.
The fact is, you could, too, if you had the time, because we are all learning it together now.
The thing about whether SARS COv-2 is blood borne is important because, typically, blood borne viruses elicit long term immunity if you survive them--measles being the classic example. But viruses which are not blood borne, like corona viruses, typically do not elicit long term immunity.
A small point but one which makes a larger point: Even the doctors who normally are up to date about infections are not up to date on COVID 19 because the news and concepts are changing too fast, and ID doctors are too busy to be listening to 4 hours of TWiV every week. But the Phantom can listen to every minute, because he has a smart phone and a bicycle and he goes for 2 hour bicycle rides four times a week and listens.
This does not make the Phantom an expert in virology, or immunology (although he does listen to the "Immune" podcast by the same crew.) But it does mean he has kept up with the shifting sands of what we know more than most doctors who are busier than the Phantom is right now.
So where are we now?
The latest TWiV episode (#645) begins with an update by the physician who sees lots of COVID 19 patients, Daniel Griffin.
Dr. Griffin is important for the very reason he himself has disparaged in other doctors: He has seen a lot of patients with the disease and so his experience, his anecdotes are illuminating.
Griffin managed to annoy a lot of docs by saying that he is purer than they are because he will not act based on "experience" but only on the basis of controlled, prospective, double blind studies--the gold standard of medical care or "evidence based medicine," as Griffin calls it.
But as Dr. Siddhartha Murhurjee (author of "The Emperor of Disease") observed, there are never enough of these elegant, rigorous studies to guide thinking on the ward where daily a myriad of problems arise for which there are no studies yet published. You are always learning as you go along, as Griffin did when he "proned" his patients whose blood oxygen levels fell--rumor had it that if you turned them on their abdomens or sides, lung blood flow improved, and, it worked, so Griffin recommended it, despite the lack of rigorous studies.
So we are all feeling our way along, gathering data not always systematically and what is true today may be disproved tomorrow. But from his broad and intense experience with COVID patients, Griffin has described a disease which looks very different in different people but usually begins with a short phase, just after the virus finds its way into the naso pharynx. The fate of the patient and the course of the illness, likely depends on how many virions get in--the dose--and the host's defenses, which depend on his immune system, his age, his general state of health, other diseases he may harbor which make him more vulnerable.
This "pre-symptomatic" phase, before the patient develops fatigue, headache, cough or fever, may last 3-7 days, our best guess.
And at some point during this phase--when the patient is either not feeling sick at all or just mildly off his game--the virus is stoking up its takeover of host cells and pumping out billions of replicas of itself--infectious virus. This is the "infectious stage" and even the more insensitive (saliva/ monoclonal antibody/instant ) tests will be positive and turn colors and ring bells.
The more sensitive PCR tests from nasal swabs which detect virus particles in the thousands will, of course, not miss the disease incubating at this point, but they take days to weeks to come back from the lab.
The idea that you're only infectious and a risk to others during this brief window when you're making millions to billions of virions, is one pushed by Michael Mina, MD, PhD at the Harvard School of Public Health. And it is or should be central to our response to this pandemic, because if this is true, it means we can reopen schools, factories and much more.
The test Dr. Mina prefers misses virus levels below the level of infectivity, but catches the infectious patient, who is the only patient a public health official cares about, the only person who places the public at risk: You want to test everyone daily, catch these guys and keep them isolated until they are no longer infectious.
Once they are infected, the patients may not get seriously ill, but if they do they become the problem of the hospital doctors, not the public health folks.
So there is a way to prevent the virus from spreading, to stop it in its tracks, with daily home testing with little cardboard strips available now, and only awaiting ramp up of manufacturing and distribution. (Assuming the anti science/anti-vax/anti-think crowed at 1600 PA Ave in WDC allow.)
If the patient gets really ill, that is usually not because the virus kills his cells--although it can do that--but because the virus elicits an explosion from the patient's immune system, like an ammo dump getting hit by a grenade, so called cytokine storm, usually 7-21 days after the virus has established a beach head and pushed inland. During this time, glucocorticoids (dexamethasone, prednisone) can douse this explosion and save the patient. Anti-virals, like remdesevir are of no use during this cytokine storm--the virus is long gone. It's the immune rampage that's killing the patient.
Antivirals only really help when the patient is incubating, pumping out millions of viral replicants from inside the cells it has infected.
Then there are the much feared sequelae. Weeks to months later, profound fatigue and breathlessness with exertion may linger. (The "long haulers.) But worst of all, clots in arteries in the brain or the fingers, legs or toes may cost patients their digits and limbs or parts of their brains.
Anti body tests were once promoted as identifying immune people who could be issued passports to go back to normal life, but the antibody tests may be of little value owing to certain new concepts: Antibodies (made by B cells) rise during the initial illness 3-7 days (IgM) but then, after a couple of weeks, the next phase of antibodies (IgG) may peak and then fall to low levels, making tests go negative.
That has been typical of other coronaviruses, the ones that cause the common cold. This may mean the patient is no longer protected against reinfection. Or it may simply mean the immune system realizes there is not much virus to fight and it brings its troops back into the barracks and awaits a second attack.
It may be the T cells are now programmed and they will be the cells roused from the forts and barracks to meet the next attack.
This is all what's called the "correlate of protection" by Brianne Barker, an immunologist from Drew University. It may be antibody (B cell products) testing is irrelevant to the question of who is immune. We might be better informed with T cell tests, but these are less widely available.
As for vaccines: The big worries here are:
1/ Most vaccines are assessed in two basic ways for efficacy:
--Measurement of antibody levels in response to the vaccine doses.
If we are measuring antibodies but antibodies are not actually what's protecting us, this may be misleading. (Antibody titers at best tell if the vaccine is likely to work.)
--Assessment of how many people who received the vaccine get the disease they were vaccinated against, vs how many in the control group (not vaccinated) get it.
(This tells us if the vaccine actually does work.)
2/ Coronaviruses have been notoriously unfazed by vaccines or prior explosure to the native virus--people get re infected with the same coronaviruses over and over in the case of the common cold and even when some immunity is attained through vaccine or infection, it wanes rapidly.
3/ Most vaccines under development have been made against the spike protein on the virus, which is the hook which attaches to the normal cells--but if that does not work, then all the scores of vaccine candidates under trial will fail for the same reason. Vincent Raccaniello, of Columbia, has complained that we have put all our eggs in one basket with the spike protein as our target. We ought to be making vaccines which target other parts of the virus as well.
In order to know whether the vaccine protects, you have 2 options:
1/ challenge the patient with the virus or
2/ vaccinate a large number (30,000) of people and let them go out into the COVID infected world and see how many of them get the disease and how many are protected compared to those who did not get the vaccine.
The problem with the "challenge" is you are giving patients disease which might kill them and there is no such thing as truly informed consent here.
The problem with the double blind prospective controlled study is that it can take months to years to get the data.
 |
| Obadiah Youngblood, Little Boar's Head, North Hampton |
So that's where the Phantom thinks we are now with COVID 19.
Here's a link to TWiV #645
https://www.microbe.tv/twiv/twiv-645/
Next month, some of what has just been said will be proved wrong and there may be new concepts.
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