I wanted to make some quick points about Coronavirus, mainly from a medical perspective. Firstly, nature is a great leveller. Self enforced or socially enforced isolation means less flights, less travelling on roads, less consumption and reduced human activity. That leaves its mark on the planet...for the better. There is far less NO2 over Italy being picked up from space. The virus has achieved what years of climate conferences could not. If you push the dice too far, at some point, nature will find a way of redressing the balance.
Worries about economic growth, recessions etc are not misplaced. However, ever increasing growth at the cost of killing the planet is self defeating. As is often said, shrouds don't have pockets. We survived 5 or 10 years ago when we were poorer, and had a lower GDP, didn't we?
Second, a lot of hope is being laid at the door of vaccines. A vaccine won't be ready in time to stem the epidemic. Even if it is lab ready, it takes a long time to be ready for the bench. Abbreviating Phase I trials to speed a vaccine through Phases II & III will not have good consequences, as Gerald Ford found out in 1976 when he fast-tracked a vaccine to the general population after a swine flu scare. People died or fell ill with the jab while the swine-flu outbreak never materialised. Ford lost the election.
Finally, there's been quite a bit of talk about strengthening one's immune system to "prepare" for the virus. This is attractive in theory but may not have legs to stand on. Pharmacologically, there are far more ways of suppressing the immune system than stimulating it. And the latter, when implemented, is targeted towards various cancers rather than infections, for eg IL-2 many years ago for renal cancer, CTLA-4 antibodies such as ipilimumab for melanoma, PD-1 and PD-L1 checkpoint inhibitors for NSCC of lung, etc, and CAR-T for acute B-cell lymphoblastic leukaemias.
Furthermore, the premise that a strong immunity saves you from a virus itself needs to be examined carefully. While COVID-19 is more likely to kill the elderly and infirm, it has spared children, whose immune system is not fully developed before 2 years of age (that's why you use conjugate vaccine in very young children- they can't form antibodies to capsular polysaccharides, unless you tag on a protein). Furthermore, among the deceased were some young people without pre-existing illnesses- like the doctor in Wuhan who raised the alarm. These young men & women died of an hyperactive immune response, manifested as the cytokine storm, typically occurring during the second week of illness, with death occurring around 18 days after falling ill. This is the same sort of response that kills AIDS patients carrying an opportunistic infection after being started on HAART-called IRIS. It's the immune system doing the killing here, not the virus. There are case reports of COVID-19 patients being treated with JAK inhibitors, for example, to turn down the cytokine storm. For relatively young people therefore, it is by no means straightforward.
To find an explanation for this, looking at the way the immune system deals with the virus might be instructive. Acute viral infections are dealt with principally by CD8 positive cytotoxic T cells and Natural Killer cells, which directly lyse virus infected cells with perforin and granzymes, and through Type I and Type III interferons, which are released in large quantities by plasmacytoid dendritic cells. While the interferon pathway is meant to overcome viruses, it can be a double edged sword.
To illustrate, single stranded RNA from viruses stimulates Toll-like receptor 7, which then leads to switching on of an adaptor protein called MyD88. MyD88 can lead to two completely different pathways. One pathway leads through kinases caled IRAK1 & IRAK4 to turn on Interferon regulatory factors-5&7 in the nucleus, leading to production of alpha & beta interferons, which in turn stimulate several interferon inducible genes to fight the virus. The other pathway though leads through IRAK4 & IRAK2 to turn on NF kappa B, and thus produces cytokines like TNF alpha and IL-6 which lead to a lot of damage- ie necrosis of innocent bystander tissues through the cytokine storm.
My suspicion is that, in a subset of patients, COVID-19 is preferentially activating this second pathway.
Worries about economic growth, recessions etc are not misplaced. However, ever increasing growth at the cost of killing the planet is self defeating. As is often said, shrouds don't have pockets. We survived 5 or 10 years ago when we were poorer, and had a lower GDP, didn't we?
Second, a lot of hope is being laid at the door of vaccines. A vaccine won't be ready in time to stem the epidemic. Even if it is lab ready, it takes a long time to be ready for the bench. Abbreviating Phase I trials to speed a vaccine through Phases II & III will not have good consequences, as Gerald Ford found out in 1976 when he fast-tracked a vaccine to the general population after a swine flu scare. People died or fell ill with the jab while the swine-flu outbreak never materialised. Ford lost the election.
Finally, there's been quite a bit of talk about strengthening one's immune system to "prepare" for the virus. This is attractive in theory but may not have legs to stand on. Pharmacologically, there are far more ways of suppressing the immune system than stimulating it. And the latter, when implemented, is targeted towards various cancers rather than infections, for eg IL-2 many years ago for renal cancer, CTLA-4 antibodies such as ipilimumab for melanoma, PD-1 and PD-L1 checkpoint inhibitors for NSCC of lung, etc, and CAR-T for acute B-cell lymphoblastic leukaemias.
Furthermore, the premise that a strong immunity saves you from a virus itself needs to be examined carefully. While COVID-19 is more likely to kill the elderly and infirm, it has spared children, whose immune system is not fully developed before 2 years of age (that's why you use conjugate vaccine in very young children- they can't form antibodies to capsular polysaccharides, unless you tag on a protein). Furthermore, among the deceased were some young people without pre-existing illnesses- like the doctor in Wuhan who raised the alarm. These young men & women died of an hyperactive immune response, manifested as the cytokine storm, typically occurring during the second week of illness, with death occurring around 18 days after falling ill. This is the same sort of response that kills AIDS patients carrying an opportunistic infection after being started on HAART-called IRIS. It's the immune system doing the killing here, not the virus. There are case reports of COVID-19 patients being treated with JAK inhibitors, for example, to turn down the cytokine storm. For relatively young people therefore, it is by no means straightforward.
To find an explanation for this, looking at the way the immune system deals with the virus might be instructive. Acute viral infections are dealt with principally by CD8 positive cytotoxic T cells and Natural Killer cells, which directly lyse virus infected cells with perforin and granzymes, and through Type I and Type III interferons, which are released in large quantities by plasmacytoid dendritic cells. While the interferon pathway is meant to overcome viruses, it can be a double edged sword.
To illustrate, single stranded RNA from viruses stimulates Toll-like receptor 7, which then leads to switching on of an adaptor protein called MyD88. MyD88 can lead to two completely different pathways. One pathway leads through kinases caled IRAK1 & IRAK4 to turn on Interferon regulatory factors-5&7 in the nucleus, leading to production of alpha & beta interferons, which in turn stimulate several interferon inducible genes to fight the virus. The other pathway though leads through IRAK4 & IRAK2 to turn on NF kappa B, and thus produces cytokines like TNF alpha and IL-6 which lead to a lot of damage- ie necrosis of innocent bystander tissues through the cytokine storm.
My suspicion is that, in a subset of patients, COVID-19 is preferentially activating this second pathway.
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