I think the current view is that the COVID19 disease is a disease of two stages.
Stage I. Viral removal by the innate immune system notably the monocyte/macrophage and also perhaps CD8 T cells abit later.
These cells are working to get rid of the virus, whilst the virus is trying to evade this immune attack. The balance of this determines what may happen next. It seems that for most people the balance falls in favour of the monocyte and it kicks some viral-butt, before it causes too much havock. Many people perhaps about 50% of people do not notice they have been infected.
For example, a couple of days ago, I woke up and my breathing was a bit heavier than usual, my nose was blocked and I blew my nose and this is what I saw….
…..a bit of bloody, nose-juice….ShI I thought “is this COVID19?”. I then got a runny nose and then a few hours later it was gone..I suspect ..and hope it was just a common cold that was dealt with. If we weren’t all bricking it , I wouldn’t have thought anything of it…as we are in the time of the sniffle and snuffle. However, living with someone who may have COVID-19 also focuses the mind.
About 80% of people do notice something, So OK and again I would bet the balance is in favour of the macrophage kicking some viral butt. The NHS and your GP say stay at home, isolate, and wait and see what happens, as most people recover. I would be much happier, if I was getting an anti-viral agent, because if the macrophage looses the battle, maybe a lot of your lung cells are going to get infected.
It is better to stop the infection developing, than firefighting once it has become established.
What happens in SARS (SARS-COV-1 infection)
Some of you know this approach. Do nothing? take a CRAB? or “watch and wait” for the lazy neurologist…However, by the time the SH1-hits the fan and you think better start using alemtuzumab, HSCT etc. it is too late and the damage is done. So whilst you may get some benefit the major benefit-value has been lost.
This is what I suspect happens in the 20% who are destined to do badly. Some anti-virals and it gives those macrophages a better chance and avoids you needing the NHS. Why no anti-virals…there are non-proven to work. So we have to wait for trials to complete. Therefore, the general public will get a taste of what its like to have to wait for useful drugs. However maybe some of you are lucky here.
I have two friends (and maybe our patient zero) and both probably have been infected with SARS-CoV-2…one had the runs, abdominal pains and a bad head and as they are getting better a cough. The other has had fever, cough, shortness of breath and has been in hosptial three times in a week due to difficulty in breathing…What’s the difference?…Not genetic. They are identical twins…but one is immunosuppressed…not with a DMT….but with a baby, pressing on the lungs is probably not helping things. Fingers crossed. So I can appreciate the worry some of you have. But my friend did not get any anti-virals, You may be luckier and not that immunosuppressed. Pregnancy drops the relapse rate by about 50%
The virus blocks the action of interferons that are produced by the tissues to stop viral replication. So you may be in luck, if terflunomide is anti-viral (no evidence I think but hypothetical) or perhaps if you are getting beta interferon, this could take the job of alpha interferon, as long as the virus does not block the signalling of the interferon receptor. This would stop viral load, allowing the macrophages to kick some viral-butt. There is some evidence that beta interferon blocks coronavirus (SARS) replication.
Stage II. The Shitstorm. Viral removal by killing the infected cells
- The virus gets inside cells, hijack the cells machinery to produce more virus and the cell bursts and dies and so the lining of your lungs are being removed and probably underpins the cough.
- CD8 T cells see virally infected lung cells and kill them damaging the lining of your lungs and creates pneumonia
- Antibodies bind to infected lung cells and get destroyed by direct attack or by attack by immune cells, leading to difficulties in breathing.
If this occurs too quickly you probably can’t repair the damage to the lungs quick enough as pneumonia sets in and bacteria get in the lungs and make your life harder.
At this point having an over-active immune system is perhaps not the best news and this is maybe where you say thank heavens for some immunosuppression as it may take some of the destructive edge off the damaging immune response that kills the virus but damages the lungs whilst doing so. Although this is an idea and unproven. Apparently there are plans to test an MS drug to seee what happens in severe disease
So what makes me think a strong immune response is damaging.
If you look at people who make the highest level of anti-SARS-CoV-2 response they get or have much more severe disease
Antibody responses to SARS-CoV-2 in patients of novel coronavirus disease 2019. Zhao J, Yuan Q, Wang H, Liu W, Liao X, Su Y, Wang X, Yuan J, Li T, Li J, Qian S, Hong C, Wang F, Liu Y, Wang Z, He Q, Li Z, He B, Zhang T, Fu Y, Ge S, Liu L, Zhang J, Xia N, Zhang Z.Clin Infect Dis. 2020 Mar 28. pii: ciaa344
Here lies the worry and it is already happened. People will think that anti-bodies for people who have recovered from COVID-19, will neutralize the infectivity of the COVID virus…which it probably will, but utilmately it could make infected people worse because it could kill off virally-infected cells. Look above the people with the highest level of anti-COVID antibodies got more severe disease.
We are racing to make a vaccine, which will gear to make antibody, they may rush to give it to someone already infected…which probably won’t work very well as vaccines work best for people who have not, but it could make them worse. We have to learn from past mistakes because this happened with vaccines against Respiratory Syncytial virus, which is another lower lung virus like SARS-CoV-2
Kim WH et al Respiratory syncytial virus dease in infants despite, prior administration of antigenic inactivated vacccine. Am J Epidemio 1969; 69:422. The said “It seems clear that ……who received this vaccine were not protected against natural infection and also, when they became naturally infected their illness was more severe” and concluded ” These findings together suggest that RS virus illness in infants is an immunologic phenomenon wherein the virus and serum antibody interact to produce severe illness” “Vaccine-induced RS virus serum antibody alone does not protect against illness
A monoclonal antibody (Motavizumab) was also made agains the RS virus and development of this was terminated die to some adverse event. Today we hear that they have made antibodies that block binding of SARS-COV-2.
Blood from people recovered from COVID19 have apparently injected into sick people, but it only take a few adverse events to stop development