The biology of coronavirus COVID-19 - including research and treatments

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'Major' breakthrough in Covid-19 drug makes UK professors millionaires
https://www.theguardian.com/world/2020/jul/24/major-breakthrough-in-covid-19-drug-makes-uk-professors-millionaires?
Three professors at the University of Southampton school of medicine have this week made a “major breakthrough” in the treatment of coronavirus patients and become paper millionaires at the same time.

Almost two decades ago professors Ratko Djukanovic, Stephen Holgate and Donna Davies discovered that people with asthma and chronic lung disease lacked a protein called interferon beta, which helps fight off the common cold. They worked out that patients’ defences against viral infection could be boosted if the missing protein were replaced.
[...]
“It is part of the coronavirus’s strategy to interfere with the immune system and suppress interferon beta, so if we can put it back in, we can have dramatic effect.”

Results of the initial trial, published this week, showed that coronavirus patients in hospital given a special formulation of the professors’ interferon beta drug, called SNG001, delivered directly to their airways via a nebuliser, were two to three times more likely to recover than those given a placebo.
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hinterland said:
I don't quite understand this paper. Of 50,000 suspected covid cases/ hospital staff they screened from March to July 2020, approx 40% had Sars-Cov-2 antibodies detected using their ELISA test (Mount Sinai).

Yet, by their conclusions the authors seems to be ignoring the 60% who had no antibodies detected.
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I disagree that they're ignoring them. A 40% test positivity rate is still very high, given people presenting with mild non-specific respiratory infection symptoms. An examination of the sensitivity/specificity of their test is not the basis of this current study (was covered in previous studies).

Yes they didn't test the entire 50,000 with PCR tests, but of those that were tested:

An earlier analysis performed with a smaller subset of 568 PCR-confirmed individuals using the same ELISA showed that >99% of them developed an anti-spike antibody response (9). In a later dataset of 2,347 patients who self-reported positive PCR, 95% of them had positive antibody titers, indicating we are not missing large numbers of patients and confirming our prior sensitivity findings.
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The data provided in Supplemental Table 1 is a bit weak due to sample size, but more so for specificity than sensitivity. Hence an assumption that the test is at least 90% sensitive is justified.
 
The people with hidden immunity against Covid-19

This arrived in my inbox on 24th July, so not sure if it's been posted already. I regret to say I haven't had time to read it completely yet (life is chaotic since we arrived at the caravan) but it looks to me like a fairly clear sum up of what we know about Covid-19 concerning antibodies and the immune system. Hopefully this post will remind me to go back and read it fully!
 
Nature: Longitudinal analyses reveal immunological misfiring in severe COVID-19 - by Carolina Lucas et al

Abstract

Recent studies have provided insights into the pathogenesis of coronavirus disease 2019 (COVID-19)1–4. Yet, longitudinal immunological correlates of disease outcome remain unclear. Here, we serially analysed immune responses in 113 COVID-19 patients with moderate (non-ICU) and severe (ICU) disease.

Immune profiling revealed an overall increase in innate cell lineages with a concomitant reduction in T cell number. We identify an association between early, elevated cytokines and worse disease outcomes. Following an early increase in cytokines, COVID-19 patients with moderate disease displayed a progressive reduction in type-1 (antiviral) and type-3 (antifungal) responses. In contrast, patients with severe disease maintained these elevated responses throughout the course of disease. Moreover, severe disease was accompanied by an increase in multiple type 2 (anti-helminths) effectors including, IL-5, IL-13, IgE and eosinophils.

Unsupervised clustering analysis identified 4 immune signatures, representing (A) growth factors, (B) type-2/3 cytokines, (C) mixed type-1/2/3 cytokines, and (D) chemokines that correlated with three distinct disease trajectories of patients.

The immune profile of patients who recovered with moderate disease was enriched in tissue reparative growth factor signature (A), while the profile for those with worsened disease trajectory had elevated levels of all four signatures. Thus, we identified development of a maladapted immune response profile associated with severe COVID-19 outcome and early immune signatures that correlate with divergent disease trajectories.
 
Your Coronavirus Antibodies Are Disappearing. Should You Care? New York Times, 26 July 2020.

Declining antibody levels do not mean less immunity, experts say. Besides, two widely used tests may detect the wrong antibodies.

But the volume of coronavirus antibodies drops sharply once the acute illness ends. Now it is increasingly clear that these tests may also produce false-negative results, missing antibodies to the coronavirus that are present at low levels.

Moreover, some tests — including those made by Abbott and Roche and offered by Quest Diagnostics and LabCorp — are designed to detect a subtype of antibodies that doesn’t confer immunity and may wane even faster than the kind that can destroy the virus.
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The most powerful antibodies recognize a piece of the coronavirus’s spike protein, the receptor binding domain, or R.B.D. That is the part of the virus that docks onto human cells. Antibodies that recognize the R.B.D. can neutralize the virus and prevent infection.

But the Roche and Abbott tests that are now widely available — and several others authorized by the Food and Drug Administration — instead look for antibodies to a protein called the nucleocapsid, or N, that is bound up with the virus’s genetic material.
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Officials at the Food and Drug Administration did not respond to requests for comment on whether the two tests target the appropriate antibodies.
There’s another wrinkle to the story. Some reports now suggest that antibodies to the viral nucleocapsid may decline faster than those to R.B.D. or to the entire spike — the really effective ones.
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An interesting account from a pulmonologist who survived covid:

https://www.salon.com/2020/04/05/what-it-feels-like-to-survive-covid-19s-dreaded-cytokine-storm/

What it feels like to survive COVID-19’s dreaded “cytokine storm”
A doctor and coronavirus patient in recovery describes his experience surviving COVID-19's worst side effect


Keith A. Spencer
April 5, 2020 11:30PM (UTC)
Of all the possible compounding effects of COVID-19, the disease caused by the novel coronavirus, the cytokine storm is one of the most feared. An immune system overreaction in which the body is flooded with the eponymous signaling molecules, those who suffer a cytokine storm are at risk of dying at the hand of their own immune system, as an indirect effect of the virus they are fighting.
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The UK Sepsis Trust:
Why do I still feel breathless even though my oxygen levels are normal? (Youtube video)

Code: 
https://www.youtube.com/watch?v=lZ0cC7IZBr0&feature=youtu.be

Youtube transcript:

[...]
on symptoms a question that's often
asked is why my blood oxygen levels
normal my saturations are normal but i'm
still feeling breathless and in fact in
hospitals we see
the opposite we see people who are
remarkably not breathless despite
very low blood oxygen levels and this
condition is really
weird there seems to be a disconnect
between the oxygen levels in the blood
and how breathless somebody feels
there's lots of reasons for this the
lungs basic function is to get
oxygen into the blood from the air and
get rid of carbon dioxide
and it can do that relatively
straightforwardly there's just a single
cell that the oxygen has to cross to get
into the bloodstream
now that can be happening well but the
lungs can still be stiff
and that will make us feel breathless
they might be stiff because they're full
of fluid from the illness they might
have
protein and inflammation products stuck
inside them from the illness
and a few people might have a degree of
scarring and they might have had blood
clots
all of those conditions will make the
lung feel abnormal make it feel stiff in
many cases
and it's thought to be these pulmonary
c-fiber receptors
that are saying to the brain look this
lung stiff
i'm finding it hard work i'm going to
make you feel breathless
the good news is your blood oxygen
levels are normal and the other bit of
good news
is that we expect that the
breathlessness will gradually improve
over time but we've got to take baby
steps with it
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That transcript sums up our problem so well it has made me tear up. There is a normal test and the patients feel ill but instead of being asked about childhood trauma, told they are converting emotional distress, seeking the benefits of the sick role, there is a long list of biological reasons for what is happening.

Psychological therapies may not do much harm, maybe, but they close the door on anyone looking elsewhere and that is where the real harm lies.
 
Does coronavirus linger in the body? What we know about how viruses in general hang on in the brain and testicles

I've seen a lot of people complaining about testicular pain. Not super common but not just a rare blip. Good to see it's finally noticed.

https://theconversation.com/does-co...ral-hang-on-in-the-brain-and-testicles-142878

As millions of people are recovering from COVID-19, an unanswered question is the extent to which the virus can “hide out” in seemingly recovered individuals. If it does, could this explain some of the lingering symptoms of COVID-19 or pose a risk for transmission of infection to others even after recovery?
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A latent virus can reactivate and produce infectious viruses, and this can occur months to decades after the initial infection. Perhaps the best example of this is chickenpox, which although seemingly eradicated by the immune system can reactivate and cause herpes zoster decades later.
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This is a large family of viruses whose genetic material, or genome, is encoded by DNA (and not RNA such as the new coronavirus). Herpes viruses include not only herpes simplex viruses 1 and 2 – which cause oral and genital herpes – but also chickenpox. Other herpes viruses, such as Epstein Barr virus, the cause of mononucleosis, and cytomegalovirus, which is a particular problem in immunodeficient individuals, can also emerge after latency.
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Hello, familiar viruses that we see all the time as potential triggers for ME-like disease.
Recovery from COVID-19 is delayed or incomplete in many individuals, with symptoms including cough, shortness of breath and fatigue. It seems unlikely that these constitutional symptoms are due to viral persistence as the symptoms are not coming from immune privileged sites.
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This is why the dogmatic belief systems over the psychosomatic nature of most neurological symptoms is facing disaster with the real world. Here is the quote about privileged sites:
There are a few places in the body that are less accessible to the immune system and where it is difficult to eradicate all viral infections. These include the central nervous system, the testes and the eye.
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There's also the fact that the CNS is basically connected to every single part of the body. As privileged sites go, this is basically a multipass.
 
Art Vandelay said:
An interesting account from a pulmonologist who survived covid:

https://www.salon.com/2020/04/05/what-it-feels-like-to-survive-covid-19s-dreaded-cytokine-storm/
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How does he know he had a cytokine storm when is cytokine levels weren't measured? He was also taking an IL-6 inhibitor, suggesting that something other than a cytokine storm was going on.

Cytokine storms are not simply high levels of inflammation, they are a specific condition.

So far clinical studies of cytokine levels of severe COVID-19 patients have shown high levels indicative of inflammation, but not so high to be indicative of a cytokine storm.

https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2767939

For these reasons, the term cytokine storm may be misleading in COVID-19 ARDS. Incorporating a poorly defined pathophysiological entity lacking a firm biological diagnosis may only further increase uncertainty about how best to manage this heterogeneous population of patients. The manifestations of elevated circulating mediators in the purported cytokine storm are likely to be endothelial dysfunction and systemic inflammation leading to fever, tachycardia, tachypnea, and hypotension. This constellation of symptoms already has a long history in critical care, known as systemic inflammatory response syndrome, and was used to define sepsis for decades. Interventions targeting single cytokines in sepsis, unfortunately, also have a long history of failure. Although the term cytokine storm conjures up dramatic imagery and has captured the attention of the mainstream and scientific media, the current data do not support its use. Until new data establish otherwise, the linkage of cytokine storm to COVID-19 may be nothing more than a tempest in a teapot.
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My total lack of trust in the medical profession has never been more justified :

Title : Covid-19 Has Turned Public Health Into a Lethal, Patient-Killing Experimental Endeavor

Link : https://ahrp.org/covid-19-has-turne...lethal-patient-killing-experimental-endeavor/

Dr. Meryl Nass has uncovered a hornet’s nest of government sponsored Hydroxychloroquine experiments that were designed to kill severely ill, Covid-19 hospitalized patients. On June 14th Dr. Nass first identified two Covid-19 experiments in which massive, high toxic doses – four times higher than usual of hydroxychloroquine were being given to severely ill hospitalized patients in intensive care units.
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I had read little snippets about this massive overdose of hydroxychloroquine being used in experiments. What I cannot understand is why a drug which was first approved for medical use in 1955, whose side-effect profile is understood, whose dosing is also understood, has been given at such massive doses. I can only assume that it was designed to stop a cheap, out-of-patent drug being used as a possible treatment while pharma companies were working on new, more expensive, and more profitable drugs.
 
Arnie Pye said:
My total lack of trust in the medical profession has never been more justified :

Title : Covid-19 Has Turned Public Health Into a Lethal, Patient-Killing Experimental Endeavor

Link : https://ahrp.org/covid-19-has-turne...lethal-patient-killing-experimental-endeavor/
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I would advise against taking that piece too seriously. It looks like a crackpot conspiracy theorist site - as much disinformation as Mr Trump saying hydroxychloroquine was a cure.

There is no reason why doses in a trial like this should be the standard daily dose for chronic usage. The author points out that there is a sink where the drug accumulates outside plasma so a loading dose makes total sense. From memory chloroquine and hydroxychloroquine both have longish half lives so if used in an emergency a loading dose would be expected. So the author seems not to know what she is talking about.

There is a lot of vested interest around but there is also an awful lot of completely phoney information written by people with an axe to grind.
 
It seems to be a conspiracy theory site with a major interest in anti-vax and also Nazi experimentation during the holocaust. (Not that the latter would be a conspiracy theory but it indicates a political agenda that probably has no relevance to current reality.) I don't think it is a site devoted to rational argument.
 
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