Doctors map body's COVID-19 immune response: study

General Discussion
#1

Paris (AFP) - Researchers in Australia said Tuesday they had mapped the body’s immune response to the novel coronavirus, in a potential breakthrough in the fight against the global killer.

A team of scientists were able to test blood samples from a patient who had contracted COVID-19 and was hospitalised with moderate symptoms.

Authors of the study, published in the journal Nature Medicine, said it was the first time experts had mapped the body’s general immune response to the new disease.

“We saw a really robust immune response that preceded clinical recovery,” Katherine Kedzierska, from the University of Melbourne’s Peter Doherty Institute for Infection and Immunity, told AFP.

“We noted an immune response but she was visually still unwell, and three days later the patient recovered.”

Researchers are in a race against time to try to find a vaccine for the novel coronavirus, which as of 0900 GMT Tuesday has registered more than 180,000 confirmed infections and over 7,000 deaths.

Keszierska said her team’s research was "an important step in understanding recovery from COVID-19.

“We have verifiable results in more patients with moderate disease. Now we can ask the question: what is different or missing in people who are fatally ill?”

She said the findings had two practical applications.

First, it will help virologists develop a vaccine because the goal in vaccination is to replicate the body’s natural immune response to viruses.

The team identified four distinct immune-cell populations in the COVID-19 patient’s blood as she underwent recovery.

Kedzierska said these were “very similar to what we see in patients with influenza”.

Although it kills hundreds of thousands of people annually, a broadly effective vaccine exists against influenza.

  • Immunity ‘markers’ -

The second practical application is screening, said Kedzierska.

Their observations could also help health authorities make better predictions in future disease outbreaks about who is most at risk.

These immune system “markers” could in theory predict with greater accuracy which patients are likely to have mild symptoms and which are at risk of dying.

The majority of COVID-19 deaths occur in patients who are elderly or have existing medical conditions, such as heart disease and diabetes.

Children, on the other hand, appear to show few or no symptoms. Kedzierska said more research was needed to work out why, but the immune system does naturally slow down as people age.

Sharon Lewin, director of the Doherty Institute and one of the world’s leading infectious diseases experts, told AFP that the study results were promising.

“It shows that the body makes a very good and powerful immune response to virus and it is associated with symptom clearing,” she said.

“Hopefully now we can fish out those antibodies and grow them up to scale,” she said.

Any positive covid 19 cases for members?
#2

It seems outside of PFS, this will continue to dominate many people’s daily lives.
“PFS” is a virus. Im kidding. I think.
I will say though, Ive talked to alot of smart Drs over the years across various fields of medicine, and this thought has been put out there a few times.

New Study Suggests Digestive Issues Can Be First Sign of COVID-19

A new study published in The American Journal of Gastroenterology reports that some people who get the coronavirus will experience digestive symptoms like diarrhea as a first sign of the virus.

COVID-19 is a new-to-humans coronavirus that primarily attacks the lungs and respiratory system. Its primary symptoms include fever, cough, shortness or breath and, if the infection worsens, chest pain, pneumonia and difficulty breathing. As medicals experts around the world race to learn new information, however, the list of the symptoms expands.

The new study published in the American Journal of Gastroenterology looked at data from 204 patients with COVID-19 in China’s Hubei province. Researchers found that 48.5% of these patients arrived at the hospital with digestive symptoms such as diarrhea, vomiting, or abdominal pain. The study suggested digestive symptoms may present before the respiratory symptoms of COVID-19. Those with digestive symptoms included in this study also had a more severe course of illness.

Related: ​ What Is the Mortality Rate of COVID-19?

This study’s findings add additional evidence to mounting suspicion that COVID-19 causes gastrointestinal symptoms for some people. A case report published in the New England Journal of Medicine on the first known COVID-19 patient in the United States, for example, noted the patient experienced loose stool and abdominal discomfort during their second day of hospitalization. Other research has found evidence the virus is shed in fecal matter, similar to other coronaviruses like SARS and MERS.

While more research is needed to understand the role and impact of digestive symptoms in those who get COVID-19, Brennan M.R. Spiegel, M.D., co-editor-in-chief of the American Journal of Gastroenterology, said in a press release that an awareness of digestive symptoms can aid efforts to detect COVID-19 earlier:

In this study, COVID-19 patients with digestive symptoms have a worse clinical outcome and higher risk of mortality compared to those without digestive symptoms, emphasizing the importance of including symptoms like diarrhea to suspect COVID-19 early in the disease course before respiratory symptoms develop. This may lead to earlier diagnosis of COVID-19, which can lead to earlier treatment and more expeditious quarantine to minimize transmission from people who otherwise remain undiagnosed.

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#3

Digestive issues, a result, rather than the cause of PSSD, PAS, and PFS, IMO.

The strong immune response to COVID mentioned is noteworthy considering a cytokine storm is an effect of great concern among young people. This might be a lazy explanation, but it’s like the body launching strategic nukes to rid itself of a pathogen with a “Scorched Earth” policy.

#4

Here the cause is the virus, another could be a drug, another could be salmon, zinc, b12, take your pick.
The point here with the virus is not the digestive issues but how the body deals with it. In this case its a foreign invader that can cause great consequence or even death that the body rapidly tries to clear.
Similar principles could be involved as to how the body deals with a drug, not only drugs but you have natural substances in nature that can almost mimic some of their effects. Its How the body mounts a response, and what follows after that.

#5

I would add to this real quick, Id maybe be careful thinking there is some heightened immunity in PFS.
I could see this going in either direction.
Some say acne itself can be part of an overactive immune response, which was permanently suppressed post Accutane.
Some people are saying they feel better when they’re sick, when most people would feel worse.
The ability to generate a fever can be a body’s defense mechanism.
Heat shock proteins, innate immunity.
Its hard to say how this would play out.

#6

Besides the article itself and all of whats going on not sounding too far off from Contagion, this jumped out at me,

The Novel Coronavirus Originated In Bats, And That’s Actually Pretty Common

However, researchers have found that when bats contract these viruses, their particularly strong immune systems prevent them from getting sick or dying from the infections. This means they can continue to carry and pass on the virus, whereas other animals that contract it may get sick and die, and therefore are less likely to pass it on. The UC Berkeley researchers found that a bat’s immune system is so strong, in fact, that when a virus infects a bat, the animal’s immune system response is thought to cause the virus to adapt and replicate even faster. That means when the virus infects an animal with a weaker immune system (let’s say a human), the virus is able to wreak havoc.

One of the reasons bats have such strong immune systems is thought to be the fact that they can fly, according to the UC Berkeley study. When they fly, bats elevate their metabolic rates to a level that would hurt other mammals, but for bats, helped them develop an immune system that is able to quickly repair the cell damage caused by flight, the researchers found.

#7

Just a quick thought on this. It seems kids are less susceptible to severe symptoms of Coronavirus in general. I would think hormones would play a insignificant role in their protection because this would be pre puberty.
On the other hand it seems the elderly might have a harder time possibly because of this “cytokine storm” or an overactive innate? immune response, without being able to tamper down the inflammation.
I suppose you could look at this in a few different ways coming from Finasteride.

Adding to this, children on average tend to run a higher body temperature then older adults.

Matthew Kluger, a retired professor and expert in body temperature. “A higher temperature makes us run a bit faster, and I contend that it also revs up our immune response as well,” he said.

Age tends to drive down temperature, so an older person with a temperature of 99 might be getting sick, while a younger one with the same temperature could be perfectly healthy, said Jack A. Yanovski, chief of the Section on Growth and Obesity at the Eunice Kennedy Shriver National Institute of Child Health and Human Development in Bethesda, Md.

#8
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#9

So how is it androgen mediated?
An over or under reactive immune response?
An overactive immune response or too much inflammation in the lungs could also impede virus clearance.

I say this because I thought testosterone was more likely to suppress autoimmune or overactive immune responses.
Testosterone or lack of is thought to be one of the reasons they say women are more inclined to autoimmune diseases.

Cleaning this up a little bit from my last post.

Sex-based differences in susceptibility to SARS-CoV infection

Enhanced susceptibility of male mice to SARS-CoV was associated with elevated virus titers, enhanced vascular leakage and alveolar edema. These changes were accompanied by increased accumulation of inflammatory monocyte macrophages (IMMs) and neutrophils in the lungs of male mice and depletion of IMMs partially protected these mice from lethal SARS. Moreover, the sex-specific differences were independent of T and B cell responses. Furthermore, ovariectomy or treating female mice with an estrogen receptor antagonist increased mortality indicating a protective effect for estrogen receptor signaling in mice infected with SARS-CoV. Together, these data suggest that sex differences in susceptibility to SARS-CoV in mice parallel those observed in patients and also identify estrogen receptor signaling as critical for protection in females.

Why the new coronavirus may kill more men than women

Why are men more likely to die from the new coronavirus?

According to researchers, there are a few reasons men are more likely to die from the new coronavirus.

Women have a heightened immune response

Research on previous outbreaks shows that women have stronger immune responses to coronaviruses.

According to Janine Clayton, director of the Office of Research on Women’s Health at NIH , “There’s something about the immune system in females that is more exuberant,” but researchers have yet to figure out what that is.

Some researchers think the higher level of estrogen, which contributes to immunity, and the fact that women have two X chromosomes, which carry immune-related genes, could factor into women’s heightened immune response.

For instance, in one experiment, researchers exposed mice to SARS and found male mice were more susceptible to the infection and were slower to clear the virus. They also died at higher rates and experienced more lung damage, according to Stanley Perlman, senior author of the study and a professor of microbiology at the University of Iowa .

However, when the researchers blocked estrogen in the female mice and removed their ovaries, they were more likely to die from the virus. Blocking testosterone in the male mice on the other hand had no effect on the death rate.
…

#10

I haven’t looked in detail at the article you posted here, but here’s the finding of the Wambier preprint to appear in JAAD:

tl;dr: Hyperandrogenic phenotype might correlate with higher viral load, increased ability to spread the virus, and severity of lung problems

The reasoning:

  • Older males are more vulnerable to COVID-19 (as probably everyone here knows)
  • Priming of “spike proteins” by an enzyme (TMPRSS2) is necessary for being infected by SARS-CoV-2
  • Androgen receptor (AR) activity is considered a requirement to transcribe the TMPRSS2 gene
  • Certain X-linked polymorphisms (genetic variants) may lead to hyperactive ARs

In the diagram you can see 5-AR on the left. One could infer that a 5-AR inhibitor might reduce activation of ARs and therefore reduce production of the TMPRSS2 protein. That in turn could reduce vulnerability to COVID-19. So one could say “let’s try finasteride to protect older, vulnerable men from COVID-19” (I’m not endorsing that).

@anon5006275 has a good challenge to this, which is why young men are not vulnerable to SARS-CoV-2 if they have high AR sensitivity. The reason may be that other aspects of their body override this potential risk factor.

The study is short, really just a page and a diagram. It’s also just correlational and there are probably many other factors involved in older men’s greater vulnerability. So this is just one piece of the puzzle which should be considered more as a hypothesis than a finding.

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#11

My guess it. AR is overexpressed in PFS, but underactivated. So probably that is the only benefit of having PFS.

Once again I would like to call here for a joint action to contact researchers and piggyback the Corona pandemy to get some extra free research into PFS. Every basic study on the AR and it’s mechanism may help us

#12

I got this email from Viome. I’ll update if and when I hear more.
They are predicting 20% of my county to be infected by early May as a worst case scenario.
They do have rapid 15 minute testing where im at, so at least I would be able to get a diagnosis pretty quick if need be.

During this crisis, our scientists at the Viome Research Institute have learned much about SARS-CoV-2, the virus that causes the COVID-19 respiratory disease, since the initial outbreak. We now know that the virus can be present and detectable in the gut microbiome, even after it is no longer detectable in the respiratory system, or in cases where people have experienced mild or no symptoms. Studies have shown that people may shed the virus in stool for weeks after the virus is cleared from respiratory samples.

To play our part in the long term solution to COVID-19, Viome has submitted our FDA application for approval of our Gut Intelligence™ Test for SARS-CoV-2 virus and COVID-19 detection . Our lab and bioinformatics teams completed validations for this test in exactly 14 days—an incredible feat! We believe that this type of testing will eventually be critical in our fight against COVID-19, and will release more news on this innovative, alternative test as soon as we are able.

I might look into this as well, an open Viome study.
Blood Transcriptome Gene Expression Cohort Study

#13

What does “overexpressed but underactivated”
mean?

#14

I am not the AR expert here, please correct me if I may be wrong. AR is overexpressed or upregulated in most PFS patients, that means more androgene receptors are on the surface of certain cells. The AR needs to get activated by testosterone or DHT. DHT is a far more powerful activator than testosterone. Now my hypothetical thoughts come in: Melcangi showed that there is a 5AR2-gene methylation in liquor in the majority of PFS patients and a lack of 5AR2 metabolites in the liquor. 5AR2 metabolites in the blood do not correlate with tissue levels of 5AR2 metabolites. I believe that the methylation of 5AR2 is tissue specific and may vary from PFS patients to PFS patient. Some guys with more neurological symptoms may have more methylated 5AR2 in the liquor with correspondingly low 5AR2 metabolites while other guys with less neurological symtoms may have less methylation in the liquor and more normal metabolites in the liquor but may have methylated 5AR2 in penile tissue and lower 5AR2 metabolites in penile tissue. This would explain the broad spectrum of different symptoms.
In the graphic you posted, DHT is activating the AR resulting in TMPRSS2, which is a necessary step for COVID. Low tissue levels of DHT due to local methylation of 5AR2 would result in low AR activation, less TMPRSS2 and therefore less COVID succeptibility. That is what primary data that Awor collected is indicating to. That PFS patients show lower viral infections although AR is overexpressed in tissue.

#16

For those who haven’t seen it, here’s the relevant Melcangi et al. study published in 2019, which also references previous studies about SRD5A2 methylation.

Melcangi RC, Casarini L, Marino M, et al. Altered methylation pattern of the SRD5A2 gene in the cerebrospinal fluid of post-finasteride patients: a pilot study. Endocr Connect. 2019;8(8):1118-1125. doi:10.1530/EC-19-0199
PubMed: https://pubmed.ncbi.nlm.nih.gov/31272082/

The article is open access.

PFS etiopathogenesis remains elusive. Three different clinical studies demonstrated that finasteride treatment not only affects the steroids directly related with the enzyme 5α-R but has broad consequences on the levels of several important physiological regulators of the nervous function, such as neuroactive steroids, both in plasma and in cerebrospinal fluid (CSF). These results were confirmed in an animal model of PFS, showing that alterations in the levels of neuroactive steroids not only occurred in plasma and CSF but also in brain areas, such as cerebral cortex, cerebellum and hippocampus, associated to depressive-like behaviour, alterations in neurogenesis, gliosis, neuroinflammation and gut microbiota composition. A possible hypothesis for the persistent side effects may be epigenetic modifications occurring in PFS patients. Indeed, downregulation and hypermethylation of 5α-R were observed in the rodent nervous system and associated with inflammation and depression, features that, as mentioned earlier, have been also observed in PFS model. In this setting, the evaluation of the methylation pattern remains challenging since it could change during adulthood and with ageing.

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Neuroactive steroids in CSF with significant differences between PFS and non-PFS groups: Pregnenolone, Dihydroprogesterone, Testosterone, Dihydrotestosterone

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#17

Did the methylation in liquor correlate with neurological symptoms?

#18

[deleted]

#19

If there is no correlation between 5AR2 methylation and neurosteroide level, how can the low 5AR2 metabolites in some patients be explained? 5AR3 methylation?

#20

Today i learned that im Covid. Another strike from the globalist elitist agenda to my body and health.

Luckily, my symptoms are pretty mild. I had 37.8 fever which went down to normal few days ago. Few couches here and there. A little tired. Sexually, flaccid penis seems smaller and libido of course went down to 0, which is even normal for healthy people i think.

Am i experiencing this mild form of Covid due to Post Accutane Syndrome? Is there any relation between AR and covid? I don’t think my own bodie’s T production is less than normal to cause a such thing.

Oh and!

Now the government will send ‘‘drugs’’ to my home.

This world is purely evil.

Create a virus in a lab.

Infect people.

And then sell drugs.

Selling drugs.

Selling drugs.

Sounds familiar?