SARS Cov 2: Science-only thread

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SARS Cov 2: Science-only thread

Postby §ê¢rꆧ » Sat May 09, 2020 6:05 pm

Of course science is a slippery beast and a riot of consensus squabbling.. SO, all views welcome in this thread, as long as posts are framed around the scientific inquiry/method. Please don't post poli stuff or humor here, unless science based, use the Coronavirus Crisis main thread or elsewhere, please.

This is a nice timeline of the mutations, with instructive graphics of the RNA sequences, that have occurred and where:
https://www.nytimes.com/interactive/202 ... tions.html
(archived: http://archive.is/wip/kjHB8)
<...>
Genome UC4, collected on Feb. 27 from a patient in Solano County, Calif.
Image
http://archive.is/kjHB8/1ab89d40ff20350 ... 6e3859.jpg
Image
<...>
<...>
In fact, researchers have found that the coronavirus is mutating relatively slowly compared to some other RNA viruses, in part because virus proteins acting as proofreaders are able to fix some mistakes. Each month, a lineage of coronaviruses might acquire only two single-letter mutations.
In the future, the coronavirus may pick up some mutations that help it evade our immune systems. But the slow mutation rate of the coronavirus means that these changes will emerge over the course of years.
That bodes well for vaccines currently in development for Covid-19. If people get vaccinated in 2021 against the new coronavirus, they may well enjoy a protection that lasts for years.
<...>
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Re: SARS Cov 2: Science-only thread

Postby liminalOyster » Sat May 09, 2020 6:13 pm

reddit.com/r/COVID19
is a nice resource for scientific info (with attendant biases like everywhere):

We only allow the following: Peer-reviewed journal articles, preprints, academic comments (Lancet, Nature News, etc.), academic institution releases, and government agency (WHO, CDC, etc.) releases. No COVID trackers. No posting studies looking for participants.


Calling it out because I just popped over there to locate this article which makes a strong case for Vitamin D deficiency playing some role in case severity:
www.medrxiv.org/content/10.1101/2020.04.08.20058578v3
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Re: SARS Cov 2: Science-only thread

Postby §ê¢rꆧ » Sat May 09, 2020 6:34 pm

liminalOyster » Sat May 09, 2020 5:13 pm wrote:
Calling it out because I just popped over there to locate this article which makes a strong case for Vitamin D deficiency playing some role in case severity:
www.medrxiv.org/content/10.1101/2020.04.08.20058578v3


Thanks, yes, You just reminded me to take my weekly 50,000 units of ergocalciferol, :jumping: Vitamin D plays a role in autoimmune diseases, like Multiple Sclerosis. I've read there there is an epidemic of low vitamin D, especially in northern latitudes. There are theories that autoimmune diseases are caused by viruses that get into the cerebral spinal fluid (CSF) and brain of the sufferer. I wonder if Covid 19 is going to be an ongoing lifelong autoimmune condition for those that are affected badly, even if most people totally recover or never really get sick.
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Re: SARS Cov 2: Science-only thread

Postby liminalOyster » Sat May 09, 2020 7:06 pm

I have a mild auto-immune disorder that I rarely need to think about much but when I caught this paper, I recalled that the last time my D was tested it was inexplicably low (despite diet, latitude, etc) and was attributed to my ai disease.

I've taken a really high grade multi-vitamin for a decade and just ordered some D3. Now wondering about ergocalciferol too.

I am mostly very, very curious to see the results of the nicotine trials in France. I guess I'm cynically assuming there's nothing to it and people just lie to their docs about smoking, but nicotine being such a powerful psych-med, I also won't be surprised if in a weirdo twist, it turns out to have some prophylactic effects too.

Here's the conclusion from the full paper linked below:

Editorial: Nicotine and SARS-CoV-2: COVID-19 may be a disease of the nicotinic cholinergic system


April 30, 2020.

In conclusion, we noticed that most of the clinical characteristics of severe COVID-19 could be explained by dysregulation of the cholinergic anti-inflammatory system. The observation that patients eventually develop cytokine storm which results in rapid clinical deterioration, led to the development of a hypothesis about the series of events associated with adverse outcomes in COVID-19 (Fig. 2). Once someone is infected with SARS-CoV-2, the immune system is mobilized. As the virus replicates, cell and viral debris or virions may interact with the nAChRs blocking the action of the cholinergic anti-inflammatory pathway. If the initial immune response is not enough to combat the viral invasion at an early stage, the extensive and prolonged replication of the virus will eventually block a large part the cholinergic anti-inflammatory pathway seriously compromising its ability to control and regulate the immune response. The uncontrolled action of pro-inflammatory cytokines will result in the development of cytokine storm, with acute lung injury leading to ARDS, coagulation disturbances and multiorgan failure. Based on this hypothesis, COVID-19 appears to eventually become a disease of the nicotinic cholinergic system.

Nicotine could maintain or restore the function of the cholinergic anti-inflammatory system and thus control the release and activity of pro-inflammatory cytokines. This could prevent or suppress the cytokine storm. This hypothesis needs to be examined in the laboratory and the clinical setting.

https://www.sciencedirect.com/science/a ... 0020302924
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Re: SARS Cov 2: Science-only thread

Postby stickdog99 » Sat May 09, 2020 7:46 pm

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Re: SARS Cov 2: Science-only thread

Postby Joe Hillshoist » Mon May 11, 2020 5:38 am

Vitamin D supplementation has been shown to lower the chances of Acure Respiratory Distress, upper and lower respiratory tract infection and possibly cytokine reactions that overwhelm the lungs as well as increasing rates of lung repair.

To the point where if you were ill with something other than COVID 19 you might have noticed that time in strong sunshine eases your symptoms and sometimes the illness itself. Like so many decisions it's a question of balancing your odds and weighing up pros and cons.
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Re: SARS Cov 2: Science-only thread

Postby §ê¢rꆧ » Wed May 13, 2020 2:59 am

youtube video




TWiV 610: Coronavirus FAQ
7,409 views
•May 6, 2020Vincent Racaniello
52.3K subscribers
The TWiV team summarizes serology-based tests for SARS-CoV-2, lack of effect of ACE inhibitors or ARBs on COVID-19 severity, and answers listener questions.

When listening to podcasts I like to load some instrumental ambient sound designy stuff quietly in the background to make it go down smoother, like Brian Eno or Lustmord or Dead Voices on Air
:headphones:
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Re: SARS Cov 2: Science-only thread

Postby 0_0 » Thu May 14, 2020 4:56 pm

here's a century-old head-scratcher:
Perhaps the most interesting epidemiological studies conducted during the 1918–1919 pandemic were the human experiments conducted by the Public Health Service and the U.S. Navy under the supervision of Milton Rosenau on Gallops Island, the quarantine station in Boston Harbor, and on Angel Island, its counterpart in San Francisco. The experiment began with 100 volunteers from the Navy who had no history of influenza. Rosenau was the first to report on the experiments conducted at Gallops Island in November and December 1918.69 His first volunteers received first one strain and then several strains of Pfeiffer's bacillus by spray and swab into their noses and throats and then into their eyes. When that procedure failed to produce disease, others were inoculated with mixtures of other organisms isolated from the throats and noses of influenza patients. Next, some volunteers received injections of blood from influenza patients. Finally, 13 of the volunteers were taken into an influenza ward and exposed to 10 influenza patients each. Each volunteer was to shake hands with each patient, to talk with him at close range, and to permit him to cough directly into his face. None of the volunteers in these experiments developed influenza. Rosenau was clearly puzzled, and he cautioned against drawing conclusions from negative results. He ended his article in JAMA with a telling acknowledgement: “We entered the outbreak with a notion that we knew the cause of the disease, and were quite sure we knew how it was transmitted from person to person. Perhaps, if we have learned anything, it is that we are not quite sure what we know about the disease.” (p. 313)

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2862332/

i'm not sure if they still do experiments like that!
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Re: SARS Cov 2: Science-only thread

Postby liminalOyster » Fri May 15, 2020 1:17 am

Masks help stop the spread of coronavirus – the science is simple and I’m one of 100 experts urging governors to require public mask-wearing

May 14, 2020 8.03am EDT

 Jeremy Howard, University of San Francisco

I’m a data scientist at the University of San Francisco and teach courses online in machine learning for fast.ai. In late March, I decided to use public mask-wearing as a case study to show my students how to combine and analyze diverse types of data and evidence.

Much to my surprise, I discovered that the evidence for wearing masks in public was very strong. It appeared that universal mask-wearing could be one of the most important tools in tackling the spread of COVID-19. Yet the people around me weren’t wearing masks and health organizations in the U.S. weren’t recommending their use.

I, along with 18 other experts from a variety of disciplines, conducted a review of the research on public mask-wearing as a tool to slow the spread SARS-CoV-2. We published a preprint of our paper on April 12 and it is now awaiting peer review at the Proceedings of the National Academy of Sciences.

Since then, there have been many morereviews that support mask-wearing.

On May 14, I and 100 of the world’s top academics released an open letter to all U.S. governors asking that “officials require cloth masks to be worn in all public places, such as stores, transportation systems, and public buildings.”

Currently, the U.S. Centers for Disease Control and Prevention recommends that everyone wears a mask – as do the governments covering 90% of the world’s population – but, so far, only 12 states in the U.S. require it. In the majority of the remaining states, the CDC recommendation has not been enough: Most people do not currently wear masks. However, things are changing fast. Every week more and more jurisdictions require mask use in public. As I write this, there are now 94 countries that have made this move.

So what is this evidence that has led myself and so many scientists to believe so strongly in masks?

Droplets ejected from people’s mouths during coughing or talking are likely the most significant source of SARS-CoV-2 transmission.Thomas Jackson/Stone via Getty ImagesThe evidence

The research that first convinced me was a laser light-scattering experiment. Researchers from the National Institutes of Health used lasers to illuminate and count how many droplets of saliva were flung into the air by a person talking with and without a face mask. The paper was only recently published officially, but I saw a YouTube video showing the experiment in early March. The results are shockingly obvious in the video. When the researcher used a simple cloth face cover, nearly all the droplets were blocked.

This evidence is only relevant if COVID-19 is transmitted by droplets from a person’s mouth. It is. There are many documented super-spreading cases connected with activities – like singing in enclosed spaces – that create a lot of droplets.

The light-scattering experiment cannot see “micro-droplets” that are smaller than 5 microns and could contain some viral particles. But experts don’t think that these are responsible for much COVID-19 transmission.

While just how much of a role these small particles play in transmission remains to be seen, recent research suggests that cloth masks are also effective at reducing the spread of these smaller particles. In a paper that has not yet been peer-reviewed, researchers found that micro-droplets fell out of the air within 1.5 meters of the person who was wearing a mask, versus 5 meters for those not wearing masks. When combined with social distancing, this suggests that masks can effectively reduce transmission via micro-droplets.

Another recent study showed that unfitted surgical masks were 100% effective in blocking seasonal coronavirusin droplets ejected during breathing.

If only people with symptoms infected others, then only people with symptoms would need to wear masks. But experts have shown that people without symptoms pose a risk of infecting others. In fact, four recent studies show that nearly half of patients are infected by people who do not themselves have symptoms.

This evidence seems, to me, clear and simple: COVID-19 is spread by droplets. We can see directly that a piece of cloth blocks those droplets and the virus those droplets contain. People without symptoms who don’t even know they are sick are responsible for around half of the transmission of the virus.

We should all wear masks.

Asking the wrong questions led to a misunderstanding of the medical literature around masks. AP Photo/Eric GayAgainst the tide

After going through all of this strong evidence in late March and early April, I wondered why mask-wearing was controversial amongst health organizations in the Western world. The U.S. and European CDCs did not recommend masks, and neither did nearly any western government except for Slovakia and Czechia, which both required masks in late March.

I think there were three key problems.

The first was that most researchers were looking at the wrong question – how well a mask protects the wearer from infection and not how well a mask prevents an infected person from spreading the virus. Masks function very differently as personal protective equipment (PPE) versus source control.

Masks are very good at blocking larger droplets and not nearly as good at blocking tiny particles. When a person expels droplets into the air, they quickly evaporate and shrink to become tiny airborne particles called droplet nuclei. These are extremely hard to remove from the air. However, in the moist atmosphere between a person’s mouth and their mask, it takes nearly a hundred times as long for a droplet to evaporate and shrink into a droplet nuclei.

This means that nearly any kind of simple cloth mask is great for source control. The mask creates humidity, this humidity prevents virus-containing droplets from turning into droplet nuclei, and this allows the fabric of the mask to block the droplets.

Unfortunately, nearly all of the research that was available at the start of this pandemic focused on mask efficacy as PPE. This measure is very important for protecting health care workers, but does not capture their value as source control. On Feb. 29, the U.S. surgeon general tweeted that masks “are NOT effective in preventing general public from catching #Coronavirus.” This missed the key point: They are extremely effective at preventing its spread, as our review of the literature showed.

The second problem was that most medical researchers are used to judging interventions on the basis of randomized controlled trials. These are the foundation of evidence based medicine. However, it is impossible and unethical to test mask-wearing, hand-washing or social distancing during a pandemic.

Experts like Trisha Greenhalgh, the author of the best-selling textbook “How to Read a Paper: The Basics of Evidence Based Healthcare,” are now asking, “Is Covid-19 evidence-based medicine’s nemesis?” She and others are suggestingthat when a simple experiment finds evidence to support an intervention and that intervention has a limited downside, policymakers should act before a randomized trial is done.

The third problem is that there is a shortage of medical masks around the world. Many policymakers were concerned that recommending face coverings for the public would lead to people hoarding medical masks. This led to seemingly contradictory guidance where the CDC said there was no reason for the public to wear masks but that masks needed to be saved for medical workers. The CDC has now clarified its stance and recommends the public use of homemade masks while saving higher-grade masks for medical professionals.

Many countries were quick to adopt public mask-wearing while others, including the U.S., still haven’t enacted nationwide rules. AP Photo/Andy WongResults of mask-wearing

There are numerous studies that suggest if 80% of people wear a mask in public, then COVID-19 transmission could be halted. Until a vaccine or a cure for COVID-19 is discovered, cloth face masks might be the most important tool we currently have to fight the pandemic.

Given all of the laboratory and epidemiological evidence, the low cost of wearing masks – which can be made at home with no tools – and the potential to slow COVID-19 transmission with widescale use, policymakers should ensure that everyone wears a mask in public


https://theconversation.com/masks-help- ... ing-138507
Last edited by liminalOyster on Fri May 15, 2020 1:19 am, edited 1 time in total.
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Re: SARS Cov 2: Science-only thread

Postby 0_0 » Fri May 15, 2020 2:40 am

Discarded coronavirus face masks and gloves rising threat to ocean life, conservationists warn
The bright colours of latex gloves risk can be mistaken as food by seabirds, turtles and other marine mammals putting them at risk of severe injuries and death
Louise BoyleNew York
Thursday 16 April 2020 21:53

The rise in disposable face masks and gloves being used to prevent the spread of coronavirus is adding to the glut of plastic pollution threatening the health of oceans and marine life, environmentalists warn. On Wednesday, New York Governor Andrew Cuomo issued an executive order, effective this weekend, that New Yorkers must now wear a mask when out in public in situations where social distancing isn’t possible. The CDC advises wearing cloth masks in public (although President Trump says it’s not mandatory and he "doesn't see it for himself") due to the concern that Covid-19 can be spread by people who are infected but not showing symptoms.

Surgeon General Jerome Adams warned Americans to stop buying medical masks that are needed by healthcare workers. It has done little to stop a wave of single-use masks and latex gloves being used and discarded.

On social media, pictures of bright blue gloves and crumpled masks littering streets, shopping carts, parking lots, beaches and green spaces are being posted around the world. It’s left to sanitation workers and grocery story staff, those essential but underpaid frontline employees, to pick them up.Those not picked up can be caught by a gust of wind or washed down drains, ending up in the ocean and waterways. Not only is there a potential health risk of dropping used masks and gloves during the pandemic but many contain materials that do not recycle and are not biodegradable. Surgical masks are made using non-woven fabrics including plastics like polypropylene.

According to NOAA, plastic wreaks havoc on marine ecosystems. As plastic swirls around in the water, much of it breaks down to tiny pieces, called micro-plastics. The Ocean Conservancy discovered that many fish species consume plastics debris, confusing it for real food and estimated that at least 600 different wildlife species are threatened by the pollution. There is also a human health risk from plastic entering the food chain with nearly a billion people around the world consuming seafood as their primary source of protein.

Used masks and gloves add to an already significant problem: At least 8m tons of plastic end up in the oceans every year, making up 80 per cent of all marine debris, according to the International Union for Conservation of Nature. The bright colours of latex gloves can be mistaken as food by seabirds, turtles and other marine mammals putting them at risk of severe injuries and death. Last year a sperm whale, which died after becoming stranded on a beach on the Isle of Harris in Scotland, was found to have 220lb of debris in its stomach including bundles of rope, plastic gloves, bags and cups.

An early warning sign of the worrying trend came in February, when conservation group OceansAsia posted a photo of dozens of surgical masks they discovered on Hong Kong beaches during a year-long research project into marine debris and micro-plastics. Co-founder Gary Stokes told The Independent: “The way I see these masks in the environment is just another addition to the ever-growing marine debris crisis our oceans are facing. No better, no worse, just shouldn’t be there in the first place. I’m waiting to hear of the first necropsy that finds masks inside a dead marine animal. It’s not a question of if, but when.” Coronavirus masks are adding to Hong Kong’s marine trash problem which flows from mainland China and elsewhere. “People think they’re protecting themselves but it’s not just about protecting yourselves, you need to protect everybody and by not throwing away the mask properly, it’s very selfish,” Tracey Read, founder of the group Plastic Free Seas in Hong Kong told Reuters.

In the US, Maria Algarra, was so concerned about the uptick in plastic waste that she started a hashtag campaign on 23 March called #TheGloveChallenge, asking people to send photos as a way to track littered gloves and raise awareness of the issue. (She made clear that people should not pick up the items unless they feel it's safe and they have personal protective equipment). Ms Algarra founded Clean This Beach Up in Miami, Florida last year. Before the pandemic, the movement had grown to 1,600 people, from high school students to octogenarians, volunteering to pick up trash on beaches across Miami-Dade and Broward counties. She told The Independent that since the coronavirus outbreak, she had seen dozens of plastic gloves floating in the bay, in parking lots and on the Venetian Causeway bridges linking Miami Beach to the mainland.

As part of the campaign, Ms Algarra has been sent 1,200 pictures of jettisoned plastic gloves – not only in Miami but in the boroughs of New York City and in Italy, Spain, Germany and New Zealand. A rough count adds up to more than 1,800 gloves in these pictures alone. She has received a lot of photos from Portugal, France and New Jersey particularly. Of the latter, Ms Algarra said: “I couldn’t believe my eyes. One girl sent a video where she found over 30 gloves from her car to the door of the store that she was going to.”

Ms Algarra said that the gloves were a growing problem both for the ocean and on dry land. "It not only causes risk to wildlife but to other people who could get infected, our sanitation workers and other shoppers for example, when gloves are left in carts.

“With the glove challenge, it's about education. That’s the key for us to do better as a community and as humans.

“We can’t expect people to change their ways if they don’t know what they’re doing wrong."

She added: “Plastic breaks down into smaller and smaller pieces until micro-plastic is everywhere. It’s toxic and it's in what we’re eating and drinking.

“There’s no way to clean up micro-plastics. Once trash makes it into the ocean and breaks into smaller pieces, it’s almost impossible to take it back."


https://www.independent.co.uk/news/coro ... 69471.html
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Re: SARS Cov 2: Science-only thread

Postby cptmarginal » Fri May 15, 2020 10:57 am

FWIW

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7185012/

Metabolism. 2020 Apr 27 : 154252.

Testosterone, a key hormone in the context of COVID-19 pandemic

Paolo Pozzillia,⁎ and Andrea Lenzib

Daily data show that entire population with SARS-CoV2 is 58% made of males [[1], [2], [3]]. The difference in the number of cases reported by gender increases progressively in favor of male subjects up to the age group ≥60–69 (66.6%) and ≥ 70–79 (66.1%), with the exception of the 20–29 years and 30–39 years group in which the number of female subjects it is slightly higher. Furthermore, higher lethality is in favor of male subjects in all age groups. Deaths among 30-39ys are 82.4% males; among 40-49ys are 73.1% males; among 50-59ys are 78.5% males; among 60-69ys are 79.7% males; among 70-79ys are 79.6% males; among 80-89ys are 66.9% males [4].

The initial clinical manifestation of the COVID-19 is pneumonia, though are described gastrointestinal symptoms and asymptomatic infections, the last not yet been definitely assessed [5]. The infection can progress to severe disease with dyspnoea and chest symptoms corresponding to pneumonia in the second or third week of a symptomatic infection. Clinical data show decreased oxygen saturation, changes visible through chest X-rays and other imaging techniques. Furthermore, lymphopenia appears to be common, and an increase of inflammatory markers (C-reactive protein and pro-inflammatory cytokines) has been reported [6].

Is low testosterone a promoter of COVID-19 infection?

It is well established that plasma testosterone concentration is reduced by age and comorbidities like obesity, diabetes and obstructive sleep apnea (OSA) [7], all comorbidities highly prevalent in COVID-19 patients [8] Several studies have shown that in men with chronic obstructive pulmonary disease (COPD) hypogonadism is associated with a prevalence ranging between 22% and 69% [9]. In this context low testosterone levels can cause a reduction of respiratory muscles activity and overall strength and exercise capacity [10], whilst normal circulating testosterone levels show a protective effect on several respiratory outcomes (i.e. forced expiratory volume in one second- FEV1, and forced vital capacity - FVC) [11]. A randomized controlled trial reported an improvement in peak oxygen consumption in men receiving testosterone replacement therapy [12]. SARS-CoV2 infects lung alveolar epithelial cells using as an entry receptor the angiotensin-converting enzyme II (ACE2) [13]. ACE2 plays a role in lung protection and therefore viral binding to this receptor may deregulate a lung protective pathway [14]. Interestingly, studies showed that ACE2 is a constitutive product of adult-type Leydig cells [15], thus implying a role in testicular function and suggesting a possible involvement of testicle in COVID-19 infected patients, a factor which may affect testosterone secretion.

Pro-inflammatory cytokines have a central role in the progression of COVID-19 infection. Reduction of cytokine activity and/or their receptors (anti-cytokine therapy), can be useful for treatment. In this context testosterone may downregulate inflammation. As a matter of fact, several studies carried out both in animals and humans showed that hypogonadism is associated with increased pro-inflammatory cytokines and that testosterone treatment reduces IL-1β, IL-6, and TNF-α [16]. Furthermore, the association between an increase of pro-inflammatory state and decline in testosterone is often observed in aging men [17] and in men with stable coronary artery disease [18]. Based on the above considerations, the hypothesis arises that testosterone may have a role in the cascade of events leading to progression of COVID-19 infection due to the cytokine storm. Suppression of ACE2 expression by inflammatory cytokines accompanied by the decrease of androgens and estrogens of the elderly, may establish a negative correlation between ACE2 expression and COVID-19 mortality [19].

Measuring testosterone levels may be recommended at the time of an identified COVID-19 positive patient.

At present data on testosterone can be collected systematically at one or more institutions. If values are low, use of testosterone may be considered to reduce the associated pulmonary syndrome, thus preventing progression to severe COVID-19 disease where pro-inflammatory cytokines play a major role. In a further selection of patients for testosterone treatment, avoidance of enrolling patients in whom therapy with the hormone is contraindicated, should be taken into account. A proper randomized trial with testosterone should be then designed.

Is high testosterone a promoter of COVID-19 infection?

As opposed to what mentioned earlier, stands the testosterone-driven COVID-19 theory [20]. This is based on the androgen receptor activation of the transcription of a transmembrane protease, serine 2 (TMPRSS2), exploring possible implications in risk stratification and transmissibility of COVID-19 infection [21]. Although other proteases were described to activate the COVID-19 spikes in vitro, only TMPRSS2 activity is regarded as essential for viral spread and pathogenesis in the infected hosts [22]. TMPRSS2 may also cleave ACE2 for augmented viral entry [23]. Androgen receptor activity has been considered a requirement for the transcription of TMPRSS2 gene as no other known TMPRSS2 gene promoter has been reported to exert the same action in humans [24,25]. The modulation of TMPRSS2 expression by testosterone has been suggested to contribute to male predominance of COVID-19 infection [26]. Finally, TMPRSS2 is both the most frequently altered gene in primary prostate cancer and a critical factor enabling cellular infection by SARS-CoV-2 [24]. The hyper adrogenic phenotype could explain the COVID-19 positivity in those few young males with severe COVID-19 infection [27], possibly with shorter AR CAG lengths, who are at greater risk of developing prostate cancer because higher receptor transcription activity [28].

A role for TMPRSS2 variants and its expression levels in modulating COVID-19 severity has been suggested, leading to foster a rapid experimental validation on large cohorts of patients with different clinical manifestations of COVID-19 infection [29]. Since TMPRSS2 are expressed also at pulmonary level, the use of TMPRSS2 inhibitors, currently used for prostate cancer, represent an appealing target for prevention or treatment of COVID-19 pneumonia [21,22]. Studies are required to validate this hypothesis and to evaluate the therapeutic and prophylactic potential of drugs that temporarily target androgen activity, such as androgen receptor inhibitors, steroidogenesis inhibitors and 5-alpha reductase inhibitors [20].

The elucidation of the role of testosterone in the battle towards COVID-19 infection turns out to be an urgent need.

Conflict of interest: none.

Funding: none.

References

[...]


Relevant:

Hitherto, both the autonomic nervous system and innate immune system were regarded as systems that cannot be voluntarily influenced. The present study demonstrates that, through practicing techniques learned in a short-term training program, the sympathetic nervous system and immune system can indeed be voluntarily influenced. Healthy volunteers practicing the learned techniques exhibited profound increases in the release of epinephrine, which in turn led to increased production of anti-inflammatory mediators and subsequent dampening of the proinflammatory cytokine response elicited by intravenous administration of bacterial endotoxin. This study could have important implications for the treatment of a variety of conditions associated with excessive or persistent inflammation, especially autoimmune diseases in which therapies that antagonize proinflammatory cytokines have shown great benefit.
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Re: SARS Cov 2: Science-only thread

Postby 0_0 » Fri May 15, 2020 12:32 pm

Daily data show that entire population with SARS-CoV2 is 58% made of males [[1], [2], [3]]. The difference in the number of cases reported by gender increases progressively in favor of male subjects up to the age group ≥60–69 (66.6%) and ≥ 70–79 (66.1%), with the exception of the 20–29 years and 30–39 years group in which the number of female subjects it is slightly higher.


You know why data shows that the older the age group the bigger the percentage of males? Because the deaths with covid have an average age of like 80 and approach normal mortality data, from which it is well known that males on average die younger than females.
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Re: SARS Cov 2: Science-only thread

Postby liminalOyster » Fri May 15, 2020 6:35 pm

cptmarginal » Fri May 15, 2020 10:57 am wrote:FWIW

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7185012/

Metabolism. 2020 Apr 27 : 154252.

Testosterone, a key hormone in the context of COVID-19 pandemic

Paolo Pozzillia,⁎ and Andrea Lenzib

Daily data show that entire population with SARS-CoV2 is 58% made of males [[1], [2], [3]]. The difference in the number of cases reported by gender increases progressively in favor of male subjects up to the age group ≥60–69 (66.6%) and ≥ 70–79 (66.1%), with the exception of the 20–29 years and 30–39 years group in which the number of female subjects it is slightly higher. Furthermore, higher lethality is in favor of male subjects in all age groups. Deaths among 30-39ys are 82.4% males; among 40-49ys are 73.1% males; among 50-59ys are 78.5% males; among 60-69ys are 79.7% males; among 70-79ys are 79.6% males; among 80-89ys are 66.9% males [4].

The initial clinical manifestation of the COVID-19 is pneumonia, though are described gastrointestinal symptoms and asymptomatic infections, the last not yet been definitely assessed [5]. The infection can progress to severe disease with dyspnoea and chest symptoms corresponding to pneumonia in the second or third week of a symptomatic infection. Clinical data show decreased oxygen saturation, changes visible through chest X-rays and other imaging techniques. Furthermore, lymphopenia appears to be common, and an increase of inflammatory markers (C-reactive protein and pro-inflammatory cytokines) has been reported [6].

Is low testosterone a promoter of COVID-19 infection?

It is well established that plasma testosterone concentration is reduced by age and comorbidities like obesity, diabetes and obstructive sleep apnea (OSA) [7], all comorbidities highly prevalent in COVID-19 patients [8] Several studies have shown that in men with chronic obstructive pulmonary disease (COPD) hypogonadism is associated with a prevalence ranging between 22% and 69% [9]. In this context low testosterone levels can cause a reduction of respiratory muscles activity and overall strength and exercise capacity [10], whilst normal circulating testosterone levels show a protective effect on several respiratory outcomes (i.e. forced expiratory volume in one second- FEV1, and forced vital capacity - FVC) [11]. A randomized controlled trial reported an improvement in peak oxygen consumption in men receiving testosterone replacement therapy [12]. SARS-CoV2 infects lung alveolar epithelial cells using as an entry receptor the angiotensin-converting enzyme II (ACE2) [13]. ACE2 plays a role in lung protection and therefore viral binding to this receptor may deregulate a lung protective pathway [14]. Interestingly, studies showed that ACE2 is a constitutive product of adult-type Leydig cells [15], thus implying a role in testicular function and suggesting a possible involvement of testicle in COVID-19 infected patients, a factor which may affect testosterone secretion.

Pro-inflammatory cytokines have a central role in the progression of COVID-19 infection. Reduction of cytokine activity and/or their receptors (anti-cytokine therapy), can be useful for treatment. In this context testosterone may downregulate inflammation. As a matter of fact, several studies carried out both in animals and humans showed that hypogonadism is associated with increased pro-inflammatory cytokines and that testosterone treatment reduces IL-1β, IL-6, and TNF-α [16]. Furthermore, the association between an increase of pro-inflammatory state and decline in testosterone is often observed in aging men [17] and in men with stable coronary artery disease [18]. Based on the above considerations, the hypothesis arises that testosterone may have a role in the cascade of events leading to progression of COVID-19 infection due to the cytokine storm. Suppression of ACE2 expression by inflammatory cytokines accompanied by the decrease of androgens and estrogens of the elderly, may establish a negative correlation between ACE2 expression and COVID-19 mortality [19].

Measuring testosterone levels may be recommended at the time of an identified COVID-19 positive patient.

At present data on testosterone can be collected systematically at one or more institutions. If values are low, use of testosterone may be considered to reduce the associated pulmonary syndrome, thus preventing progression to severe COVID-19 disease where pro-inflammatory cytokines play a major role. In a further selection of patients for testosterone treatment, avoidance of enrolling patients in whom therapy with the hormone is contraindicated, should be taken into account. A proper randomized trial with testosterone should be then designed.

Is high testosterone a promoter of COVID-19 infection?

As opposed to what mentioned earlier, stands the testosterone-driven COVID-19 theory [20]. This is based on the androgen receptor activation of the transcription of a transmembrane protease, serine 2 (TMPRSS2), exploring possible implications in risk stratification and transmissibility of COVID-19 infection [21]. Although other proteases were described to activate the COVID-19 spikes in vitro, only TMPRSS2 activity is regarded as essential for viral spread and pathogenesis in the infected hosts [22]. TMPRSS2 may also cleave ACE2 for augmented viral entry [23]. Androgen receptor activity has been considered a requirement for the transcription of TMPRSS2 gene as no other known TMPRSS2 gene promoter has been reported to exert the same action in humans [24,25]. The modulation of TMPRSS2 expression by testosterone has been suggested to contribute to male predominance of COVID-19 infection [26]. Finally, TMPRSS2 is both the most frequently altered gene in primary prostate cancer and a critical factor enabling cellular infection by SARS-CoV-2 [24]. The hyper adrogenic phenotype could explain the COVID-19 positivity in those few young males with severe COVID-19 infection [27], possibly with shorter AR CAG lengths, who are at greater risk of developing prostate cancer because higher receptor transcription activity [28].

A role for TMPRSS2 variants and its expression levels in modulating COVID-19 severity has been suggested, leading to foster a rapid experimental validation on large cohorts of patients with different clinical manifestations of COVID-19 infection [29]. Since TMPRSS2 are expressed also at pulmonary level, the use of TMPRSS2 inhibitors, currently used for prostate cancer, represent an appealing target for prevention or treatment of COVID-19 pneumonia [21,22]. Studies are required to validate this hypothesis and to evaluate the therapeutic and prophylactic potential of drugs that temporarily target androgen activity, such as androgen receptor inhibitors, steroidogenesis inhibitors and 5-alpha reductase inhibitors [20].

The elucidation of the role of testosterone in the battle towards COVID-19 infection turns out to be an urgent need.

Conflict of interest: none.

Funding: none.

References

[...]


Relevant:

Hitherto, both the autonomic nervous system and innate immune system were regarded as systems that cannot be voluntarily influenced. The present study demonstrates that, through practicing techniques learned in a short-term training program, the sympathetic nervous system and immune system can indeed be voluntarily influenced. Healthy volunteers practicing the learned techniques exhibited profound increases in the release of epinephrine, which in turn led to increased production of anti-inflammatory mediators and subsequent dampening of the proinflammatory cytokine response elicited by intravenous administration of bacterial endotoxin. This study could have important implications for the treatment of a variety of conditions associated with excessive or persistent inflammation, especially autoimmune diseases in which therapies that antagonize proinflammatory cytokines have shown great benefit.


Thanks for posting this. Low-testosterone is associated with many bad outcomes for men including heart disease and cancer. According to my doc, it was long overlooked because it so strongly culturally associated with negative traits.
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Re: SARS Cov 2: Science-only thread

Postby JackRiddler » Fri May 15, 2020 8:23 pm

T cells found in COVID-19 patients ‘bode well’ for long-term immunity

By Mitch Leslie

May. 14, 2020, 9:00 PM

https://www.sciencemag.org/news/2020/05 ... m-immunity
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Re: SARS Cov 2: Science-only thread

Postby Joe Hillshoist » Sun May 17, 2020 8:04 am

Highlights


Measuring immunity to SARS-CoV-2 is key for understanding COVID19 and vaccine development

Epitope pools detect CD4+ and CD8+ T cells in 100 and 70% of convalescent COVID patients

T cell responses are focused not only on spike but also on M, N and other ORFs

T cell reactivity to SARS-CoV-2 epitopes is also detected in non-exposed individuals
Summary

Understanding adaptive immunity to SARS-CoV-2 is important for vaccine development, interpreting coronavirus disease 2019 (COVID-19) pathogenesis, and calibration of pandemic control measures. Using HLA class I and II predicted peptide ‘megapools’, circulating SARS-CoV-2−specific CD8+ and CD4+ T cells were identified in ∼70% and 100% of COVID-19 convalescent patients, respectively. CD4+ T cell responses to spike, the main target of most vaccine efforts, were robust and correlated with the magnitude of the anti-SARS-CoV-2 IgG and IgA titers. The M, spike and N proteins each accounted for 11-27% of the total CD4+ response, with additional responses commonly targeting nsp3, nsp4, ORF3a and ORF8, among others. For CD8+ T cells, spike and M were recognized, with at least eight SARS-CoV-2 ORFs targeted. Importantly, we detected SARS-CoV-2−reactive CD4+ T cells in ∼40-60% of unexposed individuals, suggesting cross-reactive T cell recognition between circulating ‘common cold’ coronaviruses and SARS-CoV-2.


https://www.cell.com/cell/fulltext/S0092-8674(20)30610-3
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