siderea | Entries tagged with sci_bio

God damn.

2023 Oct 3: bioRxiv (pre-print, scientific article not yet peer-reviewed): "A Drug-Free Pathogen Capture and Neutralizing Nasal Spray to Prevent Emerging Respiratory Infections" by John Joseph, Helna Mary Baby, et al. Emphasis mine:

Herein, we report a Pathogen Capture and Neutralizing Spray (PCANS) that overcomes the aforementioned limitations of previously developed chemoprophylactic nasal sprays, thereby achieving superior efficacy. [...] To ensure safety during daily or repeated use, PCANS was meticulously designed as a "drug-free" formulation, incorporating biopolymers surfactants, and alcohols that are listed in the inactive ingredient database (IID) or generally recognized as safe (GRAS) list of the Food and Drug Administration (FDA), and are present as excipients in commercially available nasal/topical formulations. These components and their unique concentrations were identified via a highly iterative approach aimed at maximizing sprayability, mucoadhesiveness, the capture of respiratory droplets, physical barrier property, pathogen neutralization activity, and nasal residence time. In vitro, PCANS demonstrated excellent physical barrier properties against multiple viruses and bacteria, and rapidly neutralized them, resulting in >99.99% reduction in the pathogen load. [...]

Overall, this extensive screening identified pectin [...] as the most effective [agent] for rapid neutralization of IAV [influenza A virus].

[.. ]

Altogether, our data on physical barrier property, spray pattern, mucosal retention, and neutralization indicate gellan, pectin, and BKC as the three critical components to formulate PCANS.

Yall. I can't even.

Pectin. Kills influenza A virus.

Pectin. Which comes from apples.

Discussion

We report a chemoprophylactic nasal spray, PCANS – a radically simple and scalable pre-exposure prophylaxis approach to offer protection against current and emerging respiratory pathogens. [...] PCANS embodies multiple advantages over previously developed chemoprophylactic nasal sprays. [...] Third, the "drug-free" nature of PCANS is favorable for the regulatory process, which could be tedious for chemoprophylactic approaches based on investigational new drugs such as IgM-14(62). Also, since all the components used in PCANS are commercially available off-the-shelf and require simple mixing without chemical modifications, our approach is amenable to scale-up and large-scale manufacturing.

1) Holy shit, they've come up with an antiviral nasal spray that's good for 8 hours, effective against a broad spectrum of viruses, from commercially available products, that you can make in your kitchen.

2) Okay, so, yes, it turns out an apple a day does in fact keep the doctor away. It's just that you have to shove it up your nose.

Canonical link: https://siderea.dreamwidth.org/1832343.html

0.

Protecting yourself from Covid requires understanding Covid correctly. One of the things that you should understand about Covid, and any infectious illness, is the dose-response relationship.

That's the fancy highfalutin' medical way of talking about a very simple idea you already have and use all the time: the bigger a dose of something you get, the stronger its effect on you.

This is usually true of medicines, of course, but it's also true of poisons. Consider lead poisoning, for example. Medical science tells us no amount of lead in the bloodstream is safe. But, as you're probably already aware, even so, having more lead in your blood is worse than having less. Somebody who has only 5 µg/dL of lead in their bloodstream is definitely lead poisoned, but they're in much better shape than somebody who has 500 µg/dL.

It turns out viruses and other infectious microbes are like poisons. Research strongly suggests viruses also have a dose-response relationship: generally speaking, the more of the virus you have inside of you, the worse your symptoms are and the greater the threat to your health.

( When you think about it, that's not really a surprise, is it? [Read more, 4,560 Words] )

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Two recent things of note in infectious disease news:

1.

Something's going on with chronic wasting disease (CWD) – a prion disease, like mad cow disease – in whitetail deer, and a couple of other species in North America: they're suddenly been a rash of stories about animals testing positive. I haven't found one news story that discusses this as a national phenomenon, just many local news stories announcing that infected animals have been found in various different states. This video, "'Zombie' deer disease is spreading" (2023 Nov 21, Fox 5 NY), has a talking head saying that it is now found in most states in the US.

Meanwhile, it turns out that back last summer, there was a research published that "Ticks may be able to spread chronic wasting disease between deer" (2023 Jul 7, U of Wisconsin press release, by Elise Mahon), that found that viable amounts of CWD prions are found in ticks that feed from infected deer, and it was already known that deer eat ticks off of one another. The press release involved an interview with the lead researcher which has the immortal sentence, "'[Ticks are] just like a little CWD Tic-Tac that are possibly being eaten by the deer,' Inzalaco says."

2023 May 15: Scientific Reports (peer-reviewed scientific research journal): "Ticks harbor and excrete chronic wasting disease prions" by H. N. Inzalaco, F. Bravo-Risi, et al.

2.

2023 Nov 20: CNN: "A mysterious respiratory illness is spreading among dogs and baffling veterinarians. Here’s what owners can do" Chris Boyette and Holly Yan:

From New Hampshire to Oregon, researchers are trying to figure out what’s causing an infectious respiratory disease among dogs that has turned deadly in rare cases.

The mysterious illness is described as an “atypical canine infectious respiratory disease,” the Oregon Department of Agriculture said in a November 9 news release. Symptoms include coughing, sneezing, eye or nose discharge and lethargy.

Veterinarians in Oregon have reported more than 200 cases of the disease since mid-August. Other cases have been reported in Colorado, Illinois and New Hampshire.

Read more at that link.

Or, "Everybody Else* Discovers the Existence of Post-Acute Infection Conditions"

* Meaning everybody but those that have them, those paying attention to those that have them, and the fine folks working in infectious disease.

So this was headline news when I got up on Friday and through at least Sunday (I've been busy, haven't checked since).

2023 Oct 7: CBS News: Similar to long COVID, people may experience "long colds," researchers find by Sara Moniuszko:

Some people may experience "long colds," or long-term symptoms following common colds, flu, pneumonia or other respiratory illnesses, similar to the pattern seen in long COVID, according to a new study from Queen Mary University of London.

Published in The Lancet's EClinicalMedicine journal Friday, researchers found that even people with acute respiratory infections who tested negative for COVID-19 could still experience long-term symptoms at least 4 weeks after infection, including coughing, stomach pain and diarrhea. [...]

While long-lasting symptoms, also known as post-acute infection syndromes, are "not a new phenomenon," the authors write, they often go undiagnosed due to a wide range of symptoms and lack of testing.

The study in question:

2023 Oct 6: eClinicalMedicine (peer reviewed journal): "Long-term symptom profiles after COVID-19 vs other acute respiratory infections: an analysis of data from the COVIDENCE UK study" by Giulia Vivaldi, Paul E. Pfeffer, et al.

Thoughts:

1) Man, that is not a great study. The two populations studied are, roughly, "those who had an upper respiratory infection and tested positive for COVID on an at-home test" and "those who had an upper respiratory infection and tested negative for COVID on an at-home test."

This means,

1.1) Some unknown percentage of the allegedly non-Covid subjects actually just had Covid, and were false negatives.

1.2) We have no idea with what pathogen the allegedly non-Covid subjects actually were infected, because they weren't tested for anything other than Covid. Not even influenza.

1.3) Consequently, contrary to the headlines, this study most definitely does not establish the existence of "long colds" because it never established that the condition the other patients had was a cold.

2) Nevertheless, it does seem to establish, "Hey, chuckleheads, post-acute infection syndromes are in fact a thing." I don't know that this actually needed establishing, but sometimes you have to act like you just discovered something in a moment in which the public is receptive to hearing about it to get the new concept to penetrate thick skulls. In which case: good job, researchers!

2.1) Unfortunately, by "the public" I mean an unfortunate number of physicians. (Stay classy, Meddit.)

3) Interestingly, there's a larger social context of hmmmmm. There was a recent paper – not even a research paper, a commentary, though it was published in a (allegedly) research journal, so looked like research to the unfamiliar – that got a lot of press as "proving" that Long Covid wasn't a thing. This earlier paper offered a bizarre argument that I'm not even going to try to explain right now (both because complicated, and also so wack you won't believe me) which the present paper, whether accidentally or on purpose, kind of treats as a bluff that they call. I have so much to say about that other paper and the present state of epistemology in medicine (not good!) that I might just write a whole post or two about just it. I had been going to try to explain it in terms of That Post I Had Made Explaining This Kind Of Shenanigan, only to discover that that post was approximately 10% written and still in my draft folder. (Eit.)

2023 Sep 25: NBCNews.com: "A blood test for long Covid is possible, a study suggests" (by Erika Edwards):

More than three years into the pandemic, the millions of people who have suffered from long Covid finally have scientific proof that their condition is real.

Scientists have found clear differences in the blood of people with long Covid — a key first step in the development of a test to diagnose the illness.
The findings, published Monday in the journal Nature [below – S.], [...] is among the first to prove that "long Covid is, in fact, a biological illness," said David Putrino, principal investigator of the new study and a professor of rehabilitation and human performance at the Icahn School of Medicine at Mount Sinai in New York.

[...]

Several differences in the blood of people with long Covid stood out from the other groups.

The activity of immune system cells called T cells and B cells — which help fight off germs — was "irregular" in long Covid patients, Putrino said. One of the strongest findings, he said, was that long Covid patients tended to have significantly lower levels of a hormone called cortisol.

2023 Sep 25: Nature: "Distinguishing features of Long COVID identified through immune profiling" (by Jon Klein, Jamie Wood, et al.) Abstract:

[...] Here, 273 individuals with or without LC [Long COVID] were enrolled in a cross-sectional study that included multi-dimensional immune phenotyping and unbiased machine learning methods to identify biological features associated with LC. Marked differences were noted in circulating myeloid and lymphocyte populations relative to matched controls, as well as evidence of exaggerated humoral responses directed against SARS-CoV-2 among participants with LC. Further, higher antibody responses directed against non-SARS-CoV-2 viral pathogens were observed among individuals with LC, particularly Epstein-Barr virus. Levels of soluble immune mediators and hormones varied among groups, with cortisol levels being lower among participants with LC. Integration of immune phenotyping data into unbiased machine learning models identified key features most strongly associated with LC status.

[The title is the actionable part. Most of the rest of this is just very interesting science.]

(h/t @unchartedworlds@scicomm.xyz)

2023 Sept 8: Northwestern Now (press release from Northwestern University): "COVID patients exhale up to 1,000 copies of virus per minute during first eight days of symptoms" (by Marla Paul) "First direct measure of SARS-CoV-2 viral copies exhaled over course of infection":

COVID patients exhale high numbers of virus during the first eight days after symptoms start, as high as 1,000 copies per minute, reports a new Northwestern Medicine study.

It is the first longitudinal, direct measure of the number of SARS-CoV-2 viral copies exhaled per minute over the course of the infection — from the first sign of symptoms until 20 days after.

On day eight, exhaled levels of virus drop steeply, down to near the limit of detection —an average of two copies exhaled per minute.

Northwestern investigators tested breath samples — collected multiple times daily from 44 individuals — over the entire course of infection to determine when a person is most infectious.

The study will be published in eLife and has been posted as a pre-print. [See below for link – S.]

Mild and moderately symptomatic patients with COVID still exhale large amounts of virus, though severely symptomatic cases exhale higher levels on average, the study reports.

Vaccinated and unvaccinated patients exhale similar levels of virus over the course of infection, the research shows.

The amount of virus being exhaled while infected was the same no matter which variant a person was infected with — people infected with Alpha exhaled just as much as those infected with Omicron, the study reports.

And:

“We developed this easy, cheap method and used it to collect over 300 breath samples from 44 patients over the course of their infections — multiple samples a day over multiple days,” Lane said.

With this new device, investigators detected viral RNA in 100% of specimens collected from COVID-positive patients who were within 10 days of symptom onset and in none of the specimens collected from COVID-19 negative patients — a very high rate of accuracy.

The study findings could be used to calculate the amount of time it takes for an individual to exhale an infectious dose of SARS-CoV-2, Lane.

“For example, if we assume the infectious dose for COVID is 300 copies, then a person who is exhaling 1,000 viral copies per minute would exhale an infectious dose in 20 seconds (highly risky in an elevator), whereas a person who is exhaling two viral copies per minute would exhale an infectious dose in about two hours (probably safe in an elevator),” Lane said.
It is not yet known what an infectious dose of viral airborne particles is.

Lots more fascinating stuff at the link above. (This may be the best press release about a research article I've ever seen.)

The study:
2023 Sep 8: medRxiv (pre-print server): "Quantity of SARS-CoV-2 RNA copies exhaled per minute during natural breathing over the course of COVID-19 infection" (by Gregory Lane, Guangyu Zhou, et al.):

Here, we collected exhaled breath specimens from COVID-19 patients and used RTq-PCR to show that numbers of exhaled SARS-CoV-2 RNA copies during COVID-19 infection do not decrease significantly until day 8 from symptom-onset. COVID-19-positive participants exhaled an average of 80 SARS-CoV-2 viral RNA copies per minute during the first 8 days of infection, with significant variability both between and within individuals, including spikes over 800 copies a minute in some patients. After day 8, there was a steep drop to levels nearing the limit of detection, persisting for up to 20 days. We further found that levels of exhaled viral RNA increased with self-rated symptom-severity, though individual variation was high. Levels of exhaled viral RNA did not differ across age, sex, time of day, vaccination status or viral variant.

Delightful serendipity this: going back through my old bookmarks looking for something else entirely, I tripped over this old article from 2017 - which I had totally forgotten about - but which tessellates with today's health headlines.

2017 July 31: inverse.com: "The Mediterranean Diet Only Works for Rich People, Study Says":

If you eat mostly fruits, vegetables, grains, carbs, and non-meat proteins, plus a moderate amount of seafood and dairy products, you're following the so-called "Mediterranean diet" based on the food traditionally eaten by people in the Mediterranean region, and you have a reduced risk of heart disease. But there's a major catch, according to a report on the ongoing "Moli-sani Study" published Monday in the International Journal of Epidemiology: The health benefits were more often experienced by wealthy eaters, because high-quality food in the diet doesn't come cheaply.

A team of Italian researchers from the Mediterranean Neurological Institute (I.R.C.C.S. Neuromed) have been working on the Moli-sani Study since 2005, administering questionnaires and performing health tests on more than 18,000 men and women from southern Italy. In this latest report, they explain how the socioeconomic status of participants has affected results.

Within the bracket of participants who best adhered to the Mediterranean diet – which is "measured by a score comprising fruits and nuts, vegetables, legumes, cereals, fish, fats, meat, dairy products and alcohol intake" – there was still a wide spectrum of results; in other words, participants who ate roughly the same amount of the appropriate foods did not exhibit the same health benefits. Wealthier and better-educated participants experienced a more reduced cardiovascular risk than others.

Researchers speculated that

"Quality of foods may be as important for health as quantity and frequency of intake," explained Licia Iacoviello, head of the Laboratory of Nutritional and Molecular Epidemiology at the institute, in a press release.

And now, today. We may have found the smoking gun:

2023 July 25: Neuroscience News: "AI Unlocks Olive Oil's Potential in Alzheimer's Battle":

[...]

The Mediterranean diet, rich in EVOO, has been associated with a reduced risk of dementia and cognitive decline.

[...]

The findings identified ten EVOO phytochemicals with the highest likelihood of impacting AD protein networks. Compounds like quercetin, genistein, luteolin, and kaempferol exhibited promising effects on [Alzheimer's disease] pathogenesis.

"EVOO" stands for "extra virgin olive oil". Olive oil comes in several grades, of which "extra virgin" is the highest. It comes from the first pressing of the highest quality olives in the best condition, and as such it has the highest concentrations of all of the desirable flavor-imparting chemical compounds.

The next grade down is "virgin olive oil". It's made from less good olives in less good condition, and consequently has additional chemical compounds in it that are not aesthetically pleasing, often a byproduct of the olives losing their freshness.

Further on down the scale is regular olive oil, called in the American market "pure olive oil". It's made by taking virgin olive oil and refining it, to remove the rancid notes - which also removes most of the other notes too; this would leave it pretty much completely characterless as an oil, so a bit of extra virgin olive oil is added back into it so it has at least a little flavor.

In an important sense, extra virgin olive oil is the least pure form of olive oil, having in it more of the essence of the olive - more of the olives' phytochemicals - which gives it its richer flavor, rather than just the bare oil, as the refined variety does.

It is, of course, usually the most expensive grade.

Sometimes it's not. As this article for the food industry explains, in times of poor olive harvests, various economic and logistical forces tend to result in simultaneous lower supply of regular olive oil and higher supply of EVOO, resulting in regular olive oil prices rising and EVOO prices dropping to meet in the middle.

But generally the way to bet, at least historically before the climate went to hell, was that EVOO was notably more expensive than virgin or pure olive oil.

Now the earlier article was about heart disease, and the newer article is about Alzheimer's disease; futhermore, this latter study is in silico, and has not been proved out on human subjects. But in light of this, I would not be surprised to find out that what differentiated the effect of the Mediterranean diet on heart disease between the rich and the poor was entirely due to the phytochemicals beneficial to heart disease being found in EVOO, and not in ordinary olive oil.

[Actionable, though highly speculative, for people with Long Covid/PASC]

2023 Apr 14: Frontiers in Immunology (peer reviewed journal): "Hypothesis: inflammatory acid-base disruption underpins Long Covid" by Vicky van der Togt and Jeremy S. Rossman.

Note: this is a journal article, but it's not an account of an experiment or other study. It's a hypothesis paper. It's not proving anything. It's making an argument, the point of which is, "Somebody should do science about this."

From the abstract:

Both acute and PASC patients show systemic dysregulation of multiple markers of the acid-base balance. Based on these data, we hypothesize that the shift to anaerobic respiration causes an acid-base disruption that can affect every organ system and underpins the symptoms of PASC. This hypothesis can be tested by longitudinally evaluating acid-base markers in PASC patients and controls over the course of a month. If our hypothesis is correct, this could have significant implications for our understanding of PASC and our ability to develop effective diagnostic and therapeutic approaches.

From the paper (emphasis mine):

[...] Based on studies on acute COVID-19, PASC and the related myalgic encephalomyelitis (ME; chronic fatigue syndrome), we hypothesize that an inflammatory acid-base disruption underpins PASC and that viral proteins, both acutely and persistently-expressed, cause disease symptomology through disseminated tissue damage and inflammatory acid-base disruptions.

In PASC, inflammation reduces microvascular blood flow (e.g. through endothelial inflammation, platelet and erythrocyte aggregation, clotting and neutrophil extracellular trap formation) (3), creating a hypoxic environment that causes cellular metabolic changes (e.g. anaerobic respiration) and altered tissue and immune functions (4). SARS-CoV-2 proteins also directly cause metabolic changes (5) similar to hypoxia, increasing anaerobic respiration and the generation of lactate and protons. Significant or persistent production of protons can exceed the cellular and systemic buffering capacity, causing localized or systemic acidosis that results in a range of symptoms, including muscle fatigue similar to that experienced after strenuous anaerobic exercise. As SARS-CoV-2 vRNA and proteins have been found in muscle tissue (6), this shift to anaerobic respiration may cause acidosis in skeletal, cardiac and smooth muscle even in the absence of strenuous exercise, leading to the most common symptoms of PASC: fatigue and muscle weakness (3). In PASC patients, abnormally high blood lactate has been found after even mild exertion, suggesting metabolic dysfunction and muscle acidosis (7). In ME, muscle usage also results in intramuscular acidosis with increased acid clearance time (8), suggesting that post-exertional malaise may be caused by persistent muscle acidosis following repeated use of hypoxic and metabolically-reprogrammed muscle tissue.

However, the body compensates for acidosis in multiple ways: by increasing the elimination of acidic compounds in the urine, by increasing bicarbonate production in the kidneys, by altering the expression of lactate dehydrogenase genes (LDH; mediating the interconversion of pyruvate to lactate) and by altering respiration to modulate the levels of CO2, and thus carbonic acid in the blood (9). In PASC patients, hyperventilation (10) may reflect a compensatory response to acidosis, lowering carbonic acid in the blood. However, over-compensation can lead to alkalosis, which is also seen in acute SARS-CoV-2 infections. 73% of patients with moderate-to-severe COVID-19 present with either acidosis or alkalosis (11), with acidosis or compensated respiratory alkalosis significantly increasing the risk of death (12). Similarly, acute disease outcomes were worse in patients with high or low blood bicarbonate levels (13) and in those with elevated LDH (14), suggesting that acidosis may play a role in the pathogenesis of acute COVID-19 (15). Additionally, dehydration during the acute infection, which can impair clearance of excess acid or base, increases the likelihood of developing PASC (16).

The effects of acid-base imbalance can affect any tissue, generating many of the symptoms of PASC, including brain fog, though acidosis in the blood does not typically affect the brain as the blood-brain barrier (BBB) is not freely permeable to protons. However, SARS-CoV-2 and viral proteins increase BBB permeability (17), which may enable the flow of protons into the brain. In addition, viral proteins have been found in the brain (3, 17) and may mediate metabolic reprogramming, inflammation and hypoxia. The resulting anaerobic respiration may directly affect the acid-base balance in the brain, as indicated by elevated lactate levels in the cerebrospinal fluid (CSF) in ME patients (18). Acidosis has been shown to impair executive functions (19), as seen in PASC patients suffering from brain fog (3). [...]

There's more. Read it at the link, above.

Now, this is where things get particularly interesting.

This hypothesis is tantalizing because if true, it suggests a line of investigation for treatment: can symptoms be ameliorated by tinkering with the body's acidity?

Well, as it happens, both authors themselves have Long Covid, and one of them has been informally experimenting on herself, and has discussed it on Mastodon.

2023 Apr 14: Vicky van der Togt @vickyvdtogt@mastodon.nl: https://mastodon.nl/@vickyvdtogt/110196831965873773

[...] I decided to put the hypothesis to the test and came up with a treatment consisting of multiple components that would, in theory, enable me to rebalance my acid-base levels.

After trying this treatment for a couple of days I started to see significant improvements in my full range of #LongCovid symptoms.

And after continuing this makeshift treatment for a couple of weeks, I improved to a point where I was completely and stably symptom free. Since then I’ve been working with Dr. Jeremy Rossman to put this mechanism on paper, so that it can be shared and further researched, tested, and proven.

( Vicky van der Togt on how she self-treated her Long Covid below this cut. CW: diet, exercise. )

[This is actionable]

A multi-site study of ICU patients with Covid found that "Dehydration during acute COVID-19 infection [...] is associated with protein degradation and physical long-COVID." That is opposed to mental long-COVID symptoms, for which they did not find a relationship.

2022 Oct 21: BMC Critical Care (peer reviewed journal): "Dehydration is associated with production of organic osmolytes and predicts physical long-term symptoms after COVID-19: a multicenter cohort study" by Michael Hultström, Miklos Lipcsey, et al. From the abstract:

The study includes 374 COVID-19 patients from the Pronmed cohort admitted to the ICU at Uppsala University Hospital. Dehydration data was available for 165 of these patients and used for the primary analysis. Validation was performed in Biobanque Québécoise de la COVID-19 (BQC19) using 1052 patients with dehydration data. Dehydration was assessed through estimated osmolality (eOSM = 2Na + 2 K + glucose + urea), and correlated to important endpoints including death, invasive mechanical ventilation, acute kidney injury, and long COVID-19 symptom score grouped by physical or mental.

Results

Increasing eOSM was correlated with increasing role of organic osmolytes for eOSM, while the proportion of sodium and potassium of eOSM were inversely correlated to eOSM. Acute outcomes were associated with pronounced dehydration, and physical long-COVID was more strongly associated with dehydration than mental long-COVID after adjustment for age, sex, and disease severity. Metabolomic analysis showed enrichment of amino acids among metabolites that showed an aestivating pattern.
Conclusions

Dehydration during acute COVID-19 infection causes an aestivation response that is associated with protein degradation and physical long-COVID.

Trial registration: The study was registered à priori (clinicaltrials.gov: NCT04316884 registered on 2020-03-13 and NCT04474249 registered on 2020-06-29).

So, uh, that old advice about drinking a lot of fluids if you get sick? Yeah, do that if you get Covid.

This result is particularly tragic – I mean no blame by this – in light of dehydration being used delibereately in ICU ARDS patients early in the pandemic to try to keep fluid out of the lungs, for want of much else to try.

[This is actionable!]

Summary:

So it turns out that high CO2 concentrations in one's local atmosphere may prolong the longevity of SARS-CoV-2 circulating as an aerosol.

A study into the factors that affect the viability of SARS-CoV-2 circulating as an aerosol finds it impacted by pH, living longer in more acidic environments.

CO2, which we exhale and which builds up in enclosed spaces, is acidic.

Consequently, flushing out indoor spaces with fresh air to reduce CO2 concentrations might not just dilute concentrations of exhaled SARS-CoV-2, it might kill it.

Details:

2023 June 20: Phys.org (press release from University of Bristol): "Scientists discover critical factors that determine the survival of airborne viruses":

Critical insights into why airborne viruses lose their infectivity have been uncovered by scientists at the University of Bristol. The findings, published in the Journal of the Royal Society Interface today, reveal how cleaner air kills the virus significantly quicker and why opening a window may be more important than originally thought. The research could shape future mitigation strategies for new viruses.
[...]

To conduct the research, the team used a next generation bioaerosol technology instrument that they developed called CELEBS (Controlled Electrodynamic Levitation and Extraction of Bioaerosols onto a Substrate), that allowed them to probe the survival of different SARS-CoV-2 variants in laboratory generated airborne particles that mimic exhaled aerosol. They examined how environmental factors, such as temperature and humidity, particle composition and the presence of acidic vapors such as nitric acid alter virus infectivity over a 40-minute period.

Through manipulating the gaseous content of the air, the team confirmed that the aerostability of the virus is controlled by the alkaline pH of the aerosol droplets containing the virus. Importantly, they describe how each of the SARS-CoV-2 variants has different stabilities while airborne, and that this stability is correlated with their sensitivities to alkaline pH conditions.

The high pH of exhaled SARS-CoV-2 virus droplets is likely a major driver of the loss of infectiousness, so the less acid in the air, the more alkaline the droplet, the faster the virus dies. Opening a window may be more important than originally thought as fresh air with lower carbon dioxide, reduces acid content in the atmosphere and means the virus dies significantly quicker.

(As a side note, if this is also true of influenzas, it would be yet another mechanism to explain the findings of William Brooks in his Oct 1918 article in The American Journal of Public Health, "The Open Air Treatment of Influenza" (also at https://ajph.aphapublications.org/doi/pdfplus/10.2105/AJPH.8.10.746 - this one a textual PDF, not just image): that the Spanish Flu patients hospitalized in the tent hospital on Corey Hill fared better than the ones hospitalized indoors.)

Freshening the air isn't the only way to reduce the acidity of the air:

Dr. Haddrell added, "Our results indicate that the high pH of exhaled aerosol drives the loss of viral infectivity. So, any gas that affects aerosol pH may play a role in how long the virus remains infectious in the air. For example, bleach gives off acidic vapor that may increase SARS-CoV-2 stability in the aerosol phase. Conversely, ammonia which gives of alkaline vapor may have the opposite effect."

Nor is that all they found. Here's the actual paper:

2023 June 21: Journal of the Royal Society Interface: "Differences in airborne stability of SARS-CoV-2 variants of concern is impacted by alkalinity of surrogates of respiratory aerosol" by Allen Haddrell, Mara Otero-Fernandez, et al.

[...] Using a next-generation bioaerosol technology, we report measurements of the aero-stability of several SARS-CoV-2 variants of concern in aerosol droplets of well-defined size and composition at high (90%) and low (40%) relative humidity (RH) upwards of 40 min. When compared with the ancestral virus, the infectivity of the Delta variant displayed different decay profiles. At low RH, a loss of viral infectivity of approximately 55% was observed over the initial 5 s for both variants. Regardless of RH and variant, greater than 95% of the viral infectivity was lost after 40 min of being aerosolized. Aero-stability of the variants correlate with their sensitivities to alkaline pH. Removal of all acidic vapours dramatically increased the rate of infectivity decay, with 90% loss after 2 min, while the addition of nitric acid vapour improved aero-stability. Similar aero-stability in droplets of artificial saliva and growth medium was observed. A model to predict loss of viral infectivity is proposed: at high RH, the high pH of exhaled aerosol drives viral infectivity loss; at low RH, high salt content limits the loss of viral infectivity.

There's lots in this paper, and I've only just begun to read it. Maybe more later! Thought I should get this out, so it gets out at all.

Okay, I really must share this with you.

2023 Apr 13: The Atlantic: "Nutrition Science’s Most Preposterous Result" (by David Merritt Johns): "Studies show a mysterious health benefit to ice cream. Scientists don’t want to talk about it."

Last summer, I got a tip about a curious scientific finding. “I’m sorry, it cracks me up every time I think about this,” my tipster said.

Back in 2018, a Harvard doctoral student named Andres Ardisson Korat was presenting his research on the relationship between dairy foods and chronic disease to his thesis committee. One of his studies had led him to an unusual conclusion: Among diabetics, eating half a cup of ice cream a day was associated with a lower risk of heart problems. [...]

Earlier, the department chair, Frank Hu, had instructed Ardisson Korat to do some further digging: Could his research have been led astray by an artifact of chance, or a hidden source of bias, or a computational error? As Ardisson Korat spelled out on the day of his defense, his debunking efforts had been largely futile. The ice-cream signal was robust. [...] “He and his committee had done, like, every type of analysis—they had thrown every possible test at this finding to try to make it go away. And there was nothing they could do to make it go away.”

[...]

“I still to this day don’t have an answer for it,” Mark A. Pereira, an epidemiologist at the University of Minnesota, told me, speaking of the association he’d stumbled upon more than 20 years earlier. “We analyzed the hell out of the data.”

Just that morning, I’d been reading one of Pereira’s early papers, on the health effects of eating dairy, because it seemed to have inspired other research that was cited in Ardisson Korat’s dissertation. But when I scrolled to the bottom of Pereira’s article, down past the headline-making conclusions, I saw in Table 5 a set of numbers that made me gasp.

[...] the international media coverage didn’t mention what I’d seen in Table 5. According to the numbers, tucking into a “dairy-based dessert”—a category that included foods such as pudding but consisted, according to Pereira, mainly of ice cream—was associated for overweight people with dramatically reduced odds of developing insulin-resistance syndrome. It was by far the biggest effect seen in the study, 2.5 times the size of what they’d found for milk. “It was pretty astounding,” Pereira told me. “We thought a lot about it, because we thought, Could this actually be the case?”

There were reasons to be wary: The data set wasn’t huge, in epidemiological terms, and participants hadn’t reported eating that many dairy-based desserts, so the margin of error was wide. And given that the study’s overall message was sure to attract criticism—Pereira recalled getting “skewered” by antidairy activists—he had little desire to make a fuss about ice cream.

[...]

Pretty soon, Pereira’s peers found themselves in the same predicament. Building on the 2002 study and the growing interest in dairy, researchers at the Harvard School of Public Health decided to break out some of their most powerful tools.

The results of Harvard’s first observational study of dairy and type 2 diabetes came out in 2005. Based on data collected from just one of their three cohorts, following men between 1986 and 1998, the authors reported that higher dairy intake, and higher low-fat-dairy intake in particular, was associated with a lower risk of diabetes. [...] Near the end of the Harvard paper, where the authors had arrayed the diabetes risks associated with various dairy foods, was a finding that was barely mentioned in the “almost exclusively” low-fat narrative given to reporters. Yes, according to that table, men who consumed two or more servings of skim or low-fat milk a day had a 22 percent lower risk of diabetes. But so did men who ate two or more servings of ice cream every week. Once again, the data suggested that ice cream might be the strongest diabetes prophylactic in the dairy aisle. Yet no one seemed to want to talk about it.

In the years that followed, research summaries generally agreed that high dairy intake overall was associated with a slightly reduced risk of diabetes, but called for more investigation of which specific dairy foods might have the greatest benefits. In 2014, Harvard’s nutrition team brought another dozen years of diet-tracking data to bear on this question. In this new study, total dairy consumption now seemed to have no effect, but the ice-cream signal was impossible to miss. Visible across hundreds of thousands of subjects, it all but screamed for more attention.

Following a pattern of incredulousness that was by then more than a decade old, Frank Hu, the study’s senior author and the future chair of Harvard’s nutrition department, asked the graduate student who’d led the project, Mu Chen, to double-check the data. “We were very skeptical,” Hu told me. [...]

So how did the Harvard team explain away the ice-cream finding? The theory went like this: Maybe some of the people in the study had developed health problems, such as high blood pressure or elevated cholesterol, and began avoiding ice cream on doctors’ orders (or of their own volition). Meanwhile, people who didn’t have those health problems would have had less reason to give up their cookies and cream. In that scenario, it wouldn’t be that ice cream prevented diabetes, but that being at risk of developing diabetes caused people to not eat ice cream. Epidemiologists call that “reverse causation.”

To test this idea, Hu and his co-authors set aside dietary data collected after people received these sorts of diagnoses, and then redid their calculations. The ice-cream effect shrank by half, though it was still statistically significant, and still bigger than the low-fat-dairy effect that Harvard had publicized in 2005. In any event, if people who received adverse diagnoses cut back on their ice cream, you might expect that they’d also cut back on, say, cake and doughnuts. So shouldn’t there be mysterious protective “effects” for cake and doughnuts too? “There should be,” Mozaffarian said. “That’s why the finding for ice cream is intriguing.”

[...] Two years later, when a team of researchers based in the Netherlands and at Harvard analyzed all the evidence it could find on dairy and diabetes, the yogurt effect popped out. A featured graph from the team’s 2016 paper in The American Journal of Clinical Nutrition summarizes data from about a dozen studies [...] The authors also found the ice-cream effect: Consuming as little as a half a cup per week was associated with a 19 percent reduced diabetes risk. [...]

[...]

Hu, the Harvard nutritionist, said that deciding what a study means requires looking beyond the numbers to what is already known about dietary science: “You need to interpret the data in the context of the rest of the literature.” Mozaffarian, Hu’s co-author, echoed this view. Still, he noted, “you’re raising a really, really important point, which is that when, as scientists, we find things that don’t fit our hypotheses, we shouldn’t just dismiss them. We should step back and say, ‘You know, could this actually be true?’ ”

Could the idea that ice cream is metabolically protective be true? It would be pretty bonkers. Still, there are at least a few points in its favor. For one, ice cream’s glycemic index, a measure of how rapidly a food boosts blood sugar, is lower than that of brown rice. [...holy shit. --S.] “There’s this perception that ice cream is unhealthy, but it’s got fat, it’s got protein, it’s got vitamins. It’s better for you than bread,” Mozaffarian said. “Given how horrible the American diet is, it’s very possible that if somebody eats ice cream and eats less starch … it could actually protect against diabetes.” The “Got Milk?” crowd also loves to talk about the “milk-fat-globule membrane,” a triple-layered biological envelope that encases the fat in mammalian milk. Some evidence suggests that dairy products in which the membrane is intact, such as ice cream, are more metabolically neutral than foods like butter, where it’s lost during the churn. (That said, regular cream has an intact membrane, and it hasn’t been consistently associated with a reduced diabetes risk.)

[...] “It’s been more or less replicated,” Pereira noted. “Whether it’s causal or not still remains an open question.” Mozaffarian agreed: “I think probably the ice cream is still reverse causation,” he said. “But I’m not sure, and I’m kind of annoyed by that.” If this had been a patented drug, he continued, “you can bet that the company would have done a $30 million randomized controlled trial to see if ice cream prevents diabetes.” [No, q.v. General Mills and Cheerios vs heart disease. -- S.]

To be clear, none of the experts interviewed for this article is inclined to believe that the ice-cream effect is real [...]

The problem with this line of thinking is that once you start contemplating all the ways that cultural biases can seep into the science, it doesn’t stop at dairy-based desserts. If the ice-cream effect can be set aside, how should we think about other signals produced by the same research tools? [...]

I recommend reading the whole thing. In addition to being deliciously amusing, it raises real and important questions about how science – particularly medical science – handles it when an unappealing finding get stuck in scientists' craws. Or doesn't handle it, as the case may be.

Alas, the above link is under a paywall, but you may find it is available as a freebie, or viewable elsewhere.

Sources, which really ought to have been linked in the original article, and all of which are free to read:

2018 Sep 07: Harvard T.H. Chan School of Public Health, Doctor of Science Dissertation: "Dairy Products and Cardiometabolic Health Outcomes" by Andres V. Ardisson Korat, advisor Frank B.Hu.

2016 Feb 24: The American Journal of Clinical Nutrition: "Consumption of dairy foods and diabetes incidence: a dose-response meta-analysis of observational studies" by Lieke Gijsbers, Eric L Ding [wait, that Eric L. (Feigl-) Ding? -- S.] et al. https://doi.org/10.3945/ajcn.115.123216

2002 April 24: JAMA (journal): "Dairy Consumption, Obesity, and the Insulin Resistance Syndrome in Young Adults: The CARDIA Study." by Pereira MA, Jacobs, Jr DR, et al. doi:10.1001/jama.287.16.2081 (Table 5!)

And now for some good news. "This compound cured mice infected with clinical bacterial isolates derived from patients with refractory bacteremia and did not evoke bacterial resistance."

Note that the following is not yet through human trials.

2023 Feb 15: eBioMedicine (peer-reviewed journal): "A broad-spectrum synthetic antibiotic that does not evoke bacterial resistance" (by Douglas M. Heithoff, Scott P. Mahan, et al.):

Summary

Background

Antimicrobial resistance (AMR) poses a critical threat to public health and disproportionately affects the health and well-being of persons in low-income and middle-income countries. Our aim was to identify synthetic antimicrobials termed conjugated oligoelectrolytes (COEs) that effectively treated AMR infections and whose structures could be readily modified to address current and anticipated patient needs.

Methods

Fifteen chemical variants were synthesized that contain specific alterations to the COE modular structure, and each variant was evaluated for broad-spectrum antibacterial activity and for in vitro cytotoxicity in cultured mammalian cells. Antibiotic efficacy was analyzed in murine models of sepsis; in vivo toxicity was evaluated via a blinded study of mouse clinical signs as an outcome of drug treatment.

Findings

We identified a compound, COE2-2hexyl, that displayed broad-spectrum antibacterial activity. This compound cured mice infected with clinical bacterial isolates derived from patients with refractory bacteremia and did not evoke bacterial resistance. COE2-2hexyl has specific effects on multiple membrane-associated functions (e.g., septation, motility, ATP synthesis, respiration, membrane permeability to small molecules) that may act together to negate bacterial cell viability and the evolution of drug-resistance. Disruption of these bacterial properties may occur through alteration of critical protein–protein or protein-lipid membrane interfaces—a mechanism of action distinct from many membrane disrupting antimicrobials or detergents that destabilize membranes to induce bacterial cell lysis.

Interpretation

The ease of molecular design, synthesis and modular nature of COEs offer many advantages over conventional antimicrobials, making synthesis simple, scalable and affordable. These COE features enable the construction of a spectrum of compounds with the potential for development as a new versatile therapy for an imminent global health crisis.

2023 Jan 29: ScienceAlert (science news): "Study of 500,000 Medical Records Links Viruses to Alzheimer's Again And Again" by Fleicity Nelson:

A study of around 500,000 medical records has suggested that severe viral infections like encephalitis and pneumonia increase the risk of neurodegenerative diseases like Parkinson's and Alzheimer's.

Researchers found 22 connections between viral infections and neurodegenerative conditions in the study of around 450,000 people.

People treated for a type of inflammation of the brain called viral encephalitis were 31 times more likely to develop Alzheimer's disease. (For every 406 viral encephalitis cases, 24 went on to develop Alzheimer's disease – around 6 percent.)

Those who were hospitalized with pneumonia after catching the flu seemed to be more susceptible to Alzheimer's disease, dementia, Parkinson's disease, and amyotrophic lateral sclerosis (ALS).

Intestinal infections and meningitis (both often caused by a virus), as well as the varicella-zoster virus, which causes shingles, were also implicated in the development of several neurodegenerative diseases.

The impact of viral infections on the brain persisted for up to 15 years in some cases. And there were no instances where exposure to viruses was protective.

Then there's this:

Around 80 percent of the viruses implicated in brain diseases were considered 'neurotrophic', which means they could cross the blood-brain barrier.

Huh.

One of the researchers explains that they were inspired by the recent discovery linking prior Epstein-Barr mononucleosis to Multiple Sclerosis (MS):

"After reading [the Epstein-Barr/Multiple Sclerosis] study, we realized that for years scientists had been searching – one-by-one – for links between an individual neurodegenerative disorder and a specific virus," said senior author Michael Nalls, a neurogeneticist at the National Institute on Aging in the US.

"That's when we decided to try a different, more data science-based approach," he said. "By using medical records, we were able to systematically search for all possible links in one shot."

First, the researchers analyzed the medical records of around 35,000 Finns with six different types of neurodegenerative diseases and compared this against a group of 310,000 controls who did not have a brain disease.

This analysis yielded 45 links between viral exposure and neurodegenerative diseases, and this was narrowed down to 22 links in a subsequent analysis of 100,000 medical records from the UK Biobank.

While this retrospective observational study cannot demonstrate a causal link, it adds to the pile of research hinting at the role of viruses in Parkinson's and Alzheimer's disease.

Here's the actual study:

2023 Jan 19: Neuron (peer reviewed research journal): "Virus exposure and neurodegenerative disease risk across national biobanks" (by Kristin S. Levine et al):

Highlights

• Identified 45 pairs of viral exposures associated with increased risk of NDDs
• Replicated 22 of the viral exposures/NDD pairings
• Replicated the previously reported Epstein-Barr and multiple sclerosis association
• Follow-up shows significantly elevated risk of NDD years after viral exposure

Summary

With recent findings connecting the Epstein-Barr virus to an increased risk of multiple sclerosis and growing concerns regarding the neurological impact of the coronavirus pandemic, we examined potential links between viral exposures and neurodegenerative disease risk. Using time series data from FinnGen for discovery and cross-sectional data from the UK Biobank for replication, we identified 45 viral exposures significantly associated with increased risk of neurodegenerative disease and replicated 22 of these associations. The largest effect association was between viral encephalitis exposure and Alzheimer’s disease. Influenza with pneumonia was significantly associated with five of the six neurodegenerative diseases studied. We also replicated the Epstein-Barr/multiple sclerosis association. Some of these exposures were associated with an increased risk of neurodegeneration up to 15 years after infection. As vaccines are currently available for some of the associated viruses, vaccination may be a way to reduce some risk of neurodegenerative disease.

Now, my biggest reservation about this study is that I am dubious about anything based on medical records for reasons I have discussed at length.

But it is intriguing, and I don't have a problem with the hypothesis, "hey, maybe infection has something to do with neurodegenerative disorder – let's check". It's not like I have a better idea of how to get at that information.

(h/t

cvirtue)

2023 Jan 26: Ars Technica (IT popular press): Antibiotic resistance induced by the widespread use of… antidepressants? (by Diana Gitig):

Jianhua Guo is a professor at the Australian Centre for Water and Environmental Biotechnology. His research focuses on removing contaminants from wastewater and the environmental dimensions of antimicrobial resistance. One of those dimensions is the overuse of antibiotics, which promotes resistance to these drugs.

Guo wondered if the same might hold true for other types of pharmaceuticals as well. His lab found that they definitely do. Specific antidepressants—SSRIs and SNRIs—promote resistance to different classes of antibiotics. This resistance is heritable over 33 bacterial generations, even once the antidepressant is removed.

[...]

To assess antidepressants’ potential effects on antibiotic resistance, Guo’s lab grew E. coli in the presence of physiologically relevant concentrations of five commonly prescribed antidepressants for 60 days and measured how well the bacteria grew on agar plates infused with different antibiotics. They looked at antibiotics with different mechanisms of action: some that worked by inhibiting DNA synthesis in the bacteria, others that worked by inhibiting protein synthesis, and others by inhibiting cell wall synthesis. They found that the antidepressants they tested induced resistance to multiple antibiotics—within a day.

This group did a ton of experiments to try to determine how this was happening, starting by sequencing the DNA, mRNA, and proteins of the antibiotic-resistant bacteria. They saw that the antidepressants caused the bacteria to produce reactive oxygen species, which can damage cellular components. This seemed to be essential for the evolution of antibiotic resistance, as the resistance didn’t arise when cells were grown without oxygen. The drugs also caused the bacteria to express more efflux pump proteins that shunt antibiotics out of the cell. Genetic mutations in the bacterial chromosomes that promoted multi-drug resistance were also more common.

The scientists then looked at time-lapse microscopy images of DNA moving between bacterial cells, a process that can enable the rapid spread of resistance genes. Guess what? The SSRI sped it up and increased its occurrence, allowing resistant bacteria to spread the resistance horizontally to their peers (in addition to vertically to their progeny).

Okay, that is a thing I had no idea was a thing. In other TILs:

The antidepressants also increased the percentage of bacterial cells that persist in the presence of high concentrations of antibiotics. These “persisters” aren’t quite antibiotic resistant, exactly—they have none of the genetic mutations that confer antibiotic resistance. They are still normal bacteria; they just randomly have a higher tolerance for antibiotics than their peers. The researchers generated a mathematical model of bacterial evolution, which suggests that antidepressants increase the rate at which both normal bacteria and persisters evolve into full-fledged multi-drug-resistant strains.

I am unclear how a bacterium can have more resistance to abx than its conspecifics without genetic differences. Epigenetics?

Anyways, here's the paper, though it's behind a paywall:

2023 Jan 23: PNAS (peer reviewed journal): "Antidepressants can induce mutation and enhance persistence toward multiple antibiotics" (by Yue Wang et al.)

Abstract: [...] Here, we demonstrate that antidepressants at clinically relevant concentrations induce resistance to multiple antibiotics, even following short periods of exposure. Antibiotic persistence was also enhanced. Phenotypic and genotypic analyses revealed the enhanced production of reactive oxygen species following exposure to antidepressants was directly associated with increased resistance. An enhanced stress signature response and stimulation of efflux pump expression were also associated with increased resistance and persistence. Mathematical modeling also predicted that antidepressants would accelerate the emergence of antibiotic-resistant bacteria, and persister cells would help to maintain the resistance. Overall, our findings highlight the antibiotic resistance risk caused by antidepressants.

Note: Maybe don't precipitously discontinue your antidepressant – if nothing else, that can be really uncomfortable (brain zaps are real), and depending on your personal situation, staying on an antidepressant anyways might be a risk woorth taking in your case – go talk to your prescriber about your concerns. It is also possible that these findings will not stand up to scrutiny, and it will turn out antidepressants are fine.

At this point, it would be sure nice if someone did a large population prescription records study to see whether antibiotic resistance (as evidenced, say, by someone being immediately put on a second antibiotic after a course of a first) happens more often in people taking antidepressants than not.

An autopsy study has found SARS-CoV-2 in the bodies of people who died of what we might term Long Covid. This, despite these subjects not testing positive for SARS-CoV-2 for months before their deaths. "Three of these patients remained PCR-negative for over 9 months" before they died.

Yeah, this looks like a smoking gun. After years of physicians insisting that once a Covid patient tests negative on a PCR nasal swab, they couldn't possibly still harbor an active infection, it would seem we have pretty good evidence that, yeah, they sure can.

Autopsies were performed on people who contracted COVID, seemed to clear the virus – testing negative – but never recovered, deteriorated and died anyways.

The study found live SARS-CoV-2 in the structures of the lungs, including the bronchial cartilage.

2023 January 18: The Journal of Pathology (peer reviewed science): "Persistent SARS-CoV-2 infection in patients seemingly recovered from COVID-19" (by Rossana Bussani et al.):

Abstract

[...] A few patients with COVID-19 appear to recover from acute viral infection but nevertheless progress in their disease and eventually die, despite persistent negativity at molecular tests for SARS-CoV-2 RNA. Here, we performed post-mortem analyses in 27 consecutive patients who had apparently recovered from COVID-19 but had progressively worsened in their clinical conditions despite repeated viral negativity in nasopharyngeal swabs or bronchioalveolar lavage for 11–300 consecutive days (average: 105.5 days). Three of these patients remained PCR-negative for over 9 months. Post-mortem analysis revealed evidence of diffuse or focal interstitial pneumonia in 23/27 (81%) patients, accompanied by extensive fibrotic substitution in 13 cases (47%). Despite apparent virological remission, lung pathology was similar to that observed in acute COVID-19 individuals, including micro- and macro-vascular thrombosis (67% of cases), vasculitis (24%), squamous metaplasia of the respiratory epithelium (30%), frequent cytological abnormalities and syncytia (67%), and the presence of dysmorphic features in the bronchial cartilage (44%). Consistent with molecular test negativity, SARS-CoV-2 antigens were not detected in the respiratory epithelium. In contrast, antibodies against both spike and nucleocapsid revealed the frequent (70%) infection of bronchial cartilage chondrocytes and para-bronchial gland epithelial cells. In a few patients (19%), we also detected positivity in vascular pericytes and endothelial cells. Quantitative RT-PCR amplification in tissue lysates confirmed the presence of viral RNA. Together, these findings indicate that SARS-CoV-2 infection can persist significantly longer than suggested by standard PCR-negative tests, with specific infection of specific cell types in the lung. Whether these persistently infected cells also play a pathogenic role in long COVID remains to be addressed.

P.S.

We owe an enormous debt to the patients and their families that gave their bodies to science upon their deaths, and to the scientists and physicians that believed these cases were worth studying.

2023 Jan 9: Neuroscience News, PR from University of Seville: "A Vaccine Against COVID-19 Found to Protect Against Infection and Brain Damage Caused by the Virus" (uncredited):

Summary: A new COVID-19 vaccine developed by researchers at the CNB-CSIC appears to protect against infection of the brain and neurological symptoms associated with coronavirus [IN MICE. - S.]

[...] it is unknown if the vaccines developed against COVID-19 prevent the spread of SARS-CoV-2 to the central nervous system and confer protection against brain injury.

Now, using a mouse model susceptible to the SARS-CoV-2 coronavirus infection, a multidisciplinary team of Spanish researchers [...] demonstrate the ability of SARS-CoV-2 to infect different regions of the brain and to cause brain damage, and how the CNB-CSIC vaccine fully protects against infection of the brain.

These findings are published in Nature Neuroscience.

[...] the researchers evaluated the efficacy of the vaccine against COVID-19 developed at the CNB-CSIC. To do this, they immunized mice with one or two doses of the MVA-CoV2-S vaccine, based on the modified vaccinia virus Ankara (MVA) expressing the spike (S) protein of SARS-CoV-2, and analyzed the capability to protect against infection and damage to the brain.

“The results obtained were spectacular, demonstrating that even the administration of a single dose of the MVA-CoV2-S vaccine completely prevents SARS-CoV-2 infection in all brain regions studied and it prevents associated brain damage, even after a reinfection with the virus. This demonstrates the great efficacy and immunogenic power of the vaccine that induces sterilizing immunity in the brain,” says Juan García-Arriaza.

Welp, I did not see that coming.

Warning: may be too good to be true. Also: don't know this would do anything for people who already have Long Covid. Also: from mouse-model to shots in human arms is a long, arduous process. The fastest – by far – any vaccine has made that journey was the mRNA Covid vaccine, and that took 11 months. There is no guarantee any candidate vaccine, such as this is, will succeed in proving out for humans.

But, hey, it could.

Also! From the same article, emphasis mine:

Researchers have studied the evolution of viral infection in different brain regions, noting that viral replication occurs mainly in neurons, producing neuropathological alterations such as neuronal loss, glial activation and vascular damage.

Oh, we know that now? That's a big deal to establish – not sure it was previously known, hadn't heard it if so.

Viral replication is a fatal process to the cell it happens in. If viral replication is happening in the neurons of the brain, then Covid attacks the brain very directly, basically eating the brain.

Here's the actual science:

2023 Jan 2023: Nature Neuroscience (journal article): "Full protection from SARS-CoV-2 brain infection and damage in susceptible transgenic mice conferred by MVA-CoV2-S vaccine candidate" (by Javier Villadiego, et al.):

Abstract:

Vaccines against SARS-CoV-2 have been shown to be safe and effective but their protective efficacy against infection in the brain is yet unclear. Here, in the susceptible transgenic K18-hACE2 mouse model of severe coronavirus disease 2019 (COVID-19), we report a spatiotemporal description of SARS-CoV-2 infection and replication through the brain. SARS-CoV-2 brain replication occurs primarily in neurons, leading to neuronal loss, signs of glial activation and vascular damage in mice infected with SARS-CoV-2. One or two doses of a modified vaccinia virus Ankara (MVA) vector expressing the SARS-CoV-2 spike (S) protein (MVA-CoV2-S) conferred full protection against SARS-CoV-2 cerebral infection, preventing virus replication in all areas of the brain and its associated damage. This protection was maintained even after SARS-CoV-2 reinfection. These findings further support the use of MVA-CoV2-S as a promising vaccine candidate against SARS-CoV-2/COVID-19.

As a side note, looking for more information about this candidate vaccine, I googled it, and discovered:

2022 Mar 16: Frontiers in Immunology (journal article): "MVA-CoV2-S Vaccine Candidate Neutralizes Distinct Variants of Concern and Protects Against SARS-CoV-2 Infection in Hamsters" (by Robbert Boudewijns, et al.)

Apparently there's already a study which shows its more general efficacy in hamsters, which, as you may recall, are a good model organism for COVID infection in humans.

(h/t

wobblegong)

[Interesting, educational, not actionable]

2022 Feb 14: The Tyee: "Is Our Pandemic the Ghost of the 1889 Russian Flu?" (by Andrew Nikiforuk) "The ‘dreaded disease’ that claimed 1.5 million looks a lot like COVID-19, including the long-term threat posed by ‘viral promiscuity.’":

In 1889, a mysterious disease arose in the Asian city of Bukhara, an ancient trade centre in what is now called Uzbekistan. [...]

The “dreaded Russian disease” persisted in waves over a five-year period, eventually killing more than 1.5 million people on a planet then inhabited by only 1.5 billion humans. It reappeared in 1900.

About one in 100 people infected by the contagion either died from pneumonia or experienced severe illness affecting the brain, lungs or stomach. The breadth and persistence of the outbreak reintroduced the word “pandemic” to the English vocabulary.

To this day, the little-known biological storm ranks as one of the globe’s great disease outbreaks in terms of scale and mortality.

Now, 133 years after that event, virologists and historians suspect that a novel coronavirus triggered the so-called “Russian flu pandemic.” Many view this pandemic as a dramatic historical preview of the current one — complete with variants, waves and longhaulers suffering from chronic neurological complications.

Here are five scenes from this fascinating and evolving story...

Click the link above to read the whole thing. About 20 minutes read. Highly recommended; fascinating science, relevant to our present situation, and implicitly horrifying commentary about the state of our medical science wrt infectious disease, e.g.:

First identified in 1967, OC43 accounts for about 10 to 30 per cent of all the sniffles and other minor ailments people associate with having “a cold.” As a consequence, medical authorities gave it short shrift.

In contrast, when veterinarians discovered a bovine coronavirus in Nebraska in 1971, they took a different attitude. The bovine coronavirus not only caused severe diarrhea in calves, but it was later found to cause winter dysentery in adult cows and shipping fever in feedlot cattle. Researchers eventually called the triumvirate illness — needing several factors to elicit sickness — Bovine Respiratory Disease Complex, or BRDC.

I'm going to stop now before I just wind up quoting the whole thing.

Recommended.

You've probably seen the headlines by now; I'm somewhat late bringing this to your attention.

The study was published in Nature, quite possibly the most prestigious science journal in the world.

2022 Dec 14: Nature (journal): "SARS-CoV-2 infection and persistence in the human body and brain at autopsy" (by Sydney R. Stein, et al.)

Abstract:

[...] Here we carried out complete autopsies on 44 patients who died with COVID-19, with extensive sampling of the central nervous system in 11 of these patients, to map and quantify the distribution, replication and cell-type specificity of SARS-CoV-2 across the human body, including the brain, from acute infection to more than seven months following symptom onset. We show that SARS-CoV-2 is widely distributed, predominantly among patients who died with severe COVID-19, and that virus replication is present in multiple respiratory and non-respiratory tissues, including the brain, early in infection. Further, we detected persistent SARS-CoV-2 RNA in multiple anatomic sites, including throughout the brain, as late as 230 days following symptom onset in one case. Despite extensive distribution of SARS-CoV-2 RNA throughout the body, we observed little evidence of inflammation or direct viral cytopathology outside the respiratory tract. Our data indicate that in some patients SARS-CoV-2 can cause systemic infection and persist in the body for months.

Here's popular press coverage:

2022 Dec 30: MedicalXpress.com: "Autopsies show COVID-19 virus in brain, elsewhere in body" (by Jim Wappes):

Analysis showed that SARS-CoV-2, as expected, primarily infected and damaged airway and lung tissue. But the researchers also found viral RNA in 84 distinct body locations and bodily fluids, and in one case they isolated viral RNA 230 days after a patient's symptoms began.

The researchers detected SARS-CoV-2 RNA and protein in the hypothalamus and cerebellum of one patient and in the spinal cord and basal ganglia of two other patients. But they found little damage to brain tissue, "despite substantial viral burden."

The investigators also isolated viable SARS-CoV-2 virus from diverse tissues in and outside the respiratory tract, including the brain, heart, lymph nodes, gastrointestinal tract, adrenal gland, and eye. They isolated virus from 25 of 55 specimens tested (45%).

[...]

Possible ramifications for long COVID

Senior study author Daniel Chertow, MD, MPH, said in an NIH news release that, prior to the work, "the thinking in the field was that SARS-CoV-2 was predominantly a respiratory virus."

Finding viral presence throughout the body—and sharing those findings with colleagues a year ago—helped scientists explore a relationship between widely infected bodily tissues and "long COVID," or symptoms that persist for weeks and months after infection.

This is a very big deal:

0) It is not usual for viruses to cross the blood-brain barrier. We've known for a while that it was possible for SARS-CoV-2 to do so, this is the first study to actually pop the cranium and check to see if it was in there, and: yep, that sure is the virus that causes Covid. In the brain.

1) The entire concept of Long Covid just swapped from being a syndrome in search of a causal hypothesis to a hypothesis for what the symptoms might be of the empirically established objective fact about Covid infection that it can attack the brain and persist in the body for months.

2) There is a phenomenon already known from at least two other viruses (chickenpox/shingles and herpes) that infect the nervous system, whereby the virus hides out in the nervous system, thwarting easy detection and then emerging years or decades later. This is now plausibly something Covid could do.

Now, none of this means that we have found the cause for Long Covid. (Still haven't really defined Long Covid. There is sort of a definition of PASC now, but it kinda sucks, and also there's at least an ICD code for it so – so help me – there are studies, or at least one study, where the clinical definition of Long Covid is, "patient had a doctor who put in the EHR/billed insurance for treating the patient for Long Covid".) This is a plausible cause. Or rather set of causes. A virus that attacks all sorts of different parts of the body can get up to many different kinds of mischeif.

And there's a lot of complexity with how infection can cause disease. There are infections which cause permanent damage to the body even after the infectious agent is completely gone; the persistence of actual virus is not actually necessary to explain Long Covid.

But it sure is hard to argue with.

Someday, maybe we'll get to live in a society in which when a bunch of patients report cognitive and affective symptoms, instead of the mainstream of doctors responding, "Phew, we thought it might actually be a real medical condition, but your symptoms are, having to do with the mind, self-evidently unimportant and signify nothing objectively real or clinically dangerous", they respond "OH SHIT, THE BRAIN'S INVOLVED."

That day is not today. But maybe not never, either.

2022 Dec 24: MedRxiv (pre-print, not yet peer reviewed): "Outpatient treatment of Covid-19 with metformin, ivermectin, and fluvoxamine and the development of Long Covid over 10-month follow-up" (by Carolyn T. Bramante, et al.)

It was a pre-registered(!) RCT(!) study of overweight adults with mild Covid (< 7 days sx), 10 months post infection, of the efficacy of three medications against Long Covid. (n=1,125)

The good news:

Metformin, the common diabetes drug, reduced the incidence of Long Covid dx by about 40% (6.3% in the metformin group and 10.6% in the metformin control).

The bad news:

Fluvoxamine (Luvox), the SSRI antidepressant previously found to apparently have a quelling effect on Covid infection and being investigated as a treatment for Covid (though that wasn't working out), was found to increase the incidence of Long Covid dx by about 35% (10.1% in the fluvoxamine group and 7.5% in the fluvoxamine control).

The definition of Long Covid they used:

Because the definition of Long Covid is rapidly changing, fluctuating symptoms are challenging to assess, and ICD codes lack specificity and sensitivity, the primary method for ascertaining Long Covid was participant-reported receipt of a Long Covid diagnosis from a medical provider.

Read the article for more details including dosing schedules. Oh, and the third drug was ivermectin, which was found to do fuck all either way.

0.

So, the straw-that-broke-the-camel's-back reason I fired my physical therapist earlier in December is that I expressed concern to him about the safety of two things, both of which he blew me off about. One of them was the safety of using NSAIDs to reduce inflamation of injured tissue, and then doing PT while thus medicated. He said that wasn't a concern, and I said I knew people who had used NSAIDs to work through the pain of repetitive strain injuries and made them much, much worse. He said "that's not a thing" and he knew of no cases where anybody ever hurt themselves by using NSAIDs, short of the standard GI problems or choking on the pills.

Uh-huh.

2022 Dec 27: Prevention.com: "Using Painkillers Like Ibuprofen May Worsen Joint Inflammation in Knees, Study Says" (by Arielle Weg) "Researchers found arthritis progressed after four years. ":

A recent study found that taking non-steroidal anti-inflammatory drugs (NSAIDs) such as over-the-counter pain relievers like ibuprofen or naproxen for joint pain due to osteoarthritis, a type of arthritis, may actually increase inflammation. [...]

Researchers set out to see how NSAIDs impact synovitis, the inflammation of the membrane lining the joint that has been found to play a role in progressing osteoarthritis. [...] They followed 277 participants from the Osteoarthritis Initiative Cohort with moderate to severe osteoarthritis who used NSAIDs as their treatment for at least one year between baseline and a four-year follow-up. These participants were compared to 793 control participants not treated with NSAIDs.

All participants in the study had an MRI of the knee, initially and during a four-year follow-up, to track cartilage thickness, composition, and other measurements to evaluate arthritis progression. The scientists found that long-term use of NSAIDs had no benefit, and joint inflammation and cartilage quality were worse at a four-year follow-up, compared to the control group.
[...]

The study’s lead author Johanna Luitjens, M.D., [...] hypothesized that those who are taking NSAIDs may be more physically active due to the pain relief, which could potentially lead to the worsening of synovitis. But, she noted that her research did adjust for physical activity in results. Additionally, it could simply be that though NSAIDs have anti-inflammatory effects, they cannot prevent synovitis. She added that more research is needed in the future.

Also, presented at the same conference, two different studies that found the same damn thing with corticosteroid injections in knee osteoarthritis:

2022 Dec 28: SciTech Daily PR from Radiological Society of North America: "Common Arthritis Treatment May Actually Accelerate Disease Progression" (unattributed):

Two recent studies have shown that corticosteroid injections, which are commonly used to treat the pain associated with knee osteoarthritis, may actually contribute to the progression of the disease. These findings were recently presented at the annual meeting of the Radiological Society of North America (RSNA).

[...]

In the first study, researchers at the University of California, San Francisco included 210 Osteoarthritis Initiative participants, 70 of whom received intraarticular injections, and a control group of 140 who did not receive injections during a two-year period. Of the 70 patients who received injections, 44 were injected with corticosteroids, and 26 were injected with hyaluronic acid. The treatment and control groups were matched by age, sex, body mass index, pain and physical activity scores, and severity of the disease.

MRI was performed on all patients at the time of the injection and two years before and after. The MRI scans were assessed using whole-organ magnetic resonance imaging score (WORMS), a grading system for knee osteoarthritis that focuses on the meniscus, bone marrow lesions, cartilage, joint effusion, and ligaments. The researchers identified osteoarthritis progression by comparing the imaging scores from the initial scans and two-year follow-up scans.

[...]

Statistical analysis showed that corticosteroid knee injections were significantly associated with the overall progression of osteoarthritis in the knee, specifically in the lateral meniscus, lateral cartilage, and medial cartilage.

But! Some good news:

Hyaluronic acid knee injections were not significantly associated with the progression of osteoarthritis in the knee. Compared to the control group, the group who received hyaluronic injections showed a decreased progression of osteoarthritis, specifically in bone marrow lesions.

“While both corticosteroid and hyaluronic acid injections are reported to help with symptomatic pain relief for knee osteoarthritis, our results conclusively show that corticosteroids are associated with significant progression of knee osteoarthritis up to two years post-injection and must be administered with caution,” Dr. Upadhyay Bharadwaj said.

“Hyaluronic acid, on the other hand, may slow down the progression of knee osteoarthritis and alleviate long-term effects while offering symptomatic relief.”

The second study was very similar, and used x-rays instead of MRIs, and found the same thing:

Compared to patients who received an injection of hyaluronic acid or no treatment at all, patients injected with corticosteroids had significantly more osteoarthritis progression, including medial joint space narrowing, a hallmark of the disease.

“Even though imaging findings for all patients were similar at baseline, the imaging hallmarks of osteoarthritis were worse two years later in patients who received corticosteroid injections compared to patients who received hyaluronic acid injections or no treatment at all,” Darbandi said.

1.

Months ago I had occasion to throw down with a bunch of fat-phobic physicians (not mine) over their misuse of thermodynamics a la "calories in, calories out". As best I can tell, none of these people had ever actually taken a thermodynamics class? Do physicians typically take classes in thermodynamics?

Anyways, I yanked their bad physics out of their hands and beat them with it, explaining that is not how thermodynamics works, pointing out what they were saying was effectively modeling humans as both perfectly efficient machines and consistently efficient machines, both of which were, given thermodynamics, wildly implausible, and that difference between humans in efficiency extracting calories from food is a very obvious explanatory hypothesis for differences in propensity to obesity, and that given the cases where fecal transplants from obese donors to non-obese recipients results in novel obesity in the recipient (observed in humans, reproduced experimentally in mice), it would seem that an obvious culprit is the GI microbiome.

This, uh, blew a few minds and upset some people.

Anyways:

2022 Dec 25: EurekAlert.org (AAAS) PR University of Copenhagen Faculty of Science: "Some guts are better than others at harvesting energy" (unattributed):

New research from the University of Copenhagen suggests that a portion of the Danish population has a composition of gut microbes that, on average, extracts more energy from food than do the microbes in the guts of their fellow Danes. The research is a step towards understanding why some people gain more weight than others, even when they eat the same.
[...]

The results show that roughly 40 percent of the participants belong to a group that, on average, extracts more energy from food compared to the other 60 percent. The researchers also observed that those who extracted the most energy from food also weighed 10 percent more on average, amounting to an extra nine kilograms.

Like I had said:

The new study in humans confirms earlier studies in mice. In these studies, it was found that germ-free mice that received gut microbes from obese donors gained more weight compared to mice that received gut microbes from lean donors, despite being fed the same diet.

Even then, the researchers proposed that the differences in weight gain could be attributable to the fact that the gut bacteria from obese people were more efficient at extracting energy from food.

More information about this study and its other interesting findings at that link.

Sibylla Bostoniensis

Everything Unravels, Everything Will Fade

How do you like them apples [sci/bio/med]

Covid and the Dose-Response Relationship [Covid, Sci/Bio/Med, Patreon]

CWD in Deer, Mystery Pneumonia in Dogs [pest, sci/bio/med]

Long Colds [sci/bio/med, Covid]

Study finds Long Covid characterized by immune disreg [sci/bio/med]

Covid exhalate drops only after 8th day of infection [COVID, sci/bio/med]

Economic class and the Mediterranean Diet [soc, sci/bio/med]

Long Covid: the acidosis/alkalosis hypothesis [COVID, sci/bio/med]

Study: dehydration during acute Covid predictive of physical Long Covid [COVID, sci/bio/med]

Aerosol SARS-CoV-2 found sensitive to pH, CO2 is acidic [COVID, sci/bio/med]

Fwd: Nutrition Science’s Most Preposterous Result [sci/med]

New class of antibiotics discovered: conjugated oligoelectrolytes (COEs) [sci/bio/med]

Study of 0.5M medical records links virus and dementia [sci/bio/med, neuro]

Cool. Cool, cool, cool. Antidepressants cause antibiotic resistance. [sci/bio/med]

Fwd: Persistent SARS-CoV-2 infection in patients seemingly recovered from COVID-19 [sci/bio/med]

Fwd: A possible vaccine against Long Covid [COVID-19, sci/bio/med]

Fwd: Is Our Pandemic the Ghost of the 1889 Russian Flu? [pestilence, sci/bio/med, COVID-19]

SARS-CoV-2 found in brain on autopsy [COVID-19, sci/bio/med]

Study re Long Covid: good news (metformin), bad news (fluvoxamine) [COVID]

Two Vindications: NSAIDS/Steroids/arthritis & obesity/microbiome; MECFS [sci/bio/med]

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