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I had, a little while ago, a pretty decent idea inspired by some recent research papers on COVID-19 (specifically ones about the vaccine blood clot issue, and interactions with the microbiome). I liked the idea I had, and shared it with a few friends and acquaintances first, then, feeling like it deserved to be critiqued by actual hospital researchers, I took a gamble and sent an email to a lab at SickKids in Toronto. With luck it will get a positive response. I chose SickKids because when I was a baby they saved my life.

I have no idea if this idea is something other people have already thought of, or if it’s novel in whole or in part, but I’m hopeful that it at least spurs some creative thought, if nothing else. I can’t possibly research it alone- I would need to know a whole lot more about the human immune system, and my background is soil microbiology, plus I’m currently unemployed- but if this idea helps, I’m all for sharing. I’m reminded of the physicist who got magnets up his nose trying to invent a COVID-19 face shield- I hope this effort to assist research relevant to treating COVID-19 will be more helpful than that!

If I can find someone to critique it (basically, it’s a complex explanation for why certain people get differing symptoms from infection or the vaccines), and it passes muster, I’ll see about publishing it. I’ve learned that no one wants just a hypothesis, not even bioRxiv, so with any luck I can work with someone to test this so it can be shared. I know I could just put it on this blog but I would like to see it formally published if I can.

I also had some ideas for clinical trial data analysis- and how to analyze sets where there may be outliers, which is probably all of them, without just omitting the outliers, which could provide important data. I wrote a quick description of the idea but it’s pretty rough- a bioinfomatician friend looked it over and didn’t quite understand the key part. I need to word it a little more clearly. So I have to revise that, and then see if I can interest anyone in trying it out. It would probably be useful in studies of COVID-19 vaccine responses, given the rarity of responses like blood clots.

I’ve had more complicated ideas for how to contrast things like complex immune system responses over time, but that’s another story entirely. I am fairly sure when I make statements like this I’m not believed, but if I gave up every time someone told me I was unable to do a thing I’d be living in a basket.

So, I have been reading up on many earnest reports describing the difficulty in transporting ultracold vials of mRNA vaccines (Pfizer especially).

People routinely lyophilize (freeze dry) RNA for shipment to sequencing facilities, and for shipment from oligo suppliers. Lyophilized nucleic acids are stable even at room temperature, at least for some time. Even RNA.

Why didn’t anyone at Pfizer consider lyophilizing their concentrated vaccines (or lyophilizing the RNAs and then shipping the diluent separately, if this would be necessary) so they can be shipped just at refrigeration temperatures? All a person would have to do on the receiving end is add diluent to the RNAs, dilute with water if needed to make the final doses of vaccine, and at each step simply make sure that RNAs are fully dissolved (usually one just waits about 5-10 minutes), mixed (you can do this by inverting the tube a few times, or gently vortexed) and treated with care to prevent addition of RNAses. Or in the case of diluting a lyophilized vaccine, you simply add the diluent and wait for dissolution, and mix gently. Why is this considered too difficult for a lab technician in a hospital or clinic? The Pfizer vaccine already has to be diluted, so presumably someone is entrusted with the ability to dilute and mix and administer.

It might be the case that the liposomes the RNAs are in won’t survive lyophilization, but they might. And if they do not, how hard would it be to mix up a liposome mix from reconstituted RNA, lipids, and buffer? Extrusion machines are probably cheaper than -80C freezers.

Hello, readers! I am trying to make good on a recurring promise I make in this blog, to provide more papers on how gut bacteria affect the human immune system (and so by doing, affect many of the maladies that humans suffer from). Today I’m focusing on COVID-19 and two papers describing how dysbiosis (or a non-optimal assortment of organisms) can impact progression of symptoms. One is a hypothesis paper, and the other study is an actual investigation of samples from patients.

The first article was first published online in May 2020: Gut microbiota and COVID-19- possible link and implications. This is basically an hypothesis paper, and it outlines the case for the assortment of bacteria in your gut to affect pathologies occurring in the rest of your body. It mentions the gut-lung axis, how influences which affect gut microbiota composition will also affect immune system functioning (diet, exercise, stress) and suggests use of probiotics or prebiotics (food which helps promote the growth of probiotics) in preventing COVID-19 symptoms. I’ve suggested something along these lines myself, although I specifically suggest lactic acid bacteria and dairy products (see my last post).

The second article was published just last month, in September 2020, and is an investigation of the actual composition of the gut microbiome versus susceptibility to COVID-19. As suspected, there is a link: they found increases in bacteria which seem to promote inflammation and decreases in ones that had the opposite effects, when patients sick from COVID-19 were contrasted with healthy controls. This was a study on a limited number of patients (6 severely ill versus 15 healthy controls) but it is intriguing.

It’s not surprising that there is a link between dysbiosis and probability of contracting serious symptoms upon viral infection, since (a) the worst symptoms of COVID-19 have to do with runaway inflammatory reactions that over-stimulate your immune system (a cytokine storm) and we already know that many bacteria influence the human immune system, and (b) it’s already known that people who are older or have more pre-existing conditions (both states in which the gut microbiome is more likely to be dysbiotic) are also more likely to suffer severe symptoms when infected.

A treatment which is nonliving and yet can mimic the effects of a healthy microbiome containing many immune system modulating probiotics (I say “modulating” because you want your immune system to be at a healthy state somewhere between over-exertion and under-exertion) would be ideal, and I have some ideas about that but they obviously require development. If I had collaborators this would be possible, but I can’t really see a point at which this will happen.

Hello, readers.

I’ve recently been thinking about how to profile immune system responses and functioning (that is, turn the entire complex set of mechanisms and cascades into a profile that can be measured and categorized). I have no idea how naive this idea is although I am fairly sure others have had it, or similar ones, before me. I wrote up some of my thoughts as part of a job application and I am fairly certain that, since it is lengthy, this document either will not be read in its entirety or it will be dismissed. I have come to realize that whether a person is thought to have anything of value to contribute is a huge factor in whether people are listened to at all, or their contributions valued. It will be a nice surprise if I’m taken seriously.

I’ve also decided, today, to revise this website to take out comments on my attempts to fund and progress with research to do with the original purpose of this website, the crowdfunded Project: Cancer-Fighting Gut Bacteria, because in hindsight and in their entirety, they are actually extremely depressing. I hope to move forward in future with more summaries of published articles and reviews on work to do with gut bacteria and the immune system, and there has been plenty in recent years, even this year some involving COVID-19.

I’m also, without explaining my thought processes, going to encourage people to eat yogurt or other dairy products containing lactic acid bacteria until there is a pandemic cure. Lactobacillus, the genus of the bacterium I wanted to work with and did a preliminary week of work with in 2014, is one such; Bifidobacterium another. The probiotics commonly found in dairy products plus the dairy are what I suspect will be very helpful for avoiding the worst symptoms of COVID-19. It’s possible there’s some vegan alternative to be found which may be as helpful but based on what I suspect to be the case, it’s important to include dairy. I still need to do some more reading to see if I can figure out alternatives for non-dairy consumers (sauerkraut and kombucha exist but I’m not sure if the probiotics in them are as useful without the “growing media” of dairy in the background). I realize this paragraph is very mysterious but it’s potentially quite important and if anyone takes my ideas seriously, they either are not allowed to talk to me or I have not been able to talk to them.

I’ve given it a lot of thought. I haven’t been to a scientific conference in over four years, and my skills have atrophied with both disuse and the fact that I’ve been distracted by both illness and attempts to pursue my first love in life, writing fiction. My scientific career is basically on life support and I see no long-term future for me in science except perhaps as a science teacher or communicator. I’m hanging up my lab coat (metaphorically, since I do no bench work and haven’t for about five years) and picking up my stylus and I’m going to spend more time and effort in figuring out ways I can package information about things I understand so that the general public finds it interesting. This is another reason I am revamping this site to remove a lot of the “update” type posts and paragraphs describing my attempts to work independently as a serious scientist.

In future, I hope to spend more time each week on posting useful, brief summaries of current research into the gut microbes that influence animal (and human, we are animals) health, and venture also into debunking a lot of marketing claims for probiotics which sound good but are not based in actual science. There are a lot of factors which will impact whether a probiotic is effective: not just the probiotic strain(s) (although that is important), but your health and medical history, including immune system challenges and antibiotic use, what you eat, how much you sleep and whether you keep a constant sleep cycle during night or day, how much exercise you get, your genetic makeup, and what microbes already exist in your gut. I am not aware of a single clinical study which has tried to take all of these into account, and indeed, I don’t know that this is even feasible. In any case, I’ve read all kinds of claims about probiotics which just aren’t established with the current state of research, and I know from experience that companies will take one trial that seems to work and champion the microbes involved as cure-alls when in fact they have a use, but that use is naturally limited. I am not here to sell probiotics, not even the one I wanted to study which one can buy and which has been or will be involved in clinical trials (I have heard good, but vague, things about human interactions but have not seen any data).

The advice I gave out earlier in this blog still holds: get enough sleep, get exercise, eat the sorts of foods your doctor is always telling you to eat (whole grains, leafy greens and colorful vegetables or fruits, don’t overeat on meat and fatty or sugary foods, sensible portions, avoid snacking, avoid empty calories), and my personal recommendation for a probiotic is to do all of these things as well as eat yogurt/kefir if you possibly can. If dairy is impossible, it’s possibly the case that vegan options for food containing lactic acid bacteria (sauerkraut, kombucha) might be useful. Please just remember that probiotic pills won’t help at all unless they land in an environment in which the bacteria can thrive and function to help you, so it’s important to not just take the pills and change nothing else about your lifestyle.

Hello! I’ve recently heard stories of how Black Americans are more susceptible to COVID-19 (such as this older one, here), and while there are racial inequities in such things as access to health care and whether one is an essential worker or not (summarized here and in references cited), I can’t help but think about the Black Lives Matter movement, and wonder: How much disease susceptibility is due to chronic stress? It’s got to be more stressful stepping out of your home (or even existing in your home) wondering if police are going to find some pretext to kill you at any given moment.

Just a thought.

I wrote a podcast episode about clinical trials, and look forward to recording it. In the meantime, a new idea.

Bacterial communities on surfaces create biofilms with capsule, produced in varying amounts by different species under different conditions. The nature of the capsule produced may also vary. What if one could predict the infectivity of COVID-19 by looking at which lung mucosal communities produce which and how much capsule? Capsule, for nonspecialists, is jellylike gooey polymer produced by many bacteria, and bacteria vary in when and what kind and how much is produced.

It is not far-fetched to assume that gut communities, which impact or are affected by a lot of risk factors for severe COVID-19 symptoms, affect lung communities or vice versa (gut-lung axis) and that these in turn will impact the amount and composition of capsule produced. Which in turn may affect viral infectivity and symptom development. Is anyone looking at this? Would administering a probiotic to the lungs actually help prevent severe symptoms? Which strain to use?

Things to consider.

One thing that puzzles me: why did people focus on swabbing the back of the nasal cavity, which is a difficult and unpleasant task and unlikely to be carried out properly by untrained people (especially when one does this to oneself)? Why can’t you just cough sputum or swab the throat?

For that matter, why can’t particulates from the lungs be exhaled (or coughed, perhaps more than once) into a collection device (like one of the air filters in aerial microbiology, or this thing) and tested? Why can’t such devices be used in public spaces to monitor air quality, or used in hospital ventilators to monitor patient progress? I will bet anyone a bottle of hand sanitizer that this will be more effective. Tests that are easier to do are less likely to be screwed up.

If one captures DNA as well as RNA and uses whole metagenome sequencing methods, one can profile many different viruses and other aerial organisms. It might even be possible to identify if other microbes (bacteria, fungi, archaea, other viruses) are contributing either to symptoms or lack of such in patients, and coughing into a filter is less intrusive than a nasal swab.

I wrote this as part of an unrelated series of musings on how to best characterize mixtures of microorganisms from complex samples. Those musings remain so, but I thought the below was worth sharing. Dysbiosis is defined as a dysregulation of the gut microbiome such that its composition is altered, and this has negative impacts on the host organism.

Might also be useful for the study of bacteria that form biofilms which may keep out viruses in mucosal surfaces like lung, nasal, throat, or intestinal tissues: which bacteria are consistently positively or negatively associated with viral presence or infection and which form capsular material that might affect the ability of viral particles (like a coronavirus particle in the lungs) to infect? Does the gut-lung axis affect the composition or thickness of lung mucus, so making it more difficult to traverse in some patients but not others, and since gut microbiome composition is associated with so many pathologies (diabetes, heart disease, lung disease, obesity, psychological conditions, cancers, inflammatory diseases) might this by why there is a relationship between these pathologies (which may come with dysbiosis) and susceptibility to novel coronavirus as well as severe cytokine storms?

Your gut microbiome composition is affected by a lot of factors: sleep cycles, stress, diet, age, general health, exercise, and probably also your genetic makeup. This is still an emerging field of study and the complexity is appreciated but has not yet been untangled, so people marketing products claiming “this product boosts the immune system” are basically only doing that- marketing products. Beware of hype (and in the case of your immune system, making it more active might result in autoimmune disorders, so you really want to talk to an immunologist if you are concerned about your immune function- not some quack selling pills).

That being said, if it is possible for you to take healthy measures, like increasing exercise if you get too little, eating more colorful fruits and vegetables, getting consistent and adequate sleep, and managing stress in a healthy way, this would be expected to alter the composition of your gut microbiome if consistently applied, and it is known that these measures will help your general health (just ask your doctor). It’s never too late to take up healthy habits.

I started a podcast which covers information I hope will give people something to look forward to, namely ways in which treatments or vaccines can be found to end the pandemic and our social isolation. In the first episode I focus on the idea I’ve had for leveraging clinical trials that are currently underway to fight the pandemic. I really do think this is an important idea. I mention this a lot, but I think it bears repeating.

Future episodes will focus on how clinical trials work, and existing research done by others into promising treatments or vaccines for COVID-19 infection.

The podcast link is here:

I am also planning on putting these episodes on YouTube, under the channel SolvingThePandemic. These videos to follow. [EDIT: The first episode video is here.]

Thanks for any support or sharing. -Liz

Hi, everyone! For the idea, you can skip to the fourth paragraph.

Being bipolar, I usually work in fits and starts- nothing for a while, then all of a sudden a ton of ideas and inspiration come to me and I will have the energy to sit and work on them, and I can actually manage to get quite a lot done. My coworkers and former employers can tell you that I will go through times where I send spates of emails with new ideas, and these sometimes get passed over because, well, a brand new idea is a lot to deal with.

For my environmental studies, I had a couple of ideas in this current spate of productivity: to take some reports I had written a year ago or so and use them (the ideas in them, which are mine) to write methods/review articles describing the analyses I did and using the data I analyzed as an example of how to do it. I personally think the data, which dealt primarily with a tillage experiment, is worth publishing on its own but it would be impossible to make solid claims (too few data points), so I think that I’ll wind up presenting it in the context of being an example data set in a methods paper (on ecological network analysis, and another paper would focus on some more abstract ideas I have for looking at things such as functional redundancy in ecosystems using network data, and probably public datasets).

So that’s good. But I’m most proud of the idea I had today, which evolved over the course of the day as I thought about how to use existing data on the probiotic I studied in 2014, Lactobacillus johnsonii 456. I don’t know what stage clinical trials are at with this probiotic, but as the day progressed, I realized: this idea can be used for ANY CLINICAL TRIAL that is sufficiently advanced to have a large number of patients.

Here is the idea:

1. Clinical trial with lots of people: treatment, no treatment.

2. Take samples or use archived samples to determine if patients were infected with the virus. 

3. You now have four groups: treatment, no treatment, both with and without viral exposure.

4. Statistical analysis to determine if the treatment can reduce the probability of infection and/or reduce the probability of experiencing severe effects of viral infection.

So instead of starting a trial now and hoping that the drugs studied will work, and waiting 12-18 months for a result, we can take a look at everything that’s being studied now which is close to ending. The wide spread of the COVID-19 virus means that a lot of people enrolled in most trials could have been exposed, and it’s not unreasonable to assume that there may be enough to make statistical tests valid, assuming that we can assay patients for exposure to the virus adequately. It may be possible to use epidemiological data and the residence of each patient to determine the probability of when patients were likely to be exposed, if this is required in determining effects. It should be possible to track symptoms, especially for patients requiring hospitalization. And if patients are monitored from now on with this analysis in mind, if they do become ill they can be watched to see what happens.

It’s not ideal, but it is a potentially effective way to leverage a large amount of existing work to rapidly find treatments which can help protect (or alternately, increase risks) from COVID-19. Current efforts to contain the virus are not sustainable- and in the case of the USA, there simply is not enough medical equipment to be able to treat cases adequately. While the government struggles to find a response and states also are doing their best, the research community can step up, and see if their clinical trials can be used to assist in the race to find treatments, or identify additional at-risk groups which may not yet be considered.

[Note: I wrote two pieces, a short hypothesis paper- rejected from biorxiv for being a hypothesis, and rejected from mBio for not having enough supporting information- and a supplementary document with this trial idea plus some noodling where I pointed out the potential of the probiotic strain I studied to interact with genes in the human immune system. This last thing I tried to send to medrxiv and it was also rejected, because it was a proposal and not a research article. I’ve since revised my hypothesis though I haven’t revised the actual document, merely made notes. I lack the expertise required to finish some analysis requested by the mBio reviewers and resubmit, and I’ve been unable to find assistance, so essentially I am giving up. If more time goes by and I can’t find help, I may someday put it up on this website as a downloadable PDF, but it will probably never be taken seriously because of that.

I took out the saga of this process as well as some thoughts on how to use existing samples for studies relating to COVID-19 which, in hindsight, seem optimistic.]