Which Mould Spores are Protective Against COVID-19?

Hi there and welcome to the final edition for 2021. Yes, it's our Christmas show for the Mould Show. And today I'm going to be presenting a fascinating research paper that just came out a couple of days ago in the research literature. But of course, we are focusing on fungus, and when we talk about fungi, many of you are probably thinking about the 2000 or so mushrooms that are actually edible.

Now, when you go to the supermarket, there's obviously a smaller selection than that, but just bear in mind that there are about 2000 known mushrooms that are edible.

Now, when we think about where we are exposed to moulds, you're probably thinking, well, they're probably all around. They're in the air we breathe, in the soil, as well as the built environment. And if you ask a biologist about how many different types of fungi or molds there are out there, certainly in the 1990s you would've been told that there were perhaps only maybe a couple of hundred thousand.

But fast forward to today and with modern genetic sequencing techniques, the number of fungi is around about 5 million. So there are a lot of different molds and fungi present all around us. But that's not surprising. But why do I want to bring this key statistic to your attention?

Well, this fascinating publication came out, and the topic of today is which mold spores are protective against COVID-19? And when I proposed this topic and when I was talking about it with a few people, I thought that this was a fantastic subject to bring to your attention for the close of 2021. Because certainly the last two years has been dominated by the COVID-19 pandemic. And obviously my interest in building biology and how the built environment impacts on health and wellness can't be underestimated.

So those two interests really dovetail together. And I want to bring to your attention this particular publication, which came out on December 16th, just a couple of days ago.

And we're going to dive straight into this publication because this is going to show you some key types of fungi and a way of looking at the fungi in the built environment to predict what the probability is that you or a loved one may have a severe adverse reaction to COVID-19. And then we're going to show how this result can be used to predict adverse health impacts for a range of other respiratory issues and diseases as well.

I'm going to jump into this publication quickly now. Now this paper came out, as I said, on December 16th, the title of it is on the left-hand side, I've put the DOI to medrXiv. It appeared as a pre-print. The title is: "The impact of environmental mycobiomes on geographic variation in COVID-19 mortality". Now that is a bit of a mouthful, but essentially what this paper is saying is that there is a subset of fungi that can be measured which are shown to correlate with adverse health.

And what the scientists did is that they examined something called the outdoor indoor diversity in 1,135 homes throughout the USA, and they found that a subset of fungi, and I've put a couple of the types of fungi that they highlighted as being strongly connected with the experience of serious adverse health from the SARS COVID-2 virus. And the typical genus that I want you to look at, which basically is the aspergillus component, and Aspergillus versicolor, that's the species type. But these particular genera, the Aspergillus, Eurotium, Epicoccum, and Alternaria, for example, have been shown to be strongly connected.

Now you might be asking why? And I urge you to download this publication, but there is a range of receptors in the human respiratory tract which are responsible for the SARS COVID-2 binding site. And similarly in allergy and inflammation too, respiratory pathogens and things in the environment, they also tend to lock into these similar receptors.

So the hypothesis goes that when preferentially mold is present, they're going to take up the ability of the receptor to bind to these foreign agents or entities. And it's going to select for the type of illness that you are going to become susceptible to.

And so I wanted to highlight firstly a couple of things about fungi. Fungi obviously grow and release spores. These spores are the reproductive units of replication, and they become airborne. And often they're a strong irritant to humans.

But the thing to bear in mind is that when we use spore traps, for example, to measure what's in the outdoor air, we're always interested in the relationship between the outdoor air to the indoor air. And certainly in the thousands of indoor air quality inspections that I've personally done, specifically in water-damaged building environments, often you'll see a skewness towards a different type of diversity.

And this is the key thing which this publication from Lawrence Berkeley Labs in the United States has discovered. And I'm really excited to bring this information to your attention for our Christmas edition.

But in order to explore exactly what we're talking about, I need to explain something called Beta Diversity. Now it sounds complicated but is really quite easy to understand, so just bear with me.

Obviously different places usually have different biological communities. Just think of the difference between an urban versus a country location. There's going to be different types of flora and fauna and types of people, and perhaps types of vehicles as well. And so the same metaphor analogy is capable of being applied to indoor air quality. And so we are looking for this Beta Diversity, which is defined as the extent of change in community composition or the degree of community differentiation in relation to the environment or a pattern in the environment.

And essentially what that means, and on the right-hand side of this slide I've put some examples to explain to you what Alpha, Gamma, and Beta Diversity stand for. So when you look at, for example, your outdoor air and then your indoor air for example in the lounge room, and maybe the indoor air in your bedroom, they're the sets that you're looking at and they represent these larger circles. And the types of mold spores that you might find in your outdoor air versus your lounge room versus your master bedroom are also reflected by the symbols in those sets, in the top panel of the figure on the right-hand side, that is entitled minimum differentiation.

And there are a couple of different ways of indexing what type of mold spores are present. And the first is something called Alpha Diversity, and this is the regional species difference. And then there is the Gamma Diversity and then there is the Beta Diversity.

Now in the show notes, I'm going to have all of the documents which allow you to drill into the detail to understand the different types of diversity.

But to make this very clear, in the top panel for minimum differentiation, you can see that in those three locations where mold spores were sampled, the same types of elements or spore types were found in each one of them. And so that means that the Beta Diversity with the Greek letter Beta is equal to one.

Now, if we look underneath at a different type of composition, where the outdoor, the lounge room, and the bedroom show different types of mold spores, we then get different measures for diversity. And you can see that the Beta Diversity down the bottom here has a number of three.

Now for the moment, don't worry about the exact specifics of how you go about calculating the Alpha, Gamma and Beta Diversity components of the equations. Just what I want you to understand is that there are obvious, intuitive differences between one location, another location, and a third location. And when you fin detail drill into what those spore types are showing you, you get to something called this Beta Diversity. And this turns out to be of fundamental importance to the assessment of health as this relates to coronavirus.

And you're probably wondering how on earth does this work? And I'm going to pull this up now in a series of extracts from the publication to focus on the important components of the research here.

And so what the scientists were looking at, and again, I've extracted one of the graphs here. And they were looking at whether COVID-19 mortality suppression occurs when outdoor fungi occurs indoors too.

So basically what I mean by this is that they discovered that when the levels and types of fungi found outdoors were the same as indoors, this suppresses the mortality associated with COVID-19.

And so when I explain the graph on the right-hand side in English, when indoor and outdoor fungal communities are similar, that means having a low Beta Diversity. COVID-19 mortality is reduced by over a factor of two versus homes with a high Beta Diversity.

Now, this is really, really groundbreaking research. And you can see by looking at the graph on the right-hand side, that as we move along the X-axis from the zero/zero mark over to the right-hand side, you can see that there is a clustering behavior which the scientists have put lines of best fit through to show you that as your Beta Diversity changes, that means the composition of the indoor living environment changes relative to the outdoors, the COVID mortality index increases.

Now that is really bad news because when this occurs it means that the impact on your respiratory health is much more serious. And over, when they validate this according to 1000 persons, they are able to determine what the impact of mortality is and then make comparisons between regions.

And remember the scientists did this across the United States, so they did this in all different types of climate. And they were able to deduce a lot of fascinating things. And I'm going to pull up another one of their figures now.

And when we drill into this this gets quite exciting, because they were also interested in correlating whether or not fungal diversity inside the home, inside your home or office, is a valid statistic to use to predict adverse COVID-19 outcomes. And they discovered that yes it was. And in fact, when they looked at the relative importance of this they were able to determine that public health policy was far less important than knowing what your indoor-outdoor Beta Diversity of fungal spores was.

Now, isn't that amazing? Think of all the public health policy initiatives for wearing masks and socially distancing, and even the mandates around vaccination, as opposed to other types of self-help approaches using nutraceuticals and positive lifestyle choices could be.

Imagine if measuring and knowing what your indoor air quality and mold spore levels were relative to outside. Could that predict your potential outcome with COVID-19?

And this groundbreaking research is saying, yes, in fact, it does. And in fact it's one of the most important statistics.

Also in this graph, I want to point out that the environment and soil pH is also important. In other live streams earlier this year I have talked about the importance of relative humidity, and the correlation with certain bands of humidity being able to suppress the likelihood of virus transmission within the home. And we've talked about a relative humidity optimum of around 50%. But that is also encompassed in the research by Lawrence Livermore National Labs.

And they also stress that the local environment and climate conditions are of course important, but they also show that the soil acidity has a big impact on the types of fungi that are selected for and are outdoors. And then conversely are able to enter into the house.

And the take-home message from this research is that fungal Beta Diversity is a much stronger predictor of COVID-19 suppression compared against other strategies like public health policies or the density of people in housing, but that variables like the acidity or alkalinity of the soil affects the microbe diversity present and therefore what might be found indoors.

So I'm going to reflect on that because I think that this is very important. I think you should recognize the importance of indoor-outdoor fungal spore levels as well. And to do this I'm going to now get to the seven fungi which have been identified as being fundamentally important to know what your counts are inside your home, but you must measure these outside and you mustn't measure them inside.

And certainly, there are a range of different ways you can do this. You can use viable Petri plates, you can also use spore trap tests, but you must be able to identify at least to these types of species that I'm going to put up on the screen next so you can measure the Beta Diversity and therefore replicate the groundbreaking research conclusions that these scientists make.

And I'm going to, again, put all the links to this in the show notes to this. So they will be available after this presentation for you to look at.

But now I want to stress that these are the seven different fungal species or... Well, really the genus of fungal types that you need to be looking for. And they include Alternaria, Aspergillus, Epicoccum, Eurotium, something called Toxicocladosporium. Now this is related to Cladosporium, I'm going to talk about this in a minute and explain the difference with Toxicocladosporium and standard Cladosporium.

We're also going to be talking or looking for Wallemia, Wallemia is again something which is commonly found in very salty foods or very sugar-rich foods and even things like bacon and nuts. And it is particularly common in water-damaged buildings because it needs a very low water activity.

So following a water inundation, a building can dry out and then easily become overgrown with species of Wallemia.

Now this last one, which is difficult to pronounce, Mycosphaerellaceae. Now this is a difficult one because these represent really thousands of different fungi that are found associated with plants.

So consider these as those fungi that grow on plants and may find their way inside to your home. So if we look at the Toxicocladosporium, then Cladosporium just as a fungus that I find in water-damaged buildings is particularly virulent and many people have a strong allergy to this.

Again, there are publications showing the extreme adverse health impacts for people who are exposed to this fungus, and if we drill into the clinical literature, I can find dozens of publications showing that the connection with adverse respiratory health is over 50, nearly 55%. And that often this fungus is found inside fluids and tissues of the body when susceptible people become colonized with this fungus.

From my own tissue or culture collection at my lab, I have a beautiful colony of Cladosporium, which I've got a micrograph up in the middle of the page. But I'm focusing attention on this to show you that these newer identified species like Toxicocladosporium, really are new taxonomic definitions on existing, genera like Cladosporium.

So the main takeaway here is that Cladosporium produces volatile, organic compounds, these mycotoxins that make people very unwell. Not just the direct infection. So whenever you were looking at your spore trap data for a home, you must look at the indoor-outdoor diversity for at least these seven classes of fungi. The Alternaria, Aspergillus, Epicoccum, Eurotium, Toxicocladosporium. And if that's not indicated which it isn't under the standard for spore trap analysis, look for Cladosporium as a surrogate.

Wallemia also may be noted certainly on visual inspection, and things like the proximity to garden beds abutting onto buildings, and the presence of indoor plants for example may give you an indication of whether or not the last class of these Mycosphaerellaceae are actually present inside your house.

Now, what I want to get back to now is talking about how you can take advantage of this, because you're probably thinking, well, this is all quite esoteric. I don't totally understand how to analyze for Beta Diversity.

And I'm going to explain to you how very simple this is to do. And to do this I'm going to pull up a graph of a spore trap that I did on a property maybe 10 days ago. And this particular property which I'm going to pull up now shows you the spore trap distribution for a building that I analyzed. And what this graph is showing you is the spore concentration in the air.

Now, this is the total number of spores in that particular location. And the first two columns in the graph represent the two outdoor controls.

Now, remember this publication is going on about making a comparison between your outdoor air and then your indoor air. So all of those bar graphs on the right-hand side of that graph are showing you your indoor levels. And a couple of things should jump out at you in this graph.

You can see that a lot of the rooms inside this house, such as the master bedroom, the third peak along from the left-hand side at the bottom of the graph, nearest to the outdoor controls, you can see that they're all quite similar in peak height or lower than the outdoor air. But some of them, like the master bedroom roof void near the en-suite or the bed two guest bedroom, or the bed two roof void or the upstairs roof void, those peaks that I've shown in red show firstly many more total count of spores.

Now that's a little bit different to the Beta Diversity that we need to focus attention on, but this flags your attention to the fact that those red peaked areas in this particular property are known to have suffered water damage and are showing problems to the occupants health. And that's why we were there to do the indoor air quality assessment on it.

But when we do spore trap testing, in the data that should be in your lab report, you're going to have a breakdown of all the different species that are found and you'll be able to do a back of the envelope type calculation to work out what your Beta Diversity is. And when I do the same thing relative to those green or control-level outdoor samples, I can immediately see in the data not only the species diversity but the total number of spores that are counted shows the dissimilarity.

And I've summarized this in English on the the top left-hand corner. The data shows the dissimilar in red peaks versus the orange indoor normal peaks versus the control or outdoor communities.

And this is how you do or dive in and dissect your spore trap data to determine whether or not you've got a problem.

And if we now move onto the last slide of this. Where are you going to go from here? What the authors concluded was that same same Beta Diversity, that means the outdoors looks the same as the indoors. You've got the same types of molds at about the same levels, so you're same same Beta Diversity. That is associated with a reduced SARS COVID-2 infection fatality ratio, a 4.7 or fewer mortalities per 1000 infections.

So when you've got the same levels of mold, give or take, same species diversity, you are to see just under five deaths per thousand infections with COVID.

Now, compare this to a water-damaged building, for example, or another type of building, which for a number of reasons may show a skewness or a difference in your indoor mold spore counts. You may see a dissimilar or a reduced Beta Diversity.

And when you see this out-of-kilter distribution between indoor-outdoor levels, this is associated with an elevated SARS COVID-2 infection fatality ratio of a bit over 12 persons or 12.4 mortalities per 1000 infections.

The take-home message that the scientists state in their paper is that the environmental microbiome, that is the fungi in the built environment, is an important missing link in our capacity to identify human populations that are vulnerable to poor outcomes from COVID-19. And it's not just COVID-19, there are a range of other respiratory allergens and other bacteria, yeasts and fungi, and other viral pathogens in the airspace, which are also breathed in.

So this type of research is fundamentally important to establish what your indoor air quality is like because as the research showed, the Beta Diversity is in fact statistically more important than policy interventions. Knowing your mold levels is more important ostensibly, according to Lawrence Berkeley National Labs, than the policy initiatives.

And their take-home conclusion was that this type of research underscores the importance of buyer surveillance in the built environment for not just COVID but for future pandemics.

As I said, I think that this is a groundbreaking piece of research. My name's Dr. Cameron Jones. I'm going to have this up in the show notes. I will put it on the blog to my website at biologicalhealthservices.com.au.

As we conclude 2021, I think it's important to stress that with all of the attention on COVID-19, other aspects of our health have really taken a back burner in a sense. But all of us are attuned to the fact that we could become sick at any moment, and research like this that I've presented today underscores the importance of each of us taking action in our own personal living environments and work environments to take control and take advantage of what the science says.

And the science is very clear, that fungal spores in the airspace are not just the hidden and visible things that might make you sneeze, but they can actually have a very significant, predictable impact on COVID-19 mortality.

In any case, my name's Dr. Cameron Jones. I'll look forward to bringing you more Mould Show live streams and podcasts next year. I hope you and your family have a wonderful Christmas break over this late December and a happy, healthy, and prosperous 2022.

Bye for now.

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REFERENCES:

The impact of environmental mycobiomes on geographic variation in COVID-19 mortality. December 16, 2021. Joshua Ladau, Katrina Abuabara, Angelica M. Walker, Marcin P. Joachimiak, Ishan Bansal, Yulun Wu, Elijah B. Hoffman, Chaincy Kuo, Nicola Falco, Jared Streich, Mark J. van der Laan, Haruko M. Wainwright, Eoin L. Brodie, Matthias Hess, Daniel Jacobson, James B. Brown

medRxiv 2021.12.14.21267549; doi: https://doi.org/10.1101/2021.12.14.21267549 

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Sandoval-Denis M, Sutton DA, Martin-Vicente A, Cano-Lira JF, Wiederhold N, Guarro J, Gené J. Cladosporium Species Recovered from Clinical Samples in the United States. J Clin Microbiol. 2015 Sep;53(9):2990-3000. doi: 10.1128/JCM.01482-15. Epub 2015 Jul 15. PMID: 26179305; PMCID: PMC4540897. 

Videira, S., Groenewald, J., Nakashima, C., Braun, U., Barreto, R., de Wit, P. and Crous, P., 2017. Mycosphaerellaceae – Chaos or clarity?. Studies in Mycology, 87, pp.257-421. 

Baselga, A., 2015. What is Beta Diversity?. [online] Methods Blog. Available at: <https://methodsblog.com/2015/05/27/beta_diversity/> [Accessed 23 December 2021].