The Science of Masks 4: Mechanistic Studies
Dummies for dummies
Welcome to Part 4 of Me Ranting About Stuff While Half Watching Reruns of Dharma & Greg Because This Is All Very Frustrating. The title is a work in progress.
For anyone who needs to be brought up to date, we’re reading through the references compiled by the intern at the CDC who was told to make a web page justifying muzzling children. That’s about the most accurate summary I can think of.
Also, Dharma & Greg Episode 4: “And Then There’s the Wedding”. If that part matters to you then I’m seriously concerned that there might be something a bit wrong with one (or both) of us. Don’t worry, after we’re done with this endless series on masks we’ll watch Pacific Rim with the volume turned all the way up. Giant robots punching giant monsters!
The previous posts covered the intern’s references on asymptomatic spread, droplet vs. aerosol transmission, and some literature reviews. This time we look at the remaining references, which involve actual lab tests - these are all mechanistic studies on mask usage.
These studies are referred to as mechanistic because they look at the mechanics of the masks (for example what percentage of an aerosol is filtered) rather than trying to track numbers of people who are infected. These studies are performed in a laboratory setting rather than a healthcare or community setting.
1. Visualizing Speech-Generated Oral Fluid Droplets with Laser Light Scattering (Anfinrud et al. 20201)
This describes the results of an experiment to measure droplets emitted when speaking, and the effect of that droplet emission when a damp washcloth is placed over the mouth. Not exactly rocket surgery here, but more than I did, which was nothing.
This experiment is straightforward, utilizing a fluorescent microscopy light sheet, a 530 nanometer (green) laser, and an iPhone 11 Pro camera. Subjects were asked to speak and the brightness of the flashes recorded by the light sheet were used to estimate the number and size of the droplets generated. Then the subjects spoke with a damp cloth over their mouths, and flashes above the background level were recorded.
Yes, this is as simple as it sounds. Any high school science teachers reading this right now should consider replicating this experiment with their students. The most effective lessons are those in which real results are demonstrated, and in this case they could compare their own results with those of professional (we hope) researchers.
The authors make no statement about the prevention of transmission, simply noting that wearing a damp cloth over the mouth reduces the emission of droplets. Get used to this sort of thing. Unlike the useless bobbleheads you see on the evening news, actual scientists limit their statements to what their experiment showed, and try to avoid speculation.
We did not assess the relative roles of droplets generated during speech, droplet nuclei, and aerosols in the transmission of viruses. Our aim was to provide visual evidence of speech-generated droplets and to qualitatively describe the effect of a damp cloth cover over the mouth to curb the emission of droplets.
This one’s a real page turner. The excitement of the researchers just drips from the page.
They describe their data as qualitative (as opposed to quantitative) because no quantitative (numerical) analysis is included. In other words, the intent here was to show that fewer droplets are detected when speaking through the damp washcloth, but not to measure how many. Hardly an earth-shattering revelation here, but in their defense the authors were not trying to revolutionize the field. They just had the afternoon free.
This next one is really interesting, less because of what the authors do talk about than for what they don’t talk about.
2. Testing the efficacy of homemade masks: would they protect in an influenza pandemic? (Davies et al. 20132)
The authors of this study are very clear about their goal:
This study examined homemade masks as an alternative to commercial face masks. (Davies)
This was accomplished by having twenty-one (healthy) volunteers manufacture their own masks using cotton t-shirts, then having those volunteers wear their homemade masks and cough while the researchers measured the microorganisms being expelled.
Is this destroying some of the mystique of “peer reviewed, published research”? They had twenty-one people (their moms?) with sewing machines do some sewing.
[I don’t intend to mock the researchers about this aspect of the paper - they’re doing something very practical, that people who don’t have access to advanced medical equipment can do, to see if it might be helpful. I have other issues with the Davies paper.]
In the opening paragraphs of this study the authors mention a previous study on this subject, which seems to support the idea that community mask usage may be an effective strategy. The study they mention did not test homemade cloth masks, but rather surgical masks and P2 masks (which are also called N95 masks).
The authors briefly summarize that other study:
A recent prospective cluster-randomized trial comparing surgical masks and non-fit-tested P2 masks (filters at least 94% of airborne particles) with no mask use in the prevention of influenza-like illness. The findings of the study found that adherence to mask use significantly reduced (95% CI, 0.09-0.77; P=.015) the risk for infection associated with influenza-like illness, but that less than 50% of participants wore masks most of the time. (Davies)
The reference given for this trial is Face mask use and control of respiratory virus transmission in households (MacIntyre et al. 20093), and the authors of that paper carefully limit the scope of their results. Quoting from that paper:
We emphasize that this level of risk reduction is dependent on the context, namely, adults in the household caring for a sick child after exposure to a single index case. We urge caution in extrapolating our results to school, workplace, or community contexts, or where multiple, repeated exposures may occur, such as in healthcare settings. (MacIntyre 2009)
Notice how the Davies paper state findings from the MacIntyre paper without any of the qualifications listed in the paper. Adults, at home, caring for a symptomatic child - this is a bit analogous to a hospital situation - where the parent puts on the mask before treating the child, then removes the mask afterwards. They are not walking around all day dressed like banditos.
The statement made in the Davies paper, without this context, can easily by taken to mean that community mask usage will significantly reduce infection, even though the authors of the MacIntyre paper specifically caution against drawing that conclusion from their results.
Here’s a big red flag: the subject of the Davies paper is cloth masks, and they talk about this MacIntyre study yet they don’t mention another by the same author, which is referenced by the study they did cite. Of course cloth masks don’t look so helpful in that one.
That study, A cluster randomised trial of cloth masks compared with medical masks in healthcare workers (MacIntyre et al. 20154), compared health care workers (abbreviated HCWs) using medical masks, some with cloth masks, and a control group.
We have provided the first clinical efficacy data of cloth masks, which suggest HCWs should not use cloth masks as protection against respiratory infection. Cloth masks resulted in significantly higher rates of infection than medical masks, and also performed worse than the control arm. (MacIntyre 2015)
Wait, what?
The cloth mask group had a higher rate of infection than the control group? But people keep telling me there are no potential downsides to wearing masks!
Based on their results the authors did not recommend the use of cloth masks by health care workers.
In the interest of providing safe, low-cost options in low income countries, there is scope for research into more effectively designed cloth masks, but until such research is carried out, cloth masks should not be recommended. (MacIntyre 2015)
It is interesting that the authors of the Davies paper chose to cite one of the MacIntyre studies and not the other. The paper they directly cited used surgical masks and N95 masks, while the paper they did not cite used cloth masks, which is what the authors of the Davies paper were testing.
So the authors have cited the MacIntyre study which suggested that masks can reduce infection (although they had several cautions attached to that) while ignoring the MacIntyre study using cloth masks, and that had a negative outcome in the cloth mask group.
Returning to the Davies paper, the authors also urge caution, noting that masks would have minimal effect without the use of other preventive measures such as hand washing, respiratory etiquette, etc. In the case of health care workers the authors state that homemade masks might be useful but only as a last resort.
An improvised face mask should be viewed as the last possible alternative if a supply of commercial face masks is not available, irrespective of the disease against which it may be required for protection. Improvised homemade face masks may be used to help protect those who could potentially, for example, be at occupational risk from close or frequent contact with symptomatic patients. However, these masks would provide the wearers little protection from microorganisms from others persons who are infected with respiratory diseases. (Davies)
So the authors of this paper conclude that improvised masks should be viewed as a last resort option for health care workers who are in close or frequent contact with people who are symptomatic, but those masks would provide little protection otherwise.
Our findings suggest that a homemade mask should only be considered as a last resort to prevent droplet transmission from infected individuals, but it would be better than no protection.
“Better than no protection” seems like a risky claim, considering that there is evidence of potential harm from these same cloth masks. “Might be better than no protection” would be more accurate.
[On that note, Dharma just received a wedding gift from her mom:
“Dharma, I want you to have this. It’s the fertility goddess that presided over your conception.”
“You’re gonna have to fight your way through two forms of birth control, my little friend.”]
3. Aerosol Filtration Efficiency of Common Fabrics Used in Respiratory Cloth Masks (Konda et al. 20205)
As explained by the title, this study reports on testing of common fabrics to determine how much aerosol they are able to filter. The experiment used an aerosol mixing chamber and a sodium chloride aerosol generator to test the various mask materials as well as a surgical mask and an N95 respirator.
As one would expect, the materials result in a reduction in the amount of sodium chloride detected and the authors summarize their results nicely.
In summary, we find that the use of cloth masks can potentially provide significant protection against the transmission of particles in the aerosol size range.
This is a good example of a narrowly written conclusion that addresses just the results of the study - without further speculation. The authors state their study shows a reduction in the transmission of aerosol particles. This study does not look at infectious agents and makes no assertions about the likelihood of infection.
Notice that the authors say masks can potentially provide protection rather than something more definitive like masks will provide protection. This is a theme we will see repeated in many studies on this subject. It’s always may, might, maybe, could - because these are not clinical studies.
4. Performance of fabrics for home-made masks against spread of respiratory infection through droplets: a quantitative mechanistic study (Aydin et al. 20206)
This is actually a preprint of a study conducted recently, and is still in peer review. It was made available online at medRxiv.org. From that website:
Caution: Preprints are preliminary reports of work that have not been certified by peer review. They should not be relied on to guide clinical practice or health-related behavior and should not be reported in news media as established information. (Aydin 2020)
This caution is repeated in bold letters on the web page with the paper.
This article is a preprint and has not been peer-reviewed. It reports new medical research that has yet to be evaluated and so should not be used to guide clinical practice. (Aydin 2020)
The CDC intern must be getting desperate if he has to reference preprints. Whatever - even if this paper’s final published text is identical to the preprint, it is another mechanistic study and can be expected to show similar results to the others.
5. Potential utilities of mask-wearing and instant hand hygiene for fighting SARS-CoV-2 (Ma et al. 20207)
This paper contains the results of experiments on mask usage plus instant hand hygiene (immediate washing of hands after exposure) to block avian influenza virus. The authors also reviewed previous papers on mask usage to control influenza spread. From their own testing the authors conclude that hand wiping can remove most viruses from the hands.
This study suggested that instant hand wiping using a wet towel containing soap or sodium hypochlorite removed most viruses from hands. (Ma 2020)
Does anyone remember that time Anthony Fauci said masks were useless, and just wash your hands? You know, before The Science (TM) changed? This gives you some idea why. Anyone who has read studies on non-pharmaceutical interventions quickly realizes that there is very little evidence that any of them work, and that the one intervention most likely to be helpful is hand washing.
The authors in this study also make broad claims about the effectiveness of masks based on their testing. Note that the results for homemade masks really only apply if the masks are constructed in the same manner as those in the study, which makes sense given the wide range of available fabrics used in clothing and home products.
This study showed that N95 masks blocked nearly all the mock virus, and medical masks blocked approximately 97% of the virus, and the homemade mask blocked approximately 95% of the virus. Therefore, the medical masks are not fully protective in hospitals but are useful for common social occasions. When medical masks are in shortage, the homemade masks made of four‐layer kitchen paper (each layer contains three thin layers) and one layer of polyester cloth should be helpful, as indicated by this study. (Ma 2020)
The “kitchen paper”, per the study, is manufactured by a company in China and each layer actually contains three thin layers so this would make a total of thirteen layers for the homemade masks they tested.
On the plus side, apparently we are stealing technological advancements from China instead of the other way around. Now we know how to build their secret cheese cloth anti-chemical warfare hoods.
Although this is a mechanistic experiment and not a randomized controlled trial (RCT), the authors believe their mask design should be helpful. Of course if masks are effective then it should be possible to validate this claim in a randomized controlled trial. In the abstract the authors give their assessment of the literature on RCTs of mask usage:
Medical mask wearing which was supported by many studies was opposed by other studies possibly due to erroneous judgment. (Ma 2020)
“Erroneous judgment?” Is that science smack talk?
They don’t really go into a lot of detail on the “many studies,” but later in the paper the authors attempt to explain the “failure” of many randomized controlled trials to show benefits from mask wearing.
Some randomized controlled trials (RCTs) did not support the efficacy of medical masks because medical masks could not reduce infection rates of some viral respiratory diseases. Consequently, people in some countries opposed to using medical masks on common social occasions. In effect, the conclusions of these RCTs could be erroneous, as reflected by the following assumed scenario. (Ma 2020)
The next part is just glorious in its logical contortions, but for brevity (and sanity) I will condense it a bit. The authors describe a scenario in which they assume a certain number of opportunities for infection per individual per day, assume a given mask efficiency, and then calculate a 30% reduction in risk. It’s like watching a drunk guy trying to balance his checkbook. They go on to say that medical mask wearing may have therefore been merely inadequate to prevent infection in those cases rather than being useless to prevent infection.
Two references are also given for the original statement about RCTs although one of these reference may be an error. That reference is to a web page for a manufacturer of air purifiers (?really?), and on that page its author describes various studies on testing of mask materials and homemade masks. That page then has a link to another page on the same site discussing RCTs on mask usage. This may have been the intended reference, although it is not clear why the authors of the Ma paper chose to reference this online article rather than the actual studies being discussed. Maybe they hired the CDC intern’s roommate.
The other reference given is a literature review of RCTs on mask usage (Xiao et al. 20208). That review did not conclude that many studies support the use of medical masks, and after reviewing 10 RCTs of face masks their main finding was a lack of effectiveness.
The evidence from RCTs suggested that the use of face masks either by infected persons or by uninfected persons does not have a substantial effect on influenza transmission. (Xiao 2020)
The authors concluded that the RCTs simply do not provide evidence that any of the four NPIs being reviewed provide any benefit against influenza (the studies being reviewed were looking at influenza transmission). The authors of the review do not suggest that the RCTs are flawed, and this review would, in fact, have been a much more useful reference than the Ma et al. (2020) paper the CDC actually cited.
So in this paper the authors feel they have compelling evidence, although mechanistic, that masks should be effective in preventing some influenza infection and they assert the randomized controlled trials that fail to show this are flawed.
[I’m taking a break right here. Someone sent me a random YouTube link for the movie trailer for Girls Und Panzer and I’m laughing too hard to continue.
“Tankery … a strong, but delicate art that aims to make girls and women alike more polite, graceful, modest and gallant, both on and off the battlefield.”
Apparently it’s about teenage girls in tanks shooting at each other for sport, as though this is a perfectly normal thing to do in middle school. I’m not making this up, go check for yourself.]
6. Respiratory virus shedding in exhaled breath and efficacy of face masks (Leung et al. 20209)
This is one of the references from the National Academies of Sciences letter described previously. In this study, 246 participants were recruited of whom 111 were infected with either coronavirus, influenza virus, or rhinovirus. The test group wore surgical masks and the control group did not wear masks. For both groups breathing samples were collected for 30 minutes, and those samples were analyzed for the presence of the three viruses.
For most of the non-mask wearing participants the researchers were not able to detect viruses at all, despite having confirmed those subjects were carrying those viruses. In addition when they did detect viruses the amount detected was low.
Among the samples collected without a face mask, we found that the majority of participants with influenza virus and coronavirus infection did not shed detectable virus in respiratory droplets or aerosols, whereas for rhinovirus we detected virus in aerosols in 19 of 34 (56%) participants (compared to 4 of 10 (40%) for coronavirus and 8 of 23 (35%) for influenza). For those who did shed virus in respiratory droplets and aerosols, viral load in both tended to be low. (Leung 2020)
However, based on their testing the authors conclude that surgical masks could potentially be of benefit against viruses in droplets.
Our findings indicate that surgical masks can efficaciously reduce the emission of influenza virus particles into the environment in respiratory droplets, but not in aerosols. (Leung 2020)
They do point out the lack of detection of viruses in most cases is a potential issue with the study.
The major limitation of our study was the large proportion of participants with undetectable viral shedding in exhaled breath for each of the viruses studied. (Leung 2020)
This study then provides mechanistic data for the potential of masks to reduce the amount of virus shed into the air by an infected person, although only through droplets. The authors have therefore concluded that masks might be helpful.
[I have just realized that the show opened with Dharma already in her wedding dress, and she has worn it for every scene in the episode. In fact, except for the opening scene the cast have worn the same thing for the whole episode. Greg has been in his tux since the credits. I wonder how long it takes to film these things? Did this episode come in under budget?]
7. A quantitative assessment of the efficacy of surgical and N95 masks to filter influenza virus in patients with acute influenza infection (Johnson et al. 200910)
This report describes the results of an experiment with nine participants who had laboratory confirmed influenza.
All nine coughed onto petri dishes while not wearing masks, then while wearing surgical masks, N95 respirator masks, and again not wearing masks (I suppose the last one was in case they got all coughed out and had no more virus in them to spread). The petri dishes were then tested for the presence of influenza virus, and as to be expected there was less virus detected on the dishes used when wearing the masks.
The authors mention the purpose of surgical masks, namely that they are intended to prevent transmission of disease to patients but not to protect health care workers (HCWs). As such the design of the experiment, measuring influenza coming from the wearer, makes sense.
Surgical masks are designed to trap respiratory secretions (including bacteria and viruses) expelled by the wearer and prevent disease transmission to others. Surgical masks are not designed to prevent inhalation of airborne particles, and their ability to protect HCWs from disease acquisition varies. (Johnson 2009)
This study was published in 2009, at which time not much data existed on mask usage.
To our knowledge, this is the first human study to assess the comparative efficacy of surgical versus N95 masks in patients with laboratory-confirmed acute influenza and suggests that, within our study design, both masks are equally effective when used for short periods to prevent the spread of infection. (Johnson 2009)
In reviewing the limitations of the study, the authors point out that they did not demonstrate the virus they detected was infectious, but that their study has value in providing information to inform the the planning of larger studies in the future.
Also keep in mind that they are measuring petri dishes, not clinical outcomes. At no point does this study show more or fewer people getting infected. They just had sick people cough on things.
Third, we did not formally demonstrate that the virus detected in the study participants was infectious and could be transmitted to other individuals.
Thus, our data provide important preliminary information to allow appropriate planning for larger future study cohorts that focus on prevention of influenza dissemination and protection from acquisition of influenza. (Johnson 2009)
The authors have concluded that N95 masks are not more effective than surgical masks, over the three to five minute period of the study, and that the same effect may or may not be seen in actual clinical situations. So this is a small (9 participants), preliminary study showing mechanistically that masks may reduce transmission of viruses but does not demonstrate this translates into fewer infections.
Are you getting a sense of the theme here? The CDC wants to mask up your kids, and part of the justification is a study with 9 participants who coughed on petri dishes. How much do we pay these people? And why?
8. Effectiveness of selected surgical masks in arresting vegetative cells and endospores when worn by simulated contagious patients (Green et al. 201211)
In this study five surgical masks were tested by placing them on mannequin head forms that were modified with a nebulizer (something that creates a mist) and breathing simulator. Aerosols of both endospores and vegetative cells were transmitted through the masks and the presence of the endospores and vegetative cells was measured.
Based on the results, the authors conclude their experiment supports the use of surgical masks as a recommended intervention.
The arrestance of airborne vegetative cells and endospores by surgical masks worn by simulated contagious patients supports surgical mask use as one of the recommended cough etiquette interventions to limit the transmission of airborne infectious agents. (Green 2012)
So this study supports the idea that masks can limit the spread of airborne infectious agents but can not in any way be used to quantify that limitation. And of course they aren’t even working with actual humans, and no infection is being measured.
Summary those who weren’t fortunate enough to attend the Derek Zoolander Center for Journalists Who Can’t Read Good and Who Wanna Learn To Do Other Stuff Good Too:
So far we have a set of reports about observed cases, asymptomatic transmission (including one that draws conclusions based on no one getting sick), and lab studies where people blew stuff through masks. But none of them provides actual clinical evidence that masks stop infections.
In fact there is very little mention of that thing pharmaceutical companies are supposed to do before they sell a new drug: randomized controlled trials.
In the next post we will look at the interesting (and more useful) parts of the science, which the CDC intern apparently skipped when putting together the web page on masks.
So next time, Part 5: “Wait, the CDC could have told us about randomized controlled trials but decided not to?” along with Episode 5: “The Ex-Files” wherein Dharma meets Greg’s ex-girlfriend and light-hearted hilarity ensues.
Anfinrud P, Stadnytskyi V, Bax CE, Bax A. Visualizing Speech-Generated Oral Fluid Droplets with Laser Light Scattering. N Engl J Med. 2020;382(21):2061-2063. doi:10.1056/NEJMc2007800
https://pubmed.ncbi.nlm.nih.gov/32294341/
Davies A, Thompson KA, Giri K, Kafatos G, Walker J, Bennett A. Testing the efficacy of homemade masks: would they protect in an influenza pandemic?. Disaster Med Public Health Prep. 2013;7(4):413-418. doi:10.1017/dmp.2013.43
https://pubmed.ncbi.nlm.nih.gov/24229526/
MacIntyre CR, Cauchemez S, Dwyer DE, et al. Face mask use and control of respiratory virus transmission in households. Emerg Infect Dis. 2009;15:233-241.
https://pubmed.ncbi.nlm.nih.gov/25903751/
MacIntyre, C. R.; Seale, H.; Dung, T. C.; Hien, N. T.; Nga, P. T.; Chughtai, A. A.; Rahman, B.; Dwyer, D. E.; Wang, Q. A Cluster Randomised Trial of Cloth Masks Compared With Medical Masks in Healthcare Workers. BMJ. Open 2015, 5, No. e006577.
https://pubmed.ncbi.nlm.nih.gov/23413265/
Konda A, Prakash A, Moss GA, Schmoldt M, Grant GD, Guha S. Aerosol Filtration Efficiency of Common Fabrics Used in Respiratory Cloth Masks [published correction appears in ACS Nano. 2020 Jun 18;:]. ACS Nano. 2020;14(5):6339-6347. doi:10.1021/acsnano.0c03252
https://pubmed.ncbi.nlm.nih.gov/32329337/
Aydin O, Emon B, Saif MTA. Performance of fabrics for home-made masks against spread of respiratory infection through droplets: a quantitative mechanistic study. medRxiv preprint doi: 10.1101/2020.04.19.20071779, posted April 24, 2020. https://www.medrxiv.org/content/10.1101/2020.04.19.20071779v2
Ma QX, Shan H, Zhang HL, Li GM, Yang RM, Chen JM. Potential utilities of mask-wearing and instant hand hygiene for fighting SARS-CoV-2 [published online ahead of print, 2020 Mar 31]. J Med Virol. 2020;10.1002/jmv.25805. doi:10.1002/jmv.25805
https://pubmed.ncbi.nlm.nih.gov/32232986/
Xiao J, Shiu E, Gao H, et al. Nonpharmaceutical Measures for Pandemic Influenza in Nonhealthcare Settings—Personal Protective and Environmental Measures. Emerging Infectious Diseases. 2020;26(5):967-975. doi:10.3201/eid2605.190994.
https://pubmed.ncbi.nlm.nih.gov/32027586/
Leung NHL, Chu DKW, Shiu EYC, et al. Respiratory virus shedding in exhaled breath and efficacy of face masks [published correction appears in Nat Med. 2020 May 27;:]. Nat Med. 2020;26(5):676-680. doi:10.1038/s41591-020-0843-2
https://pubmed.ncbi.nlm.nih.gov/32371934/
Johnson DF, Druce JD, Birch C, Grayson ML. A quantitative assessment of the efficacy of surgical and N95 masks to filter influenza virus in patients with acute influenza infection. Clin Infect Dis. 2009;49(2):275-277. doi:10.1086/600041
https://pubmed.ncbi.nlm.nih.gov/19522650/
Green CF, Davidson CS, Panlilio AL, et al. Effectiveness of selected surgical masks in arresting vegetative cells and endospores when worn by simulated contagious patients. Infect Control Hosp Epidemiol. 2012;33(5):487-494. doi:10.1086/665321
https://pubmed.ncbi.nlm.nih.gov/22476275/