Adriaan Bax, molecular biophysicist and Chief of the Section on Biophysical NMR Spectroscopy at the National Institutes of Health
3rd APS COVID webinar – Adriaan Bax
Disclaimer: Many of my replies below are a matter of opinion, not peer-reviewed scientific facts. For the aerosol-related questions, I also urge you to tune in to the APS COVID Webinar on Dec 2 by Prof. Jose Jimenez. He is a world expert in this area; I am not.
Reply: Yes, very nice paper that also lists the backpressure generated by each of these materials. In my experience, the air resistance generated is a key factor. It's easy to make a 100% effective mask out of a plastic bag, but hard to breathe through it! The N95 and KN95 (as well as dust masks) solve this problem by having a cup shape, which has a large surface area that the exhaled/inhaled air can pass through while providing excellent filtration. The disadvantage is the "recycle volume": 150-300 mL of exhaled air never leaves the mask, forcing one to take deeper breaths such that the % of recycled breath becomes lower. This is a nuisance when at rest. Surgical and home-made masks tend to leak around the edges, in particular next to the nose, causing glasses to fog up, and lowering protection. They also offer less emission protection against coughing, where the burst speed of exhaled air is high, lifting the mask of the face. But they are perfectly fine for stopping speech droplets, because the flow volume per second while speaking is rather low.
Reply: I've used several but prefer the 3W 447 nm laser from www.laserglow.com. It has nice safety features and is very robust and fairly well focused. I've also used an 8W 452 nm laser purchased from China on Ebay, but it's too powerful, difficult to regulate, and not nearly as stable.
Reply: I believe people should adopt Donald Milton's definition https://doi.org/10.1093/jpids/piaa079
Droplets larger than 100 micron diameter will often not fully dehydrate before they hit the ground, and therefore the term droplet (or drop) seems appropriate. Anything smaller than that will fully dehydrate before landing (unless relative humidity is very high) and then hang around for close to a minute or longer. and from a disease transmission perspective therefore must be considered aerosol.
Reply: The optical resolution of my camera (SONY alpha SII, with thanks to Roy Sewall and Richard Chitty for recommending this gem) equipped with a FE 24mm, F1.4 GM lens) is only about 100 micron, so nowhere near good enough to directly observe particle size. However, scattering intensity scales with the square of the particle diameter, and particles with diameters down to ~0.5 micron are easily detected with the 3W blue laser and a 2 mm thickness of the light sheet. Dynamic range (8-bit), and log scale detection on these commercial cameras, with the conversion tables not quite matching the actual photon counts, is a bit of a pain.
Reply: The conventional definition is found in wiki, but from a COVID perspective it concerns transfer of infectious virus from an index patient to another person, followed by an active infection (at least one round of virus replication, typically resulting in ~1000 new virions). The recipient can remain without symptoms, but the disease has been transmitted.
Reply: The answer is not really known. Some virus may fare better at high humidity (polio), but most remain infectious longer at low RH and low temperature. Chemical reactions often require water, so it's conceivable that chemical reaction rates are slowed down upon full dehydration. Chemical reactions (e.g. lipid or structural protein oxidation) also slow down with temperature, leaving the virus intact longer.
Reply: All of our speed measurements are dominated by air convection. Even with no wind or airflow, convection in the presence of a human body, or any other temperature gradient generating factor, is enormous. The main difference between indoors and outdoors is the limited z dimension that applies indoors.
Reply: It's really MIE scattering that we're observing, so there is a very sharp angular dependence. However, unless fully spherical (glycerol droplets) the angular dependence in practice is fairly smooth, in particular for the larger particles, speculatively attributed to deviation from spherical shape of the tumbling particles.
Reply: I do not believe there to be any "free virus". Virions are tiny particles, covered by a rough ("spiky") hydrophilic (glycosylated and phospholipid headgroup) surface that can only leave the mucosal layer when embedded in a particle that contains saliva/mucous.
Reply: For sure, the observed droplets are not spontaneous nucleation of supersaturated exhaled air, because they are not seen when the same volume of air is exhaled through N95 mask material. However, 2 days after the presentation I discovered that the (battery-supplied) reference voltage on the hygrometer chip had dropped, causing the readout voltage (and reported relative humidity) to be lower than it should have been by about 0.5V. Difficult to tell how much that may have affected the RH values I reported for the measurements at 90% RH (made a week earlier). If the real RH was close to 100%, it indeed is likely that after exhalation of saturated 35C breath into the colder air, the particles may have become enlarged due to condensation rather than shrunk through evaporation.
Reply: To a good approximation, photon counts scale with the square of the particle diameter. So does the terminal velocity, so the relation between velocity and photon counts is fairly linear.
Reply: Yes, the very vast majority (in terms of numbers) of droplets fully evaporate before falling to ground. This even applies for relatively large droplets of diameters up to 100 microns, which then behave like aerosol and will be blown around by ventilation and convection currents. "Ballistic droplets" (larger than ~200 microns) typically fall to the ground prior to dehydration, and since they are still wet, I assume they will mostly stick to the surface on which they land. These would be the primary source for fomite transmission as they constitute a large fraction of the total emitted saliva (See Duguid's table in slide 43 of my presentation)
Reply: Within this range, respiratory particles will fully dehydrate, with the dehydration kinetics roughly scaling with (1 – RH). At higher RH, above ~70%, the kinetics may be impacted by the phase-separation phenomenon discussed by Vejerano and Marr (J. Roy. Soc. Interface, 2018), which could cause a substantially higher fraction of droplets in the 50-200 micron range to fall to the ground before full dehydration. However, from a comfort perspective, such high RH values are probably not feasible.
Reply: While asleep, mask use will not prevent self-infection through speech droplets. Although not measured, I anticipate that any droplets generated by snoring will be rather large as they do not originate from the vocal folds, and will not shrink to Milton's small aerosol size upon dehydration. However, if the infection is in the lungs, breathing particles could carry virus, and mask use while asleep could reduce exposure to others.
Reply: High humidity will increase the volume fraction of droplets that land prior to dehydration, and thereby reduce airborne exposure. High RH also reduces the time a virion remains infectious, although this time scale is in the hour range and I would expect this latter aspect not to be all that important. The precise relation between dehydration kinetics of oral fluid droplets and relative humidity is not yet known, so I can't give a quantitative number for the RH value where the increase in humidity provides a meaningful reduction in exposure. Based on Vejerano and Marr's numbers, I expect it to be somewhere in the 60-90% range.
Reply: Considering that documented outdoor transmission is at least an order of magnitude lower than indoors, whereas large droplet transfer (ballistic droplets in Milton's definition) should be comparable, I believe it is likely that the vast majority is through aerosol.
Reply: I expect we'll end up in an Asian-like scenario, where mask-wearing will remain fairly wide-spread in urban areas.
Reply: Removal of background aerosol is a critical aspect of all speech or breathing particle measurements, and even HEPA-filtered air is rich in particles in the 100-300 nm range. We are using about 10-20 air exchanges through two sequential high-pressure air filters to get the background down to non-detectable levels.
Reply: Only respiratory virus will exit the mouth in significant quantities while embedded in respiratory droplets (see D. Musher, N Engl J Med 2003;348:1256-66) with the high likelihood to become airborne. Other viruses, like hepatitis, Zika, or HIV are transmitted through other routes. Some pathogens, like TB, that predominantly colonize in the lungs (alveolar macrophages are often considered to be the primary host cells) will primarily exit through breathing, not as speech droplets.
Reply: You raise a very important point. The volume fraction of emitted droplets that remain airborne is relatively small. We believe that the numbers listed by Duguid are accurate for larger sizes (>~40 microns) but strongly undercount the smallest of particles. Xie et al. (Xie, X.; Li, Y.; Chwang, A. T. Y.; Ho, P. L.; Seto, W. H.: How far droplets can move in indoor environments - revisiting the Wells evaporation-falling curve. Indoor Air 2007, 17, 211) made a serious attempt to provide an improved quantitative evaluation of the small vs large volumes, but even they may not have been able to accurately quantify the total numbers of small droplets, considering that we see much larger numbers by laser light scattering.
Reply: As per above questions, the volume fraction of droplets that transform into aerosol remains ill-defined, with Duguid's ~5% providing a rough estimate. Most of this is "large aerosol" with an airborne lifetime of at most a few minutes, but that's still more than sufficient to travel well over 6 ft. Consider how far cigarette smoke travels in 1 minute, for example. Considering that even though the airborne fraction is a small fraction of the total emission, it is far more likely to result in disease transmission and therefore likely to dominate. I believe penetration through mask material is not the primary limitation for most masks in non-hospital settings. Even emission of tiny (~ 1 micron) breathing droplets is substantially reduced when forced to pass through a surgical mask. Whether this conclusion may be extrapolated to all other mask materials (e.g. spandex) remains an open question. Blocking inhalation of dehydrated breathing droplets, which have shrunk to well below 1 micron, and may be found in a hospital setting, will require high quality mask material such as KN95 or N95. With our laser setup, we can only easily measure the effect of masks on exhaled particles, however.
Reply: You are correct, I don't feel qualified to comment on the merits of antiseptic mouthwash. One might expect some benefit in terms of reducing emission, but impossible to quantify how much. We hypothesize that self-infection through speech droplets would involve primarily the smallest, vocal-fold generated droplets, which presumably would be little impacted by the use of mouth wash as they originate further down, where the mouthwash doesn't quite reach
Reply: You are correct, direct viewing of the size of droplets is impossible with a cell phone or other commercial camera without using a high degree of magnification. However, Stokes law allows measurements down to a few microns and below that, the correlation between scattered light intensity and particle size provides an approximate measure for size.
Reply: The probability of coalescence once emitted is extremely small considering the volume fractions we are dealing with (making a collision very unlikely). I defer to the fluid dynamics experts on commenting about break-up but have been told that this is not an easy/likely process.
Reply: I must refer you to the work of Charles Haas (e.g. Environ. Sci. Technol. 2015, 49, 3, 1245–1259) and his colleagues in the risk analysis community for a detailed answer to this question. My hand-waiving response: It is like buying lottery tickets. The chance that an inhaled virion causes an infection is low, but not zero. The more tickets you purchase, the higher your chances. In terms of the immune system becoming overwhelmed, as clearly applies for many other types of infections: It's difficult to envision how the immune response at one jeopardized cell is impacted by another infectious virion landing on a different cell that on a cellular size scale is many miles apart. Warning: Much of the medical community appears to disagree with Haas (and me) on this.
Reply: Good question and my apologies for having rushed through this too quickly. At the time the small vocal fold droplets are exiting the mouth, they are mostly still too large to be inhaled into the lungs. If one wears a mask, the vocal fold droplets will not get the chance to dehydrate and be re-inhaled as much smaller size particles. If stuck in the mask, they could be inhaled if dislodged, but that doesn't seem to happen considering the empirical observation that mask wearing reduces the severity of disease (Gandhi: DOI:10.1007/s11606-020-06067-8). The explanation by Gandhi does not make a lot of sense to me, because that explanation relies on the dogma "lower exposure causes lower disease severity". If that were true, the opposite result might have been expected: Masks lower disease incidence (by filtering out inhaled particles), but the smallest particles are known not to be well filtered out by generic masks. These smallest particles are associated with severe disease (Gralton: doi:10.1016/j.jinf.2010.11.010 ). So, if their interpretation were correct, one would expect lower incidence of disease, but that lower incidence should apply primarily to the upper respiratory tract, and therefore one would expect mask wearers that do get sick to have a higher degree of severity, contrary to observations.
Reply: From an emission perspective, covering the nose is only important when the person has an infection of the lungs, often (but not always!) associated with symptoms. From a protect-the-wearer perspective, covering the nose is very important.
Reply: Based on the literature, COVID-19 can infect a range of pets, but most seem to be less susceptible to the virus than humans
Reply: In principle, yes. In practice, the effect will not be very strong. My wife (the linguist) suggests cultural differences in language use, and person-to-person variation tend to be far larger than the typical variation in sounds associated with different languages.
Reply: Yes, it seems that the medical community had erroneously discounted the ability of virus to remain airborne when embedded in 5-100 micron particles.
Reply: Yes, there now is an avalanche of publications that aims to make this semi-quantitative analysis, many based on the Skagitt choir superspreader event where the numbers were fairly well defined. Most of these analyses are either on MEDXRIV or have just appeared (https://www.cdc.gov/mmwr/volumes/69/wr/pdfs/mm6919e6-H.pdf; see also the insightful analysis by J.L. Jimenez, COVID-19 Aerosol Transmission Estimator, https://tinyurl.com/covid-estimator )
Reply: I must defer to Jose Jimenez and his Dec.2 APS webinar for an answer to this question.
Reply: Computational fluid dynamics modeling should be very good for homogeneous droplets, but if phase separation (e.g. formation of an oil-like monolayer of phospholipid on their surface) is found to be important (e.g. Vejerano and Marr J. Roy. Soc. Interface, 2018), there may be problems with such modeling as phase separation seems mostly not to be accounted for.
Reply: As per above response, it is difficult to envision a physical mechanism by which exhaled air, which will be in the laminar flow regime,could dislodge virus from the high viscosity upper respiratory tract mucosal layer. If an athlete were having the infection in the lungs, exhaled breath could be infectious. However, outdoors, the quantity of exhaled breath emitted by another infected cyclist or runner that would be re-inhaled by others (despite quadratically increased risk, as both exhalation and inhalation increase with activity), I guesstimate this risk to be low, as for virtually all other outdoor activity. Indoor exercise is a different issue, however, and well documented cases of indoor exercise transmission exist. Not clear how much of this was speech or breathing mediated. See also: see also J.L. Jimenez, COVID-19 Aerosol Transmission Estimator, https://tinyurl.com/covid-estimator
Reply: Yes, velocities are comparable but sizes are not. The volume of exhaled droplets is 20-100 fold larger than for inhaled, dehydrated particles.
Reply: There are a number of documented airline transmission cases, although some but not all of these could be attributed to transfer inside an airline lounge. https://wwwnc.cdc.gov/eid/article/26/11/20-3299_article There are far more cases of passengers traveling in very close proximity to infected/infectious carriers for more than 8h where no transmission occurred. I note that air turnover and flow direction on modern jet aircraft is as good as one could hope for. However, not that cough droplets can escape the non N95/KN95 masks relatively easily due to the high burst flow rate of a cough, and exposure will never be zero and increase linearly with duration. Removal of masks during food service, combined with conversation, could be another factor.
Reply: Considering that documented outdoor transmission is at least an order of magnitude lower than indoors, whereas large droplet transfer (ballistic droplets in Milton's definition) should be comparable, I believe it is likely that the vast majority is through aerosol. I expect Jose to give you more information on this in his Dec. 2 APS webinar.
Reply: Yes, the nose is known to be a fairly efficient aerosol filter, so nose breathing decreases the probability of particles to reach the lungs. Quantitatively, I do not believe it is known by how much for what particle size range, and this percentage is likely to change with inhalation speed.
Reply: the fogging up of glasses is primarily caused by the supersaturation of the 95% RH 35 deg C air when it hits a cold surface (glasses), not by breathing droplets which are far too small in total volume to yield visible condensation.
Reply: we have not tested the efficiency of such masks, but there is a substantial amount of literature that suggests this material to work well. Question really is how breathable the material is and how tight the fit is.
Post webinar questions:
Reply: It seems unlikely that large particles that hit the ground within seconds will be blown around by any kind of ventilation. Exposure to medium sized particles that remain airborne for say 1 minute, will vary depending on prevailing airflow direction, which competes with regular convection currents. The restaurant superspreader event is an example where the directional ventilation flow overwhelmed the regular convection flow and shifted the fraction of infectees in a non-random fashion relative to the index case. Recirculation of ventilated air (if not passed through a HEPA) filter should be minimized, as has long been known: https://pubmed.ncbi.nlm.nih.gov/665658/
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