1 00:00:10,940 --> 00:00:12,610 PROFESSOR: So we've discussed the extent 2 00:00:12,610 --> 00:00:15,640 to which the size of a droplet can influence 3 00:00:15,640 --> 00:00:19,200 the infectivity or the ability of a virion 4 00:00:19,200 --> 00:00:22,510 to escape from that droplet and, also, to be transmitted 5 00:00:22,510 --> 00:00:26,440 to the deepest, smallest passages in the lungs 6 00:00:26,440 --> 00:00:28,600 as a function of its size. 7 00:00:28,600 --> 00:00:31,660 There is also a dependence on the relative humidity 8 00:00:31,660 --> 00:00:33,790 of the air, which is related to size. 9 00:00:33,790 --> 00:00:36,340 And so, as we've seen, humidity does vary the size, 10 00:00:36,340 --> 00:00:38,590 but there's believed to be also a more direct effect 11 00:00:38,590 --> 00:00:42,000 of humidity, as I will now try to explain. 12 00:00:42,000 --> 00:00:43,930 So I'm relying here on the recent work 13 00:00:43,930 --> 00:00:51,380 of the group of Linsey Marr, two papers cited here. 14 00:00:51,380 --> 00:00:53,560 So we can distinguish between two different types 15 00:00:53,560 --> 00:00:54,400 of pathogens. 16 00:00:54,400 --> 00:00:56,800 The first are the bacteria. 17 00:00:56,800 --> 00:00:59,740 And here there's a monotonic dependence 18 00:00:59,740 --> 00:01:04,060 of the relative viability of the pathogen, of the bacteria, 19 00:01:04,060 --> 00:01:05,260 after a certain time period. 20 00:01:05,260 --> 00:01:06,860 Let's say one hour. 21 00:01:06,860 --> 00:01:10,480 And what is found is that, above a certain threshold 22 00:01:10,480 --> 00:01:13,539 of humidity, around 80% relative humidity, 23 00:01:13,539 --> 00:01:16,270 that there's, essentially, no change in the viability 24 00:01:16,270 --> 00:01:17,170 of the bacteria. 25 00:01:17,170 --> 00:01:17,860 They're alive. 26 00:01:17,860 --> 00:01:19,750 They're infectious. 27 00:01:19,750 --> 00:01:22,850 But, as the humidity, relative humidity, is reduced, 28 00:01:22,850 --> 00:01:25,539 then there's a significant drop off in viability, which 29 00:01:25,539 --> 00:01:28,890 depends on the specific type of bacteria, 30 00:01:28,890 --> 00:01:31,120 but it's a fairly general trend that it comes down 31 00:01:31,120 --> 00:01:33,789 significantly as you approach more dry air. 32 00:01:33,789 --> 00:01:38,420 Now what's happening is the size of the droplets is shrinking. 33 00:01:38,420 --> 00:01:41,930 In the case of the bacteria, we can understand, to some extent, 34 00:01:41,930 --> 00:01:46,460 why this dependence might be here by thinking about solutes 35 00:01:46,460 --> 00:01:49,970 that are present, especially salts, in the system, 36 00:01:49,970 --> 00:01:51,530 but, also, mucus-- 37 00:01:51,530 --> 00:01:54,710 mucosal proteins that we've also discussed. 38 00:01:54,710 --> 00:02:00,020 And, when the particles become more dry, then what happens 39 00:02:00,020 --> 00:02:01,700 is that the concentration goes up, 40 00:02:01,700 --> 00:02:04,310 and there's an increase in the osmotic pressure 41 00:02:04,310 --> 00:02:07,700 of the fluid around the bacteria relative to the inside. 42 00:02:07,700 --> 00:02:10,460 And, as with many other kinds of cells, 43 00:02:10,460 --> 00:02:14,210 when exposed to such high osmotic pressures, 44 00:02:14,210 --> 00:02:17,540 that can cause stress on the cell and, potentially, even 45 00:02:17,540 --> 00:02:20,660 rupturing of membranes or other structures within the cell. 46 00:02:20,660 --> 00:02:23,300 And, obviously, then it is not good for the viability 47 00:02:23,300 --> 00:02:26,220 of that cell and leads to deactivation. 48 00:02:26,220 --> 00:02:29,590 The case of viruses is a bit more complicated. 49 00:02:29,590 --> 00:02:36,090 So some old data of Harper from the 1960s on the seasonal flu, 50 00:02:36,090 --> 00:02:39,600 in particular, human influenza virus A, 51 00:02:39,600 --> 00:02:43,140 which was recently analyzed by Marr's group, 52 00:02:43,140 --> 00:02:45,329 showed that there was a viral deactivation 53 00:02:45,329 --> 00:02:47,820 rate that, essentially, was scaling linearly 54 00:02:47,820 --> 00:02:50,250 with the relative humidity. 55 00:02:50,250 --> 00:02:54,240 So there's a faster deactivation rate in more humid air, 56 00:02:54,240 --> 00:02:55,710 less in dry air. 57 00:02:55,710 --> 00:02:58,230 This is one way we can understand the seasonal nature 58 00:02:58,230 --> 00:03:02,020 of the flu in that, in more dry, wintry environments, 59 00:03:02,020 --> 00:03:03,490 especially away from-- 60 00:03:03,490 --> 00:03:06,840 in sort of the northern or southern hemispheres, 61 00:03:06,840 --> 00:03:09,150 we can expect that then the virus 62 00:03:09,150 --> 00:03:11,010 would be deactivating less. 63 00:03:11,010 --> 00:03:13,260 But, of course, that's compounded by the effect 64 00:03:13,260 --> 00:03:16,150 that, in the winter, people spend more time indoors, 65 00:03:16,150 --> 00:03:20,140 and so that's also leading to more seasonal transmission. 66 00:03:20,140 --> 00:03:21,810 Now, if we convert the deactivation rate 67 00:03:21,810 --> 00:03:25,260 into relative viability again, then we 68 00:03:25,260 --> 00:03:28,320 see an interesting dependence in recent experiments, which 69 00:03:28,320 --> 00:03:30,300 were done using bacteriophages, which 70 00:03:30,300 --> 00:03:35,310 are models of different kinds of human pathogens, 71 00:03:35,310 --> 00:03:40,440 including the seasonal flu and influenza viruses. 72 00:03:40,440 --> 00:03:42,690 And, in particular, there's a non-monotonic dependence 73 00:03:42,690 --> 00:03:45,840 where, essentially, there's a maximum rate of deactivation 74 00:03:45,840 --> 00:03:51,090 around the range of 70% or 80% humidity, or 60% to 80%. 75 00:03:51,090 --> 00:03:55,510 And, similarly, the viability was the lowest in that range. 76 00:03:55,510 --> 00:03:57,930 And the way the authors proposed to explain 77 00:03:57,930 --> 00:04:01,950 that was a hypothesis that there are solutes that are present, 78 00:04:01,950 --> 00:04:04,230 which may be, for example, sodium 79 00:04:04,230 --> 00:04:07,830 chloride or, in particular, chloride ions, perhaps, that, 80 00:04:07,830 --> 00:04:10,740 when we reach the higher concentration in the shrunken 81 00:04:10,740 --> 00:04:15,180 droplets, that there is, again, a stress on the virus, 82 00:04:15,180 --> 00:04:20,310 but, in this case, regardless of the details of the mechanism 83 00:04:20,310 --> 00:04:23,400 of deactivation for these encapsulated viruses, 84 00:04:23,400 --> 00:04:25,410 the idea is that the cumulative dose 85 00:04:25,410 --> 00:04:28,020 or exposure of those solutes is what's important. 86 00:04:28,020 --> 00:04:30,000 So, if the shrinking happens very fast, 87 00:04:30,000 --> 00:04:32,250 and we end up with a droplet nucleus of, mostly, 88 00:04:32,250 --> 00:04:35,340 bound water, and it happens over a short period of time, 89 00:04:35,340 --> 00:04:37,590 the exposure to those solutes is limited. 90 00:04:37,590 --> 00:04:41,100 And, hence, we end up with high viability, low deactivation 91 00:04:41,100 --> 00:04:43,470 rate in dry conditions. 92 00:04:43,470 --> 00:04:45,630 Conversely, in very humid conditions, 93 00:04:45,630 --> 00:04:46,740 the droplets stay big. 94 00:04:46,740 --> 00:04:48,480 In fact, they may even grow because 95 00:04:48,480 --> 00:04:50,670 of the hygroscopic solutes. 96 00:04:50,670 --> 00:04:53,250 And, in that case, there's plenty of solutes present, 97 00:04:53,250 --> 00:04:54,250 but they're very dilute. 98 00:04:54,250 --> 00:04:57,150 And so, again, the effect on the virus is minimal. 99 00:04:57,150 --> 00:05:00,780 And the greatest deactivation and, also, the maximum-- 100 00:05:00,780 --> 00:05:03,450 the sort of minimum viability is actually 101 00:05:03,450 --> 00:05:05,400 at an intermediate range of humidities. 102 00:05:05,400 --> 00:05:07,350 So this tells you that maintaining 103 00:05:07,350 --> 00:05:10,320 a comfortable humidity in the range of 50% to 80% 104 00:05:10,320 --> 00:05:14,490 may, actually, be the best for minimizing the viability 105 00:05:14,490 --> 00:05:17,480 of viral pathogens.