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T r a n s m i s s i o n o f V i r u s e s i n D r o p l e t s a n d A e r o s o l s LINSEY C. MARR CHARLES P. LUNSFORD PROFESSOR CIVIL AND ENVIRONMENTAL ENGINEERING VIRGINIA TECH
20 MARCH 2020
Topics
1. Respiratoryviruses2. Transmissionmodes3. Sizedistributionsandevaporation4. Virusaerosoldynamics5. Impactofhumidity6. SARS-CoV-2
LinseyMarr,VirginiaTech,March2020https://phil.cdc.gov/Details.aspx?pid=11160
2
LinseyMarr,VirginiaTech,March2020 3https://www.intechopen.com/books/respiratory-disease-and-infection-a-new-insight/pathogenesis-of-viral-respiratory-infection
Virus Size
LinseyMarr,VirginiaTech,March2020 4
influenza0.1µm
SARS-CoV-20.12µm
rhinovirus0.03µm
https://www.cdc.gov/flu/resource-center/freeresources/graphics/images.htm,http://solutionsdesignedforhealthcare.com/rhinovirus,https://phil.cdc.gov/Details.aspx?pid=23312,https://pdb101.rcsb.org/motm/132
adenovirus0.1µm
Size Matters • Airbornevirusisnotnaked!
• Sizedetermines• Lifetimeintheatmosphere• Whereitdepositsintherespiratorysystem
0.1 µm
0.5 µm (0.2-100 µm)
respiratoryfluid
LinseyMarr,VirginiaTech,March2020 5
Modes of Transmission
http://www.phac-aspc.gc.ca/cpip-pclcpi/annf/v2-eng.php
direct contact indirect contact
large droplets aerosols LinseyMarr,VirginiaTech,March2020 6
Definedbymedicalcommunityas>5µmandhappeningatclose-rangeonly(<2m)
Definedbymedicalcommunityas<5µmandhappeningatlong-rangeonly(>2m)
Reality is More Complicated
LinseyMarr,VirginiaTech,March2020 7
The image cannot be displayed. Your computer may not have enough memory to open the image, or the image may have been corrupted. Restart your computer, and then open the file again. If the red x still appears, you may have to delete the image and then insert it again.
Tellieretal.,2019,BMCInfect.Dis,https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-019-3707-y
LinseyMarr,VirginiaTech,March2020 8
Droplets that are expelled into air can be inhaled, land on people’s mucus membranes, or deposit onto surfaces, where someone can touch them or they can be resuspended into air.
What size are these droplets?
Size Distributions: Breathing
LinseyMarr,VirginiaTech,March2020 9Johnsonetal.,2011,J.AerosolSci.,https://www.sciencedirect.com/science/article/pii/S0021850211001200
Diameter (µm) 0.1 1 10 100
Measuredbyaerodynamicparticlesizerovertherange0.3-20µm
Size Distributions: Speaking
LinseyMarr,VirginiaTech,March2020 10Johnsonetal.,2011,J.AerosolSci.,https://www.sciencedirect.com/science/article/pii/S0021850211001200
Diameter (µm) 0.1 1 10 100
Measuredbyaerodynamicparticlesizerovertherange0.3-20µm
Size Distributions: Coughing
LinseyMarr,VirginiaTech,March2020 11Johnsonetal.,2011,J.AerosolSci.,https://www.sciencedirect.com/science/article/pii/S0021850211001200
Measuredbyaerodynamicparticlesizerovertherange0.3-20µm
Corrected Size Distributions
LinseyMarr,VirginiaTech,March2020 12Johnsonetal.,2011,J.AerosolSci.,https://www.sciencedirect.com/science/article/pii/S0021850211001200
Measuredbydropletdepositionanalysisovertherange20-2000µm
Speaking
Coughing
Infe
rred
num
ber c
once
ntra
tion
in u
pper
resp
irato
ry tr
act
LinseyMarr,VirginiaTech,March2020 13
Breathing, talking, and coughing release droplets that range from submicron to millimeter in size.
What size droplets carry viruses?
Virus Detection Methods
1. Totalvirus• Numberofgenomecopies(GC)determinedbymoleculartechniques(quantitativepolymerasechainreaction,qPCR)
• ReflectsnumberofviruseswithintactDNAorRNA
• DoesNOTindicatewhethervirusisinfectiousornot
LinseyMarr,VirginiaTech,March2020 14https://www.cdc.gov/flu/resource-center/freeresources/graphics/images.htm
RNAiswrappedaroundtheribonucleoprotein
Virus Detection Methods
2. Infectiousvirus• Numberofvirusesthatareabletoinfectcellsdeterminedbyculture(growing)
• PFU=plaqueformingunits,numberofvirusescapableofformingplaquesonhostcells,focusformingunits(FFU)arerelated
• TCID50=mediantissuecultureinfectiousdose,concentrationatwhichhalfofcellsareinfectedafterbeingexposedtothesample
LinseyMarr,VirginiaTech,March2020 15https://phil.cdc.gov/Details.aspx?pid=23213
Relationship Between the Two Methods for Flu Virus
LinseyMarr,VirginiaTech,March2020 16Yanetal.,2018,PNAS,https://www.ncbi.nlm.nih.gov/pubmed/29348203
Thereisaweak,butsignificant,correlationbetweenvirusRNAcopiesandinfectiousvirus.
Amount of Flu Virus in Coarse vs. Fine Droplets (Particles) in Exhaled Breath
LinseyMarr,VirginiaTech,March2020 17Miltonetal.,2013,PLoSPathogens,https://www.ncbi.nlm.nih.gov/pubmed/23505369
Flu Virus in Droplets (Aerosols)
LinseyMarr,VirginiaTech,March2020 18
coarseaerosols>5µm fineaerosols<5µm
30-minsamplerecitealphabetat5,15,25minYanetal.,2018,PNAS,https://www.ncbi.nlm.nih.gov/pubmed/29348203
LinseyMarr,VirginiaTech,March2020 19
The majority of flu virus (RNA copies) is found in fine (<5 µm), rather than coarse (>5 µm), droplets/aerosols.
How do these droplets move around the indoor environment?
Settling Velocity and Time
Dropletssmallerthan10µmcanremainsuspendedformanyminutes
LinseyMarr,VirginiaTech,March2020 20
𝑠𝑒𝑡𝑡𝑖𝑛𝑔 𝑣𝑒𝑙𝑜𝑐𝑖𝑡𝑦 𝑣= 𝑔𝐷↓𝑝↑2 𝜌↓𝑝 /18𝜇
particlediameterparticledensity
dynamicviscosityofair
0.0
0.2
0.4
0.6
0.8
1.0
0 20 40 60 80 100
final
/ in
itial
dia
met
er
RH (%)
Humidity Controls Final Size
)6exp()4exp(RH 3dvn
dRTM
pp ws
w
ww
sat
d
πρσ
−==
10µm
4µm
LinseyMarr,VirginiaTech,March2020 21
KohlerequationappliedtoadropletcontainingphysiologicallevelsofNaClandprotein
Mikhailov,2004,Atmos.Chem.Phys.,https://www.atmos-chem-phys.net/4/323/2004/
• Settlingvelocityvdependsondiameterd• DiameterdependsonRH• InactivationratekdependsonRH
Virus Dynamics in Indoor Air
dd Ck
Hv
dtdC )( ++−= λ
concentration of infectious virus in
aerosols of diameter d
ventilation
settling
inactivation
LinseyMarr,VirginiaTech,March2020 22YangandMarr,2011,PLoSOne,https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3123350/
H
relativehumidity(RH)
Virus Viability vs. RH
k = 0.044 RH - 0.0063 r² = 0.98
0.000
0.005
0.010
0.015
0.020
0.025
0.030
0.035 0% 20% 40% 60% 80% 100%
Dec
ay ra
te (m
in-1
)
RH
LinseyMarr,VirginiaTech,March2020 23YangandMarr,2011,PLoSOne,https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3123350/
virusdecaysless(survivesbetter)atlowRH
virusdecaysmoreathighRH(y-axisisupsidedown)
Virus-Aerosols From a Cough
0
10
20
30
40
50
60
0 10 20 30 40 50 60 70 80 90 100
ΔC
/Δd e
q (#
m-3
µm
-1)
deq (µm)
λ = 1 ACH at RH = 50%
0 min 1 min 5 min 10 min 15 min 30 min 45 min
Thereisasizeshiftduetolossoflargerdropletsbygravitationalsettling.
evaporationandgravitationalsettling
YangandMarr,2011,PLoSOne,https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3123350/LinseyMarr,VirginiaTech,March2020 24
Infectious Concentrations vs. RH
ConcentrationsarehigheratlowerRHmainlybecauselab-determinedinactivationrateislower.
0
5
10
15
20
0 5 10 15 20 25 30 35 40 45
ΔC
/Δd e
q (#
m-3
µm
-1)
deq (µm)
10% RH 30% RH 50% RH 70% RH 90% RH
YangandMarr,2011,PLoSOne,https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3123350/LinseyMarr,VirginiaTech,March2020 25
RH and Removal Mechanisms • Settling:mainremovalmechanism,efficientforlargebutnotsmalldroplets• Ventilation:effectiveforallsizes,importantinpublicplaces• Inactivation:effectiveforallsizes,importantforsmalldroplets
YangandMarr,2011,PLoSOne,https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3123350/LinseyMarr,VirginiaTech,March2020 26
Conflictingresultsintheliterature
Virus Viability vs. RH
k = 0.044 RH - 0.0063 r² = 0.98
0.000
0.005
0.010
0.015
0.020
0.025
0.030
0.035 0% 20% 40% 60% 80% 100%
Dec
ay ra
te (m
in-1
)
RH
salt only
salt + protein
LinseyMarr,VirginiaTech,March2020 27YangandMarr,2011,PLoSOne,https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3123350/
LinseyMarr,VirginiaTech,March2020 28
Might humidity factor into the seasonality of the flu?
Viruses can be removed from indoor air by settling, ventilation, and inactivation; some of these processes are depend on humidity.
Seasonality of the Flu
Viboudetal.,2006,Science,https://science.sciencemag.org/content/312/5772/447LinseyMarr,VirginiaTech,March2020 29
Tameriusetal.,2011,EHP,https://ehp.niehs.nih.gov/doi/10.1289/ehp.1002383LinseyMarr,VirginiaTech,March2020 30
How Might RH Affect Transmission?
LinseyMarr,VirginiaTech,March2020 31
LowRH VeryhighRH
Physics
Chem
istry
MediumRH
settlesin1min
25µm10µm settlesin8min
Does RH Contribute to Seasonality?
LinseyMarr,VirginiaTech,March2020 32
LowRH VeryhighRHMediumRH
WintertimeindoorairSmalleraerosolsandnoinactivation⇒FLUSEASON!
RainyseasonintropicalregionsContacttransmissionfromlargedropletsthathavesettled?
Spring,summer,andfallSmallaerosolsandhighlyconcentratedsolutes?
LinseyMarr,VirginiaTech,March2020 33
What do we know about SARS-CoV-2 in droplets/aerosols?
https://twitter.com/VirusesImmunity/status/1238475009712160769LinseyMarr,VirginiaTech,March2020 34
LinseyMarr,VirginiaTech,March2020 35Ongetal.,2020,JAMA,https://jamanetwork.com/journals/jama/fullarticle/2762692
SamplesinpatientA’sandB’sroomswerenegativeaftercleaning.TheseresultsareforpatientCbeforecleaning.
table,bedrail,locker,chair,lightswitches,stethoscope,sink,floor,window,doorandhandle,toilet,airoutletfan
controlpanelonbed,callbell,railinbathroom,outerrimofsinkinbathroom,allanteroom,air
negative
positive
Liuetal.,2020,preprint,https://doi.org/10.1101/2020.03.08.982637
SARS-CoV-2 Size Distributions
LinseyMarr,VirginiaTech,March2020 36
SARS-CoV-2 Survival in Aerosols
LinseyMarr,VirginiaTech,March2020 37vanDoremalenetal.,2020,NEJM,https://www.nejm.org/doi/full/10.1056/NEJMc2004973
Major Unknowns
• Whichtransmissionrouteisdominant:directcontact,indirectcontactwithcontaminatedobjects(fomites),inhalationofaerosols,depositionofdroplets?
• Howarevirusesinactivatedinairandonsurfaces?• Howmuchvirusisreleasedinwhatsizeaerosolsatdifferentstagesofinfection?
• HowwelldoesSARS-CoV-2surviveinaerosolsunderreal-worldconditions?
LinseyMarr,VirginiaTech,March2020 38
Acknowledgments KarenKormuthSeemaLakdawalaWeinanLengKaisenLinAJPrussinIIElankumaranSubbiahEricVejeranoPeterVikeslandHaoranWeiWanYang
LinseyMarr,VirginiaTech,March2020 39