Transmission of Viruses in Droplets and Aerosols · Linsey Marr, Virginia Tech, March 2020 32 Low...

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

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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