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Bioaerosols, microdroplets, droplets and COVID-19

see also:Negative Pressure Face Shield (NPFS) for Transnasal Laryngoscopy to Mitigate Dispersion of Bioaerosol in COVID Era  and    Singing Safely in the COVID Era with Negative Pressure Face ShieldN95 Respirators (HEPA or High-Efficiency-Particulate-Air Filter Respirators) as Personal Protective Equipment (PPE)Otolaryngology COVID 19 ResourcesWind Instrument Aerosol in Covid Era - COVID-19 and horns, trumpets, trombones, euphoniums, tubas, recorders, flutes, oboes, clarinets, saxophones and bassoonsDream a Little Dream of Me with the NPFS - Safe Singing in the COVID Era

Henry Hoffman and Alessandra Pratt (11-07-2020)

Definitions

1. Humility: a form of temperance without pride or haughtiness.  Important attribute in making statements about COVID in light of incomplete knowledge

2. Modes of transmission of respiratory droplets (droplet diameters estimated range from 0.5 microns to 1000 microns as per Drosinos 2020) - others define respirable particles to be much smaller 0.001-10µm as per Hinds 1999)

    a. Contact: direct or indirect contact with pathogen laden droplet

        i. Direct: physical touch with infected host (hand contact)

        ii. Indirect: settled droplets on a structure (fomite) is transferred without contacting infected host

    b. Droplet transmission - large droplets (> 20 µm  also termed >20 microns) transported by spray to directly deposit on muscus membranes or conjunctive of asusceptible host. Considered important at close range

    c. Airborne transmission ('aerosol transmission') transmission by small respiratory droplets (less than 10 microns) also termed 'droplet nuclei' - more likely to deposite deep in respiratory tract. Overall particle size for aerosols are 0.002-100µm (Hinds 1999)

3. Aerosol = a suspension of particles; accepted scientific term for 'particulate suspensions in a gaseous medium' (Hinds 1999) 

         aerosols are two phase systems and consist of both the particles and the gas in which they are suspended - an include dust, fume, smoke mist,fog, haze, clouds and smog

         term aerosol coined ~ 1920 as analog to the term hydrosol (a stable liquid suspension of solid particles)

         The medical community (when compared to the aerosol scientist definition of aerosol above) offers diversity of opinion as to what defines 'aerosol' versus 'droplet'

               Li et al 2020 in comparing the impact of face mask mandates in states with and without mandates concluded that airborne transmission of SARS-CoV-2 viruse plays a dominant role in spreading the disease

               In their (Li 2020) discussion they defined respiratory particles as either droplets (>5 microns) or aerosols (<5 microns)

        As cited by Searle et al (Searle 2020):

             There is currently some confusion in the literature as the terms ‘airborne’ and ‘aerosols’ are occasionally used interchangeably. For the purposes of this article, we have adhered to the Public Health England definition of ‘aerosols’ as particles of < 5 lm in diameter.

              citing: Public Health England. COVID-19: infection prevention and control (IPC). Glossary of Terms. Available at: https://www.gov.uk/government/publications/wuhannovel-coronavirus-infect... ry-of-terms (accessed 14 May 2020)

         In a non-scientific manner, aerosol has been associated with the concept of pressurized spray-can products

       Others consider droplets with a diameter > 10 microns and aerosols ≤ 10 microns (Dharmarajan 2020)

4. Aerosol Science - includes study of aero-allergology, detection of biowarfare agents, population biology - with diversity of involvement including scientists, engineers, and health practitioners spread widely across unrelated communities with separate networks (Huffman and Ratnesar-Shuamate 2020)

5. Bioaerosol = primary biological aerosol particles (PBAPs)

   a. "Airborne particles derived from biological process" - tremendously complex to study - many questions remain unanswered (Huffman 2020)

   b. (Huffman 2020) defined (Despres 2012): "solid airborne particles derived from biological organisms, including miroorganisms and fragments of biological materials such as plant debris and animal dander' 

                  Bioaerosols include viruses, viable organisms, such as bacteria and fungi, and products of organisms, such as fungal spores or pollen (Hinds 1999)

6. Aerosol plume

             with cough: airborne droplets of airway secretions expelled from mouth in high-velocity

             with breathing/singing (see 8. Breath Cloud below)

    Surgical plume: a cloud of surgical smoke produced by electrosurgical and ablative laser devices with toxic, carcinogenic and infectious potential (Searle 2020). Also produced by other types of surgery - such as powered instrumentation (Dharmarajan 2020)

7. Droplets 

     a. Diameter of 100 µm or more tend to settle rapidly

     b. Droplets as large as 200µm may travel 1.5 meters from a coughing patient before settling (Xie 2005)

     c. Diameter need be  < 20 µm to become 'droplet nuclei' (Nicas 2005); others use cutoff of  <5µm

     d. Influenza-laden particles with diameters >4.7µm could be found 6 feet from a patient

8. Breath Cloud and viral transmission 

  Transmission of viral disease in general:

"The exhaled air of an infected human is a source of infectious viruses. These viruses then disperse in the enclosed spaces depending on the airflow distribution. Finally, these viruses enter the body of the victim through inhalation, deposit on a surface, or are extracted through a ventilation exhaust, which are called sinks" (Gupta 2010)

Through study 25 healthy subjects and employing computational fluid dynamics Gupta et al reported in 2010 that "The peak flow rate observed during coughing for the subject was higher than the talking and breathing flow rate but the total volume of exhaled air during breathing and talking for two hours is an order of magnitude higher than 100 coughs. This clearly indicates that breathing and talking can also play an important role in spreading the infection as they have higher event frequency than coughing even though the peak flow rate is relatively lower"(Gupta 2009)

   Transmission of COVID specifically:

As per Seminara et al (2020) "in the normal breathing and speaking functions, a large number of aerosols is released in the air. They consist of small droplets, invisible to the naked eye, and easily inhaled, which are however large enough to host virus particles."

"a sizable probability exists that normal speaking causes airborne virus transmission, espcially in confined environments" (Seminara 2020) 

"Overall, the prevailing view (although not yet universally accepted) is that airborne transmission is highly virulent and represents the dominant route of spread of the disease [COVID]".(Seminara 2020)

Widely considered that asymptomatic and presymptomatic individuals are the largest source of infection

Microparticles evaporate at rates dependent on temperature and relative humidity of the emitted clouds. 

Complexity of aerosol experiments leads to some diversity in findings with the overall impression (Seminara 2020) that the majority of droplets produced range from 0.1 to 1.0 microns and are maximal with coughing and least with normal breathing - with speech an order of magnitude greater than normal breathing - but also dependant on voice loudness. 

"facial protection devices must be maintained in place when speaking, as speaking is associated with an increase of exhalations" (Seminara 2020)

9. One micron is short for one micrometer designated as 1 µm = micrometer (1 micrometer = 0.001 millimeter = 0.0000393701 inches = 3.93701E-5 in)

SARS-CoV-2 is 0.05 to 0.2  µm (micron) in diameter - on average 125 nanometers (0.125 microns) (Cyranoski D (2020)  

10.  Settling rates; settling velocities 'large particles have a much greater settling velocity in compariosn to small particles' (Johnson 1999)

11. MERV = Minimum Efficiency Report Value - developed by the American Society of Heating Refrigeration and Air Conditioner Engineers to characterize effectiveness of a filter. 

     MERV 1 traps less than 20% of particles 3.0 to 10.0 microns //  MERV 16 traps 95% or better particles 0.3 - 1.0 microns (ref: What Does MERV or MERV Rating Mean?)

11. Minimum infectious dose:

from Sima Asadi, Nicole Bouvier, Anthony S. Wexler & William D. Ristenpart (2020) The coronavirus pandemic and aerosols: Does COVID-19 transmit via expiratory particles?, Aerosol Science and Technology, 54:6, 635-638, DOI: 10.1080/02786826.2020.1749229

minimum infectious dose for COVID-19 in susceptible individuals.  Neither the aerosol viral load nor the minimum infectious dose for COVID-19 have been definitively established, although it is believed  (as per Nicas et al) for other viral respiratory illnesses that a single virus can serve to initiate infection (Nicas, Nazaroff, and Hubbard 2005). Note below re: minimum infectious dose for influenza (Han 2019) measured as significantly more than a single viruse - with consideration for other factors influencing infectivity  including immune status of the target (see also: Paulo 2010).

viral load analysis on nasal,oropharyngeal and sputum swabs of SARS-CoV-2 showed salivary secretions to have peaks exceeding 2 x 109 irions per milliliter (Wölfel 2020)

As per Seminar et al (2020): "It must be underlined, however, that the presence of viral RNA does not imply the presence of the infectious virus."

12. July 30 2020: "The complete picture of tranmission modes of severe acute respiratory syndrome conronavirus 2 (SARS-CoV-2) is unknown.

from Ong SWX, Coleman KK, Chia PY et al published ahead of print "Transmission modes of severe acute respiratory syndrome coronavirus 2 and implications on infection control: a review" 

https://doi.org/10.11622/smedj.2020114

"The complete picture of transmission modes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unknown."

"Transmission via environmental surfaces or fomites is likely, but decontamination protocols are effective in minimising this risk. The extent of airborne transmission is also unclear. While several studies have detected SARS-CoV-2 RNA in air samples, none has isolated viable virus in culture." 

13 Classification based on dependance for airborne spread of infection 

"Diseases can be classified as obligate (e.g. tuberculosis), preferential (e.g. varicella, measles) or opportunistic (e.g. influenza, SARS) airborne diseases. quoted from Seto WH. Airborne transmission and precautions: facts and myths. J Hosp Infect 2015; 89:225-8.

  Seto: aerosols < 5microns    Seto WH. Airborne transmission and precautions: facts and myths. J Hosp Infect 2015; 89:225-8.

Airborne transmission 3 categories (Roy 2004 cited by Seto 2015)

a. Obligate - infection soley through aerosol  classic example tuberculosis

b. Preferential - infection through multiple routes - but predominately aerosol - classic examples are chickenpox and measles

c. Opportunistic - typically infect through other routes, but under favourable conditions (aerosol-generating procedures)  - transmission can occur - note that this article was written in 2015 before SARS-CoV-2 and made the comment that SARS (at that time on type 1) 'is generally ot taken as airborne, since, in the routine care of the patients, only droplet and contact precautions are required' 

Furthermore, airborne transmission is strongly influenced by environmental factors such as airflow, ventilation, temperature and humidity, which can affect droplet desiccation and movement, as well as virus stability.

Emerging evidence offers additional support for microaerosol transmission as a mode for spread of COVID (Shen 2020). Shen et al identified likely spread of COVID in two buses in China January 2020 - with detailed analysis identifying a likely index pre-symptomatic case in one bus resulted in multiple infectious of travellers situated at distant seats in the bus - presumably from airborne spread through an airconditioner that recirculated the air.  The other bus  at the same time took a similar group of travelers to the same worship event attended by all and had no cases.   

14. Influenza Challenge - Dose of Innoculum Relating to Infection

cid 2019:69 (15 December) • Han et al A Dose-finding Study of a Wild-type Influenza A(H3N2) Virus in a Healthy Volunteer Human Challenge Model

Participants were inoculated intranasally using the MAD Nasal, an intranasal mucosal atomization device (Teleflex, Morrisville, North Carolina) attached to a 1-mL syringe at doses ranging from 104 to 107 TCID50 (50% tissue culture infectious dose).

Doses administered to cohorts in a stepwise fashion based on the outcome of the previous dose until ≥60% MMID was achieved or the maximum dose of 107 TCID50

Material to be innoculated into the nose in a 1-mL syringe at doses ranging from 104 to 107 TCID50 (50% tissue culture infectious dose)

 The TCID50 (Median Tissue Culture Infectious Dose) is one of the methods used when verifying viral titer. TCID50 signifies the concentration at which 50% of the cells are infected when a test tube or well plate upon which cells have been cultured is inoculated with a diluted solution of viral fluid.

37 participants were challenged:

16 (43%) had viral shedding

27 (73%) developed symptoms,

12 (32%) participants experiencing mild to moderate influenza disease (MMID), defined as shedding and symptoms.

Only participants receiving 106 and 107 TCID50 experienced MMID at 44% and 40%, respectively. Symptom severity peaked on day 3, whereas most viral shedding occurred 1–2 days after challenge. Only 10 (29%) participants had a ≥4-fold rise in hemagglutination inhibition antibody titer after challenge.

 preexisting immunity factors other than anti-HA antibody may limit infection and shedding in healthy volunteers.

15. Other definitions

Nosocomial: disease originating under medical care such as in a hospital 

Zoonotic: diseases (also known as zoonoses) caused by germs that spread between animals and people.

Zoonotic disease = an infectious disease caused by a pathogen (bacterium, virus, parasite, prion) that jumped from a non-human animal to a human.

Fomite: an inanimate object that, when contaminated with infectious agents can transfer disease to a new host. Is a material likely to carry infection - examples: clothes, utensils, furniture     fomites = Latin plural of 'fomes' (meaning tinder - such as a catalyst for fire)

 

16. False Negatives for COVID PCR testing

Kucirka LM, Lauer SA, Laeyendecker O, Boon D, Lessler J. Variation in False-Negative Rate of Reverse Transcriptase Polymerase Chain Reaction-Based SARS-CoV-2 Tests by Time Since Exposure [published online ahead of print, 2020 May 13]. Ann Intern Med. 2020;M20-1495. doi:10.7326/M20-1495

Through literature review and pooled analysis these investigators conclude:

"In summary, care must be taken when interpreting RT-PCR tests for SARS-CoV-2 infection, particularly early in the course of infection and especially when using these results as a basis for removing precautions intended to prevent onward transmission. "

Infection = day 1; typical onset of symptoms = day 5  - over the 4 days of infection before the typical time of symptom onset (day 5), the probability of a false negative result in an infected person decreased from

100% false negative rate on day 1 to 68% false negative rate on day 4.

On the day of symptom onset (day 5), the median false-negative rate was 38%. This false negative rate decreased to 20% on day 8 (3 days after symptom onset) then began to increase again, from 21% on day 9 to 66% on day 21.

The false-negative rate was minimized 8 days after exposure—that is, 3 days after the onset of symptoms on average.

 "We would not recommend making decisions regarding removing contact precautions or ending quarantine on the basis of results obtained in this period in the absence of symptoms".

and "Serial testing would almost certainly reduce the false-negative rate"

17. Hopkins Webinar Discussion 

HTH Notes from webinar (viewed 7-11-2020  https://www.youtube.com/watch?v=W3w0Xc_MrWo&feature=youtu.be

“Leading with Science: Returning to Music Instruction and Performance in the Time of COVID-19” 

Speaking, breathing, singing, sneezing, wind instruments playing generates a spectrum of sizes of droplets

4 pillars driving mitigation permitting their (Peabody Institute of the Johns Hopkins University)  reopening - 'risk mitigating'

  I. Face coverings  (cloth face coverings aka 'masking' are not PPE = personal protective equipment but are designed to keep the wearer from spreading to others)

     update 9-16-2020:More recent evidence identifies the protective value of masking for the person wearing the mask - as PPE (Chu 2020,  Lyu 2020, Doung-Ngern 2020 )

  II. Distancing  minimally 6 feet (more is better)

  III. Hygiene  - personal (wash your hands) and room and building hygienc (clean surface contamination)

  IV. Environmental control  good ventilation and air filtration (address the smaller aerosols for which the magic s 6 foot rule does not apply)

a lot of controversy about how much we should care about smaller aerosols - 'lets not argue about it' but if we can increase ventilation/air exchange - will do it

also controversy - how much surface contamination matters - don't have a lot of scientific evidence yet- but do what we can - to cirvumvent the uncertainty that will be with us for some time

 

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Vijgen L, Keyaerts E, Moës E, et al. Complete genomic sequence of human coronavirus OC43: molecular clock analysis suggests a relatively recent zoonotic coronavirus transmission event. J Virol. 2005;79(3):1595-1604. doi:10.1128/JVI.79.3.1595-1604.2005

 

Interesting conjecture of historical note:  

  cited from Vijgen (2005): "We suggest that around 1890, BCoV [bovine coronavirus] might have jumped the species barrier and became able to infect humans, resulting in the emergence of a new type of human coronavirus (HCoV-OC43), a scenario similar to the origin of the SARS outbreak." and   "However, it is tempting to speculate about an alternative hypothesis, that the 1889-1890 pandemic may have been the result of interspecies transmission of bovine coronaviruses to humans, resulting in the subsequent emergence of HCoV-OC43."

    cited from Seminara (2020): The OC43 coronavirus offers a model for where this pandemic might go. That virus also gives humans common colds, but genetic research from the University of Leuven in Belgium suggests that OC43 might have been a killer in the past. That study indicates that OC43 spilled over to humans in around 1890 from cows, which got it from mice. The scientists suggest that OC43 was responsible for a pandemic that killed more than one million people worldwide in 1889–90 — an outbreak previously blamed on influenza. Today, OC43 continues to circulate widely and it might be that continual exposure to the virus keeps the great majority of people immune to it.