Respiratory Transmission of SARS-CoV-2: What Do We Really Know?

Businessman sneezing
Although influenza virus and respiratory syncytial virus are considered to be spread by droplets and aerosol transmission, the mode of respiratory transmission of SARS-CoV-2 is not completely understood.

Respiratory viruses are transmissible via inhalation or by touching contaminated surfaces and then touching the mouth, nose, or eyes. Although respiratory viruses may be inhaled as part of an “aerosol” and as part of a “droplet,” it is not clear that the virus is inhaled exclusively one way or the other. This has important implications as to how we protect ourselves from inhaling these viruses.

Droplets are exhaled when we breathe, speak, laugh, cough, or sneeze,1 and the size of the droplet determines whether it is considered “droplet” or “aerosol” (also referred to in the literature as “droplet nuclei” and even more confusingly as “airborne”). Droplets >5 µm in diameter are generally referred to as droplets, and those ≤5 µm are generally referred to as aerosols,2-4 although even these terms might be defined by other sizes in some literature.3-5 The droplet size distinction is important; the smaller the droplet, the longer and farther it may travel in the air and the more likely it can avoid becoming trapped by mucus or cilia and reach the alveoli of the lower respiratory tract.1,3,5,6

Examples of viruses well known to spread via aerosols are the measles virus and varicella zoster virus.5,7 The common respiratory viruses influenza virus and respiratory syncytial virus are considered to be spread mostly by droplets; however, aerosol transmission also is believed to occur.3-6,8-10 Respiratory spread of virus during the outbreak of severe acute respiratory syndrome (SARS) in China in 2003 is thought to have principally occurred via respiratory droplets.11 However, aerosol spread of this virus has also been postulated,12-14 and this virus has been shown to occur in laboratory-generated aerosols.15

The mode of respiratory transmission of SARS-CoV-2 is not completely understood. In a study by van Doremalen et al, experimentally generated aerosol particles with SARS-CoV-2 were found to have virus that was viable in cell culture throughout the 3 hours of aerosol testing.15 Such laboratory-generated aerosols may not be exactly analogous to human exhaled aerosols, and measurement of virus exhaled from patients with COVID-19 infection has been reported in several studies. In China, aerosol particles were isolated from air samples collected from various areas in 2 hospitals and from outdoor spaces in Wuhan; virus genome was detectable in some aerosols but at very low concentrations.7 A study at another hospital detected SARS-CoV-2 RNA in 35% of aerosol specimens from the intensive care unit and in 12.5% of specimens obtained from a COVID-19 ward.16 An epidemiologic analysis from China concluded that cases of COVID-19 traced to possible shopping mall exposure may have occurred via aerosol.17 In a study from Iran, air samples taken from a distance of 2 to 5 m from patient beds were negative for SARS-CoV-2 RNA.18 However, a study from the University of Nebraska Medical Center demonstrated SARS-CoV-2 genome in 63.2% of air samples from rooms of 11 patients infected with COVID-19, with some samples obtained at distances >6 ft from the patient, and in 66.7% of 12 air samples obtained from hallways outside the patients’ rooms.19

In patient care settings, face masks have been used for protection against organisms that may be transmitted by the respiratory route, and use of masks in the community has been recommended for protection against COVID-19.20 N95 respirators are masks designed to filter and protect the wearer from aerosols, while surgical masks are designed to protect the wearer from large droplets and sprays and protect the patient from droplets and sprays emitted by the wearer.21 Clinical studies on the effectiveness of face masks are limited and difficult to conduct.22 A meta-analysis of studies in health care workers concluded that during the 2003 SARS-CoV-1 epidemic, both N95 respirators and medical masks significantly reduced health care worker risk compared with no protection.23 A meta-analysis of subsequent studies that compared N95 respirators to medical masks showed no difference between the 2 types of masks for preventing laboratory-confirmed viral infection, laboratory-confirmed influenza infection, influenza-like illness, or clinical respiratory illness.24 A case study from China reported that of 41 health care workers (85% wearing a surgical mask and 15% wearing an N95 mask) identified to have had exposure for ≥10 min at a distance of <2 m from patients with SARS-CoV-2 undergoing aerosol-generating procedures, none became positive by nasopharyngeal swab within 14 days of exposure.25 A study from South Korea compared viral loads exhaled by 4 patients after coughing without a mask, with a surgical mask, or with a cotton mask, and showed no differences in viral loads.26

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Is it really so important whether a pathogen is spread via aerosol most of the time or just sometimes? The distinctions of obligate, preferential, and opportunistic aerosol transmission have been proposed. Organisms that transmit as obligate or preferential aerosols are considered to cause infection upon reaching the most distal airways.27 Opportunistic aerosol transmission might occur when the chance arises, but other routes such as contact, droplet, or ingestion can also transmit infection.27 Over short distances, both droplet and aerosol transmission are important; therefore, aerosol-generating medical procedures28,29 or close proximity to an infected person requires face protection that will filter aerosols as well as droplets (ie, an N95 mask). Over longer distances, droplet transmission of infection through the air becomes less important as the droplets fall to surfaces. In poorly ventilated indoor areas aerosols may continue to be important in transmitting infection as they remain in the air — and therefore an N95 mask is desirable in COVID-19 patient areas — but in well-ventilated areas the aerosols may be diluted in the air. The viral load necessary for infection is not known. But how far is far enough to elude droplets and to diffuse aerosols? It is generally accepted that droplets can travel 1 to 2 m before falling to surfaces and that aerosols can travel much farther.30 The US Centers for Disease Control and Prevention advise that persons maintain 6 ft of separation.31 However, a “gas cloud” model suggests that a cough or sneeze could send respiratory particles as far as 8 m.32 Also, airflow patterns in a room might influence the distance even a droplet may travel.33 In a model of moving persons, such as walking or running, the distance to encounter exhaled respiratory droplets may be greater than for those standing still.34 Recommendations for face protection will therefore be based on evolving knowledge of all these issues.


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