Editor’s note: Ask the Expert is a column aimed at providing pediatricians information on pressing topics related to COVID-19. Email your questions to [email protected].
Coronaviruses are a large group of viruses infecting mammals and birds, resulting in a wide variety of diseases. Seven coronaviruses are known to infect humans and include four conventional or low-pathogenicity viruses and three high-pathogenicity viruses (SARS-CoV-1, MERS, SARS-CoV-2). Consistent with other respiratory viruses, the most important portal of entry for SARS-CoV-2 coronavirus is the mucous membranes of the respiratory tract.
Airborne transmission
An infectious person sheds respiratory viruses and expels contaminated mucosalivary secretions from the upper or lower respiratory tract while talking, coughing, singing, sneezing or undergoing an aerosol-generating procedure. The secretions contain a continuum of particle sizes that are expelled at various velocities.
Droplets less than 100 microns in diameter generally are not visible to the naked eye. Respiratory droplets greater than 5 microns in diameter are recognized to be the major mode of transmission of SARS-CoV-2 and are unlikely to travel more than 3 to 6 feet. They are likely to settle rapidly due to gravitational pull within a 6-foot radius of the index person. A susceptible person who is not wearing personal protective equipment and is within this distance (close contact) is at risk of becoming infected.
Conventional understanding is that when droplets greater than 5 microns are inhaled, they likely settle on the mucous membranes of the upper respiratory tract. In contrast, particles less than 5 microns in diameter are more likely to bypass the anatomic obstacles of the upper airway (such as nasal turbinates and the cilia) and travel directly to the mucous membranes of the distal lower respiratory tract.
Smaller respiratory droplets equal to or less than 5 microns in diameter are referred to as droplet nuclei. Whether SARS-CoV-2 can be transmitted by droplet nuclei has been a subject of much discussion. Several reports suggest that airborne droplet nuclei may result in viral transmission over distances greater than 6 feet, particularly in a closed setting with poor ventilation.
As expelled particles transition from the warm, moist environment of the respiratory tract, respiratory droplets larger than 5 microns partially evaporate in the air, resulting in smaller particles that may travel more than 6 feet. The rate of evaporation is influenced by ambient temperature, humidity and airflow. At least one study has found SARS-CoV-2 is more stable at low-temperature and low-humidity conditions. Warmer temperature and higher humidity result in a shorter half-life of infectious virus in mucosal secretions, suggesting that season of the year may influence risk of transmission (Matson MJ, et al.Emerg Infect Dis.https://wwwnc.cdc.gov/eid/article/26/9/20-2267_article).
It is unknown how much replication-competent virus in droplet nuclei is necessary to result in transmission to a susceptible person. While RNA-containing aerosols have been detected for hours after an infected person is in a room, it is not known if this is infectious (replication-competent) virus or whether the inoculum contains sufficient virus to result in transmission.
Other routes of transmission
SARS-CoV-2 has been detected in urine and stool, but transmission by these routes has not been documented.
Low levels of SARS-CoV-2 RNA have been detected by polymerase chain reaction assay (PCR) in serum and plasma. Whether virus can be transmitted by the bloodborne route is not known, but the risk appears to be small.
Limited data are available regarding intrauterine transmission from mother to fetus, and the degree of risk is poorly understood. PCR assays have detected SARS-CoV-2 RNA in breast milk, but transmission by breast milk would require replication-competent virus and available data do not suggest this is a likely route of transmission. Although data are limited, current recommendations do not restrict breastfeeding by mothers infected with SARS-CoV-2.
Fomites are generated when infectious respiratory secretions are expelled and land on a hard surface (e.g., stethoscope, otoscope, door knob, keyboard). Autoinoculation occurs when contaminated secretions from such surfaces are transferred to the ocular, nasal or oral mucosa of a susceptible person. The precise role of fomites in transmission of SARS-CoV-2 is not clear but appears to be less important than aerosol transmission.
Transmission from asymptomatic, pre-symptomatic, symptomatic people
A positive PCR result from a nasopharyngeal specimen may indicate an asymptomatically infected person, a pre-symptomatic person who soon will develop symptoms or a symptomatic person with active infection. Current understanding indicates that approximately one-third of adults infected with SARS-CoV-2 will remain asymptomatic throughout the infection.
The relative importance of pre-symptomatic vs. asymptomatic vs. symptomatic patients in viral dissemination is not well understood and may correlate with viral load, but it is likely that all three situations contribute to viral spread. Transmission from an asymptomatic person presumably occurs in the absence of cough or sneeze. Viral transmission from an infected person who remains asymptomatic is difficult to study.
The amount of virus (viral load) detected in a nasopharyngeal swab can be inferred from the reverse transcription PCR (RT-PCR) testing cycle threshold (Ct). During a PCR assay, the cycle threshold is the number of cycles required for the fluorescent signal to exceed background level. The Ct is a measure of the amount of viral RNA in the swab (specimen). Low Ct values indicate a large quantity of viral RNA is present. One uncertainty with this measure is whether the Ct equates to replication-competent virus or total viral RNA that may not be infectious.
Studies of adults suggest no significant differences are found in the amount of viral RNA detected by PCR assays from asymptomatic, pre-symptomatic or symptomatic patients. This suggests asymptomatic and pre-symptomatic adults transmit the virus that causes COVID-19. This also indicates that screening for symptoms will fail to identify all people who can transmit virus to susceptible contacts.
At the present time, it appears the risk of symptomatic disease among infected people is directly proportional to age, with children and adolescents younger than 18 years least likely to become symptomatic.
Available data suggest that SARS-CoV-2 RNA shedding begins two to three days before symptom onset and continues in the first few days of illness when viral loads are at their highest as measured by PCR assays. While PCR assays may remain positive for weeks, current understanding indicates that an amount of replication-competent virus sufficient to result in transmission from an otherwise healthy patient (immunocompetent) with mild or moderately severe disease is unlikely to be present after 10 days regardless of PCR status. Studies that use cell culture to evaluate shedding of infectious virus (replication-competent) are limited to date.
The important steps for mitigation and reducing the risk of SARS-CoV-2 infection can be remembered by avoiding the three C’s: closed spaces, crowded spaces and close contact settings. Covering respiratory mucosal surfaces with a face mask in a setting of risk is the fourth C.
Dr. Meissner is professor of pediatrics at Floating Hospital for Children, Tufts Medical Center. He also is an ex officio member of the AAP Committee on Infectious Diseases and associate editor of the AAP Visual Red Book.
