As the COVID-19 pandemic rages on, the global community has become accustomed to comprehensive, interventional strategies such as wearing a mask, social distancing, hand hygiene, and surface cleaning and disinfection. It is well known that transmission of SARS-CoV-2 occurs through direct, indirect, or close contact with infected people through infectious secretions, such as saliva and respiratory secretions or their respiratory droplets. In addition, the scientific community has confirmed that the airborne transmission of SARS-CoV-2 viruses in aerosols (smaller than 100 μm) can remain suspended in air for many seconds to hours and are highly concentrated near an infected person, thus infecting people most easily in close proximity (1). Furthermore, aerosols containing infectious virus can also travel more than 2 m and accumulate in poorly ventilated indoor air, leading to superspreading events. World Health Organization and Centers for Disease Control and Prevention have also acknowledged this under certain circumstances, such as enclosed spaces, prolonged exposure to respiratory particles (i.e., shouting, singing, and exercising), and inadequate ventilation or air (2, 3). Thus, effective control strategies and standardized guidance to the public are integral in mitigating COVID-19. In particular, understanding the duration of infectiousness in infected persons with SARS-CoV-2 is critical for developing evidence-based public health policies on isolation, contact tracing and returning to work. In general, the levels of viral RNA were determined by using quantitative reverse transcription-polymerase chain reaction. However, detection of viral RNA does not necessarily indicate that a person is infectious and able to transmit the virus to another person. Although it is critical to determine the levels of infectious virus particles in infected COVID-19 patients, requirement of Biosafety Level-3 laboratory for the virus titration has hindered this approach. In this perspective section, we will discuss currently available scientific data regarding the levels of infectious virus particles in asymptomatic individuals, in mild and severe COVID-19 patients and in children and young adults.
Asymptomatic and presymptomatic individuals represent a source of potentially transmissible virus (4). Asymptomatic infections have no specific incubation period due to no clinical signs. However, the viral loads detected in asymptomatic populations have been reported in several studies to be similar to those in symptomatic patients. In a nursing facility, quantitative SARS-CoV-2 viral loads detected in residents were similarly high in the four symptom groups (residents with typical symptoms, those with atypical symptoms, those who were presymptomatic, and those who remained asymptomatic). Notably, 17 of 24 specimens (71%) from presymptomatic persons had viable virus by culture 1 to 6 days before the development of symptoms. In a surveillance study, asymptomatic cases of samples were collected through swabbing of contacts or facility/family/household testing in the context of outbreak investigations. Despite the uncertainty of their date of exposure or start of infection, cultivable virus was isolated from samples collected from asymptomatic individuals (41% of tested samples).
Detection of infectious SARS-CoV-2 from upper respiratory tract of mild-to-moderate COVID-19 patients showed that infectious virus can persist for more than a week after symptom onset, declining over time (5). At 10 days after symptom onset, probability of culturing virus declines to 6%. This is in line with current WHO guidance on release from isolation. Similarly, shedding of the virus in mild COVID-19 patients was determined by measuring the levels of transcribed subgenomic mRNA and isolation of infectious viruses (6). Pharyngeal virus shedding was very high during the first week of symptoms, with a peak at 7.1 × 108 RNA copies per throat swab on day 4. In addition, infectious viruses were successfully isolated from these samples, confirming active virus replication in the upper respiratory tract. No viruses were isolated after day 7 onset. These findings suggest efficient transmission of SARS-CoV-2, through active pharyngeal viral shedding at a time at which symptoms are still mild and typical of infections of the upper respiratory tract. In a surveillance study in Manitoba, Canada, the presence of infectious viruses was determined by evaluating samples from day of symptom onset (day 0) up to 21 days after symptom onset (7). Within this range of samples, positive cultures were observed up to day 8 after symptom onset with the probability of obtaining peak titers on day 3. Similarly, in Hong Kong, virus was isolated from the samples of mild patients collected within the first 8 days of illness with median viral RNA load of 7.54 log10 genome copies/mL (8). From severe COVID patients, prolonged duration of cultivable virus was detected for up to 20 days after symptom onset, suggesting that prolonged excretion of infectious virus is associated to the severity of the disease (9).
Severity in most children is limited, and children do not seem to be major drivers of transmission. However, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects children of all ages. In South Korea, large-scale testing, aggressive contact tracing and testing, and isolation/direct observation of asymptomatic or mildly symptomatic children have identified the presence of asymptomatic (20 of 91 ), presymptomatic (18 of 91 ), and symptomatic children (53 of 91 ) (10). Presymptomatic children remained symptom free for a median (range) of 2.5 (1-25) days before exhibiting any symptoms. A minority of children (6 ) were identified as infected; this highlights the concept that infected children may be more likely to go unnoticed either with or without symptoms and continue on with their usual activities, which may contribute to viral circulation in the community. In a separate study with 12 symptomatic children, infectious viruses were detected at a median of 2 days after symptom onset (11). Median viral RNA load at diagnosis was 3.0 × 106 copies/mL (mean 4.4 × 108 ranging from 6.9 × 103 to 4.4 × 108 copies/mL. A limitation of this study is the small number of children assessed. However, viral load at diagnosis is comparable to that of adults and symptomatic children of all ages shed infectious virus in early acute illness, a prerequisite for further transmission. Considering the relatively low frequency of infected children, even in severely affected areas, biological or other unknown factors could lead to the lower transmission in this population. Large serologic investigations and systematic surveillance for acute respiratory diseases and asymptomatic presentations are still needed to assess the role of children in this pandemic.
Although the spectrum of COVID-19 ranges from asymptomatic to severe infections, most patients experience mild disease (80%). Scientific data indicate that infectious virus in mild patients can persist for a week after symptom onset. Furthermore, infectious virus can be isolated from asymptomatic individuals. This clearly enforces the importance of wearing a mask, quarantine, and contact tracing to mitigate the transmission of SARS-CoV-2. Recent studies support that wearing masks can save lives not only by cutting down the chances of both transmitting and catching the coronavirus (12) but also by reducing the severity of infection in contracted individuals (13). It is well demonstrated that self-quarantine of close contacts exposed to COVID-19 prevents transmission to others. Contact tracing must be conducted for close contacts (any individual within 6 feet of an infected person for at least 15 minutes) of laboratory-confirmed or probable COVID-19 patients. However, relaxed social distancing and opposition of wearing masks are hindering the mitigation of SARS-CoV-2, resulting in continuous increase of COVID-19 cases. Even when the vaccine will be available, we would not immediately stop social distancing, wearing masks, and other interventional measures until reaching efficient levels of viral mitigation. The message is clear that a simple practice of wearing masks can protect ourselves and save other lives from circulating SARS-CoV-2.
- PRATHER, K.A., MARR, L.C., SCHOOLEY, R.T. MCDIARMID, M.A., WILSON, M.E., MILTON, D.K. 2020. Airborne transmission of SARS-CoV-2. DOI: 10.1126/science.abf0521
- 2020. Transmission of SARS-CoV-2: implications for infection prevention precautions. https://www.who.int/news-room/commentaries/detail/transmission-of-sars-cov-2-implications-for-infection-prevention-precautions
- 2020. Scientific Brief: SARS-CoV-2 and Potential Airborne Transmission. https://www.cdc.gov/coronavirus/2019-ncov/more/scientific-brief-sars-cov-2.html
- Arons MM, Hatfield KM, Reddy SC, et al. 2020. Presymptomatic SARS-CoV-2 infections and transmission in a skilled nursing facility. N Engl J Med 382:2081-2090.
- Singanayagam Anika, Patel Monika , Charlett Andre , Lopez Bernal Jamie , Saliba Vanessa , Ellis Joanna , Ladhani Shamez , Zambon Maria , Gopal Robin. 2020. Duration of infectiousness and correlation with RT-PCR cycle threshold values in cases of COVID-19, England, January to May 2020. Euro Surveill. 25.
- Wölfel R, Corman VM, Guggemos W, Seilmaier M, Zange S, Müller MA, et al. 2020. Virological assessment of hospitalized patients with COVID-2019. Nature. 581:465–469.
- Bullard J, Dust K, Funk D, Strong JE, Alexander D, Garnett L, et al. 2020. Predicting infectious SARS-CoV-2 from diagnostic samples. Clin Infect Dis. ciaa638.
- Perera RAPM, Tso E, Tsang OTY, Tsang DNC, Fung K, Leung YWY, et al. SARS-CoV-2 virus culture and subgenomic RNA for respiratory specimens from patients with mild coronavirus disease. Emerg Infect Dis. 2020;26(11).
- van Kampen JJA, van de Vijver DAMC, Fraaij PLA, Haagmans BL, Lamers MM, Okba N, et al. Shedding of infectious virus in hospitalized patients with coronavirus disease-2019 (COVID-19): duration and key determinants. medRxiv. 2020.06.08.20125310.
- Han MS, Choi EH, Chang SH, et al. Clinical characteristics and viral RNA detection in children with coronavirus disease 2019 in the Republic of Korea. JAMA Pediatr. doi:10.1001/jamapediatrics.2020.3988.
- L’Huillier AG, Torriani G, Pigny F, Kaiser L, Eckerle I. Culture-Competent SARS-CoV-2 in Nasopharynx of Symptomatic Neonates, Children, and Adolescents. Emerg Infect Dis. 2020 Oct;26(10):2494-2497. doi: 10.3201/eid2610.202403. Epub 2020 Jun 30. PMID: 32603290; PMCID: PMC7510703.
- Leffler, C. T. et al.Preprint at medRxiv https://doi.org/10.1101/2020.05.22.20109231 (2020).
- Gandhi, M., Beyrer, C. & Goosby, E. Gen. Intern. Med. https://doi.org/10.1007/s11606-020-06067-8 (2020).