BALTIMORE, MD, June 12, 2020: According to the Global Virus Network (GVN), a coalition comprised of the world’s preeminent human and animal virologists from 53 Centers of Excellence and 10 Affiliates in 32 countries, whether or not asymptomatic COVID-19 infected subjects can transmit the virus has tremendous impact on the global public health strategy against SARS-CoV-2 viral infection. In this context, the recent statement on that topic offered by the World Health Organization (WHO) and the discussions around this statement clearly provide an excellent opportunity to discuss this major issue.
We understand that there is confusion between asymptomatic and pre-symptomatic cases. Pre-symptomatic transmission has been defined as the transmission of SARS-CoV-2 from an infected person to a secondary patient before the source patient has developed symptoms. Published studies have shown substantial transmission of SARS-CoV-2 before symptom onset; indeed, importantly, shedding of the virus may begin 2 to 3 days before the appearance of the first symptoms (1), and this is in contrast to what had been observed with SARS-CoV-1. Although virus shedding has not been quantitated, specimens (71%) from pre-symptomatic persons had viable virus by culture 1 to 6 days before the development of symptoms in a nursing facility (2). After symptom onset, viral loads decreased monotonically. The proportion of pre-symptomatic transmission ranged from 46% to 55% (1). In general, as expected, the reported proportion of pre-symptomatic transmission is higher in those geographical areas where diagnostic tests for SARS-CoV-2 have been widely used. Pre-symptomatic transmission occurs through generation of respiratory droplets, as well as, possibly, aerosol or through indirect transmission (3-5). In contrast to the pre-symptomatic transmission, it has been a challenge to quantify the contributions of asymptomatic individuals to the transmission of SARS-CoV-2 (3). Lack of quantitative analysis of viral shedding also hindered in evaluating the role of asymptomatic individuals in viral transmission. However, clinical studies showed that asymptomatic individuals had substantial viral shedding for potential transmission (2, 6). For example, a recent study clearly pointed to viral transmission by asymptomatic individuals (6). Certainly, comprehensive studies are required for quantitative analysis of viral shedding, viremia, and innate immune responses in asymptomatic and pre-symptomatic individuals.
Unfortunately, the current COVID-19 pandemic is expanding because it is difficult to trace mild or pre-symptomatic infections. We have learned a very important lesson from the initial response to the outbreaks of SARS-CoV-2. For example, most countries worldwide had delayed state and local responses, thus allowing SARS-CoV-2 to spread rapidly (7). A critical problem was testing: symptom-based screening alone failed to detect a high proportion of infectious cases and was not enough to control transmission in this setting. Consequently, many countries have been shut down to prevent a rapidly expanding epidemic because only isolating people who are sick might not be enough to contain the epidemic. In contrary, several countries, such as Australia, South Korea, Germany, Singapore, and Taiwan, managed to contain the virus early and have worked hard to keep it suppressed with efficient testing and contact tracing system.
Until vaccines are widely available, available infection prevention approaches are case isolation, contact tracing and quarantine, physical distancing, decontamination, and hygiene measures. To implement the right measures at the right time, it is of crucial importance to understand the routes and timings of transmission. It is certain that the existence of pre-symptomatic transmission would present difficult challenges to contact tracing. More inclusive criteria for contact tracing to capture potential transmission events 2 to 3 days before symptom onset should be urgently considered for effective control of the outbreak as has been done in Hong Kong and mainland China since late February (1). Although WHO recently clarified its position on COVID-19 asymptomatic transmission, all these scientific findings emphasize that efficient control of asymptomatic and pre-symptomatic transmission is a critical intervention strategy for COVID-19. To support this, a massive testing with contact tracing system should be provided for the detection of viral shedding in asymptomatic individuals.
- He X, Lau EHY, Wu P, et al. Temporal dynamics in viral shedding and transmissibility of COVID-19. Nat Med 26, 672–675. 2020.
- Arons MM, Hatfield KM, Reddy SC, et al. Presymptomatic SARS-CoV-2 infections and transmission in a skilled nursing facility. NEJM 2020 382:2081-2090.
- Gandhi M, Yokoe DS, Havlir DV. Asymptomatic transmission, the Achilles’ Heel of current strategies to control Covid-19; NEJM 2020 382:2158-2160.
- Asadi S, Wexler AS, Cappa CD, Barreda S, Bouvier NM, Ristenpart WD. Aerosol emission and superemission during human speech increase with voice loudness. Sci Rep 2019 9:2348.
- Hijnen D, Marzano AV, Eyerich K, GeurtsvanKessel C, Giménez-Arnau AM, Joly P, et al. SARS-CoV-2 transmission from presymptomatic meeting attendee, Germany. Emerg Infect Dis. 2020 Jul. DOI: 10.3201/eid2608.201235.
- Chau NVV, Lam VT, et al. The natural history and transmission potential of asymptomatic SARS-CoV-2 infection, Clinical Infectious Diseases, https://doi.org/10.1093/cid/ciaa711.
- Schneider EC. Failing the test — the tragic data gap undermining the U.S. pandemic response. NEJM. 2020. DOI: 10.1056/NEJMp2014836.