COVID-19: Asymptomatic Transmission of SARS-CoV-2 (15 June 2020)

In an 8 June press briefing, Maria Van Kerkhove, the World Health Organization’s (WHO) coronavirus technical lead, stated that asymptomatic transmission of the SARS-CoV-2 virus was “very rare.” The comment, which seemingly suggested that infected people without symptoms were not spreading the disease, contradicted studies that showed that asymptomatic shedding accounts for up to 40–50% of new COVID-19 cases. Understandably, Dr. Van Kerkhove’s comment generated confusion about the role of wearing masks, social distancing, and sheltering in place — something the public has been exhorted to do in order to curtail asymptomatic spread of the virus. Van Kerkhove’s comment also drew rebukes from other scientists and physicians, such as Dr. Anthony Fauci, Director of the National Institute of Allergy and Infectious Diseases (NIAID), who told Science News: “[The WHO assertion] is not backed up by any data…We know that there is asymptomatic transmission. What we do not know is the extent to which that occurs. So, when we hear statements that this is very rare, we do not know that as a fact.” (https://www.sciencenews.org/article/coronavirus-covid-19-who-asymptomatic-cases-spread) Similarly, Dr. Lawrence Gostin, director of the O’Neill Institute for National and Global Health Law at Georgetown University commented: “WHO is tarnishing its reputation as a science agency by putting out conflicting and confusing statements.” (https://www.buzzfeednews.com/article/danvergano/who-coronavirus-asymptomatic-cases-scientists)

In a follow-up briefing the next day, Dr. Van Kerkhove attempted to clarify her comment about the role of asymptomatic transmission. (https://www.youtube.com/watch?v=7RcJ2yyNkUk) She acknowledged that her use of the term “very rare” had been a “miscommunication”, and had been based on a small number of studies done in “member states” that followed the contacts of infected but asymptomatic individuals. She added that the infected individuals in these studies were neither mildly symptomatic nor pre-symptomatic (That is to say, they never developed symptoms). Van Kerkhove concluded by saying that although “asymptomatically-infected individuals are much less likely to transmit the virus than those who develop symptoms”, these studies should not be construed to mean that “asymptomatic transmission globally” was very rare, because “that has not yet been determined”. However, despite her attempt to clarify her comment, many questioned whether Dr. Van Kerkhove’s explanation was sufficient. Dr. Marm Kilpatrick, an infectious diseases researcher at the University of California, Santa Cruz referred to the comment and ensuing media coverage as “a disaster public relations–wise” and “counterproductive”. (https://www.the-scientist.com/news-opinion/who-comments-breed-confusion-over-asymptomatic-spread-of-covid-19-67626)

Despite its genetic similarity to SARS-CoV-1, SARS-CoV-2 is in many respects a novel coronavirus, and our understanding of it is evolving. We do know that infected individuals may begin shedding virus several days before symptom onset and that shedding may persist for weeks after the resolution of symptoms. However, because this data derives from studies using polymerase chain reaction (PCR) amplification, which detects nucleic acid and cannot distinguish viable from nonviable virus, the significance of shedding by asymptomatic persons is not yet known. Nonetheless, there are a number of other pathogens for which transmission before the onset of symptoms (i.e. during the incubation period) is well documented, including the influenza and herpes simplex viruses. A role for asymptomatic shedding in new COVID-19 cases is suggested by several recent studies published in peer reviewed medical journals. In one study published in Nature Medicine of 94 infected patients and another 77 documented cases of transmission, an estimated 44% of transmission occurred during the pre-symptomatic period, with infectiousness starting from 2.3 days (95% CI, 0.8–3.0 days) before symptom onset and peaking at 0.7 days (95% CI, −0.2–2.0 days) before symptom onset. (https://www.nature.com/articles/s41591-020-0869-5) In another study published in the New England Journal of Medicine that documented transmission of SARS-CoV-2 in a skilled nursing facility in King County, Washington, 56% of residents with positive test results were asymptomatic at the time of testing and “most likely contributed to transmission”. (https://www.nejm.org/doi/full/10.1056/NEJMoa2008457) In an accompanying editorial to the New England Journal of Medicine paper, the authors claim the study shows that “asymptomatic persons are playing a major role in the transmission of SARS-CoV-2”. (https://www.nejm.org/doi/full/10.1056/NEJMe2009758) They add that “Ultimately, the rapid spread of COVID-19 across the United States and the globe, the clear evidence of SARS-CoV-2 transmission from asymptomatic persons, and the eventual need to relax current social distancing practices argue for broadened SARS-CoV-2 testing to include asymptomatic persons in prioritized settings (and) support the case for the general public to use face masks when in crowded outdoor or indoor spaces.”

Thus far, my comments have focused on viral shedding early in the course of infection. By now, it is widely understood that shedding may also persist for weeks after the resolution of symptoms. In one study of the Wuhan outbreak, the median duration of viral shedding was 20 days, with the longest duration of viral shedding being 37 days. (Zou L Ruan F Huang M et al. SARS-CoV-2 viral load in upper respiratory specimens of infected patients. N Engl J Med. 2020) Prolonged convalescent shedding has been described in other studies, and my own clinical observations suggest that shedding may actually persist for months. However, as mentioned previously, the mere presence of viral DNA or RNA does not necessarily mean infectivity, and at least one study employing viral cultures suggests that the shedding of viable virus persists for no more than 8–10 days after the onset of symptoms. (https://www.medrxiv.org/content/10.1101/2020.03.05.20030502v1) Nonetheless, more studies are required to better elucidate the duration of infectivity of SARS-CoV-2.

The first known COVID-19 case was identified in Wuhan, China in November 2019. In the ensuing seven months, the virus spread globally causing 7.4 million infections with more than 400,000 deaths to date. (https://covid19.who.int/) Because there does not yet exist an effective vaccine or reliable therapeutic, efforts to stem the pandemic have focused on individual and collective preventive measures such as cough hygiene, social distancing, avoiding congregate settings, and wearing masks — all with the intent of preventing the number of cases from exceeding the local health care capacity (i.e. “flattening the curve”). Undeniably, these measures have been uncomfortable and inconvenient and they have damaged the economy. They cannot be sustained indefinitely, and local governments and industry have recently begun moving into the “recovery phase” of the pandemic (i.e. normalization of activities). Invariably, some are arguing that this is premature, and they warn of a second wave (similar to that seen with the 1918 influenza pandemic), while others lament that we are not moving quickly enough towards resumption of our pre-pandemic posture. Among the latter, some even decry the restrictions that have been imposed as being unnecessary and unconstitutional and they impugn the motives of those who recommended them, sometimes invoking outlandish conspiracies. Of course, the reasonable person recognizes these restrictions for what they are: a collective attempt by a community to curb a public health threat and to protect its most vulnerable members. In his book When Bad Things Happen to Good People (Schocken Books, 1981), Rabbi Harold Kushner contends that while we may not always have control over our circumstances, crises afford each of us the opportunity to rise to the occasion and to demonstrate our character, mettle, and humanity. The current pandemic has always represented such an opportunity.

Until my next update — regards.

Michael Zapor, MD, PhD, CTropMed, FACP, FIDSA

(15 June 2020)