Wednesday, May 06, 2020

EID Journal: Asymptomatic or Presymptomatic Transmission Of SARS-CoV-2


A little more than 4 months into COVID-19's world tour we now know a good deal more about the SARS-CoV-2 virus than we did even a month ago, but there are still a great questions that need answering if we are to re-open our societies and economies safely. 
While we've known of asymptomatic COVID-19 cases since late January, and have seen evidence suggestive of asymptomatic transmission, the jury is still out on how much of a factor asymptomatic (or presymptomatic) transmission plays in the spread of the virus. 
And early assumptions that anyone infected with the SARS-CoV-2 virus (asymptomatically or symptomatically) would develop long lasting immunity seems to losing some ground as well (see WHO Scientific Brief: `Immunity Passports' For COVID-19).
Several times over the past few years I've written about the limited, and often short-term immunity observed in mild or asymptomatic MERS-CoV infections (see COVID-19: From Here To Immunity).   
A month ago, epidemiologist Dr. Marc Lipsitch published an opinion piece in the New York Times that went over the still slim and sometimes conflicting evidence for acquired immunity from COVID-19 infection, along with some of the challenges of creating a vaccine (see Who Is Immune to the Coronavirus?).

These are all terribly inconvenient questions, and I'm sure they are particularly irksome to those demanding a simple and quick solution to this pandemic. But proceeding without solid answers to these, and other nagging questions, could lead to tragic mistakes going forward.
All of which brings us to an online report in the CDC's EID Journal, which looks at the accumulated evidence to date.  It's a lengthy report, so I've only posted some excerpts (reformatted for readability). You'll want to follow the link to read it in its entirety. 
Spoiler alert.  While this report reviews the evidence we have on these crucial questions, definitive answers are still hard to come by.

Online Report
Evidence Supporting Transmission of Severe Acute Respiratory Syndrome Coronavirus 2 While Presymptomatic or Asymptomatic
Nathan W. Furukawa , John T. Brooks, and Jeremy Sobel
Author affiliations: Centers for Disease Control and Prevention, Atlanta, Georgia, USA

Recent epidemiologic, virologic, and modeling reports support the possibility of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission from persons who are presymptomatic (SARS-CoV-2 detected before symptom onset) or asymptomatic (SARS-CoV-2 detected but symptoms never develop). 
SARS-CoV-2 transmission in the absence of symptoms reinforces the value of measures that prevent the spread of SARS-CoV-2 by infected persons who may not exhibit illness despite being infectious.
Critical knowledge gaps include the relative incidence of asymptomatic and symptomatic SARS-CoV-2 infection, the public health interventions that prevent asymptomatic transmission, and the question of whether asymptomatic SARS-CoV-2 infection confers protective immunity.

As the coronavirus disease (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) unfolds, an increasing number of reports have indicated that some infected persons may not exhibit signs or symptoms of illness, including persons who are presymptomatic (SARS-CoV-2 RNA is detectable before symptom onset) or asymptomatic (SARS-CoV-2 RNA is detectable but symptoms never develop) (18).
The detection of SARS-CoV-2 RNA in presymptomatic or asymptomatic persons does not prove that they can transmit the virus to others. We describe evidence that supports the concept of transmission while presymptomatic and asymptomatic, which we found during a rapid literature review conducted at the Centers for Disease Control and Prevention (CDC) in early April 2020. 
Evidence Supporting Presymptomatic and Asymptomatic Transmission
We searched the literature in PubMed for articles that were published from January 1 through April 2, 2020, and pertained to presymptomatic or asymptomatic SARS-CoV-2 transmission. This search captured the literature until the time CDC made policy changes recommending community cloth face coverings and universal masking in healthcare facilities. We used combinations of the search terms SARS-CoV-2, COVID-19, asymptomatic, presymptomatic, and transmission. We included original articles, brief reports, and correspondences and excluded reviews, commentaries, opinions, and preprint manuscripts (with the exception of CDC-authored studies that were in review).
We classified studies as reporting epidemiologic, virologic, or modeling evidence for presymptomatic or asymptomatic transmission of SARS-CoV-2.
Epidemiologic Evidence
Virologic Evidence
Modeling Evidence

Public Health Implications of Transmission While Asymptomatic
The existence of persons with asymptomatic SARS-CoV-2 infection who are capable of transmitting the virus to others has several implications. 
  • First, the case-fatality rate for COVID-19 may be lower than currently estimated ratios if asymptomatic SARS-CoV-2 infections are included (34,35). 
  • Second, transmission while asymptomatic reinforces the value of community interventions to slow the transmission of COVID-19. Knowing that asymptomatic transmission was a possibility, CDC recommended key interventions including physical distancing (36), use of cloth face coverings in public (37), and universal masking in healthcare facilities (38) to prevent SARS-CoV-2 transmission by asymptomatic and symptomatic persons with SARS-CoV-2 infection. 
  • Third, asymptomatic transmission enhances the need to scale up the capacity for widespread testing and thorough contact tracing to detect asymptomatic infections, interrupt undetected transmission chains, and further bend the curve downward.

Science Questions to Inform Public Health Action
The existence of SARS-CoV-2 transmission while infected persons are presymptomatic and asymptomatic raises 3 key questions that need to be answered to inform public health action. 
First, the incidence of asymptomatic compared with symptomatic SARS-CoV-2 infection needs to be determined. The extent of presymptomatic or asymptomatic SARS-CoV-2 infection may be clarified by studies using serial virologic data, serologic data, or a combination of both in observational cohorts or surveillance systems.
If a substantial proportion of infections are asymptomatic, enhanced testing strategies may be needed to detect these persons. Second, given that a large proportion of infections probably result from transmission from asymptomatic or presymptomatic persons (32,33,39), the effectiveness of public health interventions aimed at reducing their infectiousness needs to be quantified. 
If the COVID-19 pandemic is found to be driven by undetected asymptomatic or mildly symptomatic SARS-CoV-2 infections, new innovations in disease detection and prevention (beyond exhaustive contact tracing, mass testing, and isolation of asymptomatic contacts) may be needed.

Last, knowledge of SARS-CoV-2 immunity among persons with asymptomatic or mild SARS-CoV-2 infection is needed; specifically, whether full or partial immunity develops in these persons, how long protective immunity lasts, and if it is possible to be immune from reinfection but still asymptomatically transmit SARS-CoV-2 while in a carrier state.
This information will be crucial for projecting the anticipated course of the pandemic and the potential for SARS-CoV-2 resurgence if immunity wanes (40). Information about immunity is also valuable for healthcare and other critical infrastructure workers for whom rates of exposure, and thereby asymptomatic infection, may be higher and who therefore warrant data-informed guidance on how to safely return to work.
The answers to these questions will be crucial for guiding the gradual relaxing of community interventions, resuming the normal functions of society, and recovering from the COVID-19 pandemic.

Dr. Furukawa is a CDC Epidemic Intelligence Service Officer in the CDC National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, working on the CDC COVID-19 response clinical team. His research interests include HIV, sexually transmitted diseases, tuberculosis, hepatitis, and Ebola.