Erin P Silverman1, Raju Reddy2, Ali Ataya2, Christina Eagan2. 1. University of Florida, College of Medicine, Department of Medicine, Division of Pulmonary, Critical Care, and Sleep Medicine, Gainesville, FL, USA. Electronic address: erin.silverman@medicine.ufl.edu. 2. University of Florida, College of Medicine, Department of Medicine, Division of Pulmonary, Critical Care, and Sleep Medicine, Gainesville, FL, USA.
Abstract
Entities:
Keywords:
COVID-19; Infectivity; Letter to editor; SARS-CoV-2
We read with interest the article by Gao et al. [1], “A study on infectivity of asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) carriers.” This case is certainly an important assessment within the context of the current global pandemic. In this study, 455 contacts of an asymptomatic patient were tested. This cohort comprised 224 health care workers (HCW), 196 family members, and 35 patients, all of whom subsequently tested negative. The authors concluded that the infectivity of asymptomatic SARS-CoV2 carriers may be weak. The authors speculated that this was likely due to a low viral load in asymptomatic patients. This article came to our attention once it began disseminating through social media platforms such as Twitter and Facebook by various “truther,” “anti-vaxxer,” and conspiracy-focused accounts, in addition to (we presume) well-meaning individuals with questions about the infectivity of SARS-CoV2, or the necessity of social distancing and protective equipment protocols. The authors should have taken steps to ensure that their findings not be misconstrued as “proof” that SARS-CoV2 is poorly, or non-, infective. Further, we have several major concerns regarding the study methodology.We strongly disagree with their conclusion that the infectivity of SARS-CoV2 is weak. Indeed, recent, and more methodologically sound, studies have suggested the opposite. Ruiyun et al. used dynamic metapopulation modeling and Bayesian inference and concluded that an extremely high (79–85%) percentage of all infections in China during late January and early February 2020 were undocumented. Many of these individuals were likely poorly symptomatic or asymptomatic [2]. The authors’ methods, as reported, do not support their assertion of poor infectivity.First, at the time of testing, the patient may have been only carrying inactive viral particles. It is well known that a positive polymerase chain reaction (PCR) only indicates the presence of viral RNA and not necessarily viable virus [3]. In this case, the patient was tested on hospital day 26. Furthermore, her respiratory symptoms were present for one month prior to admission. Therefore, the patient was tested almost 56 days after her initial symptom onset. Given that the patient had a month of symptoms prior to admission, she could well have had SARS-CoV2 initially and cleared the infection by the time of admission. Thus, the positive test could well have detected non-viable viral particles only. Secondly, if the authors considered the patient to have an active infection at the time of testing, they should have reported the viral cycle threshold (Ct), which is the number of replication cycles required to produce a signal. Although we recognize that this testing isn't universally accessible, we are curious to know if it was something the authors considered and, in any case, this should have been presented as a limitation. In general, a Ct value of less than 40 is considered positive, but this information is unknown [4]. Thirdly, the authors defined infectiousness yet failed to obtain a positive viral culture. This would have been particularly useful given that the patient was tested long after she initially had respiratory symptoms. Wölfel et al. [2] were unable to isolate the virus in a culture obtained from the nasopharynx eight days after illness onset. In this case, the patient's specimen was obtained from the nasopharynx and we therefore cannot know if the patient can be considered infectious in this setting. Lastly, they reached their conclusion from exposure to one case which is, by no means, generalizable. The authors acknowledge that their findings stem from a single case. In fact, this was the only limitation they present. However, they then proceed to state that these same findings are “representative to some extent.” We question the veracity of this statement and, given the methodological issues mentioned above, also question its appropriateness.We appreciate the authors’ effort to answer a very important question about the infectiousness of SARS-CoV2. However, their methodology is severely flawed. Further, their conclusion can, and is, being easily misinterpreted by the lay public. Such misinterpretation may carry dangerous consequences. This is particularly true when social anxiety is high, when clear directives from leading governmental and public health officials are frequently contradictory, and when quarantine and social distancing measures are being relaxed. We welcome any additional insights the authors can offer.
Authors: Roman Wölfel; Victor M Corman; Wolfgang Guggemos; Michael Seilmaier; Sabine Zange; Marcel A Müller; Daniela Niemeyer; Terry C Jones; Patrick Vollmar; Camilla Rothe; Michael Hoelscher; Tobias Bleicker; Sebastian Brünink; Julia Schneider; Rosina Ehmann; Katrin Zwirglmaier; Christian Drosten; Clemens Wendtner Journal: Nature Date: 2020-04-01 Impact factor: 49.962