The Proportion of SARS-CoV-2 Infections That Are Asymptomatic
Authors: Fan Yang, Dan Ma
Journal: Annals of Internal Medicine (2021)

LettersSeptember 2021The Proportion of SARS-CoV-2 Infections That Are AsymptomaticFREEFan Yang, MD, Dan Ma, MDFan Yang, MDPeople's Hospital of Leshan, Leshan, China, and Changhai Hospital, Second Military Medical University/Naval Medical University, Shanghai, ChinaSearch for more papers by this author, Dan Ma, MDChanghai Hospital, Second Military Medical University/Naval Medical University, Shanghai, ChinaSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/L21-0490 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR: Oran and Topol's review (1) concluded that at least one third of SARS-CoV-2 infections are completely asymptomatic. On the basis of the included large-scale representative data, this conclusion seems more convincing than that from their initial narrative review published in 2020 (2).Of note, the evidence gap remained substantial. Except for a nationwide program in England, all other eligible studies included participants before September 2020. Moreover, the duration of most studies was less than 3 months. Therefore, Oran and Topol's review was less likely to disclose whether the proportion of asymptomatic SARS-CoV-2 infections would remain stable for a long period.Because the SARS-CoV-2 genome has developed many variants over 1 year of evolution, suspecting that it might undergo phenotypic “drift” is reasonable. Circumstantial evidence came from almost 20 million international visitors to China. Between mid-April and mid-October 2020, the proportion of asymptomatic infections among all persons who tested positive for SARS-CoV-2 increased significantly from 27.8% to 59.4% (3). This may signal an increase in asymptomatic infection globally in which the transition from D614 to G614 might have a place.The problem of viral variants became prominent at the end of 2020. Take the fast-spreading B.1.1.7 (alpha) variant as an example: The tendencies of spike-gene dropout transition in the Pillar 2 sample (obtained from community testing of symptomatic persons) closely matched the trends of a random sampling of the community (4). This could suggest that the proportion of asymptomatic infections with this variant remained relatively stable, whereas the risk for death was estimated to be higher than with previously circulating variants (4). Furthermore, the efficacy of first-generation vaccines in reducing asymptomatic infections will soon face the imminent challenges of new variants (5)—especially more worrisome lineages, such as the B.1.351 (beta) and P.1 (gamma) variants.Keeping track of mutations in the SARS-CoV-2 genome is vital. An interactive mutation tracker system based on SARS-CoV-2 isolate genomes deposited to GISAID might provide an option to accrue the clinical metadata. However, with sizable missing data and a lack of longitudinal follow-up on symptoms, such a tool could give only a patchy understanding of disease severity (6).Global coordination in productive expansion of sequencing efforts and robust collection of outcome data can allow us to truly develop the capacity to comprehend new variants and asymptomatic infections. This insight will support meaningful public health actions to choose the vaccine with the highest efficacy and make timely alterations in the existing vaccines, which could reduce selective pressure for emergence of more variants.References1. Oran DP, Topol EJ. The proportion of SARS-CoV-2 infections that are asymptomatic: a systematic review. Ann Intern Med. 2021;174:655-62. [PMID: 33481642] doi:10.7326/M20-6976 LinkGoogle Scholar2. Oran DP, Topol EJ. Prevalence of asymptomatic SARS-CoV-2 infection. A narrative review. Ann Intern Med. 2020;173:362-7. doi:10.7326/M20-3012 Google Scholar3. Ren R, Zhang Y, Li Q, et al. Asymptomatic SARS-CoV-2 infections among persons entering China from April 16 to October 12, 2020. JAMA. 2021;325:489-92. [PMID: 33528529] doi:10.1001/jama.2020.23942 CrossrefMedlineGoogle Scholar4. Davies NG, Jarvis CI, Edmunds WJ, et al; CMMID COVID-19 Working Group. Increased mortality in community-tested cases of SARS-CoV-2 lineage B.1.1.7. Nature. 2021;593:270-4. [PMID: 33723411] doi:10.1038/s41586-021-03426-1 CrossrefMedlineGoogle Scholar5. Hall VJ, Foulkes S, Saei A, et al; SIREN Study Group. COVID-19 vaccine coverage in health-care workers in England and effectiveness of BNT162b2 mRNA vaccine against infection (SIREN): a prospective, multicentre, cohort study. Lancet. 2021;397:1725-35. [PMID: 33901423] doi:10.1016/S0140-6736(21)00790-X CrossrefMedlineGoogle Scholar6. Alam I, Radovanovic A, Incitti R, et al. CovMT: an interactive SARS-CoV-2 mutation tracker, with a focus on critical variants [Letter]. Lancet Infect Dis. 2021;21:602. [PMID: 33571446] doi:10.1016/S1473-3099(21)00078-5 CrossrefMedlineGoogle Scholar Comments 0 Comments Sign In to Submit A Comment Author, Article, and Disclosure InformationAuthors: Fan Yang, MD; Dan Ma, MDAffiliations: People's Hospital of Leshan, Leshan, China, and Changhai Hospital, Second Military Medical University/Naval Medical University, Shanghai, ChinaChanghai Hospital, Second Military Medical University/Naval Medical University, Shanghai, China* Drs. Yang and Ma contributed equally to this work.Disclosures: Authors have reported no disclosures of interest. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=L21-0490. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoThe Proportion of SARS-CoV-2 Infections That Are Asymptomatic Daniel P. Oran and Eric J. Topol The Proportion of SARS-CoV-2 Infections That Are Asymptomatic Daniel P. Oran , Eric J. Topol The Proportion of SARS-CoV-2 Infections That Are Asymptomatic Ali Haider Bangash Metrics September 2021Volume 174, Issue 9 Page: 1343-1344 ePublished: 21 September 2021 Issue Published: September 2021 Copyright & PermissionsCopyright © 2021 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...