CEBM and Oxford University Logos

The role of asymptomatic SARS-CoV-2 infections: systematic review

The role of asymptomatic SARS-CoV-2 infections: systematic review. Spencer EA,  Heneghan C.

https://www.cebm.net/study/the-role-of-asymptomatic-sars-cov-2-infections-systematic-review/

Published on July 23, 2020

Reference Diana C Buitrago-Garcia, Dianne Egli-Gany, Michel J Counotte, Stefanie Hossmann, Hira Imeri, Aziz Mert Ipekci, Georgia Salanti, Nicola Low. The role of asymptomatic SARS-CoV-2 infections: rapid living systematic review and meta-analysis. medRxiv 2020.04.25.20079103 2020
Study type
Country Global
Setting Systematic review
Protocol https://osf.io/9ewys/
Funding Details Swiss National Science Foundation; European Union Horizon 2020 research and innovation programme, project EpiPose
Transmission mode Presymptomatic, Asymptomatic
Exposures

Bottom Line

Evidence from early in the pandemic suggests that most SARS-CoV-2 infections are not asymptomatic throughout the course of infection, and that transmission by presymptomatic accounts for around 40-60% of transmission and asymptomatic cases accounts for around 15% of transmission.

Evidence Summary

The overall estimate of the proportion of people who become infected with SARS-CoV-2 and remain asymptomatic throughout infection was 15% (95% CI 10 to 22%) with a prediction interval of 3 to 55% in 28 studies that addressed this review question. 

There was some evidence that bias in the selection of participants influences the outcome. 

The proportion of people that is pre-symptomatic could not be summarised, owing to heterogeneity. 

In modelling studies, 40 to 60% of all SARS-CoV-2 infections are the result of transmission from pre-symptomatic individuals, with a smaller contribution from asymptomatic individuals. 

What did they do?

Rapid living systematic review and meta-analysis set out to answer the following questions

  1. amongst people who become infected with SARS-CoV-2, what proportion does not experience symptoms at all during their infection? 
  2. Amongst people with SARS-CoV-2 infection who are asymptomatic when diagnosed, what proportion will develop symptoms later? 
  3. What proportion of SARS-CoV-2 transmission is accounted for by people who are either asymptomatic throughout infection, or pre-symptomatic? 

The review searched PubMed, Embase, bioRxiv and medRxiv using a living evidence database of SARS-CoV-2 literature, searched on 25 March 2020 and updated on 20 April 2020. 

Studies of people with SARS-CoV-2 diagnosed by reverse transcriptase PCR that documented follow-up and symptom status at the beginning and end of follow-up or modelling studies. 

One reviewer extracted data and a second verified the extraction, with disagreement resolved by discussion or a third reviewer. Risk of bias was assessed with an adapted checklist for case series and a questionnaire to assess relevance and credibility of modelling studies.

Study reliability

High quality systematic review based on studies of variable quality. Some included studies were at high risk of bias due to selecting participants based on symptom status. 

This study was not able to consider the impact of false negative tests on the results.

Clearly defined setting Demographic characteristics described Follow-up length was sufficient Transmission outcomes assessed Main biases are taken into consideration
Yes Yes Yes Yes Yes

What else should I consider?

Included studies:

  • Arima Y, Shimada T, Suzuki M, et al. Severe Acute Respiratory Syndrome Coronavirus 2 Infection among Returnees to Japan from Wuhan, China, 2020. Emerg Infect Dis 2020;26(7) doi: 10.3201/eid2607.200994 [published Online First: 2020/04/11]
  • Bai Y, Yao L, Wei T, et al. Presumed Asymptomatic Carrier Transmission of COVID-19. JAMA 2020;54(0):E017. Doi: 10.1001/jama.2020.2565
  • Breslin N, Baptiste C, Gyamfi-Bannerman C, et al. COVID-19 infection among asymptomatic and symptomatic pregnant women: Two weeks of confirmed presentations to an affiliated pair of New York City hospitals. Am J Obstet Gynecol MFM 2020:100118. doi: 10.1016/j.ajogmf.2020.100118 [published Online First: 2020/04/16]
  • Chan JF, Yuan S, Kok KH, et al. A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster. Lancet 2020;395(10223):514-23. Doi: 10.1016/S0140-6736(20)30154-9 [published Online First: 2020/01/28]
  • Chang L, Zhao L, Gong H, et al. Severe Acute Respiratory Syndrome Coronavirus 2 RNA Detected in Blood Donations. Emerg Infect Dis 2020;26(7) doi: 10.3201/eid2607.200839 [published Online First: 2020/04/04]
  • Danis K, Epaulard O, Benet T, et al. Cluster of coronavirus disease 2019 (Covid-19) in the French Alps, 2020. Clin Infect Dis 2020 doi: 10.1093/cid/ciaa424 [published Online First: 2020/04/12]
  • Hoehl S, Rabenau H, Berger A, et al. Evidence of SARS-CoV-2 Infection in Returning Travelers from Wuhan, China. N Engl J Med 2020;382(13):1278-80. doi: 10.1056/NEJMc2001899 [published Online First: 2020/02/19]
  • Hu Z, Song C, Xu C, et al. Clinical characteristics of 24 asymptomatic infections with COVID-19 screened among close contacts in Nanjing, China. Sci China Life Sci 2020;63(5):706-11. doi: 10.1007/s11427-020-1661-4 [published Online First: 2020/03/09]
  • Kimball A, Hatfield KM, Arons M, et al. Asymptomatic and Presymptomatic SARS-CoV-2 Infections in Residents of a Long-Term Care Skilled Nursing Facility – King County, Washington, March 2020. MMWR Morb Mortal Wkly Rep 2020;69(13):377-81. doi: 10.15585/mmwr.mm6913e1 [published Online First: 2020/04/03]
  • Le TQM, Takemura T, Moi ML, et al. Severe Acute Respiratory Syndrome Coronavirus 2 Shedding by Travelers, Vietnam, 2020. Emerg Infect Dis 2020;26(7) doi: 10.3201/eid2607.200591 [published Online First: 2020/04/03]
  • Liao J, Fan S, Chen J, et al. Epidemiological and clinical characteristics of COVID-19 in adolescents and young adults. medRxiv 2020 doi: 10.1101/2020.03.10.20032136
  • Luo L, Liu D, Liao X-l, et al. Modes of contact and risk of transmission in COVID-19 among close contacts. medRxiv 2020 doi: 10.1101/2020.03.24.20042606
  • Luo SH, Liu W, Liu ZJ, et al. A confirmed asymptomatic carrier of 2019 novel coronavirus. Chin Med J (Engl) 2020;133(9):1123-25. doi: 10.1097/CM9.0000000000000798 [published Online First: 2020/03/10]
  • Lytras T, Dellis G, Flountzi A, et al. High prevalence of SARS-CoV-2 infection in repatriation flights to Greece from three European countries. J Travel Med 2020 doi: 10.1093/jtm/taaa054 [published Online First: 2020/04/17]
  • Meng H, Xiong R, He R, et al. CT imaging and clinical course of asymptomatic cases with COVID-19 pneumonia at admission in Wuhan, China. J Infect 2020 doi: 10.1016/j.jinf.2020.04.004 [published Online First: 2020/04/16]
  • Pongpirul WA, Mott JA, Woodring JV, et al. Clinical Characteristics of Patients Hospitalized with Coronavirus Disease, Thailand. Emerg Infect Dis 2020;26(7) doi: 10.3201/eid2607.200598 [published Online First: 2020/04/09]
  • Qian G, Yang N, Ma AHY, et al. A COVID-19 Transmission within a family cluster by presymptomatic infectors in China. Clin Infect Dis 2020 doi: 10.1093/cid/ciaa316  16
  • Qiu H, Wu J, Hong L, et al. Clinical and epidemiological features of 36 children with coronavirus disease 2019 (COVID-19) in Zhejiang, China: an observational cohort study. Lancet Infect Dis 2020 doi: 10.1016/S1473-3099(20)30198-5 [published Online First: 2020/03/30]
  • See KC, Liew SM, Ng DCE, et al. COVID-19: Four Paediatric Cases in Malaysia. Int J Infect Dis 2020;94:125-27. Doi: 10.1016/j.ijid.2020.03.049 [published Online First: 2020/04/19]
  • Tabata S, Imai K, Kawano S, et al. Non-severe vs severe symptomatic COVID-19: 104 cases from the outbreak on the cruise ship ‘Diamond Princess’ in Japan. medRxiv 2020 doi: 10.1101/2020.03.18.20038125
  • Tan YP, Tan BY, Pan J, et al. Epidemiologic and clinical characteristics of 10 children with coronavirus disease 2019 in Changsha, China. J Clin Virol 2020;127:104353. doi: 10.1016/j.jcv.2020.104353 [published Online First: 2020/04/18]
  • Tian S, Wu M, Chang Z, et al. Epidemiological investigation and intergenerational clinical characteristics of 24 COVID-19 patients associated with supermarket cluster. medRxiv 2020 doi: 10.1101/2020.04.11.20058891
  • Tong ZD, Tang A, Li KF, et al. Potential Presymptomatic Transmission of SARS-CoV-2, Zhejiang Province, China, 2020. Emerg Infect Dis 2020;26(5):1052-54. doi: 10.3201/eid2605.200198 [published Online First: 2020/02/25]
  • Wang X, Fang J, Zhu Y, et al. Clinical characteristics of non-critically ill patients with novel coronavirus infection (COVID-19) in a Fangcang Hospital. Clin Microbiol Infect 2020 doi: 10.1016/j.cmi.2020.03.032 [published Online First: 2020/04/07]
  • Wang Y, Liu Y, Liu L, et al. Clinical outcome of 55 asymptomatic cases at the time of hospital admission infected with SARS-Coronavirus-2 in Shenzhen, China. J Infect Dis 2020 doi: 10.1093/infdis/jiaa119 [published Online First: 2020/03/18]
  • Wang Z, Ma W, Zheng X, et al. Household transmission of SARS-CoV-2. J Infect 2020 doi: 10.1016/j.jinf.2020.03.040 [published Online First: 2020/04/14]
  • Yang N, Shen Y, Shi C, et al. In-flight Transmission Cluster of COVID-19: A Retrospective Case Series. medRxiv 2020 doi: 10.1101/2020.03.28.20040097
  • Zhang J, Tian S, Lou J, et al. Familial cluster of COVID-19 infection from an asymptomatic. Crit Care 2020;24 doi: 10.1186/s13054-020-2817-7
  • Zhou X, Li Y, Li T, et al. Follow-up of asymptomatic patients with SARS-CoV-2 infection. Clin Microbiol Infect 2020 doi: 10.1016/j.cmi.2020.03.024 [published Online First: 2020/04/03]
  • 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;382(12):1177-79. doi: 10.1056/NEJMc2001737 [published Online First: 2020/02/20]
  • Ferretti L, Wymant C, Kendall M, et al. Quantifying SARS-CoV-2 transmission suggests epidemic controlwith digital contact tracing. Science 2020;368(6491):2020.03.08.20032946. doi: 10.1126/science.abb6936 [published Online First: 2020/04/03]
  • Ganyani T, Kremer C, Chen D, et al. Estimating the generation interval for coronavirus disease (COVID-19) based on symptom onset data, March 2020. Euro Surveill 2020;25(17):2020.03.05.20031815. doi: 10.2807/1560- 7917.ES.2020.25.17.2000257 [published Online First: 2020/05/07]
  • He X, Lau EHY, Wu P, et al. Temporal dynamics in viral shedding and transmissibility of COVID-19. Nat Med 2020 doi: 10.1038/s41591-020-0869-5 [published Online First: 2020/04/17]
  • Zhang W. Estimating the presymptomatic transmission of COVID19 using incubation period and serial interval data.medRxiv 2020 doi: 10.1101/2020.04.02.20051318

About the authors

Carl Heneghan

Carl is Professor of EBM & Director of CEBM at the University of Oxford. He is also a GP and tweets @carlheneghan. He has an active interest in discovering the truth behind health research findings

Elizabeth Spencer

Dr Elizabeth Spencer; MMedSci, PhD. Epidemiologist, Nuffield Department for Primary Care Health Sciences, University of Oxford.

Tweet
Share
Share
« COVID-19 Evidence Service Home