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#258 Stealth style transmission? Covert data on COVID-19


CLINICAL QUESTION
What is the evidence for asymptomatic transmission of COVID-19 (including those who will remain asymptomatic and those who are early and not symptomatic yet)?


BOTTOM LINE
Transmission of COVID-19 can occur in people who are currently asymptomatic. Case reports suggest this occurs in 6-13% of cases, although modelling suggests this might be higher. The importance of asymptomatic transmission is heightened by reports that ~50% of carriers are asymptomatic when an entire population (example cruise ship) is tested. Physical distancing should assist in preventing transmission from asymptomatic individuals.



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EVIDENCE
Transmission: 
  • 468 COVID-19 transmission cases in China.1 
    • In 13% (59/468) of cases, the secondary patient reported symptoms before the source. 
  • 157 COVID-19 transmission cases in Singapore.2 
    • In 6% (10/157) of cases, the secondary patient reported symptoms 1-3 days before the source. 
  • Other case reports of pre-symptomatic/asymptomatic transmission in family, business and hospital settings reported.3-7 
Proportion of COVID-19 positive patients who are asymptomatic at time of testing: 
  • From testing all individuals in a closed environment: 
    • 331/712 (47%): cruise ship passengers.8 
    • 13/23 (57%): long-term care residents.9 
    • 50-75%: entire small town in Italy (Numbers not reported).10 
  • Modelling studies estimate that pre-symptomatic or asymptomatic transmission may occur in 23-62% of cases.11-13 
Limitations: 
  • Difference between asymptomatic (those who test positive for COVID-19, but never become symptomatic7,14) and pre-symptomatic (transmission from the source to a secondary patient before the source develops symptoms) often not clearly reported. 
  • Recall bias of symptoms, dates and exposures. 
  • Presumption that symptomatic exposure ‘trumps’ asymptomatic transmission. 
  • Asymptomatic cases not always identified. 
  • Assumption that those who test positive for COVID-19 are infectious. 
Incubation period and time to spread: 
  • The mean incubation period (time before person becomes symptomatic) is ~5 days, may be up to 14 days.15 
  • Infected individuals can transmit ~4-8 days after becoming infected, possibly before symptoms develop.11,12,16-19 
Viral Load: 
  • Viral loads of asymptomatic and symptomatic patients appear similar.9,20 
  • Viral load is highest at symptom onset or in the first week.13,20-24 
    • Theoretically may increase pre-symptomatic transmission.13 
    • In contrast, peak viral load of MERS and SARS patients is ~ 7-10 days after symptom onset.22 
Context: 
  • Initially WHO suggested that pre-symptomatic and asymptomatic infections were "rare/not a major driver of transmission"25, but now recognize it may occur.11 
  • Physical distancing and other methods should reduce transmission between asymptomatic individuals. 


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Author(s):

  • Christina Korownyk MD CCFP
  • Michael R Kolber MD CCFP MSc

1. Du Z, Xu X, Wu Y, et al. Serial interval of COVID-19 among publicly reported confirmed cases. Emerg Infect Dis. 2020 Jun [April 9, 2020]. https://doi.org/10.3201/eid2606.200357

2. Wei W, Li Z, Chiew CJ, et al. Presymptomatic Transmission of SARS-CoV-2 - Singapore, January 23-March 16, 2020. MMWR Morb Mortal Wkly Rep. 2020. Epub April 1, 2020. https://www.cdc.gov/mmwr/volumes/69/wr/pdfs/mm6914e1-H.pdf Accessed April 9, 2020.

3. Li C, Ji F, Wang L, et al. Asymptomatic and human-to-human transmission of SARS-CoV-2 in a 2-family cluster, Xuzhou, China. Emerg Infect Dis. 2020 Jul [April 9, 2020]. https://doi.org/10.3201/eid2607.200718

4. 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 Mar 23. pii: ciaa316. doi: 10.1093/cid/ciaa316. [Epub ahead of print]

5. Li P, Fu JB, Li KF, et al. Transmission of COVID-19 in the terminal stage of incubation period: a familial cluster. Int J Infect Dis. 2020 Mar 16. pii: S1201-9712(20)30146-6. doi: 10.1016/j.ijid.2020.03.027. [Epub ahead of print]

6. Rothe C, Schunk M, Sothmann P, et al. Transmission of 2019-nCoV infection from an asymptomatic contact in Germany. N Engl J Med. 2020; 382:970-971. DOI: 10.1056/NEJMc2001468

7. Zhang J, Tian S, Lou J, et al. Familial cluster of COVID-19 infection from an asymptomatic. Crit Care. 2020;24(1):119. doi: 10.1186/s13054-020-2817-7.

8. Moriarty L, Plucinski M, Marston B, et al. Public Health Responses to COVID-19 Outbreaks on Cruise Ships - Worldwide, February-March 2020. MMWR Morb Mortal Wkly Rep. 2020;69:347-352. DOI: http://dx.doi.org/10.15585/mmwr.mm6912e3

9. 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;69:377-381. DOI: http://dx.doi.org/10.15585/mmwr.mm6913e1

10. Day M. Covid-19: identifying and isolating asymptomatic people helped eliminate virus in Italian village. BMJ. 2020;368:m1165 doi:https://doi.org/10.1136/bmj.m1165 (Published 23 March 2020)

11. Liu Y, Funk S, Flasche S. The contribution of pre-symptomatic infection to the transmission dynamics of COVID-2019 [version 1; peer review: awaiting peer review]. Wellcome Open Res. 2020, 5:58 (https://doi.org/10.12688/wellcomeopenres.15788.1)

12. Tapiwa G, Cécile K, Dongxuan C, et al. Estimating the generation interval for COVID-19 based on symptom onset data. medRxiv preprint. https://www.medrxiv.org/content/10.1101/2020.03.05.20031815v1.full.pdf Accessed April 7, 2020.

13. He X, Lau E, Wu P, et al. Temporal dynamics in viral shedding and transmissibility of COVID-19. med Rxiv preprint. https://www.medrxiv.org/content/10.1101/2020.03.15.20036707v2. Accessed April 9, 2020.

14. World Health Organization. Coronavirus disease 2019 (COVID-19) Situation Report - 73. https://www.who.int/docs/default-source/coronaviruse/situation-reports/20200402-sitrep-73-covid-19.pdf?sfvrsn=5ae25bc7_2 Accessed April 9, 2020.

15. Lauer SA, Grantz KH, Bi Q et al. The incubation period of coronavirus disease 2019 (COVID-19) from publicly reported confirmed cases: estimation and application. Ann Intern Med. 2020 Mar 10. doi: 10.7326/M20-0504. [Epub ahead of print]

16. Nishiura H, Linton NM, Akhmetzhanov AR. Serial interval of novel coronavirus (COVID-19) infections. Int J Infect Dis. 2020 Mar 4. pii: S1201-9712(20)30119-3. doi: 10.1016/j.ijid.2020.02.060. [Epub ahead of print]

17. Zhang J, Litvinova M, Wang W, et al. Evolving epidemiology and transmission dynamics of coronavirus disease 2019 outside Hubei province, China: a descriptive and modelling study. Lancet Infect Dis. 2020 Apr 2. pii: S1473-3099(20)30230-9. doi: 10.1016/S1473-3099(20)30230-9. [Epub ahead of print]

18. Tindale L, Coombe M, Stockdale J, et al. Transmission interval estimates suggest pre-symptomatic spread of COVID-19. med Rxiv preprint. https://www.medrxiv.org/content/10.1101/2020.03.03.20029983v1.full.pdf  Accessed April 9, 2020.

19. Li Q, Guan X, Wu P, et al. Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus-Infected Pneumonia. N Engl J Med. 2020 Mar 26;382(13):1199-1207. doi: 10.1056/NEJMoa2001316. Epub 2020 Jan 29.

20. 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 Mar 19;382(12):1177-1179. doi: 10.1056/NEJMc2001737. Epub 2020 Feb 19.

21. Hill K, Russell C, Clifford S, et al. The index case of SARS-CoV-2 in Scotland: a case report. J Infection (2020). doi: https://doi.org/10.1016/j.jinf.2020.03.022.

22. To KK, Tsang OT, Leung WS, et al. Temporal profiles of viral load in posterior oropharyngeal saliva samples and serum antibody responses during infection by SARS-CoV-2: an observational cohort study. Lancet Infect Dis. 2020 Mar 23. pii: S1473-3099(20)30196-1. doi: 10.1016/S1473-3099(20)30196-1. [Epub ahead of print]

23. Young BE, Ong SWX, Kalimuddin S, et al. Epidemiologic Features and Clinical Course of Patients Infected With SARS-CoV-2 in Singapore. JAMA. 2020 Mar 3. doi: 10.1001/jama.2020.3204. [Epub ahead of print]

24. Wölfel R, Corman V, Guggemos W et al. Virological assessment of hospitalized patients with COVID-2019. Nature. 2020 Apr 1. doi: 10.1038/s41586-020-2196-x. [Epub ahead of print]

25. WHO. Report of the WHO-China joint mission on coronavirus disease 2019 (COVID-19). www.who.int/docs/default-source/coronaviruse/who-china-joint-mission-on-covid-19-final-report.pdf. 

Authors do not have any conflicts of interest to declare.