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Volume 26, Number 7—July 2020
Online Report

Evidence Supporting Transmission of Severe Acute Respiratory Syndrome Coronavirus 2 While Presymptomatic or Asymptomatic

Author affiliations: Centers for Disease Control and Prevention, Atlanta, Georgia, USA

Suggested citation for this article

Abstract

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

Most reports of presymptomatic (912), asymptomatic (1315), or a combination of presymptomatic or asymptomatic SARS-CoV-2 transmission (16,17) were from China (Table 1). Presymptomatic or asymptomatic primary patients were typically exposed to SARS-CoV-2 during travel from Wuhan or another city in Hubei Province, China (916). One couple was exposed during a mass gathering in Shanghai for the Chinese Spring Festival (17). Reported cases of infected persons who transmitted the virus to others while presymptomatic or asymptomatic have occurred within families or households (911,1317), during shared meals (10,12), or during visits with hospitalized family members (9,13). An inherent confounder to these reports from China is the inability to entirely rule out alternative SARS-CoV-2 exposure in the community early in the outbreak, when transmission in the community may have been undetected.

However, cases of presymptomatic transmission have been reported from other countries before widespread community transmission occurred. A report from Germany documented infection of a German businessman after exposure to a mildly symptomatic colleague visiting from China (18). Before becoming symptomatic, this businessman exposed 2 other colleagues who subsequently received a COVID-19 diagnosis but did not have contact with the primary patient from China or any other known source. A report from Singapore described 7 COVID-19 clusters resulting from presymptomatic transmission; presymptomatic primary patients varied from persons with travel from high-incidence countries to persons exposed in the local community (19). All primary patients experienced distinct periods of initial exposure and presymptomatic close contact with secondary patients who had no other known exposure risks. The incubation periods for presymptomatic primary patients with distinct exposures ranged from 3 to 11 days; for presymptomatic primary patients with travel history to an area with active transmission, the time from last exposure to symptom onset ranged from >2 to >9 days.

Virologic Evidence

Currently, SARS-CoV-2 infection is primarily diagnosed by detection of viral RNA via reverse transcription PCR (RT-PCR) or by viral culture and demonstration of cytopathic effect (20). Although RT-PCR identifies viral RNA and cannot determine whether infectious virus is present, infectiousness can be inferred from cycle threshold (Ct) values. The RT-PCR Ct value represents the number of PCR cycles required to detect SARS-CoV-2 RNA; lower values indicate higher viral load and imply higher infectiousness (2022). The exact RT-PCR Ct values associated with the presence of infectious SARS-CoV-2 is unknown, but infectious virus has been isolated from a specimen with an RT-PCR Ct of 34 (23).

Four reports documented the presence of SARS-CoV-2 RNA with lower Ct values in samples collected from persons in whom symptoms of COVID-19 never developed (2427) (Table 2). Two reports described specimens with low RT-PCR Ct values among presymptomatic and asymptomatic residents of a nursing home identified as part of the same outbreak investigation (23,28). Among these reports, RT-PCR Ct values for SARS-CoV-2 RNA in asymptomatically infected persons ranged from 14 to 40 (2327). The study with data on presymptomatic infected patients reported an average RT-PCR Ct value of 24 (range 15–38) (23). Two reports described culture of infectious virus from persons with asymptomatic (24) and presymptomatic (23) SARS-CoV-2 infection. Although these reports did not identify actual virus transmission while presymptomatic or asymptomatic, the low RT-PCR Ct values (i.e., high viral load) and ability to isolate infectious SARS-CoV-2 provide plausible virologic evidence for SARS-CoV-2 transmission by persons not demonstrating symptoms.

Modeling Evidence

Two studies used models to estimate the serial interval (time between symptom onset in a primary patient and the secondary patient) (29,30) (Table 3). They estimated the serial interval of COVID-19 to be 4 days, which is shorter than the estimated median incubation period for COVID-19 of 5 days (31). One report suggested that up to 13% of infections may be transmitted during the presymptomatic period of illness (29). These studies relied on reports of primary and secondary cases and may be limited by recall bias; secondary patients are more likely to remember proximal exposures, biasing results toward a shorter serial interval.

Two models attempted to estimate the number of infections caused by asymptomatic, presymptomatic, or mildly symptomatic infected persons (30,32). These models varied widely; 1 model suggested that up to half of infections were transmitted from infected persons who were presymptomatic (33), and another suggested that up to four fifths of infections were transmitted by persons with no symptoms or mild symptoms (32). Both models suggested that a large number of persons with asymptomatic or mildly symptomatic infections were not detected by the health system and that these persons meaningfully contributed to ongoing community transmission (32,33). Although models are highly dependent on the assumptions built into them, these models suggest that the speed and extent of SARS-CoV-2 transmission cannot be accounted for solely by transmission from symptomatic persons.

Each of the epidemiologic, virologic, and modeling studies described has limitations. However, in the aggregate, these diverse studies suggest that SARS-CoV-2 can be transmitted by persons with presymptomatic or asymptomatic infection, which may meaningfully contribute to the propagation of the COVID-19 pandemic. This literature summation was conducted to support changes in CDC recommendations to reduce the risk for asymptomatic transmission and was not a systematic review. These conclusions are drawn from the literature available at the time and may change, given the rapidly evolving nature of the evidence base for asymptomatic transmission.

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.

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References

  1. Wang  Y, Liu  Y, Liu  L, Wang  X, Luo  N, Ling  L. Clinical outcome of 55 asymptomatic cases at the time of hospital admission infected with SARS-Coronavirus-2 in Shenzhen, China. J Infect Dis. 2020;jiaa119; Epub ahead of print. DOIPubMedGoogle Scholar
  2. Chan  JF, Yuan  S, Kok  KH, To  KK, Chu  H, Yang  J, 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;395:51423. DOIPubMedGoogle Scholar
  3. Chang  L, Zhao  L, Gong  H, Wang  L, Wang  L. Severe acute respiratory syndrome coronavirus 2 RNA detected in blood donations. Emerg Infect Dis. 2020;26: Epub ahead of print. DOIPubMedGoogle Scholar
  4. Dong  Y, Mo  X, Hu  Y, Qi  X, Jiang  F, Jiang  Z, et al. Epidemiological characteristics of 2143 pediatric patients with 2019 coronavirus disease in China. Pediatrics. 2020; [Epub ahead of print]. DOIGoogle Scholar
  5. Mizumoto  K, Kagaya  K, Zarebski  A, Chowell  G. Estimating the asymptomatic proportion of coronavirus disease 2019 (COVID-19) cases on board the Diamond Princess cruise ship, Yokohama, Japan, 2020. Euro Surveill. 2020;25:25; Epub ahead of print. DOIPubMedGoogle Scholar
  6. Roxby  AC, Greninger  AL, Hatfield  KM, Lynch  JB, Dellit  TH, James  A, et al. Detection of SARS-CoV-2 among residents and staff members of an independent and assisted living community for older adults– Seattle, Washington, 2020. MMWR Morb Mortal Wkly Rep. 2020;69:4168. DOIPubMedGoogle Scholar
  7. Tian  S, Hu  N, Lou  J, Chen  K, Kang  X, Xiang  Z, et al. Characteristics of COVID-19 infection in Beijing. J Infect. 2020;80:4016. DOIPubMedGoogle Scholar
  8. Ng  O-T, Marimuthu  K, Chia  P-Y, Koh  V, Chiew  CJ, De Wang  L, et al. SARS-CoV-2 infection among travelers returning from Wuhan, China. N Engl J Med. 2020;382:14768. DOIPubMedGoogle Scholar
  9. Li  C, Ji  F, Wang  L, Wang  L, Hao  J, Dai  M, et al. Asymptomatic and human-to-human transmission of SARS-CoV-2 in a 2-family cluster, Xuzhou, China. Emerg Infect Dis. 2020 Mar 31 [Epub ahead of print].
  10. Tong  ZD, Tang  A, Li  KF, Li  P, Wang  HL, Yi  JP, et al. Potential presymptomatic transmission of SARS-CoV-2, Zhejiang Province, China, 2020. Emerg Infect Dis. 2020;26:10524. DOIPubMedGoogle Scholar
  11. Yu  P, Zhu  J, Zhang  Z, Han  Y, Huang  L. A familial cluster of infection associated with the 2019 novel coronavirus indicating potential person-to-person transmission during the incubation period. J Infect Dis. 2020;jiaa077; Epub ahead of print. DOIPubMedGoogle Scholar
  12. Ye  F, Xu  S, Rong  Z, Xu  R, Liu  X, Deng  P, et al. Delivery of infection from asymptomatic carriers of COVID-19 in a familial cluster. Int J Infect Dis. 2020;94:1338; Epub ahead of print. DOIPubMedGoogle Scholar
  13. Bai  Y, Yao  L, Wei  T, Tian  F, Jin  DY, Chen  L, et al. Presumed asymptomatic carrier transmission of COVID-19. JAMA. 2020;323:1406. DOIPubMedGoogle Scholar
  14. Hu  Z, Song  C, Xu  C, Jin  G, Chen  Y, Xu  X, et al. Clinical characteristics of 24 asymptomatic infections with COVID-19 screened among close contacts in Nanjing, China. Sci China Life Sci. 2020;63:70611. DOIPubMedGoogle Scholar
  15. Zhang  J, Tian  S, Lou  J, Chen  Y. Familial cluster of COVID-19 infection from an asymptomatic. Crit Care. 2020;24:119. DOIPubMedGoogle Scholar
  16. Pan  X, Chen  D, Xia  Y, Wu  X, Li  T, Ou  X, et al. Asymptomatic cases in a family cluster with SARS-CoV-2 infection. Lancet Infect Dis. 2020;20:4101. DOIPubMedGoogle Scholar
  17. Qian  G, Yang  N, Ma  AHY, Wang  L, Li  G, Chen  X, et al. A COVID-19 Transmission within a family cluster by presymptomatic infectors in China. Clin Infect Dis. 2020;ciaa316; Epub ahead of print. DOIPubMedGoogle Scholar
  18. Rothe  C, Schunk  M, Sothmann  P, Bretzel  G, Froeschl  G, Wallrauch  C, et al. Transmission of 2019-nCoV infection from an asymptomatic contact in Germany. N Engl J Med. 2020;382:9701. DOIPubMedGoogle Scholar
  19. Wei  WE, Li  Z, Chiew  CJ, Yong  SE, Toh  MP, Lee  VJ. Presymptomatic Transmission of SARS-CoV-2 - Singapore, January 23-March 16, 2020. MMWR Morb Mortal Wkly Rep. 2020;69:4115. DOIPubMedGoogle Scholar
  20. Loeffelholz  MJ, Tang  YW. Laboratory diagnosis of emerging human coronavirus infections - the state of the art. Emerg Microbes Infect. 2020;9:74756. DOIPubMedGoogle Scholar
  21. Corman  VM, Landt  O, Kaiser  M, Molenkamp  R, Meijer  A, Chu  DKW, et al. Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR. Euro Surveill. 2020;25:25; Epub ahead of print. DOIPubMedGoogle Scholar
  22. Wölfel  R, Corman  VM, Guggemos  W, Seilmaier  M, Zange  S, Müller  MA, et al. Virological assessment of hospitalized patients with COVID-2019. Nature. 2020; Epub ahead of print. DOIPubMedGoogle Scholar
  23. Arons  MM, Hatfield  KM, Reddy  SC, Kimball  A, James  A, Jacobs  JR, et al. Presymptomatic SARS-CoV-2 infections and transmission in a skilled nursing facility. N Engl J Med. 2020;NEJMoa2008457; Epub ahead of print. DOIPubMedGoogle Scholar
  24. Hoehl  S, Rabenau  H, Berger  A, Kortenbusch  M, Cinatl  J, Bojkova  D, et al. Evidence of SARS-CoV-2 infection in returning travelers from Wuhan, China. N Engl J Med. 2020;382:127880. DOIPubMedGoogle Scholar
  25. Kam  KQ, Yung  CF, Cui  L, Lin Tzer Pin  R, Mak  TM, Maiwald  M, et al. A well infant with coronavirus disease 2019 with high viral load. Clin Infect Dis. 2020;ciaa201; Epub ahead of print. DOIPubMedGoogle Scholar
  26. Le  TQM, Takemura  T, Moi  ML, Nabeshima  T, Nguyen  LKH, Hoang  VMP, et al. Severe acute respiratory syndrome coronavirus 2 shedding by travelers, Vietnam, 2020. Emerg Infect Dis. 2020;26: Epub ahead of print. DOIPubMedGoogle Scholar
  27. Zou  L, Ruan  F, Huang  M, Liang  L, Huang  H, Hong  Z, et al. SARS-CoV-2 viral load in upper respiratory specimens of infected patients. N Engl J Med. 2020;382:11779. DOIPubMedGoogle Scholar
  28. Kimball  A, Hatfield  KM, Arons  M, James  A, Taylor  J, Spicer  K, et al.; Public Health – Seattle & King County; CDC COVID-19 Investigation Team. Public Health – Seattle & King County; CDC COVID-19 Investigation Team. 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;69:37781; Epub ahead of print. DOIPubMedGoogle Scholar
  29. Du  Z, Xu  X, Wu  Y, Wang  L, Cowling  BJ, Meyers  LA. Serial interval of COVID-19 among publicly reported confirmed cases. Emerg Infect Dis. 2020;26: Epub ahead of print. DOIPubMedGoogle Scholar
  30. Nishiura  H, Linton  NM, Akhmetzhanov  AR. Serial interval of novel coronavirus (COVID-19) infections. Int J Infect Dis. 2020;93:2846. DOIPubMedGoogle Scholar
  31. Lauer  SA, Grantz  KH, Bi  Q, Jones  FK, Zheng  Q, Meredith  HR, et al. The incubation period of coronavirus disease 2019 (COVID-19) from publicly reported confirmed cases: estimation and application. Ann Intern Med. 2020; Epub ahead of print. DOIPubMedGoogle Scholar
  32. Li  R, Pei  S, Chen  B, Song  Y, Zhang  T, Yang  W, et al. Substantial undocumented infection facilitates the rapid dissemination of novel coronavirus (SARS-CoV-2). Science. 2020;368:48993; Epub ahead of print. DOIPubMedGoogle Scholar
  33. Ferretti  L, Wymant  C, Kendall  M, Zhao  L, Nurtay  A, Abeler-Dörner  L, et al. Quantifying SARS-CoV-2 transmission suggests epidemic control with digital contact tracing. Science. 2020;eabb6936; Epub ahead of print.
  34. Verity  R, Okell  LC, Dorigatti  I, Winskill  P, Whittaker  C, Imai  N, et al. Estimates of the severity of coronavirus disease 2019: a model-based analysis. Lancet Infect Dis. 2020;S1473-3099(20)30243-7; Epub ahead of print. DOIPubMedGoogle Scholar
  35. Wu  JT, Leung  K, Bushman  M, Kishore  N, Niehus  R, de Salazar  PM, et al. Estimating clinical severity of COVID-19 from the transmission dynamics in Wuhan, China. Nat Med. 2020;26:50610. DOIPubMedGoogle Scholar
  36. Lasry  A, Kidder  D, Hast  M, Poovey  J, Sunshine  G, Winglee  K, et al. Timing of community mitigation and changes in reported covid-19 and community mobility—four US metropolitan areas, February 26–April 1, 2020. MMWR Morb Mortal Wkly Rep. 2020 Apr 13 [Epub ahead of print].
  37. Mahase  E. Covid-19: What is the evidence for cloth masks? BMJ. 2020;369:m1422. DOIPubMedGoogle Scholar
  38. Klompas  M, Morris  CA, Sinclair  J, Pearson  M, Shenoy  ES. Universal masking in hospitals in the COVID-19 era. N Engl J Med. 2020;NEJMp2006372; Epub ahead of print. DOIPubMedGoogle Scholar
  39. He  X, Lau  EHY, Wu  P, Deng  X, Wang  J, Hao  X, et al. Temporal dynamics in viral shedding and transmissibility of COVID-19. Nat Med. 2020; Epub ahead of print. DOIPubMedGoogle Scholar
  40. Kissler  SM, Tedijanto  C, Goldstein  E, Grad  YH, Lipsitch  M. Projecting the transmission dynamics of SARS-CoV-2 through the postpandemic period. Science. 2020;eabb5793; Epub ahead of print.

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Suggested citation for this article: Furukawa NW, Brooks JT, Sobel J. Evidence supporting transmission of severe acute respiratory syndrome coronavirus 2 while presymptomatic or asymptomatic. Emerg Infect Dis. 2020 Jul [date cited]. https://doi.org/10.3201/eid2607.201595

DOI: 10.3201/eid2607.201595

Original Publication Date: May 04, 2020

Table of Contents – Volume 26, Number 7—July 2020

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Address for correspondence: Nathan W. Furukawa, Centers for Disease Control and Prevention, 1600 Clifton Rd NE, Mailstop US8-4, Atlanta, GA 30329-4027, USA

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Page created: May 04, 2020
Page updated: June 18, 2020
Page reviewed: June 18, 2020
The conclusions, findings, and opinions expressed by authors contributing to this journal do not necessarily reflect the official position of the U.S. Department of Health and Human Services, the Public Health Service, the Centers for Disease Control and Prevention, or the authors' affiliated institutions. Use of trade names is for identification only and does not imply endorsement by any of the groups named above.
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