The contribution of asymptomatic SARS-CoV-2 infections to transmission on the Diamond Princess cruise ship
- London School of Hygiene and Tropical Medicine, United Kingdom
Abstract
A key unknown for SARS-CoV-2 is how asymptomatic infections contribute to transmission. We used a transmission model with asymptomatic and presymptomatic states, calibrated to data on disease onset and test frequency from the Diamond Princess cruise ship outbreak, to quantify the contribution of asymptomatic infections to transmission. The model estimated that 74% (70-78%, 95% posterior interval) of infections proceeded asymptomatically. Despite intense testing, 53% (51-56%) of infections remained undetected, most of them asymptomatic. Asymptomatic individuals were the source for 69% (20-85%) of all infections. The data did not allow identification of the infectiousness of asymptomatic infections, however low ranges (0-25%) required a net reproduction number for individuals progressing through presymptomatic and symptomatic stages of at least 15. Asymptomatic SARS-CoV-2 infections may contribute substantially to transmission. Control measures, and models projecting their potential impact, need to look beyond the symptomatic cases if they are to understand and address ongoing transmission.
Data availability
All data analysed during this study are included in the manuscript and supporting files. Model code is available through github.
Article and author information
Author details
Funding
European Research Council Starting Grant (Action Number 757699)
- Jon C Emery
- Rein M G J Houben
Wellcome (206250/Z/17/Z)
- Timothy W Russell
- Adam J Kucharski
Wellcome (208812/Z/17/Z)
- Stefan Flasche
Wellcome (210758/Z/18/Z)
- Joel Hellewell
- Sebastian Funk
Bill and Melinda Gates Foundation (INV-003174)
- Yang Liu
Bill and Melinda Gates Foundation (NTD Modelling Consortium OPP1184344)
- Carl AB Pearson
DFID/Wellcome Trust (Epidemic Preparedness Coronavirus research programme 221303/Z/20/Z)
- Carl AB Pearson
European Union Horizon 2020 (project EpiPose (101003688))
- Yang Liu
HDR UK (MR/S003975/1)
- Rosalind M Eggo
National Institute for Health Research (16/137/109)
- Yang Liu
Medical Research Council (MC_PC 19065)
- Rosalind M Eggo
Medical Research Council (MR/P014658/1)
- Gwenan M Knight
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Marc Lipsitch, Harvard TH Chan School of Public Health, United States
Version history
- Received: May 8, 2020
- Accepted: August 23, 2020
- Accepted Manuscript published: August 24, 2020 (version 1)
- Version of Record published: September 30, 2020 (version 2)
Copyright
© 2020, Emery et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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The contribution of asymptomatic SARS-CoV-2 infections to transmission on the Diamond Princess cruise ship
eLife 9:e58699.
https://doi.org/10.7554/eLife.58699
Further reading
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- Microbiology and Infectious Disease
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eLife has published articles on a wide range of infectious diseases, including COVID-19, influenza, tuberculosis, HIV/AIDS, malaria and typhoid fever.
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Background:
Although there are several efficacious vaccines against COVID-19, vaccination rates in many regions around the world remain insufficient to prevent continued high disease burden and emergence of viral variants. Repurposing of existing therapeutics that prevent or mitigate severe COVID-19 could help to address these challenges. The objective of this study was to determine whether prior use of bisphosphonates is associated with reduced incidence and/or severity of COVID-19.
Methods:
A retrospective cohort study utilizing payer-complete health insurance claims data from 8,239,790 patients with continuous medical and prescription insurance January 1, 2019 to June 30, 2020 was performed. The primary exposure of interest was use of any bisphosphonate from January 1, 2019 to February 29, 2020. Bisphosphonate users were identified as patients having at least one bisphosphonate claim during this period, who were then 1:1 propensity score-matched to bisphosphonate non-users by age, gender, insurance type, primary-care-provider visit in 2019, and comorbidity burden. Main outcomes of interest included: (a) any testing for SARS-CoV-2 infection; (b) COVID-19 diagnosis; and (c) hospitalization with a COVID-19 diagnosis between March 1, 2020 and June 30, 2020. Multiple sensitivity analyses were also performed to assess core study outcomes amongst more restrictive matches between BP users/non-users, as well as assessing the relationship between BP-use and other respiratory infections (pneumonia, acute bronchitis) both during the same study period as well as before the COVID outbreak.
Results:
A total of 7,906,603 patients for whom continuous medical and prescription insurance information was available were selected. A total of 450,366 bisphosphonate users were identified and 1:1 propensity score-matched to bisphosphonate non-users. Bisphosphonate users had lower odds ratios (OR) of testing for SARS-CoV-2 infection (OR = 0.22; 95%CI:0.21–0.23; p<0.001), COVID-19 diagnosis (OR = 0.23; 95%CI:0.22–0.24; p<0.001), and COVID-19-related hospitalization (OR = 0.26; 95%CI:0.24–0.29; p<0.001). Sensitivity analyses yielded results consistent with the primary analysis. Bisphosphonate-use was also associated with decreased odds of acute bronchitis (OR = 0.23; 95%CI:0.22–0.23; p<0.001) or pneumonia (OR = 0.32; 95%CI:0.31–0.34; p<0.001) in 2019, suggesting that bisphosphonates may protect against respiratory infections by a variety of pathogens, including but not limited to SARS-CoV-2.
Conclusions:
Prior bisphosphonate-use was associated with dramatically reduced odds of SARS-CoV-2 testing, COVID-19 diagnosis, and COVID-19-related hospitalizations. Prospective clinical trials will be required to establish a causal role for bisphosphonate-use in COVID-19-related outcomes.
Funding:
This study was supported by NIH grants, AR068383 and AI155865, a grant from MassCPR (to UHvA) and a CRI Irvington postdoctoral fellowship, CRI2453 (to PH).
