We used contact tracing to document how COVID-19 was transmitted across 5 generations involving 10 cases, starting with an individual who became ill on January 27. We calculated the incubation period of the cases as the interval between infection and development of symptoms. The median incubation period was 6.0 days (interquartile range, 3.5-9.5 days). The last two generations were infected in public places, 3 and 4 days prior to the onset of illness in their infectors. Both had certain underlying conditions and comorbidity. Further identification of how individuals transmit prior to being symptomatic will have important consequences.
Pre-symptomatic transmission of novel coronavirus in community settings
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Keywords
median incubation periodpre-symptomatic transmissionincubation periodinterquartile rangecommunity settingsunderlying conditionsinfectorscoronavirusgenerationsAbstract
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Decision Letter
2020/05/2929-May-2020
Dear Dr. Pan:
It is a pleasure to accept your manuscript entitled "Pre-symptomatic transmission of novel coronavirus in community settings" in its current form for publication in Influenza and Other Respiratory Viruses.
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Author Response
2020/05/27Reviewer Comments to Author:
The authors present a detailed contact tracing exercise and identified two pre-symptomatic transmission events, such reports would help understand the transmission of SARS-CoV-2.
- Copyediting is needed.
Authors’ response: We appreciate all the comments from the reviewer, and have made minor edits throughout to improve grammar.
- Introduction, “The incubation period is composed of latent period and infectious period.” Please cite a reference to support the statement, especially this implies that COVID-19 cases were infectious before symptom onset.
Authors’ response: We agree this sentence is confusing so we have deleted it. The subsequent sentence (Line 81: “The challenge for controlling COVID-19 is to determine at what point an individual becomes infectious, which can have implications for contact tracing and other epidemiological investigations”) is an adequate topic sentence for the paragraph.
- It would be helpful for the reader to clarify that in this study, the index case was actually the last case among all reported cases.
Authors’ response: We have now clarified this in the first sentence of the Methods (Line 98: “An index case (i.e., the last case) was first identified in our study”).
- L100, Methods, please elaborate what has been done to confirm that there were ‘no obvious previous contact’ for the index case.
Authors’ response: We have explained contact tracing in more detail throughout the methods. In regards to the index case, we now write (line 99): “For the index case we identified 3 close contacts in the 14 days prior to disease onset, none of which had COVID-19 at the time of contact.”
- Please provide more information on the contact tracing, for example how many contacts were interviewed. Some of the cases were senior, what has been done to minimize recall bias? What criteria was used to determine an epidemiological link? How symptoms were reported / symptom onset was determined? These are crucial to understand the data and should be further described in the appendix.
Authors’ response: We have included information on what constitutes a contact in the methods (line 101):
“We used contact tracing to identify possible people who could have exposed the case. Close contacts were defined as people who live, study, work, or otherwise have close contact with the case; medical personnel, family members, or other people who have similarly had close contact with the case and who did not take effective protective measures; other patients and their accompanying staff in the same ward of the case; persons in the same vehicle as the case and who had close contact with the case; and other persons who were deemed close contacts by the field investigator. “
As we now mention in the methods (line 115): “Information about symptoms and date of illness onset was provided directly by the cases. We acknowledge recall bias: cases may not have been able to remember every contact they had.”
- Figure, please add labels to indicate symptom onset, time of exposure, etc.
Authors’ response: We have edited the figure to be clearer and include these labels.
- Figure, cases #6, 5, 7 were placed on the leftmost. Why?
Authors’ response: This was an error while designing the figure. We have edited the figure and removed the dotted line.
- Figure, times of contact were not fully presented. For example, case 1 and index case also met on January 18. There may be other contacts among other cases. The authors may like to include other contacts separately that was considered not leading to transmission events.
Authors’ response: We have now expanded the information about numbers of cases in the figure legend: “Not shown are additional close contacts (with individuals who remained symptom-free after a 14-day quarantine): 3 for the index case, 1 for case 1, 1 for case 2, 11 for case 3, 12 for case 5, 1 for case 8, and 1 for case 9.” To create a concise image, we have decided to not include these contacts, and instead focus on events which presumably resulted in transmission.
- Case #1 was presumably infected on Jan 19 and was infectious within 2 days. How likely would that be?
Authors’ response: We agree this is a relatively short period. A modeling study estimates that latency period to be 3.69 days on average (https://science.sciencemag.org/content/sci/368/6490/489.full.pdf), and future studies in diverse settings should assess the lower bounds of the latency period.
- Case #1 was infectious on Jan 21, 4 days prior to symptom onset. How likely would that be?
Authors’ response: This is not a likely scenario for every COVID-19 patient. However, other investigations have used a boundary of 4 days (line 182): “a study of COVID-19 cases in Taiwan also started investigations of COVID-19 up to 4 days before symptom onset, although this was not consistently done.”
- L181, WHO recommendation (reference 10) did not suggest a close contact with exposure 4 days prior to illness onset of the cases
Authors’ response: We have looked at the latest WHO guidelines and agree that it should be 2 days not 4 days. We modified this sentence to be (line 180):
“Thus, we suggest advancing the upper time limit of close contact to 4 days prior to illness onset of a COVID-19 case, which is greater than the China CDC and WHO guidelines of 2 days.8,9 We note that guidelines in Beijing use a time limit of 4 days as of May 18, 2020.10“
- L181, the suggestion to extend the upper limit of close contact to 4 days may be premature, as it relied on one transmission event only.
Authors’ response: We agree that we should temper our recommendation. We now write (line 193):
“We recognize that increasing the duration of a possible time of infection can add to the workload of routine epidemiological investigations during the epidemic of COVID-19. Consequently, we recommend it should be applied to cases with an unknown source of infection, such as the index case in our study. Contact tracing guidelines should also rely on the capacity of contact tracing and on updated information on when presymptomatic transmission can occur. For example, a study of COVID-19 cases in Taiwan also started investigations of COVID-19 up to 4 days before symptom onset, although this was not consistently done.11”
Minor comments
13. L78, ‘lower’ should be ‘shorter’Authors’ response: Changed.
- L80 is repetitive
Authors’ response: We deleted this sentence. As the reviewer mentions, most of the information is already in a previous sentence (line 75: “The Chinese Center for Disease Control and Prevention (CDC) has estimated that the mean serial interval for COVID-19 is 7.5 days, which is slightly longer than the estimated incubation period of 5.2 days”).
- L94, ‘infections’ should be ‘infectious’
Authors’ response: Changed.
- L128, replace ‘double’ with ‘two occasions of’
Authors’ response: Changed.
- L157, L170, L177, ‘lower’ should be ‘shorter’
Authors’ response: All changed.
- Please update the references that have been published, e.g. ref 6, 8 and others
Authors’ response: We went through all references and searched to find published versions of the citations.
- Reference 8, delete the word ‘Running’. The study has also been published.
Authors’ response: Changed.
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- pre-publication peer review (ROUND 1)
Decision Letter
2020/05/1010-May-2020
Dear Dr. Pan
Manuscript ID IRV-2020-142 entitled "Pre-symptomatic transmission of novel coronavirus in community settings" which you submitted to the Influenza and Other Respiratory Viruses, has been reviewed. The comments of the reviewer are included at the bottom of this letter.
They have recommended some revisions to your manuscript and I would like to give you the opportunity to respond to their comments and revise your manuscript.
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We recognise that the impact of the COVID-19 pandemic may affect your ability to return your revised manuscript to us within the requested timeframe. If this is the case, please let us know.
Once again, thank you for submitting your manuscript to the Influenza and Other Respiratory Viruses and I look forward to receiving your revision.
Yours sincerely,
Prof. Benjamin Cowling
Editor in Chief, Influenza and Other Respiratory VirusesReviewer Comments to Author:
The authors present a detailed contact tracing exercise and identified two pre-symptomatic transmission events, such reports would help understand the transmission of SARS-CoV-2.
- Copyediting is needed.
- Introduction, “The incubation period is composed of latent period and infectious period.” Please cite a reference to support the statement, especially this implies that COVID-19 cases were infectious before symptom onset.
- It would be helpful for the reader to clarify that in this study, the index case was actually the last case among all reported cases.
- L100, Methods, please elaborate what has been done to confirm that there were ‘no obvious previous contact’ for the index case.
- Please provide more information on the contact tracing, for example how many contacts were interviewed. Some of the cases were senior, what has been done to minimize recall bias? What criteria was used to determine an epidemiological link? How symptoms were reported / symptom onset was determined? These are crucial to understand the data and should be further described in the appendix.
- Figure, please add labels to indicate symptom onset, time of exposure, etc.
- Figure, cases #6, 5, 7 were placed on the leftmost. Why?
- Figure, times of contact were not fully presented. For example, case 1 and index case also met on January 18. There may be other contacts among other cases. The authors may like to include other contacts separately that was considered not leading to transmission events.
- Case #1 was presumably infected on Jan 19 and was infectious within 2 days. How likely would that be?
- Case #1 was infectious on Jan 21, 4 days prior to symptom onset. How likely would that be?
- L181, WHO recommendation (reference 10) did not suggest a close contact with exposure 4 days prior to illness onset of the cases
- L181, the suggestion to extend the upper limit of close contact to 4 days may be premature, as it relied on one transmission event only.
Minor comments - L78, ‘lower’ should be ‘shorter’
- L80 is repetitive
- L94, ‘infections’ should be ‘infectious’
- L128, replace ‘double’ with ‘two occasions of’
- L157, L170, L177, ‘lower’ should be ‘shorter’
- Please update the references that have been published, e.g. ref 6, 8 and others
- Reference 8, delete the word ‘Running’. The study has also been published.
Decision letter by
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Reviewer report
2020/05/09The authors present a detailed contact tracing exercise and identified two pre-symptomatic transmission events, such reports would help understand the transmission of SARS-CoV-2.
Comments to the authors
1. Copyediting is needed.
2. Introduction, “The incubation period is composed of latent period and infectious period.” Please cite a reference to support the statement, especially this implies that COVID-19 cases were infectious before symptom onset.
3. It would be helpful for the reader to clarify that in this study, the index case was actually the last case among all reported cases.
4. L100, Methods, please elaborate what has been done to confirm that there were ‘no obvious previous contact’ for the index case.
5. Please provide more information on the contact tracing, for example how many contacts were interviewed. Some of the cases were senior, what has been done to minimize recall bias? What criteria was used to determine an epidemiological link? How symptoms were reported / symptom onset was determined? These are crucial to understand the data and should be further described in the appendix.
6. Figure, please add labels to indicate symptom onset, time of exposure, etc.
7. Figure, cases #6, 5, 7 were placed on the leftmost. Why?
8. Figure, times of contact were not fully presented. For example, case 1 and index case also met on January 18. There may be other contacts among other cases. The authors may like to include other contacts separately that was considered not leading to transmission events.
9. Case #1 was presumably infected on Jan 19 and was infectious within 2 days. How likely would that be?
10. Case #1 was infectious on Jan 21, 4 days prior to symptom onset. How likely would that be?
11. L181, WHO recommendation (reference 10) did not suggest a close contact with exposure 4 days prior to illness onset of the cases
12. L181, the suggestion to extend the upper limit of close contact to 4 days may be premature, as it relied on one transmission event only.
Minor comments
13. L78, ‘lower’ should be ‘shorter’
14. L80 is repetitive
15. L94, ‘infections’ should be ‘infectious’
16. L128, replace ‘double’ with ‘two occasions of’
17. L157, L170, L177, ‘lower’ should be ‘shorter’
18. Please update the references that have been published, e.g. ref 6, 8 and others
19. Reference 8, delete the word ‘Running’. The study has also been published.Reviewed by
Cite this review
