We present to you a series of daily questions related to various aspects of COVID-19, which summarizes what is known and what additional information is needed.

Incubation Period (Part 4)

How long after the infection do symptoms appear? Are people infectious during this time?

What do we know?

• The best estimate of the incubation period of COVID-19 at present stands at 5.1 days, with 99% of individuals exhibiting symptoms within 14 days following exposure.¹Less than 2.5% of infected individuals exhibit symptoms sooner than 2 days following exposure. ¹
• The range of incubation periods is wide, with estimates of 24,² 3, ³ and 18 days.⁴
• COVID-19 test can be positive in individuals lacking clinical symptoms.^2,5-8
• Individuals can be infectious while they are asymptomatic.^7-10  Additionally, asymptomatic individuals can carry similar amounts of virus in their nose and throat as symptomatic individuals.¹¹
• While the infectious period is largely unknown, it could possibly be up to 10-14 days.^12-14
• Approximately 4¹⁵ to 7.5⁴ days are there, on an average, between symptom onset in successive cases of a single transmission chain.
• A majority of individuals is admitted to the hospital within 8-14 days of symptom onset.¹⁶
• Patients are positive for COVID-19 via PCR for 8-37 days following symptom onset.¹⁶
• Individuals may test positive via PCR for 5-13 days after symptoms disappear and hospital discharge.¹⁷ The ability of these individuals to infect others is not clearly known.
• As per WHO, no evidence of re-infection with SARS-CoV-2 after recovery exists.¹⁸
• Experimentally infected macaques could not be reinfected after their primary infection resolved.¹⁹

 What do we need to know?

• The average infectious period during which individuals can transmit the disease?
• Are individuals infectious after hospital discharge and clinical recovery, or do positive PCR tests only detect non-infectious virus?
• Can individuals become re-infected after recovery? If yes, how long after?

 References

1. 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. Annals of Internal Medicine 2020.
2. Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, et al. Clinical characteristics of 2019 novel coronavirus infection in China. medRxiv 2020, 2020.02.06.20020974.
3. Backer JA, Klinkenberg D, Wallinga J. The incubation period of 2019-nCoV infections among travellers from Wuhan, China. medRxiv 2020, 2020.01.27.20018986.
4. Li Q, Guan X, Wu P, Wang X, Zhou L, Tong Y, et al. Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus–Infected Pneumonia. New England Journal of Medicine 2020.
5. Bai Y, Yao L, Wei T, Tian F, Jin DY, Chen L, Wang M. Presumed Asymptomatic Carrier Transmission of COVID-19. JAMA.
6. Chan JFW, Yuan S, Kok KH, to KKW, 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. The Lancet 2020.
7. The Novel Coronavirus Pneumonia Emergency Response Epidemiology, T., The Epidemiological Characteristics of an Outbreak of 2019 Novel Coronavirus Diseases (COVID-19) — China, 2020. China CDC Weekly 2020, 2, 1-10.
8. Zhen-Dong T, An T, Ke-Feng L, Peng L, Hong-Ling W, Jing-Ping Y, et al. Potential Presymptomatic Transmission of SARS-CoV-2, Zhejiang Province, China, 2020. Emerging Infectious Disease journal 2020, 26 (5).
9. CDC, Situation summary. https://www.cdc.gov/coronavirus/2019-nCoV/summary.html.
10. 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. New England Journal of Medicine 2020.
11. 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. New England Journal of Medicine 2020.
12. [Wuhan Pneumonia] The Hospital Authority stated that 2 critically ill patients needed external life support treatment. https://www.singtao.ca/4037242/2020-01-14/news-%E3%80%90%E6%AD%A6%E6%BC%A2%E8%82%BA%E7%82%8E%E3%80%91%E9%86%AB%E7%AE%A1%E5%B1%80%E6%8C%872%E5%90%8D%E9%87%8D%E7%97%87%E7%97%85%E6%82%A3%E9%9C%80%E9%AB%94%E5%A4%96%E7%94%9F%E5%91%BD%E6%94%AF%E6%8C%81%E6%B2%BB%E7%99%82/?variant=zh-hk.
13. 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-CoV2). Science 2020, eabb3221.
14. Security, J. C. f. H., 2019-nCoV resources and updates on the emerging novel coronavirus. 2020.
15. Du Z, Xu X, Wu Y, Wang L, Cowling BJ, Meyers LA. The serial interval of COVID-19 from publicly reported confirmed cases. medRxiv 2020, 2020.02.19.20025452.
16. Zhou F, Yu T, Du R, Gan G, Liu Y, Liu Z, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. The Lancet.
17. Lan L, Xu D, Ye G, Xia C, Wang S, Li Y, et al. Positive RT-PCR Test Results in Patients Recovered From COVID-19. Jama 2020.
18. Lau S. Coronavirus: WHO official says there’s no evidence of ‘reinfected’ patients in China https://www.scmp.com/news/china/society/article/307404/coronavirus-who-official-says-theres-no-evidence-reinfected.
19. Bao L, Deng W, Gao H, Xiao C, Liu J, Xue J, et al. Reinfection could not occur in SARS-CoV-2 infected rhesus macaques. bioRxiv 2020, 2020.03.13.990226.

(Source: DHS Science and Technology, Master Question List for COVID-19 (caused by SARS-CoV-2), Weekly Report, 18 March 2020)

(To be continued)

Dr KK Aggarwal

President CMAAO, HCFI and Past National President IMA