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Incubation Period of COVID-19 From 11545 Patients
in Observation Study
Cheng Cheng
Zhengzhou University
Dongdong Zhang
Zhengzhou University
Dejian Dang
The Fifth Aliated Hospital of Zhengzhou University
Juan Geng
Zhengzhou University of Light Industry
Peiyu Zhu
Zhengzhou University
Mingzhu Yuan
Zhengzhou University
Ruonan Liang
Zhengzhou University
Haiyan Yang
Zhengzhou University
Yuefei Jin
Zhengzhou University
Jing Xie
Peter MacCallum Cancer Centre
Shuaiyin Chen ( sychen@zzu.edu.cn )
Zhengzhou University
Guangcai Duan
Zhengzhou University
Research Article
Keywords: COVID-19, Incubation period, Mainland China
Posted Date: April 5th, 2021
DOI: https://doi.org/10.21203/rs.3.rs-332666/v1
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Abstract
Background
The incubation period is a key index of epidemiology in understanding of the spread of infectious
diseases and the decision-making of the disease control. However, the incubation period of the emerging
COVID-19 is still unclear.
Methods
Between January 19, 2020 and September 21, 2020, we collected information on 11545 patients in
Mainland China outside Hubei. The 218 patients with precise data was validation population. The
incubation period was tted with lognormal model by the coarseDataTools package in R.
Results
In 11545 patients, the mean incubation period of COVID-19 was 7.1 days (95% Condence interval [CI],
7.0–7.2). About 5.4% of patients had precise incubation period less than 3 days, 10.2% longer than 14
days, and 2.1% longer than 21 days. There was no statistically signicant difference in incubation period
between male and female (
P
= 0.603). It was similar in the 218 patients. The mean accurate incubation
period was 6.8 days (6.2–7.4). Of which, 14.7% (32/218) of patients had incubation period less than 3
days, 12.4% (27/218) longer than 14 days, and 0.9% (2/218) longer than 21 days.
Conclusions
For COVID-19, the mean incubation period is 7.1 days and 10.2% of patients developed disease 14 days
after infection, which challenges the current 14-day quarantine strategy.
Background
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus (SARS-
CoV-2), has spread over 223 countries and was declared a pandemic on March 11, 2020, by World Health
Organization
1
. The number of COVID-19 patients is rapidly increasing globally. There were more than
113.5million conrmed cases and 2.5million deaths globally by March 2, 2021
1
. The pandemic of
COVID-19 has become a worldwide public health issue.
Incubation period, known as the interval between initial infection and onset of disease, is an important
index to characterize the spread of infectious disease and formulate quarantine measures. For example,
the mean incubation period is often used to calculate the reproduction number, and the maximum
incubation period is the evidence to inform the duration of quarantine. In previously published studies, the
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mean/median incubations period of COVID-19 varied from 2.87 days
2
to 17.6 days
3
. Most patients with
COVID-19 had exposure intervals longer than one day, so the exact date of their infection cannot be easily
determined. Several studies used the earliest exposure time to dene of the infection date and provided
mean incubation periods of COVID-19 of about 8 days in mainland China outside Hubei province
4–6
.
Other studies used the latest exposure time to dene of the date of infection and reported a shorter mean
incubation periods of COVID-19 of about 5 days
7–9
. Obviously, the incubation period of COVID-19 was
overestimated using the earliest exposure and underestimated using the latest exposure, which resulted
in unreliable incubation periods. For the patients with unclear data on the date of infection or the date of
onset of disease, Nicholas et al provided a method to represent their data as doubly interval-censored to
accurate the incubation period distribution
10
. This method has been used to estimate the incubation
period in several previously studies with less than 1200 patients with COVID-19
11–13
, but the sample size
of these studies is much smaller than the total number of patients. Therefore, a study with large sample
is needed to estimate the incubation period of COVID-19.
This study aims to estimate the incubation period of COVID-19. We collect the information on conrmed
cases with COVID-19 in mainland China outside Hubei and extract data from 11,545 patients to estimate
the incubation periods. To verify the reliability of incubation period, sensitivity analysis is performed in
patients with precise date of infection and onset of disease.
Patients And Methods
Study Population
By September 21, 2020, a total of 17168 patients with COVID-19 have been diagnosed with positive
nucleic acid and clinical symptoms in Mainland China outside Hubei. Among them, the available
information of 11545 patients can be collected from the national and local health commissions in China
14
. We extracted the patients’ information including age, sex, date of the earliest exposure, date of the
latest exposure, date of the nucleic acid test report, date of onset of disease, date of rst visit, and date of
diagnosis. All 11545 patients were included to estimate the incubation period.
Further, 218 patients with precise date of infection and onset of disease were selected to estimate the
accurate incubation period. The exclude criteria included that the patient 1) did not report the date of
onset of disease, 2) did not report the date of the earliest exposure or the date of the latest exposure, and
3) had exposure intervals longer than 1 day.
This study was approved by the Zhengzhou University Medical Ethics Committee (Zhengzhou, China).
The information on all cases was collected from publicly available sources, and informed consent was
waived.
Date Of Onset And Date Of Infection
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The incubation period was dened as the time interval between the date of infection and the date of
onset of disease. There were 7303 patients with the date of onset of disease (Denition 1). In the patients
without the date of onset, we dened the date of onset as the date of rst visit minus 2.5 days (Denition
2) or the date of diagnosis minus 5.4 days (Denition 3)
14
. The date of infection is between the date of
the earliest exposure and the date of the latest exposure. If exposed to the source of infection only within
one day, the date of infection is the date of exposure, otherwise it was represented as doubly interval-
censored
10
. When the date of the latest exposure was not reported, we dened it as the earliest date
among date of the nucleic acid positive, date of onset of disease, date of rst visit, and date of diagnosis
minus one days. When the date of the earliest exposure was not reported or the exposure interval (from
the earliest exposure to the latest exposure) was longer than 14 days, we dened it as the date of the
latest exposure minus 14 days.
Statistical Analysis
We presented mean ((95% Condence interval [CI]) for continuous variables and count (percentage) for
categorical variables. The distribution curve of the incubation period was tted with lognormal model by
"coarseDataTools" package in the R software
10
. Wilcoxon signed-rank test was used to compare
differences in subgroup analysis by age and gender. Signicantly difference was identied with adjusted
P
value with false discovery rate at 0.05. Sensitivity analysis explored the impact of different denitions
of date of onset.
Statistical analyses were conducted using R version 4.0.2. Two-sided P < 0.05 indicated statistically
signicant.
Results
Estimating incubation period in observation study
Table1 presents the characteristics of 11545 patients with COVID-19. The median age was 45 years (IQR:
33–56), and there were 5814 males (52.7%). The mean incubation period is 7.1 days (95% CI, 7.0–7.2) in
total population. The tted curve (Fig.1) shows that there are 5.4% of patients with the incubation period
less than 3 days, 10.2% more than 14 days, and 2.1% more than 21 days.
