
On January 20, 2020, the Chinese State Council added the latest coronavirus disease (COVID19) to the Category B list of nationally notifiable diseases under Category A management (12). This means that if a case is diagnosed with COVID19, it must be reported by the physician to the National Notifiable Disease Reporting System (NNDRS) within two hours. However, new cases reported every day from the surveillance system often contain cases that had onset on or before the reporting date, indicating a lag between onset and diagnosis. A more accurate assessment of incidence will allow public health professionals to better assess ongoing outbreaks, the pattern and scale of further epidemics, and the effectiveness of current prevention and control strategies, etc. (3). However, in the case of an emerging infectious diseases, such as COVID19, the precise distribution of lag time between the dates of onset and the reporting times at the early stage of transmission was not known due to lack of historical data. Furthermore, all statistical incidence counts of each day are censored or truncated, i.e. up to the last reporting date, making it more difficult to estimate the precise distribution of delayed onsetreporting times. In this study, a Bayesian statistical method was proposed to estimate the exact probability distribution of the lag time between the onset date and the reporting time, and then to predict the actual number of new incident cases and the number of unreported cases per day.
All data for this study were obtained from NNDRS. The dataset for all suspected and confirmed cases of COVID19 was downloaded from NNDRS around 24∶00 on March 26, 2020, and the difference between date of onset and report time was used to calculate the lag time for each case. The lag time was assumed to follow the same probability distribution over a certain timeframe if the case diagnostic criteria, diagnostic methods, and other factors related to case reporting remained relatively stable. For this reason, new cases with onset dates between February 5 and February 28 were chosen for this analysis, and a training dataset (data reported as February 28 at 24∶00) and a validation dataset (data reported as March 25 at 24∶00) were built. Based on the distributions of time delays for other infectious diseases, particularly influenza cases in the last few years and the empirical distribution of time delays for all COVID19 cases in NNDRS, the gamma probability distribution was selected to be validated with high priority in this study. At first, the lag times were transformed using the base2 logarithm. A random variable X that is gammadistributed with parameters α and β is denoted as follows:
$$X \sim \Gamma \left( {\alpha ,\beta } \right) \equiv Gamma\left( {\alpha ,\beta } \right). $$ (1) Where α is a shape parameter and β is a scale parameter, also called a rate parameter. Its corresponding probability density function is as follows:
$$f\left( {x;\alpha ,\beta } \right) = \frac{{{\beta ^\alpha }{x^{\alpha  1}}{e^{  \beta x}}}}{{\Gamma \left( \alpha \right)}}\;\;\;{\rm{for}}\;x > 0\;\;\;\alpha ,\beta > 0 $$ (2) In our study, the logarithms of lag times were assumed to follow the truncated gamma distribution.
$$\begin{aligned} & {log _2}\left( {lagtime\left[ i \right]} \right) \sim \Gamma \left( {\alpha ,\beta } \right)T\left( {0,index\left[ i \right]} \right) \equiv \\ & \quad Gamma\left( {\alpha ,\beta } \right)T\left( {0,index\left[ i \right]} \right) \end{aligned}$$ (3) $$\alpha \sim uniform\left( {9.0,15} \right) $$ (4) $$\beta \sim uniform\left( {3.5,6.5} \right) $$ (5) Where the α and β are the parameters to be estimated for the gamma distribution, the prior distributions of both parameters were set to follow the uniform distributions, lagtime[i] is the logarithm of the lag time of the ith case, T stands for the truncated distribution, and index[i] is the logarithm of the time interval from the start date of the ith case to the end of the study time frame (24∶00 on February 28) of the training dataset.
The cumulative reported rate was calculated using the posterior parameters of gamma distribution estimated from the abovementioned steps and the gamma cumulative distribution as follows.
$$rate\left[ n \right] = F\left( {n;\alpha ,\beta } \right) = \int_0^n {f\left( {u;\alpha ,\beta } \right)} du $$ (6) Where F and f are the gamma cumulative probability function and gamma probability density function, respectively. The number of unreported incident cases was assumed to follow the negative binomial distribution. The number of cases of incidence for each day were estimated as follows.
$$NR\left( n \right) \sim dnegbin\left( {rate\left[ n \right],reported\left[ n \right]} \right) $$ (7) $$NN\left( n \right) = NR\left[ n \right] + reported\left[ n \right] $$ (8) Where n is the number of days from date of onset to the 24∶00 on February 28, the dnegbin is the negative binomial distribution, the rate[n] is the cumulative probability of reporting of n days, the reported[n] is the numbers of reported cases of n days calculated from the training data samples, and the NR[n] is the number of unreported cases, and the NN[n] is the predicted total number of cases. Since the number of new cases reported within two days was almost zero, we estimated the real incident cases from February 5 to February 26, 2020.
The validation data included all the cases with onset dates between February 5 and February 28, which were reported until 24∶00 on March 26. The logarithm of the lag times in the validation dataset were fitted with gamma and other probability distribution models. The parameters of gamma probability distribution were estimated in both the training dataset using Bayesian Markov chain Monte Carlo (MCMC) method with truncated distribution and in the validation dataset using maximum likelihood method, respectively. The parameters of gamma probability distribution from training were used to estimate unreported and total number of incident cases every day. The estimated number of unreported and total incident cases were compared with the actual reported ones in the validation dataset. All statistical analyses were performed in R statistical software (version 4.0.3; The R Foundation for Statistical Computing, Vienna, Austria) (4), where Bayesian statistics were performed using the rjages (5) and runjags (6) packages, and general probability distribution fitting was performed using the fitdistrplus (7) package.
As of 24∶00 on March 26, there were 24,551 cases in the validation dataset with onset dates between February 5 and February 28. The median lag time was 4.92 days, with 25 and 75 percentile values of 3.41 and 8.43 days, respectively. Gamma distribution was found to be the best fitted model compared to other probabilistic distribution models based on either the Akaike information criterion (AIC) or the Bayesian information criterion (BIC) values. The shape and rate parameters of the gamma distribution of the validation dataset were 8.56 and 3.54, respectively (Table 1).
Distribution LogLikelihood Akaike information criterion（AIC） Bayesian information criterion (BIC) Gamma –29,206.3 58,416.6 58,432.8 Burr –29,705.1 59,416.3 59,440.6 Weibull –29,757.8 59,519.6 59,535.8 Normal –30,102.4 60,208.7 60,224.9 Pareto –46,263.8 92,531.6 92,547.8 Table 1. The results of probability distribution fittings of the logarithm of the lagtimes based on validation dataset.
The gamma probability distribution curves obtained for the two different methods as mentioned above are shown in Figure 1.
Figure 1. Comparison of the curves of the two gamma probability distributions of lag time based on the training and validation datasets.For the number of cases with an onset date between February 5 and February 26, the model predicted that there would be 2,112 unreported cases, while the actual reporting resulted in 1,665 newly reported cases as of March 26. The number of unreported cases predicted by the Bayesian model was 26.84% higher than the actual number of reported cases, with a ratio of 1∶0.7881.
The model’s prediction of the total number of incident cases per day and its trend from February 5 to February 26 were generally consistent with the actual incidence data reported as of March 26. However, the model’s predictions after February 21 were significantly higher than the actual data reported as shown in Figure 2 and Table 2.
Figure 2. Comparison of the predicted number of COVID19 incident cases by the Bayesian probability model and the number actually reported.Date of onset Number of incident cases reported by February 28 Number of unreported cases and 95% CI predicted by model Total number of incident cases and the 95% CI predicted by model Number of incident cases reported by
March 26Cases reported
from February 29
to March 262020/2/5 2,529 24(15–34) 2,553(2,544–2,563) 2,559 30 2020/2/6 2,072 22(13–32) 2,094(2,085–2,104) 2,087 15 2020/2/7 2,007 25(16–36) 2,032(2,023–2,043) 2,036 29 2020/2/8 1,814 26(17–37) 1,840(1,831–1,851) 1,833 19 2020/2/9 1,438 24(15–35) 1,462(1,453–1,473) 1,453 15 2020/2/10 1,830 36(25–49) 1,866(1,855–1,879) 1,875 45 2020/2/11 1,343 31(21–43) 1,374(1,364–1,386) 1,366 23 2020/2/12 1,465 41(28–54) 1,506(1,493–1,519) 1,495 30 2020/2/13 1,265 42(30–56) 1,307(1,295–1,321) 1,313 48 2020/2/14 1,027 42(30–55) 1,069(1,057–1,082) 1,111 84 2020/2/15 816 41(29–54) 857(845–870) 868 52 2020/2/16 739 46(33–61) 785(772–800) 787 48 2020/2/17 642 50(37–65) 692(679–707) 893 251 2020/2/18 813 81(64–101) 894(877–914) 851 38 2020/2/19 616 81(63–100) 697(679–716) 684 68 2020/2/20 384 68(51–86) 452(435–470) 461 77 2020/2/21 365 89(70–111) 454(435–476) 570 205 2020/2/22 379 134(109–161) 513(488–540) 452 73 2020/2/23 371 201(167–238) 572(538–609) 445 74 2020/2/24 282 259(217–305) 541(499–587) 350 68 2020/2/25 181 335(277–398) 516(458–579) 347 166 2020/2/26 74 408(314–517) 482(388–591) 281 207 Total 22,452 2,106(1,641–2,628) 24,558(24,093–25,080) 24,117 1,665 Table 2. Comparison of the predicted number of COVID19 incident cases by the Bayesian probability model and the number actually reported.
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