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Quantifying the improvement in confirmation efficiency of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during the early phase of the outbreak in Hong Kong in 2020

Open AccessPublished:May 10, 2020DOI:https://doi.org/10.1016/j.ijid.2020.05.015

      Highlights

      • Since the first imported case was confirmed in Hong Kong on January 23, 2020, local public interventions for SARS-CoV-2 control and prevention have been enhanced.
      • A regression model is adopted to quantify the association between the confirmation delay and the calendar time, validated by a Cox proportional hazard model.
      • We estimate that the SARS-CoV-2 confirmation efficiency improved 5.40% (95%CI: 2.54% − 8.33%) per day in Hong Kong.
      • The sustaining enforcement in timely confirmation and other effective control measures are recommended to prevent the spreading of the SARS-CoV-2 infection.

      Abstract

      Backgrounds

      The emerging virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), caused a large outbreak of coronavirus disease, COVID-19, in Wuhan, China, since December 2019. COVID-19 soon spread to other regions of China and overseas. In Hong Kong, local mitigation measures were implemented since the first imported case was confirmed on January 23, 2020. Here we evaluated the temporal variation of detection delay from symptoms onset to laboratory confirmation of SARS-CoV-2 in Hong Kong.

      Methods

      A regression model is adopted to quantify the association between the SARS-CoV-2 detection delay and calendar time. The association is tested and further validated by a Cox proportional hazard model.

      Findings

      The estimated median detection delay was 9.5 days (95%CI: 6.5 − 11.5) in the second half of January, reduced to 6.0 days (95%CI: 5.5 − 9.5) in the first half of February 2020. We estimate that SARS-CoV-2 detection efficiency improved at a daily rate of 5.40% (95%CI: 2.54 − 8.33) in Hong Kong.

      Conclusions

      The detection efficiency of SARS-CoV-2 was likely being improved substantially in Hong Kong since the first imported case was detected. Sustaining enforcement in timely detection and other effective control measures are recommended to prevent the SARS-CoV-2 infection.

      Keywords

      1. Backgrounds

      The deadly coronavirus disease (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, formerly 2019-nCoV), has emerged in Wuhan, China, in December 2019 (

      ’Pneumonia of unknown cause – China,’ Emergencies preparedness, response, Disease outbreak news, World Health Organization (WHO) [https://www.who.int/csr/don/05-january-2020-pneumonia-of-unkown-cause-china/en/]

      ). COVID-19 cases were soon exported to other Chinese cities and overseas, mainly owing to the traffic surge near the Chinese Lunar New Year (
      • Bogoch I.I.
      • Watts A.
      • Thomas-Bachli A.
      • Huber C.
      • Kraemer M.U.
      • Khan K.
      Pneumonia of unknown etiology in Wuhan, China: potential for international spread via commercial air travel.
      ,
      • Wu J.T.
      • Leung K.
      • Leung GM:
      Nowcasting and forecasting the potential domestic and international spread of the 2019-nCoV outbreak originating in Wuhan, China: a modelling study.
      ). The first imported cases in Hong Kong were confirmed and reported on January 23, 2020, see Fig. 1(a) . Since then, the government of Hong Kong has implemented a series of control and prevention measures for COVID-19, including enhanced border screening and traffic restrictions (

      Summary of data and outbreak situation of the Severe Respiratory Disease associated with a Novel Infectious Agent, Centre for Health Protection, the government of Hong Kong. [https://www.chp.gov.hk/en/features/102465.html]

      ,

      The collection of Press Releases by the Centre for Health Protection (CHP) of Hong Kong. [https://www.chp.gov.hk/en/media/116/index.html]

      ). The official news related to the COVID-19 outbreak was first released by the CHP on December 31, 2019. Outbreak-related news reports have been released daily since January 2 and updated at least twice per day since January 23, 2020 (

      The collection of Press Releases by the Centre for Health Protection (CHP) of Hong Kong. [https://www.chp.gov.hk/en/media/116/index.html]

      ). After the first week of February, COVID-19 was controlled at 1 incidence onset from February 9 to the present (as of February 15), 2020.
      Fig. 1
      Fig. 1The daily SARS-CoV-2 cases time series in (a), and count of tested cases (b) and the association between detection delay (τ) and time in (c). Panel (a) shows the time series of the daily number of SARS-CoV-2 cases aggregated by the date of onset (grey horizontal bars) and by the laboratory-confirmed date (black vertical bars). Panel (b) shows the time series of the daily number of tested cases. Panel (c) shows the detection delays (τ) of the cases who are Hong Kong residence (blue dots) and of the cases who are not Hong Kong residence (red triangles) vary over the calendar date. The bold curves are the fitting results of the regression in Eqn (1), and the dashed curves are the 95% confidence interval (95%CI).
      In this study, we quantify the improving rate of detection efficiency of SARS-CoV-2 in Hong Kong.

      2. Data and methods

      The follow-up data of individual patients were collected via the official website of the Centre for Health Protection (CHP) of Hong Kong (

      Summary of data and outbreak situation of the Severe Respiratory Disease associated with a Novel Infectious Agent, Centre for Health Protection, the government of Hong Kong. [https://www.chp.gov.hk/en/features/102465.html]

      ). All cases were laboratory-confirmed following the case definition, referring to the official diagnostic protocol released by WHO (

      Laboratory testing for 2019 novel coronavirus (2019-nCoV) in suspected human cases, World Health Organization (WHO) [https://www.who.int/health-topics/coronavirus/laboratory-diagnostics-for-novel-coronavirus]

      ).
      The case detection efficiency is the reciprocal of detection delay, denoted by τ. The detection delay (τ) is measured by the time interval between the date of COVID-19 symptoms onset and the date of laboratory confirmation. For the i-th patient, the detection delay is denoted by τi,t, where t denotes symptoms onset on the t-th day. Thus, the time evolution of the detection delay is formulated by a regression model in Eqn (1).
      Elogτi,t=βt+β1lognt,t+τ+β2isHKi+β0,
      (1)


      where E[·] represents the expectation. The ‘isHKi’ is an indicator that is 1 if the i-th patient is a Hong Kong resident but 0 otherwise. The nt,t+τ denotes the average number of cases being tested between the t-th and (t + τ)-th days, and thus it accounts for the effect of time-varying working load. The β is the regression coefficient for the onset time variable t. The β quantifies the rate of change in the detection delay. Since a shorter detection delay means a higher detection efficiency, we expect a negative estimate of β for an improving detection efficiency over time. The [exp(− β) − 1] × 100% quantifies the percentage improvement in the detection efficiency per day in Hong Kong. We fit the model by a Gamma-distributed likelihood framework. The 95% confidence interval (95%CI) of β is calculated by using its mean estimate plus and minus its standard deviation (SD) multiplied by the Student's t quantile.
      Validation analysis is conducted by using the Cox proportional hazard (PH) model defined as S(τ)=S0(τ)expαt+α1lognt,t+τ+α2isHK+α0, which has a similar form as Eqn (1). The S(·) is the survival function, and the S0(·) is the baseline survival function. Similarly, the α is the regression coefficient for t in the hazard function, and thus exp(α) is the hazard ratio (HR). In contrast to β, we expect a positive estimate of α for an improving detection efficiency over time. For validation, we exam the signs of the estimated α and β, and their statistical significance levels.

      3. Results and discussion

      Fig. 1(a) shows the epidemic curve of all 56 COVID-19 cases as of February 15, 2020, in Hong Kong. We reported that the onset cases peaked on January 30, and the confirmed cases peaked on February 9, 2020. The daily number of tests started increasing rapidly from January 23 until the end of January, see Fig. 1(b). The estimated median detection delay was 9.5 days (95%CI: 6.5 − 11.5) in the second half of January, and this number was reduced to 6.0 days (95%CI: 5.5 − 9.5) in the first half of February 2020. These estimates indicate the enhancement of infection screening and public interventions for the prevention and control of SARS-CoV-2.
      The fitting results of Eqn (1) are shown in Fig. 1(c); and the Nagelkerke's pseudo-R-squared is 0.38. The non-resident cases are likely to be detected earlier than the resident cases even though there were only 5 non-Hong Kong resident cases. We estimate that SARS-CoV-2 detection efficiency improves 5.40% per day (95%CI: 2.54 − 8.33) in Hong Kong. The estimates of α and β are consistent in signs, i.e., α is positive, and β is negative, and statistical significance levels, i.e., both are significant with p-values < 0.05, which validate our estimates. Therefore, we report that the SARS-CoV-2 infection detection efficiency was likely being improved substantially and significantly since January 23, 2020, when the first imported case was detected in Hong Kong.
      Due to the unavailability of data, our findings are restricted to the early phase of the COVID-19 outbreak in Hong Kong. However, our analytical approach can be extended to a more complex context. In Table 1, the events and control measures during the early outbreak are summarized. Most of the control measures aimed at strengthening the testing efforts, i.e., number of tests and testing efficiency, and reducing the size of the outbreak. Though the control measures would partially affect the testing efforts, we have accounted for these effects by adjusting the nt,t+τ term in the models. Hence, our estimates should quantify the temporal improvement in detection efficiency.
      Table 1Summary of the events and control measures during the early phase of the COVID-19 outbreak in Hong Kong (HK).
      Date or periodEvent typeDetails
      January 17 -control measureTemperature check of all inbound travellers at borders
      January 19FactFirst COVID-19 case in HK symptom onset
      January 21 -control measureCOVID-19 reporting system in operation
      January 24 -control measureTesting for all suspected, confirmed cases and close contacts Isolation and quarantine
      January 25 -control measureActivate the ‘Emergency’ level of response plan against the outbreak
      January 23 -fact and control measureLocal schools’ holiday, and school closure
      January 25 - January 28FactChinese lunar new year holiday
      January 26 -control measureCancellation of major gathering events, and closure of parks
      January 27 -control measureFlight suspension between HK and Wuhan Boarder restriction for non-HK residents with travel history to Hubei
      January 30 -control measureClose 6 border-control points
      February 4 -control measureClose 4 additional border-control points
      February 9 -control measureQuarantine for all individuals coming from mainland China
      We note that the sustaining enforcement in timely detection and other effective control measures are recommended in response to reduce the risk associated with SARS-CoV-2.

      Declarations

      Ethics approval and consent to participate

      The follow-up data of individual patients were collected via the public domain (

      Summary of data and outbreak situation of the Severe Respiratory Disease associated with a Novel Infectious Agent, Centre for Health Protection, the government of Hong Kong. [https://www.chp.gov.hk/en/features/102465.html]

      ), and thus neither ethical approval nor individual consent was required.

      Availability of data and materials

      All data and materials used in this work were publicly available via (

      Summary of data and outbreak situation of the Severe Respiratory Disease associated with a Novel Infectious Agent, Centre for Health Protection, the government of Hong Kong. [https://www.chp.gov.hk/en/features/102465.html]

      ).

      Consent for publication

      Not applicable.

      Funding

      DH was supported by the General Research Fund (Grant Number 15205119) of the Research Grants Council (RGC) of Hong Kong, China, and an Alibaba (China) - Hong Kong Polytechnic University Collaborative Research project (0031768). WW was supported by the National Natural Science Foundation of China (Grant Number 61672013) and Huaian Key Laboratory for Infectious Diseases Control and Prevention (Grant Number HAP201704), Huaian, Jiangsu, China.

      Competing Interests

      DH was supported by an Alibaba-Hong Kong Polytechnic University Collaborative Research project. Other authors declared no competing interests.

      Disclaimer

      The funding agencies had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication.

      Conflict of Interests

      The authors declared no competing interests.

      Authors’ Contributions

      SZ conceived the study, carried out the analysis. JR and SZ drafted the first manuscript. All authors discussed the results, critically read and revised the manuscript, and gave final approval for publication.

      Acknowledgments

      None.

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