Rapid global spread of Variant of Concern of SARS-CoV-2 (preprint)

In this work, we show the spatiotemporal spread and replacement of different Variant of Concern (VOC) of SARS-COV-2. We define a metric to quantify the spread speed of each COV. We discuss the basic reproductive number of these VOC’s and possible impact of travel ban.

Insights into COVID-19 epidemiology and control from temporal changes in serial interval distributions in Hong Kong (preprint)

The serial interval distribution is used to approximate the generation time distribution, an essential parameter to predict the effective reproductive number "Rt", a measure of transmissibility. However, serial interval distributions may change as an epidemic progresses rather than remaining constant. Here we show that serial intervals in Hong Kong varied over time, closely associated with the temporal variation in COVID-19 case profiles and public health and social measures that were implemented in response to surges in community transmission. Quantification of the variation over time in serial intervals led to improved estimation of Rt, and provided additional insights into the impact of public health measures on transmission of infections. One-Sentence SummaryReal-time estimates of serial interval distributions can improve assessment of COVID-19 transmission dynamics and control.

Impact of public health and social measures on hand-foot-mouth disease transmission and prediction of upcoming season after relaxation of COVID-19 control measures (preprint)

Background School based-measures such as school closure and school holidays have been considered a viable intervention during the hand-foot-mouth disease (HFMD) epidemic. However, the impact of public health and social measures (PHSMs) on HFMD transmission and the consequences of the HFMD epidemic after relaxing the PHSMs remains unclear.Methods Korean national surveillance data on HFMD from 2014 to 2019 was used to estimate the temporal changes in HFMD transmissibility (instantaneous reproductive number, \({R}_{t}\)). Furthermore, we used a simulation based stochastic transmission model to predict the future burden of HFMDs after relaxation of COVID-19 PHSMs, assuming all the Korean population was susceptible to HFMD in 2023, the stochastic transmission model simulated the number of HFMD cases in South Korea.Results We found that school holidays and 2015 PHSMs reduced the \({R}_{t}\) by 2–7% and 13%, respectively. Model projections indicated that the peak magnitude for season 2023, after relaxation of COVID-19 PHSMs in late 2022, could be 2·5–8·5 fold larger than that of the HFMD seasons during the pre-pandemic.Conclusions PHSMs likely have a larger impact on HFMD transmission than school-based measures alone (i.e. school holidays). Furthermore, complete relaxation of COVID-19 PHSMs could significantly increase the HFMD infection burden for the upcoming HFMD season. Preventive measures targeting preschoolers could be considered as potential options for reducing the future burden of HFMD.

Inferring time-varying generation time, serial interval and incubation period distributions for COVID-19 (preprint)

The generation time distribution, reflecting the time between successive infections in transmission chains, is a key epidemiological parameter for describing COVID-19 transmission dynamics. However, because exact infection times are rarely known, it is often approximated by the serial interval distribution. This approximation holds under the assumption that infectors and infectees share the same incubation period distribution, which may not always be true. We investigated incubation period and serial interval distributions in data on 2989 confirmed cases in China in January-February 2020, and developed an inferential framework to estimate the generation time distribution that accounts for variation over time due to changes in epidemiology, sampling biases and public health and social measures. We identified substantial reductions over time in the serial interval and generation time distributions. Our proposed method provides more reliable estimation of the temporal variation in the generation time distribution, improving assessment of transmission dynamics.

Inferring time-varying generation time, serial interval and incubation period distributions for COVID-19 (preprint)

Background The generation time distribution, reflecting the time between successive infections in transmission chains, is one of the fundamental epidemiological parameters for describing COVID-19 transmission dynamics. However, because exact infection times are rarely known, it is often approximated by the serial interval distribution, reflecting the time between illness onsets of infector and infectee. This approximation holds under the assumption that infectors and infectees share the same incubation period distribution, which may not always be true. Methods We analyzed data on observed incubation period and serial interval distributions in China, during January and February 2020, under different sampling approaches, and developed an inferential framework to estimate the generation time distribution that accounts for variation over time due to changes in epidemiology, sampling biases and public health and social measures. Results We analyzed data on a total of 2989 confirmed cases for COVID-19 during January 1 to February 29, 2020 in Mainland China. During the study period, the empirical forward serial interval decreased from a mean of 8.90 days to 2.68 days. The estimated mean backward incubation period of infectors increased from 3.77 days to 9.61 days, and the mean forward incubation period of infectees also increased from 5.39 days to 7.21 days. The estimated mean forward generation time decreased from 7.27 days (95% confidence interval: 6.42, 8.07) to 4.21 days (95% confidence interval: 3.70, 4.74) days by January 29. We used simulations to examine the sensitivity of our modelling approach to a number of assumptions and alternative dynamics. Conclusions The proposed method can provide more reliable estimation of the temporal variation in the generation time distribution, enabling proper assessment of transmission dynamics.

Epidemiology of infections with SARS-CoV-2 Omicron BA.2 variant in Hong Kong, January-March 2022 (preprint)

Hong Kong reported 12,631 confirmed COVID-19 cases and 213 deaths in the first two years of the pandemic but experienced a major wave predominantly of Omicron BA.2.2 in early 2022 with over 1.1 million reported SARS-CoV-2 infections and more than 7900 deaths. Our data indicated a shorter incubation period, serial interval, and generation time of infections with Omicron than other SARS-CoV-2 variants. Omicron BA.2.2 cases without a complete primary vaccination series appeared to face a similar fatality risk to those infected in earlier waves with the ancestral strain.

Incorporating temporal distribution of population-level viral load enables real-time estimation of COVID-19 transmissibility (preprint)

Many locations around the world have used real-time estimates of the time-varying effective reproductive number (\({R}_{t}\)) of COVID-19 to provide evidence of transmission intensity to inform control strategies. Estimates of \({R}_{t}\) are typically based on statistical models applied to case counts and typically suffer lags of more than a week because of the incubation period and reporting delays. Noting that viral loads tend to decline over time since illness onset, analysis of the distribution of viral loads among confirmed cases can provide insights into epidemic trajectory. Here, we analyzed viral load data on confirmed cases during two local epidemics in Hong Kong, identifying a strong correlation between temporal changes in the distribution of viral loads (measured by cycle threshold values) and estimates of \({R}_{t}\) based on case counts. We demonstrate that cycle threshold values could be used to improve real-time \({R}_{t}\) estimation, enabling more timely tracking of epidemic dynamics.

Changes in the serial interval and transmission dynamics associated with the SARS-CoV-2 Delta variant in South Korea (preprint)

We estimated the mean serial interval and superspreading potential for the Delta variant SARS-CoV-2. As the Delta variant increased in prevalence, the mean serial interval declined from 4.0 to 2.5 days. However, the risk of superspreading events was similar, as 25% to 27% of cases seeded 80% of all transmissions.

Transmission dynamics and epidemiological characteristics of Delta variant infections in China (preprint)

BackgroundThe Delta variant of SARS-CoV-2 has become predominant globally. We evaluated the transmission dynamics and epidemiological characteristics of the Delta variant in an outbreak in southern China. MethodsData on confirmed cases and their close contacts were retrospectively collected from the outbreak that occurred in Guangdong, China in May-June 2021. Key epidemiological parameters, temporal trend of viral loads and secondary attack rates were estimated and compared between the Delta variant and the wild-type SARS-CoV-2 virus. We also evaluated the association of vaccination with viral load and transmission. ResultsWe identified 167 patients infected with the Delta variant in the Guangdong outbreak. The mean estimates of the latent period and the incubation period were 4.0 days and 5.8 days, respectively. A relatively higher viral load was observed in Delta cases than in wild-type infections. The secondary attack rate among close contacts of Delta cases was 1.4%, and 73.9% (95% confidence interval: 67.2%, 81.3%) of the transmissions occurred before onset. Index cases without vaccination (OR: 2.84, 95% confidence interval: 1.19, 8.45) or with one dose of vaccination (OR: 6.02, 95% confidence interval: 2.45, 18.16) were more likely to transmit infection to their contacts than those who had received 2 doses of vaccination. DiscussionPatients infected with the Delta variant had more rapid symptom onset. The shorter and time-varying serial interval should be accounted in estimation of reproductive numbers. The higher viral load and higher risk of pre-symptomatic transmission indicated the challenges in control of infections with the Delta variant.

Late surges in COVID-19 cases and varying transmission potential partially due to public health policy changes in 5 Western states, March 10, 2020-January 10, 2021 (preprint)

Objective: This study investigates how the SARS-CoV-2 transmission potential varied in North Dakota, South Dakota, Montana, Wyoming, and Idaho from March 2020 through January 2021. Methods: Time-varying reproduction numbers, Rt, of a 7-day-sliding-window and of non-overlapping-windows between policy changes were estimated utilizing the instantaneous reproduction number method. Linear regression was performed to evaluate if per-capita cumulative case-count varied across counties with different population size. Results: The median 7-day-sliding-window Rt estimates across the studied region varied between 1 and 1.25 during September through November 2020. Between November 13 and 18, Rt was reduced by 14.71% (95% credible interval, CrI, [14.41%, 14.99%]) in North Dakota following a mask mandate; Idaho saw a 1.93% (95% CrI [1.87%, 1.99%]) reduction and Montana saw a 9.63% (95% CrI [9.26%, 9.98%]) reduction following the tightening of restrictions. High-population counties had higher per-capita cumulative case-count in North Dakota at four time points (June 30, August 31, October 31, and December 31, 2020). In Idaho, North Dakota, and South Dakota, there was a positive correlation between population size and per-capita weekly incident case-count, adjusted for calendar time and social vulnerability index variables. Conclusions: Rt decreased after mask mandate during the region's case-count spike suggested reduction in SARS-CoV-2 transmission.

Pandemic fatigue impedes mitigation of COVID-19 in Hong Kong (preprint)

Community-wide social distancing has been a cornerstone of pandemic control prior to mass vaccinations. The extent to which pandemic fatigue is undermining adherence to such measures and accelerating transmission remains unclear. Using large-scale weekly telephone surveys and mobility data, we characterize the evolution of risk perception and protective behaviours in Hong Kong. We estimate a 1.5% to 5.5% reduction in population compliance with protective policies for the fourth wave (October 2020 to January 2021) versus the third wave (July to August 2020), inducing prolonged disease circulation with increased infections. Mathematical models incorporating population protective behaviours estimates that the fourth wave would have been 14% smaller if not for pandemic fatigue. Mitigating pandemic fatigue is essential in maintaining population protective behaviours for controlling COVID-19.

Transmission Dynamics and Control of Two Epidemic Waves of SARS-CoV-2 in South Korea (preprint)

Background: After relaxing social distancing measures, South Korea experienced a resurgent second epidemic wave of coronavirus disease 2019 (COVID-19). In this study, we aimed to identify the transmission dynamics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and assess the impact of COVID-19 case finding and contact tracing in each epidemic wave.Methods: We collected data on COVID-19 cases published by local public health authorities in South Korea and divided the study into two epidemic periods (19 January–19 April 2020 for the first epidemic wave and 20 April–11 August 2020 for the second epidemic wave). To identify changes in the transmissibility of SARS-CoV-2, the daily effective reproductive number (Rt) was estimated using the illness onset of the cases. Furthermore, to identify the characteristics of each epidemic wave, frequencies of cluster types were measured, and age-specific transmission probability matrices and serial intervals were estimated. The proportion of asymptomatic cases and cases with unknown sources of infection were also estimated to assess the changes of infections identified as cases in each wave.Results: In early May 2020, within 2-weeks of a relaxation in strict social distancing measures, Rt increased rapidly from 0.2 to 1.8 within a week and was around 1 until early July 2020. In both epidemic waves, the most frequent cluster types were religious-related activities and transmissions among the same age were more common. Furthermore, children were rarely infectors or infectees, and the mean serial intervals were similar (~3 days) in both waves. The proportion of asymptomatic cases at presentation increased from 22% (in the first wave) to 27% (in the second wave), while the cases with unknown sources of infection were similar in both waves (22% and 24%, respectively).Conclusions: Our study shows that relaxing social distancing measures was associated with increased SARS-CoV-2 transmission despite rigorous case findings in South Korea. Along with social distancing measures, the enhanced contact tracing including asymptomatic cases could be an efficient approach to control further epidemic waves.

International risk of the new variant COVID-19 importations originating in the United Kingdom (preprint)

A fast-spreading SARS-CoV-2 variant identified in the United Kingdom in December 2020 has raised international alarm. We estimate that, in all 15 countries analyzed, there is at least a 50% chance the variant was imported by travelers from the United Kingdom by December 7th.

Epidemiology and Control of Two Epidemic Waves of SARS-CoV-2 in South Korea (preprint)

Background: Since the first case of pandemic COVID-19 in South Korea, identified on 19 January 2020, two epidemic waves have occurred. We characterised the epidemiology, transmission dynamics and effectiveness of control measures in each epidemic wave of COVID-19.Methods: We analysed publicly available data on confirmed cases of COVID-19 outside of Daegu-Gyeongbuk Regions in South Korea during first (19 January–19 April 2020) and second (20 April–11 August 2020) epidemic waves. Transmissibility of SARS-CoV-2 was measured by daily effective reproductive number, Rt. Frequencies of cluster types, age-specific transmission probability matrices, proportion of asymptomatic and unlinked cases, and serial interval distribution were estimated for each wave.Results: In early May, within 2-weeks of relaxation on strict social distancing measures, Rt increased rapidly from 0.2 to 2.3 within a week and was around 1 until early July. The most frequent clusters type were the religious related activities in both waves, but noticed more workplace-related clusters in the second wave. The proportion of asymptomatic cases at presentation increased from 22% during first wave to 27% during second wave. The proportion of unlinked local cases were similar in both waves (22% and 24%). Transmissions among same age were more common, and children were rarely infectors or infectees. The mean serial interval were similar (~3 days) in both waves.Interpretation: Our study shows that relaxing social distancing measures was associated with increased SARS-CoV-2 transmission. Enhanced contact tracing including asymptomatic cases could be more efficient with social distancing to control further waves of the pandemic.Funding: This study was supported by the Basic Science Research Program through the National Research Foundation of Korea funded by the Korean Ministry of Education (NRF2020R1I1A3066471).Declaration of Interests: BJC reports honoraria from Sanofi Pasteur and Roche. All other authors declare no competing interests.Ethics Approval Statement: This study did not require institutional review board approval or informed consent, because all data used were anonymous and publicly available on local public health agency websites.

Epidemiology and Control of Two Epidemic Waves of SARS-CoV-2 in South Korea (preprint)

Background: Since the first case of pandemic COVID-19 in South Korea, identified on 19 January 2020, two epidemic waves have occurred. We characterised the epidemiology, transmission dynamics and effectiveness of control measures in each epidemic wave of COVID-19.Methods: We analysed publicly available data on confirmed cases of COVID-19 outside of Daegu-Gyeongbuk Regions in South Korea during first (19 January–19 April 2020) and second (20 April–11 August 2020) epidemic waves. Transmissibility of SARS-CoV-2 was measured by daily effective reproductive number, Rt. Frequencies of cluster types, age-specific transmission probability matrices, proportion of asymptomatic and unlinked cases, and serial interval distribution were estimated for each wave. Results: In early May, within 2-weeks of relaxation on strict social distancing measures, Rt increased rapidly from 0.2 to 2.3 within a week and was around 1 until early July. The most frequent clusters type were the religious related activities in both waves, but noticed more workplace-related clusters in the second wave. The proportion of asymptomatic cases at presentation increased from 22% during first wave to 27% during second wave. The proportion of unlinked local cases were similar in both waves (22% and 24%). Transmissions among same age were more common, and children were rarely infectors or infectees. The mean serial interval were similar (~3 days) in both waves. Conclusions: Our study shows that relaxing social distancing measures was associated with increased SARS-CoV-2 transmission. Enhanced contact tracing including asymptomatic cases could be more efficient with social distancing to control further waves of the pandemic.

Suppressing COVID-19 transmission in Hong Kong: an observational study of the first four months (preprint)

Background: Hong Kong was one of the first locations outside of mainland China to identify COVID-19 cases in January 2020. We assessed the impact of various public health measures on transmission.Methods: We analysed data on all COVID-19 cases and public health measures in Hong Kong up to 7 May 2020. We described case-based, travel-based and community-based measures and examined their potential effects on case identification and transmission. Changes in transmissibility measured by the effective reproductive number Rt were estimated by comparing the Rt between periods when public health measures were and were not in effect. Delays in case confirmation in imported cases and locally infected cases were analysed to indicate the possible impact of expansion of laboratory testing capacity.Findings: Introduction of a 14-day quarantine on persons arriving from affected areas was associated with a 95% reduction in transmissibility from imported cases. Testing all arriving travelers reduced mean delays between arrival and detection of imported cases. Increases in laboratory testing capacity for pneumonia inpatients and symptomatic outpatients reduced the delay from onset to confirmation. Working from home and physical distancing measures implemented in high-risk facilities were associated with 67% and 58% reductions in transmission of COVID-19, respectively.Interpretation: Suppression of COVID-19 transmission in the first pandemic wave in Hong Kong was achieved through integration of travel-based, case-based and community-based public health measures focusing on early case identification and isolation and physical distancing.

Evolution of effective serial interval of SARS-CoV-2 by non-pharmaceutical interventions (preprint)

Studies of novel coronavirus disease (COVID-19) have reported varying estimates of epidemiological parameters such as serial intervals and reproduction numbers. By compiling a unique line-list database of transmission pairs in mainland China, we demonstrated that serial intervals of COVID-19 have shortened substantially from a mean of 7.8 days to 2.6 days within a month. This change is driven by enhanced non-pharmaceutical interventions, in particular case isolation. We also demonstrated that using real-time estimation of serial intervals allowing for variation over time would provide more accurate estimates of reproduction numbers, than by using conventional definition of fixed serial interval distributions. These findings are essential to improve the assessment of transmission dynamics, forecasting future incidence, and estimating the impact of control measures.

Impact assessment of non-pharmaceutical interventions against COVID-19 and influenza in Hong Kong: an observational study (preprint)

Background: A range of public health measures have been implemented to delay and reduce local transmission of COVID-19 in Hong Kong, and there have been major changes in behaviours of the general public. We examined the effect of these interventions and behavioral changes on the incidence of COVID-19 as well as on influenza virus infections which may share some aspects of transmission dynamics with COVID-19. Methods: We reviewed policy interventions and measured changes in population behaviours through two telephone surveys, on January 20-23 and February 11-14. We analysed data on laboratory-confirmed COVID-19 cases, influenza surveillance data in outpatients of all ages, and influenza hospitalisations in children. We estimated the daily effective reproduction number (R_t), for COVID-19 and influenza A(H1N1). Findings: COVID-19 transmissibility has remained at or below 1, indicating successful containment to date. Influenza transmission declined substantially after the implementation of social distancing measures and changes in population behaviours in late January, with a 44% (95% confidence interval, CI: 34% to 53%) reduction in transmissibility in the community, and a 33% (95% CI: 24% to 43%) reduction in transmissibility based on paediatric hospitalization rates. In the two surveys we estimated that 74.5% and 97.5% of the general adult population wore masks when going out, and 61.3% and 90.2% avoided going to crowded places, respectively. Implications: Containment measures, social distancing measures and changes in population behaviour have successfully prevented spread of COVID-19. The social distancing measures and behavioural changes led to a substantial reduction in influenza transmission in early February 2020. However, it may be challenging to avoid fatigue and sustain these measures and population behaviours as COVID-19 continues to spread globally. Funding: Health and Medical Research Fund, Hong Kong

Close contacts and household transmission of SARS-CoV-2 in China: a content analysis based on local Heath Commissions' public disclosures. (preprint)

Question: What are the characteristics of household and social transmissions of COVID-19 areas outside of epidemic centers? Findings: Based on 1,407 COVID-19 reported infection events in China outside of Hubei Province between 20 January and 19 February 2020, we estimate the distribution of secondary infection sizes, frequency of super spreading events, serial intervals and age-stratified hazard of infection. Young and older people have higher risks of being infected with households while males 65+ of age are responsible for a disproportionate number of household infections. Meaning: This report is the first large-scale analysis of the household and social transmission events in the COVID-19 pandemic.

The estimate of infected individuals of the 2019-Novel Coronavirus in South Korea by incoming international students from the countries of risk of 2019-Novel Coronavirus: a simulation study (preprint)

Background: In March 2020, overall, 37,000 international students from the country at risk of the 2019-novel coronavirus (COVID-19) infection will arrive in Seoul, South Korea. Individuals from the country at risk of COVID-19 infection have been included in a home-quarantine program, but the efficacy of the program is uncertain. Methods: To estimate the possible number of infected individuals within the large influx of international students, we used a deterministic compartmental model for epidemic and perform a simulation-based search of different rates of compliance with home-quarantine. Results: Under the home-quarantine program, the total number of the infected individuals would reach 24-53 from March 17-March 20, 50-86 from March 18-March 16, and 234-343 from March 4-March 23 with the arrival of 0.1%, 0.2%, and 1% of pre-infectious individuals, in Seoul, South Korea, respectively. Our findings indicated when incoming international students showed strict compliance with quarantine, epidemics were less likely to occur in Seoul, South Korea. Conclusion: To mitigate possible epidemics, additional efforts to improve the compliance of home-quarantine are warranted along with other containment policies.