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

The serial interval distribution is used to approximate the generation time distribution, an essential parameter to infer the transmissibility (${R}_t$) of an epidemic. However, serial interval distributions may change as an epidemic progresses. We examined detailed contact tracing data on laboratory-confirmed cases of COVID-19 in Hong Kong during the five waves from January 2020 to July 2022. We reconstructed the transmission pairs and estimated time-varying effective serial interval distributions and factors associated with longer or shorter intervals. Finally, we assessed the biases in estimating transmissibility using constant serial interval distributions. We found clear temporal changes in mean serial interval estimates within each epidemic wave studied and across waves, with mean serial intervals ranged from 5.5 days (95% CrI: 4.4, 6.6) to 2.7 (95% CrI: 2.2, 3.2) days. The mean serial intervals shortened or lengthened over time, which were found to be closely associated with the temporal variation in COVID-19 case profiles and public health and social measures and could lead to the biases in predicting ${R}_t$. Accounting for the impact of these factors, the time-varying quantification of serial interval distributions could lead to improved estimation of ${R}_t$, and provide additional insights into the impact of public health measures on transmission.

Ozone as an environmental driver of influenza.

Under long-standing threat of seasonal influenza outbreaks, it remains imperative to understand the drivers of influenza dynamics which can guide mitigation measures. While the role of absolute humidity and temperature is extensively studied, the possibility of ambient ozone (O3) as an environmental driver of influenza has received scant attention. Here, using state-level data in the USA during 2010-2015, we examined such research hypothesis. For rigorous causal inference by evidence triangulation, we applied 3 distinct methods for data analysis: Convergent Cross Mapping from state-space reconstruction theory, Peter-Clark-momentary-conditional-independence plus as graphical modeling algorithms, and regression-based Generalised Linear Model. The negative impact of ambient O3 on influenza activity at 1-week lag is consistently demonstrated by those 3 methods. With O3 commonly known as air pollutant, the novel findings here on the inhibition effect of O3 on influenza activity warrant further investigations to inform environmental management and public health protection.

Association of public health and social measures on the hand-foot-mouth epidemic in South Korea.

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. The aim of this study was to explore the association of nationwide public health and social measures (PHSMs) including planned school vacation on the transmissibility and attack rate of the HFMD epidemic in South Korea. METHODS: In this study, we used Korean national surveillance data on HFMD from 2014 to 2019 to estimate the temporal changes in HFMD transmissibility (instantaneous reproductive number, Rt). Furthermore, to assess the changes in the HFMD attack rate, we used a stochastic transmission model to simulate the HFMD epidemic with no school vacation and nationwide PHSMs in 2015 South Korea. RESULTS: We found that school vacations and 2015 PHSMs were associated with the reduced Rt by 2-7 % and 13 %, respectively. Model projections indicated school vacations and 2015 PHSMs were associated with reduced HFMD attack rate by an average of 1.10 % (range: 0.38-1.51 %). CONCLUSIONS: PHSMs likely have a larger association with reduced HFMD transmissibility than school-based measures alone (i.e. school vacations). Preventive measures targeting preschoolers could be considered as potential options for reducing the future burden of HFMD.

Rapid global spread of variants of concern of SARS-CoV-2.

Objectives: Variants of concern (VOCs) of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), such as the Delta variant and the Omicron variant, have reached all countries/regions of the world and have had a tremendous impact. This study analyses the global spread of VOCs of SARS-CoV-2. Methods: Biweekly aggregated numbers of several VOCs were retrieved for 58 locations. The time interval for the proportion of VOC samples to exceed 60% (indicating dominance) among all samples sequenced in each location was calculated. The times taken for a VOC to become dominant in 12 (or 36) locations was defined in order to quantify the speed of spread. Results: It took 63, 56 and 28 days for the Alpha, Delta and Omicron variants to become dominant in 12 locations, respectively, and 133, 70 and 28 days for the Alpha, Delta and Omicron variants to become dominant in 36 locations. Conclusions: The Omicron variant has much higher transmission potential compared with the Delta variant, and the Delta variant has higher transmission potential compared with the pre-Delta VOCs.

Inferring time-varying generation time, serial interval, and incubation period distributions for COVID-19.

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 estimated incubation period and serial interval distributions using 629 transmission pairs reconstructed by investigating 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.

Late Surges in COVID-19 Cases and Varying Transmission Potential Partially Due to Public Health Policy Changes in 5 Western States, March 10, 2020, to January 10, 2021.

OBJECTIVE: This study investigates the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission potential in North Dakota, South Dakota, Montana, Wyoming, and Idaho from March 2020 through January 2021. METHODS: Time-varying reproduction numbers, R t , of a 7-d-sliding-window and of non-overlapping-windows between policy changes were estimated using the instantaneous reproduction number method. Linear regression was performed to evaluate if per-capita cumulative case-count varied across counties with different population size or density. RESULTS: The median 7-d-sliding-window R t estimates across the studied region varied between 1 and 1.25 during September through November 2020. Between November 13 and 18, R t 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 and high-density counties had higher per-capita cumulative case-count in North Dakota on June 30, August 31, October 31, and December 31, 2020. In Idaho, North Dakota, South Dakota, and Wyoming, there were positive correlations between population size and per-capita weekly incident case-count, adjusted for calendar time and social vulnerability index variables. CONCLUSIONS: R t 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.

Hong Kong has implemented stringent public health and social measures (PHSMs) to curb each of the four COVID-19 epidemic waves since January 2020. The third wave between July and September 2020 was brought under control within 2 m, while the fourth wave starting from the end of October 2020 has taken longer to bring under control and lasted at least 5 mo. Here, we report the pandemic fatigue as one of the potential reasons for the reduced impact of PHSMs on transmission in the fourth wave. We contacted either 500 or 1,000 local residents through weekly random-digit dialing of landlines and mobile telephones from May 2020 to February 2021. We analyze the epidemiological impact of pandemic fatigue by using the large and detailed cross-sectional telephone surveys to quantify risk perception and self-reported protective behaviors and mathematical models to incorporate population protective behaviors. Our retrospective prediction suggests that an increase of 100 daily new reported cases would lead to 6.60% (95% CI: 4.03, 9.17) more people worrying about being infected, increase 3.77% (95% CI: 2.46, 5.09) more people to avoid social gatherings, and reduce the weekly mean reproduction number by 0.32 (95% CI: 0.20, 0.44). Accordingly, the fourth wave would have been 14% (95% CI%: -53%, 81%) smaller if not for pandemic fatigue. This indicates the important role of mitigating pandemic fatigue in maintaining population protective behaviors for controlling COVID-19.

Epidemiology and Transmission Dynamics of Infectious Diseases and Control Measures.

The epidemiology and transmission dynamics of infectious diseases must be understood at the individual and community levels to improve public health decision-making for real-time and integrated community-based control strategies. Herein, we explore the epidemiological characteristics for assessing the impact of public health interventions in the community setting and their applications. Computational statistical methods could advance research on infectious disease epidemiology and accumulate scientific evidence of the potential impacts of pharmaceutical/nonpharmaceutical measures to mitigate or control infectious diseases in the community. Novel public health threats from emerging zoonotic infectious diseases are urgent issues. Given these direct and indirect mitigating impacts at various levels to different infectious diseases and their burdens, we must consider an integrated assessment approach, 'One Health', to understand the dynamics and control of infectious diseases.

Prediction of upcoming global infection burden of influenza seasons after relaxation of public health and social measures during the COVID-19 pandemic: a modelling study.

BACKGROUND: The transmission dynamics of influenza were affected by public health and social measures (PHSMs) implemented globally since early 2020 to mitigate the COVID-19 pandemic. We aimed to assess the effect of COVID-19 PHSMs on the transmissibility of influenza viruses and to predict upcoming influenza epidemics. METHODS: For this modelling study, we used surveillance data on influenza virus activity for 11 different locations and countries in 2017-22. We implemented a data-driven mechanistic predictive modelling framework to predict future influenza seasons on the basis of pre-COVID-19 dynamics and the effect of PHSMs during the COVID-19 pandemic. We simulated the potential excess burden of upcoming influenza epidemics in terms of fold rise in peak magnitude and epidemic size compared with pre-COVID-19 levels. We also examined how a proactive influenza vaccination programme could mitigate this effect. FINDINGS: We estimated that COVID-19 PHSMs reduced influenza transmissibility by a maximum of 17·3% (95% CI 13·3-21·4) to 40·6% (35·2-45·9) and attack rate by 5·1% (1·5-7·2) to 24·8% (20·8-27·5) in the 2019-20 influenza season. We estimated a 10-60% increase in the population susceptibility for influenza, which might lead to a maximum of 1-5-fold rise in peak magnitude and 1-4-fold rise in epidemic size for the upcoming 2022-23 influenza season across locations, with a significantly higher fold rise in Singapore and Taiwan. The infection burden could be mitigated by additional proactive one-off influenza vaccination programmes. INTERPRETATION: Our results suggest the potential for substantial increases in infection burden in upcoming influenza seasons across the globe. Strengthening influenza vaccination programmes is the best preventive measure to reduce the effect of influenza virus infections in the community. FUNDING: Health and Medical Research Fund, Hong Kong.

Evaluation of Effectiveness of Global COVID-19 Vaccination Campaign.

To model estimated deaths averted by COVID-19 vaccines, we used state-of-the-art mathematical modeling, likelihood-based inference, and reported COVID-19 death and vaccination data. We estimated that >1.5 million deaths were averted in 12 countries. Our model can help assess effectiveness of the vaccination program, which is crucial for curbing the COVID-19 pandemic.

Epidemiology of Infections with SARS-CoV-2 Omicron BA.2 Variant, Hong Kong, January-March 2022.

Our analysis of data collected from multiple epidemics in Hong Kong indicated a shorter serial interval and generation time of infections with the SARS-CoV-2 Omicron variant. The age-specific case-fatality risk for Omicron BA.2.2 case-patients without complete primary vaccination was comparable to that of persons infected with ancestral strains in earlier waves.

Transmission dynamics and epidemiological characteristics of SARS-CoV-2 Delta variant infections in Guangdong, China, May to June 2021.

BackgroundThe Delta variant of SARS-CoV-2 had become predominant globally by November 2021.AimWe evaluated transmission dynamics and epidemiological characteristics of the Delta variant in an outbreak in southern China.MethodsData on confirmed COVID-19 cases and their close contacts were retrospectively collected from the outbreak that occurred in Guangdong, China in May and June 2021. Key epidemiological parameters, temporal trend of viral loads and secondary attack rates were estimated. 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. Mean estimates of latent and incubation period were 3.9 days and 5.8 days, respectively. Relatively higher viral load was observed in infections with Delta than in infections with wild-type SARS-CoV-2. Secondary attack rate among close contacts of cases with Delta was 1.4%, and 73.1% (95% credible interval (CrI): 32.9-91.4) of the transmissions occurred before onset. Index cases without vaccination (adjusted odds ratio (aOR): 2.84; 95% CI: 1.19-8.45) or with an incomplete vaccination series (aOR: 6.02; 95% CI: 2.45-18.16) were more likely to transmit infection to their contacts than those who had received the complete primary vaccination series.DiscussionPatients infected with the Delta variant had more rapid symptom onset compared with the wild type. The time-varying serial interval should be accounted for in estimation of reproduction numbers. The higher viral load and higher risk of pre-symptomatic transmission indicated the challenges in control of infections with the Delta variant.

Incorporating temporal distribution of population-level viral load enables real-time estimation of COVID-19 transmission.

Many locations around the world have used real-time estimates of the time-varying effective reproductive number ([Formula: see text]) of COVID-19 to provide evidence of transmission intensity to inform control strategies. Estimates of [Formula: see text] are typically based on statistical models applied to case counts and typically suffer lags of more than a week because of the latent 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 RT-qPCR cycle threshold values) and estimates of [Formula: see text] based on case counts. We demonstrate that cycle threshold values could be used to improve real-time [Formula: see text] estimation, enabling more timely tracking of epidemic dynamics.

Estimation of Serial Interval and Reproduction Number to Quantify the Transmissibility of SARS-CoV-2 Omicron Variant in South Korea.

The omicron variant (B.1.1.529) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was the predominant variant in South Korea from late January 2022. In this study, we aimed to report the early estimates of the serial interval distribution and reproduction number to quantify the transmissibility of the omicron variant in South Korea between 25 November 2021 and 31 December 2021. We analyzed 427 local omicron cases and reconstructed 73 transmission pairs. We used a maximum likelihood estimation to assess serial interval distribution from transmission pair data and reproduction numbers from 74 local cases in the first local outbreak. We estimated that the mean serial interval was 3.78 (standard deviation, 0.76) days, which was significantly shorter in child infectors (3.0 days) compared to adult infectors (5.0 days) (p < 0.01). We estimated the mean reproduction number was 1.72 (95% CrI, 1.60−1.85) for the omicron variant during the first local outbreak. Strict adherence to public health measures, particularly in children, should be in place to reduce the transmission risk of the highly transmissible omicron variant in the community.

Serial Intervals and Case Isolation Delays for Coronavirus Disease 2019: A Systematic Review and Meta-Analysis.

BACKGROUND: Estimates of the serial interval distribution contribute to our understanding of the transmission dynamics of coronavirus disease 2019 (COVID-19). Here, we aimed to summarize the existing evidence on serial interval distributions and delays in case isolation for COVID-19. METHODS: We conducted a systematic review of the published literature and preprints in PubMed on 2 epidemiological parameters, namely, serial intervals and delay intervals relating to isolation of cases for COVID-19 from 1 January 2020 to 22 October 2020 following predefined eligibility criteria. We assessed the variation in these parameter estimates using correlation and regression analysis. RESULTS: Of 103 unique studies on serial intervals of COVID-19, 56 were included, providing 129 estimates. Of 451 unique studies on isolation delays, 18 were included, providing 74 estimates. Serial interval estimates from 56 included studies varied from 1.0 to 9.9 days, while case isolation delays from 18 included studies varied from 1.0 to 12.5 days, which were associated with spatial, methodological, and temporal factors. In mainland China, the pooled mean serial interval was 6.2 days (range, 5.1-7.8) before the epidemic peak and reduced to 4.9 days (range, 1.9-6.5) after the epidemic peak. Similarly, the pooled mean isolation delay related intervals were 6.0 days (range, 2.9-12.5) and 2.4 days (range, 2.0-2.7) before and after the epidemic peak, respectively. There was a positive association between serial interval and case isolation delay. CONCLUSIONS: Temporal factors, such as different control measures and case isolation in particular, led to shorter serial interval estimates over time. Correcting transmissibility estimates for these time-varying distributions could aid mitigation efforts.

Influenza seasonality and its environmental driving factors in mainland China and Hong Kong.

BACKGROUND: Influenza epidemics occur during winter in temperate zones, but have less regular seasonality in the subtropics and tropics. Here we quantified the role of environmental drivers of influenza seasonality in temperate and subtropical China. METHODS: We used weekly surveillance data on influenza virus activity in mainland China and Hong Kong from 2005 through 2016. We estimated the transmissibility via the instantaneous reproduction number (Rt), a real-time measure of transmissibility, and examined its relationship with different climactic drivers and allowed for the timing of school holidays and the decline in susceptibility in the population as an epidemic progressed. We developed a multivariable regression model for Rt to quantify the contribution of various potential environmental drivers of transmission. FINDINGS: We found that absolute humidity is a potential driver of influenza seasonality and had a U-shaped association with transmissibility and hence can predict the pattern of influenza virus transmission across different climate zones. Absolute humidity was able to explain up to 15% of the variance in Rt, and was a stronger predictor of Rt across the latitudes. Other climatic drivers including mean daily temperature explained up to 13% of variance in Rt and limited to the locations where the indoor measures of these factors have better indicators of outdoor measures. The non-climatic driver, holiday-related school closures could explain up to 7% of variance in Rt. INTERPRETATION: A U-shaped association of absolute humidity with influenza transmissibility was able to predict seasonal patterns of influenza virus epidemics in temperate and subtropical locations.