Inactivated Influenza Vaccines or Live Attenuated Influenza Vaccines? Parental Vaccine Hesitancy and Influenza Vaccine Type Preferences during COVID-19 Pandemic (preprint)

Seasonal influenza vaccine (SIV) significantly reduces influenza-related illnesses among school-aged children, yet parental vaccine hesitancy remains a persistent challenge. Two types of SIV are available for children in Hong Kong and other locations: inactivated influenza vaccine (IIV), administered through intramuscular injection, and live attenuated influenza vaccine (LAIV), administered via nasal spray. While injection or needle fears are important barriers to childhood vaccination uptake, little research has explored how vaccine hesitancy can shape parental preference for LAIV versus IIV, particularly amidst important public health events, such as the COVID-19 pandemic and the massive rollout of COVID-19 vaccination campaigns. Our study employs a concurrent mixed-methods design to address this gap comprehensively. The quantitative part involves longitudinal surveys spanning three years, from pre-pandemic to post-pandemic periods, tracking parental vaccine hesitancy and preference for SIV types. The qualitative part involves 48 in-depth interviews, providing in-depth insights into parental preference for SIV types, underlying reasons, and corresponding values. Our quantitative analyses revealed an overall increase in parental vaccine hesitancy and preference for LAIV over IIV after the onset of the COVID-19 pandemic and especially after the rollout of the COVID-19 vaccination campaign. Further logistic regression modelling based on the cohort data showed that higher vaccine hesitancy, coupled with the COVID-19 vaccination campaign rollout, predicts a greater preference for LAIV over IIV. The qualitative analysis complements these results, highlighting that LAIV’s non-invasive nature aligns with parental values of prioritizing natural immunity and concerns about overmedication. Consequently, hesitant parents perceive LAIV as less intrusive and more acceptable, emphasizing the need for future tailored risk communication. Leveraging the higher acceptability of LAIV compared to IIV among parents with high vaccine hesitancy could promote childhood vaccination uptake.

Revisiting assumptions in test-negative studies for estimating vaccine effectiveness: the need for a clinical case definition (preprint)

Test negative studies have been used extensively for the estimation of COVID-19 vaccine effectiveness (VE). Such studies are able to estimate VE against medically-attended illness under certain assumptions. Selection bias may be present if the probability of participation is associated with vaccination or COVID-19, but this can be mitigated through use of a clinical case definition to screen patients for eligibility, which increases the likelihood that cases and non-cases come from the same source population. We examined the extent to which this type of bias could harm COVID-19 VE through systematic review and simulation. A systematic review of test-negative studies was re-analysed to identify studies ignoring the need for clinical criteria. Studies using a clinical case definition had a lower pooled VE estimate compared with studies that did not. Simulations varied the probability of selection by case and vaccination status. Positive bias away from the null (i.e., inflated VE consistent with the systematic review) was observed when there was a higher proportion of healthy, vaccinated non-cases, which may occur if a dataset contains many results from asymptomatic screening in settings where vaccination coverage is high. We provide an html tool for researchers to explore site-specific sources of selection bias in their own studies. We recommend all group consider the potential for selection bias in their vaccine effectiveness studies, particularly when using administrative data.

Predictive efficacies of vaccine dose fractionation using neutralizing antibody levels (preprint)

Background With the emergence of SARS-CoV-2 variants that eluded immunity from vaccines and prior infections, vaccine shortages and their effectiveness pose unprecedented challenges for governments to expand booster vaccination programs. Fractionation of vaccine doses might be an effective strategy to help society to face these challenges, which may have comparable efficacies in contrast with the standard doses. Methods In this study, we analyzed the relationship between in-vitro neutralization levels and the observed efficacies against asymptomatic and symptomatic infection of ten types of COVID-19 vaccines using data from 13 studies from vaccination and convalescent cohorts. We further projected efficacies for fractional doses based on 51 studies included in our systematic review. Results By comparing with the convalescent level, vaccine efficacy increases from 8.8% (95% CI: 1.4%, 16.1%) to 71.8% (95% CI: 63.0%, 80.7%) against asymptomatic infection, and from 33.6% (95% CI: 23.6%, 43.6%) to 98.6% (95% CI: 97.6%, 99.7%) against symptomatic infection, respectively, along with the mean neutralization level from 0.1 to 10 folds of convalescent level. And mRNA vaccines provide the strongest protection, and decrease slowly for fractional dosing between 50% and 100% dosage. Conclusions Our results are consistent with studies for immune protection from COVID-19 infection. Based on our study, we expect that fractional dose vaccination could provide a partial immunity for SARS-CoV-2 virus. Fractional doses of vaccines could be a viable vaccination strategy compared to full-dose vaccination and deserves further exploration. Key points We analyzed the relationship between neutralization levels and efficacies against asymptomatic and symptomatic infection of ten types of COVID-19 vaccines from convalescent cohorts. Fractional doses of vaccines could be a viable strategy compared to full-dose vaccination and deserves further exploration.

Viral shedding among symptomatic COVID-19 cases infected with the ancestral strain and Omicron BA.2 (preprint)

Assessment of viral kinetics of SARS-CoV-2 may inform host immune responses to and transmission potential of the virus. We analyzed longitudinal data of RT-PCR tests conducted for symptomatic COVID-19 patients at confirmation and during hospital isolation in Hong Kong during three major epidemic waves, and modeled the temporal trajectories of viral burden in these patients. Our analysis demonstrated that a longer duration of viral shedding appeared in more severe and older cases. Vaccinated individuals with a breakthrough infection of Omicron BA.2 exhibited a lower viral burden than non-vaccinated Omicron cases in early days following onset and a shorter duration of viral shedding particularly in more recently vaccinated patients. The viral kinetics characterized in our study provided insight into further studies on host immune responses to SARS-CoV-2 infection, prognosis of COVID-19 patients as well as possible protective mechanisms of vaccination against infection and severe outcomes.

Encoding generation time changes within reproduction numbers (preprint)

We derive and introduce the angular reproduction number, {Omega}, which measures time-varying changes in epidemic transmissibility resulting from variations in both the effective reproduction number, R, and the generation time distribution, w. Predominant approaches for tracking the dynamics of pathogen spread either infer R or the epidemic growth rate r. However, R is easily biased by mismatches between the assumed and true w, while r is difficult to interpret in terms of the individual-level branching process underpinning transmission. Moreover, R and r may disagree on the relative transmissibility of two epidemics or variants (i.e., rA > rB does not imply RA > RB for variants A and B). We find that {Omega} responds meaningfully to mismatches in w while maintaining most of the interpretability of R. Additionally, we prove that {Omega} > 1 if and only if R > 1 and that {Omega} agrees with r on the relative transmissibility of pathogens. Estimating {Omega} is no harder than inferring R, uses existing software, and requires no generation time measurement. These advantages come at the expense of selecting one free parameter. We propose {Omega} as a useful statistic for tracking and comparing the spread of infectious diseases that may better reflect the impact of interventions when those interventions concurrently change both R and w or alter the relative risk of co-circulating pathogens.

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.

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.

Priming conditions shape breadth of neutralizing antibody responses to sarbecoviruses (preprint)

Vaccines that are broadly cross-protective against current and future SARS-CoV-2 variants of concern (VOC) or across the sarbecoviruses subgenus remain a priority for public health. Virus neutralization is the best available correlate of protection. We used sera from cohorts of individuals vaccinated with two or three doses of RNA (BNT162b2) or inactivated SARS-CoV-2 (Coronavac or Sinopharm) vaccines with or without a history of previous SARS-CoV-2 or SARS-CoV-1 (in 2003) infection, to define the magnitude and breath of cross-neutralization in a multiplex surrogate neutralization assay based on virus spike receptor binding domain of multiple SARS-CoV-2 variants of concern (VOC), SARS-CoV-2 related bat and pangolin viruses, SARS-CoV-1 and related bat sarbecoviruses. SARS-CoV-2 or SARS-CoV-1 infection followed by BNT162b2 vaccine, Omicron BA.2 breakthrough infection following BNT162b2 vaccine or a third dose of BNT162b2 following two doses of BNT162b2 or CoronaVac elicited the highest and broadest neutralization across VOCs. Considering breadth and magnitude of neutralization across all sarbecoviruses, those infected with SARS-CoV-1 immunized with BNT162b2 outperformed all other combinations of infection and/or vaccination. These data may inform vaccine design strategies for generating broadly neutralizing antibodies to SARS-CoV-2 variants or across the sarbecovirus subgenus.

Real-world effectiveness of molnupiravir and nirmatrelvir/ritonavir against mortality, hospitalization, and in-hospital outcomes among community-dwelling, ambulatory COVID-19 patients during the BA.2.2 wave in Hong Kong: an observational study (preprint)

Background Evidence evaluating real-world effectiveness of oral antivirals against Omicron variants is lacking. Methods An unselected, territory-wide cohort of all initially non-hospitalized patients with an officially registered diagnosis of SARS-CoV-2 infection between 26th February and 3rd May 2022 during the Omicron BA.2.2 wave in Hong Kong, was identified. We undertook a retrospective cohort design as primary analysis, and case-control design as sensitivity analysis. Outpatient oral antiviral users were matched with controls using 1:10 propensity-score matching. Study outcomes were mortality, COVID-19-related hospitalization, composite outcome of in-hospital disease progression (in-hospital mortality, invasive mechanical ventilation, or intensive care unit admission) and its individual outcomes. Hazard ratios (HR) were estimated by Cox regression, and odds ratios in oral antiviral users compared with non-users by logistic regression. Subgroup analyses evaluated the associations by vaccination status and age. Findings Among 1,072,004 non-hospitalized COVID-19 patients, 5,257 and 5,663 were initiated molnupiravir and nirmatrelvir/ritonavir in the community setting with a median follow-up of 42 and 38 days, respectively. Molnupiravir use was associated with lower risks of mortality (HR=0·61, 95%CI=0·46-0·82, p<0·001) and in-hospital composite outcome (HR=0·64, 95%CI=0·50-0·83, p<0·001) than non-use, while that of hospitalization was comparable to controls (HR=1·06, 95%CI=0·97-1·16, p=0·191). Nirmatrelvir/ritonavir use was associated with lower risks of mortality (HR=0·25, 95%CI=0·13-0·47, p<0·001), hospitalization (HR=0·69, 95%CI=0·60-0·79, p<0·001), and in-hospital outcome (HR=0·47, 95%CI=0·31-0·71, p<0·001) than non-use. Similar protective effects of nirmatrelvir/ritonavir were observed across vaccination status (fully vaccinated versus otherwise) and age (dichotomized at 65 years), whereas those for molnupiravir were less consistent. Findings from case-control analysis broadly confirmed those of primary analysis. Interpretation Amid the Omicron BA.2.2 wave, early initiation of oral antivirals among non-institutionalised COVID-19 patients was associated with reduced risks of mortality and in-hospital outcomes. Nirmatrelvir/ritonavir use was associated with greater and more consistent protection than molnupiravir. Funding Health and Medical Research Fund, Food and Health Bureau Research in context Evidence before this study Oral antivirals have been initiating in non-hospitalized COVID-19 patients to lower their risks of hospitalization and death, and hence to reduce the burden on healthcare systems. We searched Scopus and PubMed for studies until 25 May 2022 using the search terms “SARS-CoV-2 OR COVID-19” AND “molnupiravir OR Lagevrio OR EIDD-2801” OR “nirmatrelvir OR Paxlovid OR PF-07321332”. Major studies examining the outpatient use of molnupiravir and nirmatrelvir/ritonavir are MOVe-OUT and EPIC-HR trials, respectively. Both have been conducted among unvaccinated, non-hospitalized patients with mild-to-moderate COVID-19 who are at risk of progression to severe disease, during a pandemic wave of SARS-CoV-2 Delta variant. Early initiation of molnupiravir or nirmatrelvir/ritonavir within five days of symptom onset has been associated with relative risk reduction of hospitalization or death by 30% and 88%, respectively. Considering the real-world evaluation of the two oral antivirals against the currently circulating Omicron variant, only one single-center, retrospective review of solid organ transplant recipients with COVID-19 has been conducted; yet their results are unlikely generalizable to other populations given its specific patient group and small sample size. Real-world effectiveness of oral antivirals is urgently needed to inform their clinical use in COVID-19 patients, considering their vaccination status and the variant of concern. Added value of this study To the best of our knowledge, this is one of the first real-world studies exploring the clinical use of oral antivirals during a pandemic wave dominated by SARS-CoV-2 Omicron variant. A territory-wide, retrospective cohort study was conducted to examine the effectiveness of molnupiravir and nirmatrelvir/ritonavir in community-dwelling COVID-19 patients. Early initiation of molnupiravir or nirmatrelvir/ritonavir within five days of symptom onset was associated with significant reduction of all-cause mortality risk by 39% and 75%, respectively, compared to not using any oral antivirals. Nirmatrelvir/ritonavir use was also associated with a reduced risk of COVID-19-related hospitalization by 31%, which was consistently observed across age and vaccination status. In terms of disease progression, both oral antivirals were effective in lowering the risk of in-hospital death, which was again more substantial with nirmatrelvir/ritonavir than molnupiravir. Intriguingly, the need for invasive ventilation might be reduced among molnupiravir users compared to matched controls. Implications of all the available evidence Based on relative efficacy, our findings give support to current guidelines prioritizing nirmatrelvir/ritonavir use over molnupiravir in community-dwelling COVID-19 patients who are at high risk of hospitalization or progression to severe disease, should the former be accessible and clinically appropriate. Amid a pandemic wave of the Omicron variant, real-world effectiveness of oral antivirals in reducing the mortality risk of community-dwelling COVID-19 patients has been demonstrated in this study consisting mostly of the elderly and those who had not been fully vaccinated, extending beyond the evidence demonstrated in clinical trials among those of the Delta variant and who were at risk of severe COVID-19 from being overweight/obese. Several clinical trials (namely RECOVERY and PANORAMIC) and observational studies of the two oral antivirals are ongoing, and further research is needed to confirm our results in other patient populations and healthcare settings.

Immunogenicity, efficacy, and safety of SARS-CoV-2 vaccine dose fractionation: a systematic review and meta-analysis (preprint)

Background: Dose fractionation of Coronavirus Disease 2019 (COVID-19) vaccine could effectively accelerate global vaccine coverage, while supporting evidence of efficacy, immunogenicity, and safety are unavailable, especially with emerging variants.Methods: We systematically reviewed clinical trials reported dose-finding results and estimated the dose-response relationship of neutralizing antibodies (nAbs) of COVID-19 vaccines using generalized additive model. We predicted the vaccine efficacy against both ancestral and variants, using previously reported correlates of protection and cross-reactivity. We also reviewed and compared seroconversion to nAbs, T-cell responses and safety profiles between fractional and standard dose groups.Results: We found that dose fractionation of mRNA and protein subunit vaccines could induce SARS-CoV-2 specific nAbs and T-cells that confer a reasonable level of protection (i.e., vaccine efficacy > 50%) against ancestral strains and variants up to Omicron. Safety profiles of fractional doses were non-inferior to the standard dose.Conclusion: Dose fractionation of mRNA and protein subunit vaccines may be safe and effective.

Time-varying transmission heterogeneity of SARS and COVID-19 in Hong Kong (preprint)

Transmission heterogeneity is a notable feature of the severe acute respiratory syndrome (SARS) and coronavirus disease 2019 (COVID-19) epidemics, though previous efforts to estimate how heterogeneity changes over time are limited. Using contact tracing data, we compared the epidemiology of SARS and COVID-19 infection in Hong Kong in 2003 and 2020-21 and estimated time-varying transmission heterogeneity (kt) by fitting negative binomial models to offspring distributions generated across variable observation windows. kt fluctuated over time for both COVID-19 and SARS on a continuous scale though SARS exhibited significantly greater (p < 0.001) heterogeneity compared to COVID-19 overall and in-time. For COVID-19, kt declined over time and was significantly associated with increasingly stringent non-pharmaceutical interventions though similar evidence for SARS was inconclusive. Underdetection of sporadic COVID-19 cases led to a moderate overestimation of kt, indicating COVID-19 heterogeneity of could be greater than observed. Time-varying or real-time estimates of transmission heterogeneity could become a critical indicator for epidemic intelligence in the future.

International risk of SARS-CoV-2 Omicron variant importations originating in South Africa (preprint)

Omicron, a fast-spreading SARS-CoV-2 variant of concern reported to the World Health Organization on November 24, 2021, has raised international alarm. We estimated there is at least 50% chance that Omicron had been introduced by travelers from South Africa into all of the 30 countries studied by November 27, 2021.

Human seasonal influenza under COVID-19 and the potential consequences of influenza lineage elimination (preprint)

Annual epidemics of seasonal influenza cause hundreds of thousands of deaths, high levels of morbidity, and substantial economic loss. Yet, global influenza circulation has been heavily suppressed by public health measures and travel restrictions since the onset of the COVID-19 pandemic. Notably, the influenza B/Yamagata lineage has not been conclusively detected since April 2020, and A(H3N2), A(H1N1), and B/Victoria viruses circulate with considerably less genetic diversity. Travel restrictions have largely confined regional outbreaks of A(H3N2) to South and Southeast Asia, B/Victoria epidemics in China, and A(H1N1) in West Africa. Seasonal influenza transmission lineages continue to perish globally, except in select hotspots, which will likely seed future epidemics. Waning population immunity and sporadic case detection will further challenge influenza vaccine strain selection and epidemic control. We offer perspective on the potential short- and long-term evolutionary dynamics of seasonal influenza and discuss potential consequences and mitigation strategies as global travel gradually returns to pre-pandemic levels.

Comparative cost-effectiveness of SARS-CoV-2 vaccine dose fractionation in India: a modelling study (preprint)

Given constrained vaccine supplies globally, fractionation of vaccine doses may be an effective strategy for reducing disease and healthcare burdens, even with the emergence of COVID-19 variants. Using a multi-scale model that incorporates population-level transmission and individual-level vaccination, we estimate the costs associated with hospitalization, vaccine costs, and the economic benefit of reducing COVID-19 deaths associated with dose-fractionation strategies. Assuming a willingness-to-pay of US$10,517 per averted year of life lost (YLL) and a price of $12 per vaccine, under various transmission scenarios, with effective reproduction numbers ranging from 1.1 to 5.0 and with vaccine efficacy against transmission from 52% to 91%, the optimal vaccination strategy would always involve fractional doses of vaccines. Vaccine dose fractionation is a cost-effective strategy for mitigating the COVID-19 pandemic and could save a large number of lives, even after the emergence of variants with higher transmissibility.

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.

Transmission dynamics of COVID-19 in Ghana and the impact of public health interventions (preprint)

The study characterized COVID-19 transmission in Ghana in 2020-21 by estimating the time-varying reproduction number (R t ) and exploring its association with various public health interventions at the national and regional levels. Ghana experienced four pandemic waves with epidemic peaks in July 2020, and January, August and December, 2021. The epidemic peak was the highest nationwide in December 2021 with R t ≥2. Throughout 2020-21, per-capita cumulative case count by region increased with population size. Mobility data suggested negative correlation between R t and staying home in the first 90 days of the pandemic. The relaxation of movement restrictions and religious gatherings were not associated with increased R t in the regions with lower case burdens. R t decreased from above 1 when schools reopened in January 2021 to below 1 after vaccination rollout in March 2021. Findings indicated most public health interventions were associated with R t reduction at the national and regional levels.

Pooling Samples as an Efficient Approach to Regular SARS-CoV-2 Testing in Residential Care Facilities (preprint)

Background: Residents of care facilities for the elderly have accounted for a large proportion of all deaths due to COVID-19 globally. In Hong Kong, care home staff are required to undergo testing for SARS-CoV-2 every two weeks, regardless of symptoms. We aimed to optimize testing strategies in order to improve on existing screening programs.Methods: We estimated the reduced sensitivity of pooled PCR testing and used a decision analysis to determine the expected number of tests required. We assumed transmission occurred according to a time-varying Poisson process and that the time from infection to isolation followed a time-varying geometric distribution. We estimated the cumulative number of cases expected under syndromic surveillance, testing without pooling and pooled testing with pool sizes 2, 5 and 10 using an age of infection model.Findings: Assuming a prevalence of 0.02%, pooling 10 samples and conducting testing every two days instead of testing without pooling every 14 days could reduce the average size of an outbreak from between 2 and 14 cases (median 7 cases) to between 1 and 6 cases (median 2 cases). Pooling to allow for daily testing further reduced the average size of an outbreak from 4 cases to 1 case compared to weekly testing.Interpretation: Health authorities can improve on existing screening programs by employing pooled testing procedures and testing individuals more frequently to make the most use of available testing resources.Funding Information: This project was supported by a commissioned grant from the Health and Medical Research Fund, Food and Health Bureau, Government of the Hong Kong Special Administrative Region, and the Theme-based Research Scheme (Project No. T11-712/19-N) of the Research Grants Council of the Hong Kong SAR Government.Declaration of Interests: BJC consults for Roche, GSK, Moderna, AstraZeneca and Sanofi Pasteur and is supported by the AIR@innoHK program of the Innovation and Technology Commission of the Hong Kong SAR Government. The authors report no other potential conflicts of interest.Ethics Approval Statement: The study was approved by the Institutional Review Board of the University of Hong Kong.

Universal Community Nucleic Acid Testing for COVID-19 in Hong Kong Reveals Insights into Transmission Dynamics (preprint)

Background: Testing of an entire community has been used as an approach to control COVID-19. In Hong Kong, a universal community testing programme (UCTP) was implemented at the fadeout phase of a community epidemic in July to September 2020, to determine the prevalence of unrecognised cases and limit any remaining transmission chains. We described the utility of the UCTP in finding unrecognised cases, and analysed data from the UCTP and other sources to characterise transmission dynamics.Methods: We described the characteristics of people participating in the UCTP, and compared the clinical and epidemiological characteristics of COVID-19 cases detected by the UCTP versus those detected by clinical diagnosis and public health surveillance. We developed a Bayesian model to estimate the age-specific incidence of infection and the proportion of cases detected by clinical diagnosis and public health surveillance.Findings: 1.77 million people, 24% of the Hong Kong population, participated in the UCTP from 1 to 14 September 2020. The UCTP identified 32 new infections (1.8 per 100,000 samples tested), consisting of 29% of all local cases reported during the two-week UCTP period. Compared with the existing clinical diagnosis and public health surveillance, the UCTP detected a higher proportion of sporadic cases (62% versus 27%, p <0.01) and identified 6 (out of 18) additional transmission chains during that period. We estimated that 27% (95% credible interval: 22%, 34%) of all infections were detected by the existing clinical diagnosis and public health surveillance in the third wave.Interpretation: We reported empirical evidence of the utility of population-wide COVID-19 testing in detecting unrecognised infections and transmission chains. Around three quarters of infections have not been identified through existing surveillance approaches including contact tracing.Funding Statement: This project was supported by the Health and Medical Research Fund, Food and Health Bureau, Government of the Hong Kong Special Administrative Region (grant no. COVID190118).Declaration of Interests: BJC consults for Roche, Sanofi Pasteur, GSK and Moderna. The authors report no other potential conflicts of interest.Ethics Approval Statement: Our project was approved by the Institutional Review Board of the University of Hong Kong/Hospital Authority Hong Kong West Cluster (HKU/HA HKW IRB).

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.