A statistical framework for tracking the time-varying superspreading potential of COVID-19 epidemic.

Timely detection of an evolving event of an infectious disease with superspreading potential is imperative for territory-wide disease control as well as preventing future outbreaks. While the reproduction number (R) is a commonly-adopted metric for disease transmissibility, the transmission heterogeneity quantified by dispersion parameter k, a metric for superspreading potential is seldom tracked. In this study, we developed an estimation framework to track the time-varying risk of superspreading events (SSEs) and demonstrated the method using the three epidemic waves of COVID-19 in Hong Kong. Epidemiological contact tracing data of the confirmed COVID-19 cases from 23 January 2020 to 30 September 2021 were obtained. By applying branching process models, we jointly estimated the time-varying R and k. Individual-based outbreak simulations were conducted to compare the time-varying assessment of the superspreading potential with the typical non-time-varying estimate of k over a period of time. We found that the COVID-19 transmission in Hong Kong exhibited substantial superspreading during the initial phase of the epidemics, with only 1 % (95 % Credible interval [CrI]: 0.6-2 %), 5 % (95 % CrI: 3-7 %) and 10 % (95 % CrI: 8-14 %) of the most infectious cases generated 80 % of all transmission for the first, second and third epidemic waves, respectively. After implementing local public health interventions, R estimates dropped gradually and k estimates increased thereby reducing the risk of SSEs to approaching zero. Outbreak simulations indicated that the non-time-varying estimate of k may overlook the possibility of large outbreaks. Hence, an estimation of the time-varying k as a compliment of R as a monitoring of both disease transmissibility and superspreading potential, particularly when public health interventions were relaxed is crucial for minimizing the risk of future outbreaks.

Mass Screening of SARS-CoV-2 With Rapid Antigen Tests in a Receding Omicron Wave: Population-Based Survey for Epidemiologic Evaluation.

BACKGROUND: The COVID-19 Omicron BA.2 epidemic wave in Hong Kong peaked in the first quarter of 2022. Following the implementation of stringent public health measures, the daily number of reported cases fell from over 50,000 to below 2000. Although outbreaks steadily receded, the government rolled out a 3-day "voluntary universal rapid testing" campaign to invite all citizens to self-perform a rapid antigen test (RAT) daily to identify undetected prevalent infections. OBJECTIVE: This study aimed to evaluate the uptake and results of RAT mass screening to estimate the population's residual epidemic burden and assess the risk of further transmission. METHODS: A cross-sectional study comprising an open web-based population-based survey was conducted a week after the RAT campaign. Participants were asked to report their COVID-19 vaccination and infection history and the RAT performance and test result during the period. They were also invited to report their coliving individuals' test performance and results. Reasons for nonuptake were enquired. Testing and positive rates were age-adjusted. Determinants of undergoing RAT were identified using univariable and multivariable logistic regression models. RESULTS: In total, particulars from 21,769 individuals were reported by 8338 participants. The overall age-adjusted testing rate was 74.94% (95% CI 73.71%-76.18%), with over 80% of participants in the age groups between 45-84 years having self-performed RAT during the campaign period. After age-adjustment, 1.03% (95% CI 0.86%-1.21%) of participants tested positive. The positive rates in the age groups between 20-29 years and >84 years exceeded 2%. Taking into account the positive rate and 5819 reported cases during the period, the cases identified in the campaign might account for 7.65% (95% CI 6.47%-9.14%) of all infections. Testers were more likely to be female, older, not previously diagnosed with COVID-19, and have received COVID-19 vaccination. Adjusting for the number of household members, those living with a child aged <12 years and whose household members were also tested were more likely to have self-performed an RAT. Main reasons for not performing an RAT included the absence of symptoms (598/1108, 53.97%), disbelief of the appropriateness of the campaign as an antiepidemic measure (355/1108, 32.04%), and a recent COVID-19 diagnosis (332/1108, 29.96%). CONCLUSIONS: The residual population burden remained substantial in spite of the clear evidence of a receding epidemic wave. Despite caution in generalization to the Hong Kong population, the high participation rate in mass screening indicated that the voluntary RAT was well accepted, making it a feasible option for implementation as a complementary means of public health surveillance.

Three-Dose Primary Series of Inactivated COVID-19 Vaccine for Persons Living with HIV, Hong Kong.

In a cohort of persons living with HIV in Hong Kong, surrogate virus neutralization testing for COVID-19 yielded a median level of 89% after the third dose of an inactivated COVID-19 vaccine, compared with 37% after the second dose. These results support using a 3-dose primary series for enhanced immune protection.

Trajectory patterns of SARS-CoV-2 neutralising antibody response in convalescent COVID-19 patients.

Background: The adaptive immune responses of COVID-19 patients contributes to virus clearance, restoration of health and protection from re-infection. The patterns of and the associated characteristics with longitudinal neutralising antibody (NAb) response following SARS-CoV-2 infection are important in their potential association with the population risks of re-infection. Methods: This is a longitudinal study with blood samples and clinical data collected in adults aged 18 or above following diagnosis of SARS-CoV-2 infection. NAb levels were measured by the SARS-CoV-2 surrogate virus neutralisation test (sVNT). Anonymous clinical and laboratory data were matched with surveillance data for each subject for enabling analyses and applying latent class mixed models for trajectory delineation. Logistic regression models were performed to compare the characteristics between the identified classes. Results: In 2020-2021, 368 convalescent patients in Hong Kong are tested for NAb. Their seroconversion occur within 3 months in 97% symptomatic patients, the level of which are maintained at 97% after 9 months. The NAb trajectories of 200 symptomatic patients are classified by the initial response and subsequent trend into high-persistent and waning classes in latent class mixed models. High-persistent (15.5%) class patients are older and most have chronic illnesses. Waning class patients (84.5%) are largely young adults who are mildly symptomatic including 2 who serorevert after 10 months. Conclusions: Characteristic sub-class variabilities in clinical pattern are noted especially among patients with waning NAb. The heterogeneity of the NAb trajectory patterns and their clinical association can be important for informing vaccination strategy to prevent re-infection.

Surrogate neutralization responses following severe acute respiratory syndrome coronavirus 2 vaccination in people with HIV: comparison between inactivated and mRNA vaccine.

OBJECTIVE: People with HIV (PWH) co-infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are at higher odds of severe diseases. Whereas the immunogenicity of mRNA vaccine and adenovirus-vectored vaccine was similar between PWH in stable condition and healthy adults, the effects of inactivated vaccines are not known. DESIGN: Prospective longitudinal observational study in real-world setting. METHODS: Adult PWH in care and planning to receive either inactivated (day 0 and day 28) or mRNA-based (day 0 and day 21) vaccine against SARS-CoV-2 were recruited, with blood samples collected over 6 months for surrogate virus neutralization test (sVNT). Demographic and clinical data including age, sex, CD4 + cell count, and suppressed viral load (SVL) status were transcribed for analyses, by simple and multivariable linear regression models, and multivariable linear generalized estimating equations (GEE). RESULTS: A total of 611 HIV patients, 91% male patients, were recruited, of whom 423 and 184 have received mRNA-based and inactivated vaccine, respectively. The seroconversion rate was 99% for mRNA-based vs, 86% for inactivated vaccine [odds ratio (OR) = 21.56, P  = 0.004]. At 6 months, mRNA-based vaccine continued to give a higher response (94 vs. 57%, P  < 0.001). The temporal pattern varied between the two vaccines. By GEE, mRNA-based vaccine ( B  = 40.59, P  < 0.001) and latest SVL status ( B  = 10.76, P  = 0.01) were positively associated with sVNT level, but not latest CD4 + cell count. CONCLUSION: In HIV patients, inactivated vaccine gave a lower peak and shorter duration of sVNT responses compared with mRNA vaccine. The results suggested that different strategies may be needed in boosting the immunity in anticipation of the emergence of variants in the community.

The double-edged impacts of COVID-19 epidemic on influenza vaccination uptake in nurses in Hong Kong.

BACKGROUND: Worldwide, the COVID-19 pandemic has disrupted influenza seasonality and impacted influenza vaccination behaviours. This study examines the patterns of influenza vaccination uptake in nurses during the pre-pandemic seasons and amidst the pandemic in 2020/21 in subtropical Hong Kong. METHODS: In April 2021, a cross-sectional survey was conducted in practising and student nurses. Six patterns were differentiated by their influenza vaccination status in 2020/21 and preceding five seasons: (a) resistance throughout, (b) negative change, (c) decreased tendency, (d) increased tendency (e) positive change, and (f) adherence throughout. Participants' characteristics and reasons for vaccination/non-vaccination and their associations with each vaccination pattern were explored using multivariable multinomial regression. RESULTS: Among 1323 nurses (88% female with a median age of 39 years), no substantial change in vaccination uptake was noted from 2019/20 (41%) to 2020/21 (42%). Some 4% were positive-changers who were older at age of ≥50 years (aOR 4.77) and more likely to anticipate a reduced risk of severe disease with COVID-19/influenza co-infection following vaccination (aOR 8.76). Negative-changers made up 3% and were more inclined to perceive an unlikelihood of widespread influenza outbreaks amidst the pandemic (aOR 3.67). Some 26 and 43% remained adherent and resistant to influenza vaccination throughout respectively notwithstanding the COVID-19 outbreak. CONCLUSIONS: In contrast to the increased uptake elsewhere, the stable influenza vaccination coverage among nurses in Hong Kong could be explained by the ubiquity of strict physical distancing regulations, which have deterred vaccination in some nurses that offsets the new uptakes induced by the mild COVID-19 outbreaks.

Shifts of SARS-CoV-2 exposure settings in the transmission clusters of 2 epidemic waves in Hong Kong.

Exposure setting is crucial in the formation and propagation of SARS-CoV-2 transmission clusters. In this cohort study, transmission networks of 2 waves were differentiated by exposure setting using territory-wide surveillance data with clinical and laboratory records in Hong Kong. Characteristically, the first wave had resulted from imported cases followed by local transmissions, while the second wave was constituted primarily by local infections. With a 4-fold higher caseload, the second wave featured predominance of epidemiologically linked, local, older and asymptomatic patients with higher viral loads and shorter inpatient days. The 1028 transmission clusters formed 155 cascades composing at least two clusters. Daily and social activities were exposure settings that bridged clusters while residences usually terminated transmission cascades. Regulatory restrictions on social activities extinguished cluster formation in bars, but shifted to private parties in the second wave. The results confirmed that strategic interventions targeting exposure settings could achieve effective epidemic control.

Impact of pre-event testing and quarantine on reducing the risk of COVID-19 epidemic rebound: a modelling study.

BACKGROUND: With the evolving growth of the COVID-19 epidemic, travel restriction policies would need to be adjusted accordingly. Prohibition of mass event may be relaxed for social and economic benefits when virus transmission stops but could bear the risk of epidemic rebound. Against the background of the varied SARS-CoV-2 prevalence internationally, we modelled the potential impacts of pre-event interventions on epidemic risk of holding a mass event when COVID-19 is under control. METHODS: We developed a mathematical model of SARS-CoV-2 transmission in Guangdong Province, China, where local virus transmission ceased to occur. A large-scale international trade fair was assumed to be held, with influx of people from overseas and rest of China over a short period of time, who participated for 2-week. Scenarios of pre-event intervention (none, quarantine arrangement and polymerase chain reaction (PCR) testing for participants) were compared. The influence of contact pattern, SARS-CoV-2 prevalence outside the province and China, and testing coverage were examined in sensitivity analyses. RESULTS: In basecase scenario (no event), the epidemic has been under control since March 2020. The event would lead to the detection of 1% more confirmed cases by 31 July when community contact rate increases to pre-epidemic level. In event scenario without additional interventions, there would be 599 (93%) more new infections comparing with basecase scenario. To avert new infections, quarantining all participants before the event would be the most effective strategy, followed by quarantining all overseas participants and testing all other participants, and testing all participants before the event and on day 7. However, testing strategy is likely to be affected by the SARS-CoV-2 prevalence outside the event province. CONCLUSIONS: Pre-event interventions are effective for reducing the risk of epidemic rebound caused by an international large-scale event. Universal testing for participants is likely to be an effective and feasible intervention.

Characterization of Unlinked Cases of COVID-19 and Implications for Contact Tracing Measures: Retrospective Analysis of Surveillance Data.

BACKGROUND: Contact tracing and intensive testing programs are essential for controlling the spread of COVID-19. However, conventional contact tracing is resource intensive and may not result in the tracing of all cases due to recall bias and cases not knowing the identity of some close contacts. Few studies have reported the epidemiological features of cases not identified by contact tracing ("unlinked cases") or described their potential roles in seeding community outbreaks. OBJECTIVE: For this study, we characterized the role of unlinked cases in the epidemic by comparing their epidemiological profile with the linked cases; we also estimated their transmission potential across different settings. METHODS: We obtained rapid surveillance data from the government, which contained the line listing of COVID-19 confirmed cases during the first three waves in Hong Kong. We compared the demographics, history of chronic illnesses, epidemiological characteristics, clinical characteristics, and outcomes of linked and unlinked cases. Transmission potentials in different settings were assessed by fitting a negative binomial distribution to the observed offspring distribution. RESULTS: Time interval from illness onset to hospital admission was longer among unlinked cases than linked cases (median 5.00 days versus 3.78 days; P<.001), with a higher proportion of cases whose condition was critical or serious (13.0% versus 8.2%; P<.001). The proportion of unlinked cases was associated with an increase in the weekly number of local cases (P=.049). Cluster transmissions from the unlinked cases were most frequently identified in household settings, followed by eateries and workplaces, with the estimated probability of cluster transmissions being around 0.4 for households and 0.1-0.3 for the latter two settings. CONCLUSIONS: The unlinked cases were positively associated with time to hospital admission, severity of infection, and epidemic size-implying a need to design and implement digital tracing methods to complement current conventional testing and tracing. To minimize the risk of cluster transmissions from unlinked cases, digital tracing approaches should be effectively applied in high-risk socioeconomic settings, and risk assessments should be conducted to review and adjust the policies.

Mining relationships between transmission clusters from contact tracing data: An application for investigating COVID-19 outbreak.

OBJECTIVE: Contact tracing of reported infections could enable close contacts to be identified, tested, and quarantined for controlling further spread. This strategy has been well demonstrated in the surveillance and control of COVID-19 (coronavirus disease 2019) epidemics. This study aims to leverage contact tracing data to investigate the degree of spread and the formation of transmission cascades composing of multiple clusters. MATERIALS AND METHODS: An algorithm on mining relationships between clusters for network analysis is proposed with 3 steps: horizontal edge creation, vertical edge consolidation, and graph reduction. The constructed network was then analyzed with information diffusion metrics and exponential-family random graph modeling. With categorization of clusters by exposure setting, the metrics were compared among cascades to identify associations between exposure settings and their network positions within the cascade using Mann-Whitney U test. RESULTS: Experimental results illustrated that transmission cascades containing or seeded by daily activity clusters spread faster while those containing social activity clusters propagated farther. Cascades involving work or study environments consisted of more clusters, which had a higher transmission range and scale. Social activity clusters were more likely to be connected, whereas both residence and healthcare clusters did not preferentially link to clusters belonging to the same exposure setting. CONCLUSIONS: The proposed algorithm could contribute to in-depth epidemiologic investigation of infectious disease transmission to support targeted nonpharmaceutical intervention policies for COVID-19 epidemic control.

Settings of virus exposure and their implications in the propagation of transmission networks in a COVID-19 outbreak.

BACKGROUND: Transmission dynamics of SARS-CoV-2 varied by the settings of virus exposure. Understanding the inter-relationship between exposure setting and transmission networks would provide a basis for informing public health control strategies. METHODS: Surveillance and clinical data from the first wave of COVID-19 outbreaks in Hong Kong were accessed. Twelve exposure setting types were differentiated - household, neighbourhood, eateries, entertainment, parties, shopping, personalised service, workplace, education, worship, healthcare, transport. Clustering was investigated followed by reconstructing the transmission cascades of clustered cases using social networking approach. Linked and unlinked cases were compared in statistical analyses. FINDINGS: Between 23 January and 19 June 2020, 1128 cases were reported. Among 324 cases related to local transmission, 123 clusters comprising two or more epidemiologically linked cases were identified. Linked cases had lower Ct value (p < 0·001) than unlinked cases. Households accounted for 63% of all clusters with half as primary setting, while entertainment accounted for the highest number of primary setting transmission cases. There were altogether 19 cascades involving >1 exposure setting, with a median reproduction number of 3(IQR: 2-4), versus 1(IQR:1-2) for cascades involving a single setting (n = 36 cascades). The longest cascade featured a bar (entertainment) as primary setting, with propagation through 30 non-primary exposure settings from seven setting types, reflecting, propensity for widespread dispersion and difficulty in containment. INTERPRETATION: There was marked heterogeneity in the characteristics of SARS-CoV-2 transmission cascades which differed by exposure setting. Network epidemiological analyses of transmission cascades can be applied as a risk assessment tool in decision-making for calibrating social distancing measures. FUNDING: Health and Medical Research Fund.

Abrupt Subsidence of Seasonal Influenza after COVID-19 Outbreak, Hong Kong, China.

The onset of the 2019-20 winter influenza season in Hong Kong coincided with the emergence of the coronavirus disease epidemic in neighboring mainland China. After widespread adoption of large-scale social distancing interventions in response to the impending coronavirus disease outbreak, the influenza season ended abruptly with a decrease to a low trough.