Residential clustering of COVID-19 cases and efficiency of building-wide compulsory testing notices as a transmission control measure in Hong Kong.

We described the frequency of residential case clusters and the efficiency of compulsory testing in identifying cases using buildings targeted in compulsory testing and locally infected COVID-19 cases matched by residence in Hong Kong. Most of the buildings (4246/7688, 55.2%) with COVID-19 cases identified had only one reported case and 13% of the daily reported cases were detected through compulsory testing. Compulsory testing notices could be essential in attempting to eliminate infections ('zero covid') and impactful early in an epidemic but appears to be relatively inefficient in response to sustained community transmission.

The effect of variation of individual infectiousness on SARS-CoV-2 transmission in households.

Quantifying variation of individual infectiousness is critical to inform disease control. Previous studies reported substantial heterogeneity in transmission of many infectious diseases including SARS-CoV-2. However, those results are difficult to interpret since the number of contacts is rarely considered in such approaches. Here, we analyze data from 17 SARS-CoV-2 household transmission studies conducted in periods dominated by ancestral strains, in which the number of contacts was known. By fitting individual-based household transmission models to these data, accounting for number of contacts and baseline transmission probabilities, the pooled estimate suggests that the 20% most infectious cases have 3.1-fold (95% confidence interval: 2.2- to 4.2-fold) higher infectiousness than average cases, which is consistent with the observed heterogeneity in viral shedding. Household data can inform the estimation of transmission heterogeneity, which is important for epidemic management.

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.

Detection of influenza in managed quarantine in Australia and the estimated risk of importation.

BACKGROUND: Influenza circulated at historically-low levels during 2020 and 2021 due to COVID-19 pandemic travel restrictions. In Australia, international arrivals to Australia were required to undertake 14 days hotel quarantine to limit new introduction of SARS-CoV-2 virus. METHODS: We used routine testing data for travellers arriving on repatriation flights to Darwin, Australia from 3 January to 11 October 2021 to identify importations of influenza virus into Australia and used this information to estimate the risk of a case exiting quarantine while still infectious. Influenza-positive samples were sequenced and cases were followed-up to identify transmission clusters. Data on the number of cases and total passengers was used to infer the risk of influenza cases existing quarantine while infectious. RESULTS: Despite very low circulation of influenza globally, 42 cases were identified among 15,026 returned travellers, of which 30 were A(H3N2), two were A(H1N1)pdm09 and 10 were B/Victoria. Virus sequencing data identified potential in-flight transmission, as well as independent infections prior to travel. Under the quarantine strategy in place at the time, the probability that these cases could initiate influenza outbreaks in Australia neared 0. However, this probability rose as quarantine requirements relaxed. CONCLUSIONS: Detection of influenza virus infections in repatriated travellers provided a source of influenza viruses otherwise unavailable and enabled development of the A(H3N2) vaccine seed viruses included in the 2022 Southern Hemisphere influenza vaccine. Failing to test quarantined returned travellers for influenza, represents a missed opportunity for enhanced surveillance to better inform public health preparedness.

Risk of within-hotel transmission of SARS-CoV-2 during on-arrival quarantine in Hong Kong: an epidemiological and phylogenomic investigation.

Background: On-arrival quarantine has been one of the primary measures to prevent the introduction of SARS-CoV-2 into Hong Kong since the start of the pandemic. Most on-arrival quarantines have been done in hotels, with the duration of quarantine and testing frequency during quarantine modified over time along with other pandemic control measures. However, hotels are not designed with infection control in mind. We aimed to systematically study the potential risk of acquisition of SARS-CoV-2 infection among individuals undergoing hotel quarantine. Methods: We examined data on each laboratory-confirmed COVID-19 case identified in on-arrival quarantine in a hotel in Hong Kong between 1 May 2020 and 31 January 2022. We sequenced the whole genomes of viruses from cases that overlapped with other confirmed cases in terms of the hotel of stay, date of arrival and date of testing positive. By combining multiple sources of evidence, we identify probable and plausible transmission events and calculate the overall risk of transmission. Findings: Among 221 imported cases that overlapped with other cases detected during hotel quarantine with available sequence data, phylogenomic analyses identified five probable and two plausible clusters of within-hotel transmission. Only two of these clusters were recognised at the time. Including other clusters reported in Hong Kong, we estimate that 8-11 per 1000 cases identified in hotel quarantine may be infected by another unlinked case during quarantine, or 2-3 per 100,000 overseas arrivals. Interpretation: We have identified additional undetected occurrences of COVID-19 transmission within hotel quarantine in Hong Kong. Although hotels provide suboptimal infection control as improvised quarantine facilities, the risk of contracting infection whilst in quarantine is low. However, these unlikely events could have high consequences by allowing the virus to spread into immunologically naïve communities. Additional vigilance should be taken in the absence of improved controls to identify such events. If on-arrival quarantine is expected to be used for a long time, quarantine facilities could be purpose-built to minimise the risk of transmission. Funding: Health and Medical Research Fund, Hong Kong.

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

BACKGROUND: Dose fractionation of a 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 that reported dose-finding results and estimated the dose-response relationship of neutralizing antibodies (nAbs) of COVID-19 vaccines using a 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. CONCLUSIONS: Dose fractionation of mRNA and protein subunit vaccines may be safe and effective, which would also vary depending on the characteristics of emerging variants and updated vaccine formulations.

Effectiveness of CoronaVac and BNT162b2 Vaccines Against Severe Acute Respiratory Syndrome Coronavirus 2 Omicron BA.2 Infections in Hong Kong.

There is limited evidence on vaccine effectiveness against asymptomatic or mild Omicron infections. We estimated that recent third doses of messenger RNA or inactivated vaccines reduced the risk of self-reported infection by 52% (95% confidence interval, 17%-73%) among randomly sampled adults during the Omicron BA.2-dominated surge in Hong Kong.

Universal Community Nucleic Acid Testing for Coronavirus Disease 2019 (COVID-19) in Hong Kong Reveals Insights Into Transmission Dynamics: A Cross-Sectional and Modeling Study.

BACKGROUND: Testing of an entire community has been used as an approach to control coronavirus disease 2019 (COVID-19). In Hong Kong, a universal community testing program (UCTP) was implemented at the fadeout phase of a community epidemic in July to September 2020. We described the utility of the UCTP in finding unrecognized infections and analyzed data from the UCTP and other sources to characterize 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 (CDPHS). We developed a Bayesian model to estimate the age-specific incidence of infection and the proportion of cases detected by CDPHS. RESULTS: In total, 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 100000 samples tested), consisting of 29% of all local cases reported during the two-week UCTP period. Compared with the CDPHS, the UCTP detected a higher proportion of sporadic cases (62% vs 27%, P<.01) and identified 6 (out of 18) additional clusters during that period. We estimated that 27% (95% credible interval: 22%, 34%) of all infections were detected by the CDPHS in the third wave. CONCLUSIONS: We reported empirical evidence of the utility of population-wide COVID-19 testing in detecting unrecognized infections and clusters. Around three quarters of infections have not been identified through existing surveillance approaches including contact tracing.

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.

Changing Disparities in Coronavirus Disease 2019 (COVID-19) Burden in the Ethnically Homogeneous Population of Hong Kong Through Pandemic Waves: An Observational Study.

BACKGROUND: Disparities were marked in previous pandemics, usually with higher attack rates reported for those in lower socioeconomic positions and for ethnic minorities. METHODS: We examined characteristics of laboratory-confirmed coronavirus disease 2019 (COVID-19) cases in Hong Kong, assessed associations between incidence and population-level characteristics at the level of small geographic areas, and evaluated relations between socioeconomics and work-from-home (WFH) arrangements. RESULTS: The largest source of COVID-19 importations switched from students studying overseas in the second wave to foreign domestic helpers in the third. The local cases were mostly individuals not in formal employment (retirees and homemakers) and production workers who were unable to WFH. For every 10% increase in the proportion of population employed as executives or professionals in a given geographic region, there was an 84% (95% confidence interval [CI], 1-97%) reduction in the incidence of COVID-19 during the third wave. In contrast, in the first 2 waves, the same was associated with 3.69 times (95% CI, 1.02-13.33) higher incidence. Executives and professionals were more likely to implement WFH and experienced frequent changes in WFH practice compared with production workers. CONCLUSIONS: Consistent findings on the reversed socioeconomic patterning of COVID-19 burden between infection waves in Hong Kong in both individual- and population-level analyses indicated that risks of infections may be related to occupations involving high exposure frequency and WFH flexibility. Contextual determinants should be taken into account in policy planning aiming at mitigating such disparities.

Using secondary cases to characterize the severity of an emerging or re-emerging infection.

The methods to ascertain cases of an emerging infectious disease are typically biased toward cases with more severe disease, which can bias the average infection-severity profile. Here, we conducted a systematic review to extract information on disease severity among index cases and secondary cases identified by contact tracing of index cases for COVID-19. We identified 38 studies to extract information on measures of clinical severity. The proportion of index cases with fever was 43% higher than for secondary cases. The proportion of symptomatic, hospitalized, and fatal illnesses among index cases were 12%, 126%, and 179% higher than for secondary cases, respectively. We developed a statistical model to utilize the severity difference, and estimate 55% of index cases were missed in Wuhan, China. Information on disease severity in secondary cases should be less susceptible to ascertainment bias and could inform estimates of disease severity and the proportion of missed index cases.

Effectiveness of International Travel Controls for Delaying Local Outbreaks of COVID-19.

During the coronavirus disease pandemic, international travel controls have been widely adopted. To determine the effectiveness of these measures, we analyzed data from 165 countries and found that early implementation of international travel controls led to a mean delay of 5 weeks in the first epidemic peak of cases.

The Usefulness of the Test-Positive Proportion of Severe Acute Respiratory Syndrome Coronavirus 2 as a Surveillance Tool.

Comparison of coronavirus disease 2019 (COVID-19) case numbers over time and between locations is complicated by limits to virological testing to confirm severe acute respiratory syndrome coronavirus 2 infection. The proportion of tested individuals who have tested positive (test-positive proportion, TPP) can potentially be used to inform trends in incidence. We propose a model for testing in a population experiencing an epidemic of COVID-19 and derive an expression for TPP in terms of well-defined parameters related to testing and presence of other pathogens causing COVID-19-like symptoms. In the absence of dramatic shifts of testing practices in time or between locations, the TPP is positively correlated with the incidence of infection. We show that the proportion of tested individuals who present COVID-19-like symptoms encodes information similar to the TPP but has different relationships with the testing parameters, and can thus provide additional information regarding dynamic changes in TPP and incidence. Finally, we compare data on confirmed cases and TPP from US states up to October 2020. We conjecture why states might have higher or lower TPP than average. Collection of symptom status and age/risk category of tested individuals can increase the utility of TPP in assessing the state of the pandemic in different locations and times.

The differential importation risks of COVID-19 from inbound travellers and the feasibility of targeted travel controls: A case study in Hong Kong.

BACKGROUND: Many countries/regions implemented strict border measures (e.g., 14-day quarantines) as a blanket policy to prevent COVID-19 importations, while proposed "travel bubbles" as an alternative to reduce the impact of border controls. We aim to examine the differential importation risks with departure origins and post-arrival controls. METHODS: We developed a Bayesian framework to model disease progress of COVID-19 and the effectiveness of travel measures and inferred the origin-specific disease prevalence among inbound travellers, using data on passengers arriving in Hong Kong and laboratory-confirmed imported cases. We estimated the origin-specific risks of releasing infectious travellers under different control strategies and traveller volumes. We also estimated the risk of having released infectious travellers when a resurgence occurs in departure locations with no imported cases during a certain period. FINDINGS: Under the then strict controls of 14-day quarantine and testing on day 12, the Philippines imposed the greatest importation risk among the studied countries/regions (95.8% of releasing at least one infectious traveller, 95% credible interval (CrI), 94.8-96.6%). This was higher than that from low prevalence countries/regions (e.g., 23.4%, 95% CrI, 21.6-25.3% for Taiwan) if controls relaxed (i.e., 7-day quarantine and test on day 5). Increased traveller volumes and resurgence in departure locations with low prevalence under relaxed controls did not impose a greater importation risk than high prevalence locations under stricter controls. INTERPRETATION: Moderate relaxation of control measures for travellers arriving from low prevalence locations did not impose higher risks of community outbreaks than strict controls on travellers from high prevalence locations. FUNDING: Health and Medical Research Fund, Hong Kong.

Effect of specific non-pharmaceutical intervention policies on SARS-CoV-2 transmission in the counties of the United States.

Non-pharmaceutical interventions (NPIs) remain the only widely available tool for controlling the ongoing SARS-CoV-2 pandemic. We estimated weekly values of the effective basic reproductive number (Reff) using a mechanistic metapopulation model and associated these with county-level characteristics and NPIs in the United States (US). Interventions that included school and leisure activities closure and nursing home visiting bans were all associated with a median Reff below 1 when combined with either stay at home orders (median Reff 0.97, 95% confidence interval (CI) 0.58-1.39) or face masks (median Reff 0.97, 95% CI 0.58-1.39). While direct causal effects of interventions remain unclear, our results suggest that relaxation of some NPIs will need to be counterbalanced by continuation and/or implementation of others.

Confidence, Acceptance and Willingness to Pay for the COVID-19 Vaccine among Migrants in Shanghai, China: A Cross-Sectional Study.

Understanding the public's attitude towards COVID-19 vaccination and their acceptance could help facilitate the COVID-19 rollout. This study aimed to assess the acceptance and willingness to pay (WTP) for the COVID-19 vaccine among migrants in Shanghai, China. A cross-sectional study was conducted among 2126 migrants in Shanghai for the period 1-20 November 2020. Convenience sampling was used to recruit respondents in workplaces with large numbers of migrant workers. Multivariable (ordered) logistic regressions were used to examine factors associated with acceptance and WTP of the COVID-19 vaccine. Most (89.1%) migrants would accept COVID-19 vaccination. Over 90.0% perceived the COVID-19 vaccine as important, while only 75.0% and 77.7% perceived vaccines safe and effective. Socio-demographic factors were not significantly associated with vaccine acceptance, but confidence in the importance (OR 8.71, 95% CI 5.89-12.89), safety (OR 1.80, 95% CI 1.24-2.61) and effectiveness (OR 2.66, 95% CI 1.83-3.87) of COVID-19 vaccine was significantly positively associated with vaccine acceptance. The top reasons for vaccine hesitancy were lack of vaccine information and confidence. The proportion of those definitely willing to get the COVID-19 vaccine was 20% lower if paid by themselves than free vaccination. Migrants were willing to pay a median amount of USD 46 for the COVID-19 vaccine. Results show that a high acceptance of the COVID-19 vaccine was universal among migrants in Shanghai. Concerns about vaccine safety, effectiveness and high costs of the COVID-19 vaccine may hinder their uptake. Effective health communication to build confidence in the COVID-19 vaccine and subsidies toward the costs of these vaccines are needed to improve uptake.

Risk for International Importations of Variant SARS-CoV-2 Originating in the United Kingdom.

A fast-spreading severe acute respiratory syndrome coronavirus 2 variant identified in the United Kingdom in December 2020 has raised international alarm. We analyzed data from 15 countries and estimated that the chance that this variant was imported into these countries by travelers from the United Kingdom by December 7 is >50%.

A systematic review of antibody mediated immunity to coronaviruses: kinetics, correlates of protection, and association with severity.

Many public health responses and modeled scenarios for COVID-19 outbreaks caused by SARS-CoV-2 assume that infection results in an immune response that protects individuals from future infections or illness for some amount of time. The presence or absence of protective immunity due to infection or vaccination (when available) will affect future transmission and illness severity. Here, we review the scientific literature on antibody immunity to coronaviruses, including SARS-CoV-2 as well as the related SARS-CoV, MERS-CoV and endemic human coronaviruses (HCoVs). We reviewed 2,452 abstracts and identified 491 manuscripts relevant to 5 areas of focus: 1) antibody kinetics, 2) correlates of protection, 3) immunopathogenesis, 4) antigenic diversity and cross-reactivity, and 5) population seroprevalence. While further studies of SARS-CoV-2 are necessary to determine immune responses, evidence from other coronaviruses can provide clues and guide future research.