Case clustering, contact stratification, and transmission heterogeneity of SARS-CoV-2 Omicron BA.5 variants in Urumqi, China: An observational study.

Background: From August to September 2022, Urumqi, the capital of the Xinjiang Uygur Autonomous Region in China, faced its largest COVID-19 outbreak caused by the emergence of the SARS-CoV-2 Omicron BA.5.2 variants. Although the superspreading of COVID-19 played an important role in triggering large-scale outbreaks, little was known about the superspreading potential and heterogeneity in the transmission of Omicron BA.5 variants. Methods: In this retrospective observational, contact tracing study, we identified 1139 laboratory-confirmed COVID-19 cases of Omicron BA.5.2 variants, and 51 323 test-negative close contacts in Urumqi from 7 August to 7 September 2022. By using detailed contact tracing information and exposure history of linked case-contact pairs, we described stratification in contact and heterogeneity in transmission across different demographic strata, vaccine statuses, and contact settings. We adopted beta-binomial models to characterise the secondary attack rate (SAR) distribution among close contacts and modelled COVID-19 transmission as a branching process with heterogeneity in transmission governed by negative binomial models. Results: After the city lockdown, the mean case cluster size decreased from 2.0 (before lockdown) to 1.6, with decreased proportions of contacts in workplace and community settings compared with household settings. We estimated that 14% of the most infectious index cases generated 80% transmission, whereas transmission in the community setting presented the highest heterogeneity, with 5% index cases seeding 80% transmission. Compared with zero, one, and two doses of inactivated vaccine (Sinopharm), index cases with three doses of vaccine had a lower risk of generating secondary cases in terms of the reproduction number. Contacts of female cases, cases with ages 0-17 years, and household settings had relatively higher SAR. Conclusions: In the context of intensive control measures, active case detection, and relatively high vaccine coverage, but with an infection-naive population, our findings suggested high heterogeneity in the contact and transmission risks of Omicron BA.5 variants across different demographic strata, vaccine statuses, and contact settings. Given the rapid evolution of SARS-CoV-2, investigating the distribution of transmission not only helped promote public awareness and preparedness among high-risk groups, but also highlighted the importance of continuously monitoring the transmission characteristics of genetic variants of SARS-CoV-2.

Changes in all-cause and cause-specific excess mortality before and after the Omicron outbreak of COVID-19 in Hong Kong.

Background: While coronavirus 2019 (COVID-19) deaths were generally underestimated in many countries, Hong Kong may show a different trend of excess mortality due to stringent measures, especially for deaths related to respiratory diseases. Nevertheless, the Omicron outbreak in Hong Kong evolved into a territory-wide transmission, similar to other settings such as Singapore, South Korea, and recently, mainland China. We hypothesized that the excess mortality would differ substantially before and after the Omicron outbreak. Methods: We conducted a time-series analysis of daily deaths stratified by age, reported causes, and epidemic wave. We determined the excess mortality from the difference between observed and expected mortality from 23 January 2020 to 1 June 2022 by fitting mortality data from 2013 to 2019. Results: During the early phase of the pandemic, the estimated excess mortality was -19.92 (95% confidence interval (CI) = -29.09, -10.75) and -115.57 (95% CI = -161.34, -69.79) per 100 000 population overall and for the elderly, respectively. However, the overall excess mortality rate was 234.08 (95% CI = 224.66, 243.50) per 100 000 population overall and as high as 928.09 (95% CI = 885.14, 971.04) per 100 000 population for the elderly during the Omicron epidemic. We generally observed negative excess mortality rates of non-COVID-19 respiratory diseases before and after the Omicron outbreak. In contrast, increases in excess mortality were generally reported in non-respiratory diseases after the Omicron outbreak. Conclusions: Our results highlighted the averted mortality before 2022 among the elderly and patients with non-COVID-19 respiratory diseases, due to indirect benefits from stringent non-pharmaceutical interventions. The high excess mortality during the Omicron epidemic demonstrated a significant impact from the surge of COVID-19 infections in a SARS-CoV-2 infection-naive population, particularly evident in the elderly group.

Superspreading potentials of SARS-CoV-2 Delta variants across different contact settings in eastern China: a retrospective observational study

Objectives As the genetic variants of SARS-CoV-2 continuously pose threats to global health, evaluating superspreading potentials of emerging variants is of importance for region-wide control of COVID-19 outbreaks. Methods By using detailed epidemiological contact tracing data of test-positive COVID-19 cases collected between July and August 2021 in Nanjing and Yangzhou, China, we assessed the superspreading potential of outbreaks seeded by SARS-CoV-2 Delta variants. The transmission chains and case-clusters were constructed according to the individual-based surveillance data. We modelled the disease transmission as a classic branching process with transmission heterogeneity governed by negative binomial models. Subgroup analysis was conducted by different contact settings and ages. Results We estimated an expected 14% (95% CI: 11-16%) of the most infectious cases generated 80% of the total transmission. Conclusions Delta variants demonstrated a significant potential of superspreading under strict COVID-19 control and active COVID-19 detecting measures. Enhancing the surveillance on disease transmissibility especially in high-risk settings of superspreading, along with rapid contact tracing and case isolations would be the key to mitigate the epidemic caused by the emerging variants.

Relationship between antidepressants and severity of SARS-CoV-2 Omicron infection: a retrospective cohort study using real-world data

Background Few studies have used real-world data to evaluate the impact of antidepressant use on the risk of developing severe outcomes after SARS-CoV-2 Omicron infection. Methods This is a retrospective cohort study using propensity-score matching to examine the relationship between antidepressant use and COVID-19 severity. Inpatient and medication records of all adult COVID-19 patients in Hong Kong during the Omicron-predominated period were obtained. Severe clinical outcomes including intensive care unit admission and inpatient death after the first positive results of reverse transcription polymerase chain reaction as well as a composite outcome of both were studied. Cox proportional hazard models were applied to estimate the crude and adjusted hazard ratios (HR). Findings Of 60,903 hospitalised COVID-19 patients admitted, 40,459 were included for matching, among which 3821 (9.4%) were prescribed antidepressants. The rates of intensive care unit admission, inpatient death, and the composite event were 3.9%, 25.5%, and 28.3% respectively in the unexposed group, 1.3%, 20.0%, and 21.1% respectively in the exposed group, with adjusted HR equal to 0.332 (95% CI, 0.245–0.449), 0.868 (95% CI, 0.800–0.942), and 0.786 (95% CI, 0.727–0.850) respectively. The result was generally consistent when stratified by selective serotonin reuptake inhibitors (SSRIs) and non-SSRIs. Antidepressants with functional inhibition of acid sphingomyelinase activity, specifically fluoxetine, were also negatively associated with the outcomes. The effect of antidepressants was more apparent in female and fully vaccinated COVID-19 patients. Interpretation Antidepressant use was associated with a lower risk of severe COVID-19. The findings support the continuation of antidepressants in patients with COVID-19, and provide evidence for the treatment potential of antidepressants for severe COVID-19. Funding This research was supported by Health and Medical Research Fund [grant numbers COVID190105, COVID19F03, INF-CUHK-1], Collaborative Research Fund of University Grants Committee [grant numbers C4139-20G], 10.13039/501100001809National Natural Science Foundation of China (NSFC) [71974165], and Group Research Scheme from The 10.13039/501100004853Chinese University of Hong Kong.

Comparing the incubation period, serial interval, and infectiousness profile between SARS-CoV-2 Omicron and Delta variants.

In January 2022, the SARS-CoV-2 Omicron variants initiated major outbreaks and dominated the transmissions in Hong Kong, displacing an earlier outbreak seeded by the Delta variants. To provide insight into the transmission potential of the emerging variants, we aimed to compare the epidemiological characteristics of the Omicron and Delta variants. We analyzed the line-list clinical and contact tracing data of the SARS-CoV-2 confirmed cases in Hong Kong. Transmission pairs were constructed based on the individual contact history. We fitted bias-controlled models to the data to estimate the serial interval, incubation period and infectiousness profile of the two variants. Viral load data were extracted and fitted to the random effect models to investigate the potential risk modifiers for the clinical viral shedding course. Totally 14 401 confirmed cases were reported between January 1 and February 15, 2022. The estimated mean serial interval (4.4 days vs. 5.8 days) and incubation period (3.4 days vs. 3.8 days) were shorter for the Omicron than the Delta variants. A larger proportion of presymptomatic transmission was observed for the Omicron (62%) compared to the Delta variants (48%). The Omicron cases had higher mean viral load over an infection course than the Delta cases, with the elder cases appearing more infectious than the younger cases for both variants. The epidemiological features of Omicron variants were likely an obstacle to contact tracing measures, imposed as a major intervention in settings like Hong Kong. Continuously monitoring the epidemiological feature for any emerging SARS-CoV-2 variants in the future is needed to assist officials in planning measures for COVID-19 control.

Estimating the serial intervals of SARS-CoV-2 Omicron BA.4, BA.5, and BA.2.12.1 variants in Hong Kong.

Empirical evidence on the epidemiological characteristics of the emerged SARS-CoV-2 variants could shed light on the transmission potential of the virus and strategic outbreak control planning. In this study, by using contact tracing data collected during an Omicron-predominant epidemic phase in Hong Kong, we estimated the mean serial interval of SARS-CoV-2 Omicron BA.4, BA.5, and BA.2.12.1 variants at 2.8 days (95% credible interval [CrI]: 1.5, 6.7), 2.7 days (95% CrI: 2.1, 3.6), and 4.4 days (95% CrI: 2.6, 7.5), respectively, with adjustment for right truncation and sampling bias. The short serial interval for the current circulating variant indicated that outbreak mitigations through contact tracing and case isolation would be quite challenging.

Dining-Out Behavior as a Proxy for the Superspreading Potential of SARS-CoV-2 Infections: Modeling Analysis.

BACKGROUND: While many studies evaluated the reliability of digital mobility metrics as a proxy of SARS-CoV-2 transmission potential, none examined the relationship between dining-out behavior and the superspreading potential of COVID-19. OBJECTIVE: We employed the mobility proxy of dining out in eateries to examine this association in Hong Kong with COVID-19 outbreaks highly characterized by superspreading events. METHODS: We retrieved the illness onset date and contact-tracing history of all laboratory-confirmed cases of COVID-19 from February 16, 2020, to April 30, 2021. We estimated the time-varying reproduction number (Rt) and dispersion parameter (k), a measure of superspreading potential, and related them to the mobility proxy of dining out in eateries. We compared the relative contribution to the superspreading potential with other common proxies derived by Google LLC and Apple Inc. RESULTS: A total of 6391 clusters involving 8375 cases were used in the estimation. A high correlation between dining-out mobility and superspreading potential was observed. Compared to other mobility proxies derived by Google and Apple, the mobility of dining-out behavior explained the highest variability of k (ΔR-sq=9.7%, 95% credible interval: 5.7% to 13.2%) and Rt (ΔR-sq=15.7%, 95% credible interval: 13.6% to 17.7%). CONCLUSIONS: We demonstrated that there was a strong link between dining-out behaviors and the superspreading potential of COVID-19. The methodological innovation suggests a further development using digital mobility proxies of dining-out patterns to generate early warnings of superspreading events.

Superspreading potentials of SARS-CoV-2 Delta variants across different contact settings in Eastern China: A retrospective observational study.

OBJECTIVES: As the genetic variants of SARS-CoV-2 continuously pose threats to global health, evaluating superspreading potentials of emerging genetic variants is of importance for region-wide control of COVID-19 outbreaks. METHODS: By using detailed epidemiological contact tracing data of test-positive COVID-19 cases collected between July and August 2021 in Nanjing and Yangzhou, China, we assessed the superspreading potential of outbreaks seeded by SARS-CoV-2 Delta variants. The transmission chains and case-clusters were constructed according to the individual-based surveillance data. We modelled the disease transmission as a classic branching process with transmission heterogeneity governed by negative binomial models. Subgroup analysis was conducted by different contact settings and age groups. RESULTS: We reported a considerable heterogeneity in the contact patterns and transmissibility of Delta variants in eastern China. We estimated an expected 14% (95% CI: 11-16%) of the most infectious cases generated 80% of the total transmission. CONCLUSIONS: Delta variants demonstrated a significant potential of superspreading under strict control measures and active COVID-19 detecting efforts. Enhancing the surveillance on disease transmissibility especially in high-risk settings, along with rapid contact tracing and case isolations would be one of the key factors to mitigate the epidemic caused by the emerging genetic variants of SARS-CoV-2.

Transmission Characteristics and Inactivated Vaccine Effectiveness Against Transmission of SARS-CoV-2 Omicron BA.5 Variants in Urumqi, China.

Importance: In 2022, Omicron variants circulated globally, and Urumqi, China, experienced a COVID-19 outbreak seeded by Omicron BA.5 variants, resulting in the highest number of infections in the city's record before the exit of the zero COVID-19 strategy. Little was known about the characteristics of Omicron variants in mainland China. Objective: To evaluate transmission characteristics of Omicron BA.5 variants and the effectiveness of inactivated vaccine (mainly BBIBP-CorV) against their transmission. Design, Setting, and Participants: This cohort study was conducted using data from an Omicron-seeded COVID-19 outbreak in Urumqi from August 7 to September 7, 2022. Participants included all individuals with confirmed SARS-CoV-2 infections and their close contacts identified between August 7 and September 7, 2022 in Urumqi. Exposures: A booster dose was compared vs 2 doses (reference level) of inactivated vaccine and risk factors were evaluated. Main Outcomes and Measures: Demographic characteristics, timeline records from exposure to laboratory testing outcomes, contact tracing history, and contact setting were obtained. The mean and variance of the key time-to-event intervals of transmission were estimated for individuals with known information. Transmission risks and contact patterns were assessed under different disease-control measures and in different contact settings. The effectiveness of inactivated vaccine against the transmission of Omicron BA.5 was estimated using multivariate logistic regression models. Results: Among 1139 individuals diagnosed with COVID-19 (630 females [55.3%]; mean [SD] age, 37.4 [19.9] years) and 51 323 close contacts who tested negative for COVID-19 (26 299 females [51.2%]; mean [SD] age, 38.4 [16.0] years), the means of generation interval, viral shedding period, and incubation period were estimated at 2.8 days (95% credible interval [CrI], 2.4-3.5 days), 6.7 days (95% CrI, 6.4-7.1 days), and 5.7 days (95% CrI, 4.8-6.6 days), respectively. Despite contact tracing, intensive control measures, and high vaccine coverage (980 individuals with infections [86.0%] received ≥2 doses of vaccine), high transmission risks were found in household settings (secondary attack rate, 14.7%; 95% CrI, 13.0%-16.5%) and younger (aged 0-15 years; secondary attack rate, 2.5%; 95% CrI, 1.9%-3.1%) and older age (aged >65 years; secondary attack rate, 2.2%; 95% CrI, 1.5%-3.0%) groups. Vaccine effectiveness against BA.5 variant transmission for the booster-dose vs 2 doses was 28.9% (95% CrI, 7.7%-45.2%) and 48.5% (95% CrI, 23.9%-61.4%) for 15-90 days after booster dose. No protective outcome was detected beyond 90 days after the booster dose. Conclusions and Relevance: This cohort study revealed key transmission characteristics of SARS-CoV-2 as they evolved, as well as vaccine effectiveness against variants. These findings suggest the importance of continuously evaluating vaccine effectiveness against emerging SARS-CoV-2 variants.

Relationship between antidepressants and severity of SARS-CoV-2 Omicron infection: a retrospective cohort study using real-world data.

Background: Few studies have used real-world data to evaluate the impact of antidepressant use on the risk of developing severe outcomes after SARS-CoV-2 Omicron infection. Methods: This is a retrospective cohort study using propensity-score matching to examine the relationship between antidepressant use and COVID-19 severity. Inpatient and medication records of all adult COVID-19 patients in Hong Kong during the Omicron-predominated period were obtained. Severe clinical outcomes including intensive care unit admission and inpatient death after the first positive results of reverse transcription polymerase chain reaction as well as a composite outcome of both were studied. Cox proportional hazard models were applied to estimate the crude and adjusted hazard ratios (HR). Findings: Of 60,903 hospitalised COVID-19 patients admitted, 40,459 were included for matching, among which 3821 (9.4%) were prescribed antidepressants. The rates of intensive care unit admission, inpatient death, and the composite event were 3.9%, 25.5%, and 28.3% respectively in the unexposed group, 1.3%, 20.0%, and 21.1% respectively in the exposed group, with adjusted HR equal to 0.332 (95% CI, 0.245-0.449), 0.868 (95% CI, 0.800-0.942), and 0.786 (95% CI, 0.727-0.850) respectively. The result was generally consistent when stratified by selective serotonin reuptake inhibitors (SSRIs) and non-SSRIs. Antidepressants with functional inhibition of acid sphingomyelinase activity, specifically fluoxetine, were also negatively associated with the outcomes. The effect of antidepressants was more apparent in female and fully vaccinated COVID-19 patients. Interpretation: Antidepressant use was associated with a lower risk of severe COVID-19. The findings support the continuation of antidepressants in patients with COVID-19, and provide evidence for the treatment potential of antidepressants for severe COVID-19. Funding: This research was supported by Health and Medical Research Fund [grant numbers COVID190105, COVID19F03, INF-CUHK-1], Collaborative Research Fund of University Grants Committee [grant numbers C4139-20G], National Natural Science Foundation of China (NSFC) [71974165], and Group Research Scheme from The Chinese University of Hong Kong.

Estimation of the serial interval of monkeypox during the early outbreak in 2022.

With increased transmissibility and novel transmission mode, monkeypox poses new threats to public health globally in the background of the ongoing COVID-19 pandemic. Estimates of the serial interval, a key epidemiological parameter of infectious disease transmission, could provide insights into the virus transmission risks. As of October 2022, little was known about the serial interval of monkeypox due to the lack of contact tracing data. In this study, public-available contact tracing data of global monkeypox cases were collected and 21 infector-infectee transmission pairs were identified. We proposed a statistical method applied to real-world observations to estimate the serial interval of the monkeypox. We estimated a mean serial interval of 5.6 days with the right truncation and sampling bias adjusted and calculated the reproduction number of 1.33 for the early monkeypox outbreaks at a global scale. Our findings provided a preliminary understanding of the transmission potentials of the current situation of monkeypox outbreaks. We highlighted the need for continuous surveillance of monkeypox for transmission risk assessment.

Estimation of Vaccine Effectiveness of CoronaVac and BNT162b2 Against Severe Outcomes Over Time Among Patients With SARS-CoV-2 Omicron.

Importance: Few studies have evaluated the waning of vaccine effectiveness against severe outcomes caused by SARS-CoV-2 Omicron infection. Hong Kong is providing inactivated and mRNA vaccines, but the population had limited protection from natural infections before the Omicron variant emerged. Objective: To examine the change in vaccine effectiveness against hospitalization and mortality due to the Omicron variant over time. Design, Setting, and Participants: This case-control study included adults with SARS-CoV-2 Omicron variant infection who died or were hospitalized in Hong Kong from January 1 to June 5, 2022 (ie, case participants), and adults with SARS-CoV-2 Omicron, sampled from the public health registry during the study period (ie, control participants), who were matched to case participants by propensity score. Exposures: Vaccination status of the individuals. Main Outcomes and Measures: Estimated vaccine effectiveness against death, death or hospitalization, and death among hospitalized patients. Vaccine effectiveness was calculated as 1 - adjusted odds ratio obtained by conditional logistic regression adjusted with covariates for each period following vaccination. Results: There were 32 823 case participants (25 546 [77.8%] ≥65 years; 16 930 [47.4%] female) and 131 328 control participants (100 041 [76.2%] ≥65 years; 66 625 [46.6%] female) in the sample analyzed for the death or hospitalization outcome. Vaccine effectiveness against death or hospitalization was maintained for at least 6 months after the second dose of both CoronaVac (74.0%; 95% CI, 71.8%-75.8%) and BNT162b2 (77.4%; 95% CI, 75.5%-79.0%) vaccines. Vaccine effectiveness against death in those aged 18 to 49 years was 86.4% (95% CI, 85.8%-87.0%) and 92.9% (95% CI, 92.6%-93.2%) for those receiving 2 doses of CoronaVac and BNT162b2, respectively, while for patients aged 80 years or older, it dropped to 61.4% (95% CI, 59.8%-63.2%) and 52.7% (95% CI, 50.2%-55.6%) for CoronaVac and BNT162b2, respectively. Nevertheless, overall vaccine effectiveness against death at 4 to 6 months after the third dose was greater than 90% for CoronaVac, BNT162b2, and the mixed vaccine schedule (eg, mixed vaccines: vaccine effectiveness, 92.2%; 95% CI, 89.2%-95.1%). Conclusions and Relevance: While vaccines were generally estimated to be effective against severe outcomes caused by SARS-CoV-2 Omicron infection, this analysis found that protection in older patients was more likely to wane 6 months after the second dose. Hence, a booster dose is recommended for older patients to restore immunity. This is especially critical in a setting like Hong Kong, where third-dose coverage is still insufficient among older residents.

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.

Differences in the superspreading potentials of COVID-19 across contact settings.

BACKGROUND: Superspreading events (SSEs) played a critical role in fueling the COVID-19 outbreaks. Although it is well-known that COVID-19 epidemics exhibited substantial superspreading potential, little is known about the risk of observing SSEs in different contact settings. In this study, we aimed to assess the potential of superspreading in different contact settings in Japan. METHOD: Transmission cluster data from Japan was collected between January and July 2020. Infector-infectee transmission pairs were constructed based on the contact tracing history. We fitted the data to negative binomial models to estimate the effective reproduction number (R) and dispersion parameter (k). Other epidemiological issues relating to the superspreading potential were also calculated. RESULTS: The overall estimated R and k are 0.561 (95% CrI: 0.496, 0.640) and 0.221 (95% CrI: 0.186, 0.262), respectively. The transmission in community, healthcare facilities and school manifest relatively higher superspreading potentials, compared to other contact settings. We inferred that 13.14% (95% CrI: 11.55%, 14.87%) of the most infectious cases generated 80% of the total transmission events. The probabilities of observing superspreading events for entire population and community, household, health care facilities, school, workplace contact settings are 1.75% (95% CrI: 1.57%, 1.99%), 0.49% (95% CrI: 0.22%, 1.18%), 0.07% (95% CrI: 0.06%, 0.08%), 0.67% (95% CrI: 0.31%, 1.21%), 0.33% (95% CrI: 0.13%, 0.94%), 0.32% (95% CrI: 0.21%, 0.60%), respectively. CONCLUSION: The different potentials of superspreading in contact settings highlighted the need to continuously monitoring the transmissibility accompanied with the dispersion parameter, to timely identify high risk settings favoring the occurrence of SSEs.

The Association Between Clinical Severity and Incubation Period of SARS-CoV-2 Delta Variants: Retrospective Observational Study.

BACKGROUND: As of August 25, 2021, Jiangsu province experienced the largest COVID-19 outbreak in eastern China that was seeded by SARS-CoV-2 Delta variants. As one of the key epidemiological parameters characterizing the transmission dynamics of COVID-19, the incubation period plays an essential role in informing public health measures for epidemic control. The incubation period of COVID-19 could vary by different age, sex, disease severity, and study settings. However, the impacts of these factors on the incubation period of Delta variants remains uninvestigated. OBJECTIVE: The objective of this study is to characterize the incubation period of the Delta variant using detailed contact tracing data. The effects of age, sex, and disease severity on the incubation period were investigated by multivariate regression analysis and subgroup analysis. METHODS: We extracted contact tracing data of 353 laboratory-confirmed cases of SARS-CoV-2 Delta variants' infection in Jiangsu province, China, from July to August 2021. The distribution of incubation period of Delta variants was estimated by using likelihood-based approach with adjustment for interval-censored observations. The effects of age, sex, and disease severity on the incubation period were expiated by using multivariate logistic regression model with interval censoring. RESULTS: The mean incubation period of the Delta variant was estimated at 6.64 days (95% credible interval: 6.27-7.00). We found that female cases and cases with severe symptoms had relatively longer mean incubation periods than male cases and those with nonsevere symptoms, respectively. One-day increase in the incubation period of Delta variants was associated with a weak decrease in the probability of having severe illness with an adjusted odds ratio of 0.88 (95% credible interval: 0.71-1.07). CONCLUSIONS: In this study, the incubation period was found to vary across different levels of sex, age, and disease severity of COVID-19. These findings provide additional information on the incubation period of Delta variants and highlight the importance of continuing surveillance and monitoring of the epidemiological characteristics of emerging SARS-CoV-2 variants as they evolve.

Characterizing superspreading potential of infectious disease: Decomposition of individual transmissibility.

In the context of infectious disease transmission, high heterogeneity in individual infectiousness indicates that a few index cases can generate large numbers of secondary cases, a phenomenon commonly known as superspreading. The potential of disease superspreading can be characterized by describing the distribution of secondary cases (of each seed case) as a negative binomial (NB) distribution with the dispersion parameter, k. Based on the feature of NB distribution, there must be a proportion of individuals with individual reproduction number of almost 0, which appears restricted and unrealistic. To overcome this limitation, we generalized the compound structure of a Poisson rate and included an additional parameter, and divided the reproduction number into independent and additive fixed and variable components. Then, the secondary cases followed a Delaporte distribution. We demonstrated that the Delaporte distribution was important for understanding the characteristics of disease transmission, which generated new insights distinct from the NB model. By using real-world dataset, the Delaporte distribution provides improvements in describing the distributions of COVID-19 and SARS cases compared to the NB distribution. The model selection yielded increasing statistical power with larger sample sizes as well as conservative type I error in detecting the improvement in fitting with the likelihood ratio (LR) test. Numerical simulation revealed that the control strategy-making process may benefit from monitoring the transmission characteristics under the Delaporte framework. Our findings highlighted that for the COVID-19 pandemic, population-wide interventions may control disease transmission on a general scale before recommending the high-risk-specific control strategies.

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.