Forecasting of influenza activity and associated hospital admission burden and estimating the impact of COVID-19 pandemic on 2019/20 winter season in Hong Kong.

Like other tropical and subtropical regions, influenza viruses can circulate year-round in Hong Kong. However, during the COVID-19 pandemic, there was a significant decrease in influenza activity. The objective of this study was to retrospectively forecast influenza activity during the year 2020 and assess the impact of COVID-19 public health social measures (PHSMs) on influenza activity and hospital admissions in Hong Kong. Using weekly surveillance data on influenza virus activity in Hong Kong from 2010 to 2019, we developed a statistical modeling framework to forecast influenza virus activity and associated hospital admissions. We conducted short-term forecasts (1-4 weeks ahead) and medium-term forecasts (1-13 weeks ahead) for the year 2020, assuming no PHSMs were implemented against COVID-19. We estimated the reduction in transmissibility, peak magnitude, attack rates, and influenza-associated hospitalization rate resulting from these PHSMs. For short-term forecasts, mean ambient ozone concentration and school holidays were found to contribute to better prediction performance, while absolute humidity and ozone concentration improved the accuracy of medium-term forecasts. We observed a maximum reduction of 44.6% (95% CI: 38.6% - 51.9%) in transmissibility, 75.5% (95% CI: 73.0% - 77.6%) in attack rate, 41.5% (95% CI: 13.9% - 55.7%) in peak magnitude, and 63.1% (95% CI: 59.3% - 66.3%) in cumulative influenza-associated hospitalizations during the winter-spring period of the 2019/2020 season in Hong Kong. The implementation of PHSMs to control COVID-19 had a substantial impact on influenza transmission and associated burden in Hong Kong. Incorporating information on factors influencing influenza transmission improved the accuracy of our predictions.

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

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

Joint Estimation of Generation Time and Incubation Period for Coronavirus Disease 2019.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has caused a heavy disease burden globally. The impact of process and timing of data collection on the accuracy of estimation of key epidemiological distributions are unclear. Because infection times are typically unobserved, there are relatively few estimates of generation time distribution. METHODS: We developed a statistical framework to jointly estimate generation time and incubation period from human-to-human transmission pairs, accounting for sampling biases. We applied the framework on 80 laboratory-confirmed human-to-human transmission pairs in China. We further inferred the infectiousness profile, serial interval distribution, proportions of presymptomatic transmission, and basic reproduction number (R0) for COVID-19. RESULTS: The estimated mean incubation period was 4.8 days (95% confidence interval [CI], 4.1-5.6), and mean generation time was 5.7 days (95% CI, 4.8-6.5). The estimated R0 based on the estimated generation time was 2.2 (95% CI, 1.9-2.4). A simulation study suggested that our approach could provide unbiased estimates, insensitive to the width of exposure windows. CONCLUSIONS: Properly accounting for the timing and process of data collection is critical to have correct estimates of generation time and incubation period. R0 can be biased when it is derived based on serial interval as the proxy of generation time.

Variation in Influenza B Virus Epidemiology by Lineage, China.

We used national sentinel surveillance data in China for 2005-2016 to examine the lineage-specific epidemiology of influenza B. Influenza B viruses circulated every year with relatively lower activity than influenza A. B/Yamagata was more frequently detected in adults than in children.

Impact of COVID-19 control measures on respiratory syncytial virus and hand-foot-and-mouth disease transmission in Hong Kong and South Korea.

The public health and social measures (PHSMs) for mitigation/control of COVID-19 pandemic influenced the transmission dynamics of many other infectious diseases, including respiratory syncytial virus (RSV) infection, and hand, foot and mouth disease (HFMD) and their disease-burden. This study aimed to infer the transmission dynamics of these respiratory viruses and assess the impact of COVID-19 PHSMs on their community activity. We developed a compartmental framework to infer the transmission dynamics of RSV and HFMD in Hong Kong and South Korea from January 2014 to May 2024. We assessed the impact of PHSMs by comparing the change in virus transmissibility, reproduction number and population susceptibility before, during, and after the COVID-19 pandemic period. A significant reduction in RSV and HFMD activity was observed starting in January 2020, with a resurgence since late 2021. Transmissibility of both diseases decreased by 46 % - 95 % during the lull, while population susceptibility was estimated to increase by maximum of 19 %. On relaxation of the PHSMs, the transmissibility were recovered up to 70 % in Hong Kong and nearly 100 % in South Korea in 2023 with significant epidemics for these viruses. Strict implementation of COVID-19 PHSMs led to low RSV and HFMD activity, but the absence of community infection resulted in reductions in population immunity, and slightly larger epidemics when these diseases re-emerged following the COVID-19 pandemic.

Global Seasonal Activities of Respiratory Syncytial Virus Before the Coronavirus Disease 2019 Pandemic: A Systematic Review.

Varied seasonal patterns of respiratory syncytial virus (RSV) have been reported worldwide. We conducted a systematic review on articles identified in PubMed reporting RSV seasonality based on data collected before 1 January 2020. RSV seasonal patterns were examined by geographic location, calendar month, analytic method, and meteorological factors including temperature and absolute humidity. Correlation and regression analyses were conducted to explore the relationship between RSV seasonality and study methods and characteristics of study locations. RSV seasons were reported in 209 articles published in 1973-2023 for 317 locations in 77 countries. Regular RSV seasons were similarly reported in countries in temperate regions, with highly variable seasons identified in subtropical and tropical countries. Longer durations of RSV seasons were associated with a higher daily average mean temperature and daily average mean absolute humidity. The global seasonal patterns of RSV provided important information for optimizing interventions against RSV infection.

vHDvDB 2.0: Database and Group Comparison Server for Hepatitis Delta Virus.

The hepatitis delta virus (HDV) is a unique pathogen with significant global health implications, affecting individuals who are coinfected with the hepatitis B virus (HBV). HDV infection has profound clinical consequences, manifesting either as coinfection with HBV, resulting in acute hepatitis and potential liver failure, or as superinfection in chronic HBV cases, substantially increasing the risk of cirrhosis and hepatocellular carcinoma. Given the complex dynamics of HDV infection and the urgent need for advanced research tools, this article introduces vHDvDB 2.0, a comprehensive HDV full-length sequence database. This innovative platform integrates data preprocessing, secondary structure prediction, and epidemiological research tools. The primary goal of vHDvDB 2.0 is to consolidate HDV sequence data into a user-friendly repository, thereby facilitating access for researchers and enhancing the broader scientific understanding of HDV. The significance of this database lies in its potential to streamline HDV research by providing a centralized resource for analyzing viral sequences and exploring genotype-specific characteristics. It will also enable more in-depth research within the HDV sequence domains.

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

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

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

The generation time distribution, reflecting the time between successive infections in transmission chains, is a key epidemiological parameter for describing COVID-19 transmission dynamics. However, because exact infection times are rarely known, it is often approximated by the serial interval distribution. This approximation holds under the assumption that infectors and infectees share the same incubation period distribution, which may not always be true. We estimated incubation period and serial interval distributions using 629 transmission pairs reconstructed by investigating 2989 confirmed cases in China in January-February 2020, and developed an inferential framework to estimate the generation time distribution that accounts for variation over time due to changes in epidemiology, sampling biases and public health and social measures. We identified substantial reductions over time in the serial interval and generation time distributions. Our proposed method provides more reliable estimation of the temporal variation in the generation time distribution, improving assessment of transmission dynamics.

The Application of Focused Medium-Energy Extracorporeal Shockwave Therapy in Hemophilic A Arthropathy.

Hemophilic arthropathy causes the damage of synovium, cartilage, and subchondral bone. The present study evaluated the safety and the effect of extracorporeal shockwave therapy (ESWT), a safe treatment widely used in musculoskeletal conditions in patients with hemophilic arthropathy. Between 1 August 2019 and 31 July 2020, seven hemophilia A patients were enrolled and treated with medium-energy ESWT on the knee joint in the first two months after prophylactic coagulation factor administration. At the beginning of the study and at 1-, 2-, 3-, and 6-month follow-ups, the Hemophilia Joint Health Score (HJHS), visual analog scale score (VAS), and Hemophilia Early Arthropathy Detection with Ultrasound score (HEAD-US) were evaluated for therapeutic effectiveness and safety, while serum bone morphogenetic protein 2 (BMP-2) and von Willebrand factor (vWF) levels were analyzed for assessing chondroprotection and bone healing. Magnetic resonance imaging (MRI) of the knee was performed at the beginning of the study and the 6-month follow-ups. As a result, a non-significant decrease in VAS scores (p = 0.151) but not HJHS after treatment was noticed. At the 3-month follow-up, there was a non-significant increase in BMP2 levels (p = 0.171) but not vWF. Ultrasonography showed no disease activity score elevation in five patients and no further disease damage in all patients. Repeated MRI examinations in three patients showed no structural progression during the 6-month follow-up. As to adverse events, redness, local heat, and mild swelling were noted in five patients without breakthrough bleeding. We concluded that medium-energy ESWT might be safe for hemophilic arthropathy once prophylactic coagulation factors are administered.

Variation by lineage in serum antibody responses to influenza B virus infections.

Two lineages of influenza B virus currently co-circulate and have distinct antigenicity, termed Victoria and Yamagata after the B/Victoria/2/87 and B/Yamagata/16/88 strains, respectively. We analyzed antibody titer dynamics following PCR-confirmed influenza B virus infection in a longitudinal community-based cohort study conducted in Hong Kong from 2009-2014 to assess patterns in changes in antibody titers to B/Victoria and B/Yamagata viruses following infections with each lineage. Among 62 PCR-confirmed cases, almost half had undetectable hemagglutination inhibition (HAI) antibody titers to the lineage of infection both pre-infection and post-infection. Among those infected with influenza B/Victoria who showed an HAI titer response after infection, we found strong rises to the lineage of infection, positive but smaller cross-lineage HAI titer boosts, a small dependence of HAI titer boosts on pre-infection titers, and a shorter half-life of HAI titers in adults. Our study is limited by the low HAI sensitivity for non-ether-treated IBV antigen and the incapacity of performing other assays with higher sensitivity, as well as the mismatch between the B/Yamagata lineage circulating strain and the assay strain in one of the study seasons.

Author Correction: Temporal dynamics in viral shedding and transmissibility of COVID-19.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Temporal dynamics in viral shedding and transmissibility of COVID-19.

We report temporal patterns of viral shedding in 94 patients with laboratory-confirmed COVID-19 and modeled COVID-19 infectiousness profiles from a separate sample of 77 infector-infectee transmission pairs. We observed the highest viral load in throat swabs at the time of symptom onset, and inferred that infectiousness peaked on or before symptom onset. We estimated that 44% (95% confidence interval, 25-69%) of secondary cases were infected during the index cases' presymptomatic stage, in settings with substantial household clustering, active case finding and quarantine outside the home. Disease control measures should be adjusted to account for probable substantial presymptomatic transmission.

Burden of influenza-associated outpatient influenza-like illness consultations in China, 2006-2015: A population-based study.

BACKGROUND: Human influenza virus infections cause a considerable burden of morbidity and mortality worldwide each year. Understanding regional influenza-associated outpatient burden is crucial for formulating control strategies against influenza viruses. METHODS: We extracted the national sentinel surveillance data on outpatient visits due to influenza-like-illness (ILI) and virological confirmation of sentinel specimens from 30 provinces of China from 2006 to 2015. Generalized additive regression models were fitted to estimate influenza-associated excess ILI outpatient burden for each individual province, accounting for seasonal baselines and meteorological factors. RESULTS: Influenza was associated with an average of 2.5 excess ILI consultations per 1000 person-years (py) in 30 provinces of China each year from 2006 to 2015. Influenza A(H1N1)pdm09 led to a higher number of influenza-associated ILI consultations in 2009 across all provinces compared with other years. The excess ILI burden was 4.5 per 1000 py among children aged below 15 years old, substantially higher than that in adults. CONCLUSIONS: Human influenza viruses caused considerable impact on population morbidity, with a consequent healthcare and economic burden. This study provided the evidence for planning of vaccination programs in China and a framework to estimate burden of influenza-associated outpatient consultations.

Influenza-associated excess respiratory mortality in China, 2010-15: a population-based study.

BACKGROUND: The estimation of influenza-associated excess mortality in countries can help to improve estimates of the global mortality burden attributable to influenza virus infections. We did a study to estimate the influenza-associated excess respiratory mortality in mainland China for the 2010-11 through 2014-15 seasons. METHODS: We obtained provincial weekly influenza surveillance data and population mortality data for 161 disease surveillance points in 31 provinces in mainland China from the Chinese Center for Disease Control and Prevention for the years 2005-15. Disease surveillance points with an annual average mortality rate of less than 0·4% between 2005 and 2015 or an annual mortality rate of less than 0·3% in any given years were excluded. We extracted data for respiratory deaths based on codes J00-J99 under the tenth edition of the International Classification of Diseases. Data on respiratory mortality and population were stratified by age group (age <60 years and ≥60 years) and aggregated by province. The overall annual population data of each province and national annual respiratory mortality data were compiled from the China Statistical Yearbook. Influenza surveillance data on weekly proportion of samples testing positive for influenza virus by type or subtype for 31 provinces were extracted from the National Sentinel Hospital-based Influenza Surveillance Network. We estimated influenza-associated excess respiratory mortality rates between the 2010-11 and 2014-15 seasons for 22 provinces with valid data in the country using linear regression models. Extrapolation of excess respiratory mortality rates was done using random-effect meta-regression models for nine provinces without valid data for a direct estimation of the rates. FINDINGS: We fitted the linear regression model with the data from 22 of 31 provinces in mainland China, representing 83·0% of the total population. We estimated that an annual mean of 88 100 (95% CI 84 200-92 000) influenza-associated excess respiratory deaths occurred in China in the 5 years studied, corresponding to 8·2% (95% CI 7·9-8·6) of respiratory deaths. The mean excess respiratory mortality rates per 100 000 person-seasons for influenza A(H1N1)pdm09, A(H3N2), and B viruses were 1·6 (95% CI 1·5-1·7), 2·6 (2·4-2·8), and 2·3 (2·1-2·5), respectively. Estimated excess respiratory mortality rates per 100 000 person-seasons were 1·5 (95% CI 1·1-1·9) for individuals younger than 60 years and 38·5 (36·8-40·2) for individuals aged 60 years or older. Approximately 71 000 (95% CI 67 800-74 100) influenza-associated excess respiratory deaths occurred in individuals aged 60 years or older, corresponding to 80% of such deaths. INTERPRETATION: Influenza was associated with substantial excess respiratory mortality in China between 2010-11 and 2014-15 seasons, especially in older adults aged at least 60 years. Continuous and high-quality surveillance data across China are needed to improve the estimation of the disease burden attributable to influenza and the best public health interventions are needed to curb this burden. FUNDING: National Science Fund for Distinguished Young Scholars, National Science and Technology Major Project of China, National Institute of Health Research, the Harvard Center for Communicable Disease Dynamics from the National Institute of General Medical Sciences, and the China-US Collaborative Program on Emerging and Re-emerging Infectious Disease.

Spino-pelvic alignment, balance, and functional disability in patients with low-grade degenerative lumbar spondylolisthesis.

OBJECTIVE: To evaluate the relationships among spino-pelvic parameters, trunk balance and functional disability in patients with degenerative lumbar spondylolisthesis. DESIGN:  Cross-sectional study. SUBJECTS: Forty-five patients with degenerative lumbar spondylolisthesis and 32 patients without degenerative lumbar spondylolisthesis. METHODS: Spino-pelvic parameters (pelvic incidence, pelvic tilt, sacral slope, lumbar lordosis) and pain severity were evaluated. Biodex balance tests (postural stability, limits of stability, modified clinical test of sensory interaction and balance, fall risk) and Quebec Back Pain Disability Scale (QBDS) scores were measured. RESULTS: Intergroup differences were found in age, low back pain, limits of stability, pelvic incidence, pelvic tilt and some subscales of QBDS. Correlations were found: (i) in the degenerative lumbar spondylolisthesis group: between pelvic incidence and sacral slope/pelvic tilt/lumbar lordosis/height/limits of stability; sacral slope and lumbar lordosis/height/limits of stability/modified clinical test of sensory interaction and balance (eyes closed on foam); lumbar lordosis and body mass index/QBDS/postural stability/modified clinical test of sensory interaction and balance (eyes open and eyes closed on foam); (ii) in the non-degenerative lumbar spondylolisthesis group: between pelvic incidence and pelvic tilt; pelvic tilt and sacral slope/lumbar lordosis; sacral slope and lumbar lordosis/fall risk. All spino-pelvic parameters in the degenerative lumbar spondylolisthesis group and pelvic tilt in the non-degenerative lumbar spondylolisthesis group correlated with QBDS. CONCLUSION: Pelvic tilt was the major compensating factor in both groups (patients with and without degenerative lumbar spondylolisthesis). Sacral slope and lumbar lordosis contributed to partial compensation in the degenerative lumbar spondylolisthesis group. Lumbar lordosis correlated with body mass index. Sacral slope could be an indicator of fall risk in the non-degenerative lumbar spondylolisthesis group.

Efficacy of Radial Extracorporeal Shock Wave Therapy on Lateral Epicondylosis, and Changes in the Common Extensor Tendon Stiffness with Pretherapy and Posttherapy in Real-Time Sonoelastography: A Randomized Controlled Study.

OBJECTIVE: To investigate the effects of radial extracorporeal shock wave therapy (rESWT) and to determine the posttreatment common extensor tendon stiffness among patients with lateral epicondylosis. DESIGN: Thirty patients with lateral epicondylosis were randomly divided into experimental and control groups. Participants in the experimental group received rESWT plus physical therapy, and those in the control group received sham shock wave plus physical therapy for 3 weeks. Visual analog scale; grip strength dynamometer; Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire; and ultrasonography in 2-dimensional image, and real-time sonoelastography were used in the assessments at baseline and after 6, 12, and 24 weeks (T3). RESULTS: The experimental group had more significant pain reduction at T3 than the control group. Compared with the control group, the experimental group had significantly higher maximal grip strength at 12 and 24 weeks, with significant increases. Compared to baseline, the experimental group had significantly lower Taiwan version DASH disability/symptom scores and work module scores at all posttreatment follow-up points. Five participants in the experimental group had partial tear within common extensor tendon at their involved elbow, and all the tears totally healed at T3. However, the inter-rater reliabilities for real-time sonoelastography were poor to fair. CONCLUSIONS: Patients with lateral epicondylosis had better and faster pain reduction, grip strength increase, and functional improvement after receiving rESWT in addition to physical therapy than those who received physical therapy only.

Static and dynamic balance performance in patients with osteoporotic vertebral compression fracture.

OBJECTIVE: Patients with osteoporotic vertebral compression fracture (OVCF) have postural changes and increased risk of falling. The aim of this study is to compare balance characteristics between patients with OVCF and healthy control subjects. METHODS: Patients with severe OVCF and control subjects underwent computerised dynamic posturography (CDP) in this case-control study. RESULTS: Forty-seven OVCF patients and 45 controls were recruited. Compared with the control group, the OVCF group had significantly decreased average stability; maximal stability under the `eye open with swayed support surface' (CDP subtest 4) and 'eye closed with swayed support surface' conditions (subtest 5); and decreased ankle strategy during subtests 4 and 5 and under the `swayed vision with swayed support surface' condition (subtest 6). The OVCF group fell more frequently during subtests 5 and 6 and had longer overall reaction time and longer reaction time when moving backward during the directional control test. CONCLUSION: OVCF patients had poorer static and dynamic balance performance compared with normal control. They had decreased postural stability and ankle strategy with increased fall frequency on a swayed surface; they also had longer reaction times overall and in the backward direction. Therefore, we suggest balance rehabilitation for patients with OVCF to prevent fall.

The electromyographic responses of paraspinal muscles during isokinetic exercise in adolescents with idiopathic scoliosis with a Cobb's angle less than fifty degrees.

BACKGROUND: Analysis of electromyographic (EMG) activities in the back during dynamic exercise is needed because more complex loading on the spine is created in comparison with that during static exercise. The purpose of this study is to investigate the difference in bilateral midback and low-back paraspinal muscle (PSM) activities during performance of different resistance isokinetic exercises in healthy subjects and those with scoliosis. METHODS: Forty-one healthy subjects and thirty-three subjects with adolescent idiopathic scoliosis (AIS) were enrolled. An isokinetic back system in combination with quantitative surface EMG was used to evaluate the dominant and nondominant PSM activities by analyzing the root mean square (RMS) during isokinetic extension and flexion exercise at velocities of 30 degree/s and 90 degree/s. RESULTS: Significantly higher RMS of EMG were found in the dominant medial and lateral PSM of the lumbar region than the non-dominant muscles in the healthy control group and in those with AIS with smaller curves (<20 degrees) during isokinetic flexion and extension exercises. In AIS patients with larger curves (20 to 50 degrees), shifting of muscle activities from the dominant to the non-dominant side occurred during isokinetic exercises, and the EMG activities of the thoracic muscle were significantly higher on the non-dominant (concave) side than on the dominant (convex) side. CONCLUSIONS: The bilateral PSM do not act symmetrically during isokinetic back exercises. The dominant lumbar PSM supply the major action in healthy subjects and patients with small curve scoliosis. For larger curve scoliosis, compensated muscle activity is needed in the midback when doing resistance exercises. More midback protection may be needed by scoliotic subjects with large curves during resistance exercise.