Effectiveness of Molnupiravir and Nirmatrelvir-Ritonavir in Hospitalized Patients With COVID-19 : A Target Trial Emulation Study.

BACKGROUND: Whether hospitalized patients benefit from COVID-19 oral antivirals is uncertain. OBJECTIVE: To examine the real-world effectiveness of molnupiravir and nirmatrelvir-ritonavir in hospitalized patients with COVID-19 during the Omicron outbreak. DESIGN: Target trial emulation study. SETTING: Electronic health databases in Hong Kong. PARTICIPANTS: The molnupiravir emulated trial included hospitalized patients with COVID-19 aged 18 years or older between 26 February and 18 July 2022 (n = 16 495). The nirmatrelvir-ritonavir emulated trial included hospitalized patients with COVID-19 aged 18 years or older between 16 March and 18 July 2022 (n = 7119). INTERVENTION: Initiation of molnupiravir or nirmatrelvir-ritonavir within 5 days of hospitalization with COVID-19 versus no initiation of molnupiravir or nirmatrelvir-ritonavir. MEASUREMENTS: Effectiveness against all-cause mortality, intensive care unit (ICU) admission, or use of ventilatory support within 28 days. RESULTS: The use of oral antivirals in hospitalized patients with COVID-19 was associated with a lower risk for all-cause mortality (molnupiravir: hazard ratio [HR], 0.87 [95% CI, 0.81 to 0.93]; nirmatrelvir-ritonavir: HR, 0.77 [CI, 0.66 to 0.90]) but no significant risk reduction in terms of ICU admission (molnupiravir: HR, 1.02 [CI, 0.76 to 1.36]; nirmatrelvir-ritonavir: HR, 1.08 [CI, 0.58 to 2.02]) or the need for ventilatory support (molnupiravir: HR, 1.07 [CI, 0.89 to 1.30]; nirmatrelvir-ritonavir: HR, 1.03 [CI, 0.70 to 1.52]). There was no significant interaction between drug treatment and the number of COVID-19 vaccine doses received, thereby supporting the effectiveness of oral antivirals regardless of vaccination status. No significant interaction between nirmatrelvir-ritonavir treatment and age, sex, or Charlson Comorbidity Index was observed, whereas molnupiravir tended to be more effective in older people. LIMITATION: The outcome of ICU admission or need for ventilatory support may not capture all severe COVID-19 cases; unmeasured confounders, such as obesity and health behaviors, may exist. CONCLUSION: Molnupiravir and nirmatrelvir-ritonavir reduced all-cause mortality in both vaccinated and unvaccinated hospitalized patients. No significant reduction in ICU admission or the need for ventilatory support was observed. PRIMARY FUNDING SOURCE: Health and Medical Research Fund Research on COVID-19, Government of the Hong Kong Special Administrative Region; Research Grants Council, Collaborative Research Fund; and Health Bureau, Government of the Hong Kong Special Administrative Region.

Messenger RNA Coronavirus Disease 2019 (COVID-19) Vaccination With BNT162b2 Increased Risk of Bell's Palsy: A Nested Case-Control and Self-Controlled Case Series Study.

BACKGROUND: Observable symptoms of Bell's palsy following vaccinations arouse concern over the safety profiles of novel coronavirus disease 2019 (COVID-19) vaccines. However, there are only inconclusive findings on Bell's palsy following messenger (mRNA) COVID-19 vaccination. This study aims to update the previous analyses on the risk of Bell's palsy following mRNA (BNT162b2) COVID-19 vaccination. METHODS: This study included cases aged ≥16 years with a new diagnosis of Bell's palsy within 28 days after BNT162b2 vaccinations from the population-based electronic health records in Hong Kong. Nested case-control and self-controlled case series (SCCS) analyses were used, where the association between Bell's palsy and BNT162b2 was evaluated using conditional logistic and Poisson regression, respectively. RESULTS: Totally 54 individuals were newly diagnosed with Bell's palsy after BNT162b2 vaccinations. The incidence of Bell's palsy was 1.58 (95% confidence interval [CI], 1.19-2.07) per 100 000 doses administered. The nested case-control analysis showed significant association between BNT162b2 vaccinations and Bell's palsy (adjusted odds ratio [aOR], 1.543; 95% CI, 1.123-2.121), with up to 1.112 excess events per 100 000 people who received 2 doses of BNT162b2. An increased risk of Bell's palsy was observed during the first 14 days after the second dose of BNT162b2 in both nested case-control (aOR, 2.325; 95% CI, 1.414-3.821) and SCCS analysis (adjusted incidence rate ratio, 2.44; 95% CI, 1.32-4.50). CONCLUSIONS: There was an overall increased risk of Bell's palsy following BNT162b2 vaccination, particularly within the first 14 days after the second dose, but the absolute risk was very low.

Estimate of COVID-19 Deaths, China, December 2022-February 2023.

China announced a slight easing of its zero-COVID rules on November 11, 2022, and then a major relaxation on December 7, 2022. We estimate that the ensuing wave of SARS-CoV-2 infections caused 1.41 million deaths in China during December 2022-February 2023, substantially higher than that reported through official channels.

Impact of a delayed second dose of mRNA vaccine (BNT162b2) and inactivated SARS-CoV-2 vaccine (CoronaVac) on risks of all-cause mortality, emergency department visit, and unscheduled hospitalization.

BACKGROUND: Safety after the second dose of the SARS-CoV-2 vaccine remains to be elucidated, especially among individuals reporting adverse events after their first dose. This study aims to evaluate the impact of a delayed second dose on all-cause mortality and emergency services. METHODS: A territory-wide, retrospective cohort of people who had completed two doses of mRNA (BNT162b2) or inactivated SARS-CoV-2 (CoronaVac) vaccine between February 23 and July 3, 2021, in Hong Kong was analyzed, with linkage to electronic health records retrieved from the Hong Kong Hospital Authority. Vaccine recipients were classified as receiving a second dose within recommended intervals (21-28 days for BNT162b2; 14-28 days for CoronaVac) or delayed. Study outcomes were all-cause mortality, emergency department (ED) visits, and unscheduled hospitalizations within 28 days after the second dose of vaccination. RESULTS: Among 417,497 BNT162b2 and 354,283 CoronaVac second dose recipients, 3.8% and 28.5% received the second dose beyond the recommended intervals (mean 34.4 and 31.8 days), respectively. During the study period, there were < 5 daily new cases of COVID-19 infections in the community. Delaying the second dose was not associated with all-cause mortality (hazard ratio [HR] = 1.185, 95% CI 0.478-2.937, P = 0.714), risk of ED visit (HR = 0.966, 95% CI 0.926-1.008, P = 0.113), and risk of unscheduled hospitalization (HR = 0.956, 95% CI 0.878-1.040, P = 0.294) compared to that within the recommended interval for CoronaVac recipients. No statistically significant differences in all-cause mortality (HR = 4.438, 95% CI 0.951-20.701, P = 0.058), ED visit (HR = 1.037, 95% CI 0.951-1.130, P = 0.411), and unscheduled hospitalization (HR = 1.054, 95% CI 0.867-1.281, P = 0.597) were identified between people who received a second dose of BNT162b2 within and beyond the recommended intervals. CONCLUSIONS: No significant association between delayed second dose of BNT162b2 or CoronaVac and all-cause mortality, ED visit, and unscheduled hospitalization was observed in the present cohort. Regardless of the recommended or delayed schedule for SARS-CoV-2 vaccination, a second dose of both vaccines should be administered to obtain better protection against infection and serious disease. The second dose should be administered within the recommended interval following the manufacturer's product information, until further studies support the benefits of delaying vaccination outweighing the risks.

Indoor Environmental Factors and Acute Respiratory Illness in a Prospective Cohort of Community-Dwelling Older Adults.

BACKGROUND: Ambient environmental factors have been associated with respiratory infections in ecological studies, but few studies have explored the impact of indoor environmental factors in detail. The current study aimed to investigate the impact of indoor environment on the risk of acute respiratory illness (ARI) in a subtropical city. METHOD: A prospective cohort study was conducted in 285 community-dwelling older adults from December 2016 through May 2019. Individual household indoor environment data and ARI incidence were continuously collected. A time-stratified case-crossover analysis was conducted to estimate the excess risk of ARI associated with per-unit increase of daily mean indoor temperature, relative humidity, and absolute humidity (AH). RESULT: In total, 168 episodes of ARI were reported with an average risk of 36.8% per year. We observed a negative association of ARI with indoor AH up to 5 lag days in cool seasons, with a 6-day cumulative excess risk estimate of -9.0% (95% confidence interval, -15.9% to -1.5%). Negative associations between household temperature or relative humidity and ARI were less consistent across warm and cool seasons. CONCLUSIONS: Lower indoor AH in household was associated with a higher risk of ARI in the community-dwelling older adults in Hong Kong during cold seasons.

Nowcasting (Short-Term Forecasting) of Influenza Epidemics in Local Settings, Sweden, 2008-2019.

The timing of influenza case incidence during epidemics can differ between regions within nations and states. We conducted a prospective 10-year evaluation (January 2008-February 2019) of a local influenza nowcasting (short-term forecasting) method in 3 urban counties in Sweden with independent public health administrations by using routine health information system data. Detection-of-epidemic-start (detection), peak timing, and peak intensity were nowcasted. Detection displayed satisfactory performance in 2 of the 3 counties for all nonpandemic influenza seasons and in 6 of 9 seasons for the third county. Peak-timing prediction showed satisfactory performance from the influenza season 2011-12 onward. Peak-intensity prediction also was satisfactory for influenza seasons in 2 of the counties but poor in 1 county. Local influenza nowcasting was satisfactory for seasonal influenza in 2 of 3 counties. The less satisfactory performance in 1 of the study counties might be attributable to population mixing with a neighboring metropolitan area.

Frequent recovery of influenza A but not influenza B virus RNA in aerosols in pediatric patient rooms.

Influenza transmission occurs through the air, but the relative importance of small droplets, or aerosols, in influenza transmission especially within healthcare facilities remains uncertain. Detections of influenza virus in aerosols in cough and exhaled breath from infected patients and from the air in outpatient or inpatient healthcare facilities have been studied, but most studies were done in adults with very few data involving children. We aimed to assess the potential of influenza transmission via aerosols in pediatric patient rooms. Two-stage cyclone (NIOSH) air samplers were used to collect the air in 5-bed pediatric patient rooms with patients with influenza-like illness. Influenza A virus RNA was recovered in 15/19 (79%) air sampling occasions with ≥1 patient with laboratory-confirmed influenza A virus infections, in all air size fractions (>4 µm, 1-4 µm and <1 µm). Influenza B virus RNA was significantly less detected (2/10 occasions, 20%). We estimated a ventilation rate of 1.46 ACH in a similar but unoccupied 5-bed patient room. High quantities of influenza A virus RNA detected in the air in pediatric patient rooms suggests other individuals in pediatric patient rooms including other patients, visitors, caretakers and healthcare workers could be exposed to influenza A virus in aerosols while caring for infected children.

Evaluation of Nowcasting for Detecting and Predicting Local Influenza Epidemics, Sweden, 2009-2014.

The growing availability of big data in healthcare and public health opens possibilities for infectious disease control in local settings. We prospectively evaluated a method for integrated local detection and prediction (nowcasting) of influenza epidemics over 5 years, using the total population in Östergötland County, Sweden. We used routine health information system data on influenza-diagnosis cases and syndromic telenursing data for July 2009-June 2014 to evaluate epidemic detection, peak-timing prediction, and peak-intensity prediction. Detection performance was satisfactory throughout the period, except for the 2011-12 influenza A(H3N2) season, which followed a season with influenza B and pandemic influenza A(H1N1)pdm09 virus activity. Peak-timing prediction performance was satisfactory for the 4 influenza seasons but not the pandemic. Peak-intensity levels were correctly categorized for the pandemic and 2 of 4 influenza seasons. We recommend using versions of this method modified with regard to local use context for further evaluations using standard methods.

Integrated Detection and Prediction of Influenza Activity for Real-Time Surveillance: Algorithm Design.

BACKGROUND: Influenza is a viral respiratory disease capable of causing epidemics that represent a threat to communities worldwide. The rapidly growing availability of electronic "big data" from diagnostic and prediagnostic sources in health care and public health settings permits advance of a new generation of methods for local detection and prediction of winter influenza seasons and influenza pandemics. OBJECTIVE: The aim of this study was to present a method for integrated detection and prediction of influenza virus activity in local settings using electronically available surveillance data and to evaluate its performance by retrospective application on authentic data from a Swedish county. METHODS: An integrated detection and prediction method was formally defined based on a design rationale for influenza detection and prediction methods adapted for local surveillance. The novel method was retrospectively applied on data from the winter influenza season 2008-09 in a Swedish county (population 445,000). Outcome data represented individuals who met a clinical case definition for influenza (based on International Classification of Diseases version 10 [ICD-10] codes) from an electronic health data repository. Information from calls to a telenursing service in the county was used as syndromic data source. RESULTS: The novel integrated detection and prediction method is based on nonmechanistic statistical models and is designed for integration in local health information systems. The method is divided into separate modules for detection and prediction of local influenza virus activity. The function of the detection module is to alert for an upcoming period of increased load of influenza cases on local health care (using influenza-diagnosis data), whereas the function of the prediction module is to predict the timing of the activity peak (using syndromic data) and its intensity (using influenza-diagnosis data). For detection modeling, exponential regression was used based on the assumption that the beginning of a winter influenza season has an exponential growth of infected individuals. For prediction modeling, linear regression was applied on 7-day periods at the time in order to find the peak timing, whereas a derivate of a normal distribution density function was used to find the peak intensity. We found that the integrated detection and prediction method detected the 2008-09 winter influenza season on its starting day (optimal timeliness 0 days), whereas the predicted peak was estimated to occur 7 days ahead of the factual peak and the predicted peak intensity was estimated to be 26% lower than the factual intensity (6.3 compared with 8.5 influenza-diagnosis cases/100,000). CONCLUSIONS: Our detection and prediction method is one of the first integrated methods specifically designed for local application on influenza data electronically available for surveillance. The performance of the method in a retrospective study indicates that further prospective evaluations of the methods are justified.

Motivators and Demotivators for COVID-19 Vaccination Based on Co-Occurrence Networks of Verbal Reasons for Vaccination Acceptance and Resistance: Repetitive Cross-Sectional Surveys and Network Analysis.

BACKGROUND: Vaccine hesitancy is complex and multifaced. People may accept or reject a vaccine due to multiple and interconnected reasons, with some reasons being more salient in influencing vaccine acceptance or resistance and hence the most important intervention targets for addressing vaccine hesitancy. OBJECTIVE: This study was aimed at assessing the connections and relative importance of motivators and demotivators for COVID-19 vaccination in Hong Kong based on co-occurrence networks of verbal reasons for vaccination acceptance and resistance from repetitive cross-sectional surveys. METHODS: We conducted a series of random digit dialing telephone surveys to examine COVID-19 vaccine hesitancy among general Hong Kong adults between March 2021 and July 2022. A total of 5559 and 982 participants provided verbal reasons for accepting and resisting (rejecting or hesitating) a COVID-19 vaccine, respectively. The verbal reasons were initially coded to generate categories of motivators and demotivators for COVID-19 vaccination using a bottom-up approach. Then, all the generated codes were mapped onto the 5C model of vaccine hesitancy. On the basis of the identified reasons, we conducted a co-occurrence network analysis to understand how motivating or demotivating reasons were comentioned to shape people's vaccination decisions. Each reason's eigenvector centrality was calculated to quantify their relative importance in the network. Analyses were also stratified by age group. RESULTS: The co-occurrence network analysis found that the perception of personal risk to the disease (egicentrality=0.80) and the social responsibility to protect others (egicentrality=0.58) were the most important comentioned reasons that motivate COVID-19 vaccination, while lack of vaccine confidence (egicentrality=0.89) and complacency (perceived low disease risk and low importance of vaccination; egicentrality=0.45) were the most important comentioned reasons that demotivate COVID-19 vaccination. For older people aged ≥65 years, protecting others was a more important motivator (egicentrality=0.57), while the concern about poor health status was a more important demotivator (egicentrality=0.42); for young people aged 18 to 24 years, recovering life normalcy (egicentrality=0.20) and vaccine mandates (egicentrality=0.26) were the more important motivators, while complacency (egicentrality=0.77) was a more important demotivator for COVID-19 vaccination uptake. CONCLUSIONS: When disease risk is perceived to be high, promoting social responsibility to protect others is more important for boosting vaccination acceptance. However, when disease risk is perceived to be low and complacency exists, fostering confidence in vaccines to address vaccine hesitancy becomes more important. Interventions for promoting vaccination acceptance and reducing vaccine hesitancy should be tailored by age.

Joint analysis of vaccination effectiveness and antiviral drug effectiveness for COVID-19: a causal inference approach.

OBJECTIVES: This study aims to estimate the causal effects of oral antivirals and vaccinations in the prevention of all-cause mortality and progression to severe COVID-19 in an integrative setting with both antivirals and vaccinations considered as interventions. METHODS: We identified hospitalized adult patients (i.e. aged 18 or above) in Hong Kong with confirmed SARS-CoV-2 infection between March 16, 2022, and December 31, 2022. An inverse probability-weighted (IPW) Andersen-Gill model with time-dependent predictors was used to address immortal time bias and produce causal estimates for the protection effects of oral antivirals and vaccinations against severe COVID-19. RESULTS: Given prescription is made within 5 days of confirmed infection, nirmatrelvir-ritonavir is more effective in providing protection against all-cause mortality and development into severe COVID-19 than molnupiravir. There was no significant difference between CoronaVac and Comirnaty in the effectiveness of reducing all-cause mortality and progression to severe COVID-19. CONCLUSIONS: The use of oral antivirals and vaccinations causes lower risks of all-cause mortality and progression to severe COVID-19 for hospitalized SARS-CoV-2 patients.

A retrospective cohort study of Paxlovid efficacy depending on treatment time in hospitalized COVID-19 patients.

Paxlovid, a SARS-CoV-2 antiviral, not only prevents severe illness but also curtails viral shedding, lowering transmission risks from treated patients. By fitting a mathematical model of within-host Omicron viral dynamics to electronic health records data from 208 hospitalized patients in Hong Kong, we estimate that Paxlovid can inhibit over 90% of viral replication. However, its effectiveness critically depends on the timing of treatment. If treatment is initiated three days after symptoms first appear, we estimate a 17% chance of a post-treatment viral rebound and a 12% (95% CI: 0-16%) reduction in overall infectiousness for non-rebound cases. Earlier treatment significantly elevates the risk of rebound without further reducing infectiousness, whereas starting beyond five days reduces its efficacy in curbing peak viral shedding. Among the 104 patients who received Paxlovid, 62% began treatment within an optimal three-to-five-day day window after symptoms appeared. Our findings indicate that broader global access to Paxlovid, coupled with appropriately timed treatment, can mitigate the severity and transmission of SARS-Cov-2.

Risk of SARS-CoV-2 breakthrough infection following NVX-CoV2373 and BNT162b2 vaccinations in Korean Adults: A population-based observational study.

South Korea experienced a low prevalence of SARS-CoV-2 until the emergence of the omicron in early 2022, triggering a major community epidemic. To evaluate effectiveness of NVX-CoV2373 and BNT162b2 vaccines in Korean population, we conducted an observational study utilizing individual-level case data on laboratory-confirmed SARS-CoV-2 infection, along with vaccination record. A total of 47,078 recipients of NVX-CoV2373 vaccine and 7,561 recipients of BNT162b2 vaccine were eligible for the study. Thirty days post-second doses, COVID-19 rates were 7.9% (595 out of 7561) of NVX-CoV2373 recipients and 8.6 % (647 out of 7561) of BNT162b2 recipients experienced COVID-19. NVX-CoV2373 rates increased to 9.8 % and 11.2 % at 60 and 90 days, while BNT162b2 rates were 10.5 % and 11.3 % at the same intervals. The 22-weeks risk ratios for recipients of the NVX-CoV2373 vaccine as compared with recipients of the BNT162b2 vaccine were 1.11 (95 % CI, 0.99 to 1.25) for laboratory-confirmed SARS-CoV-2 infection. Continued monitoring is essential to evaluate the duration of protection across different vaccine platforms and schedules.

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.

Why Do Chinese Older Adults in Hong Kong Delay or Refuse COVID-19 Vaccination? A Qualitative Study Based on Grounded Theory.

OBJECTIVES: Older adults have been disproportionately affected by the coronavirus disease 2019 (COVID-19) pandemic. While COVID-19 vaccines are effective for reducing mortality and severe complications, vaccine hesitancy remains a substantial concern particularly among older adults. This was a qualitative study to explore how Chinese older adults reached a decision to delay or refuse the COVID-19 vaccines in Hong Kong. METHODS: Semi-structured in-depth interviews were conducted with 27 older adults aged ≥60 years who had never received COVID-19 vaccines. The grounded theory approach guided the selection of informants, data collection, data analysis, and report writing. RESULTS: Older adults' vaccine hesitancy and resistance weaved into the context of lacking sufficient decisional support and attitude roots of negative perception of aging, fatalistic risk attitudes, present-oriented time perspectives, and negative values on western biomedicine. Attitude roots were used as the decisional anchors to further shape older adults' peripheral processing of vaccine-related information, resulting into a spectrum of vaccine-resistant and vaccine-hesitant attitudes. While participants refused or delayed COVID-19 vaccination, they engaged in alternative coping strategies to regain self-control and justify their vaccination disengagement in the pandemic. DISCUSSION: Interventions to address vaccine hesitancy in older adults should focus on addressing attitude roots and strengthening the connectivity of older adults with family, doctors, and government to engage older adults in the vaccination decision making. Risk communication should shift to provide more personal relevant information in a caring style, meet older adults' preference for peripheral information processing, and address their existing misperceptions about COVID-19 vaccines.

Environment- and epigenome-wide association study of obesity in 'Children of 1997' birth cohort.

Background: Increasing childhood obesity is a global issue requiring potentially local solutions to ensure it does not continue into adulthood. We systematically identified potentially modifiable targets of obesity at the onset and end of puberty in Hong Kong, the most economically developed major Chinese city. Methods: We conducted an environment-wide association study (EWAS) and an epigenome-wide association study of obesity to systematically assess associations with body mass index (BMI) and waist-hip ratio (WHR) in Hong Kong's population-representative 'Children of 1997' birth cohort. Univariable linear regression was used to select exposures related to obesity at ~11.5 years (BMI and obesity risk n ≤ 7119, WHR n = 5691) and ~17.6 years (n = 3618) at Bonferroni-corrected significance, and multivariable regression to adjust for potential confounders followed by replicated multivariable regression (n = 308) and CpG by CpG analysis (n = 286) at ~23 years. Findings were compared with evidence from published randomized controlled trials (RCTs) and Mendelian randomization (MR) studies. Results: At ~11.5 and~17.6 years the EWAS identified 14 and 37 exposures associated with BMI, as well as 7 and 12 associated with WHR, respectively. Most exposures had directionally consistent associations at ~23 years. Maternal second-hand smoking, maternal weight, and birth weight were consistently associated with obesity. Diet (including dairy intake and artificially sweetened beverages), physical activity, snoring, binge eating, and earlier puberty were positively associated with BMI at ~17.6 years, while eating before sleep was inversely associated with BMI at ~17.6 years. Findings for birth weight, dairy intake, and binge eating are consistent with available evidence from RCTs or MR studies. We found 17 CpGs related to BMI and 17 to WHR. Conclusions: These novel insights into potentially modifiable factors associated with obesity at the outset and the end of puberty could, if causal, inform future interventions to improve population health in Hong Kong and similar Chinese settings. Funding: This study including the follow-up survey and epigenetics testing was supported by the Health and Medical Research Fund Research Fellowship, Food and Health Bureau, Hong Kong SAR Government (#04180097). The DNA extraction of the samples used for epigenetic testing was supported by CFS-HKU1.

Antibiotic use in hospitalized patients with COVID-19: a population-based study in Hong Kong.

Background: Hong Kong experienced four epidemic waves caused by the ancestral strain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 2020-2021 and a large Omicron wave in 2022. Few studies have assessed antibacterial prescribing for coronavirus disease 2019 (COVID-19) inpatients throughout the pandemic. Objectives: To describe inpatient antibacterial prescribing and explore factors associated with their prescription. Methods: Electronic health records of patients with COVID-19 admitted to public hospitals in Hong Kong from 21 January 2020 to 30 September 2022 were used to assess the prevalence and rates of inpatient antibacterial drug use (days of therapy/1,000 patient days [DOT/1,000 PD]). We used multivariable logistic regression to investigate potential associations between patients' baseline characteristics and disease severity and prescription of an antibacterial drug during hospital admission. Results: Among 65,810 inpatients with COVID-19, 54.0% were prescribed antibacterial drugs (550.5 DOT/1,000 PD). Compared to waves 1-2 (46.7%; 246.9 DOT/1,000 PD), the prescriptions were lowest during wave 4 (28.0%; 246.9; odds ratio (OR): 0.39, 95% CI: 0.31-0.49) and peaked in early wave 5 (64.6%; 661.2; 0.82, 0.65-1.03). Older age (≥80 years: OR 2.66, 95% CI, 2.49-2.85; 60-79 years: 1.59, 1.51-1.69, compared with 20-59 years), more severe disease (fatal: 3.64, 3.2-4.16; critical: 2.56, 2.14-3.06, compared with severe), and COVID-19 vaccine doses (two doses: 0.74, 0.69-0.78; three doses: 0.69, 0.64-0.74; four doses: 0.52, 0.44-0.62, compared with unvaccinated) were associated with inpatient antibacterial drug use. Conclusions: Antibacterial prescribing changed over time for hospitalized patients with confirmed COVID-19 and was potentially related to patients' demographics, medical conditions, and COVID-19 vaccination status as well as healthcare capacity during epidemic waves.

Epidemiology and risk factors for carbapenemase-producing Enterobacteriaceae carriage in the hospital: A population-based nested case-control study.

OBJECTIVES: This study aims to study the epidemiology of carbapenemase-producing Enterobacteriaceae (CPE) in Hong Kong. METHODS: This is a longitudinal population-based study reporting monthly CPE incidence rate and a nested case-control study for identifying risk factors for CPE carriage. The cases were patients with at least one CPE-positive genotypic test, while the controls were randomly selected from the cohort with negative tests. Up to four controls per case were matched by sex, age group, and admission year-month. The independent risk factors were identified from a conditional logistic regression with potential covariates. RESULTS: From 1 January 2008 to 31 December 2019, 8588 patients received CPE genotyping tests, and 2353 had at least one positive result. Class B carbapenemase was the predominant enzyme in the samples (78.6%). The incidence rate increased from 0.04 in 2015 to 1.62 in 2019 per 10,000 person-year. In the nested case-control study, 1709 cases and 6664 controls were matched. Previous use of any beta-lactam antibiotics (odds ratio:1.37 [1.22-1.53], P < 0.001) was found as an independent risk factor for carriage of CPE. CONCLUSION: The carriage of CPE was found with an increasing trend in Hong Kong. Previous use of any beta-lactam antibiotics is a risk factor for CPE.

Add-on Rehmannia-6-Based Chinese Medicine in Type 2 Diabetes and CKD: A Multicenter Randomized Controlled Trial.

BACKGROUND: Diabetes is the leading cause of CKD and kidney failure. We assessed the real-world effectiveness of Rehmannia-6-based Chinese medicine treatment, the most used Chinese medicine formulation, on the change in eGFR and albuminuria in patients with diabetes and CKD with severely increased albuminuria. METHODS: In this randomized, assessor-blind, standard care-controlled, parallel, multicenter trial, 148 adult patients from outpatient clinics with type 2 diabetes, an eGFR of 30-90 ml/min per 1.73 m 2 , and a urine albumin-to-creatinine ratio (UACR) of 300-5000 mg/g were randomized 1:1 to a 48-week add-on protocolized Chinese medicine treatment program (using Rehmannia-6-based formulations in the granule form taken orally) or standard care alone. Primary outcomes were the slope of change in eGFR and UACR between baseline and end point (48 weeks after randomization) in the intention-to-treat population. Secondary outcomes included safety and the change in biochemistry, biomarkers, and concomitant drug use. RESULTS: The mean age, eGFR, and UACR were 65 years, 56.7 ml/min per 1.73 m 2 , and 753 mg/g, respectively. Ninety-five percent ( n =141) of end point primary outcome measures were retrievable. For eGFR, the estimated slope of change was -2.0 (95% confidence interval [CI], -0.1 to -3.9) and -4.7 (95% CI, -2.9 to -6.5) ml/min per 1.73 m 2 in participants treated with add-on Chinese medicine or standard care alone, resulting in a 2.7 ml/min per 1.73 m 2 per year (95% CI, 0.1 to 5.3; P = 0.04) less decline with Chinese medicine. For UACR, the estimated proportion in the slope of change was 0.88 (95% CI, 0.75 to 1.02) and 0.99 (95% CI, 0.85 to 1.14) in participants treated with add-on Chinese medicine or standard care alone, respectively. The intergroup proportional difference (0.89, 11% slower increment in add-on Chinese medicine, 95% CI, 0.72 to 1.10; P = 0.28) did not reach statistical significance. Eighty-five adverse events were recorded from 50 participants (add-on Chinese medicine versus control: 22 [31%] versus 28 [36%]). CONCLUSIONS: Rehmannia-6-based Chinese medicine treatment stabilized eGFR on top of standard care alone after 48 weeks in patients with type 2 diabetes, stage 2-3 CKD, and severely increased albuminuria. CLINICAL TRIAL REGISTRY: Semi-individualized Chinese Medicine Treatment as an Adjuvant Management for Diabetic Nephropathy (SCHEMATIC), NCT02488252 .