Effectiveness of Molnupiravir and Nirmatrelvir-Ritonavir in CKD Patients With COVID-19.

Introduction: Even with effective vaccines, patients with CKD have a higher risk of hospitalization and death subsequent to COVID-19 infection than those without CKD. Molnupiravir and nirmatrelvir-ritonavir have been approved for emergency use, but their effectiveness for the CKD population is still unknown. This study was conducted to determine the effectiveness of these drugs in reducing mortality and severe COVID-19 in the CKD population. Methods: This was a target trial emulation study using electronic health databases in Hong Kong. Patients with CKD aged 18 years or older who were hospitalized with COVID-19 were included. The per-protocol average treatment effect among COVID-19 oral antiviral initiators, including all-cause mortality, intensive care unit (ICU) admission, and ventilatory support within 28 days, were compared to noninitiators. Results: Antivirals have been found to lower the risk of all-cause mortality, with Molnupiravir at a hazard ratio (HR) of 0.85 (95% confidence interval [CI], 0.77 to 0.95] and nirmatrelvir-ritonavir at an HR of 0.78 [95% CI, 0.60 to 1.00]. However, they do not significantly reduce the risk of ICU admission (molnupiravir: HR, 0.88 [95% CI, 0.59 to 1.30]; nirmatrelvir-ritonavir: HR, 0.86 [95% CI, 0.56 to 1.32]) or ventilatory support (molnupiravir: HR, 1.00 [95% CI, 0.76 to 1.33]; nirmatrelvir-ritonavir: HR, 1.01 [95% CI, 0.74 to 1.37]). There was a greater risk reduction in males and those with higher Charlson Comorbidity Index (CCI). The nirmatrelvir-ritonavir trial also showed reduced risk for those who had antiviral treatment and received 3 or more vaccine doses. Conclusion: Both molnupiravir and nirmatrelvir-ritonavir reduced mortality rates for hospitalized COVID-19 patients with CKD.

Effectiveness of a self-determination theory-based smoking cessation intervention plus instant messaging via mobile application for smokers with cancer: Protocol for a pragmatic randomized controlled trial.

BACKGROUND AND AIMS: Despite evidence that patients living with cancer who continue to smoke after diagnosis are at higher risk for all-cause mortality and reduced treatment efficacy, many cancer patients continue to smoke. This protocol is for a study to test the effectiveness of a self-determination theory-based intervention (quit immediately or progressively) plus instant messaging (WhatsApp or WeChat) to help smokers with cancer to quit smoking. DESIGN: This will be a multi-centre, two-arm (1:1), single-blind, pragmatic, individually randomized controlled trial. SETTING: Taking part will be specialist outpatient clinics in five major hospitals in different location-based clusters in Hong Kong. PARTICIPANTS: The sample will include 1448 Chinese smokers living with cancer attending medical follow-ups at outpatient clinics. INTERVENTIONS: The intervention group will receive brief advice (approximately 5-8 minutes) from research nurses in the outpatient clinics and then be invited to choose their own quit schedules (immediate or progressive). During the first 6-month follow-up period they will receive instant messaging with smoking cessation advice once per week for the first 3 months, and thereafter approximately once per month. They will also receive four videos, and those opting to quit progressively will receive a smoking reduction leaflet. The control group will also receive brief advice but be advised to quit immediately, and instant messaging with general health advice during the first 6-month follow-up period using the same schedule as the intervention group. Participants in both groups will receive smoking cessation leaflets. MEASUREMENTS: The primary outcome is biochemically validated smoking abstinence at 6 months, as confirmed by saliva cotinine level and carbon monoxide level in expired air. Secondary outcomes include biochemically validated smoking abstinence at 12 months, self-reported 7-day point prevalence of smoking abstinence at 6 and 12 months, self-reported ≥ 50% reduction of cigarette consumption at 6 and 12 months and quality of life at 6 and 12 months. All time-points for outcomes measures are set after randomization. COMMENTS: The results could inform research, policymaking and health-care professionals regarding smoking cessation for patients living with cancer, and therefore have important implications for clinical practice and health enhancement.

Effect of Adding Personalized Instant Messaging Apps to a Brief Smoking Cessation Model in Community Smokers in Hong Kong: Pragmatic Randomized Clinical Trial.

BACKGROUND: While text messaging has proven effective for smoking cessation (SC), engagement in the intervention remains suboptimal. OBJECTIVE: This study aims to evaluate whether using more interactive and adaptive instant messaging (IM) apps on smartphones, which enable personalization and chatting with SC advisors, can enhance SC outcomes beyond the provision of brief SC advice and active referral (AR) to SC services. METHODS: From December 2018 to November 2019, we proactively recruited 700 adult Chinese daily cigarette users in Hong Kong. Participants were randomized in a 1:1 ratio. At baseline, all participants received face-to-face brief advice on SC. Additionally, they were introduced to local SC services and assisted in selecting one. The intervention group received an additional 26 personalized regular messages and access to interactive chatting through IM apps for 3 months. The regular messages aimed to enhance self-efficacy, social support, and behavioral capacity for quitting, as well as to clarify outcome expectations related to cessation. We developed 3 sets of messages tailored to the planned quit date (within 30 days, 60 days, and undecided). Participants in the intervention group could initiate chatting with SC advisors on IM themselves or through prompts from regular messages or proactive inquiries from SC advisors. The control group received 26 SMS text messages focusing on general health. The primary outcomes were smoking abstinence validated by carbon monoxide levels of <4 parts per million at 6 and 12 months after the start of the intervention. RESULTS: Of the participants, 505/700 (72.1%) were male, and 450/648 (69.4%) were aged 40 or above. Planning to quit within 30 days was reported by 500/648 (77.2%) participants, with fewer intervention group members (124/332, 37.3%) reporting previous quit attempts compared with the control group (152/335, 45.4%; P=.04). At the 6- and 12-month follow-ups (with retention rates of 456/700, 65.1%, and 446/700, 63.7%, respectively), validated abstinence rates were comparable between the intervention (14/350, 4.0%, and 19/350, 5.4%) and control (11/350, 3.1% and 21/350, 6.0%) groups. Compared with the control group, the intervention group reported greater utilization of SC services at 12 months (RR 1.26, 95% CI 1.01-1.56). Within the intervention group, engaging in chat sessions with SC advisors predicted better validated abstinence at 6 months (RR 3.29, 95% CI 1.13-9.63) and any use of SC services (RR 1.66, 95% CI 1.14-2.43 at 6 months; RR 1.67, 95% CI 1.26-2.23 at 12 months). CONCLUSIONS: An IM-based intervention, providing support and assistance alongside brief SC advice and AR, did not yield further increases in quitting rates but did encourage the utilization of SC services. Future research could explore whether enhanced SC service utilization leads to improved long-term SC outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT03800719; https://clinicaltrials.gov/ct2/show/NCT03800719.

A comparison of cardiovascular disease, cancer, mortality, and Graves' ophthalmopathy following treatment for hyperthyroidism: A Bayesian network meta-analysis.

OBJECTIVES: This network meta-analysis aimed to evaluate the association of anti-thyroid drugs (ATD), radioactive iodine (RAI), and thyroidectomy with subsequent outcomes in patients with newly-diagnosed hyperthyroidism. METHODS: The Ovid Medline, Ovid Embase, and Cochrane Library databases were searched for observational studies and randomized controlled trials. Included studies were published on or before 1st May 2022 involving at least two of the treatments among ATD, RAI, and thyroidectomy for hyperthyroidism. Pairwise comparisons and Bayesian network meta-analysis were used to estimate hazard ratios (HRs) and their credible interval (CrI) of outcomes, including cardiovascular disease (CVD), cancer, overall mortality, and Graves' ophthalmopathy (GO). RESULTS: A total of 22 cohort studies with 131,297 hyperthyroidism patients were included. Thyroidectomy was associated with lower risks of mortality and GO than ATD (HR = 0.54, 95% CrI: 0.31, 0.96; HR = 0.31, 95% CrI: 0.12, 0.64) and RAI (HR = 0.62, 95% CrI: 0.41, 0.95; HR = 0.18, 95% CrI: 0.07, 0.35). RAI had a higher risk of GO (HR = 1.70, 95% CrI: 1.02, 2.99) than ATD treatment. CONCLUSIONS: This Bayesian network meta-analysis indicated that thyroidectomy was associated with lower risks of mortality and GO in newly-diagnosed hyperthyroid patients compared to ATD and RAI. Relative to ATD, RAI therapy increased the risk of GO.

Self-Administered Acupressure for Probable Knee Osteoarthritis in Middle-Aged and Older Adults: A Randomized Clinical Trial.

Importance: The effects of self-administered acupressure (SAA) on knee osteoarthritis (OA) pain remain unclear. Objective: To evaluate the effectiveness of SAA taught via a short training course on reducing knee OA pain in middle-aged and older adults. Design, Setting, and Participants: This randomized clinical trial was conducted among community-dwelling individuals in Hong Kong who were aged 50 years or older with probable knee OA from September 2019 to May 2022. Interventions: The intervention included 2 training sessions for SAA with a brief knee health education (KHE) session, in which participants practiced acupressure twice daily for 12 weeks. The control group (KHE only) received only education about maintaining knee health on the same schedule and duration. Main Outcomes and Measures: The primary outcome was the numerical rating scale (NRS) pain score at 12 weeks. Other outcomes included Western Ontario and McMaster University Osteoarthritis Index, Short Form 6 Dimensions (SF-6D), Timed Up and Go, and Fast Gait Speed tests. Results: A total of 314 participants (mean [SD] age, 62.7 [4.5] years; 246 [78.3%] female; mean [SD] knee pain duration, 7.3 [7.6] years) were randomized into intervention and KHE-only groups (each 157). At week 12, compared with the KHE-only group, the intervention group had a significantly greater reduction in NRS pain score (mean difference [MD], -0.54 points; 95% CI, -0.97 to -0.10 points; P = .02) and higher enhancement in SF-6D utility score (MD, 0.03 points; 95% CI, 0.003 to 0.01 points; P = .03) but did not have significant differences in other outcome measures. The cost-effectiveness acceptability curve demonstrated a greater than 90% probability that the intervention is cost-effective at a willingness to pay threshold of 1 GDP per capita. Conclusions and Relevance: In this randomized clinical trial, SAA with a brief KHE program was efficacious and cost-effective in relieving knee pain and improving mobility in middle-aged and older adults with probable knee OA. Trial Registration: ClinicalTrials.gov Identifier: NCT04191837.

Recalibration of a Non-Laboratory-Based Risk Model to Estimate Pre-Diabetes/Diabetes Mellitus Risk in Primary Care in Hong Kong.

INTRODUCTION/OBJECTIVES: A non-laboratory-based pre-diabetes/diabetes mellitus (pre-DM/DM) risk prediction model developed from the Hong Kong Chinese population showed good external discrimination in a primary care (PC) population, but the estimated risk level was significantly lower than the observed incidence, indicating poor calibration. This study explored whether recalibrating/updating methods could improve the model's accuracy in estimating individuals' risks in PC. METHODS: We performed a secondary analysis on the model's predictors and blood test results of 919 Chinese adults with no prior DM diagnosis recruited from PC clinics from April 2021 to January 2022 in HK. The dataset was randomly split in half into a training set and a test set. The model was recalibrated/updated based on a seven-step methodology, including model recalibrating, revising and extending methods. The primary outcome was the calibration of the recalibrated/updated models, indicated by calibration plots. The models' discrimination, indicated by the area under the receiver operating characteristic curves (AUC-ROC), was also evaluated. RESULTS: Recalibrating the model's regression constant, with no change to the predictors' coefficients, improved the model's accuracy (calibration plot intercept: -0.01, slope: 0.69). More extensive methods could not improve any further. All recalibrated/updated models had similar AUC-ROCs to the original model. CONCLUSION: The simple recalibration method can adapt the HK Chinese pre-DM/DM model to PC populations with different pre-test probabilities. The recalibrated model can be used as a first-step screening tool and as a measure to monitor changes in pre-DM/DM risks over time or after interventions.

Risk of Incident Thyroid Dysfunction in the Post-Acute Phase of COVID-19: A Population-Based Cohort Study in Hong Kong.

OBJECTIVE: The evidence of thyroid dysfunction in the post-acute phase of SARS-CoV-2 infection is limited. This study aimed to evaluate the risk of incident thyroid dysfunction in the post-acute phase of COVID-19. METHODS: This retrospective, propensity-score matched, population-based study included COVID-19 patients and non-COVID-19 individuals between January 2020 and March 2022, identified from the electronic medical records of the Hong Kong Hospital Authority. The cohort was followed up until the occurrence of outcomes, death, or 31 January 2023, whichever came first. Patients with COVID-19 were 1:1 matched to controls based on various variables. The primary outcome was a composite of thyroid dysfunction (hyperthyroidism, hypothyroidism, initiation of antithyroid drug or levothyroxine, and thyroiditis). Cox regression was employed to evaluate the risk of incident thyroid dysfunction during the post-acute phase. RESULTS: A total of 84 034 COVID-19 survivors and 84 034 matched controls were identified. Upon a median follow-up of 303 days, there was no significant increase in the risk of diagnosed thyroid dysfunction in the post-acute phase of COVID-19 (hazard ratio [HR] 1.058, 95% confidence interval 0.979-1.144, P = .154). Regarding the secondary outcomes, patients with COVID-19 did not have increased risk of hyperthyroidism (HR 1.061, P = .345), hypothyroidism (HR 1.062, P = .255), initiation of antithyroid drug (HR 1.302, P = .070), initiation of levothyroxine (HR 1.086, P = .426), or thyroiditis (P = .252). Subgroup and sensitivity analyses were largely consistent with the main analyses. CONCLUSION: Our population-based cohort study provided important reassuring data that COVID-19 was unlikely to be associated with persistent effects on thyroid function.

Effects of SARS-CoV-2 infection on incidence and treatment strategies of hepatocellular carcinoma in people with chronic liver disease.

BACKGROUND: Chronic liver disease (CLD) was associated with adverse clinical outcomes among people with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. AIM: To determine the effects of SARS-CoV-2 infection on the incidence and treatment strategy of hepatocellular carcinoma (HCC) among patients with CLD. METHODS: A retrospective, territory-wide cohort of CLD patients was identified from an electronic health database in Hong Kong. Patients with confirmed SARS-CoV-2 infection [coronavirus disease 2019 (COVID-19)+CLD] between January 1, 2020 and October 25, 2022 were identified and matched 1:1 by propensity-score with those without (COVID-19-CLD). Each patient was followed up until death, outcome event, or November 15, 2022. Primary outcome was incidence of HCC. Secondary outcomes included all-cause mortality, adverse hepatic outcomes, and different treatment strategies to HCC (curative, non-curative treatment, and palliative care). Analyses were further stratified by acute (within 20 d) and post-acute (21 d or beyond) phases of SARS-CoV-2 infection. Incidence rate ratios (IRRs) were estimated by Poisson regression models. RESULTS: Of 193589 CLD patients (> 95% non-cirrhotic) in the cohort, 55163 patients with COVID-19+CLD and 55163 patients with COVID-19-CLD were included after 1:1 propensity-score matching. Upon 249-d median follow-up, COVID-19+CLD was not associated with increased risk of incident HCC (IRR: 1.19, 95%CI: 0.99-1.42, P = 0.06), but higher risks of receiving palliative care for HCC (IRR: 1.60, 95%CI: 1.46-1.75, P < 0.001), compared to COVID-19-CLD. In both acute and post-acute phases of infection, COVID-19+CLD were associated with increased risks of all-cause mortality (acute: IRR: 7.06, 95%CI: 5.78-8.63, P < 0.001; post-acute: IRR: 1.24, 95%CI: 1.14-1.36, P < 0.001) and adverse hepatic outcomes (acute: IRR: 1.98, 95%CI: 1.79-2.18, P < 0.001; post-acute: IRR: 1.24, 95%CI: 1.13-1.35, P < 0.001), compared to COVID-19-CLD. CONCLUSION: Although CLD patients with SARS-CoV-2 infection were not associated with increased risk of HCC, they were more likely to receive palliative treatment than those without. The detrimental effects of SARS-CoV-2 infection persisted in post-acute phase.

COVID-19 vaccine effectiveness against the Omicron variant of SARS-CoV-2 in multimorbidity: A territory-wide case-control study.

Multimorbidity entails a higher risk of SARS-CoV-2 infection and COVID-19 complications. We examined vaccine effectiveness (VE) stratified by multimorbidity using a case-control study of territory-wide electronic health records in Hong Kong. Cases of infection (testing positive), hospitalization, and mortality were identified from January to March 2022. Controls were matched by age, sex, outpatient attendance/hospitalization date, and Charlson Comorbidity Index. We demonstrated a consistently good VE among people with increased multimorbidity burden; even more so than among those with minimal such burden. There was also a significantly greater VE after a third dose of BNT162b2 or CoronaVac against infection. The difference in VE between those with multimorbidity and those without was less pronounced for hospitalization, and such difference for COVID-19-related mortality was negligible. In conclusion, VE of both examined vaccines against SARS-CoV-2 infection among people with more complex multimorbidity burden is significant. Further vaccine roll-out should prioritize people with multimorbidity.

Risks of incident major osteoporotic fractures following SARS-CoV-2 infection among older individuals: a population-based cohort study in Hong Kong.

Population-based epidemiological studies on post-acute phase COVID-19-related fractures in older adults are lacking. This study aims to examine the risk of incident major osteoporotic fractures following COVID-19 infection among individuals aged ≥50, compared to individuals without COVID-19. It was a retrospective, propensity-score matched, population-based cohort study of COVID-19 patients and non-COVID individuals identified from the electronic database of the Hong Kong Hospital Authority from January 2020 to March 2022. The primary outcome was a composite of major osteoporotic fractures (hip, clinical vertebral, and upper limb). COVID-19 patients were 1:1 matched to controls using propensity-score according to age, sex, vaccination status, medical comorbidities and baseline medications. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using Cox proportional hazards regression models. A total of 429 459 COVID-19 patients were included, 1:1 matched to non-COVID individuals. Upon median follow-up of 11 months, COVID-19 patients had higher risks of major osteoporotic fractures (5.08 vs 3.95 per 1000 persons; HR 1.22 95%CI [1.15-1.31]), hip fractures (2.71 vs 1.94; 1.33 [1.22-1.46]), clinical vertebral fractures (0.42 vs 0.31; 1.29 [1.03-1.62]) and falls (13.83 vs 10.36; 1.28 [1.23-1.33]). Subgroup analyses revealed no significant interaction. In acute (within 30 days) and post-acute phases (beyond 30 days) following SARS-CoV-2 infection, we consistently observed a significant increase in fractures and falls risks. Our study demonstrated increased risk of major osteoporotic fractures after SARS-CoV-2 infection in both acute and post-acute phases in older adults, partly due to increased fall risk. Clinicians should be aware of musculoskeletal health of COVID-19 survivors.

Our study showed that older individuals with COVID-19 infection are at a higher risk of suffering from major osteoporotic fractures, i.e. serious bone fractures related to osteoporosis, compared to those not infected. The study analysed the health records of 429 459 patients aged 50 and older in Hong Kong who had been diagnosed with COVID-19 between January 2020 and March 2022. These patients were compared with a matched group without COVID-19, considering age, sex, vaccination status, medical comorbidities, and concomitant medications. Findings indicated that individuals who had contracted COVID-19 experienced a higher risk of major osteoporotic fractures, hip fractures, and clinical vertebral fractures. The risk of falls, a common cause of these fractures, was also higher in the COVID-19 group. This increased risk of major osteoporotic fractures and falls persists both shortly after infection and in the following months, underscoring the lasting impact of COVID-19 on the bone health of older adults. These results support the recommendations for the assessment of bone health and fall risks, and an urgent review of the requirement for interventions to reduce the risk of fragility fractures in older adult COVID-19 survivors.

Effectiveness of a 5-year health empowerment programme on promoting cardiovascular health for adults from low-income families in Hong Kong.

OBJECTIVE: This study aimed to evaluate the effectiveness of a health empowerment programme (HEP) to enhance cardiovascular health for adults from low-income families. METHODS: A prospective cohort study (N = 219, Intervention group: n = 103, comparison group: n = 116) was conducted with participants recruited from January 2013 to November 2015 and followed up until January 2022. Throughout the study duration, intervention group were invited to participate in the HEP. The cardiovascular health status of both groups at baseline and follow-up were assessed using the adapted Ideal Cardiovascular Health Index (ICHI) defined by the American Heart Association. After inverse propensity score weighting, multiple linear regression and Poisson regression were employed to examine the effects of the HEP. RESULTS: The HEP was associated with a greater increase in ICHI total score (B = 0.33, p < 0.001), and the increase of proportion of people achieving a normal blood pressure (Incidence rate ratio: 3.39, p < 0.05). CONCLUSION: HEP can be an effective and sustainable strategy to reduce social disparities in cardiovascular health of adults from low-income families, as indicated by improvement in the ICHI total score and blood pressure status. PRACTICAL IMPLICATIONS: The sustainable HEP in the community setting has potential for generalizability and scalability to other financially challenged families.

Persistence in risk and effect of COVID-19 vaccination on long-term health consequences after SARS-CoV-2 infection.

The persisting risk of long-term health consequences of SARS-CoV-2 infection and the protection against such risk conferred by COVID-19 vaccination remains unclear. Here we conducted a retrospective territory-wide cohort study on 1,175,277 patients with SARS-CoV-2 infection stratified by their vaccination status and non-infected controls to evaluate the risk of clinical sequelae, cardiovascular and all-cause mortality using a territory-wide public healthcare database with population-based vaccination records in Hong Kong. A progressive reduction in risk of all-cause mortality was observed over one year between patients with SARS-CoV-2 infection and controls. Patients with complete vaccination or have received booster dose incurred a lower risk of health consequences including major cardiovascular diseases, and all-cause mortality than unvaccinated or patients with incomplete vaccination 30-90 days after infection. Completely vaccinated and patients with booster dose of vaccines did not incur significant higher risk of health consequences from 271 and 91 days of infection onwards, respectively, whilst un-vaccinated and incompletely vaccinated patients continued to incur a greater risk of clinical sequelae for up to a year following SARS-CoV-2 infection. This study provided real-world evidence supporting the effectiveness of COVID-19 vaccines in reducing the risk of long-term health consequences of SARS-CoV-2 infection and its persistence following infection.

The Effect of the COVID-19 Pandemic on Non-COVID-19 Deaths: Population-Wide Retrospective Cohort Study.

BACKGROUND: Health care avoidance in the COVID-19 pandemic has been widely reported. Yet few studies have investigated the dynamics of hospital avoidance behavior during pandemic waves and inferred its impact on excess non-COVID-19 deaths. OBJECTIVE: This study aimed to measure the impact of hospital avoidance on excess non-COVID-19 deaths in public hospitals in Hong Kong. METHODS: This was a retrospective cohort study involving 11,966,786 patients examined between January 1, 2016, and December 31, 2021, in Hong Kong. All data were linked to service, treatment, and outcomes. To estimate excess mortality, the 2-stage least squares method was used with daily tallies of emergency department (ED) visits and 28-day mortality. Records for older people were categorized by long-term care (LTC) home status, and comorbidities were used to explain the demographic and clinical attributes of excess 28-day mortality. The primary outcome was actual excess death in 2020 and 2021. The 2-stage least squares method was used to estimate the daily excess 28-day mortality by daily reduced visits. RESULTS: Compared with the prepandemic (2016-2019) average, there was a reduction in total ED visits in 2020 of 25.4% (548,116/2,142,609). During the same period, the 28-day mortality of non-COVID-19 ED deaths increased by 7.82% (2689/34,370) compared with 2016-2019. The actual excess deaths in 2020 and 2021 were 3143 and 4013, respectively. The estimated total excess non-COVID-19 28-day deaths among older people in 2020 to 2021 were 1958 (95% CI 1100-2820; no time lag). Deaths on arrival (DOAs) or deaths before arrival (DBAs) increased by 33.6% (1457/4336) in 2020, while non-DOA/DBAs increased only by a moderate 4.97% (1202/24,204). In both types of deaths, the increases were higher during wave periods than in nonwave periods. Moreover, non-LTC patients saw a greater reduction in ED visits than LTC patients across all waves, by more than 10% (non-LTC: 93,896/363,879, 25.8%; LTC: 7,956/67,090, 11.9%). Most of the comorbidity subsets demonstrated an annualized reduction in visits in 2020. Renal diseases and severe liver diseases saw notable increases in deaths. CONCLUSIONS: We demonstrated a statistical method to estimate hospital avoidance behavior during a pandemic and quantified the consequent excess 28-day mortality with a focus on older people, who had high frequencies of ED visits and deaths. This study serves as an informed alert and possible investigational guideline for health care professionals for hospital avoidance behavior and its consequences.

Risk of carditis among adolescents after extending the interdose intervals of BNT162b2.

Previous studies indicate an increased carditis risk among adolescents following the two-dose messenger RNA COVID-19 vaccine. Several jurisdictions have extended the interdose interval between the first and second doses to reduce the risk. However, the effectiveness of such an extension policy remains inconclusive. Using the territory-wide vaccine record-linked electronic health records in Hong Kong, we conducted a nested case-control study from February 23, 2021 to August 15, 2022. Adolescents aged between 12 and 17 who received two-dose BNT162b2 were included for comparing risks between standard interdose interval (21-27 days) versus extended interdose interval ( ≥ 56 days). The carditis cumulative incidence within 28 days following the second dose was calculated. The adjusted odds ratio was estimated from multivariable conditional logistic regression. We identified 49 adolescents with newly diagnosed carditis within 28 days following the second dose. The crude cumulative incidence is 37.41 [95% confidence interval (CI): 27.68-49.46] per million vaccinated adolescents. Compared to the standard interdose interval group, adolescents with an extended interval had a significantly lower risk of carditis [adjusted odds ratio (aOR) 0.34 (95% CI: 0.16-0.73)]. Sensitivity analysis of carditis occurring within 14 days following the second dose yielded a similar estimate [aOR 0.30 (95% CI: 0.13-0.73)]. Extending the interdose interval of the BNT162b2 vaccine from 21 to 27 days to 56 days or longer is associated with 66% lower risk of incident carditis among adolescents. Our findings contribute towards an evidence-based vaccination strategy for a vulnerable population and potentially informs product label updates.

Effectiveness of mRNA BNT162b2 and inactivated CoronaVac vaccines against severe COVID-19 outcomes among non-hospitalised children aged 1-3 years with SARS-CoV-2 Omicron infection.

OBJECTIVES: Clinical evidence on the effectiveness of COVID-19 vaccines for children aged 1-3 years is scarce. The effectiveness of COVID-19 vaccines was evaluated among non-hospitalised children aged 1-3 years with SARS-CoV-2 Omicron infection in Hong Kong. METHODS: A retrospective cohort of all non-hospitalised children aged 1-3 years with confirmed SARS-CoV-2 infection between 4 August 2022 and 29 January 2023 in Hong Kong was analysed. Vaccinated group was defined as the recipients of one or more doses of CoronaVac or mRNA vaccine BNT162b2 (original, monovalent) at least 14 days prior to infection. Hazard ratios (HR) with 95% confidence intervals (95% CI) of study outcomes were estimated using Cox regression models. Effectiveness outcomes included 28-day all-cause mortality and COVID-19-related hospitalisation. RESULTS: A total of 5552 vaccinated patients and 5552 propensity-score matched controls (unvaccinated patients) were included for analysis. The cumulative incidence of COVID-19-related hospitalisation over 28 days was 2.3% and 2.9% in the vaccinated and control groups, respectively. There were no deaths in both groups. COVID-19 vaccination was associated with a significant reduction in 28-day COVID-19-related hospitalisation risk (HR=0.785, 95% CI=0.626-0.985, P=0.037), particularly for children aged 3 years, those who had received two or more vaccine doses, and those who received CoronaVac as the last dose. CONCLUSION: COVID-19 vaccination is associated with a significantly lower risk of 28-day COVID-19-related hospitalisation among infected children aged 1-3 years, particularly those who had received two or more vaccine doses. This observation emphasises the importance of completing the full two-dose or three-dose series to optimise vaccine effectiveness.

Effectiveness and Respiratory Adverse Events Following Inactivated and mRNA COVID-19 Vaccines in Patients with COPD and Asthma: A Chinese Population-Based Study.

INTRODUCTION: Effectiveness and respiratory adverse events following coronavirus disease-2019 (COVID-19) vaccines have not been well investigated in Chinese patients with chronic obstructive pulmonary disease (COPD) and asthma. METHODS: Using electronic health care records in Hong Kong, we included adults with COPD or asthma or both and hospitalised for severe respiratory exacerbation in a self-controlled case series (SCCS) study between 23/02/2021 and 30/11/2022. Conditional Poisson regression models were used to estimate the incidence of outcomes within exposure periods (28 days after each dose) compared with baseline periods. Cox proportional hazard models evaluated vaccine effectiveness (VE) against COVID-related mortality, hospitalisation, and severe complications, including admission to intensive care units or ventilatory support. The VE assessment was based on vaccine types and the number of doses. RESULTS: In the SCCS, 343 CoronaVac recipients and 212 BNT162b2 recipients were included. No increased risk of outcomes was observed within the exposure periods. In the cohort study, 108,423 and 83,323 patients received ≥ 2 doses of CoronaVac and BNT162b2, respectively. The VE (95% CI) against COVID-related mortality, hospitalisation, and severe complications after two-dose CoronaVac was 77% (74-80%), 18% (6-23%), and 29% (12-43%), respectively, while for the two-dose regimen of BNT162b2, it was 92% (91-94%), 33% (30-37%), and 57% (45-66%), respectively. Higher VE against COVID-related mortality, hospitalisation, and severe complications was found for the three-dose regimen of CoronaVac (94%, 40%, and 71%) and BNT162b2 (98%, 65%, and 83%). Administering a fourth dose of either vaccine showed additional reductions in COVID-related outcomes. CONCLUSIONS: Among people with COPD and asthma, the COVID-19 vaccines CoronaVac and BNT162b2 did not increase severe exacerbations and achieved moderate-to-high effectiveness against COVID-related outcomes. COVID-19 vaccination remains essential and should be encouraged to protect this vulnerable population in future epidemic waves.

Comparison of Bivalent and Monovalent mRNA Vaccine Boosters.

In this cohort study conducted in Hong Kong where both bivalent and monovalent formulations of BNT162b2 were available, there were no significant differences in the mortality or hospitalization between those who received bivalent and monovalent mRNA as second boosters. Bivalent and monovalent mRNA boosters appear equally protective against clinical outcomes.

Nirmatrelvir/ritonavir use in pregnant women with SARS-CoV-2 Omicron infection: a target trial emulation.

To date, there is a lack of randomized trial data examining the use of the antiviral nirmatrelvir/ritonavir in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected pregnant persons. This target trial emulation study aimed to address this gap by evaluating the use of nirmatrelvir/ritonavir in nonhospitalized pregnant women with symptomatic SARS-CoV-2 Omicron variant infection. Among patients diagnosed between 16 March 2022 and 5 February 2023, exposure was defined as outpatient nirmatrelvir/ritonavir treatment within 5 days of symptom onset or coronavirus disease 2019 (COVID-19) diagnosis. Primary outcomes were maternal morbidity and mortality index (MMMI), all-cause maternal death and COVID-19-related hospitalization, while secondary outcomes were individual components of MMMI, preterm birth, stillbirth, neonatal death and cesarean section. One-to-ten propensity-score matching was conducted between nirmatrelvir/ritonavir users and nonusers, followed by cloning, censoring and weighting. Overall, 211 pregnant women on nirmatrelvir/ritonavir and 1,998 nonusers were included. Nirmatrelvir/ritonavir treatment was associated with reduced 28-day MMMI risk (absolute risk reduction (ARR) = 1.47%, 95% confidence interval (CI) = 0.21-2.34%) but not 28-days COVID-19-related hospitalization (ARR = -0.09%, 95% CI = -1.08% to 0.71%). Nirmatrelvir/ritonavir treatment was also associated with reduced risks of cesarean section (ARR = 1.58%, 95% CI = 0.85-2.39%) and preterm birth (ARR = 2.70%, 95% CI = 0.98-5.31%). No events of maternal or neonatal death or stillbirth were recorded. The findings suggest that nirmatrelvir/ritonavir is an effective treatment in symptomatic pregnant women with SARS-CoV-2 Omicron variant infection.

Vaccine Effectiveness of BNT162b2 and CoronaVac against SARS-CoV-2 Omicron BA.2 in CKD.

BACKGROUND: The ongoing coronavirus disease 2019 (COVID-19) pandemic has posed increased risks of hospitalization and mortality in patients with underlying CKD. Current data on vaccine effectiveness of COVID-19 vaccines are limited to patients with CKD on dialysis and seroconversion in the non-dialysis population. METHODS: A case-control study was conducted of adults with CKD using data extracted from the electronic health record database in Hong Kong. Adults with CKD and COVID-19 confirmed by PCR were included in the study. Each case was matched with up to ten controls attending Hospital Authority services without a diagnosis of COVID-19 on the basis of age, sex, and index date (within three calendar days). The vaccine effectiveness of BNT162b2 and CoronaVac in preventing COVID-19 infection, hospitalizations, and all-cause mortality was estimated using conditional logistic regression adjusted by patients' comorbidities and medication history during the outbreak from January to March 2022. RESULTS: A total of 20,570 COVID-19 cases, 6604 COVID-19-related hospitalizations, and 2267 all-cause mortality were matched to 81,092, 62,803, and 21,348 controls, respectively. Compared with the unvaccinated group, three doses of BNT162b2 or CoronaVac were associated with a reduced risk of infection (BNT162b2: 64% [95% confidence interval (CI), 60 to 67], CoronaVac: 42% [95% CI, 38 to 47]), hospitalization (BNT162b2: 82% [95% CI, 77 to 85], CoronaVac: 80% [95% CI, 76 to 84]), and mortality (BNT162b2: 94% [95% CI, 88 to 97], CoronaVac: 93% [95% CI, 88 to 96]). Vaccines were less effective in preventing infection and hospitalization in the eGFR <15 and 15-29 ml/min per 1.73 m 2 subgroups as compared with higher GFR subgroups. However, receipt of vaccine, even for one dose, was effective in preventing all-cause mortality, with estimates similar to the higher eGFR subgroups, as compared with unvaccinated. CONCLUSIONS: A dose-response relationship was observed between the number of BNT162b2 or CoronaVac doses and the effectiveness against COVID-19 infection and related comorbidity in the CKD population.