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.

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.

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 coronavirus 2019 (COVID-19)-related fractures in older adults are lacking. This study aims to examine the risk of incident major osteoporotic fractures following SARS-CoV-2 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 severe acute respiratory syndrome coronavirus 2 (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 coronavirus 2019 (COVID-19) infection are at a higher risk of suffering from major osteoporotic fractures, ie serious bone fractures related to osteoporosis, compared to those not infected. The study analyzed 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 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.

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.

Optimal timing of nirmatrelvir/ritonavir treatment after COVID-19 symptom onset or diagnosis: target trial emulation.

Reports of symptomatic rebound and/or test re-positivity among COVID-19 patients following the standard five-day treatment course of nirmatrelvir/ritonavir have sparked debates regarding optimal treatment timing and dosage. It is unclear whether initiating nirmatrelvir/ritonavir immediately after symptom onset would improve clinical outcomes and/or lead to post-treatment viral burden rebound due to inadequate viral clearance during treatment. Here we show that, by emulating a randomized target trial using real-world electronic medical record data from all 87,070 adult users of nirmatrelvir/ritonavir in Hong Kong between 16th March 2022 and 15th January 2023, early initiation of nirmatrelvir/ritonavir treatment (0 to 1 days after symptom onset or diagnosis) significantly reduced the incidence of 28-day all-cause mortality and hospitalization compared to delayed initiation (2 or more days) (absolute risk reduction [ARR]: 1.50% (95% confidence interval 1.17-1.80%); relative risk [RR]: 0.77 (0.73, 0.82)), but may be associated with a significant elevated risk of viral burden rebound (ARR: -1.08% (-1.55%, -0.46%)), although the latter estimates were associated with high uncertainty due to limited sample sizes. As such, patients should continue to initiate nirmatrelvir/ritonavir early after symptom onset or diagnosis to better protect against the more serious outcomes of hospitalization and mortality.

Risks of COVID-19-related hospitalisation and mortality among individuals with mental disorders following BNT162b2 and CoronaVac vaccinations: A case-control study.

Concerns have been raised regarding potential weaker vaccine immunogenicity with higher immune suppression for individuals with pre-existing mental disorders. Yet, data on the effectiveness of COVID-19 vaccinations among this vulnerable population are limited. A case-control study was conducted to investigate the risks of COVID-19-related hospitalisation and mortality among individuals with mental disorders following one to three doses of BNT162b2 and CoronaVac vaccinations in Hong Kong. Data were extracted from electronic health records, vaccination and COVID-19 confirmed case records. Conditional logistic regression was applied with adjustment for comorbidities and medication history. Subgroup analyses were performed with stratification: by age (< 65 and ≥ 65) and mental disorders diagnosis (depression, schizophrenia, anxiety disorder, and bipolar disorder). Two doses of BNT162b2 and CoronaVac significantly reduced COVID-19-related hospitalisation and mortality. Further protection for both outcomes was provided after three doses of BNT162b2 and CoronaVac. The vaccine effectiveness magnitude of BNT162b2 was generally higher than CoronaVac, but the difference diminished after the third dose. Individuals with mental disorders should be prioritised in future mass vaccination programmes of booster doses or bivalent COVID-19 vaccines. Targeted strategies should be developed to resolve the reasons behind vaccine hesitancy among this population and increase their awareness on the benefits of vaccination.

Bariatric surgery, novel glucose-lowering agents, and insulin for type 2 diabetes and obesity: Bayesian network meta-analysis of randomized controlled trials.

BACKGROUND: This network meta-analysis aimed to compare the effects of bariatric surgery, novel glucose-lowering agents (SGLT2i, GLP1RA, DPP4i), and insulin for patients with type 2 diabetes mellitus (T2DM) and obesity. METHODS: Four databases were searched from inception to April 2023 to identify randomized controlled trials (RCTs) comparing bariatric surgery, SGLT2i, GLP1RA, DPP4i, insulin, and/or placebo/usual care among patients with T2DM and obesity in the achievement of HbA1c < 7.0 per cent within one year, and 12-month changes in HbA1c and body weight. RESULTS: A total of 376 eligible RCTs (149 824 patients) were analysed. Bariatric surgery had significantly higher rates of achieving HbA1c < 7.0 per cent than SGLT2i (RR = 2.46, 95 per cent c.i. = 1.28, 4.92), DPP4i (RR = 2.59, 95 per cent c.i. = 1.36, 5.13), insulin (RR = 2.27, 95 per cent c.i. = 1.18, 4.58) and placebo/usual care (RR = 4.02, 95 per cent c.i. = 2.13, 7.93), but had no statistically significant difference from GLP1RA (RR = 1.73, 95 per cent c.i. = 0.91, 3.44), regardless of oral (RR = 1.33, 95 per cent c.i. = 0.66, 2.79) or injectable (RR = 1.75, 95 per cent c.i. = 0.92, 3.45) administration. Significantly more GLP1RA patients achieved HbA1c < 7.0 per cent than other non-surgical treatments. Bariatric surgery had the greatest reductions in HbA1c (∼1 per cent more) and body weight (∼15 kg more) at 12 months. Among novel glucose-lowering medications, GLP1RA was associated with greater reductions in HbA1c than SGLT2i (-0.39 per cent, 95 per cent c.i. = -0.55, -0.22) and DPP4i (-0.51 per cent, 95 per cent c.i. = -0.64, -0.39) at 12 months, while GLP1RA (-1.74 kg, 95 per cent c.i. = -2.48, -1.01) and SGLT2i (-2.23 kg, 95 per cent c.i. = -3.07, -1.39) showed greater reductions in body weight than DPP4i at 12 months. CONCLUSION: Bariatric surgery showed superiority in glycaemic control and weight management compared to non-surgical approaches. GLP1RA administered by oral or injectable form demonstrated reduced HbA1c and body weight at 12 months, and was preferable over other non-surgical treatments among patients with T2DM and obesity. PROSPERO REGISTRATION NO: CRD42020201507.

A Web-Based Sexual Health Intervention to Prevent Sexually Transmitted Infections in Hong Kong: Model-Based Cost-Effectiveness Analysis.

BACKGROUND: Sexually transmitted infections (STIs) remain a significant public health concern, particularly among young adults, and Chlamydia trachomatis (CT) infections are the most common STIs in young women. One of the most effective ways to prevent STIs is the consistent use of condoms during sexual intercourse. There has been no economic evaluation of the interactive web-based sexual health program, Smart Girlfriend, within the Chinese population. OBJECTIVE: This study aimed to evaluate the long-term cost-effectiveness of Smart Girlfriend in preventing STIs in the Chinese population. The evaluation compared the program with a control intervention that used a 1-page information sheet on condom use. METHODS: A decision-analytic model that included a decision tree followed by a Markov structure of CT infections was developed since CT is the most prevalent STI among young women. The model represents the long-term experience of individuals who received either the intervention or the control. One-way and probabilistic sensitivity analyses were conducted. The main outcomes were the number of CT infections and the incremental cost as per quality-adjusted life year (QALY). RESULTS: A cohort of 10,000 sexually active nonpregnant young women initially entered the model in a noninfectious state (ie, "well"). In the base-case analysis, the implementation of the Smart Girlfriend program resulted in the prevention of 0.45% of CT infections, 0.3% of pelvic inflammatory disease, and 0.04% of chronic pelvic pain, leading to a gain of 70 discounted QALYs and cost savings over a 4-year time horizon, compared to the control group. With more than 4548 users, the intervention would be cost-effective, and with more than 8315 users, the intervention would be cost saving. A 99% probability of being cost-effective was detected with a willingness to pay US $17,409 per QALY. CONCLUSIONS: Smart Girlfriend is a cost-effective and possibly cost-saving program over a 4-year time horizon. This result was particularly sensitive to the number of website users; launching the website would be cost-effective if more than 4548 people used it. Further work is warranted to explore if the findings could be expanded to apply to women who have sex with women and in the context of other STIs. TRIAL REGISTRATION: ClinicalTrial.gov NCT03695679; https://clinicaltrials.gov/study/NCT03695679.

Risk of autoimmune diseases following COVID-19 and the potential protective effect from vaccination: a population-based cohort study.

Background: Case reports suggest that SARS-CoV-2 infection could lead to immune dysregulation and trigger autoimmunity while COVID-19 vaccination is effective against severe COVID-19 outcomes. We aim to examine the association between COVID-19 and development of autoimmune diseases (ADs), and the potential protective effect of COVID-19 vaccination on such an association. Methods: A retrospective cohort study was conducted in Hong Kong between 1 April 2020 and 15 November 2022. COVID-19 was confirmed by positive polymerase chain reaction or rapid antigen test. Cox proportional hazard regression with inverse probability of treatment weighting was applied to estimate the risk of incident ADs following COVID-19. COVID-19 vaccinated population was compared against COVID-19 unvaccinated population to examine the protective effect of COVID-19 vaccination on new ADs. Findings: The study included 1,028,721 COVID-19 and 3,168,467 non-COVID individuals. Compared with non-COVID controls, patients with COVID-19 presented an increased risk of developing pernicious anaemia [adjusted Hazard Ratio (aHR): 1.72; 95% Confidence Interval (CI): 1.12-2.64]; spondyloarthritis [aHR: 1.32 (95% CI: 1.03-1.69)]; rheumatoid arthritis [aHR: 1.29 (95% CI: 1.09-1.54)]; other autoimmune arthritis [aHR: 1.43 (95% CI: 1.33-1.54)]; psoriasis [aHR: 1.42 (95% CI: 1.13-1.78)]; pemphigoid [aHR: 2.39 (95% CI: 1.83-3.11)]; Graves' disease [aHR: 1.30 (95% CI: 1.10-1.54)]; anti-phospholipid antibody syndrome [aHR: 2.12 (95% CI: 1.47-3.05)]; immune mediated thrombocytopenia [aHR: 2.1 (95% CI: 1.82-2.43)]; multiple sclerosis [aHR: 2.66 (95% CI: 1.17-6.05)]; vasculitis [aHR: 1.46 (95% CI: 1.04-2.04)]. Among COVID-19 patients, completion of two doses of COVID-19 vaccine shows a decreased risk of pemphigoid, Graves' disease, anti-phospholipid antibody syndrome, immune-mediated thrombocytopenia, systemic lupus erythematosus and other autoimmune arthritis. Interpretation: Our findings suggested that COVID-19 is associated with an increased risk of developing various ADs and the risk could be attenuated by COVID-19 vaccination. Future studies investigating pathology and mechanisms would be valuable to interpreting our findings. Funding: Supported by RGC Collaborative Research Fund (C7154-20GF).

Discharge of postoperative patients with an opioid prescription is associated with increased persistent opioid use, healthcare expenditures and mortality: a retrospective cohort study.

BACKGROUND: The risk factors for persistent opioid use after surgical discharge and the association between opioid prescription at discharge and postoperative emergency department visits, readmission, and mortality are unclear. METHODS: This population-based retrospective cohort study involved opioid-naive patients who underwent surgical procedures from January 1, 2000 to November 30, 2020. The data source was Hong Kong Hospital Authority Clinical Management System electronic health record. The primary outcome was the incidence of new persistent opioid use. Other study outcomes included 30-day emergency department visits, 30-day readmission, and 30-day all-cause mortality. Multivariable logistic regression models were used to estimate the association between opioid prescription at discharge and persistent opioid use, emergency department visits, readmission, and all-cause mortality. RESULTS: Over a median follow-up of 1 month with 36 104 person-years, 438 128 patients (opioid prescription: 32 932, no opioid prescription: 405 196) who underwent surgical procedures were analysed, of whom 15 112 (3.45%) had persistent opioid use after discharge. Prescribing opioids on discharge was associated with increased risks of developing persistent opioid use (odds ratio [OR]: 2.30, 95% confidence interval [CI]: 2.19-2.40, P<0.001), 30-day emergency department visits (OR: 1.28, 95% CI: 1.23-1.33, P<0.001), 30-day readmission (OR: 1.17, 95% CI: 1.13-1.20, P<0.001), and 30-day all-cause mortality (OR: 1.68, 95% CI: 1.53-1.86, P<0.001). CONCLUSIONS: In this large cohort of patients undergoing surgery, an opioid prescription on discharge was associated with a higher chance of persistent opioid use and increased risks of postoperative emergency department visits, readmission, and mortality. Minimising opioid prescriptions on discharge could improve perioperative patient outcomes.

Risk of Adverse Events and Delirium after COVID-19 Vaccination in Patients Living with Dementia.

OBJECTIVES: The aim of this study was to compare incidences of adverse events of special interest (AESI) and delirium in 3 cohorts: after COVID-19 vaccination, prepandemic, and SARS-CoV-2 polymerase chain reaction (PCR) test positive. DESIGN: This is a population-based cohort study using electronic medical records linked with vaccination records in Hong Kong. SETTING AND PARTICIPANTS: A total of 17,449 older people with dementia received at least 1 dose of CoronaVac (n = 14,719) or BNT162b2 (n = 2730) between February 23, 2021, and March 31, 2022. Moreover, 43,396 prepandemic and 3592 SARS-CoV-2 test positive patients were also included in this study. METHODS: The incidences of AESI and delirium up to 28 days after vaccination in the vaccinated dementia cohort were compared with the prepandemic and SARS-CoV-2 test positive dementia cohorts by calculating incidence rate ratios (IRRs). Patients who received multiple doses were followed up separately for each dose, up to the third dose. RESULTS: We did not detect an increased risk of delirium and most AESI following vaccination compared to the prepandemic period and those tested positive for SARS-CoV-2. No AESI group nor delirium incidence exceeded 10 per 1000 person-days in vaccinated individuals. CONCLUSIONS AND IMPLICATIONS: The findings provide evidence for the safe use of COVID-19 vaccines in older patients with dementia. In the short run, benefit appears to outweigh the harm due to vaccine; however, longer follow-up should be continued to identify remote adverse events.

Vaccine effectiveness of BNT162b2 and CoronaVac against SARS-CoV-2 omicron infection and related hospital admission among people with substance use disorder in Hong Kong: a matched case-control study.

BACKGROUND: People with substance use disorder have a high risk of SARS-CoV-2 infection and subsequent poor outcomes. Few studies have evaluated COVID-19 vaccine effectiveness among people with substance use disorder. We aimed to estimate the vaccine effectiveness of BNT162b2 (Fosun-BioNTech) and CoronaVac (Sinovac) against SARS-CoV-2 omicron (B.1.1.529) infection and related hospital admission in this population. METHODS: We did a matched case-control study using electronic health databases in Hong Kong. Individuals diagnosed with substance use disorder between Jan 1, 2016, and Jan 1, 2022, were identified. People aged 18 years and older with SARS-CoV-2 infection from Jan 1 to May 31, 2022, and people with COVID-19-related hospital admission from Feb 16 to May 31, 2022, were included as cases and were matched by age, sex, and previous clinical history with controls from all individuals diagnosed with substance use disorder who attended the Hospital Authority health services: up to three controls for SARS-CoV-2 infection and up to ten controls for hospital admission. Conditional logistical regression was used to evaluate the association between vaccination status (ie, one, two, or three doses of BNT162b2 or CoronaVac) and the risk of SARS-CoV-2 infection and COVID-19-related hospital admission, adjusted for baseline comorbidities and medication use. FINDINGS: Among 57 674 individuals with substance use disorder, 9523 people with SARS-CoV-2 infections (mean age 61·00 years, SD 14·90; 8075 [84·8%] males and 1448 [15·2%] females) were identified and matched to 28 217 controls (mean age 60·99 years, 14·67; 24 006 [85·1%] males and 4211 [14·9%] females), and 843 people with COVID-19-related hospital admissions (mean age 70·48 years, SD 14·68; 754 [89·4%] males and 89 [10·6%] females) were identified and matched to 7459 controls (mean age 70·24 years, 13·87; 6837 [91·7%] males and 622 [8·3%] females). Data on ethnicity were not available. We observed significant vaccine effectiveness against SARS-CoV-2 infection for two-dose BNT162b2 vaccination (20·7%, 95% CI 14·0-27·0, p<0·0001) and three-dose vaccination (all BNT162b2 41·5%, 34·4-47·8, p<0·0001; all CoronaVac 13·6%, 5·4-21·0, p=0·0015; BNT162b2 booster after two-dose CoronaVac 31·3%, 19·8-41·1, p<0·0001), but not for one dose of either vaccine or two doses of CoronaVac. Significant vaccine effectiveness against COVID-19-related hospital admission was detected after one dose of BNT162b2 vaccination (35·7%, 3·8-57·1, p=0·032), two-dose vaccination (both BNT162b2 73·3%, 64·3 to 80·0, p<0·0001; both CoronaVac 59·9%, 50·2-67·7, p<0·0001), and three-dose vaccination (all BNT162b2 86·3%, 75·6-92·3, p<0·0001; all CoronaVac 73·5% 61·0-81·9, p<0·0001; BNT162b2 booster after two-dose CoronaVac 83·7%, 64·6-92·5, p<0·0001), but not after one dose of CoronaVac. INTERPRETATION: For both BNT162b2 and CoronaVac, two-dose or three-dose vaccination was protective against COVID-19-related hospital admission and the booster dose provided protection against SARS-CoV-2 infection among people with substance use disorder. Our findings confirm the importance of booster doses in this population during the period dominated by the omicron variant. FUNDING: Health Bureau, the Government of the Hong Kong Special Administrative Region.

Analysis of All-Cause Hospitalization and Death Among Nonhospitalized Patients With Type 2 Diabetes and SARS-CoV-2 Infection Treated With Molnupiravir or Nirmatrelvir-Ritonavir During the Omicron Wave in Hong Kong.

Importance: Diabetes and COVID-19 are both global pandemics, and type 2 diabetes is a common comorbidity in patients with acute COVID-19 and is proven to be a key determinant of COVID-19 prognosis. Molnupiravir and nirmatrelvir-ritonavir are oral antiviral medications recently approved for nonhospitalized patients with mild to moderate COVID-19, following demonstration of their efficacies in reducing adverse outcomes of the disease; it is crucial to clarify whether both oral antiviral medications are efficacious in a population consisting exclusively of patients with type 2 diabetes. Objective: To evaluate the effectiveness of molnupiravir and nirmatrelvir-ritonavir in a contemporary population-based cohort comprising exclusively nonhospitalized patients with type 2 diabetes and SARS-CoV-2 infection. Design, Setting, and Participants: This retrospective cohort study was performed using population-based electronic medical record data for patients in Hong Kong with type 2 diabetes and confirmed SARS-CoV-2 infection between February 26 and October 23, 2022. Each patient was followed up until death, outcome event, crossover of oral antiviral treatment, or end of the observational period (October 30, 2022), whichever came first. Outpatient oral antiviral users were divided into molnupiravir and nirmatrelvir-ritonavir treatment groups, respectively, and nontreated control participants were matched through 1:1 propensity score matching. Data analysis was performed on March 22, 2023. Exposures: Molnupiravir (800 mg twice daily for 5 days) or nirmatrelvir-ritonavir (300 mg nirmatrelvir and 100 mg ritonavir twice daily for 5 days, or 150 mg nirmatrelvir and 100 mg ritonavir for patients with an estimated glomerular filtration rate of 30-59 mL/min per 1.73 m2). Main Outcomes and Measures: The primary outcome was a composite of all-cause mortality and/or hospitalization. The secondary outcome was in-hospital disease progression. Hazard ratios (HRs) were estimated with Cox regression. Results: This study identified 22 098 patients with type 2 diabetes and COVID-19. A total of 3390 patients received molnupiravir and 2877 received nirmatrelvir-ritonavir in the community setting. After application of exclusion criteria followed by 1:1 propensity score matching, this study comprised 2 groups. One group included 921 molnupiravir users (487 men [52.9%]), with a mean (SD) age of 76.7 (10.8) years, and 921 control participants (482 men [52.3%]), with a mean (SD) age of 76.6 (11.7) years. The other group included 793 nirmatrelvir-ritonavir users (401 men [50.6%]), with a mean (SD) age of 71.7 (11.5) years, and 793 control participants (395 men [49.8%]), with a mean (SD) age of 71.9 (11.6) years. At a median follow-up of 102 days (IQR, 56-225 days), molnupiravir use was associated with a lower risk of all-cause mortality and/or hospitalization (HR, 0.71 [95% CI, 0.64-0.79]; P < .001) and in-hospital disease progression (HR, 0.49 [95% CI, 0.35-0.69]; P < .001) compared with nonuse. At a median follow-up of 85 days (IQR, 56-216 days), nirmatrelvir-ritonavir use was associated with a lower risk of all-cause mortality and/or hospitalization (HR, 0.71 [95% CI, 0.63-0.80]; P < .001) and a nonsignificantly lower risk of in-hospital disease progression (HR, 0.92 [95% CI, 0.59-1.44]; P = .73) compared with nonuse. Conclusions and Relevance: These findings suggest that both molnupiravir and nirmatrelvir-ritonavir oral antiviral medications were associated with a lower risk of all-cause mortality and hospitalization among patients with COVID-19 and type 2 diabetes. Further studies in specific populations, such as individuals in residential care homes and individuals with chronic kidney disease, are suggested.

BNT162b2 or CoronaVac Vaccinations Are Associated With a Lower Risk of Myocardial Infarction and Stroke After SARS-CoV-2 Infection Among Patients With Cardiovascular Disease.

Background COVID-19 vaccines have demonstrated effectiveness against SARS-CoV-2 infection, hospitalization, and mortality. The association between vaccination and risk of cardiovascular complications shortly after SARS-CoV-2 infection among patients with cardiovascular disease remains unknown. Methods and Results A case-control study was conducted with cases defined as patients who had myocardial infarction or stroke within 28 days after SARS-CoV-2 infection between January 1, 2022 and August 15, 2022. Controls were defined as all other patients who attended any health services and were not cases. Individuals without history of cardiovascular disease were excluded. Each case was randomly matched with 10 controls according to sex, age, Charlson comorbidity index, and date of hospital admission. Adjusted odds ratio with 95% CI was estimated using conditional logistic regression. We identified 808 cases matched with 7771 controls among all patients with cardiovascular disease. Results showed that vaccination with BNT162b2 or CoronaVac was associated with a lower risk of myocardial infarction or stroke after SARS-CoV-2 infection with a dose-response relationship. For BNT162b2, risk decreased from 0.49 (95% CI, 0.29-0.84) to 0.30 (95% CI, 0.20-0.44) and 0.17 (95% CI, 0.08-0.34) from 1 to 3 doses, respectively. Similar trends were observed for CoronaVac, with risk decreased from 0.69 (95% CI, 0.57-0.85) to 0.42 (95% CI, 0.34-0.52) and 0.32 (95% CI, 0.21-0.49) from 1 to 3 doses, respectively. Conclusions Vaccination with BNT162b2 or CoronaVac is associated with a lower risk of myocardial infarction or stroke after SARS-CoV-2 infection among patients with cardiovascular disease.

Viral burden rebound in hospitalised patients with COVID-19 receiving oral antivirals in Hong Kong: a population-wide retrospective cohort study.

BACKGROUND: Viral rebound after nirmatrelvir-ritonavir treatment has implications for the clinical management and isolation of patients with COVID-19. We evaluated an unselected, population-wide cohort to identify the incidence of viral burden rebound and associated risk factors and clinical outcomes. METHODS: We did a retrospective cohort study of hospitalised patients with a confirmed diagnosis of COVID-19 in Hong Kong, China, for an observation period from Feb 26 to July 3, 2022 (during the omicron BA.2.2 variant wave). Adult patients (age ≥18 years) admitted 3 days before or after a positive COVID-19 test were selected from medical records held by the Hospital Authority of Hong Kong. We included patients with non-oxygen-dependent COVID-19 at baseline receiving either molnupiravir (800 mg twice a day for 5 days), nirmatrelvir-ritonavir (nirmatrelvir 300 mg with ritonavir 100 mg twice a day for 5 days), or no oral antiviral treatment (control group). Viral burden rebound was defined as a reduction in cycle threshold (Ct) value (≥3) on quantitative RT-PCR test between two consecutive measurements, with such decrease sustained in an immediately subsequent Ct measurement (for those patients with ≥3 Ct measurements). Logistic regression models were used to identify prognostic factors for viral burden rebound, and to assess associations between viral burden rebound and a composite clinical outcome of mortality, intensive care unit admission, and invasive mechanical ventilation initiation, stratified by treatment group. FINDINGS: We included 4592 hospitalised patients with non-oxygen-dependent COVID-19 (1998 [43·5%] women and 2594 [56·5%] men). During the omicron BA.2.2 wave, viral burden rebound occurred in 16 of 242 patients (6·6% [95% CI 4·1-10·5]) receiving nirmatrelvir-ritonavir, 27 of 563 (4·8% [3·3-6·9]) receiving molnupiravir, and 170 of 3787 (4·5% [3·9-5·2]) in the control group. The incidence of viral burden rebound did not differ significantly across the three groups. Immunocompromised status was associated with increased odds of viral burden rebound, regardless of antiviral treatment (nirmatrelvir-ritonavir: odds ratio [OR] 7·37 [95% CI 2·56-21·26], p=0·0002; molnupiravir: 3·05 [1·28-7·25], p=0·012; control: 2·21 [1·50-3·27], p<0·0001). Among patients receiving nirmatrelvir-ritonavir, the odds of viral burden rebound were higher in those aged 18-65 years (vs >65 years; 3·09 [1·00-9·53], p=0·050), those with high comorbidity burden (score >6 on the Charlson Comorbidity Index; 6·02 [2·09-17·38], p=0·0009), and those concomitantly taking corticosteroids (7·51 [1·67-33·82], p=0·0086); whereas the odds were lower in those who were not fully vaccinated (0·16 [0·04-0·67], p=0·012). In patients receiving molnupiravir, those aged 18-65 years (2·68 [1·09-6·58], p=0·032) or on concomitant corticosteroids (3·11 [1·23-7·82], p=0·016) had increased odds of viral burden rebound. We found no association between viral burden rebound and occurrence of the composite clinical outcome from day 5 of follow-up (nirmatrelvir-ritonavir: adjusted OR 1·90 [0·48-7·59], p=0·36; molnupiravir: 1·05 [0·39-2·84], p=0·92; control: 1·27 [0·89-1·80], p=0·18). INTERPRETATION: Viral burden rebound rates are similar between patients with antiviral treatment and those without. Importantly, viral burden rebound was not associated with adverse clinical outcomes. FUNDING: Health and Medical Research Fund, Health Bureau, The Government of the Hong Kong Special Administrative Region, China. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Estimating the transmission dynamics of SARS-CoV-2 Omicron BF.7 in Beijing after adjustment of the zero-COVID policy in November-December 2022.

We tracked the effective reproduction number (Rt) of the predominant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant Omicron BF.7 in Beijing in November-December 2022 by fitting a transmission dynamic model parameterized with real-time mobility data to (i) the daily number of new symptomatic cases on 1-11 November (when China's zero-COVID interventions were still strictly enforced) and (ii) the proportion of individuals who participated in online polls on 10-22 December and self-reported to have been test-positive since 1 November. After China's announcement of 20 measures to transition from zero-COVID, we estimated that Rt increased to 3.44 (95% credible interval (CrI): 2.82-4.14) on 18 November and the infection incidence peaked on 11 December. We estimated that the cumulative infection attack rate (IAR; that is, proportion of the population infected since 1 November) in Beijing was 75.7% (95% CrI: 60.7-84.4) on 22 December 2022 and 92.3% (95% CrI: 91.4-93.1) on 31 January 2023. Surveillance programs should be rapidly set up to monitor the evolving epidemiology and evolution of SARS-CoV-2 across China.