Aspirin is associated with lower risks of severe covid-19 disease: a population-based study

IntroductionThe use of aspirin has been hypothesized to improve severe clinical outcomes in COVID-19 infection. The present study aims to evaluate the effect of both antecedent and inpatient aspirin use, individually and concomitant with other medications, on severe disease outcomes in COVID-19 positive patients treated with steroids/antiviral therapy.MethodsConsecutive patients who attended Hong Kong's public hospitals or outpatient clinics between 1st January and 8th December 2020 for COVID-19 reverse transcription-polymerase chain reaction (RT-PCR) and received steroids/antiviral therapy were included. Propensity score matching (1:1) between aspirin users and non-users was performed. The primary endpoint was the composite outcome of the need for intubation and 30-day all-cause mortality.ResultsA total of 2664 RT-PCR positive and hospitalized COVID-19 patients receiving steroids/antiviral therapy were included (male= 50.7%, baseline age= 52.3 [35.2-64.6] years old). Over follow-up, 2.96% suffered from 30-day all-cause mortality. Univariable logistic regression showed that aspirin use was associated with lower odds of severe COVID-19 in the propensity score-matched cohort (odds ratio [OR]: 0.33, 95% confidence interval [CI]: [0.18, 0.6];P=0.0003). This association remained significant following adjustment for significant confounders (OR= 0.33, 95% CI= [0.18, 0.59], P= 0002).ConclusionAspirin use was associated with lower odds of severe outcomes in COVID-19.Conflict of InterestNone

Post-acute sequelae of COVID-19 in older persons: multi-organ complications and mortality.

INTRODUCTION: Evidence on long-term associations between COVID-19 and risks of multi-organ complications and mortality in older population is limited. This study evaluates these associations. RESEARCH DESIGN AND METHODS: The cohorts included patients aged ≥60 year diagnosed with COVID-19 infection (cases), between 16 March 2020 and 31 May 2021 from the UK Biobank (UKB cohort, n = 11 330); and between 01 April 2020 and 31 May 2022 from the electronic health records in Hong Kong (HK cohort, n = 213 618). Each patient was randomly matched with up to 10 individuals without COVID-19 infection based on age and sex (UKB, n = 325 812; HK, n = 1 411 206) and were followed for up to 18 months until 31 August 2021 for UKB, and up to 28 months until 15 August 2022 for HK cohort. Caracteristics between cohorts were further adjusted with propensity score-based marginal mean weighting through stratification. For evaluating long-term association of COVID-19 with multi-organ disease complications and mortality after 21-days of diagnosis, Cox regression was employed. RESULT: Older adults with COVID-19 were associated with a significantly higher risk of cardiovascular outcomes [major cardiovascular disease (stroke, heart failure and coronary heart disease): hazard ratio (UKB): 1.4 (95% Confidence interval: 1.2,1.7), HK:1.2 (95% CI: 1.1,1.3)]; myocardial infarction: HR (UKB): 1.8 (95% CI: 1.4,2.5), HK:1.2 (95% CI: 1.1,1.5)]; respiratory outcomes [interstitial lung disease: HR (UKB: 3.5 (95% CI: 2.6,4.7), HK:6.6 (95% CI: 2.1,21.2); chronic pulmonary disease: HR (UKB): 1.6 (95% CI: 1.2,2.1), HK:1.7 (95% CI: 1.4,2.1)]; neuropsychiatric outcomes [seizure: HR (UKB): 2.7 (95% CI: 1.7,4.2), HK:1.8 (95% CI: 1.4,2.3)]; and renal outcomes [acute kidney disease: HR (UKB): 1.4 (95% CI: 1.1,1.6), HK:1.7 (95% CI: 1.4,2.1)]; and all-cause mortality [HR (UKB): 4.8 (95% CI: 4.4,5.4), HK:2.7 (95% CI: 2.6,2.8)]. CONCLUSION: COVID-19 is associated with long-term risks of multi-organ complications in older adults (aged ≥60). Infected patients in this age-group may benefit from appropriate monitoring of signs/symptoms for developing these complications.

Efficacy and effectiveness of inactivated vaccines against symptomatic COVID-19, severe COVID-19, and COVID-19 clinical outcomes in the general population: a systematic review and meta-analysis.

Background: Inactivated, whole-virion vaccines have been used extensively in the SARS-CoV-2 pandemic. Its efficacy and effectiveness across regions have not been systematically evaluated. Efficacy refers to how well a vaccine performs in a controlled environment. Effectiveness refers to how well it performs in real world settings. Methods: This systematic review and meta-analysis reviewed published, peer-reviewed evidence on all WHO-approved inactivated vaccines and evaluated their efficacy and effectiveness against SARS-CoV-2 infection, symptomatic infection, severe clinical outcomes, and severe COVID-19. We searched Pubmed (including MEDLINE), EMBASE (via OVID), Web of Science Core Collection, Web of Science Chinese Science Citation Database, and Clinicaltrials.gov. Findings: The final pool included 28 studies representing over 32 million individuals reporting efficacy or effectiveness estimates of complete vaccination using any approved inactivated vaccine between January 1, 2019 and June 27, 2022. Evidence was found for efficacy and effectiveness against symptomatic infection (OR 0.21, 95% CI 0.16-0.27, I2 = 28% and OR 0.32, 95% CI 0.16-0.64, I2 = 98%, respectively) and infection (OR 0.53, 95% CI 0.49-0.57, I2 = 90% and OR 0.31, 95% CI 0.24-0.41, I2 = 0%, respectively) for early SARS-CoV-2 variants of concern (VoCs) (Alpha, Delta), and for waning of vaccine effectiveness with more recent VoCs (Gamma, Omicron). Effectiveness remained robust against COVID-related ICU admission (OR 0.21, 95% CI 0.04-1.08, I2 = 99%) and death (OR 0.08, 95% CI 0.00-2.02, I2 = 96%), although effectiveness estimates against hospitalization (OR 0.44, 95% CI 0.37-0.53, I2 = 0%) were inconsistent. Interpretation: This study showed evidence of efficacy and effectiveness of inactivated vaccines for all outcomes, although inconsistent reporting of key study parameters, high heterogeneity of observational studies, and the small number of studies of particular designs for most outcomes undermined the reliability of the findings. Findings highlight the need for additional research to address these limitations so that more definitive conclusions can be drawn to inform SARS-CoV-2 vaccine development and vaccination policies. Funding: Health and Medical Research Fund on COVID-19, Health Bureau of the Government of the Hong Kong SAR.

Benefits v. risks of COVID-19 vaccination: an examination of vaccination policy impact on the occurrence of myocarditis and pericarditis.

Studies of myocarditis/pericarditis following mRNA COVID-19 vaccines in Hong Kong have been published. Data are consistent with data from other active surveillance or healthcare databases. The mRNA COVID-19 vaccines have been shown to rarely increase risk of myocarditis, with the highest risk among males aged 12-17 after the second dose. An increased risk of pericarditis has also been shown after the second dose, though less common than myocarditis and more evenly distributed among different sex and age groups. Because of the increased risk of post-vaccine myocarditis, Hong Kong implemented a single dose mRNA COVID-19 vaccine policy on September 15, 2021 for adolescents (age 12-17 years). Post-policy, there were no cases of carditis. 40,167 first dose patients did not receive a second dose. This policy was highly successful in the reduction of carditis, but the trade-off is the potential risk of disease and cost to population-level immunity. This commentary brings forward some important global policy considerations.

Waning effectiveness against COVID-19-related hospitalization, severe complications, and mortality with two to three doses of CoronaVac and BNT162b2: a case-control study.

BACKGROUND: This study aims to evaluate waning effectiveness against severe and fatal COVID-19 with two to three doses of CoronaVac/BNT162b2, where data are limited. METHODS: A case-control study included individuals aged ≥18 years, unvaccinated or received two to three doses of CoronaVac/BNT162b2, using electronic healthcare databases in Hong Kong. Those with first COVID-19-related hospitalization, severe complications, or mortality between 1 January and 15 August 2022 were defined as cases and matched with up-to-10 controls by age, sex, index date, and Charlson Comorbidity Index. Vaccine effectiveness (VE) against COVID-19-related outcomes was estimated at different time intervals from second and third-dose vaccination (0-13 up-to 210-240 days) using conditional logistic regression adjusted for comorbidities and medications. RESULTS: By 211-240 days after second dose, VE against COVID-19-related hospitalization reduced to 46.6% (40.7-51.8%) for BNT162b2 and 36.2% (28.0-43.4%) for CoronaVac, and VE against COVID-19-related mortality were 73.8% (55.9-84.4%) and 76.6% (60.8-86.0%). After third dose, VE against COVID-19-related hospitalization decreased from 91.2% (89.5-92.6%) for BNT162b2 and 76.7% (73.7-79.4%) for CoronaVac at 0-13 days, to 67.1% (60.4-72.6%) and 51.3% (44.2-57.5%) at 91-120 days. VE against COVID-19-related mortality for BNT162b2 remained high from 0-13 days [98.2% (95.0-99.3%)] to 91-120 days [94.6% (77.7-98.7%)], and for CoronaVac reduced from 0-13 days [96.7% (93.2-98.4%)] to 91-120 days [86.4% (73.3-93.1%)]. CONCLUSIONS: Significant risk reduction against COVID-19-related hospitalization and mortality after CoronaVac or BNT162b2 vaccination was observed for >240 and >120 days after second and third doses compared to unvaccinated, despite significant waning over time. Timely administration of booster doses could provide higher levels of protection.

Long-term post-acute sequelae of COVID-19 infection: a retrospective, multi-database cohort study in Hong Kong and the UK.

Background: Evidence on post-acute sequelae of SARS-CoV-2 (PASC) has shown inconsistent findings. This study aimed to generate coherent evidence on the post-acute sequelae of COVID-19 infection using electronic healthcare records across two regions. Methods: In this retrospective, multi-database cohort study, patients with COVID-19 aged 18 or above between April 1st 2020 and May 31st 2022 from the Hong Kong Hospital Authority (HKHA) and March 16th 2020 and May 31st 2021 from the UK Biobank (UKB) databases and their matched controls were followed for up to 28 and 17 months, respectively. Covariates between patients with COVID-19 and non-COVID-19 controls were adjusted using propensity score-based inverse probability treatment weighting. Cox proportional regression was used to estimate the hazard ratio (HR) of clinical sequelae, cardiovascular, and all-cause mortality 21 days after COVID-19 infection. Findings: A total of 535,186 and 16,400 patients were diagnosed with COVID-19 from HKHA and UKB, of whom 253,872 (47.4%) and 7613 (46.4%) were male, with a mean age (±SD) of 53.6 (17.8) years and 65.0 (8.5) years, respectively. Patients with COVID-19 incurred greater risk of heart failure (HR 1.82; 95% CI 1.65, 2.01), atrial fibrillation (1.31; 1.16, 1.48), coronary artery disease (1.32; 1.07, 1.63), deep vein thrombosis (1.74; 1.27, 2.37), chronic pulmonary disease (1.61; 1.40, 1.85), acute respiratory distress syndrome (1.89; 1.04, 3.43), interstitial lung disease (3.91; 2.36, 6.50), seizure (2.32; 1.12, 4.79), anxiety disorder (1.65; 1.29, 2.09), post-traumatic stress disorder (1.52; 1.23, 1.87), end-stage renal disease (1.76; 1.31, 2.38), acute kidney injury (2.14; 1.69, 2.71), pancreatitis (1.42; 1.10, 1.83), cardiovascular (2.86; 1.25, 6.51) and all-cause mortality (4.16; 2.11, 8.21) mortality during their post-acute phase of infection. Interpretation: The consistent greater risk of PASC highlighted the need for sustained multi-disciplinary care for COVID-19 survivors. Funding: Health Bureau, The Government of the Hong Kong Special Administrative Region, Collaborative Research Fund, The Government of the Hong Kong Special Administrative Region and AIR@InnoHK, administered by the Innovation and Technology Commission, The Government of the Hong Kong Special Administrative Region.

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.

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 three cohorts: after COVID-19 vaccination, pre-pandemic 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 one dose of CoronaVac (n=14,719) or BNT162b2 (n=2730) between 23 February 2021 and 31 March 2022. 43,396 pre-pandemic 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 pre-pandemic 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 pre-pandemic 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.

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.

Risk of glomerular diseases, proteinuria and hematuria following mRNA (BNT162b2) and inactivated (CoronaVac) SARS-CoV-2 vaccines.

BACKGROUND: With accruing case reports on de novo or relapsing glomerular diseases (GD) following different severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines, we evaluated the risk of GD following BNT162b2 and CoronaVac vaccines. METHODS: A modified self-controlled case series analysis was conducted using anonymized, territory-wide SARS-CoV-2 vaccination records in Hong Kong. All Hong Kong residents aged 18 years or above with outcomes of interest were included. Outcomes of interest were GD, proteinuria or hematuria within 42 days following each dose of SARS-CoV-2 vaccines. Incidence per 100 000 doses of SARS-CoV-2 vaccines administered was calculated, and incidence rate ratios (IRRs) were estimated using conditional Poisson regression with seasonality adjustment. RESULTS: Between 23 February 2021 and 31 March 2022, 4062 patients had an incident diagnosis of GD, proteinuria or hematuria, with 2873 of them being vaccinated during the observation period. The incidences of the composite events 1-41 days after vaccination were 3.7 (95% CI 3.1-4.4) per 100 000 doses of BNT162b2 administered, and 6.5 (95% CI 5.7-7.5) per 100 000 doses CoronaVac administered. There was no significant increase in the risks of composite events following the first (BNT162b2: IRR = 0.76, 95% CI 0.56-1.03; CoronaVac: IRR = 0.92, 95% CI 0.72-1.19), second (BNT162b2: IRR = 0.92, 95% CI 0.72-1.17; CoronaVac: IRR = 0.88. 95% CI 0.68-1.14) or third (BNT162b2: IRR = 0.39. 95% CI 0.15-1.03; CoronaVac: IRR = 1.18. 95% CI 0.53-2.63) dose of SARS-CoV-2 vaccines. CONCLUSIONS: There was no evidence of increased risks of de novo or relapsing GD with either BNT162b2 or CoronaVac vaccines.

Risk of carditis after three doses of vaccination with mRNA (BNT162b2) or inactivated (CoronaVac) covid-19 vaccination: a self-controlled cases series and a case–control study

Background Large-scale comparative research exploring the risk after the third dose and after inactivated covid-19 vaccination is limited. This study aimed to assess the risk of carditis following three doses of BNT162b2 or CoronaVac. Methods We conducted a self-controlled case series (SCCS) and a case–control study using electronic health and vaccination records in Hong Kong. Carditis incidents within 28 days of covid-19 vaccination were included as cases. In the case–control study, up to 10 hospitalized controls were selected with stratified probability sampling by age, sex, and hospital admission (±1 day). The incidence rate ratios (IRRs) were reported from conditional Poisson regressions for SCCS, and adjusted odds ratios (ORs) were reported from multivariable logistic regressions. Findings A total of 8,924,614 doses of BNT162b2 and 6,129,852 doses of CoronaVac were administered from February 2021 to March 2022. The SCCS detected increased carditis risks after BNT162b2: 4.48 (95%confidence interval [CI]:2.99–6.70] in 1–14 days and 2.50 (95%CI:1.43–4.38) in 15–28 days after first dose;10.81 (95%CI:7.63–15.32) in 1–14 days and 2.95 (95%CI:1.82–4.78) in 15–28 days after second dose;4.72 (95%CI:1.40–15.97) in 1–14 days after third dose. Consistent results were observed from the case–control study. Risks were specifically found in people aged below 30 years and males. No significant risk increase was observed after CoronaVac in all primary analyses. Interpretations We detected increased carditis risks within 28 days after all three doses of BNT162b2 but the risk after the third doses were not higher than that of the second dose when compared with baseline period. Continuous monitoring of carditis after both mRNA and inactivated covid-19 vaccines is needed. Funding : This study was funded by Hong Kong 10.13039/501100005407Health Bureau (COVID19F01).

Drug Repurposing for the Treatment of COVID-19: A Knowledge Graph Approach.

Identifying effective drug treatments for COVID-19 is essential to reduce morbidity and mortality. Although a number of existing drugs have been proposed as potential COVID-19 treatments, effective data platforms and algorithms to prioritize drug candidates for evaluation and application of knowledge graph for drug repurposing have not been adequately explored. A COVID-19 knowledge graph by integrating 14 public bioinformatic databases containing information on drugs, genes, proteins, viruses, diseases, symptoms and their linkages is developed. An algorithm is developed to extract hidden linkages connecting drugs and COVID-19 from the knowledge graph, to generate and rank proposed drug candidates for repurposing as treatments for COVID-19 by integrating three scores for each drug: motif scores, knowledge graph PageRank scores, and knowledge graph embedding scores. The knowledge graph contains over 48 000 nodes and 13 37 000 edges, including 13 563 molecules in the DrugBank database. From the 5624 molecules identified by the motif-discovery algorithms, ranking results show that 112 drug molecules had the top 2% scores, of which 50 existing drugs with other indications approved by health administrations reported. The proposed drug candidates serve to generate hypotheses for future evaluation in clinical trials and observational studies.

The indirect impact of the COVID-19 pandemic on people with type 2 diabetes mellitus and without COVID-19 infection: Systematic review and meta-analysis

Background The effect directly from the coronavirus disease 2019 (COVID-19) infection on health and fatality has received considerable attention, particularly among people with type 2 diabetes mellitus (T2DM). However, evidence on the indirect impact of disrupted healthcare services during the pandemic on people with T2DM is limited. This systematic review aims to assess the indirect impact of the pandemic on the metabolic management of T2DM people without a history of COVID-19 infection. Methods PubMed, Web of Science, and Scopus were systematically searched for studies that compared diabetes-related health outcomes between pre-pandemic and during-pandemic periods in people with T2DM and without the COVID-19 infection and published from January 1, 2020, to July 13, 2022. A meta-analysis was performed to estimate the overall effect on the diabetes indicators, including hemoglobin A1c (HbA1c), lipid profiles, and weight control, with different effect models according to the heterogeneity. Results Eleven observational studies were included in the final review. No significant changes in HbA1c levels [weighted mean difference (WMD), 0.06 (95% CI −0.12 to 0.24)] and body weight index (BMI) [0.15 (95% CI −0.24 to 0.53)] between the pre-pandemic and during-pandemic were found in the meta-analysis. Four studies reported lipid indicators;most reported insignificant changes in low-density lipoprotein (LDL, n = 2) and high-density lipoprotein (HDL, n = 3);two studies reported an increase in total cholesterol and triglyceride. Conclusions This review did not find significant changes in HbA1c and BMI among people with T2DM after data pooling, but a possible worsening in lipids parameters during the COVID-19 pandemic. There were limited data on long-term outcomes and healthcare utilization, which warrants further research. Systematic review registration PROSPERO CRD42022360433.

Sex-based differences in risk of ischemic stroke or systemic embolism after BNT162b2 or CoronaVac COVID-19 vaccination in patients with atrial fibrillation: A self-controlled case series and nested case-control study.

AIMS: Patients with atrial fibrillation (AF) have a higher risk of ischemic stroke or systemic embolism with a greater risk for female patients. This study aims to evaluate the risk of ischemic stroke or systemic embolism and bleeding following COVID-19 vaccination in patients with AF and the sex differences. METHODS AND RESULTS: Self-controlled case series (SCCS) analysis was conducted to evaluate the risk of ischemic stroke or systemic embolism and bleeding following BNT162b2 or CoronaVac in patients with AF, using the territory-wide electronic medical records from the Hospital Authority and vaccination records from the Department of Health in Hong Kong. Patients with a primary diagnosis of ischemic stroke or systemic embolism or bleeding in the inpatient setting between February 23, 2021 and March 31, 2022 were included. A nested case-control analysis was also conducted with each case randomly matched with ten controls according to sex, age, Charlson comorbidity index and date of hospital admission. Conditional Poisson regression was used in the SCCS analysis and conditional logistic regression was used in nested case-control analysis to assess the risks and all analyses were stratified by sex and type of vaccines. Among 51 158 patients with AF, we identified an increased risk of ischemic stroke or systemic embolism after the first dose of BNT162b2 in SCCS analysis during 0-13 days (incidence rate ratio 6.60[95% CI 1.51-28.77]) and 14-27 days (6.53[95% CI 1.31-32.51]), and nested case-control analysis during 0-13 days (adjusted odds ratio 6.21 [95% CI 1.14-33.91]) and 14-27 days (5.52 [95% CI 1.12-27.26]) only in female patients. The increased risk in female patients following the first dose of CoronaVac was only detected during 0-13 days (3.88 [95% CI 1.67-9.03]) in the nested case-control analysis. No increased risk of ischemic stroke or systemic embolism was identified in male patients and no increased risk of bleeding was detected in all patients with AF for both vaccines. An increased risk of ischemic stroke or systemic embolism after COVID-19 was also observed in both females (17.42 [95% CI 5.08-59.73]) and males (6.63 [95% CI 2.02-21.79]). CONCLUSIONS: The risk of ischemic stroke or systemic embolism after COVID-19 vaccination was only increased in female patients with AF. However, as the risk after COVID-19 was even higher, proactive uptake of COVID-19 vaccines is recommended to prevent the potential severe outcomes after infection.

Effectiveness of BNT162b2 and CoronaVac vaccines in preventing SARS-CoV-2 Omicron infections, hospitalizations, and severe complications in the pediatric population in Hong Kong: a case-control study.

Severe COVID-19 appears to be disproportionately more common in children and adolescents since the emergence of Omicron. More evidence regarding vaccine effectiveness (VE) is urgently needed to assist policymakers in making decisions and minimize vaccine hesitancy among the public. This was a case-control study in the pediatric population using data extracted from the electronic health records database in Hong Kong. Individuals aged 3-17 with COVID-19 confirmed by polymerase chain reaction were included in the study. Each case was matched with up to 10 controls based on age, gender, and index date (within 3 calendar days). The VE of BNT162b2 and CoronaVac in preventing COVID-19, hospitalizations, and severe outcomes were estimated using conditional logistic regression adjusted by patients' comorbidities and medication history during the outbreak from January to August 2022. A total of 36,434 COVID-19 cases, 2231 COVID-19-related hospitalizations, and 1918 severe COVID-19 cases were matched to 109,004, 21,788, and 18,823 controls, respectively. Compared to the unvaccinated group, three doses of BNT162b2 or CoronaVac was associated with reduced risk of infection [VE: BNT162b2: 56.0% (95% CI: 49.6-61.6), CoronaVac: 39.4% (95% CI: 25.6-50.6)], hospitalization [VE: BNT162b2: 58.9% (95% CI: 36.1-73.6), CoronaVac: 51.7% (11.6-73.6)], and severe outcomes [VE: BNT162b2: 60.2% (95% CI: 33.7-76.1), CoronaVac: 42.2% (95% CI: -6.2-68.6)]. Our findings showed that three doses of BNT162b2 or CoronaVac was effective in preventing COVID-19, hospitalizations, and severe outcomes among the pediatric population during Omicron-dominant pandemic, which was further enhanced after a booster dose.

The indirect impact of the COVID-19 pandemic on people with type 2 diabetes mellitus and without COVID-19 infection: Systematic review and meta-analysis.

BACKGROUND: The effect directly from the coronavirus disease 2019 (COVID-19) infection on health and fatality has received considerable attention, particularly among people with type 2 diabetes mellitus (T2DM). However, evidence on the indirect impact of disrupted healthcare services during the pandemic on people with T2DM is limited. This systematic review aims to assess the indirect impact of the pandemic on the metabolic management of T2DM people without a history of COVID-19 infection. METHODS: PubMed, Web of Science, and Scopus were systematically searched for studies that compared diabetes-related health outcomes between pre-pandemic and during-pandemic periods in people with T2DM and without the COVID-19 infection and published from January 1, 2020, to July 13, 2022. A meta-analysis was performed to estimate the overall effect on the diabetes indicators, including hemoglobin A1c (HbA1c), lipid profiles, and weight control, with different effect models according to the heterogeneity. RESULTS: Eleven observational studies were included in the final review. No significant changes in HbA1c levels [weighted mean difference (WMD), 0.06 (95% CI -0.12 to 0.24)] and body weight index (BMI) [0.15 (95% CI -0.24 to 0.53)] between the pre-pandemic and during-pandemic were found in the meta-analysis. Four studies reported lipid indicators; most reported insignificant changes in low-density lipoprotein (LDL, n = 2) and high-density lipoprotein (HDL, n = 3); two studies reported an increase in total cholesterol and triglyceride. CONCLUSIONS: This review did not find significant changes in HbA1c and BMI among people with T2DM after data pooling, but a possible worsening in lipids parameters during the COVID-19 pandemic. There were limited data on long-term outcomes and healthcare utilization, which warrants further research. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022360433.

Effectiveness of BNT162b2 after extending the primary series dosing interval in children and adolescents aged 5-17.

Extended intervals between the first and second doses of mRNA Covid-19 vaccines may reduce the risk of myocarditis in children and adolescents. However, vaccine effectiveness after this extension remains unclear. To examine this potential variable effectiveness, we conducted a population-based nested case-control study of children and adolescents aged 5-17 years who had received two doses of BNT162b2 in Hong Kong. From January 1 to August 15, 2022, 5396 Covid-19 cases and 202 Covid-19 related hospitalizations were identified and matched with 21,577 and 808 controls, respectively. For vaccine recipients with extended intervals [≥28 days, adjusted odds ratio 0.718, 95% Confidence Interval: 0.619, 0.833] there was a 29.2%-reduced risk of Covid-19 infection compared to those with regular intervals (21-27 days). If the threshold was set at eight weeks, the risk reduction was estimated at 43.5% (aOR 0.565, 95% CI: 0.456, 0.700). In conclusion, longer dosing intervals for children and adolescents should be considered.

Risk of carditis after three doses of vaccination with mRNA (BNT162b2) or inactivated (CoronaVac) covid-19 vaccination: a self-controlled cases series and a case-control study.

Background: Large-scale comparative research exploring the risk after the third dose and after inactivated covid-19 vaccination is limited. This study aimed to assess the risk of carditis following three doses of BNT162b2 or CoronaVac. Methods: We conducted a self-controlled case series (SCCS) and a case-control study using electronic health and vaccination records in Hong Kong. Carditis incidents within 28 days of covid-19 vaccination were included as cases. In the case-control study, up to 10 hospitalized controls were selected with stratified probability sampling by age, sex, and hospital admission (±1 day). The incidence rate ratios (IRRs) were reported from conditional Poisson regressions for SCCS, and adjusted odds ratios (ORs) were reported from multivariable logistic regressions. Findings: A total of 8,924,614 doses of BNT162b2 and 6,129,852 doses of CoronaVac were administered from February 2021 to March 2022. The SCCS detected increased carditis risks after BNT162b2: 4.48 (95%confidence interval [CI]:2.99-6.70] in 1-14 days and 2.50 (95%CI:1.43-4.38) in 15-28 days after first dose; 10.81 (95%CI:7.63-15.32) in 1-14 days and 2.95 (95%CI:1.82-4.78) in 15-28 days after second dose; 4.72 (95%CI:1.40-15.97) in 1-14 days after third dose. Consistent results were observed from the case-control study. Risks were specifically found in people aged below 30 years and males. No significant risk increase was observed after CoronaVac in all primary analyses. Interpretations: We detected increased carditis risks within 28 days after all three doses of BNT162b2 but the risk after the third doses were not higher than that of the second dose when compared with baseline period. Continuous monitoring of carditis after both mRNA and inactivated covid-19 vaccines is needed. Funding: : This study was funded by Hong Kong Health Bureau (COVID19F01).