Myocarditis/pericarditis following vaccination with BNT162b2, CoronaVac, and ChAdOx1 among adolescent and adult in Malaysia.

This study evaluates 21-day risk of myocarditis/pericarditis following COVID-19 vaccination among those aged 12 years and older in Malaysia. We used data from nationwide COVID-19 vaccine registry linked to hospital episode database to identify individuals vaccinated with BNT162b2, CoronaVac, or ChAdOx1 and hospitalised for myocarditis/pericarditis between 1 February 2021 and 28 February 2022. There were 87 myocarditis/pericarditis cases identified within 1-21 days after vaccination. Most cases were reported following BNT16262 vaccination (77.0%) with absolute risk of 0.33 cases/100,000 vaccinated persons or 1.73 per million doses administered. Highest risk was observed following second dose and in younger, male individuals. The risk of myocarditis/pericarditis following CoronaVac and ChAdOx1 were much lower compared to BNT162b2. The findings on higher risk observed among younger following mRNA vaccine were consistent with literature and important for targeted surveillance.

Influence of Population Density for COVID-19 Spread in Malaysia: An Ecological Study.

The rapid transmission of highly contagious infectious diseases within communities can yield potential hotspots or clusters across geographies. For COVID-19, the impact of population density on transmission models demonstrates mixed findings. This study aims to determine the correlations between population density, clusters, and COVID-19 incidence across districts and regions in Malaysia. This countrywide ecological study was conducted between 22 January 2021 and 4 February 2021 involving 51,476 active COVID-19 cases during Malaysia's third wave of the pandemic, prior to the reimplementation of lockdowns. Population data from multiple sources was aggregated and spatial analytics were performed to visualize distributional choropleths of COVID-19 cases in relation to population density. Hierarchical cluster analysis was used to synthesize dendrograms to demarcate potential clusters against population density. Region-wise correlations and simple linear regression models were deduced to observe the strength of the correlations and the propagation effects of COVID-19 infections relative to population density. Distributional heats in choropleths and cluster analysis showed that districts with a high number of inhabitants and a high population density had a greater number of cases in proportion to the population in that area. The Central region had the strongest correlation between COVID-19 cases and population density (r = 0.912; 95% CI 0.911, 0.913; p < 0.001). The propagation effect and the spread of disease was greater in urbanized districts or cities. Population density is an important factor for the spread of COVID-19 in Malaysia.

Time from last immunity event against infection during Omicron-dominant period in Malaysia.

OBJECTIVES: To study the incidence of Omicron infections in Malaysia and the exposures that could reduce the hazard of attaining Omicron infection. METHODS: We used a multicenter, prospective cohort to study 482 healthcare workers vaccinated with two and three doses of BNT162b2 for SARS-CoV-2 infection during the Omicron-dominant period in Malaysia. RESULTS: Between January 31 and July 31, 2022, the cumulative incidence was 44.6% (95% CI 40.2-49.1%), and the incidence rate was 3.33 (95% CI 2.91-3.80) per 1000 person-days. Our study found that protection against Omicron infection was significantly higher for persons with previous SARS-CoV-2 infection (hazard ratio [HR] 0.41, 95% CI 0.27-0.62) and persons with a more recent immunity event (<30 days [reference] vs >90 days, HR 3.82, 95%CI 1.34-10.90) from the beginning of the Omicron period. CONCLUSION: Pre-Omicron natural infection and a recent immunity event protect against future Omicron infections.

A Case-Based Monitoring Approach to Evaluate Safety of COVID-19 Vaccines in a Partially Integrated Health Information System: A Study Protocol.

In response to Coronavirus disease 2019 (COVID-19) global pandemic, various COVID-19 vaccines were rapidly administered under emergency use authorization. Rare outcomes associated with COVID-19 vaccines might be less likely to be captured in clinical trials, leading to a knowledge gap in real-world vaccine safety. In contrast with high-income countries, many low-to-middle income countries have limited capacity to conduct active surveillance, owing to the absence of large and fully-integrated health information databases. This paper describes the study protocol, which aims to investigate risk of prespecified adverse events of special interests following COVID-19 vaccination in a partially integrated health information system with non-shareable electronic health records. The SAFECOVAC study is a longitudinal, observational retrospective study of active safety surveillance using case-based monitoring approach. This involves linkage of several administrative databases and hospitalization data monitoring to identify adverse events of special interests following administration of COVID-19 vaccines in Malaysia. The source population comprises of all individuals who received at least one dose of COVID-19 vaccine. Self-controlled design and vaccinated case-coverage design will be employed to assess risk of adverse events of special interests and determine the association with vaccine exposure. Data on vaccination records will be obtained from the national COVID-19 vaccination register to identify the vaccination platforms, doses and the timing of vaccinations. The outcome of this study is hospitalization for the adverse events of special interests between March 2021 and June 2022. The outcomes will be obtained through linkage with hospital admission database and national pharmacovigilance database. Findings will provide analysis of real-world data which can inform deliberations by government and public health decision makers relative to the refinement of COVID-19 vaccination recommendations.

Efficacy of telemedicine for the management of cardiovascular disease: a systematic review and meta-analysis.

BACKGROUND: Telemedicine has been increasingly integrated into chronic disease management through remote patient monitoring and consultation, particularly during the COVID-19 pandemic. We did a systematic review and meta-analysis of studies reporting effectiveness of telemedicine interventions for the management of patients with cardiovascular conditions. METHODS: In this systematic review and meta-analysis, we searched PubMed, Scopus, and Cochrane Library from database inception to Jan 18, 2021. We included randomised controlled trials and observational or cohort studies that evaluated the effects of a telemedicine intervention on cardiovascular outcomes for people either at risk (primary prevention) of cardiovascular disease or with established (secondary prevention) cardiovascular disease, and, for the meta-analysis, we included studies that evaluated the effects of a telemedicine intervention on cardiovascular outcomes and risk factors. We excluded studies if there was no clear telemedicine intervention described or if cardiovascular or risk factor outcomes were not clearly reported in relation to the intervention. Two reviewers independently assessed and extracted data from trials and observational and cohort studies using a standardised template. Our primary outcome was cardiovascular-related mortality. We evaluated study quality using Cochrane risk-of-bias and Newcastle-Ottawa scales. The systematic review and the meta-analysis protocol was registered with PROSPERO (CRD42021221010) and the Malaysian National Medical Research Register (NMRR-20-2471-57236). FINDINGS: 72 studies, including 127 869 participants, met eligibility criteria, with 34 studies included in meta-analysis (n=13 269 with 6620 [50%] receiving telemedicine). Combined remote monitoring and consultation for patients with heart failure was associated with a reduced risk of cardiovascular-related mortality (risk ratio [RR] 0·83 [95% CI 0·70 to 0·99]; p=0·036) and hospitalisation for a cardiovascular cause (0·71 [0·58 to 0·87]; p=0·0002), mostly in studies with short-term follow-up. There was no effect of telemedicine on all-cause hospitalisation (1·02 [0·94 to 1·10]; p=0·71) or mortality (0·90 [0·77 to 1·06]; p=0·23) in these groups, and no benefits were observed with remote consultation in isolation. Small reductions were observed for systolic blood pressure (mean difference -3·59 [95% CI -5·35 to -1·83] mm Hg; p<0·0001) by remote monitoring and consultation in secondary prevention populations. Small reductions were also observed in body-mass index (mean difference -0·38 [-0·66 to -0·11] kg/m2; p=0·0064) by remote consultation in primary prevention settings. INTERPRETATION: Telemedicine including both remote disease monitoring and consultation might reduce short-term cardiovascular-related hospitalisation and mortality risk among patients with heart failure. Future research should evaluate the sustained effects of telemedicine interventions. FUNDING: The British Heart Foundation.

Evaluation of BNT162b2 vaccine effectiveness in Malaysia: test negative case-control study.

There is a notable lack of vaccine effectiveness studies using test-negative case-controlled approach in low- and middle-income countries which have different logistic, demographic and socio-economic conditions from high-income countries. We aimed to estimate the effectiveness of BNT162b2 vaccine against COVID-19 infection over time, intensive care unit admission, severe or critical disease and death due to COVID-19. This study was conducted in the resident population of Labuan aged ≥18 years who had been tested for SARS-CoV-2 by Reverse-Transcriptase Polymerase Chain Reaction between 1 March 2021 and 31 October 2021. We used a test-negative case-control design where 2644 pairs of cases and controls were matched by age, sex, testing date, nationality and testing reason. Analysis was stratified by age group to estimate age effect (<60 years and ≥60 years). Of 22217 individuals tested by Reverse-Transcriptase Polymerase Chain Reaction, 5100 were positive for SARS-CoV-2 and aged 18 years and above. Overall vaccine effectiveness ≥ 14 days after the second dose was 65.2% (95% CI: 59.8-69.9%) against COVID-19 infection, 92.5% (95% CI: 72.3-98.8%) against intensive care unit admission, and 96.5% (95% CI: 82.3-99.8%) against COVID-19 deaths. Among infected individuals, vaccine effectiveness was 79.2% (95% CI: 42.3-94.1%) in preventing severe or critical disease due to COVID-19. Vaccine effectiveness for ≥60 years was 72.3% (95% CI: 53.4-83.9%) in fully vaccinated individuals, higher than 64.8% (95% CI: 49.3-59.1%) for those <60 years. Two doses of BNT162b2 were highly effective against COVID-19 infection, severe or critical disease, intensive care unit admission and death due to COVID-19. This study addresses a gap in literature on BNT162b2 vaccine effectiveness in low- and middle-income populations and demonstrates the feasibility of such a study design in a resource limited setting while supporting evidence of waning immunity.

Clinical testing on SARS-CoV-2 swab samples using reverse-transcription loop-mediated isothermal amplification (RT-LAMP).

BACKGROUND: High cost of commercial RNA extraction kits limits the testing efficiency of SARS-CoV-2. Here, we developed a simple nucleic acid extraction method for the detection of SARS-CoV-2 directly from nasopharyngeal swab samples. METHODS: A pH sensitive dye was used as the end point detection method. The obvious colour changes between positive and negative reactions eliminates the need of other equipment. RESULTS: Clinical testing using 260 samples showed 92.7% sensitivity (95% CI 87.3-96.3%) and 93.6% specificity (95% CI 87.3-97.4%) of RT-LAMP. CONCLUSIONS: The simple RNA extraction method minimizes the need for any extensive laboratory set-up. We suggest combining this simple nucleic acid extraction method and RT-LAMP technology as the point-of care diagnostic tool.

Assessment of Heterologous and Homologous Boosting With Inactivated COVID-19 Vaccine at 3 Months Compared With Homologous Boosting of BNT162b2 at 6 Months.

Importance: Evidence for the timing of booster vaccination after completion of BNT162b2 and CoronaVac primary vaccination is crucial to guide policy recommendations. Objective: To compare the odds of symptomatic SARS-CoV-2 infection and COVID-19-related outcomes after heterologous and homologous boosting of CoronaVac at 3-month intervals and homologous boosting of BNT162b2 at 6-month intervals, with BNT162b2 primary series (2 doses) as the reference group. Design, Setting, and Participants: This population-based retrospective cohort study used national data for Malaysia. Participants included all individuals aged 18 years and older who received a complete primary series of CoronaVac or BNT162b2 vaccine and were eligible for a booster dose between November 21, 2021, and December 28, 2021. Data were analyzed from November 21, 2021, to January 7, 2022. Exposures: Receipt of a booster vs no booster and categorized into primary series BNT162b2 (2 doses of BNT162b2), primary series CoronaVac (2 doses of CoronaVac), 3 doses of BNT162b2, primary series CoronaVac plus a BNT162b2 booster, and 3 doses of CoronaVac. Main Outcomes and Measures: The primary outcome was symptomatic SARS-CoV-2 infection. The secondary outcomes were COVID-19-related intensive care unit admission and death. All outcomes were observed from the day an individual was considered fully boosted (≥14 days after booster dose). Results: Our cohort included 13 840 240 individuals (mean [SD] age, 39.9 [15.5] years; 7 040 298 [50.9%] men; 4 451 180 individuals [32.2%] with ≥1 comorbidities), of whom 5 081 641 individuals (36.7%) had received a booster dose. Using the primary series BNT162b2 recipients as reference, the adjusted odds against symptomatic SAR-CoV-2 infection were lower for individuals who received the primary series CoronaVac plus a BNT162b2 (adjusted odds ratio [aOR], 0.06 [95% CI, 0.05-0.06]), 3 doses of CoronaVac (aOR, 0.08 [95% CI, 0.06-0.10]), or 3 doses of BNT162b2 (aOR, 0.01 [95% CI, 0.00-0.01]). Receipt of heterologous booster (primary series of CoronaVac plus a BNT162b2 booster) was associated with lower odds of SARS-CoV-2 infection (aOR, 0.17 [95% CI, 0.17-0.18]) compared with homologous booster (3 doses of CoronaVac) for individuals aged 60 years and older (aOR, 0.19 [95% CI, 0.19-0.20]). Conclusions and Relevance: In this cohort study, for individuals who received the CoronaVac primary series and a booster dose of BNT162b2 or CoronaVac at 3 months, the observed odds of symptomatic SARS-CoV-2 infection were similar to individuals who received the BNT162b2 primary series plus a third dose of BNT162b2 at 6 months. Heterologous booster is recommended for individuals aged 60 years or older who received the CoronaVac primary series, given the lower observed odds against symptomatic SARS-CoV-2 infection among those who received a BNT1612b2 booster.

A Case-Based Monitoring Approach to Evaluate Safety of COVID-19 Vaccines in a Partially Integrated Health Information System: A Study Protocol

In response to Coronavirus disease 2019 (COVID-19) global pandemic, various COVID-19 vaccines were rapidly administered under emergency use authorization. Rare outcomes associated with COVID-19 vaccines might be less likely to be captured in clinical trials, leading to a knowledge gap in real-world vaccine safety. In contrast with high-income countries, many low-to-middle income countries have limited capacity to conduct active surveillance, owing to the absence of large and fully-integrated health information databases. This paper describes the study protocol, which aims to investigate risk of prespecified adverse events of special interests following COVID-19 vaccination in a partially integrated health information system with non-shareable electronic health records. The SAFECOVAC study is a longitudinal, observational retrospective study of active safety surveillance using case-based monitoring approach. This involves linkage of several administrative databases and hospitalization data monitoring to identify adverse events of special interests following administration of COVID-19 vaccines in Malaysia. The source population comprises of all individuals who received at least one dose of COVID-19 vaccine. Self-controlled design and vaccinated case-coverage design will be employed to assess risk of adverse events of special interests and determine the association with vaccine exposure. Data on vaccination records will be obtained from the national COVID-19 vaccination register to identify the vaccination platforms, doses and the timing of vaccinations. The outcome of this study is hospitalization for the adverse events of special interests between March 2021 and June 2022. The outcomes will be obtained through linkage with hospital admission database and national pharmacovigilance database. Findings will provide analysis of real-world data which can inform deliberations by government and public health decision makers relative to the refinement of COVID-19 vaccination recommendations.

Risk of serious adverse events after the BNT162b2, CoronaVac, and ChAdOx1 vaccines in Malaysia: A self-controlled case series study.

BACKGROUND: Rapid deployment of COVID-19 vaccines is challenging for safety surveillance, especially on adverse events of special interest (AESIs) that were not identified during the pre-licensure studies. This study evaluated the risk of hospitalisations for predefined diagnoses among the vaccinated population in Malaysia. METHODS: Hospital admissions for selected diagnoses between 1 February 2021 and 30 September 2021 were linked to the national COVID-19 immunisation register. We conducted self-controlled case-series study by identifying individuals who received COVID-19 vaccine and diagnosis of thrombocytopenia, venous thromboembolism, myocardial infarction, myocarditis/pericarditis, arrhythmia, stroke, Bell's Palsy, and convulsion/seizure. The incidence of events was assessed in risk period of 21 days postvaccination relative to the control period. We used conditional Poisson regression to calculate the incidence rate ratio (IRR) and 95% confidence interval (CI) with adjustment for calendar period. RESULTS: There was no increase in the risk for myocarditis/pericarditis, Bell's Palsy, stroke, and myocardial infarction in the 21 days following either dose of BNT162b2, CoronaVac, and ChAdOx1 vaccines. A small increased risk of venous thromboembolism (IRR 1.24; 95% CI 1.02, 1.49), arrhythmia (IRR 1.16, 95% CI 1.07, 1.26), and convulsion/seizure (IRR 1.26; 95% CI 1.07, 1.48) was observed among BNT162b2 recipients. No association between CoronaVac vaccine was found with all events except arrhythmia (IRR 1.15; 95% CI 1.01, 1.30). ChAdOx1 vaccine was associated with an increased risk of thrombocytopenia (IRR 2.67; 95% CI 1.21, 5.89) and venous thromboembolism (IRR 2.22; 95% CI 1.17, 4.21). CONCLUSION: This study shows acceptable safety profiles of COVID-19 vaccines among recipients of BNT162b2, CoronaVac, and ChAdOx1 vaccines. This information can be used together with effectiveness data for risk-benefit analysis of the vaccination program. Further surveillance with more data is required to assess AESIs following COVID-19 vaccination in short- and long-term.

Waning COVID-19 Vaccine Effectiveness for BNT162b2 and CoronaVac in Malaysia: An Observational Study.

OBJECTIVES: We aimed to investigate and compare waning vaccine effectiveness (VE) against COVID-19 infection, COVID-19 related ICU admission, and COVID-19-related death for BNT162b2 and CoronaVac vaccines. METHODS: We consolidated national data on COVID-19 vaccination and outcomes, and used cases from September 1st-30th, 2021 to compare VE between the 'early' (fully vaccinated in April-June 2021) and 'late' (July-August 2021) groups. We estimated VE against COVID-19 infection with a negative binomial regression and VE against ICU admission and death among confirmed COVID-19 cases with a logistic regression. RESULTS: For BNT162b2, VE against COVID-19 infections declined from 90.8% (95% CI 89.4, 92.1) in the 'late' group to 79.3% (95% CI 76.1, 82.1) in the 'early' group. VE for BNT162b2 against ICU admission and death were stable. For CoronaVac, VE waned against COVID-19 infections from 74.5% (95% CI 70.6, 78.0) to 30.4% (95% CI 18.8, 40.3). Effectiveness against ICU admission waned from 56.0% (95% CI 51.2, 60.2) to 28.7% (95% CI 12.2, 42.1). CoronaVac's effectiveness against death remained stable. CONCLUSION: VE against COVID-19 infection waned after 3-5 months of full vaccination for both BNT162b2 and CoronaVac vaccines in Malaysia. For CoronaVac, protection against ICU admission also declined.

Real-world effectiveness of homologous and heterologous BNT162b2, CoronaVac, and AZD1222 booster vaccination against Delta and Omicron SARS-CoV-2 infection.

Given emerging evidence of immune escape in the SARS-CoV-2 Omicron viral variant, and its dominance, effectiveness of heterologous and homologous boosting schedules commonly used in low-to-middle income countries needs to be re-evaluated. We conducted a test-negative design using consolidated national administrative data in Malaysia to compare the effectiveness of homologous and heterologous BNT162b2, CoronaVac, and AZD1222 booster vaccination against SARS-CoV-2 infection in predominant-Delta and predominant-Omicron periods. Across both periods, homologous CoronaVac and AZD1222 boosting demonstrated lower effectiveness than heterologous boosting for CoronaVac and AZD1222 primary vaccination recipients and homologous BNT162b2 boosting. Broadly, marginal effectiveness was smaller by 40-50 percentage points in the Omicron period than the Delta period. Without effective and accessible second-generation vaccines, heterologous boosting using BNT162b2 for inactivated and vectored primary vaccination recipients is preferred.

Real-world effectiveness of BNT162b2 vaccine against SARS-CoV-2 infection among adolescents (12 to 17-year-olds) in Malaysia.

OBJECTIVES: In this study, we aimed to investigate vaccine effectiveness (VE) against SARS-CoV-2 infections among adolescents aged 12 to 17 years in Malaysia and examine potential VE differences after full vaccination. METHODS: We consolidated data on COVID-19 testing, vaccination, and outcomes for all public school-going adolescents in Malaysia from September 1, 2021, to December 31, 2021, and estimated the VE against SARS-CoV-2 infections during this period. Cases were defined as positive tests, either by reverse transcriptase- PCR (RT-PCR) or rapid antigen (RTK-Ag) testing, while controls were negative tests. Secondarily, we restricted the analysis to all tests performed in December 2021 and compared VE by month of full vaccination. RESULTS: A total of 175,880 eligible tests (53.4% or 93,995 RT-PCR tests) were included. After full vaccination with BNT162b2, VE against SARS-CoV-2 infections was 65.7% (95% confidence interval [CI] 64.4, 66.9) over the study period. When restricted to tests in December 2021, VEs for those fully vaccinated in September 2021, October 2021, and November 2021 were comparable (60.6% [95% CI 23.7, 81.5], 56.9% [95% CI 51.1, 62.0], and 65.7% [95% CI 59.8, 70.7] respectively). CONCLUSIONS: Among adolescents, full vaccination with BNT162b2 offered considerable protection against SARS-CoV-2 infections over at least three months without substantial evidence of waning.

COVID-19 breakthrough infections and humoral immune response among BNT162b2 vaccinated healthcare workers in Malaysia.

The evaluation of breakthrough infection and humoral immunity responses are important outcomes for vaccination policy for healthcare staff. This prospective cohort study collected blood samples at 5-time points; before primary vaccine doses, and at 2, 10 and 24 weeks after BNT162b2 vaccination from 551 HCWs, between March and October 2021. We investigated the association between anti-spike-1 protein receptor-binding domain (anti-S1-RBD) antibody geometric mean titre (GMT) and breakthrough infections. Two weeks post-vaccination, the GMT of anti-S1-RBD antibodies was measured at almost maximum detectable value (3115 BAU/ml [95% CI, 3051-3180]); it decreased to 1486 BAU/ml (95% CI, 1371-1610) at 10 weeks; and to 315 BAU/ml (95% CI, 283-349) at 24 weeks. Prior COVID-19 infection and age significantly affected the antibody titres. Fifty-six participants, none of whom were COVID-19 convalescents, had breakthrough infections between 10 and 24 weeks post-vaccination. Before breakthrough infections, the GMT was not different between the breakthrough and non-breakthrough individuals. After infection, the GMT was significantly higher in individuals with breakthrough infections (2038 BAU/ml [95%CI, 1547-2685]), specifically in symptomatic breakthroughs, compared to those without infection (254 BAU/ml [95%CI, 233-278]). A notable surge in breakthrough infections among healthcare workers coincided with the emergence of the Delta variant and when BNT162b2-elicited antibody responses waned in 10-24 weeks (i.e. approximately 3-6 months). Post-breakthrough, the antibody response was boosted in individuals with symptomatic presentations, but not asymptomatic individuals. The study finding supports administering booster vaccination for healthcare staff, including those who recovered from asymptomatic breakthrough infection.

Waning COVID-19 Vaccine Effectiveness for BNT162b2 and CoronaVac in Malaysia: An Observational Study

Objectives : We aimed to investigate and compare waning vaccine effectiveness (VE) against COVID-19 infection, COVID-19 related ICU admission and COVID-19 related death for BNT162b2 and CoronaVac vaccines. Methods : We consolidated national data on COVID-19 vaccination and outcomes, and used cases from 1 to 30 September 2021 to compare VE between the ‘early’ (fully vaccinated in April to June 2021) and ‘late’ (July to August 2021) groups. We estimated VE against COVID-19 infection with a negative binomial regression, and VE against ICU admission and death among confirmed COVID-19 cases with a logistic regression. Results : For BNT162b2, VE against COVID-19 infections declined from 90•8% (95% CI 89•4, 92•1) in the ‘late’ group to 79•3% (95% CI 76•1, 82•1) in the ‘early’ group. VE for BNT162b2 against ICU admission and death were stable. For CoronaVac, VE waned against COVID-19 infections from 74•5% (95% CI 70•6, 78•0) to 30•4% (95% CI 18•8, 40•3). Effectiveness against ICU admission waned from 56•0% (95% CI 51•2, 60•2) to 28•7% (95% CI 12•2, 42•1). CoronaVac's effectiveness against death remained stable. Conclusion : VE against COVID-19 infection waned after three to five months of full vaccination for both BNT162b2 and CoronaVac vaccines in Malaysia. For CoronaVac, protection against ICU admission also declined.

PICK-ing Malaysia's Epidemic Apart: Effectiveness of a Diverse COVID-19 Vaccine Portfolio.

Malaysia rolled out a diverse portfolio of predominantly three COVID-19 vaccines (AZD1222, BNT162b2, and CoronaVac) beginning 24 February 2021. We evaluated vaccine effectiveness with two methods, covering 1 April to 15 September 2021: (1) the screening method for COVID-19 (SARS-CoV-2) infection and symptomatic COVID-19; and (2) a retrospective cohort of confirmed COVID-19 cases for COVID-19 related ICU admission and death using logistic regression. The screening method estimated partial vaccination to be 48.8% effective (95% CI: 46.8, 50.7) against COVID-19 infection and 33.5% effective (95% CI: 31.6, 35.5) against symptomatic COVID-19. Full vaccination is estimated at 87.8% effective (95% CI: 85.8, 89.7) against COVID-19 infection and 85.4% effective (95% CI: 83.4, 87.3) against symptomatic COVID-19. Among the cohort of confirmed COVID-19 cases, partial vaccination with any of the three vaccines is estimated at 31.3% effective (95% CI: 28.5, 34.1) in preventing ICU admission, and 45.1% effective (95% CI: 42.6, 47.5) in preventing death. Full vaccination with any of the three vaccines is estimated at 79.1% effective (95% CI: 77.7, 80.4) in preventing ICU admission and 86.7% effective (95% CI: 85.7, 87.6) in preventing deaths. Our findings suggest that full vaccination with any of the three predominant vaccines (AZD1222, BNT162b2, and CoronaVac) in Malaysia has been highly effective in preventing COVID-19 infection, symptomatic COVID-19, COVID-19-related ICU admission, and death.

Efficacy of Ivermectin Treatment on Disease Progression Among Adults With Mild to Moderate COVID-19 and Comorbidities: The I-TECH Randomized Clinical Trial.

Importance: Ivermectin, an inexpensive and widely available antiparasitic drug, is prescribed to treat COVID-19. Evidence-based data to recommend either for or against the use of ivermectin are needed. Objective: To determine the efficacy of ivermectin in preventing progression to severe disease among high-risk patients with COVID-19. Design, Setting, and Participants: The Ivermectin Treatment Efficacy in COVID-19 High-Risk Patients (I-TECH) study was an open-label randomized clinical trial conducted at 20 public hospitals and a COVID-19 quarantine center in Malaysia between May 31 and October 25, 2021. Within the first week of patients' symptom onset, the study enrolled patients 50 years and older with laboratory-confirmed COVID-19, comorbidities, and mild to moderate disease. Interventions: Patients were randomized in a 1:1 ratio to receive either oral ivermectin, 0.4 mg/kg body weight daily for 5 days, plus standard of care (n = 241) or standard of care alone (n = 249). The standard of care consisted of symptomatic therapy and monitoring for signs of early deterioration based on clinical findings, laboratory test results, and chest imaging. Main Outcomes and Measures: The primary outcome was the proportion of patients who progressed to severe disease, defined as the hypoxic stage requiring supplemental oxygen to maintain pulse oximetry oxygen saturation of 95% or higher. Secondary outcomes of the trial included the rates of mechanical ventilation, intensive care unit admission, 28-day in-hospital mortality, and adverse events. Results: Among 490 patients included in the primary analysis (mean [SD] age, 62.5 [8.7] years; 267 women [54.5%]), 52 of 241 patients (21.6%) in the ivermectin group and 43 of 249 patients (17.3%) in the control group progressed to severe disease (relative risk [RR], 1.25; 95% CI, 0.87-1.80; P = .25). For all prespecified secondary outcomes, there were no significant differences between groups. Mechanical ventilation occurred in 4 (1.7%) vs 10 (4.0%) (RR, 0.41; 95% CI, 0.13-1.30; P = .17), intensive care unit admission in 6 (2.4%) vs 8 (3.2%) (RR, 0.78; 95% CI, 0.27-2.20; P = .79), and 28-day in-hospital death in 3 (1.2%) vs 10 (4.0%) (RR, 0.31; 95% CI, 0.09-1.11; P = .09). The most common adverse event reported was diarrhea (14 [5.8%] in the ivermectin group and 4 [1.6%] in the control group). Conclusions and Relevance: In this randomized clinical trial of high-risk patients with mild to moderate COVID-19, ivermectin treatment during early illness did not prevent progression to severe disease. The study findings do not support the use of ivermectin for patients with COVID-19. Trial Registration: ClinicalTrials.gov Identifier: NCT04920942.

Spatial Dynamics and Multiscale Regression Modelling of Population Level Indicators for COVID-19 Spread in Malaysia.

As COVID-19 dispersion occurs at different levels of gradients across geographies, the application of spatiotemporal science via computational methods can provide valuable insights to direct available resources and targeted interventions for transmission control. This ecological-correlation study evaluates the spatial dispersion of COVID-19 and its temporal relationships with crucial demographic and socioeconomic determinants in Malaysia, utilizing secondary data sources from public domains. By aggregating 51,476 real-time active COVID-19 case-data between 22 January 2021 and 4 February 2021 to district-level administrative units, the incidence, global and local Moran indexes were calculated. Spatial autoregressive models (SAR) complemented with geographical weighted regression (GWR) analyses were executed to determine potential demographic and socioeconomic indicators for COVID-19 spread in Malaysia. Highest active case counts were based in the Central, Southern and parts of East Malaysia regions of Malaysia. Countrywide global Moran index was 0.431 (p = 0.001), indicated a positive spatial autocorrelation of high standards within districts. The local Moran index identified spatial clusters of the main high-high patterns in the Central and Southern regions, and the main low-low clusters in the East Coast and East Malaysia regions. The GWR model, the best fit model, affirmed that COVID-19 spread in Malaysia was likely to be caused by population density (ß coefficient weights = 0.269), followed by average household income per capita (ß coefficient weights = 0.254) and GINI coefficient (ß coefficient weights = 0.207). The current study concluded that the spread of COVID-19 was concentrated mostly in the Central and Southern regions of Malaysia. Population's average household income per capita, GINI coefficient and population density were important indicators likely to cause the spread amongst communities.