Economic Evaluation of Nirmatrelvir/Ritonavir Among Adults Against Hospitalization During the Omicron Dominated Period in Malaysia: A Real-World Evidence Perspective.

BACKGROUND AND OBJECTIVES: Nirmatrelvir/ritonavir was administered orally to manage mild to moderate symptoms of COVID-19 in adult patients. The objectives of this study were to (i) evaluate the cost-effectiveness of prescribing nirmatrelvir/ritonavir within 5 days of a COVID-19 illness in order to avert hospitalization within a 30-day period in the Malaysia setting; (ii) determine how variations in pricing and hospitalization rates will affect the cost-effectiveness of nirmatrelvir/ritonavir. METHODS: The 30-day hospitalization related to COVID-19 was determined using 1 to 1 propensity score-matched real-world data in Malaysia from 14 July 2022 to 14 November 2022. To determine the total per-person costs related to COVID-19, we added the cost of drug (nirmatrelvir/ritonavir or control), clinic visits and inpatient care. Incremental cost-effectiveness ratio (ICER) per hospitalization averted was calculated. RESULTS: Our cohort included 31,487 patients. The rate of hospitalization within 30 days was found to be 0.35% for the group treated with nirmatrelvir/ritonavir, and 0.52% for the control group. The nirmatrelvir/ritonavir group cost an additional MYR 1,625.72 (USD 358.88) per patient. This treatment also resulted in a reduction of 0.17% risk for hospitalization, which corresponded to an ICER of MYR 946,801.26 (USD 209,006.90) per hospitalization averted. CONCLUSION: In Malaysia, where vaccination rates were high, nirmatrelvir/ritonavir has been shown to be beneficial in the outpatient treatment of adults with COVID-19 who have risk factors; however, it was only marginally cost effective against hospitalization for healthy adults during the Omicron period.

Real-world nirmatrelvir-ritonavir outpatient treatment in reducing hospitalization for high-risk patients with COVID-19 during Omicron BA.4, BA.5 and XBB subvariants dominance in Malaysia: A retrospective cohort study.

OBJECTIVE: To determine if nirmatrelvir-ritonavir 300mg/100mg treatment for 5 days in high-risk outpatients with mild to moderate COVID-19 symptoms was associated with a reduction in hospitalization, intensive care unit (ICU) admission, and death. METHODS: This 1:1 propensity score matched cohort study from 647 public health clinics in Malaysia included all patients with COVID-19 with positive tests aged 18 years and older, who were eligible for nirmatrelvir-ritonavir treatment within 5 days of illness from July 14, 2022, to November 14, 2022. The exposed group was patients with COVID-19 initiated with nirmatrelvir-ritonavir treatment, whereas those not initiated with the drug served as the control group. Data was analyzed from July 14, 2022 to December 31, 2022. RESULTS: A total of 20,966 COVID-19 high-risk outpatients (n = 10,483 for nirmatrelvir-ritonavir group and n = 10,483 for control group) were included in the study. Nirmatrelvir-ritonavir treatment was associated with a 36% reduction (adjusted hazard ratio 0.64 [95% CI 0.43, 0.94]) in hospitalization compared with those not given the drug. There was a single ICU admission for the control group and one death each was reported in the nirmatrelvir-ritonavir and control group, respectively. CONCLUSIONS: Nirmatrelvir-ritonavir treatment was associated with reduced hospitalization in high-risk patients with COVID-19 even in highly vaccinated populations.

Stigma, Sociodemographic Factors, and Clinical Factors Associated with Psychological Distress among COVID-19 Survivors during the Convalescence Period: A Multi-Centre Study in Malaysia.

High rates of psychological distress among COVID-19 survivors and stigmatisation have been reported in both early and late convalescence. This study aimed to compare the severity of psychological distress and to determine the associations among sociodemographic and clinical characteristics, stigma, and psychological distress among COVID-19 survivors across two different cohorts at two different time points. Data were collected cross-sectionally in two groups at one month and six months post-hospitalisation among COVID-19 patient from three hospitals in Malaysia. This study assessed psychological distress and the level of stigma using the Kessler Screening Scale for Psychological Distress (K6) and the Explanatory Model Interview Catalogue (EMIC) stigma scale, respectively. At one month after discharge, significantly lower psychological distress was found among retirees (B = -2.207, 95% confidence interval [95% CI] = -4.139 to -0.068, p = 0.034), those who received up to primary education (B = -2.474, 95% CI = -4.500 to -0.521, p = 0.014), and those who had an income of more than RM 10,000 per month (B = -1.576, 95% CI = -2.714 to -0.505, p = 0.006). Moreover, those with a history of psychiatric illness [one month: (B = 6.363, 95% CI = 2.599 to 9.676, p = 0.002), six months: (B = 2.887, CI = 0.469-6.437, p = 0.038)] and sought counselling services [one month: (B = 1.737, 95% CI = 0.385 to 3.117, p = 0.016), six months: (B = 1.480, CI = 0.173-2.618, p = 0.032)] had a significantly higher severity of psychological distress at one month and six months after discharge from the hospital. The perceived stigma of being infected with COVID-19 contributed to greater severity of psychological distress. (B = 0.197, CI = 0.089-0.300, p = 0.002). Different factors may affect psychological distress at different periods of convalescence after a COVID-19 infection. A persistent stigma contributed to psychological distress later in the convalescence period.

Clinical predictors of efavirenz-based regimen treatment durability: A two-year case-control study of antiretroviral-naïve patients.

BACKGROUND: While efavirenz-associated adverse drug events (ADEs) were widely established, the clinical relevance is uncertain. OBJECTIVES: We aimed to assess the extent of treatment interruption caused by efavirenz-associated ADEs. METHODS: A case-control study of efavirenz recipients who did, versus did not (control) develop adverse drug events (ADE), and who were matched for baseline CD4 + at a ratio of 1:1.3 was conducted. Antiretroviral -naïve patients who were started on efavirenz were followed up retrospectively, and their records scrutinized every month for 2 years. Demographic and clinical predictors of treatment interruption were computed using Cox proportional hazard models. Kaplan- Meier curves were plotted to assess time to treatment interruption for the two groups. Clinical endpoints were: i) efficacy -improved CD4 + counts and/or viral load (VL) suppression, ii) safety -absence of treatment-limiting toxicities, and iii) durability - no interruption until follow-up ended. RESULTS: Both groups had comparable CD4 + counts at baseline (p = 0.15). At t = 24-months, VL in both groups were suppressed to undetectable levels (<20 copies/mL) while median CD4 + was 353 cells/µL (IQR: 249-460). The mean time on treatment was 23 months (95% CI, 22.3 -23.4) in the control group without ADE and 20 months (95% CI, 18.9 - 21.6) in the ADE group (p = 0.001). Kaplan-Meier plots demonstrated that 59.5% of patients who experienced ≥ 1 ADE versus 81% of those who did not experience any ADE were estimated to continue treatment for up to 24 months with no interruption (p = 0.001). Most interruptions to EFV treatment occurred in the presence of opportunistic infections and these were detected within the first 5 months of treatment initiation. Independent predictors which negatively impacted the dependent variable i.e., treatment durability, were intravenous drug use (adjusted hazard ratio, aHR 2.17, 95% CI, 1.03-4.61, p = 0.043), presence of ≥ 1 opportunistic infection(s) (aHR 2.2, 95% CI, 1.13-4.21, p = 0.021), and presence of ≥ 1 serious ADE(s) (aHR 4.18, 95% CI, 1.98-8.85, p = 0.00). CONCLUSION: Efavirenz' role as the preferred first-line regimen for South-East Asia's resource-limited regions will need to be carefully tailored to suit the regional population. Findings have implications to policy-makers and clinicians, particularly for the treatment of patients who develop ADEs and opportunistic infections, and for intravenous drug user subgroups.

COVID-19 death and kidney disease in a multiracial Asian country.

INTRODUCTION: COVID-19 infection and kidney disease (KD) carry a considerable risk of mortality. Understanding predictors of death and KD may help improve management and patient outcome. METHODS: This is a prospective multicentre observational study conducted in a multiracial Asian country to identify predictors of death and acute kidney injury (AKI) in hospitalized COVID-19 patients from January to June 2020. RESULTS: A total of 6078 patients were included in this study. Mean age was 37.3 (±16.8) years, 71% were male, 59.4% Malay, 6.7% Chinese, 2.3% Indian and 31.7% other ethnicities. AKI was seen in 3.5% of patients while 1.6% had pre-existing chronic kidney disease (CKD). Overall case fatality rate (CFR) was 1.3%. Patients with KD (AKI and CKD) had CFR of 20%. Many factors were associated with increased risk of death and AKI. However, significant predictors of death after adjustment for covariates were age (>70 years), Chinese ethnicity, diabetes mellitus (DM) and KD. Adjusted predictors of AKI were age (>51 years), DM and severity at presentation. Chinese were 2.58 times more likely to die (p = .036) compared to Malay. Centre capacity to manage, ventilate and dialyze patients significantly influenced death. Among those with AKI, the most common symptoms were fever, cough, and dyspnea. They had lower absolute lymphocyte count, were more likely to be admitted to ICU, required more ventilation and longer hospitalization. CONCLUSION: Patient and centre factors influence death and AKI among COVID-19 patients. This study also demonstrates death disparities across different racial groups and centre capacities in this multiracial Asian country.

The role of procalcitonin in predicting risk of mechanical ventilation and mortality among moderate to severe COVID-19 patients.

BACKGROUND: Serum procalcitonin (PCT) has become an emerging prognostic biomarker of disease progression in patients with COVID-19. This study aims to determine the optimal cut-off value of PCT with regards to important clinical outcomes, especially for mechanical ventilation and all-cause mortality among moderate to severe COVID-19 patients in Malaysia. METHODS: A total of 319 moderate to severe COVID-19 patients hospitalized at the National Referral Hospital in December 2020 were included in the study retrospectively. Demographics, comorbidities, the severity of COVID-19 infection, laboratory and imaging findings, and treatment given were collected from the hospital information system for analysis. The optimal cut-point values for PCT were estimated in two levels. The first level involved 276 patients who had their PCT measured within 5 days following their admission. The second level involved 237 patients who had their PCT measured within 3 days following their admission. Further, a propensity score matching analysis was performed to determine the adjusted relative risk of patients with regards to various clinical outcomes according to the selected cut-point among 237 patients who had their PCT measured within 3 days. RESULTS: The results showed that a PCT level of 0.2 ng/mL was the optimal cut-point for prognosis especially for mortality outcome and the need for mechanical ventilation. Before matching, patients with PCT ≥ 0.2 ng/mL were associated with significantly higher odds in all investigated outcomes. After matching, patients with PCT > 0.2 ng/mL were associated with higher odds in all-cause mortality (OR: 4.629, 95% CI 1.387-15.449, p = 0.0127) and non-invasive ventilation (OR: 2.667, 95% CI 1.039-6.847, p = 0.0415). Furthermore, patients with higher PCT were associated with significantly longer days of mechanical ventilation (p = 0.0213). There was however no association between higher PCT level and the need for mechanical ventilation (OR: 2.010, 95% CI 0.828-4.878, p = 0.1229). CONCLUSION: Our study indicates that a rise in PCT above 0.2 ng/mL is associated with an elevated risk in all-cause mortality, the need for non-invasive ventilation, and a longer duration of mechanical ventilation. The study offers concrete evidence for PCT to be used as a prognostication marker among moderate to severe COVID-19 patients.

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.

Efficacy of Early Treatment With Favipiravir on Disease Progression Among High-Risk Patients With Coronavirus Disease 2019 (COVID-19): A Randomized, Open-Label Clinical Trial.

BACKGROUND: The role of favipiravir in preventing disease progression in coronavirus disease 2019 (COVID-19) remains uncertain. We aimed to determine its effect in preventing disease progression from nonhypoxia to hypoxia among high-risk COVID-19 patients. METHODS: This was an open-label, randomized clinical trial conducted at 14 public hospitals across Malaysia (February-July 2021) among 500 symptomatic, RT-PCR-confirmed COVID-19 patients, aged ≥50 years with ≥1 comorbidity, and hospitalized within first 7 days of illness. Patients were randomized 1:1 to favipiravir plus standard care or standard care alone. Favipiravir was administered at 1800 mg 2×/day on day 1 followed by 800 mg 2×/day until day 5. The primary endpoint was rate of clinical progression from nonhypoxia to hypoxia. Secondary outcomes included rates of mechanical ventilation, intensive care unit (ICU) admission, and in-hospital mortality. RESULTS: Of 500 patients randomized (mean [SD] age, 62.5 [8.0] years; 258 women [51.6%]; 251 [50.2%] had COVID-19 pneumonia), 487 (97.4%) patients completed the trial. Clinical progression to hypoxia occurred in 46 (18.4%) patients on favipiravir plus standard care and 37 (14.8%) on standard care alone (OR, 1.30; 95% CI: .81-2.09; P = .28). All 3 prespecified secondary endpoints were similar between both groups. Mechanical ventilation occurred in 6 (2.4%) vs 5 (2.0%) (OR, 1.20; 95% CI: .36-4.23; P = .76), ICU admission in 13 (5.2%) vs 12 (4.8%) (OR, 1.09; 95% CI: .48-2.47; P = .84), and in-hospital mortality in 5 (2.0%) vs 0 (OR, 12.54; 95% CI: .76-207.84; P = .08) patients. CONCLUSIONS: Among COVID-19 patients at high risk of disease progression, early treatment with oral favipiravir did not prevent their disease progression from nonhypoxia to hypoxia. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov (NCT04818320).

Diagnostic accuracy of fresh drooled saliva for SARS-CoV-2 in travelers.

BACKGROUND: The standard for SARS-CoV-2 diagnosis is RT-PCR from nasopharyngeal or oropharyngeal swabs. Major airports require COVID-19 screening, and saliva has the potential as a substitute specimen for SARS-CoV-2 diagnosis. We investigated the utility of fresh drooled saliva against NPS for COVID-19 screening of travelers. METHODS: We recruited 81 travelers and 15 non-travelers (including ten controls) prospectively within a mean of 3·22 days of RT-PCR confirmed COVID-19. Each study participant provided 2 mls of early morning fresh drooled whole saliva separately into a sterile plastic container and GeneFiX™ saliva collection kit. The saliva specimens were processed within 4 h and tested for SARS-CoV-2 genes (E, RdRP, and N2) and the results compared to paired NPS RT-PCR for diagnostic accuracy. RESULTS: Majority of travellers were asymptomatic (75·0%) with a mean age of 34·26 years. 77 travelers were RT-PCR positive at the time of hospitalization whilst three travelers had positive contacts. In this group, the detection rate for SARS-CoV-2 with NPS, whole saliva, and GeneFiX™ were comparable (89·3%, 50/56; 87·8%, 43/49; 89·6%, 43/48). Both saliva collection methods were in good agreement (Kappa = 0·69). There was no statistical difference between the detection rates of saliva and NPS (p > 0·05). Detection was highest for the N2 gene whilst the E gene provided the highest viral load (mean = 27·96 to 30·10, SD = 3·14 to 3·85). Saliva specimens have high sensitivity (80·4%) and specificity (90·0%) with a high positive predictive value of 91·8% for SARS-CoV-2 diagnosis. CONCLUSION: Saliva for SARS-CoV-2 screening is a simple accurate technique comparable with NPS RT-PCR.

Survival and Prognostic Factors of HIV-positive Patients after Antiretroviral Therapy Initiation at a Malaysian Referral Hospital.

BACKGROUND: Antiretroviral therapy (ART) has transformed the management of human immunodeficiency virus (HIV) infection and significantly improved survival rates, but there is lack of such survival data from Malaysia. OBJECTIVE: The objective was to determine the survival rates and prognostic factors of survival in HIV-infected adults treated with ART in Malaysia. MATERIALS AND METHODS: This retrospective cohort study considered all HIV-positive adult patients registered in Sungai Buloh Hospital, a major referral center in Malaysia, between January 1, 2007 and December 31, 2016. Then, patients were selected through a systematic sampling method. Demographic, clinical, and treatment data were extracted from electronic medical records. Person-years at risk and incidence of mortality rate per 100 person-years were calculated. The Kaplan-Meier survival curve and log-rank test were used to compare the overall survival rates. Cox proportional hazards regression was applied to determine the prognostic factors for survival. RESULTS: A total of 339 patients were included. The estimated overall survival rates were 93.8%, 90.4%, 84.9%, and 72.8% at 1, 3, 5, and 10 years, respectively, from ART initiation. The results of multiple Cox proportional hazard regression indicated that anemic patients were at a 3.76 times higher risk of mortality (95% confidence interval [CI]: 1.97-7.18; P < 0.001). The hazard risk was 2.09 times higher for HIV patients co-infected with tuberculosis (95% CI: 1.10, 3.96; P = 0.024). CONCLUSION: The overall survival rates among HIV-infected adults in this study are higher than that from low-income countries but lower than that from high-income countries. Low baseline hemoglobin levels of <11 g/dL and tuberculosis co-infection were strong prognostic factors for survival.

Risk factors of carbapenem-resistant Enterobacteriaceae infection and colonisation: a Malaysian tertiary care hospital based case-control study.

BACKGROUND: Carbapenem-resistant Enterobacteriaceae (CRE) infection has become a major challenge to clinicians. The aim of this study is to identify the risk factors of acquiring CRE to guide more targeted screening for hospital admissions. METHODS: This is a retrospective case-control study (ratio 1:1) where a patient with CRE infection or colonisation was matched with a control. The control was an individual who tested negative for CRE but was a close contact of a patient testing positive and was admitted at the same time and place. Univariate and multivariate statistical analyses were done. RESULTS: The study included 154 patients. The majority of the CRE was Klebsiella species (83%). From univariate analysis, the significant risk factors were having a history of indwelling devices (OR: 2.791; 95% CI: 1.384-5.629), concomitant other MDRO (OR: 2.556; 95% CI: 1.144-5.707) and hospitalisation for more than three weeks (OR: 2.331; 95% CI: 1.163-4.673). Multivariate analysis showed that being unable to ambulate on admission (adjusted OR: 2.345; 95% CI: 1.170-4.699) and antibiotic exposure (adjusted OR: 3.515; 95% CI: 1.377-8.972) were independent predictors. The in-hospital mortality rate of CRE infection was high (64.5%). CRE acquisition resulted in prolonged hospitalisation (median=35 days; P<0.001). CONCLUSION: CRE infection results in high morbidity and mortality. On top of the common risk factors, patients with mobility restriction, prior antibiotic exposures and hospitalisation for more than three weeks should be prioritised in the screening strategy to control the spread of CRE.

Serology surveillance of SARS-CoV-2 antibodies among healthcare workers in COVID-19 designated facilities in Malaysia.

BACKGROUND: Asymptomatic severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infections are well documented. Healthcare workers (HCW) are at increased risk of infection due to occupational exposure to infected patients. We aim to determine the prevalence of SARS-CoV-2 antibodies among HCW who did not come to medical attention. METHODS: We prospectively recruited 400 HCW from the National Public Health Laboratory and two COVID-19 designated public hospitals in Klang Valley, Malaysia between 13/4/2020 and 12/5/2020. Quota sampling was used to ensure representativeness of HCW involved in direct and indirect patient care. All participants answered a self-administered questionnaire and blood samples were taken to test for SARS-CoV-2 antibodies by surrogate virus neutralization test. FINDINGS: The study population comprised 154 (38.5%) nurses, 103 (25.8%) medical doctors, 47 (11.8%) laboratory technologists and others (23.9%). A majority (68.9%) reported exposure to SARS-CoV-2 in the past month within their respective workplaces. Adherence to personal protection equipment (PPE) guidelines and hand hygiene were good, ranging from 91-100% compliance. None (95% CI: 0, 0.0095) of the participants had SARS-CoV-2 antibodies detected, despite 182 (45.5%) reporting some symptoms one month prior to study recruitment. One hundred and fifteen (29%) of participants claimed to have had contact with known COVID-19 persons outside of their workplace. INTERPRETATION: Zero seroprevalence among HCW suggests a low incidence of undiagnosed COVID-19 infection in our healthcare setting during the first local wave of SARS-CoV-2 infection. The occupational risk of SARS-CoV-2 transmission within healthcare facilities can be prevented by adherence to infection control measures and appropriate use of PPE.

QT prolongation associated with hydroxychloroquine and protease inhibitors in COVID-19.

WHAT IS KNOWN AND OBJECTIVE: Hydroxychloroquine and protease inhibitors were widely used as off-label treatment options for COVID-19 but the safety data of these drugs among the COVID-19 population are largely lacking. Drug-induced QTc prolongation is a known adverse reaction of hydroxychloroquine, especially during chronic treatment. However, when administered concurrently with potential pro-arrhythmic drugs such as protease inhibitors, the risk of QTc prolongation imposed on these patients is not known. We aim to investigate the incidence of QTc prolongation events and potential factors associated with its occurrence in COVID-19 population. METHODS: We included 446 SARS-CoV-2 RT-PCR-positive patients taking at least one treatment drug for COVID-19 within a period of one month (March-April 2020). In addition to COVID-19-related treatment (HCQ/PI), concomitant drugs with risks of QTc prolongation were considered. We defined QTc prolongation as QTc interval of ≥470 ms in postpubertal males, and ≥480 ms in postpubertal females. RESULTS AND DISCUSSION: QTc prolongation events occurred in 28/446 (6.3%) patients with an incidence rate of 1 case per 100 person-days. A total of 26/28 (93%) patients who had prolonged QTc intervals received at least two pro-QT drugs. Multivariate analysis showed that HCQ and PI combination therapy had five times higher odds of QTc prolongation as compared to HCQ-only therapy after controlling for age, cardiovascular disease, SIRS and the use of concurrent QTc-prolonging agents besides HCQ and/or PI (OR 5.2; 95% CI, 1.11-24.49; p = 0.036). Independent of drug therapy, presence of SIRS resulted in four times higher odds of QTc prolongation (OR 4.3; 95% CI, 1.66-11.06; p = 0.003). In HCQ-PI combination group, having concomitant pro-QT drugs led to four times higher odds of QTc prolongation (OR 3.8; 95% CI, 1.53-9.73; p = 0.004). Four patients who had prolonged QTc intervals died but none were cardiac-related deaths. WHAT IS NEW AND CONCLUSION: In our cohort, hydroxychloroquine monotherapy had low potential to increase QTc intervals. However, when given concurrently with protease inhibitors which have possible or conditional risk, the odds of QTc prolongation increased fivefold. Interestingly, independent of drug therapy, the presence of systemic inflammatory response syndrome (SIRS) resulted in four times higher odds of QTc prolongation, leading to the postulation that some QTc events seen in COVID-19 patients may be due to the disease itself. ECG monitoring should be continued for at least a week from the initiation of treatment.

Clinical characteristics and risk factors for severe COVID-19 infections in Malaysia: A nationwide observational study.

BACKGROUND: COVID-19 emerged as a major public health outbreak in late 2019. Malaysia reported its first imported case on 25th January 2020, and adopted a policy of extensive contact tracing and hospitalising of all cases. We describe the clinical characteristics of COVID-19 cases nationwide and determine the risk factors associated with disease severity. METHOD: Clinical records of all RT-PCR confirmed COVID-19 cases aged ≥12 years admitted to 18 designated hospitals in Malaysia between 1st February and 30th May 2020 with complete outcomes were retrieved. Epidemiological history, co-morbidities, clinical features, investigations, management and complications were captured using REDCap database. Variables were compared between mild and severe diseases. Univariate and multivariate regression were used to identify determinants for disease severity. FINDINGS: The sample comprised of 5889 cases (median age 34 years, male 71.7%). Majority were mild (92%), and 3.3% required intensive care, with 80% admitted within the first five days. Older age (≥51 years), underlying chronic kidney disease and chronic pulmonary disease, fever, cough, diarrhoea, breathlessness, tachypnoea, abnormal chest radiographs and high serum CRP (≥5 mg/dL) on admission were significant determinants for severity (p<0.05). The case fatality rate was 1.2%, and the three commonest complications were liver injuries (6.7%), kidney injuries (4%), and acute respiratory distress syndrome (2.3%). INTERPRETATIONS: Lower case fatality rate was possibly contributed by young cases with mild diseases and early hospitalisation. Abnormal chest radiographic findings in elderly with tachypnoea require close monitoring in the first five days to detect early deterioration.

Zika virus infection in Malaysia: an epidemiological, clinical and virological analysis.

BACKGROUND: A major outbreak of the Zika virus (ZIKV) has been reported in Brazil in 2015. Since then, it spread further to other countries in the Americas and resulted in declaration of the Public Health Emergency of International Concern (PHEIC) by World Health Organization. In 2016, Singapore reported its first minor ZIKV epidemic. Malaysia shares similar ecological environment as Brazil and Singapore which may also favor ZIKV transmission. However, no ZIKV outbreak has been reported in Malaysia to date. This study aimed to discuss all confirmed ZIKV cases captured under Malaysia ZIKV surveillance system after declaration of the PHEIC; and explore why Malaysia did not suffer a similar ZIKV outbreak as the other two countries. METHODS: This was an observational study reviewing all confirmed ZIKV cases detected in Malaysia through the ZIKV clinical surveillance and Flavivirus laboratory surveillance between June 2015 and December 2017. All basic demographic characteristics, co-morbidities, clinical, laboratory and outcome data of the confirmed ZIKV cases were collected from the source documents. RESULTS: Only eight out of 4043 cases tested positive for ZIKV infection during that period. The median age of infected patients was 48.6 years and majority was Chinese. Two of the subjects were pregnant. The median interval between the onset of disease and the first detection of ZIKV Ribonucleic Acid (RNA) in body fluid was 3 days. Six cases had ZIKV RNA detected in both serum and urine samples. Phylogenetic analysis suggests that isolates from the 7 cases of ZIKV infection came from two clusters, both of which were local circulating strains. CONCLUSION: Despite similar ecological background characteristics, Malaysia was not as affected by the recent ZIKV outbreak compared to Brazil and Singapore. This could be related to pre-existing immunity against ZIKV in this population, which developed after the first introduction of the ZIKV in Malaysia decades ago. A serosurvey to determine the seroprevalence of ZIKV in Malaysia was carried out in 2017. The differences in circulating ZIKV strains could be another reason as to why Malaysia seemed to be protected from an outbreak.