Evaluation of hydroxychloroquine or chloroquine for the prevention of COVID-19 (COPCOV): A double-blind, randomised, placebo-controlled trial.

BACKGROUND: Hydroxychloroquine (HCQ) has proved ineffective in treating patients hospitalised with Coronavirus Disease 2019 (COVID-19), but uncertainty remains over its safety and efficacy in chemoprevention. Previous chemoprevention randomised controlled trials (RCTs) did not individually show benefit of HCQ against COVID-19 and, although meta-analysis did suggest clinical benefit, guidelines recommend against its use. METHODS AND FINDINGS: Healthy adult participants from the healthcare setting, and later from the community, were enrolled in 26 centres in 11 countries to a double-blind, placebo-controlled, randomised trial of COVID-19 chemoprevention. HCQ was evaluated in Europe and Africa, and chloroquine (CQ) was evaluated in Asia, (both base equivalent of 155 mg once daily). The primary endpoint was symptomatic COVID-19, confirmed by PCR or seroconversion during the 3-month follow-up period. The secondary and tertiary endpoints were: asymptomatic laboratory-confirmed Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection; severity of COVID-19 symptoms; all-cause PCR-confirmed symptomatic acute respiratory illness (including SARS-CoV-2 infection); participant reported number of workdays lost; genetic and baseline biochemical markers associated with symptomatic COVID-19, respiratory illness and disease severity (not reported here); and health economic analyses of HCQ and CQ prophylaxis on costs and quality of life measures (not reported here). The primary and safety analyses were conducted in the intention-to-treat (ITT) population. Recruitment of 40,000 (20,000 HCQ arm, 20,000 CQ arm) participants was planned but was not possible because of protracted delays resulting from controversies over efficacy and adverse events with HCQ use, vaccine rollout in some countries, and other factors. Between 29 April 2020 and 10 March 2022, 4,652 participants (46% females) were enrolled (HCQ/CQ n = 2,320; placebo n = 2,332). The median (IQR) age was 29 (23 to 39) years. SARS-CoV-2 infections (symptomatic and asymptomatic) occurred in 1,071 (23%) participants. For the primary endpoint the incidence of symptomatic COVID-19 was 240/2,320 in the HCQ/CQ versus 284/2,332 in the placebo arms (risk ratio (RR) 0.85 [95% confidence interval, 0.72 to 1.00; p = 0.05]). For the secondary and tertiary outcomes asymptomatic SARS-CoV-2 infections occurred in 11.5% of HCQ/CQ recipients and 12.0% of placebo recipients: RR: 0.96 (95% CI, 0.82 to 1.12; p = 0.6). There were no differences in the severity of symptoms between the groups and no severe illnesses. HCQ/CQ chemoprevention was associated with fewer PCR-confirmed all-cause respiratory infections (predominantly SARS-CoV-2): RR 0.61 (95% CI, 0.42 to 0.88; p = 0.009) and fewer days lost to work because of illness: 104 days per 1,000 participants over 90 days (95% CI, 12 to 199 days; p < 0.001). The prespecified meta-analysis of all published pre-exposure RCTs indicates that HCQ/CQ prophylaxis provided a moderate protective benefit against symptomatic COVID-19: RR 0.80 (95% CI, 0.71 to 0.91). Both drugs were well tolerated with no drug-related serious adverse events (SAEs). Study limitations include the smaller than planned study size, the relatively low number of PCR-confirmed infections, and the lower comparative accuracy of serology endpoints (in particular, the adapted dried blood spot method) compared to the PCR endpoint. The COPCOV trial was registered with ClinicalTrials.gov; number NCT04303507. INTERPRETATION: In this large placebo-controlled, double-blind randomised trial, HCQ and CQ were safe and well tolerated in COVID-19 chemoprevention, and there was evidence of moderate protective benefit in a meta-analysis including this trial and similar RCTs. TRIAL REGISTRATION: ClinicalTrials.gov NCT04303507; ISRCTN Registry ISRCTN10207947.

Determinants of COVID-19 severity and mortality in children: A retrospective and multicenter cohort study in Medan, Indonesia.

This study investigated indicators of the severity and mortality of COVID-19 in children in Medan, Sumatera Utara Province, Indonesia. The aim of this study was to identify determinants of severity and outcome of children with COVID-19 as the lesson learned from the COVID-19 pandemic, particularly the limited health facilities in Indonesia. This retrospective cohort study was conducted in 2020, 2021, and 2022 at multiple centers. Inpatient and outpatient children confirmed to be SARS-CoV-2 positive were randomly recruited in the selected hospitals. Baseline data (demographic, clinical, laboratory and radiological data) were collected, and outcomes were classified as recovered/deceased (for the inpatient group) or returned to the hospital (for the outpatient group). Severity status was identified based on the Indonesia COVID-19 guidelines. The laboratory data were categorized according to international standards and data were analyzed using univariate analyzes followed by multivariate logistic regression. A total of 303 inpatient and 114 outpatient children were included in the analysis. Out of the total inpatient cases, nine patients died, with 2.9 mortality rate. Our final multivariate indicated that the presence of shortness of breath (SOB), anemia, and abnormal C-reactive protein (CRP) levels were significantly associated with the severity or the presence of emergency signs, while the presence of SOB and comorbidities were significantly associated with mortality in inpatient children with COVID-19. The presence of fever, cough, SOB, muscle ache and diarrhea were the reasons why the children were returned to the hospital from self-isolation at home among outpatient COVID-19 cases; however, the cough was the only significant factor in the final multivariate mode. This study highlights important determinants of COVID-19 severity and mortality in children, which should be considered during clinical decision-making in low-resource settings of healthcare centers in Indonesia.

The Body Weights' Follow Up Before and After 6 Months Therapy of Oral Anti-Tuberculosis Therapy in Children in Medan, Sumatra Utara.

BACKGROUND: Tuberculosis remains an important issue of children health, particularly in developing countries. Body Weight is one of the tuberculosis symptoms and used to identified children tuberculosis scoring in Indonesia. AIM: The study aims to get an overview of body weight and body weight increment during oral anti-tuberculosis in Medan, Sumatra Utara. METHODS: Medical records of children with tuberculosis in the Haji Hospital of Sumatra Utara located in Medan during January 2018 till July 2018 were compiled for the children characteristic, body weight before and after oral anti-tuberculosis treatment. RESULTS: There were 99 children medical records included in the study, 42.4% children 1 to 5 years old treated as tuberculosis. At the early treatment, many children were in severe malnutrition (85%). However, after 6 months of tuberculosis treatment, there were many children (78%) got their body weight increment. CONCLUSION: Body weight is an important sign and symptom of children with tuberculosis.