The Anti-Coronavirus Therapies (ACT) Trials: Design, Baseline Characteristics, and Challenges.

Background: Effective treatments for COVID-19 are urgently needed, but conducting randomized trials during the pandemic has been challenging. Methods: The Anti-Coronavirus Therapy (ACT) trials are parallel factorial international trials that aimed to enroll 3500 outpatients and 2500 inpatients with symptomatic COVID-19. The outpatient trial is evaluating colchicine vs usual care, and aspirin vs usual care. The primary outcome for the colchicine randomization is hospitalization or death, and for the aspirin randomization, it is major thrombosis, hospitalization, or death. The inpatient trial is evaluating colchicine vs usual care, and the combination of rivaroxaban 2.5 mg twice daily and aspirin 100 mg once daily vs usual care. The primary outcome for the colchicine randomization is need for high-flow oxygen, need for mechanical ventilation, or death, and for the rivaroxaban plus aspirin randomization, it is major thrombotic events, need for high-flow oxygen, need for mechanical ventilation, or death. Results: At the completion of enrollment on February 10, 2022, the outpatient trial had enrolled 3917 patients, and the inpatient trial had enrolled 2611 patients. Challenges encountered included lack of preliminary data about the interventions under evaluation, uncertainties related to the expected event rates, delays in regulatory and ethics approvals, and in obtaining study interventions, as well as the changing pattern of the COVID-19 pandemic. Conclusions: The ACT trials will determine the efficacy of anti-inflammatory therapy with colchicine, and antithrombotic therapy with aspirin given alone or in combination with rivaroxaban, across the spectrum of mild, moderate, and severe COVID-19. Lessons learned from the conduct of these trials will inform planning of future trials.

Contexte: Il est urgent de mettre au point des traitements efficaces contre la COVID-19, mais il n'est pas facile de réaliser des essais à répartition aléatoire dans un contexte pandémique. Méthodologie: Les essais internationaux factoriels ACT (Anti-Coronavirus Therapy) avaient un objectif d'inscription de 3 500 patients externes et de 2 500 patients hospitalisés présentant une COVID-19 symptomatique. L'essai mené auprès de patients externes visait à évaluer la colchicine par rapport aux soins habituels, et l'aspirine par rapport aux soins habituels. Le paramètre d'évaluation principal au terme de la répartition aléatoire des patients était l'hospitalisation ou le décès dans le groupe traité par la colchicine, et la thrombose majeure, l'hospitalisation ou le décès dans le groupe traité par l'aspirine. L'essai mené auprès de patients hospitalisés visant à évaluer la colchicine par rapport aux soins habituels, et un traitement associant le rivaroxaban à 2,5 mg deux fois par jour et l'aspirine à 100 mg une fois par jour par rapport aux soins habituels. Le paramètre d'évaluation principal au terme de la répartition aléatoire des patients était le recours à l'oxygénothérapie à haut débit ou à la ventilation mécanique ou le décès dans le groupe traité par la colchicine, et la survenue de manifestations thrombotiques majeures, le recours à l'oxygénothérapie à haut débit ou à la ventilation mécanique ou le décès dans le groupe traité par l'association rivaroxaban-aspirine. Résultats: À la fin de la période d'inscription, le 10 février 2022, 3 917 patients externes et 2 611 patients hospitalisés formaient la population des essais. Certains aspects se sont révélés problématiques, notamment le manque de données préliminaires sur les interventions à évaluer, les incertitudes liées aux taux d'événements prévus, les retards touchant les approbations réglementaires et éthiques et les interventions de recherche, de même que l'évolution de la pandémie de COVID-19. Conclusions: Les essais ACT détermineront l'efficacité du traitement anti-inflammatoire par la colchicine et du traitement antithrombotique par l'aspirine, administrée seule ou en association avec le rivaroxaban, contre la COVID-19 légère, modérée ou sévère. Les leçons tirées de ces essais orienteront la planification d'essais ultérieurs.

Experience of Rwanda on COVID-19 Case Management: From Uncertainties to the Era of Neutralizing Monoclonal Antibodies.

The management of COVID-19 in Rwanda has been dynamic, and the use of COVID-19 therapeutics has gradually been updated based on scientific discoveries. The treatment for COVID-19 remained patient-centered and entirely state-sponsored during the first and second waves. From the time of identification of the index case in March 2020 up to August 2021, three versions of the clinical management guidelines were developed, with the aim of ensuring that the COVID-19 patients treated in Rwanda were receiving care based on the most recent therapeutic discoveries. As the case load increased and imposed imminent heavy burdens on the healthcare system, a smooth transition was made to enable that the asymptomatic and mild COVID-19 cases could continue to be closely observed and managed while they remained in their homes. The care provided to patients requiring facility-based interventions mainly focused on the provision of anti-inflammatory drugs, anticoagulation, broad-spectrum antibiotic therapy, management of hyperglycemia and the provision of therapeutics with a direct antiviral effect such as favipiravir and neutralizing monoclonal antibodies. The time to viral clearance was observed to be shortest among eligible patients treated with neutralizing monoclonal antibodies (bamlanivimab). Moving forward, as we strive to continue detecting COVID-19 cases as early as possible, and promptly initiate supportive interventions, the use of neutralizing monoclonal antibodies constitutes an attractive and cost-effective therapeutic approach. If this approach is used strategically along with other measures in place (i.e., COVID-19 vaccine roll out, etc.), it will enable us to bring this global battle against the COVID-19 pandemic under full control and with a low case fatality rate.

COVID-19 Vaccines: Ensuring Social Justice and Health Equity among Refugees in Africa.

COVID-19 poses a particular threat to refugees in Africa. Overcrowded living conditions and lack of effective sanitation make refugees highly vulnerable to infection. Furthermore, migration has the potential to undermine measures to control viral spread. As a result, vaccination of the refugee community in Africa must be considered key in the vaccination plan to end the worldwide COVID-19 pandemic. Although the WHO has approved vaccines for emergency use worldwide in vulnerable groups through the COVID-19 Vaccines Global Access (COVAX) program, there is a lack of a strategy for achieving vaccination in the African refugee population. A specific strategy for refugee vaccination must be among the top priorities at national, regional, and global levels to ensure all refugees and asylum seekers in African countries have equitable and quality vaccine assistance regardless of displacement, statelessness, and financial hardship. We call on leaders in Africa and worldwide to ensure that refugee vaccination is a priority to protect this highly at-risk population and achieve an end to the current pandemic.

Injury burdens and care delivery in relation to the COVID-19 pandemic in Kigali, Rwanda: A prospective interrupted cross-sectional study.

INTRODUCTION: Injuries cause significant burdens in sub-Saharan Africa. In Rwanda, national regulations to reduce COVID-19 altered population mobility and resource allocations. This study evaluated epidemiological trends and care among injured patients preceding and during the COVID-19 pandemic at the Centre Hospitalier Universitaire de Kigali (CHUK) in Kigali, Rwanda. METHODS: This prospective interrupted cross-sectional study enrolled injured adult patients (≥15 years) presenting to the CHUK emergency department (ED) from January 27th-March 21st (pre-COVID-19 period) and June 1st-28th (intra-COVID-19 period). Trained study personnel continuously collected standardized data on enrolled participants through the first six-hours of ED care. The Kampala Trauma Score (KTS) was calculated as a metric of injury severity. Case characteristics prior to and during the pandemic were compared, statistical differences were assessed using χ2 or Fisher's exact tests. RESULTS: Data were collected from 409 pre-COVID-19 and 194 intra-COVID-19 cases. Median age was 32, with a male predominance (74.3%). Road traffic injuries (RTI) were the most common injury mechanism pre-COVID-19 (47.8%) and intra-COVID-19 (53.6%) (p = 0.27). There was a significant increase in the number of transfer cases during the intra-COVID-19 period (52.1%) versus pre-COVID-19 (41.3%) (p = 0.01). KTS was significantly lower among intra-COVID-19 patients (p = 0.04), indicating higher severity of presentation. In the intra-COVID-19 period, there was a significant increase in the number of surgery consultations (40.7%) versus pre-COVID-19 (26.7%) (p < 0.001). The number of hospital admissions increased from 35.5% pre-COVID-19 to 46.4% intra-COVID-19 (p = 0.01). There was no significant mortality difference pre-COVID-19 as compared to the intra-COVID-19 period among injured patients (p = 0.76). CONCLUSION: Emergency injury care showed increased injury burden, inpatient admission and resource requirements during the pandemic period. This suggests the spectrum of disease may be more severe and that greater resources for injury management may continue to be needed during the ongoing COVID-19 pandemic in Rwanda and other similar settings.