Ivermectin exposures reported to the Poisons Information Helpline in South Africa during the COVID-19 pandemic.

BACKGROUND: Ivermectin is an antiparasitic drug that has shown in vitro activity against COVID­19. Clinical studies supporting ivermectin for COVID­19 prevention and treatment are conflicting, with important limitations. Public support for ivermectin is significant, with extensive off-label use despite the conflicting views on its efficacy. Ivermectin tablets and injectable formulations are not registered in South Africa for human use by the South African Health Products Regulatory Authority. The National Department of Health does not currently recommend the use of ivermectin for COVID­19. OBJECTIVES: To describe cases of ivermectin exposure reported to the Poisons Information Helpline of the Western Cape (PIHWC) before and after publication of the drug's in vitro activity against SARS-CoV-2. METHODS: In a retrospective review, ivermectin-related calls reported to the PIHWC from 1 June 2015 to 30 June 2020 (period 1) were compared with calls received from 1 July 2020 to 31 July 2021 (period 2), dichotomised according to the first publication indicating ivermectin activity against SARS-CoV-2. RESULTS: Seventy-one cases were screened, and 65 were included for analysis; 19 cases were reported during period 1 and 46 during period 2. During period 2, 25 ivermectin cases (54.3%) were related to COVID­19 use. Of these, 24 cases (52.2%) involved veterinary preparations, 3 (6.5%) human preparations and 19 (41.3%) unknown preparations. Fourteen cases (73.7%) during period 1 and 30 (65.2%) during period 2 were reported to be symptomatic. The most common organ systems involved were the central nervous (n=26 cases; 40.0%), gastrointestinal (n=18; 27.7%), ocular (n=9; 13.8%) and dermatological (n=5; 7.7%) systems. CONCLUSION: Ivermectin-related exposure calls increased during study period 2, probably as a result of ivermectin being used as preventive and definitive therapy for COVID­19 in the absence of robust evidence on efficacy, dosing recommendations or appropriate formulations.

Bleeding and thrombosis outcomes in hospitalised COVID-19 patients on low-molecular-weight heparin and antiplatelet therapy.

BACKGROUND: An increased incidence of thromboembolic events in hospitalised COVID­19 patients has been demonstrated despite the use of low-molecular-weight heparin (LMWH). Antiplatelet therapy prior to admission and early in the disease course has been hypothesised to be protective against thrombosis. OBJECTIVES: To describe the bleeding and thrombosis outcomes in hospitalised patients with confirmed COVID­19 receiving LMWH, with and without concomitant antiplatelet therapy. Secondary objectives were to explore predictors of bleeding and thrombosis outcomes, and dosing practices of antiplatelet therapy and LMWH. METHODS: We conducted a descriptive, cross-sectional study of bleeding and thrombosis outcomes at Tygerberg Academic Hospital, Cape Town, South Africa, during the first COVID­19 wave, in 808 hospitalised patients with confirmed COVID­19 receiving LMWH with and without concomitant antiplatelet therapy. Multivariate logistic regression analysis was performed if predictors were deemed statistically and clinically significant. RESULTS: Patients receiving both LMWH and antiplatelet therapy had similar bleeding outcomes compared with patients only receiving LMWH (odds ratio (OR) 1.5; 95% confidence interval (CI) 0.6 - 4.0). Patients receiving both LMWH and antiplatelet therapy had increased odds of developing thrombosis compared with patients only receiving LMWH (OR 4.8; 95% CI 2.1 - 10.7). CONCLUSION: The bleeding risk in COVID­19 patients receiving both LMWH and antiplatelet therapy was not significantly increased. A potentially higher risk of thrombosis in patients receiving LMWH and antiplatelet therapy was observed. However, this could reflect confounding by indication. Randomised studies are required to further evaluate the use of antiplatelet therapy to treat hospitalised patients with COVID­19.

Current evidence for directed and supportive investigational therapies against COVID-19.

Coronavirus disease 2019 (COVID-19) is a global health crisis. There is currently a great need for effective and safe therapies directed at the disease, but no drugs are presently registered for use in COVID-19. Several directed therapies have been proposed, and most are still in clinical trials. Currently available published, peer-reviewed results mostly involve small sample sizes with study limitations restricting the interpretation of the findings. Many trials currently published also do not have a control group, limiting the interpretation of the effect of the intervention. Investigational directed therapies as well as investigational supportive therapies against COVID-19 are reviewed here. Chloroquine and hydroxychloroquine show promise as directed therapies, but current trial results are conflicting. Lopinavir/ritonavir also shows potential, but was started late in the disease course in most trials. No randomised controlled evidence is currently available for remdesivir and favipiravir. Corticosteroid use is not recommended for directed therapy against COVID-19, and the role of tocilizumab is currently unclear, based on limited evidence. Early initiation of investigational directed therapies may provide benefit in selected patients. The results from larger randomised controlled trials will clarify the place of these therapies in COVID-19 treatment.