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Through the Ebola outbreak in 2014, the WHO advised the use of convalescent plasma or whole-blood therapies

Through the Ebola outbreak in 2014, the WHO advised the use of convalescent plasma or whole-blood therapies. drugs are being investigated, predominately those with activity against various influenza subtypes and other RNA viruses. These include favipiravir (T-705, Avigan), umifenovir (Arbidol), triazavirin (TZV), and baloxavir marboxil (Xofluza). Many trials are focusing on drugs typically used in the management of RNA viruses, such as HCV and HIV. These include danoprevir/ritonavir, azvudine, sofosbuvir/ledipasvir, sofosbuvir/daclatasvir, darunavir/cobicistat, and emtricitabine/ tenofovir (Table 1A: Antivirals). Additionally, there are 26 studies investigating the utility of antiviral interferon-based ITI214 free base treatments, interestingly also looking at various different routes of administration (e.g., nasal). Antimalarial Treatments Thirty-five trials are now investigating the use of the antimalarial drugs chloroquine and hydroxychloroquine against COVID-19 (Table 1A: Antimalarials). Chloroquine was found to have significant inhibitory effects on viral cell entry and replication [12]. An early report of clinical experience in 100 patients with COVID-19 reported both beneficial clinical and virological outcomes with chloroquine treatment [16]. More recently, a nonrandomised open-label study examining the effect of hydroxychloroquine (EU Clinical Trial Numbervii: 2020-000890-25; recruitment target stated as 25 participants in the registry) reported on a cohort of 36 patients [17]. It reported a significant reduction in nasopharyngeal swab viral positivity 6 days after inclusion in the hydroxychloroquine group compared with control. However, in a deviation from their Mouse monoclonal to R-spondin1 registry-described protocol, 16 patients were designated as controls and six patients received concurrent treatment with azithromycin to prevent bacterial superinfection. Selection of patients receiving azithromycin was based on clinical judgement. The subgroup receiving azithromycin all ITI214 free base had unfavorable viral swabs after 6 days compared with 57% (8/14) of hydroxychloroquine alone and 12.5% (2/16) of control [17]. This study is limited by its lack of randomisation and blinding, and small sample size. There is much interest in chloroquine or hydroxychloroquine for the treatment of COVID-19, with a further 34 studies registered (Table 1A: Antimalarials); however, only four report using a robust double-blind randomised controlled protocol to investigate efficacy. Immunosuppressants/Immunomodulators There is evidence that a hyperinflammatory response significantly contributes to mortality in COVID-19 infections [18]. Corticosteroids were previously trialled in SARS-CoV; however, the results were inconclusive and adverse effects were associated [19]. Seven registered studies are evaluating the effect of corticosteroids in COVID-19 (Table 1A: Immunosuppressants). There is also interest in the anti-IL-6 drug, tocilizumab (used in the treatment of rheumatoid arthritis), with seven registered trials. Other immunosuppressants being investigated include adalimumab (anti-TNF), eculizumab (anti-C5), sarilumab (anti-IL-6), ixekizumab (anti-17A), and fingolimod (sphingosine-1-phosphate receptor modulator, used against multiple sclerosis). Meplazumab (anti-CD147) inhibits not only T cell chemotaxis, but also virus cell entry [20]. A preprint of a study of 17 patients compared with 11 controls (“type”:”clinical-trial”,”attrs”:”text”:”NCT04275245″,”term_id”:”NCT04275245″NCT04275245, original recruitment target 20) reported improved clinical and virological outcomes [20]. Conversely, several studies are investigating immune stimulation. These include the anti-PD-1 antibody camrelizumab, recombinant IL-2, CSA0001 (LL-37 antiviral peptide with immunomodulatory functions), CD24FC [fusion protein that prevents Toll-like receptor (TLR) activation and activates immunosuppressive Siglec signalling] and recombinant human granulocyte colony-stimulating factor (rhG-CSF) (Table 1A: Immune Modulators). Three studies (“type”:”clinical-trial”,”attrs”:”text”:”NCT04299724″,”term_id”:”NCT04299724″NCT04299724, “type”:”clinical-trial”,”attrs”:”text”:”NCT04276896″,”term_id”:”NCT04276896″NCT04276896, and ChiCTR2000030750) examine the efficacy of experimental vaccines in infected patients. Three further studies are investigating nonpharmaceutical interventions to modulate the immune system using cytokine filtration devices, such as oXiris and CytoSorb, to reduce circulating cytokines and inflammatory mediators (Table 1A: Cytokine Removal). Cell and Plasma-Based Therapy Twenty-four registered studies plan to investigate the role of mesenchymal stem cells (MSCs) (Table 1A: Cell-Based Therapies). MSCs have immunomodulatory and tissue repair effects through the secretion of cytokines and ITI214 free base growth factors. They have previously been examined in a Phase I trial in Adult Respiratory Distress Syndrome (ARDS) [21]. Given that most of the deaths in COVID-19 are from respiratory failure, MSCs are postulated to have a beneficial effect. So far, one study of MSCs (ChiCTR2000029990, recruitment target stated as 120 participants in the registry) has reported results in seven patients with COVID-19, showing improvement in.