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Hydroxychloroquine and Interferons for the Prophylaxis and Early Treatment of Covid-19-Current Clinical Advances

Alexander Chuan Yang, Youcheng Liu, Yongzhao Shao, Charlotte Zhong Yang, Jinping Xu, Bing Yang

Coronavirus disease 2019 (Covid-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV- 2) calls for unprecedented measures to control the spread of the virus. SARS-CoV-2 enters into the cell by direct fusion to the cell membrane or fusion to the membrane of endocytic vesicles. Hydroxychloroquine (HCQ) inhibits enzymes in the endocytic vesicle and has been studied for its efficacy since the beginning of the pandemic. Retrospective analysis of healthcare workers (HCWs) and observational studies suggest protective effect of taking HCQ prophylactically. However, studies on autoimmune patients taking HCQ provide conflicting results. In a postexposure prophylaxis randomized controlled trial (RCT), Boulware et al. found a non-significant difference in incidence between HCQ and placebo group (11.8% vs. 14.3%, p=0.35). However, our re-analysis of the data suggests HCQ use for Covid-19 is time-sensitive. Early use of HCQ after exposure appears to confer some protection from symptomatic Covid-19 (p=0.0496). Another RCT by Mitja et al. found that on day 14 after the exposure, 55.6% more patients given HCQ had IgM/IgG against the virus (p=0.01) compared to placebo group, suggesting early activation of adaptive immune response. No reportable major side effects occurred in either study. In the current urgent pandemic crisis without any established protocols for prophylaxis, these results indicate that the use of HCQ in prophylaxis and early treatment of Covid-19 soon after exposure offers benefit. Initial data using interferon (IFN) beta-1 and nebulized IFN alpha-2 for the treatment of Covid-19 have been promising. The prophylactic use of IFN alpha-2b intranasally against Covid-19 as suggested by us at the early stage of the pandemic has not yet been tested. More RCT studies are needed to evaluate the efficacy of HCQ and IFN alpha-2 separately and in combination for prophylaxis against Covid-19. Future studies should give us more definitive answers.