COVID-19: a recommendation to examine the effect of hydroxychloroquine in preventing infection and progression

Abstract

A novel coronavirus disease (COVID-19), caused by infection with SARS-CoV-2, has swept across 31 provinces in China and over 40 countries worldwide. The transition from first symptoms to acute respiratory distress syndrome (ARDS) is highly likely to be due to uncontrolled cytokine release. There is an urgent need to identify safe and effective drugs for treatment. Chloroquine (CQ) exhibits a promising inhibitory effect. However, the clinical use of CQ can cause severe side effects. We propose that hydroxychloroquine (HCQ), which exhibits an antiviral effect highly similar to that of CQ, could serve as a better therapeutic approach. HCQ is likely to attenuate the severe progression of COVID-19, inhibiting the cytokine storm by suppressing T cell activation. It has a safer clinical profile and is suitable for those who are pregnant. It is cheaper and more readily available in China. We herein strongly urge that clinical trials are performed to assess the preventive effects of HCQ in both disease infection and progression.

Figure 1.

The chemical structures of CQ and HCQ.

Figure 2.

A graphical illustration of the antiviral mechanisms of CQ and HCQ. Both chemicals can interfere with the glycosylation of ACE2 and reduce the binding efficiency between ACE2 on the host cells and the spike protein on the surface of the coronavirus. They can also increase the pH of endosomes and lysosomes, through which the fusion process of the virus with host cells and subsequent replication are prevented. When HCQ enters APCs, it prevents antigen processing and MHC class II-mediated autoantigen presentation to T cells. The subsequent activation of T cells and expression of CD154 and other cytokines are repressed. In addition, HCQ disrupts the interaction of DNA/RNA with TLRs and the nucleic acid sensor cGAS and therefore the transcription of pro-inflammatory genes cannot be stimulated. As a result, administration of CQ or HCQ not only blocks the invasion and replication of coronavirus, but also attenuates the possibility of cytokine storm. This figure appears in colour in the online version of JAC and in black and white in the print version of JAC.