Dear Editor.The coronavirus disease 2019(COVID-19)pandemic caused by widespread infection with the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)(Chen et al.,2020;Guan et al.,2020)has led to a global health crisis.More than 3.5 million infections and 246,838 deaths have occurred as of May 4,2020(Saqrane and El Mhammedi,2020),with a rapid upward trend.Many CO VID-19 patients suffer from complicated systemic injuries such as cardiac(Chen et al.,2020)and hepatic(Huang et al.,2020)damages.
Bo YuChenze LiPeng ChenJia LiHualiang JiangDao-Wen Wang
Recent evidences suggested that cyclic guanosine monophosphate-specific phosphodiesterase 5 （PDE5） inhibitor represents an important therapeutic target for cardiovascular diseases. Whether and how it ameliorates cardiac fibrosis, a major cause of diastolic dysfunction and heart failure, is unknown. The purpose of this study was to investigate the effects of PDE5 inhibitor on cardiac fibrosis. We assessed cardiac fibrosis and pathology in mice subjected to transverse aortic constriction （TAC）. Oral sildenafil, a PDE5 inhibitor, was administered in the therapy group. In control mice, 4 weeks of TAC induced significant cardiac dysfunction, cardiac fibrosis, and cardiac fibroblast activation （proliferation and transformation to myofibroblasts）. Sildenafil treatment markedly prevented TAC-induced cardiac dysfunction, cardiac fibrosis and cardiac fibroblast activation but did not block TAC-induced transforming growth factor-β0 （TGF-β1） production and phosphorylation of Smad2/3. In isolated cardiac fibroblasts, sildenafil blocked TGF-β1-induced cardiac fibroblast transformation, proliferation and collagen synthesis. Furthermore, we found that sildenafil induced phosphorylated cAMP response element binding protein （CREB） and reduced CREB-binding protein 1 （CBP1） recruitment to Smad transcriptional complexes. PDE5 inhibition prevents cardiac fibrosis by reducing CBP1 recruitment to Smad transcriptional complexes through CREB activation in cardiac fibroblasts.
Wei Gong＊ Mengwen Yan Junxiong Chen Sandip Chaugai Chen Chen Daowen Wang
Coronavirus disease 2019(COVID-19)is a pandemic with no specific drugs and high fatality.The most urgent need is to find effective treatments.We sought to determine whether hydroxychloroquine(HCQ)application may reduce the death risk of critically ill COVID-19 patients.In this retrospective study,we included 550 critically ill COVID-19 patients who need mechanical ventilation in Tongji Hospital,Wuhan,from February 1,2020 to April 4,2020.All 550 patients received comparable basic treatments including antiviral drugs and antibiotics,and 48 of them were treated with oral HCQ treatment(200 mg twice a day for 7–10 days)in addition to the basic treatments.Primary endpoint is fatality of patients,and inflammatory cytokine levels were compared between HCQ and non-hydroxychloroquine(NHCQ)treatments.We found that fatalities are 18.8%(9/48)in HCQ group,which is significantly lower than 47.4%(238/502)in the NHCQ group(P<0.001).The time of hospital stay before patient death is 15(10–21)days and 8(4–14)days for the HCQ and NHCQ groups,respectively(P<0.05).The levels of inflammatory cytokine IL-6 were significantly reduced from 22.2(8.3–118.9)pg mL–1 at the beginning of the treatment to 5.2(3.0–23.4)pg mL–1(P<0.05)at the end of the treatment in the HCQ group but there is no change in the NHCQ group.These data demonstrate that addition of HCQ on top of the basic treatments is highly effective in reducing the fatality of critically ill patients of COVID-19 through attenuation of inflammatory cytokine storm.Therefore,HCQ should be prescribed as a part of treatment for critically ill COVID-19 patients,with possible outcome of saving lives.
Bo YuChenze LiPeng ChenNing ZhouLuyun WangJia LiHualiang JiangDao-Wen Wang
