The Use of Adjuvant Therapy in Preventing Progression to Severe Pneumonia in Patients with Coronavirus Disease 2019: A Multicenter Data Analysis

Zhichao Feng; Jennifer Li; Shanhu Yao; Qizhi Yu; Wenming Zhou; Xiaowen Mao; Huiling Li; Wendi Kang; Xin Ouyang; Ji Mei; Qiuhua Zeng; Jincai Liu; Xiaoqian Ma; Pengfei Rong; Wei Wang

SARS-CoV-2 can gain entry into the host cell through binding of the S-protein to the membrane-bound ACE2 aminopeptidase, which then is cleaved by serine proteases to allow for membrane fusion and invasion. 14,28 Following infection, there is a reduction in pulmonary ACE2, either through internalization with viral entry and/or downregulation of ACE2 enzyme during this process. Hence this may exacerbate the lower baseline ACE2 function in hypertensive patients to lead to the accumulation of AII and reduced angiotensin 1-7 and subsequently worse immune-related cytolysis and lung injury, which was validated by the linear association between elevated plasma AII level and viral load or lung injury in COVID-19 patients. 29 The use of ACEI or ARB likely promotes feedback upregulation of ACE2 expression in hypertension, although there are animal and human studies which have also found either no effect or downregulation of ACE2 level in the setting of diabetes, hypertension or cardiovascular disease, with or without ACE/ARB therapy. 25, [30] [31] [32] [33] Nonetheless, this may explain our finding that ACEI/ARB therapy can be protective in SARS-CoV-2 infection. Further evidence that would support this come from earlier studies in which ACEI/statins were protective in severe pneumonia, recombinant ACE2 protected mice from lung injury following SARS-CoV infection, and RAAS blockade reduced acute lung injury in rats injected with SARS-CoV S-protein. 34, 35 Currently, there is still no specific treatment for COVID-19 except for supportive care. In our cohort, 94.2% of non-severe patients received nonspecial antiviral therapy from just after admission. The combination protocol and medication dose varied in different hospitals. However, our results did not support any single or combined antiviral treatments to limit the progression of COVID-19. In addition, none of 25 patients treated with chloroquine developed severe pneumonia, though without statistical significance. This is unfortunately limited by the degree of heterogeneity . CC-BY-NC-ND 4.0 International license It is made available under a author/funder, who has granted medRxiv a license to display the preprint in perpetuity.