Treating severe COVID-19 patients with the anticancer drug bevacizumab may reduce mortality and speed up recovery, according to a small clinical study in Italy and China that was led by researchers at Karolinska Institutet in Sweden between February and April 2020. On average, blood oxygen levels, body temperature and inflammatory markers significantly improved in patients treated with a single dose of bevacizumab in addition to standard care. The research is published inNature Communications。

"To reduce COVID-19 mortality, we aim to develop an effective therapeutic paradigm for treating patients with severe COVID-19," says corresponding author Yihai Cao, professor of vascular biology at the Department of Microbiology, Tumor and Cell Biology at Karolinska Institutet. "Our findings suggest that bevacizumab plus standard care is highly beneficial for patients with severe COVID-19 and should be considered as a potential first-line therapeutic regimen for this group."

Bevacizumab is a medication that has been used to treat various types of cancer since 2004. It works by slowing the formation of new blood vessels by inhibiting a growth factor known as VEGF. Many patients with severe COVID-19 have elevated levels of VEGF as well as symptoms associated with this marker, including excess fluid and disorganized blood vessels in the lungs. Against this background, the researchers designed a clinical trial to investigate the effect of combining bevacizumab with standard care for treating patients with severe COVID-19.

2020年2月中旬至4月初，从中国和意大利的两家医院招募了26名患者。这些患者确认了19例COVID和呼吸困难，低血氧水平和肺炎等症状。他们与26名具有相似特征的患者进行了回顾性匹配，这些患者大致在同一时期在同一医院接受了标准护理，因此作为对照组。

The recruits received standard care plus a single low dose of about 7.5 mg/kg bevacizumab, which markedly improved blood oxygen levels within 24 hours compared to the control group. By the end of the 28-day follow-up period, 92 percent of the bevacizumab-treated patients no longer needed the same level of oxygen support as before the trial began, compared with an improvement rate of 62 percent for the controls.

不ne of the bevacizumab-treated patients died and 17 (65 percent) improved so much that they were able to leave the hospital within the follow-up period. In the control group, three died and only 46 percent were discharged within 28 days. Bevacizumab also shortened the duration of oxygen-support to a median of nine days compared with 20 for the standard care group.

其他interesting findings include reduction in fever, an increase in white blood cells and a sharp decrease of c-reactive protein (CRP) levels, an inflammatory marker. No severe safety concerns were detected.

Yihai Cao说：“许多严重的Covid-19患者在长期住院期间需要大量的氧气支持，这对医疗用品构成了全球挑战。”“我们的研究表明，贝伐单抗可以帮助减少对氧气支持的需求，并减少医院的天数，从而改善个人患者的结果，同时减轻医疗资源的压力。”

The limitations of the study include the non-randomized nature of the trial, the short-term follow-up and the small size of the cohort.

下一步将是通过招募大量患者来设计随机和安慰剂对照试验，从而进一步评估贝伐单抗本身以及与其他疗法（例如抗病毒药和抗炎药）的潜在益处。

参考：Pang J, Xu F, Aondio G, et al. Efficacy and tolerability of bevacizumab in patients with severe Covid-19.Nat Comm。2021; 12（1）：814。doi：10.1038/S41467-021-21085-8

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