【Cochrane简语概要】瑞德西韦是治疗 COVID-19 的有效方法吗？

关键信息

• 对于COVID-19成年住院者，与安慰剂或常规照护相比，瑞德西韦对治疗后28天内的全因死亡率可能没有或没多大影响。

• 我们不确定瑞德西韦是否改善或加重患者的病情，这是基于患者是否需要有更多或更少的呼吸帮助。

• 科研人员应就COVID-19的关键结局达成一致，未来相关研究也应对这些领域进行探究。这就使得未来更新本系统综述时，对瑞德西韦治疗COVID-19得出更确切的结论。

（图片来源于new.qq.com）

瑞德西韦是什么？

瑞德西韦是一种对抗病毒的药物。已有显示，此药可预防引起疾病COVID-19的病毒 SARS-CoV-2 的繁殖。医疗监管机构已批准紧急使用瑞德西韦治疗 COVID-19患者。

我们想知道什么？

我们想了解的是，与安慰剂或常规照护相比，瑞德西韦是否可有效治疗COVID-19住院患者，以及是否会引起不良反应。

COVID-19患者接受不同类型的呼吸支持，这取决于其呼吸困难的严重程度。我们以患者所接受的通气支持类型来衡量瑞德西韦治疗COVID-19是否成功。呼吸支持的类型包括：

• 严重呼吸困难者：采用有创机械通气，将气管插管置入患者肺部，再由机器（呼吸机）进行呼吸。患者带呼吸机通气时要进行药物镇静。

中重度呼吸困难者：经口鼻式或头盔式面罩进行无创机械通气。空气或氧气被推送入面罩内。患者接受这种治疗时通常是清醒得。

• 中度呼吸困难者：经面罩或鼻内接口给氧。患者仍然可以呼吸室内空气。

我们对以下结局感兴趣：

• 治疗后28天内的全因死亡；

• 患者治疗后是否好转，以机械通气或给氧时间来衡量；

• 患者的病情是否恶化，以致需要给氧或机械通气；

• 生活质量；

• 任何不良反应；以及

• 任何严重不良反应。

我们做了什么？

我们检索了瑞德西韦治疗 COVID-19 成年患者的研究，并与安慰剂或标准照护进行比较。任何因COVID-19入院的患者，不论性别或种族。

我们比较和总结了相关研究结果，并根据研究方法和规模等对证据质量进行了评价。

我们发现了什么？

我们发现了5项研究，涉及7452名COVID-19住院者。其中3886人接受了瑞德西韦治疗。受试者平均年龄59岁。相关研究来自世界各地，主要是高收入和中高收入国家。

主要结果

纳入的研究对COVID-19住院者进行瑞德西韦治疗，最长达28天，并与安慰剂或常规照护将行比较。

全因死亡

• 瑞德西韦可能对全因死亡没有或没多大影响（4项研究共7142人）。与安慰剂或标准照护相比，每1000人中因瑞德西韦治疗而死亡者多减少了8名。

瑞德西韦使患者病情好转了吗？

• 瑞德西韦对患者的有创机械通气时间可能没有或没多大影响（2项研究共1298名受试者）。

• 我们不知道瑞德西韦是增加还是降低了补充给氧时间（3项研究共1691名受试者）。

患者服用瑞德西韦后病情加重了吗？

• 我们不知道瑞德西韦治疗的患者是有更大或更小的可能需要机械通气（有创或无创）（3项研究共6696名受试者）。

• 患者可能有更小的可能需要有创机械通气（2项研究共1159名受试者）。

• 我们不知道瑞德西韦治疗的患者是有更大或更小的可能需要无创机械通气（1项研究共573名受试者）。

• 我们不知道患者是有更大或更小的可能需要面罩或鼻内接口给氧（1项研究共138名受试者）。

生活质量

纳入的研究均未报告生活质量。

不良影响

• 我们不知道瑞德西韦是否会增加或降低不良反应（3项研究共1674名受试者）。

• 与安慰剂或标准照护相比，瑞德西韦治疗者发生严重不良反应的可能性更低（3项研究共 1674名受试者）。与安慰剂或标准照护相比，瑞德西韦治疗使每 1000人中有不良反应者多减少63名或更多。

证据的局限性有哪些？

关于全因死亡和严重不良反应，我们有中等质量证据；但因各研究所用的测量与结果记录方法存在差异，其他方面的质量证据比较有限，我们也未找到很多与所感性的结果有关的研究。

证据的时效性如何？

证据截至 2021年4月16日。

结论: 

根据目前可及的证据，瑞德西韦对感染SARS-CoV-2的成年住院者28天内的全因死亡率可能没有或没多大影响。我们不确定瑞德西韦对临床改善和恶化的影响。尚没有足够的资料以检验瑞德西韦对不同亚组死亡的影响，这些亚组以基线时的呼吸支持来界定。

有关瑞德西韦治疗COVID-19的有效性和安全性，未来的研究应提供更多已有界定的结局的资料，尤其是不同的人群亚组。这就使我们在未来更新本系统综述时，能够对瑞德西韦的潜在益处和危害得出更可靠的结论。本工作采用实时性方法，因此我们会定期更新本综述。

作者：Ansems K, Grundeis F, Dahms K, Mikolajewska A, Thieme V, Piechotta V, Metzendorf M-I, Stegemann M, Benstoem C, Fichtner F；译者：臧渝梨，Cochrane Hong Kong，香港中文大学医学院那打素护理学院；审校：李迅，Cochrane中国协作网成员单位，北京中医药大学循证医学中心；编辑排版：张晓雯、索于思，Cochrane中国协作网成员单位，北京中医药大学循证医学中心

相关文章链接

【Cochrane Plain Language Summary】Is remdesivir (an antiviral medicine) an effective treatment for COVID-19?

Key messages

• For adults hospitalised with COVID-19, remdesivir probably has little or no effect on deaths from any cause up to 28 days after treatment compared with placebo (sham treatment) or usual care. 

• We are uncertain whether remdesivir improves or worsens patients’ condition, based on whether they needed more or less help with breathing.

• Researchers should agree on key outcomes to be used in COVID-19 research, and future studies should investigate these areas. This would allow future updates of this review to draw more certain conclusions about the use of remdesivir to treat COVID-19.

What is remdesivir?

Remdesivir is a medicine that fights viruses. It has been shown to prevent the virus that causes COVID-19 (SARS-CoV-2) from reproducing. Medical regulators have approved remdesivir for emergency use to treat people with COVID-19. 

What did we want to find out?

We wanted to know if remdesivir is an effective treatment for people in hospital with COVID-19 and if it causes unwanted effects compared to placebo or usual care.

People with COVID-19 are given different kinds of breathing support, depending on how severe their breathing difficulties are. We used the types of breathing support people received as a measure of the success of remdesivir in treating COVID-19. Types of breathing support included:

• for severe breathing difficulties: invasive mechanical ventilation, when a breathing tube is put into patients’ lungs, and a machine (ventilator) breathes for them. Patients are given medicine to make them sedated whilst they are on a ventilator.

• for moderate to severe breathing difficulties: non-invasive mechanical ventilation through a mask over the nose and/or mouth, or a helmet. Air or oxygen is pushed through the mask. Patients are generally awake for this treatment.

• for moderate breathing difficulties: oxygen via a mask or prongs that sit in the nostrils. Patients can still breathe room air.

We were interested in the following outcomes:

• deaths from any cause in the 28 days after treatment;

• whether patients got better after treatment, measured by how long they spent on mechanical ventilation or oxygen;

• whether patients’ condition worsened so that they needed oxygen or mechanical ventilation;

• quality of life;

• any unwanted effects; and 

• serious unwanted effects.

What did we do? 

We searched for studies that investigated remdesivir to treat adults with COVID-19 compared to placebo or standard care. Patients were hospitalised with COVID-19 and could be of any gender or ethnicity.  

We compared and summarised the results of the studies and rated our confidence in the evidence, based on factors such as study methods and sizes.

What did we find? 

We found 5 studies with 7452 people hospitalised with COVID-19. Of these, 3886 people were given remdesivir. The average age of patients was 59 years. Studies took place around the world, mainly in high- and upper-middle-income countries. 

Main results 

The included studies compared remdesivir to placebo or usual care in people hospitalised with COVID-19 for up to 28 days.

Deaths from any cause

• Remdesivir probably makes little or no difference to deaths from any cause (4 studies, 7142 people). In 1000 people, 8 fewer die with remdesivir compared to placebo or standard care.

Did patients get better with remdesivir?

• Remdesivir may have little or no effect on the length of time patients spent on invasive mechanical ventilation (2 studies, 1298 people). 

• We do not know whether remdesivir increases or decreases time on supplemental oxygen (3 studies, 1691 people).

Did patients get worse with remdesivir?

• We do not know whether patients are more or less likely to need any mechanical ventilation (invasive or non-invasive) with remdesivir (3 studies, 6696 people).

• Patients may be less likely to need invasive mechanical ventilation (2 studies, 1159 people).

• We do not know whether patients are more or less likely to need non-invasive mechanical ventilation (1 study, 573 people). 

• We do not know whether patients are more or less likely to need oxygen by mask or nasal prongs (1 study, 138 people).

Quality of life

• None of the included studies reported quality of life.

Unwanted effects

• We do not know whether remdesivir leads to more or fewer unwanted effects of any level (3 studies, 1674 people). 

• Patients are probably less likely to experience serious unwanted effects with remdesivir than with placebo or standard care (3 studies, 1674 people). In 1000 people, 63 fewer would experience a serious unwanted effect compared to placebo or standard care.

What are the limitations of the evidence?

We are moderately confident in the evidence for deaths from any cause and serious unwanted effects; however, our confidence in the other evidence is limited because studies used different methods to measure and record their results, and we did not find many studies for some of our outcomes of interest. 

How up-to-date is this evidence?

The evidence is current to 16 April 2021.

Authors' conclusions: 

Exercise did not reduce the number of ARI episodes, proportion of participants experiencing at least one ARI during the study, or the number of symptom days per episode of illness. However, exercise reduced the severity of ARI symptoms (two studies) and the number of symptom days during the study follow-up period (four studies). Small study size, risk of bias, and heterogeneity in the populations studied contributed to the uncertainty of the findings. Larger trials that are designed to avoid risk of bias associated with participant selection, blinding of outcomes assessors, and with adequate reporting of all outcomes proposed for measurement in trials, would help to provide more robust evidence.

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