1 COVID‐19: AN URGENT PROBLEM WITH LIMITED TREATMENT OPTIONS

The novel severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) pandemic poses a serious threat to public health and local economies around the globe. This has created an urgent need to identify effective medications for its prevention and treatment.1 Among these treatments, the off‐label use of hydroxychloroquine (HCQ), a less toxic derivate of chloroquine, has become a common practice among clinicians, including paediatricians, despite lack of evidence of its clinical efficacy for this indication (especially for paediatric patients) at present time.2

Hydroxychloroquine is an attractive option as it has been shown to have in vitro antiviral and immunomodulatory activities, there is considerable experience of its use in a range variety of acute and chronic paediatric and adult diseases, and it has relatively low cost and availability.3 It is also accumulated in the lungs (and other tissues), achieving concentrations 200‐700 times higher in the lungs than in plasma, and the expectation is that it would act to inhibit SARS‐CoV‐2 infection.4, 5 There is preliminary albeit controversial evidence showing that HCQ might shorten the duration of the viral shedding.6 Although it is generally accepted that children are at less risk of serious illness and aggressive clinical course, younger age may be associated with a longer duration of viral shedding.7 It is theoretically desirable to target a reduction in the duration of viral shedding, as this could limit the community spread of SARS‐CoV‐2 and to prevent the transmission of the virus to high‐risk adults and healthcare workers.

However, it is not yet clear if the benefits outweigh the risks. The majority of children will have mild symptoms, and widespread use of hydroxychloroquine may confer only minimal benefit. There are concerns with the safety profile of HCQ, and many uncertainties around dosing for this indication, particularly in children.8 Furthermore, it is important to consider the cost‐effectiveness of any intervention used during the COVID‐19 pandemic. In low‐, middle‐ and high‐income settings, resources such as personal protective equipment (PPE) and intensive care supplies may be in short supply. Informed choices may need to be made in prioritising the most cost‐effective interventions, pharmacological or not, at individual and societal level. As the pandemic draws to a close, the societal and economic impact of COVID‐19 will have generational effects on child health and well‐being. The reversal of this will require a systemic and concerted effort at national and international level.

中文翻译：

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羟氯喹对 COVID-19 儿童的疗效、安全性和成本效益：需要证据。

1 COVID-19：治疗选择有限的紧迫问题

新型严重急性呼吸系统综合症冠状病毒 2 (SARS-CoV-2) 大流行对全球公共卫生和当地经济构成严重威胁。这就迫切需要确定有效的药物来预防和治疗。1在这些治疗中，羟氯喹 (HCQ) 是一种毒性较小的氯喹衍生物，已成为临床医生（包括儿科医生）的普遍做法，尽管缺乏证据表明其对这一适应症的临床疗效（尤其是对于儿科患者） ) 目前。2

羟氯喹是一种有吸引力的选择，因为它已被证明具有体外抗病毒和免疫调节活性，在各种急慢性儿科和成人疾病中的使用经验丰富，而且成本和可用性相对较低。3它还在肺部（和其他组织）中蓄积，在肺部的浓度是血浆中的 200-700 倍，预计它会抑制 SARS-CoV-2 感染。4, 5尽管存在争议，但初步证据表明 HCQ 可能会缩短病毒脱落的持续时间。6尽管普遍认为儿童患严重疾病和侵袭性临床病程的风险较小，但年龄越小可能与病毒脱落持续时间越长有关。7从理论上讲，减少病毒脱落的持续时间是可取的，因为这可以限制 SARS-CoV-2 的社区传播，并防止病毒传播给高危成人和医护人员。

但是，目前尚不清楚收益是否大于风险。大多数儿童会有轻微症状，广泛使用羟氯喹可能只会带来微乎其微的益处。人们对 HCQ 的安全性存在担忧，并且该适应症的剂量存在许多不确定性，尤其是在儿童中。8此外，重要的是要考虑在 COVID-19 大流行期间使用的任何干预措施的成本效益。在低收入、中等收入和高收入环境中，个人防护设备 (PPE) 和重症监护用品等资源可能会短缺。在个人和社会层面，可能需要做出明智的选择，以优先考虑最具成本效益的干预措施，无论是否药理学。随着大流行接近尾声，COVID-19 的社会和经济影响将对儿童健康和福祉产生世代影响。要扭转这种局面，需要在国家和国际层面进行系统和协调一致的努力。