Role of Ibuprofen and Other Medicines on Severity of Coronavirus Disease 2019 (COVID-19) Infections: a Case-control Study
试验速览
- 阶段
- 不适用
- 状态
- 撤回
- 发起方
- 主要终点
- Describe medications used prior to admission associated with worse infection in COVID-19 patients in France.
研究概览
简要总结
It has been suggested that ibuprofen might be associated with more severe cases of coronavirus infections, based on the observation that severe COVID cases had been exposed to ibuprofen, resulting in a warning by the French authorities.
This was attributed to:
- a suggestion that ibuprofen might upregulate ACE-2 thereby increasing the entrance of COVID-19 into the cells,
- an analogy with bacterial soft-tissue infections where more severe infections on NSAIDs are attributed to an immune-depressive action of NSAIDs, or to belated treatment because of initial symptom suppression,
- fever is a natural response to viral infection, and reduces virus activity: antipyretic activity might reduce natural defenses against viruses. However fever reduction in critically ill patients had no effect on survival.
However, these assertions are unclear: upregulation of ACEII would increase the risk of infection, not necessarily its severity, and would only apply to the use of NSAIDs before the infection, i.e. chronic exposure. It would be irrelevant to the infection once the patients are infected, i.e., to symptomatic treatment of COVID-19 infection.
Anti-inflammatory effect masking the early symptoms of bacterial infections resulting in later antibiotic or other treatment is not applicable: there is no treatment of the virus that might be affected by masking symptoms.
Antipyretic effect increasing the risk or the severity of infection would apply equally to all antipyretic agents including paracetamol, which share the same mechanism of action for fever reduction.
EMA remains prudent about this assertion
In addition, excess reliance on paracetamol while discouraging the use of ibuprofen might increase the risk of hepatic injury from paracetamol overdose. Paracetamol is the prime drug associated with liver injury and transplantation, in voluntary and inadvertent overdose or even at normal doses. This might be increased by COVID-related liver function alterations.
It is therefore proposed to conduct a case-control study in a cohort of patients admitted to hospital in France with COVID-19 infection.
详细描述
It has been suggested that ibuprofen might be associated with more severe cases of coronavirus infections, based on the observation that severe COVID cases had been exposed to ibuprofen, resulting in a warning by the French authorities (published in a french journal called "Le Monde" = The world).
This was attributed to:
- a suggestion that ibuprofen might upregulate ACE-2 thereby increasing the entrance of COVID-19 into the cells.This is based on a single study in streptozotocin-induced diabetic rats where ibuprofen decreases cardiac fibrosis. There seems to be no study in man. (https://www.dw.com/en/coronavirus-confusion-about-safety-of-ibuprofen/a-52824043) These authors noted an increased risk of severe COVID-19 in patients with hypertension or diabetes, and a possible role of Angiotensin converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) which also upregulate ACE-2, as do also thiazolidinedione antidiabetic drugs. The relevance of this up-regulation seems disputed.
- an analogy with bacterial soft-tissue infections where more severe infections on NSAIDs are attributed to an immune-depressive action of NSAIDs, or to belated treatment because of initial symptom suppression.
- fever is a natural response to viral infection, and reduces virus activity: antipyretic activity might reduce natural defenses against viruses. However fever reduction in critically ill patients had no effect on survival. A meta-analysis of fever reduction in children found no difference on outcomes between paracetamol and ibuprofen.
However, these assertions are unclear: upregulation of ACEII would increase the risk of infection, not necessarily its severity, and would only apply to the use of NSAIDs before the infection, i.e. chronic exposure. It would be irrelevant to the infection once the patients are infected, i.e., to symptomatic treatment of COVID-19 infection.
Anti-inflammatory effect masking the early symptoms of bacterial infections resulting in later antibiotic or other treatment is not applicable: there is no treatment of the virus that might be affected by masking symptoms.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Prospective
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •All patients tested for COVID-19 in hospital centers participating to the study.
- •No exclusion Criteria.
排除标准
- 未提供
结局指标
主要结局
Describe medications used prior to admission associated with worse infection in COVID-19 patients in France.
时间窗: At inclusion day
Describe medications including ibuprofen used prior to admission associated with worse infection in COVID-19 patients in France. Thanks to a questionnaire created for the study, with 5 questions on existing pathology, drugs administrated symptom onset and when, hospitalisation. Each questions have a multiple choice.
Quantify medications used prior to admission associated with worse infection in COVID-19 patients in France.
时间窗: At inclusion day
Quantify medications including ibuprofen used prior to admission associated with worse infection in COVID-19 patients in France. Thanks to a questionnaire created for the study, with 5 questions: existing pathology, drugs administrated symptoms onset and when, hospitalisation. Each questions have a multiple choice.
次要结局
- Quantify other patient characteristics with worse infection in COVID-19 patients in France.(At inclusion day)
- Describe other patient characteristics with worse infection in COVID-19 patients in France.(At inclusion day)