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Practice Rapid Recommendations

A living WHO guideline on drugs to prevent covid-19

BMJ 2021; 372 doi: https://doi.org/10.1136/bmj.n526 (Published 02 March 2021) Cite this as: BMJ 2021;372:n526
Visual summary of recommendation Last updated 24 Mar 2023
Interventions Population This recommendation applies only to people with these characteristics: People who do not have covid-19 Hydroxychloroquine Recommendation against (strong) Tixagevimab-cilgavimab Recommendation against (conditional)

Hydroxychloroquine

Recommendation 1No interventionHydroxychloroquineorPeople who do not havecovid-19We recommend not usinghydroxychloroquine to prevent covid-19StrongAll or nearly all informed people would likelywant the intervention to the left. Benefitswould outweigh harms for almost everyoneWeakMost people would likely want the interventionto the left. Benefits would outweigh harms forthe majority, but not for everyoneWeakMost people would likely want the interventionto the right. Benefits would outweigh harmsfor the majority, but not for everyoneStrongAll or nearly all informed people would likelywant the intervention to the right. Benefitswould outweigh harms for almost everyone

Evidence profile

Favours no interventionFavours hydroxychloroquineNo important differenceThe panel found that this difference was not important for most patients,because the intervention effects were negligible and/or very imprecise, forexample confidence intervals that include both important benefit and harm
Evidence qualityEvents per 1000 people

Mortality No important difference33HighMore

Based on data from 6822 patients in 7 studiesHydroxychloroquine has little or noeffect on mortalityHighGRADE rating,because of:Risk of biasNo serious concernsImprecisionNo serious concernsIndirectnessNo serious concernsInconsistencyNo serious concernsPublication biasNo serious concernsGRADE certainty ratingsHighThe authors have a lot ofconfidence that the trueeffect is similar to theestimated effectModerateThe authors believe thatthe true effect is probablyclose to theestimated effectLowThe true effect might bemarkedly different fromthe estimated effectVery lowThe true effect isprobably markedlydifferent from theestimated effect

Admission to hospital No important difference31HighMore

Based on data from 7432 patients in 10 studiesHydroxychloroquine has little or noeffect on hospital admissionHighGRADE rating,because of:Risk of biasNo serious concernsImprecisionNo serious concernsIndirectnessNo serious concernsInconsistencyNo serious concernsPublication biasNo serious concernsGRADE certainty ratingsHighThe authors have a lot ofconfidence that the trueeffect is similar to theestimated effectModerateThe authors believe thatthe true effect is probablyclose to theestimated effectLowThe true effect might bemarkedly different fromthe estimated effectVery lowThe true effect isprobably markedlydifferent from theestimated effect

Lab confirmed SARS-CoV-2 No important difference6259HighMore

Based on data from 8379 patients in 12 studiesHydroxychloroquine has little or noeffect on laboratory confirmedSARS-CoV-2 infectionHighGRADE rating,because of:Risk of biasNo serious concernsImprecisionNo serious concernsIndirectnessNo serious concernsInconsistencyNo serious concernsPublication biasNo serious concernsGRADE certainty ratingsHighThe authors have a lot ofconfidence that the trueeffect is similar to theestimated effectModerateThe authors believe thatthe true effect is probablyclose to theestimated effectLowThe true effect might bemarkedly different fromthe estimated effectVery lowThe true effect isprobably markedlydifferent from theestimated effect

Adverse events6 fewer2228HighMore

Based on data from 6153 patients in 9 studiesHydroxychloroquine has a smallincrease in adverse effects leading todiscontinuationHighGRADE rating,because of:Risk of biasNo serious concernsImprecisionNo serious concernsIndirectnessNo serious concernsInconsistencyNo serious concernsPublication biasNo serious concernsGRADE certainty ratingsHighThe authors have a lot ofconfidence that the trueeffect is similar to theestimated effectModerateThe authors believe thatthe true effect is probablyclose to theestimated effectLowThe true effect might bemarkedly different fromthe estimated effectVery lowThe true effect isprobably markedlydifferent from theestimated effect
See all outcomes

Individual considerations

The panel inferred that almost all well informed patients would not want to receive hydroxychloroquine given there are probably no positive effects and there was a risk of adverse events. The panel did not expect there would be much variation in values and preferences between patients for this intervention Values and preferences

Tixagevimab-cilgavimab

Recommendation 1No interventionTixagevimab-cilgavimaborPeople who do not havecovid-19We suggest not using tixagevimab-cilgavimab to prevent covid-19StrongAll or nearly all informed people would likelywant the intervention to the left. Benefitswould outweigh harms for almost everyoneWeakMost people would likely want the interventionto the left. Benefits would outweigh harms forthe majority, but not for everyoneWeakMost people would likely want the interventionto the right. Benefits would outweigh harmsfor the majority, but not for everyoneStrongAll or nearly all informed people would likelywant the intervention to the right. Benefitswould outweigh harms for almost everyone

Individual considerations

The panel reviewed in vitro evidence reducing the applicability of available trial data; while prophylactic use demonstrated modest reduction in laboratory-confirmed symptomatic covid-19, lack of in vitro neutralisation of new SARS-CoV-2 sub-lineages was considered to have rendered these results obsolete Justification Conditions for use of treatment The panel inferred that, in the absence of compelling evidence of clinical effectiveness for the currently circulating SARS-CoV-2 sublineages, the majority of informed individuals would not choose to receive tixagevimab-cilgavimab Values and preferences Any prophylactic use of this intervention should be restricted to extremely vulnerable individuals, and patients presenting a sublineage that is neutralised in-vitro Typical characteristics of extremely vulnerable individuals include: People highly unlikely to mount an immune response following covid-19 vaccination People at increased risk of developing severe manifestations of covid-19 because of limited physiological reserve

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