Intended for healthcare professionals

Rapid response to:

Practice Rapid Recommendations

A living WHO guideline on drugs for covid-19

BMJ 2020; 370 doi: https://doi.org/10.1136/bmj.m3379 (Published 04 September 2020) Cite this as: BMJ 2020;370:m3379
Visual summary of recommendation Last updated 10 Nov 2023
Interventions Population Disease severity Non-severe Severe Critical Requires life sustaining treatment Acute respiratory distress syndrome Sepsis Septic shock Absence of signs Risk of admissionto hospital: of severe or critical disease This recommendation applies only to people with these characteristics: Patients with confirmed covid-19 Oxygen saturation <90% on room air Signs of pneumonia Strong recommendations in favour Weak or conditional recommendations in favour Weak or conditional recommendations against Strong recommendations against Lopinavir-ritonavir Casirivimab and imdevimab Sotrovimab Hydroxychloroquine Colchicine Ivermectin Convalescentplasma Corticosteroids Ruxolitinib and tofacitinib Should be considered only if neither baricitinib nor IL-6 receptor blockers are available Remdesivir Remdesivir Molnupiravir Mitigation strategies to reduce potential harms should be implemented Remdesivir Molnupiravir Mitigation strategies to reduce potential harms should be implemented Molnupiravir Nirmatrelvirand ritonavir Nirmatrelvirand ritonavir Remdesivir Remdesivir All three may be combined IL-6 receptor blockers Corticosteroids Baricitinib M M M L L L Use the interactive multiple comparison tool to compare and choose treatments for patients at moderate or high risk of hospital admission Fluvoxamine Fluvoxamine Only in research settings The panel inferred that most patients would want to receive fluvoxamine only in the context of a randomised trial, given the uncertainty around potential benefits and the possibility of harms Convalescentplasma Only in research settings The panel inferred that most patients would want to receive convalescent plasma only in the context of a randomised trial, given the uncertainty around potential benefits and the possibility of harms There are also several practical issues related to the use of convalescent plasma, including but not limited to: Collection of plasma Storage and distribution of plasma Infusion of convalescent plasma into recipients Identification and recruitment of potential donors Only in research settings The panel inferred that most patients would want to receive ivermectin only in the context of a randomised trial, given the uncertainty around potential benefits and the possibility of harms Ivermectin Only in research settings The panel inferred that most patients would want to receive VV116 only in the context of a randomised trial, given the uncertainty around potential benefits and the possibility of harms VV116 UPDATE New recommendation UPDATE Ivermectin is no longer recommended for people with non-severe disease, even in research settings Nirmatrelvirand ritonavir H H H UPDATE The following recommendations for people with non-severe disease are now stratified by how likely it is for someone to be admitted to hospital Nirmatrelvir and ritonavir Remdesivir Molnupiravir UPDATE Low L Patients at low risk of hospital admission (0.5%)Includes people who are neither moderate nor high risk. Most patients are at low risk Moderate M Patients at moderate risk of hospital admission (3%)Includes people: over 65 years old with obesity with diabetes with active cancer with disabilities with comorbidities of chronic disease with chronic kidney or liver disease with chronic cardiopulmonary disease High H Patients at high risk of hospital admission (6%)Includes people who have: been diagnosed with immunodeficiency syndromes been diagnosed with immunodeficiency syndromes autoimmune illness, and are receiving immunosuppressants undergone sold organ transplant and are receiving immunosuppressants Signs of severe respiratory distress In adults: Accessory muscle use Inability to complete full sentences Respiratory rate > 30 breaths per minute In children: Very severe chest wall indrawing Grunting Central cyanosis Inability to breastfeed or drink Reduced level of consciousness Lethargy Convulsions

Corticosteroids

Corticosteroids Suggested regimen Acceptable alternative regimens Dexamethasone 6 mg Oral or intravenous Hydrocortisone 50 mg Intravenous Every 8 hours for 7-10 days Daily for7-10 days Every 6 hours for 7-10 days Methylprednisolone 10 mg Intravenous Daily for7-10 days Prednisone 40 mg Oral
Recommendation 1Supportive careCorticosteroidsorPatients withnon-severe covid-19We suggest no corticosteroidsStrongAll 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
Recommendation 2Supportive careCorticosteroidsorPatients with severe orcritical covid-19We recommend corticosteroidsStrongAll 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

Interleukin-6 (IL-6) receptor blockers

Suggested regimen Tocilizumab Max 800 mg 8 mg per kg Intravenous Initial dose over 1 hour or Sarilumab 400 mg Intravenous Initial dose over 1 hour A second dose may be administered after 12 to 48 hours
Recommendation 1Supportive careIL-6 receptor blockersorPatients with severe orcritical covid-19We recommend treatment with IL-6 receptor blockers(tocilizumab or sarilumab)StrongAll 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

Janus kinase (JAK) inhibitors

Suggested regimen Baricitinib 4 mg Oral Daily Ruxolitinib 5 mg Oral Twice daily Tofacitinib 10 mg Oral Twice daily For 14 days or until hospital discharge
Recommendation 1Supportive careBaricitiniborPatients with severe orcritical covid-19We recommend treatment with baricitinibStrongAll 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
Recommendation 2Supportive careRuxolitiniborPatients with severe orcritical covid-19We suggest not using ruxolitinibStrongAll 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
Recommendation 3Supportive careTofacitiniborPatients with severe orcritical covid-19We suggest not using tofacitinibStrongAll 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

Nirmatrelvir and ritonavir

Suggestedregimen Nirmatrelvir and ritonavir Nirmatrelvir 300 mg Ritonavir 100 mg Oral Every 12 hoursfor 5 days Nirmatrelvir and ritonavir Nirmatrelvir 150 mg Ritonavir 100 mg Oral Every 12 hoursfor 5 days With renalinsufficiencyGFR 30-59 ml/min
Recommendation 1Supportive careNirmatrelvir and ritonavirorNon-severe covid-19,high admission riskWe recommend nirmatrelvir and ritonavir, for those athigh risk of hospital admissionStrongAll 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
Recommendation 2Supportive careNirmatrelvir and ritonavirorNon-severe covid-19,moderate admission riskWe suggest nirmatrelvir and ritonavir, for those atmoderate risk of hospital admissionStrongAll 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
Recommendation 3Supportive careNirmatrelvir and ritonavirorNon-severe covid-19,low admission riskWe suggest no nirmatrelvir and ritonavir, for thoseat low risk of hospital admissionStrongAll 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

Molnupiravir

Suggested regimen Molnupiravir 800 mg Oral Every 12 hoursfor 5 days
Recommendation 1Supportive careMolnupiravirorNon-severe covid-19,high admission riskWe suggest treatment with molnupiravir, for those athigh risk of hospital admissionStrongAll 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
Recommendation 2Supportive careMolnupiravirorNon-severe covid-19,moderate admission riskWe suggest no treatment with molnupiravir, for thoseat moderate risk of hospital admissionStrongAll 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
Recommendation 3Supportive careMolnupiravirorNon-severe covid-19,low admission riskWe recommend no treatment with molnupiravir, forthose at low risk of hospital admissionStrongAll 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

Remdesivir

Suggested regimen Remdesivir 200 mg Intravenous Remdesivir 100 mg Intravenous Daily on days 2 and 3 then Patients with non-severe covid-19 Remdesivir 100 mg Intravenous Daily from day 2 up to 5-10 days Patients with severe or critical covid-19 On thefirst day
Recommendation 1Supportive careRemdesivirorNon-severe covid-19,high admission riskWe suggest treatment with remdesivir, for those athigh risk of hospital admissionStrongAll 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
Recommendation 2Supportive careRemdesivirorNon-severe covid-19,moderate admission riskWe suggest no treatment with remdesivir, for those atmoderate risk of hospital admissionStrongAll 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
Recommendation 3Supportive careRemdesivirorNon-severe covid-19,low admission riskWe recommend no treatment with remdesivir, for thoseat low risk of hospital admissionStrongAll 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
Recommendation 4Supportive careRemdesivirorPatients with severecovid-19We suggest treatment with remdesivirStrongAll 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
Recommendation 5Supportive careRemdesivirorPatients with criticalcovid-19We suggest not using remdesivirStrongAll 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

VV116

No suggested regimen
Recommendation 1Supportive careVV116orPatients with covid-19at any severityWe recommend not using VV116, except inthe context of a clinical trialStrongAll 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

Ivermectin

No suggested regimen
Recommendation 1Supportive careIvermectinorPatients withnon-severe covid-19We recommend not using ivermectinStrongAll 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
Recommendation 2Supportive careIvermectinorPatients with severe orcritical covid-19We recommend not using ivermectin,except in research settingsStrongAll 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

Fluvoxamine

No suggested regimen
Recommendation 1Supportive careFluvoxamineorPatients withnon-severe covid-19We recommend not to use fluvoxamine,except in research settingsStrongAll 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

Convalescent plasma

No suggested regimen
Recommendation 1Supportive careConvalescent plasmaorPatients withnon-severe covid-19We recommend against administering convalescentplasma for treatment of 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
Recommendation 2Supportive careConvalescent plasmaorPatients with severe orcritical covid-19We recommend against using convalescentplasma, except in research settingsStrongAll 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

Colchicine

No suggested regimen
Recommendation 1Supportive careColchicineorPatients withnon-severe covid-19We recommend against treatment withcolchicineStrongAll 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

Hydroxychloroquine

No suggested regimen
Recommendation 1Supportive careHydroxychloroquineorPatients with covid-19at any severityWe recommend against administeringhydroxychloroquine or chloroquineStrongAll 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

Lopinavir-ritonavir

No suggested regimen
Recommendation 1Supportive careLopinavir-ritonavirorPatients with covid-19at any severityWe recommend against administeringlopinavir-ritonavirStrongAll 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

Casirivimab and imdevimab

No suggested regimen
Recommendation 1Supportive careCasirivimab and imdevimaborPatients with covid-19at any severityWe recommend against treatment withcasirivimab-imdevimabStrongAll 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

Sotrovimab

No suggested regimen
Recommendation 1Supportive careSotrovimaborPatients withnon-severe covid-19We recommend against treatment withsotrovimabStrongAll 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

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Rapid Response:

Re: Covid-19: Where is the virus?

Dear Editor

We are told that the virus is everywhere – in the air, in our breath, on fomites, trapped in masks - yet public health authorities seem not to be in possession of any cultivable clinical samples of the offending pathogen.

In March 2020, the World Health Organisation instructed authorities not to look for a virus but to rely instead on a genome test, the RT-PCR, which is not specific for SARS-CoV-2 (1) (2).

A Freedom of Information request to Public Health England about cultivable clinical samples or direct evidence of viral isolation has no information and refers to the proxy RT-PCR test, quoting Eurosurveillance (3).

Eurosurveillance states: “Virus detection by reverse transcription-PCR (RT-PCR) from respiratory samples is widely used to diagnose and monitor SARS-CoV-2 infection and, increasingly, to infer infectivity of an individual. However, RT-PCR does not distinguish between infectious and non-infectious virus. Propagating virus from clinical samples confirms the presence of infectious virus but is not widely available (and) requires biosafety level 3 facilities” (4).

The CDC admits that, "no quantified virus isolates of the 2019-nCoV are currently available", and used a genetically modified human lung alveolar adenocarcinoma cell culture to, “mimic clinical specimen”(5).

It appears, therefore, that we have public health bodies without clinical samples, a test which is non-specific and does not distinguish between infectivity and non-infectivity, a requirement for biosafety level 3 facilities to even look for a virus, yet we are led to believe that it is up all our noses.

So, where is the virus?

(1) https://www.who.int/publications/i/item/10665-331501
(2) https://www.bmj.com/content/369/bmj.m2420/rr-5
(3) https://www.whatdotheyknow.com/request/679566/response/1625332/attach/ht...
(4) https://www.eurosurveillance.org/content/10.2807/1560-7917.ES.2020.25.32...
(5) https://www.fda.gov/media/134922/download

Competing interests: No competing interests

12 October 2020
Janet Menage
GP retired
None
Wales, UK