Last reviewed: 29 May 2022
Last updated: 12 May 2022
12 May 2022

WHO strongly recommends Paxlovid® for people at high risk of severe disease

The World Health Organization (WHO) has updated its living guideline on COVID-19 therapeutics to include a strong recommendation for the oral antiviral nirmatrelvir/ritonavir (available as Paxlovid®). The WHO recommends the drug for patients with non-severe disease who are at highest risk of hospitalisation, calling it the best therapeutic choice for high-risk patients to date. The recommendation is based on new data that shows that nirmatrelvir/ritonavir reduces the risk of hospitalisation by 85% in this group of patients.

See the Emerging section for more information.

See Management: emerging

Original source of update

Summary

Definition

History and exam

Key diagnostic factors

  • fever
  • cough
  • dyspnoea
  • altered sense of smell/taste

Other diagnostic factors

  • headache
  • sore throat
  • rhinorrhoea/nasal congestion
  • sneezing
  • fatigue
  • myalgia or arthralgia
  • sputum production/expectoration
  • chest tightness
  • gastrointestinal symptoms
  • dizziness
  • neurological symptoms
  • ocular symptoms
  • audio-vestibular symptoms
  • chest pain
  • haemoptysis
  • bronchial breath sounds
  • tachypnoea
  • tachycardia
  • cyanosis
  • crackles/rales on auscultation
  • cutaneous symptoms
  • oral mucosal lesions
  • lower urinary tract symptoms

Risk factors

  • contact with probable or confirmed case
  • residence/work/travel in location with high risk of transmission
  • older age
  • male sex
  • ethnicity
  • residence in a long-term care facility
  • presence of comorbidities
  • obesity
  • cardiovascular disease
  • diabetes
  • chronic respiratory disease
  • chronic kidney disease
  • chronic liver disease
  • pregnancy
  • smoking
  • malignancy
  • cerebrovascular disease
  • mental health disorders
  • solid organ or blood stem cell transplant
  • disabilities
  • dementia
  • immunosuppression
  • HIV infection
  • haemoglobin disorders
  • hypertension
  • substance use disorders
  • children with certain underlying conditions
  • vitamin D deficiency
  • proton-pump inhibitor use
  • autoimmune disease
  • thyroid disease
  • Parkinson's disease
  • physical inactivity
  • gout
  • dyslipidaemia
  • surgery
  • blood groups A and B
  • gut dysbiosis
  • environmental factors

Diagnostic investigations

1st investigations to order

  • real-time reverse transcription polymerase chain reaction (RT-PCR)
  • pulse oximetry
  • ABG
  • FBC
  • comprehensive metabolic panel
  • thyroid function tests
  • blood glucose level
  • coagulation screen
  • cardiac biomarkers
  • serum C-reactive protein
  • serum erythrocyte sedimentation rate
  • serum lactate dehydrogenase
  • serum interleukin (IL) level
  • serum procalcitonin
  • serum ferritin level
  • serum amyloid A level
  • serum creatine kinase and myoglobin
  • blood and sputum cultures
  • chest x-ray

Investigations to consider

  • computed tomography (CT) chest
  • rapid antigen test
  • serology

Emerging tests

  • lung ultrasound
  • reverse transcription loop-mediated isothermal amplification (RT-LAMP)
  • CRISPR-based diagnostics
  • breathalysers
  • calprotectin

Treatment algorithm

Contributors

Expert advisers

Nicholas J. Beeching, MA, BM BCh, FRCP, FRACP, FFTM RCPS (Glasg), FESCMID, DCH, DTM&H

Consultant and Emeritus Professor of Tropical and Infectious Diseases

Royal Liverpool University Hospital and Liverpool School of Tropical Medicine

Liverpool

UK

Disclosures

NJB is partially supported by the National Institute of Health Research Health Protection Unit (NIHR HPRU) in Emerging and Zoonotic Infections at University of Liverpool in partnership with the UK Health Security Agency (UKHSA; formerly Public Health England), in collaboration with Liverpool School of Tropical Medicine. He is affiliated with Liverpool School of Tropical Medicine. The views expressed are those of the author and not necessarily those of the NHS, the NIHR, the Department of Health, or UKHSA.

Tom E. Fletcher, MBE, PhD, MBChB, MRCP, DTM&H

Senior Clinical Lecturer and Defence Consultant in Infectious Diseases

Royal Liverpool University Hospital and Liverpool School of Tropical Medicine

Liverpool

UK

Disclosures

TEF is a consultant/expert panel member to the World Health Organization, and is funded by the UK Surgeon General, the NHS, and Liverpool School of Tropical Medicine. TEF is partially supported by the National Institute of Health Research Health Protection Unit (NIHR HPRU) in Emerging and Zoonotic Infections at University of Liverpool in partnership with the UK Health Security Agency (UKHSA; formerly Public Health England), in collaboration with Liverpool School of Tropical Medicine. He is affiliated with Liverpool School of Tropical Medicine. He has received research grants from the Wellcome Trust, Medical Research Council, and the UK Public Health Rapid Support Team (UK-PHRST). The views expressed are those of the author and not necessarily those of the NHS, the NIHR, the Department of Health, or UKHSA.

Robert Fowler, MDCM, MS (Epi), FRCP(C)

H. Barrie Fairley Professor of Critical Care

University Health Network and Interdepartmental Division of Critical Care Medicine

Director

Clinical Epidemiology and Health Care Research

Institute of Health Policy, Management and Evaluation

Dalla Lana School of Public Health

University of Toronto

Chief

Tory Trauma Program

Sunnybrook Hospital

Toronto

Canada

Disclosures

RF declares that he has no competing interests.

Peer reviewers

William A. Petri, Jr., MD, PhD

Professor

Division of Infectious Diseases and International Health

University of Virginia

Charlottesville

VA

Disclosures

WAP declares that he has no competing interests.

Xin Zhang, MD, PhD

Attending Physician

The Fifth Medical Center of PLA General Hospital

Clinical Division and Research Center of Infectious Disease

Beijing

China

Disclosures

XZ declares that he has no competing interests.

Ran Nir-Paz, MD

Associate Professor in Medicine

Department of Clinical Microbiology and Infectious Diseases

Hadassah Hebrew University Medical Center

Jerusalem

Israel

Disclosures

RNP has received research grants from US-Israel Binational Science Foundation, Hebrew University, Rosetrees Trust, and SpeeDx. He is chair of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study Group for Mycoplasma and Chlamydia Infections (ESGMAC). RNP is a consultant for and has stocks in eDAS Healthcare. He is also chairperson of the Israeli Society for Infectious Diseases guidelines committee.

Editors

Adam Mitchell,

Section Editor (Infectious Diseases)/Drug Editor, BMJ Best Practice

Disclosures

AM declares that he has no competing interests.

Irene Chiwele,

Lead Section Editor, BMJ Best Practice

Disclosures

IC declares that she has no competing interests.

Julie Costello,

Comorbidities Editor, BMJ Best Practice

Disclosures

JC declares that she has no competing interests.

Expert advisers: comorbidities

Martyn Patel, BMBcH, FRCP, MA

Consultant, Older People's Medicine

Norfolk and Norwich University Hospitals

NHS Foundation Trust

Norwich

UK

Disclosures

MP is a contributor to the Oxford Textbook of Otolaryngology, Oxford University Press, 2021, having written a chapter about mental capacity law, for which he received no fee. MP is the NHS representative on the board for Norwich Institute for Healthy Ageing (unpaid role). MP has spoken at the International Forum on Quality and Safety in Healthcare virtual conference in November 2020, for which he received no fee. MP has accepted speaker fees and/or travel expenses to deliver lectures from: University of East Anglia, Leicester University (speaker fees only); Astellas Pharma Ltd (speaker fees and travel expenses). MP has accepted travel expenses from Newton Europe to present a joint project conducted by his main employer (Norfolk and Norwich University Hospitals NHS Trust) and Newton Europe at the NHS Confederation conference (Manchester 2018).

Andrew Lewington, BSc (Hons), MBBS, MEd, MD, FRCP

Consultant Renal Physician

Honorary Associate Professor

Nephrology Department

Leeds Teaching Hospitals NHS Trust

Leeds

UK

Disclosures

AL is Associate Clinical Director of NIHR Leeds In-Vitro Diagnostics Co-operative, Co-Chair of UK Kidney Research Consortium Renal Clinical Study Group, Member of Kidney Research UK Research Grant Committee, Committee Member of NICE Kidney Injury Clinical Guideline Update 2018-20, Committee Member of NICE Diagnostic Assessment for Point of Care Creatinine Testing 2018-19. AL attended the Acute Dialysis Quality Initiative Meeting in San Diego 2018 (accommodation expenses); AL was a speaker at the AKI & CRRT Conference in San Diego 2019 (travel and accommodation expenses), the AKI Conference in Coventry 2019 (travel expenses), and the NIHR AKI and Sepsis Meeting in Leeds 2019 (no expenses).

Martin Cowie, MD, MSc, FRCP, FRCP (Ed), FESC, FHFA, FACC

Professor of Cardiology

Imperial College London (Royal Brompton Hospital)

London

UK

Disclosures

MC is chair of the European Society of Cardiology Digital Health Committee and a trustee of the Atrial Fibrillation Society. He has previously been a non-executive director of the National Institute for Health and Care Excellence. MC provides consultancy advice to AstraZeneca, Servier, Abbott, Medtronic, Boston Scientific, and Genomics PLC. MC declares that none of these interests is directly related to topics advised on for this project.

Rachael Evans, MBChB, FRCP (UK), PhD

Associate Professor (Clinical)

University of Leicester

Honorary Consultant Respiratory Physician

Glenfield Hospital

Leicester

UK

Disclosures

RAE has given lectures for non-promotional industry-led sessions on COPD management, including for GSK and Chiesi for individual payment and travel expenses totalling <£2,000.

Gerry Rayman, MD, FRCP

Consultant Physician and Head of Service

Diabetes and Endocrine Centre and the Diabetes Research Unit

Ipswich Hospitals NHS Trust

Ipswich

UK

Disclosures

GR has been paid for advisory board meetings with the following companies: Safoni Aventis, Abbott Diabetes UK, Lilly Diabetes, Bayer. GR has received lecture fees from Safoni Aventis, Abbott Diabetes UK, Lilly Diabetes, Novonordisk, Napp Pharmaceuticals Ltd.

Sotiris Posporelis, MD, MRCPsych

Consultant Liaison Neuropsychiatrist

King’s College Hospital

South London and Maudsley NHS Foundation Trust

Honorary Senior Clinical Lecturer

Institute of Psychiatry, Psychology & Neuroscience

King’s College London

London

UK

Disclosures

SP declares that he has no competing interests.

Acknowledgements,

BMJ Best Practice would like to gratefully acknowledge Dr Matthew Jones for his advice on a section of the stroke comorbidity content.

Matthew Jones, MD, FRCP

Consultant Neurologist

Greater Manchester Neurosciences Centre

Salford Royal Foundation Trust

Honorary Senior Lecturer

University of Manchester

Manchester

UK

Disclosures

AA and MJ declare that they have no competing interests.

Peer reviewers: comorbidities

Martyn Patel, BMBcH, FRCP, MA

Consultant, Older People's Medicine

Norfolk and Norwich University Hospitals

NHS Foundation Trust

Norwich

UK

Disclosures

MP is a contributor to the Oxford Textbook of Otolaryngology, Oxford University Press, 2021, having written a chapter about mental capacity law, for which he received no fee. MP is the NHS representative on the board for Norwich Institute for Healthy Ageing (unpaid role). MP has spoken at the International Forum on Quality and Safety in Healthcare virtual conference in November 2020, for which he received no fee. MP has accepted speaker fees and/or travel expenses to deliver lectures from: University of East Anglia, Leicester University (speaker fees only); Astellas Pharma Ltd (speaker fees and travel expenses). MP has accepted travel expenses from Newton Europe to present a joint project conducted by his main employer (Norfolk and Norwich University Hospitals NHS Trust) and Newton Europe at the NHS Confederation conference (Manchester 2018).

Asangaedem Akpan, MPH, FRCP

Consultant Geriatrician

Liverpool University Hospitals NHS Foundation Trust

Visiting Professor

University of Cumbria

Carlisle

Honorary Clinical Associate Professor

University of Liverpool

Liverpool

UK

Disclosures

AA declares that he has no competing interests.

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