COVID-19
`Clinical management
`Living guidance
`25 January 2021
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`MASIMO 2004
`Apple v. Masimo
`IPR2020-01526
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`Clinical management of COVID-19: living guidancClinical management of COVID-19: living guidanccc
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`COVID-19
`Clinical management
`Living guidance
`25 January 2021
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`This document is the update of an interim guidance originally published under the title “Clinical management
`of COVID-19: interim guidance, 27 May 2020".
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`WHO continues to monitor the situation closely for any changes that may affect this interim guidance. Should
`any factors change, WHO will issue a further update. Otherwise, this interim guidance document will expire 2
`years after the date of publication.
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`© World Health Organization 2021. Some rights reserved. This work is available under the CC BY-NC-SA 3.0
`IGO licence.
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`WHO reference number: WHO/2019-nCoV/clinical/2021.1
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`Clinical management of COVID-19: living guidance
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`Contents
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`Foreword and summary ................................................................................................................................... 4
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`Abbreviations ................................................................................................................................................... 7
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`1. Background .............................................................................................................................................. 9
`2. Methods ................................................................................................................................................. 11
`3. The latest evidence ................................................................................................................................ 13
`4. Who the recommendations apply to ...................................................................................................... 14
`5. COVID-19 care pathway (see Annex 1) ................................................................................................ 15
`6. Screening, triage and clinical assessment: early recognition of patients with COVID-19 ..................... 16
`7.
`Immediate implementation of appropriate infection prevention and control measures ......................... 21
`8. Laboratory diagnosis .............................................................................................................................. 23
`9. Management of mild COVID-19: symptomatic treatment ...................................................................... 25
`10. Management of moderate COVID-19: pneumonia treatment ................................................................ 26
`11. Management of severe COVID-19: severe pneumonia treatment ........................................................ 29
`12. Management of critical COVID-19: acute respiratory distress syndrome (ARDS) ................................ 32
`13. Management of critical COVID-19: septic shock ................................................................................... 36
`14. Prevention of complications in hospitalized and critically ill patients with COVID-19 ............................ 38
`15. Therapeutics and COVID-19 .................................................................................................................. 44
`16. Treatment of other acute and chronic infections in patients with COVID-19 ......................................... 45
`17. Management of neurological and mental manifestations associated with COVID-19 ........................... 46
`18. Noncommunicable diseases and COVID-19 ......................................................................................... 49
`19. Rehabilitation for patients with COVID-19 ............................................................................................. 50
`20. Caring for women with COVID-19 during and after pregnancy ............................................................. 53
`21. Feeding and caring for infants and young children of mothers with COVID-19 .................................... 55
`22. Caring for older people with COVID-19 ................................................................................................. 58
`23. Palliative care and COVID-19 ................................................................................................................ 59
`24. Care of COVID-19 patients after acute illness (new chapter) ................................................................ 60
`25. Ethical principles for optimum care during the COVID-19 pandemic .................................................... 61
`26. Reporting and coding during the COVID-19 pandemic (mortality and morbidity) ................................. 63
`27. Clinical research during the COVID-19 pandemic ................................................................................. 64
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`Acknowledgements ........................................................................................................................................ 65
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`References .................................................................................................................................................... 69
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`Annex 1: COVID-19 care pathway ................................................................................................................ 78
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`Annex 2: Resources for supporting clinical management of COVID-19 ....................................................... 79
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`Web annex: GRADE recommendations – additional information
`https://apps.who.int/iris/bitstream/handle/10665/338871/WHO-2019-nCoV-clinical-web_annex-2021.1-eng.pdf
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`Clinical management of COVID-19: living guidance
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`Foreword and summary
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`The Strategic preparedness and response plan outlines the World Health Organization (WHO) strategic
`objectives to end the COVID-19 pandemic and assists national stakeholders with developing a structured
`approach to their response. The WHO's main objectives for COVID-19 are to:
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`1) supress transmission;
`2) provide optimized care for all patients; and save lives
`3) minimize the impact of the epidemic on health systems, social services and economic activity.
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`To achieve these objectives, the WHO Operational considerations for case management of COVID-19 in
`health facility and community describes key actions that should be taken in different scenarios: no cases;
`sporadic cases; clusters of cases; and community transmission, in order to enable delivery of clinical and
`public health services in a timely fashion.
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`The guidance in this document is based on the above strategic priorities, and is intended for clinicians
`involved in the care of patients with suspected or confirmed COVID-19. It is not meant to replace clinical
`judgment or specialist consultation but rather to strengthen frontline clinical management and the public
`health response. Considerations for special and vulnerable populations, such as paediatric patients, older
`people and pregnant women, are highlighted throughout the text.
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`In this document we refer to the COVID-19 care pathway (Annex 1). This describes a coordinated and
`multidisciplinary care pathway that a patient enters after s/he is screened for COVID-19 and becomes a
`suspect COVID-19 case, and follows the continuum of their care until release from the pathway. The
`objective is to ensure delivery of safe and quality care while stopping onwards viral transmission. All others
`enter the health system in the non-COVID-19 pathway. For the most up-to-date technical guidance related to
`the COVID-19 response, visit WHO Country & Technical Guidance (1).
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`Basic psychosocial support skills are at the core of any clinical intervention for COVID-19. Such skills are
`indispensable for all involved in the COVID-19 clinical response, whether they identify as mental health and
`psychosocial providers or not. Basic psychosocial skills are essential for supporting the emotional well-being
`of people who have COVID-19, those who have lost someone to COVID-19, or are family members and
`carers who are caring for someone with COVID-19 or have recovered from COVID-19.
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`Summary: what is this living guidance?
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`Clinical questions: What is the clinical management of patients with COVID-19?
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`Target audience: The target audience is clinicians and health care decision-makers.
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`Current practice: Current practice to treat COVID-19 is variable reflecting large-scale uncertainty.
`Numerous clinical trials are underway looking at various interventions that will inform clinical practice.
`Providing trustworthy guidance that is comprehensive and holistic for the optimal care of COVID-19 patients,
`throughout their entire illness, is necessary. The previous version of the Clinical management of COVID-19
`provided recommendations that can be applied when caring for patients during the COVID-19 care pathway.
`This guideline now also includes information on caring for COVID-19 patients after their acute illness.
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`Updates to this guidance: The panel made the following new recommendations:
`(cid:120)(cid:120) A conditional recommendation to use clinical judgment, including consideration of patients’ values and
`preferences and local and national policy if available, to guide management decisions including
`admission to hospital and to the intensive care unit (ICU), rather than currently available prediction
`models for prognosis when caring for patients with COVID-19 of any severity assessed in a clinic or
`hospital (very low certainty).
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`(cid:120)(cid:120) A conditional recommendation for use of pulse oximetry monitoring at home as part of a package of
`care, including patient and provider education and appropriate follow-up, in symptomatic patients with
`COVID-19 and risk factors for progression to severe disease who are not hospitalized (very low
`certainty).
`(cid:120) A conditional recommendation for the use of awake prone positioning in patients with severe COVID-19
`that are hospitalized requiring supplemental oxygen or non-invasive ventilation (low certainty).
`(cid:120) A conditional recommendation to use thromboprophylaxis dosing of anticoagulation rather than
`intermediate or therapeutic dosing in patients hospitalized with COVID-19, without an established
`indication for higher dose of anticoagulation (very low certainty).
`(cid:120) A conditional recommendation for the use of existing care bundles (defined as three or more evidence-
`informed practices delivered together and consistently to improve care) chosen locally by hospital or
`ICU and adapted as necessary for local circumstances in patients with critical COVID-19 (very low
`certainty).
`(cid:120) Best practice statement: patients who have had suspected or confirmed COVID-19 (of any disease
`severity) who have persistent, new or changing symptoms should have access to follow-up care (see
`the new Chapter 24. Care of COVID-19 patients after acute illness).
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`For chapters without new recommendations, each responsible technical unit (member of steering
`committee) reviewed the chapter and provided narrative updates to reflect new literature searches. Two
`technical units used expert panel reviews to review and update their chapters (neurological and mental
`manifestations [Chapter 17] and rehabilitation [Chapter 19]).
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`How this guideline was created: This living guideline is an innovation from WHO, driven by the urgent
`need for global collaboration to provide trustworthy and evolving COVID-19 guidance informing policy and
`practice worldwide. An international Guideline Development Group (GDG) of content experts, clinicians,
`patients, ethicists and methodologists produced recommendations following standards for trustworthy
`guideline development using the Grading of Recommendations Assessment, Development and Evaluation
`(GRADE) approach. No conflict of interest was identified for any panel member. WHO has partnered with
`the non-profit MAGIC (Making GRADE the Irresistible Choice) Evidence Ecosystem Foundation for support
`through their publication platform that facilitates continued updating.
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`The latest evidence: The evidence included in this guidance update includes six rapid reviews on specific
`topics that can be found in Annex 3. No conflict of interest was identified for any external contributors.
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`Understanding the recommendations: When moving from evidence to recommendations, the panel
`made five conditional recommendations based primarily on low to very low certainty evidence.
`(cid:120) For suggested use of clinical judgment rather than available prediction models, the panel considered the
`evidence in favour of prognostic models in patients with COVID-19 to be of very low certainty, lack
`validation studies, and lack evidence of the impact of using models on decision-making and patient
`outcomes.
`(cid:120) For suggested use of pulse oximetry monitoring at home, the panel felt the potential benefits would
`outweigh the potential harms, especially if used in patients that were symptomatic and at risk for severe
`disease; but only as part of a larger package of care including education and follow-up.
`(cid:120) For suggested use of awake prone positioning in hospitalized patients with severe COVID-19, the panel
`emphasized the low certainty evidence of reduction in mortality, downgraded from higher certainty
`evidence for mechanically ventilated critically ill patients with acute respiratory distress syndrome
`(ARDS) and the limited harm with the experience thus far from different resource settings.
`(cid:120) For suggested use of existing care bundles, the panel emphasized the low to very low certainty
`evidence of reduction in mortality and possible administrative burdens for implementation; but if the
`hospital or ICU selected among existing care bundles and adapted them to local circumstances that
`would take into account contextual factors of resource considerations and increase feasibility.
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`For these four recommendations the panel did not expect much variation in values and preferences.
`(cid:120)(cid:120) For suggested use of thromboprophylaxis dosing rather than intermediate or therapeutic dosing, the
`panel emphasized the very low certainty evidence of reduction in mortality or pulmonary embolism with
`higher anticoagulant dosing but also an increased risk of major bleeding; the possible harm indicated by
`studies of therapeutic anticoagulation rather than intermediate dosing.
`For this last recommendation, some panellists anticipated variability in patient values and preferences.
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`Update 1.4 Clinical Management of COVID-19: Living Guidance
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`This updated version of the Clinical management of COVID-19 guidance includes five new recommendations
`and a new chapter on care for patients after acute illness with COVID-19, adding to the interim guidance
`published 27 May 2020. Please view section text for a summary of these new recommendations, also available
`within each section of the guidelines, labelled as new. Other recommendations remain unchanged although
`underlying content and references have been updated in this version. Concerning therapeutics for COVID-19,
`please see the linked WHO living guidelines also published as BMJ Rapid Recommendations, which replace
`the initial guidance (e.g. for corticosteroids).
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`As described in Methods (Chapter 2), the first interim guidance applied a simplified approach to produce rapid
`guidance. In this 4th updated version the GDG applied GRADE and standards for trustworthy guidelines. To
`reflect these two different approaches, the recommendations are therefore marked with different labels and
`colour codings.
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`This is a living guidance, so the recommendations included here will be updated, and new recommendations
`will be added as evidence emerges. The guideline is therefore written, disseminated and updated in
`MAGICapp, with a format and structure aiming to make it user friendly and easy to navigate while
`accommodating for dynamically updated evidence and recommendations, focusing on what is new while
`keeping existing recommendations within the guideline.
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`Clinical management of COVID-19: living guidance
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`Abbreviations
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`activities of daily living
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`ADL
`acute respiratory distress syndrome
`ARDS
`Access, Watch or Reserve (antibiotics)
`AWaRe
`bilevel positive airway pressure
`BiPAP
`body mass index
`BMI
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`blood pressure
`BP
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`beats per minute
`bpm
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`chronic obstructive pulmonary disease
`COPD
`continuous positive airway pressure
`CPAP
`case record form
`CRF
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`computed tomography
`CT
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`disseminated intravascular coagulation
`DIC
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`deep vein thrombosis
`DVT
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`extracorporeal membrane oxygenation
`ECMO
`FiO2
`fraction of inspired oxygen
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`Guideline Development Group
`GDG
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`Grading of Recommendations Assessment, Development and Evaluation
`GRADE
`high-flow nasal oxygen
`HFNO
`human immunodeficiency virus
`HIV
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`intensive care unit
`ICU
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`International Federation of Red Cross and Red Crescent Societies
`IFRC
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`International Forum for Acute Care Trialists
`InFACT
`infection prevention and control
`IPC
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`interquartile range
`IQR
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`International Severe Acute Respiratory and emerging Infection Consortium
`ISARIC
`lower respiratory tract
`LRT
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`long-term care facility
`LTCF
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`Magic Evidence Ecosystem Foundation
`MAGIC
`mean arterial pressure
`MAP
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`MERS-CoV Middle East respiratory syndrome coronavirus
`MHPSS
`mental health and psychosocial support
`MISC- C
`multisystem inflammatory syndrome temporally associated with COVID-19 in children
`and adults
`nucleic acid amplification test
`noncommunicable disease
`neonatal intensive care unit
`non-invasive ventilation
`Oxygenation Index
`Oxygenation Index using SpO2
`partial pressure arterial oxygen
`predicted body weight
`positive end-expiratory pressure
`post-intensive care syndrome
`personal protective equipment
`post-traumatic stress disorder
`person/patient under investigation
`randomized controlled trial
`rapid diagnostic test
`recruitment manoeuvre
`reverse transcription polymerase chain reaction
`severe acute respiratory syndrome coronavirus
`systolic blood pressure
`systemic inflammatory response syndrome
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`NAAT
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`NCD
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`NICU
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`NIV
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`OI
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`OSI
`PaO2
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`PBW
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`PEEP
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`PICS
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`PPE
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`PTSD
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`PUI
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`RCT
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`RDT
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`RM
`RT-PCR
`SARS-CoV
`SBP
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`SIRS
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`SOFA
`SpO2
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`TB
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`UNICEF
`URT
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`VTE
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`WHO
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`sequential organ failure assessment
`oxygen saturation
`tuberculosis
`United Nations Children’s Fund
`upper respiratory tract
`venous thromboembolism
`World Health Organization
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`1. Background
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`Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus
`2 (SARS-CoV-2), a newly emergent coronavirus, that was first recognized in Wuhan, Hubei province, China,
`in December 2019. SARS-CoV-2 is a positive-sense single-stranded RNA virus that is contagious in
`humans. It is the successor to SARS-CoV-1, the strain that caused the 2002–2004 SARS outbreak.
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`Epidemiology and virologic studies suggest that transmission mainly occurs from both symptomatic and
`asymptomatic people to others by close contact through respiratory droplets or by direct contact with infected
`persons, or by contact with contaminated objects and surfaces (2,3,4,5,6), or by aerosols, i.e. in enclosed
`spaces indoors, crowded and inadequately ventilated spaces, where infected persons spend long periods of
`time with others, which may include restaurants, choir practices, fitness classes, nightclubs, offices and
`places of worship (7), or during aerosol-generating procedures. Clinical and virologic studies that have
`collected repeated biological samples from confirmed patients demonstrate that shedding of SARS-CoV-2 is
`highest in the upper respiratory tract (URT) (nose and throat) early in the course of the disease (8,9,10),
`within the first 3 days from onset of symptoms (10,11,12,13). A study of 77 infector-infectee transmission
`pairs observed the highest viral load in throat swabs at the time of symptom onset, suggesting infectiousness
`peak on or before symptom onset with an estimated 44% (95% confidence interval, 30–57%) of onward
`infections happening during the pre-symptomatic phase of the index case (14). The incubation period for
`COVID-19, which is the time between exposure to the virus (becoming infected) and symptom onset, is, on
`average, 5–7 days, but can be up to 14 days. During this period, also known as the “presymptomatic” period,
`some infected persons can be contagious, from 1–3 days before symptom onset (12). It is important to
`recognize that presymptomatic transmission still requires the virus to be spread via infectious droplets or by
`direct or indirect contact with bodily fluids from an infected person. An asymptomatic case is a person
`infected with SARS-CoV-2 who does not develop symptoms (15,16). Among symptomatic patients, the
`duration of infectious virus shedding has been estimated at 8 days from the onset of any symptoms
`(17,18,19).
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`The proportion of persons who become infected with SARS-CoV-2 and remain asymptomatic remains to be
`better understood, recent meta-analysis reported an overall estimate of 31%, from seven studies with
`predefined screened populations, prediction interval ranging between 26–37% (20). One systematic review
`of 79 studies found that 20% (17–25%) of people remained asymptomatic throughout the course of infection
`(20). Another systematic review, which included 13 studies considered to be at low risk of bias, estimated
`that 17% of cases remain asymptomatic (14–20%) (21). A further meta-analysis included 28 studies. There
`was wide variance between two general population studies with the proportion of asymptomatic infections at
`the time of testing being 20% and 75% respectively, in contacts the proportion was 8.2–50% and 59% (49–
`68%) of obstetric patients remained asymptomatic throughout whilst 54% (42%-65%) of nursing home
`residents were asymptomatic at testing of which 28% (13–50%) remained asymptomatic through follow-up
`(22). Whole cohort testing such as in the Diamond Princess cruise ship found an asymptomatic proportion
`(among all infected cases) of 17.9% (95% CI: 15.5–20.2%) (23) and in a cohort of 356 dialysis patients,
`52 (40.3%) had asymptomatic disease or disease which was not detected using RT-PCR when serological
`testing for antibodies were done (24). In those patients that do become symptomatic, most people with
`COVID-19 develop only mild (40%) or moderate (40%) disease (see Table 6.3), approximately 15% develop
`severe disease that requires oxygen support, and 5% have critical disease with complications such as
`respiratory failure, acute respiratory distress syndrome (ARDS), sepsis and septic shock, thromboembolism,
`and/or multiorgan failure, including acute kidney injury and cardiac injury (25). Older age, smoking (26,27)
`and underlying noncommunicable diseases (NCDs), such as diabetes, hypertension, cardiac disease,
`chronic lung disease and cancer, have been reported as risk factors for severe disease and death, and
`multivariable analyses have confirmed older age, higher sequential organ failure assessment (SOFA) score
`and D-dimer > 1 μg/L on admission were associated with higher mortality (28,29) (see Table 6.3). This study
`also observed a median duration of viral RNA detection of 20.0 days (IQR 17–24 days) in survivors, but
`COVID-19 viral RNA was detectable until death in non-survivors. In a study of 20 immunocompromised
`haemoncology patients viral RNA was detected for up to 78 days after the onset of symptoms (IQR 24–64
`days). Viable virus was detected up to 61 days after the onset of symptoms (30).
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`COVID-19 is associated with mental and neurological manifestations, including anxiety, depression, sleep
`problems, headache, dizziness, impaired sense of smell or taste (31), myalgias, delirium/encephalopathy,
`agitation, stroke, hypoxic ischaemic brain injury, seizures, coma, meningo-encephalitis and Guillain-Barré
`syndrome (32,33,34,35). Anxiety and depression appear to be common amongst people hospitalized for
`COVID-19, with one hospitalized cohort from Wuhan, China, revealing over 34% of people experiencing
`symptoms of anxiety and 28% experiencing symptoms of depression (36). Preliminary findings from
`retrospective cohort studies of over 60 000 COVID-19 cases in the United States of America indicate an
`18.1% incidence of psychiatric diagnoses (including anxiety disorders and insomnia) in the first 2 weeks to
`3 months after COVID-19 diagnosis, 5.8% of which were new diagnoses (37).
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`In many cases, neurological manifestations have been reported even without respiratory symptoms. Over
`80% of COVID-19 patients in a hospitalized United States' cohort experienced neurological symptoms during
`the course of their illness and these manifestations were associated with a four-fold higher risk of severe
`COVID-19 in this cohort (38). An observational case series from France found that 65% of people with
`COVID-19 in ICUs showed signs of confusion (or delirium) and 69% experienced agitation (39). Delirium, in
`particular, has been associated with increased mortality risk in the context of COVID-19 (40). Moreover
`COVID-19 has been associated with acute cerebrovascular disease (including ischaemic and haemorrhagic
`stroke) with reports from multiple case series and/or cohort series from China, France, the Netherlands, the
`United Kingdom and the United States of America (36,39,41,42,43). Case reports of Guillain-Barré syndrome
`and meningo-encephalitis among people with COVID-19 have also been reported (44,45,46).
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`Clinical manifestations of COVID-19 are generally milder in children compared with adults (47,48,49).
`Relatively few cases of infants confirmed with COVID-19 have been reported; infants also experience mild
`illness (49,50). However, an acute presentation with a hyperinflammatory syndrome leading to multiorgan
`failure and shock has been reported (51,52), described as multisystem inflammatory syndrome temporally
`associated with COVID-19 in children and adolescents. Underlying conditions with severe illness in children
`appear to be similar to adults. Among 655 children with laboratory-confirmed COVID-19 and complete
`information about underlying conditions, 23% had an underlying condition, with obesity, chronic lung disease
`(including asthma), cardiovascular disease and immunosuppression most commonly reported (52).
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`The results of a living systematic review (as of 6 October 2020) show that pregnant and recently pregnant
`women with COVID-19 appear to be less likely to be symptomatic (0.28, 95% CI 0.13–0.62; 4 studies; 462
`051 women), or manifest common symptoms such as fever, dyspnoea and myalgia, compared with non-
`pregnant women of reproductive age (53). These findings are largely influenced by studies of pregnant
`women who were managed in hospitals for any reason, with limited data on women during early pregnancy
`or postpartum. Pregnant or recently pregnant women with severe COVID-19 are at higher risk of requiring
`admission to an ICU (OR=2.13, 95% CI 1.53–2.95; 7 studies, 601 108 women), invasive ventilation
`(OR=2.59, 95% CI 2.28–2.94; 6 studies, 601 044 women) or extra corporeal membrane oxygenation
`(ECMO) (OR=2.02, 95% CI 1.22–3.34; 2 studies, 461 936 women). Older maternal age, high body mass
`index (BMI), non-white ethnicity, pre-existing comorbidities, chronic hypertension, pre-existing diabetes, are
`risk factors for developing severe COVID-19. Complications related to COVID-19 did not seem to be
`increased in women presenting in the third trimester compared with earlier trimester of pregnancy or in
`multiparous compared with primiparous women, but the existing sample sizes for these comparisons are not
`large.
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`The understanding of the mid- and long-term sequelae of COVID-19 is emerging. This new condition which
`has been described as post-COVID syndrome or long COVID (54) still lacks a consensus worldwide on
`terminology and clinical definition. The post-intensive care syndrome (PICS) has been well described in
`other critically ill patients and it seems is also being observed in COVID-19 patients. However, non-
`hospitalized patients (or those with mild and moderate COVID-19) and children are also reporting persisting
`clustering of symptoms and mid- and long-term sequalae, and children. Recent data (in press at The Lancet
`by Bin Cao et al.) on the long-term consequences of COVID-19 for patients in Wuhan, warned that
`dysfunctions and complications could persist in some discharged patients for at least 6 months (55).
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`2. Methods
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`The original version (v1.1) of this document was developed in consultation with the International Forum for
`Acute Care Trialists (InFACT), the International Severe Acute Respiratory and Emerging Infection
`Consortium (ISARIC) and the Surviving Sepsis Campaign. This is the fourth edition of this document, which
`was originally adapted from Clinical management of severe acute respiratory infection when Middle East
`respiratory syndrome coronavirus (MERS-CoV) infection is suspected (WHO, 2019).
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`For the development of the third version (v1.3) of the COVID-19 clinical guidance, a formal Guideline
`Development Group (GDG) comprising individuals with broad expertise spanning multiple specialties and all
`regions was convened. Confidentiality and declarations of interest were collected and reviewed and no
`conflict of interest was identified (see Acknowledgements). Because of the accelerated timeline and very
`broad scope of the third version of the guideline, it was not feasible to undertake a formal GRADE process
`(PICO questions; systematic reviews; formal documentation of values and preferences and incorporation of
`considerations of costs, resources, and feasibility). The topics for consideration originated in the WHO
`interim guidance for MERS, but for COVID-19 were greatly expanded to reflect the full spectrum of illness,
`from screening to rehabilitation. Published evidence was synthesized under the coordination of the Science
`Division in rapid systematic reviews, which were pre-circulated to the GDG. The WHO Steering Committee
`initially drafted the recommendations about interventions based on these reviews and input from expert
`clinicians participating in twice-weekly clinical network teleconferences. The GDG held four virtual meetings
`via teleconference (total of 12 hours) to discuss all previous and new recommendations. Suggested revisions
`were incorporated into the guidance. Consensus was achieved for all recommendations presented in the
`final version. The direction and strength of recommendations are presented using symbols rather than formal
`GRADE terminology (strong and conditional recommendations with grading of certainty of evidence, or best
`practice statements).
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`For this fourth version (v1.4) of the guidance, new recommendations have been developed according to
`standards and methods for trustworthy guidelines, making use of an innovative process to achieve efficiency
`in dynamic updating of recommendations. The methods are aligned with the WHO Handbook for guideline
`development (56).
`Related guidelines
`This living WHO guidance for the clinical management of COVID-19 is related to the Living Guideline for
`therapeutics and COVID-19, also published in the BMJ and available in MAGICapp.
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`Timing
`This guidance aims to be trustworthy and living; dynamically updated and globally disseminated once new
`evidence warrants a change in recommendations for COVID-19. We aim for an ambitious timeframe from
`trials that trigger guideline development process to WHO publication, within 1 month, while maintaining
`standards and methods for trustworthy guidelines (WHO Handbook of guideline development) (56).
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`Stepwise approach
`Here we outline the stepwise approach we take to improve efficiency and timeliness of the living, trustworthy
`guidance, in the development and dissemination of the recommendations. To do so, vario