Coronavirus 2019-nCoV Infection

COVID-19 Outbreak Summary

Last updated 20 February 2020
2019新型冠状病毒 (2019-nCoV) | 冠狀病毒指南 中文

Coronaviruses (CoV)

A large family of viruses that cause a variety of illness:

  • Common cold
  • Middle East Respiratory Syndrome (MERS-CoV)
  • Severe Acute Respiratory Syndrome (SARS-CoV)

Novel Coronavirus (2019-nCoV)

  • A new strain identified in late 2019 that has not been previously seen in humans.
  • Declared by WHO and US Centers for Disease Control and Prevention (CDC) as a public health emergency of international concern January 2020.[1],[2]
  • Disease caused by this strain labeled COVID-19 by the World Health Organization (WHO) on February 11, 2020.[3]
  • No vaccine or specific treatment for 2019-nCoV infection is yet available; care is supportive (see Treatment)
  • Drugs that are being evaluated for COVID-19 include:
    • Remdesivir (Gilead; GS-5734)
    • Lopinavir / ritonavir and lopinavir / ritonavir combined with interferon-β
    • Convalescent plasma
    • Monoclonal antibodies
    • Efficacy and safety of these therapies for COVID-19 needs to be assessed by clinical trials

COVID-19 Cases as of February 19, 2020

Total and New COVID-19 cases in last 24 hours

Confirmed Cases

Deaths

Total

New

Total

New

China

74,280

1,752

2,006

136

Outside China (25 Countries)*

924

120

3

Source: World Health Organization as of 19 February 2020[3]

As of February 18, 2020 cases include both laboratory-confirmed as well as clinically diagnosed in Hubei province, China.

*On the Diamond Princess cruise ship quarantined at Yokohama Port, Japan 2 patients have died and 643 of the 3,063 patients have tested positive for 2019-nCoV (including 328 asymptomatic pathogen carriers).[4]

Coronavirus Outbreak Map by Johns Hopkins CSSE
Coronavirus 2019 Outbreak Map

Source: Johns Hopkins Center for Systems Science and Engineering (CSSE). Click for CSSE interactive map.

Case Definition and Patient Under Investigation (PUI)

  • WHO has developed a Surveillance Case Definition and the US Centers for Disease Control (CDC) a Patient Under Investigation (PUI) clinical criteria for 2019-nCoV. These definitions are based on what is known about MERS-CoV and SARS-CoV (see Case Definitions for details).
  • If a PUI for 2019-nCoV is identified, notify your health department immediately (in the US, contact your local or state health department).
  • A detailed travel history is recommended for all patients being evaluated with fever and acute respiratory illness.
2019-nCoV Identify & Assess Flowchart (CDC)
2019-nCoV identify and Assess flowchart

For the evaluation of patients who may be ill with or who many have been exposed to 2019 Novel Coronavirus (2019-nCoV; COVID-19). Source: US Centers for Disease Control and Prevention.[5]

Preparedness Checklist (CDC)

Front-line healthcare personnel in the United States should be prepared to evaluate patients for 2019 novel coronavirus (2019-nCoV). The following checklist highlights key steps for healthcare personnel in preparation for transport and arrival of patients potentially infected with 2019-nCoV.[6]

Case Definitions

World Health Organization

Severe Acute Respiratory Infection (SARI)

  • An ARI with history of fever or measured temperature ≥38 C° and cough; onset within the last ~10 days; and requiring hospitalization.[7] However, the absence of fever does NOT exclude viral infection.[8]

Surveillance Case Definitions for 2019-nCoV[9]

  1. Patients with severe acute respiratory infection (fever, cough, and requiring admission to hospital), AND with no other etiology that fully explains the clinical presentation[10]AND at least one of the following:
    • History of travel to or residence in the city of Wuhan, Hubei Province, China in the 14 days prior to symptom onset,
      or
    • Patient is a health care worker who has been working in an environment where severe acute respiratory infections of unknown etiology are being cared for.
  2. Patients with any acute respiratory illness AND at least one of the following:
    • Close contact* with a confirmed or probable case of 2019-nCoV in the 14 days prior to illness onset,
      or
    • Visiting or working in a live animal market in Wuhan, Hubei Province, China in the 14 days prior to symptom onset,
      or
    • Worked or attended a health care facility in the 14 days prior to onset of symptoms where patients with hospital associated 2019-nCov infections have been reported.

*Close contact is defined as:

  • Health care associated exposure, including providing direct care for nCoV patients, working with health care workers infected with novel coronavirus, visiting patients or staying in the same close environment as a nCoV patient.
  • Working together in close proximity or sharing the same classroom environment with a nCoV patient
  • Traveling together with a nCoV patient in any kind of conveyance
  • Living in the same household as a nCoV patient

The epidemiological link may have occurred within a 14-day period from onset of illness in the case under consideration

US Centers for Disease Control

Criteria to Guide Evaluation of Patients Under Investigation (PUI) for 2019-nCoV

Fever1 or signs/symptoms of lower respiratory illness (e.g., cough or shortness of breath)

AND

Any person, including health care workers, who has had close contact2 with a laboratory-confirmed3,4 2019-nCoV patient within 14 days of symptom onset

Fever1 and signs/symptoms of a lower respiratory illness (e.g., cough or shortness of breath)

AND

A history of travel from Hubei Province, China5 within 14 days of symptom onset

Fever1 and signs/symptoms of a lower respiratory illness (e.g., cough or shortness of breath) requiring hospitalization4

AND

A history of travel from mainland China5 within 14 days of symptom onset

1Fever may be subjective or confirmed

2Close contact is defined as—

a) being within approximately 6 feet (2 meters) of a 2019-nCoV case for a prolonged period of time while not wearing recommended personal protective equipment or PPE (e.g., gowns, gloves, NIOSH-certified disposable N95 respirator, eye protection); close contact can occur while caring for, living with, visiting, or sharing a health care waiting area or room with a 2019-nCoV case
– or –

b) having direct contact with infectious secretions of a 2019-nCoV case (e.g., being coughed on) while not wearing recommended personal protective equipment.

See CDC’s updated Interim Healthcare Infection Prevention and Control Recommendations for Patients Under Investigation for 2019 Novel Coronavirus.[11]

Data to inform the definition of close contact are limited. Considerations when assessing close contact include the duration of exposure (e.g., longer exposure time likely increases exposure risk) and the clinical symptoms of the person with 2019-nCoV (e.g., coughing likely increases exposure risk as does exposure to a severely ill patient). Special consideration should be given to those exposed in health care settings.

3Documentation of laboratory-confirmation of 2019-nCoV may not be possible for travelers or persons caring for patients in other countries.

4Category also includes any member of a cluster of patients with severe acute lower respiratory illness (e.g., pneumonia, ARDS) of unknown etiology in which 2019-nCoV is being considered that requires hospitalization. Such persons should be evaluated in consultation with state and local health departments regardless of travel history.

5For persons with travel to China within 14 days that are being regularly monitored by local health departments or referred for evaluation from border screening, testing for nCoV can be considered at the discretion of the health officials for all persons with illnesses with fever and lower respiratory symptoms (those hospitalized and those not hospitalized)

Clinical Syndromes

  • Spectrum of clinical illness is not yet well understood but below are likely categories based on prior Coronavirus outbreaks (adapted from [9]).

Abbreviations

ARI, acute respiratory infection; BP, blood pressure; bpm, beats/minute; CPAP, continuous positive airway pressure; FiO2, fraction of inspired oxygen; LRT, Lower Respiratory Tract; MAP, mean arterial pressure; NIV, noninvasive ventilation; OI, Oxygenation Index; OSI, Oxygenation Index using SpO2; PaO2, partial pressure of oxygen; PEEP, positive end-expiratory pressure; PPE, Personal Protective Equipment; RT-PCR, Reverse Transcription Polymerase Chain Reaction RT-PCR; SBP, systolic blood pressure; SD, standard deviation; SIRS, systemic inflammatory response syndrome; SpO2, oxygen saturation; URT, Upper Respiratory Tract.

Uncomplicated illness

  • Patients with uncomplicated upper respiratory tract viral infection may have non-specific symptoms such as fever, cough, sore throat, nasal congestion, malaise, headache, muscle pain or malaise.
  • The elderly and immunosuppressed may present with atypical symptoms.
  • These patients do not have any signs of dehydration, sepsis or shortness of breath.

Mild pneumonia

  • Patient with pneumonia and no signs of severe pneumonia.
  • Child with non-severe pneumonia has cough or difficulty breathing + fast breathing: fast breathing (in breaths/min): < 2 months, ≥60; 2–11 months, ≥50; 1–5 years, ≥40 and no signs of severe pneumonia.

Severe pneumonia

  • Adolescent or adult: fever or suspected respiratory infection, plus one of respiratory rate >30 breaths/min, severe respiratory distress, or SpO2 < 90% on room air (adapted from [10]).
  • Child with cough or difficulty in breathing, plus at least one of the following: central cyanosis or SpO2 < 90%; severe respiratory distress (e.g. grunting, very severe chest indrawing); signs of pneumonia with a general danger sign: inability to breastfeed or drink, lethargy or unconsciousness, or convulsions. Other signs of pneumonia may be present: chest indrawing, fast breathing (in breaths/min): < 2 months, ≥60; 2–11 months, ≥50; 1–5 years, ≥40. [12] The diagnosis is clinical; chest imaging can exclude complications.

Acute Respiratory Distress Syndrome

Onset: new or worsening respiratory symptoms within one week of known clinical insult.

Chest imaging (radiograph, CT scan, or lung ultrasound): bilateral opacities, not fully explained by effusions, lobar or lung collapse, or nodules.

Origin of edema: respiratory failure not fully explained by cardiac failure or fluid overload. Need objective assessment (eg, echocardiography) to exclude hydrostatic cause of edema if no risk factor present.

Oxygenation (adults)

  • Mild ARDS: 200 mmHg < PaO2/FiO2 ≤ 300 mmHg (with PEEP or CPAP ≥5 cm H2O,[13] or non-ventilated[14])
  • Moderate ARDS: 100 mmHg < PaO2/FiO2 ≤200 mmHg with PEEP ≥5 cm H2O,[13] or non-ventilated[14])
  • Severe ARDS: PaO2/FiO2 ≤ 100 mmHg with PEEP ≥5 cm H2O, or non-ventilated[14])
  • When PaO2 is not available, SpO2/FiO2 ≤315 suggests ARDS (including in non-ventilated patients)

Oxygenation (children; note OI = Oxygenation Index and OSI = Oxygenation Index using SpO2)[15]

  • Bilevel NIV or CPAP ≥5 cmH2O via full face mask: PaO2/FiO2 ≤ 300 mmHg or SpO2/FiO2 ≤264
  • Mild ARDS (invasively ventilated): 4 ≤ OI < 8 or 5 ≤ OSI < 7.5
  • Moderate ARDS (invasively ventilated): 8 ≤ OI < 16 or 7.5 ≤ OSI < 12.3
  • Severe ARDS (invasively ventilated): OI ≥ 16 or OSI ≥ 12.3

Sepsis

Adults[16]

  • Life-threatening organ dysfunction caused by a dysregulated host response to suspected or proven infection, with organ dysfunction*.
  • Signs of organ dysfunction include: altered mental status, difficult or fast breathing, low oxygen saturation, reduced urine output, fast heart rate, weak pulse, cold extremities or low blood pressure, skin mottling, or laboratory evidence of coagulopathy, thrombocytopenia, acidosis, high lactate or hyperbilirubinemia.

Children[17]

  • Suspected or proven infection and ≥2 SIRS criteria, of which one must be abnormal temperature or white blood cell count.

* Sequential [Sepsis-related] Organ Failure Assessment (SOFA)score[18] ranges from 0 to 24 and includes points related to 6 organ systems: respiratory (hypoxemia defined by low PaO2/FiO2), coagulation (low platelets), liver (high bilirubin), cardiovascular (hypotension), central nervous system (low level of consciousness defined by Glasgow Coma Scale), and renal (low urine output or high creatinine). Sepsis is defined by an increase in (SOFA) score of ≥2 points. Assume the baseline score is zero if data are not available.

Septic shock

Adults[16]

  • Persisting hypotension despite volume resuscitation, requiring vasopressors to maintain MAP ≥65 mmHg and serum lactate level >2 mmol/L.

Children (based on [19]])

  • Any hypotension (SBP < 5th percentile or >2 SD below normal for age) or 2–3 of the following: altered mental state; tachycardia or bradycardia (HR < 90 bpm or >160 bpm in infants and HR < 70 bpm or >150 bpm in children); prolonged capillary refill (>2 sec) or warm vasodilation with bounding pulses; tachypnea; mottled skin or petechial or purpuric rash; increased lactate; oliguria; hyperthermia or hypothermia.

Infection Control

Adapted from [9], [20]

At triage

  • Give suspect patient a medical mask and direct patient to separate area, an isolation room if available.
  • Keep at least 1 meter distance between suspected patients and other patients.
  • Instruct all patients to cover nose and mouth during coughing or sneezing with tissue or flexed elbow for others.
  • Perform hand hygiene after contact with respiratory secretions.

Droplet precautions

  • Droplet precautions prevent large droplet transmission of respiratory viruses.
  • Use a medical mask if working within 1-2 meters of the patient.
  • Place patients in single rooms, or group together those with the same etiological diagnosis.
  • If an etiological diagnosis is not possible, group patients with similar clinical diagnosis and based on epidemiological risk factors, with a spatial separation.
  • When providing care in close contact with a patient with respiratory symptoms (e.g. coughing or sneezing), use eye protection (face-mask or goggles), because sprays of secretions may occur.
  • Limit patient movement within the institution and ensure that patients wear medical masks when outside their rooms.

Contact precautions

  • Droplet and contact precautions prevent direct or indirect transmission from contact with contaminated surfaces or equipment (i.e. contact with contaminated oxygen tubing/interfaces).
  • Use PPE (medical mask, eye protection, gloves and gown) when entering room and remove PPE when leaving.
  • If possible, use either disposable or dedicated equipment (e.g. stethoscopes, blood pressure cuffs and thermometers).
  • If equipment needs to be shared among patients, clean and disinfect between each patient use.
  • Ensure that health care workers refrain from touching their eyes, nose, and mouth with potentially contaminated gloved or ungloved hands.
  • Avoid contaminating environmental surfaces that are not directly related to patient care (e.g. door handles and light switches). Ensure adequate room ventilation. Avoid movement of patients or transport.
  • Perform hand hygiene.

Airborne precautions when performing an aerosol generating procedure

  • Ensure that healthcare workers performing aerosol-generating procedures (i.e. open suctioning of respiratory tract,intubation, bronchoscopy, cardiopulmonary resuscitation) use PPE, including gloves, long-sleeved gowns, eye protection,and fit-tested particulate respirators (N95 or equivalent, or higher level of protection). (The scheduled fit test should not be confused with user seal check before each use.)
  • Whenever possible, use adequately ventilated single rooms when performing aerosol-generating procedures, meaning negative pressure rooms with minimum of 12 air changes per hour or at least 160litres/second/patient in facilities with natural ventilation.
  • Avoid the presence of unnecessary individuals in the room.
  • Care for the patient in the same type of room after mechanical ventilation commences.

Laboratory Diagnosis

  • Rapid collection and testing of appropriate specimens from suspected cases is a priority and should be guided by a laboratory expert.

Samples to be collected

  • Respiratory material
    • Nasopharyngeal and oropharyngeal (URT) swab in ambulatory patients and sputum (if produced) and/or endotracheal aspirate or bronchoalveolar lavage (LRT) in patients with more severe respiratory disease. Send for 2019-nCoV testing by RT-PCR.
    • In hospitalized patients with confirmed 2019-nCoV infection, repeat URT and LRT samples should be collected to demonstrate viral clearance. The frequency of specimen collection will depend on local circumstances but should be at least every 2 to 4 days until there are two consecutive negative results (both URT and LRT samples if both are collected) in a clinically recovered patient at least 24 hours apart. If local infection control practice requires two negative results before removal of droplet precautions, specimens may be collected as often as daily. [21]
  • Serum for serological testing, acute sample and convalescent sample (this is additional to respiratory materials and can support the identification of the true agent, once serologic assay is available). Serology for diagnostic purposes is recommended only when RT-PCR is not available.[21]
  • Blood cultures for bacteria that cause pneumonia and sepsis, ideally before antimicrobial therapy. DO NOT delay antimicrobial therapy to collect blood cultures.
  • Additional WHO guidance is available on specimen collection, processing, and laboratory testing, including related biosafety procedures[21]

Interpretation

  • A single negative RT-PCR result, particularly if this is from an URT specimen, does not exclude infection. Repeat sampling and testing, LRT specimen is strongly recommended in severe or progressive disease.
  • A positive alternate pathogen does not necessarily rule out either, as little is yet known about the role of coinfections.

Treatment

Adapted from [9]

Specific COVID-19 treatments and clinical research

  • There is no current evidence from RCTs to recommend any specific anti-nCoV treatment for patients with suspected or confirmed 2019-nCoV infection.
  • Antiviral drugs commonly used in clinical practice, including neuraminidase inhibitors (oseltamivir, paramivir, and zanamivir), ganciclovir, acyclovir and ribavirin, are not recommended for 2019-nCoV.
  • Drugs that are being evaluated for 2019-nCoV include: remdesivir, lopinavir / ritonavir, lopinavir / ritonavir combined with interferon-β, convalescent plasma, and monoclonal antibodies. But the efficacy and safety of these drugs for COVID-19 patients needs to be assessed by clinical trials.
  • Unlicensed treatments should be administered only in the context of ethically-approved clinical trials or the Monitored Emergency Use of Unregistered Interventions Framework (MEURI), with strict monitoring.

Supportive therapy and monitoring

  • Give supplemental oxygen therapy immediately to patients with SARI and respiratory distress, hypoxaemia, or shock.
  • Use conservative fluid management in patients with SARI when there is no evidence of shock.[22]
  • Give empiric antimicrobials to treat all likely pathogens causing SARI within one hour of initial patient assessment for patients with sepsis.[23]
  • Do not routinely give systemic corticosteroids for treatment of viral pneumonia or ARDS outside of clinical trials unless they are indicated for another reason.[24],[25],[26],[27]
  • Closely monitor patients with SARI for signs of clinical deterioration, such as rapidly progressive respiratory failure and sepsis, and apply supportive care interventions immediately.
  • Understand the patient’s co-morbid condition(s) to tailor the management of critical illness and appreciate the prognosis. Communicate early with patient and family.

Management of hypoxemic respiratory failure and ARDS

  • Recognize severe hypoxemic respiratory failure when a patient with respiratory distress is failing standard oxygen therapy.
  • High-flow nasal oxygen (HFNO) or non-invasive ventilation (NIV) should only be used in selected patients with hypoxemic respiratory failure. The risk of treatment failure is high in patients with MERS treated with NIV, and patients treated with either HFNO or NIV should be closely monitored for clinical deterioration.[28],[29],[30]
  • Endotracheal intubation should be performed by a trained and experienced provider using airborne precautions.[31]
  • Implement mechanical ventilation using lower tidal volumes (4–8 ml/kg predicted body weight, PBW) and lower inspiratory pressures (plateau pressure < 30 cmH2O).[23],[32],[33]
  • In patients with severe ARDS, prone ventilation for >12 hours per day is recommended.[32],[33],[34]
  • Use a conservative fluid management strategy for ARDS patients without tissue hypoperfusion.[23],[35]
  • In patients with moderate or severe ARDS, higher PEEP instead of lower PEEP is suggested.[32],[36],[37]
  • In patients with moderate-severe ARDS (PaO2/FiO2 < 150), neuromuscular blockade by continuous infusion should not be routinely used.[38],[39]
  • In settings with access to expertise in extracorporeal life support (ECLS), consider referral of patients with refractory hypoxemia despite lung protective ventilation.[40],[41],[42],[43]
  • Avoid disconnecting the patient from the ventilator, which results in loss of PEEP and atelectasis. Use in-line catheters for airway suctioning and clamp endotracheal tube when disconnection is required (for example, transfer to a transport ventilator).

Management of septic shock

  • Recognize septic shock in adults when infection is suspected or confirmed AND vasopressors are needed to maintain mean arterial pressure (MAP) ≥65 mmHg AND lactate is ≥2 mmol/L, in absence of hypovolemia.[44],[23]
  • Recognize septic shock in children with any hypotension (systolic blood pressure [SBP] < 5th percentile or >2 SD below normal for age) or 2-3 of the following: altered mental state; tachycardia or bradycardia (HR < 90 bpm or >160 bpm in infants and HR < 70 bpm or >150 bpm in children); prolonged capillary refill (>2 sec) or warm vasodilation with bounding pulses; tachypnea; mottled skin or petechial or purpuric rash; increased lactate; oliguria; hyperthermia or hypothermia.[19]
  • In resuscitation from septic shock in adults, give at least 30 ml/kg of isotonic crystalloid in adults in the first 3 hours. In resuscitation from septic shock in children in well-resourced settings, give 20 ml/kg as a rapid bolus and up to 40-60 ml/kg in the first 1 hr.
  • Do not use hypotonic crystalloids, starches, or gelatins for resuscitation.
  • Fluid resuscitation may lead to volume overload, including respiratory failure. If there is no response to fluid loading and signs of volume overload appear (for example, jugular venous distension, crackles on lung auscultation, pulmonary edema on imaging, or hepatomegaly in children), then reduce or discontinue fluid administration. This step is particularly important where mechanical ventilation is not available. Alternate fluid regimens are suggested when caring for children in resource-limited settings.[23][45],[46],[47]
  • Administer vasopressors when shock persists during or after fluid resuscitation. The initial blood pressure target is MAP ≥65 mmHg in adults and age-appropriate targets in children.
  • If central venous catheters are not available, vasopressors can be given through a peripheral IV, but use a large vein and closely monitor for signs of extravasation and local tissue necrosis. If extravasation occurs, stop infusion. Vasopressors can also be administered through intraosseous needles.
  • If signs of poor perfusion and cardiac dysfunction persist despite achieving MAP target with fluids and vasopressors, consider an inotrope such as dobutamine.[48]

Online Resources

Emerging Respiratory Viruses, Including 2019-nCoV: Methods for Detection, Prevention, Response and Control
https://openwho.org…
Course provides a general introduction to 2019-nCoV and emerging respiratory viruses and is intended for public health professionals, incident managers and personnel working for the United Nations, international organizations and NGOs. WHO teams are working to translate the resources into all WHO official languages and Portuguese. Many countries have also initiated translation into their own local languages.

WHO Critical Care Severe Acute Respiratory Infection Course
https://openwho.org…

Course includes content on clinical management of patients with a severe acute respiratory infection. The course is intended for clinicians who are working in intensive care units in low- and middle-income countries and managing adult and pediatric patients with severe forms of Severe Acute Respiratory Infection, including evere pneumonia, acute respiratory distress syndrome, sepsis and septic shock.

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