Coronavirus Disease 2019 (COVID-19)

William M. Detmer, MD, supported by the Unbound Medicine Team

Updated: March 29, 2020 14:35 EDT

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Coronavirus 2019-20 Outbreak Overview

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 (SARS-CoV-2; 2019-nCoV) History

  • In late 2019, a new coronavirus – not seen previously in humans – was identified as the cause of human illness in China and given the name 2019-nCoV.
  • By late January 2020, outbreak declared a public health emergency of international concern by WHO and US Centers for Disease Control and Prevention (CDC).[1],[2]
  • Categorized as a pandemic by WHO in March 2020.[3]

Epidemiology

  • Spread by human-to-human transmission via respiratory droplets or fomites.
  • Incubation period of 6.4 days with likely asymptomatic transmission.[4]

Case Definition and Patient Under Investigation (PUI)

  • COVID-19 name given by WHO to the disease caused by the SARS-CoV-2 (2019-nCoV) virus.
  • See Case Definitions for WHO Surveillance Case Definition and CDC Patient Under Investigation (PUI) Clinical Criteria for COVID-19.
  • If a PUI for COVID-19 is identified, notify your health department immediately. See Reporting COVID-19 in the United States for details.
  • A detailed travel history is recommended for all patients being evaluated with fever and acute respiratory illness.

COVID-19 Treatment Overview

  • No drugs have yet been approved for the specific treatment of COVID-19.
  • Care is primarily supportive (see Treatment or details)
  • Treatments under study:
    • Convalescent plasma: in an uncontrolled case series of 5 critically ill patients with COVID-19 and ARDS, administration of convalescent plasma containing neutralizing antibody was followed by improvement in clinical status.[5] Other Convalescent Plasma Clinical Trials are underway.
    • Hydroxychloroquine and chloroquine inhibit growth of SARS-CoV-2 in vitro, but no clinical trials have demonstrated conclusively their effectiveness in humans. See Chloroquine / Hydroxychloroquine in Coronavirus COVID-19.
    • Remdesivir (Gilead), an investigational IV drug with broad antiviral activity, is being investigated in multiple clinical trials. In the US, it can be obtained as part of participation in a clinical trial.
    • Lopinavir-ritonavir (AbbVie; Kaletra, Aluvia) showed "no benefit" in hospitalized adult patients with severe COVID-19 according to a study published in the New England of Journal of Medicine.[6] Many other trials are underway, see Lopinavir-Ritonavir Clinical Trials.
    • Tocilizumab (Genentech; Actemra) a monoclonal antibody which blocks the IL-6 signalling pathway is being investigated in a number of Tocilizumab Clinical Trials.
    • Favipiravir (Toyama Chemical; Avigan), an antiviral drug that is under study alone and in combination with tocilizumab. See Favipiravir Clinical Trials.
    • Systemic corticosteroids are under investigation in clinical trials. Some authors advise that they should not given routinely for the treatment of COVID-19.[7]
  • Vaccines
  • For the latest journal research, see Expert PubMed Searches for Coronavirus COVID-19.

Preparedness Checklist

Front-line healthcare personnel in the United States should be prepared to evaluate patients for coronavirus disease 2019 (COVID-19). The following checklist from the CDC highlights key steps for healthcare personnel in preparation for transport and arrival of patients with confirmed or possible COVID-19.[10]

  • Stay up to date on the latest information about signs and symptoms, diagnostic testing, and case definitions for coronavirus disease 2019
  • Review your infection prevention and control policies and CDC infection control recommendations for COVID-19 for:
    • Assessment and triage of patients with acute respiratory symptoms
    • Patient placement
    • Implementation of Standard, Contact, and Airborne Precautions, including the use of eye protection
    • Visitor management and exclusion
    • Source control measures for patients (e.g., put facemask on suspect patients)
    • Requirements for performing aerosol generating procedures
  • Be alert for patients who meet the persons under investigation (PUI) definition
  • Know how to report a potential COVID-19 case or exposure to facility infection control leads and public health officials
  • Know who, when, and how to seek evaluation by occupational health following an unprotected exposure (i.e., not wearing recommended PPE) to a suspected or confirmed coronavirus disease 2019 patient
  • Remain at home, and notify occupational health services, if you are ill
  • Know how to contact and receive information from your state or local public health agency (See Reporting COVID-19 in the United States)

Case Definitions

World Health Organization

Objectives of global surveillance

  1. Monitor trends in COVID-19 disease at national and global levels.
  2. Rapidly detect new cases in countries where the virus is not circulating, and monitor cases in countries where the virus has started to circulate.
  3. Provide epidemiological information to conduct risk assessments at the national, regional and global level.
  4. Provide epidemiological information to guide preparedness and response measures.

Surveillance Case Definitions for COVID-19

  • Case and contact definitions are based on the current available information and are regularly revised as new information accumulates.
  • Countries may need to adapt case definitions depending on their local epidemiological situation and other factors.
  • All countries are encouraged to publish definitions used online and in regular situation reports, and to document periodic updates to definitions which may affect the interpretation of surveillance data.

WHO Surveillance Case Definitions for COVID-19

Suspected Case

The case definitions are based on the current information available and will be revised as new information accumulates. Countries may need to adapt case definitions depending on their own epidemiological situation.

  1. Patient with acute respiratory illness (fever and at least one sign/symptom of respiratory disease (e.g., cough, shortness of breath), AND a a history of travel to or residence in a location reporting community transmission of COVID-19 disease during the 14 days prior to symptom onset;
    OR
  2. Patient with any acute respiratory illness AND having been in contact with a confirmed or probable COVID-19 case (see below for definition of contact) in the last 14 days prior to symptom onset;
    OR
  3. A patient with severe acute respiratory illness (fever and at least one sign/symptom of respiratory disease, e.g., cough, shortness of breath; AND requiring hospitalization) AND in the absence of an alternative diagnosis that fully explains the clinical presentation.

Probable case

  1. A suspect case for whom testing for COVID-19 is inconclusive.1
    OR
  2. A suspect case for whom testing could not be performed for any reason.

Confirmed case

  • A person with laboratory confirmation of COVID-19 infection[11], irrespective of clinical signs and symptoms.

*Definition of contact

A contact is a person who experienced any one of the following exposures during the 2 days before and the 14 days after the onset of symptoms of a probable or confirmed case:

  1. Face-to-face contact with a probable or confirmed case within 1 meter and for more than 15 minutes;
    OR
  2. Direct physical contact with a probable or confirmed case;
    OR
  3. Direct care for a patient with probable or confirmed COVID-19 disease without using proper personal protective equipment;2
    OR
  4. Other situations as indicated by local risk assessments.
Note: for confirmed asymptomatic cases, the period of contact is measured as the 2 days before through the 14 days after the date on which the sample was taken which led to confirmation.

Source: Global surveillance for COVID-19 caused by human infection with COVID-19 virus. World Health Organization. Revised 20 March 2020.[12]

1 Inconclusive being the result of the test reported by the laboratory.
2 World Health Organization. Infection prevention and control during health care when COVID-19 is suspected.

Classification of transmission scenarios

  • WHO recommends using the following categories to describe transmission patterns at national and sub-national levels (wherever possible) to guide decisions for preparedness, readiness and response activities.
Definition of the categories for transmission pattern

Category number

Category name

Definition

1

No cases

Countries/territories/areas with no cases

2

Sporadic cases

Countries/territories/areas with one or more cases, imported or locally detected

3

Clusters of cases

Countries/territories/areas experiencing cases, clustered in time, geographic locationand/or by common exposures

4

Community transmission

Countries/area/territories experiencing larger outbreaks of local transmission definedthrough an assessment of factors including, but not limited to: - Large numbers of cases not linkable to transmission chains - Large numbers of cases from sentinel lab surveillance - Multiple unrelated clusters in several areas of the country/territory/area

Recommendations for laboratory testing

Any suspected case should be tested for COVID-19 infection using available molecular tests.[11] However, depending on the intensity of the transmission, the number of cases and the laboratory capacity, only a subset of the suspect cases may prioritized for testing.

During community transmission WHO recommends prioritizing persons to be tested as indicated in the WHO global testing strategy for COVID-19.

To monitor the full extent of the circulation of the virus in the general population, WHO recommends implementing testing for COVID-19 via existing national sentinel surveillance sites for influenza-like illness (ILI) and severe acute respiratory infection (SARI). Guidance will be made available here:

U.S. Centers for Disease Control

  • For any patient meeting criteria for evaluation for COVID-19, clinicians are encouraged to contact and collaborate with their state or local health department. See Reporting COVID-19 in the United States.
  • For patients that are severely ill, evaluation for COVID-19 may be considered even if a known source of exposure has not been identified.

COVID-19 testing

  • Clinicians should continue to work with their local and state health departments to coordinate testing through public health laboratories.
  • In addition, COVID-19 diagnostic testing, authorized by the Food and Drug Administration under an Emergency Use Authorization (EUA), is becoming available in clinical laboratories. This additional testing capacity will allow clinicians to consider COVID-19 testing for a wider group of symptomatic patients.
  • Clinicians should use their judgment to determine if a patient has signs and symptoms compatible with COVID-19 and whether the patient should be tested. Most patients with confirmed COVID-19 have developed fever1 and/or symptoms of acute respiratory illness (e.g., cough, difficulty breathing). Priorities for testing may include:
Priorities for COVID-19 Testing

  1. Hospitalized patients who have signs and symptoms compatible with COVID-19 in order to inform decisions related to infection control.
  2. Chronic medical conditions. Other symptomatic individuals such as, older adults and individuals with chronic medical conditions and/or an immunocompromised state that may put them at higher risk for poor outcomes (e.g., diabetes, heart disease, receiving immunosuppressive medications, chronic lung disease, chronic kidney disease).
  3. Close contacts. Any persons including healthcare personnel2, who within 14 days of symptom onset had close contact3 with a suspect or laboratory-confirmed4 COVID-19 patient, or who have a history of travel from affected geographic areas5 (see below) within 14 days of their symptom onset.

1Fever may be subjective or confirmed

2For healthcare personnel, testing may be considered if there has been exposure to a person with suspected COVID-19 without laboratory confirmation. Because of their often extensive and close contact with vulnerable patients in healthcare settings, even mild signs and symptoms (e.g., sore throat) of COVID-19 should be evaluated among potentially exposed healthcare personnel. Additional information is available from the CDC.

3Close contact is defined as—

a) being within approximately 6 feet (2 meters) of a COVID-19 case for a prolonged period of time; close contact can occur while caring for, living with, visiting, or sharing a healthcare waiting area or room with a COVID-19 case
– or –

b) having direct contact with infectious secretions of a COVID-19 case (e.g., being coughed on)

If such contact occurs while not wearing recommended personal protective equipment or PPE (e.g., gowns, gloves, NIOSH-certified disposable N95 respirator, eye protection), criteria for PUI consideration are met”

See CDC’s updated Interim Healthcare Infection Prevention and Control Recommendations for Patients Under Investigation for 2019 Novel Coronavirus.[13]

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 COVID-19 (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.[13]

4Documentation of laboratory-confirmation of COVID-19 may not be possible for travelers or persons caring for patients in other countries.

5Affected areas are defined as geographic regions where sustained community transmission has been identified. Relevant affected areas will be defined as a country with at least a CDC Level 2 Travel Health Notice. See all COVID-19 Travel Health Notices.

Source: CDC Criteria to Guide Evaluation and Testing of PUI for COVID-19. Revised March 4, 2020.[14]

Recommendations for Reporting, Testing, and Specimen Collection

  • Clinicians should immediately implement recommended infection prevention and control practices if a patient is suspected of having COVID-19 and notify infection control personnel at their healthcare facility and their state or local health department if a patient is classified as a PUI for COVID-19.
  • State health departments that have identified a PUI or a laboratory-confirmed case should complete a PUI and Case Report form through the processes identified on CDC’s Coronavirus Disease 2019 website. State and local health departments can contact CDC’s Emergency Operations Center (EOC) at 770-488-7100 for assistance with obtaining, storing, and shipping appropriate specimens to CDC for testing, including after hours or on weekends or holidays.
  • For initial diagnostic testing for COVID-19, CDC recommends collecting and testing upper respiratory tract specimens (nasopharyngeal swab) and lower respiratory tract specimens, if available.
  • For patients who develop a productive cough, sputum should be collected and tested for COVID-19. The induction of sputum is not recommended.
  • For patients for whom it is clinically indicated (e.g., those receiving invasive mechanical ventilation), a lower respiratory tract aspirate or bronchoalveolar lavage sample should be collected and tested as a lower respiratory tract specimen.
  • Specimens should be collected as soon as possible once a PUI is identified, regardless of the time of symptom onset.
  • See Interim Guidelines for Collecting, Handling, and Testing Clinical Specimens from Patients Under Investigation (PUIs) for COVID-19 and Biosafety FAQs for handling and processing specimens from suspected cases and PUIs.

Infection Control

  • On March 19th, WHO issued guidance on infection prevention and control strategies for healthcare workers (HCW) when COVID-19 is suspected.
  • See [15] for full details and references.
  • Infection prevention and control (IPC) strategies to prevent or limit transmission in health care settings include the following:
    1. Ensuring triage, early recognition, and source control (isolating patients with suspected COVID-19);
    2. Applying standard precautions for all patients;
    3. Implementing empiric additional precautions (droplet and contact and, whenever applicable, airborne precautions) for suspected cases of COVID-19;
    4. Implementing administrative controls;
    5. Using environmental and engineering controls.

Contact and droplet precautions

  • In addition to using standard precautions, all individuals, including family members, visitors and HCWs, should use contact and droplet precautions before entering the room of suspected or confirmed COVID-19 patients.

Treatment areas

  • Patients should be placed in adequately ventilated single rooms. For general ward rooms with natural ventilation, adequate ventilation is considered to be 60 L/s per patient.
  • When single rooms are not available, patients suspected of having COVID-19 should be grouped together.
  • All patients’ beds should be placed at least 1 metre apart regardless of whether they are suspected to have COVID-19.
  • Where possible, a team of HCWs should be designated to care exclusively for suspected or confirmed cases to reduce the risk of transmission.

Healthcare Worker (HCW) Protection

  • HCWs should:
    • Wear a medical mask.
    • Wear eye protection (goggles) or facial protection (face shield) to avoid contamination of mucous membranes.
    • Wear a clean, non-sterile, long-sleeved gown.
    • Use gloves.
    • Boots, coverall, and apron is not required during routine care.
    • Carry out hand hygiene and appropriate doffing and disposal of all Personal Protective Equipment (PPE) after care of each patient.
    • Refrain from touching eyes, nose, or mouth with potentially contaminated gloved or bare hands.
    • Use new set of PPE when care is given to a different patient.

Healthcare setting

  • Equipment should be either single-use and disposable or dedicated equipment (e.g., stethoscopes, blood pressure cuffs and thermometers).
  • If equipment needs to be shared among patients, clean and disinfect it between use for each individual patient (e.g., by using ethyl alcohol 70%).
  • Avoid moving and transporting patients out of their room or area unless medically necessary.
  • Use designated portable X-ray equipment or other designated diagnostic equipment. If transport is required, use predetermined transport routes to minimize exposure for staff, other patients and visitors, and have the patient wear a medical mask.
  • Ensure that HCWs who are transporting patients perform hand hygiene and wear appropriate PPE as described in this section.
  • Notify the area receiving the patient of any necessary precautions as early as possible before the patient’s arrival.
  • Routinely clean and disinfect surfaces with which the patient is in contact.
  • Limit the number of HCWs, family members, and visitors who are in contact with suspected or confirmed COVID-19 patients.
  • Maintain a record of all persons entering a patient’s room, including all staff and visitors.

Airborne precautions for aerosol-generating procedures

  • Some aerosol-generating procedures, such as tracheal intubation, non-invasive ventilation, tracheotomy, cardiopulmonary resuscitation, manual ventilation before intubation, and bronchoscopy, have been associated with an increased risk of transmission of coronaviruses.
  • Ensure that HCWs performing aerosol-generating procedures:
    • Perform procedures in an adequately ventilated room – that is, natural ventilation with air flow of at least 160 L/s per patient or in negative- pressure rooms with at least 12 air changes per hour and controlled direction of air flow when using mechanical ventilation.
    • Use a particulate respirator at least as protective as a US National Institute for Occupational Safety and Health (NIOSH)-certified N95, European Union (EU) standard FFP2, or equivalent.
    • When HCWs put on a disposable particulate respirator, they must always perform the seal check.Note that facial hair (e.g. a beard) may prevent a proper respirator fit.
    • Use eye protection (i.e., goggles or a face shield).
    • Wear a clean, non-sterile, long-sleeved gown and gloves. If gowns are not fluid-resistant, HCWs should use a waterproof apron for procedures expected to create high volumes of fluid that might penetrate the gown.
    • Limit the number of persons present in the room to the absolute minimum required for the patient’s care and support.

Clinical Syndromes

  • For abbreviations used below see Glossary of Coronavirus terms.
  • Syndromes range from mild upper respiratory infection to severe pneumonia, ARDS and death.
  • All age groups are susceptible to the virus, but elderly patients with comorbidities are more likely to experience severe illness.
  • The mean age of hospitalized patients in an early reports was 59 years old, with a predominance of male patients (56%).[16]
  • The mean incubation time has been reported as 4.1 to 7 days.[16]

Symptoms

Symptoms of Coronavirus COVID-19

Common Symptoms

  • Fever (98%)
  • Fatigue (70%)
  • Non-productive cough (59%)
  • Myalgia (35%)
  • Shortness of breath (31%)
  • Sore throat (17%)

Less common (< 10%)

  • Diarrhea
  • Dizziness
  • Headache
  • Other GI symptoms

Source: Wang D et al. Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China. JAMA. 2020 Feb 07[17]

Severe Pneumonia and ARDS

  • A subgroup of patients will develop dyspnea and hypoxemia that can rapidly progress in one week to:
    • Acute Respiratory Distress Syndrome (ARDS)
    • Septic shock
    • Metabolic acidosis
    • Coagulation dysfunction
    • Multiple Organ Dysfunction Syndrome (MODS)

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. [18]
  • 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.[18]
  • 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[18]

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

Specific COVID-19 treatments

  • There is no current evidence from RCTs to recommend any specific anti-nCoV treatment for patients with suspected or confirmed COVID-19.
  • Care is primarily supportive (see Treatment or details)
  • Antiviral drugs commonly used in clinical practice, including ganciclovir, acyclovir and ribavirin, are not currently recommended for SARS-CoV-2.
  • Treatments under study:
    • Convalescent plasma: in an uncontrolled case series of 5 critically ill patients with COVID-19 and ARDS, administration of convalescent plasma containing neutralizing antibody was followed by improvement in clinical status.[5] Other Convalescent Plasma Clinical Trials are underway.
    • Hydroxychloroquine and chloroquine inhibit growth of SARS-CoV-2 in vitro, but no clinical trials have demonstrated conclusively their effectiveness in humans. See Chloroquine / Hydroxychloroquine in Coronavirus COVID-19.
    • Remdesivir (Gilead), an investigational IV drug with broad antiviral activity, is being investigated in multiple clinical trials. In the US, it can be obtained as part of participation in a clinical trial.
    • Lopinavir-ritonavir (AbbVie; Kaletra, Aluvia) showed "no benefit" in hospitalized adult patients with severe COVID-19 according to a study published in the New England of Journal of Medicine.[6] Many other trials are underway, see Lopinavir-Ritonavir Clinical Trials.
    • Tocilizumab (Genentech; Actemra) a monoclonal antibody which blocks the IL-6 signalling pathway is being investigated in a number of Tocilizumab Clinical Trials.
    • Favipiravir (Toyama Chemical; Avigan), an antiviral drug under study alone and in combination with tocilizumab, see Favipiravir Clinical Trials.
    • Systemic corticosteroids are under investigation in clinical trials. Some authors advise that they should not given routinely for the treatment of COVID-19.[7]
  • Vaccines

Drugs under investigation for COVID-19

Selected Drugs Under Investigation to Treat COVID-19

Drug or combination

Originator company

Status and mechanisms

Clinical trials (trial posting date)

ASC09 / ritonavir, lopinavir / ritonavir, with or without umifenovir

Ascletis, AbbVie, Pharmstandard

ASC09 is an experimental HIV-1 protease inhibitor; ritonavir and lopinavir/ritonavir are approved protease inhibitors for HIV/AIDS; umifenovir is an approved entry inhibitor against influenza

At least three trials (e.g., ChiCTR2000029603, 2/6/20)

ASC09 / oseltamivir, ritonavir / oseltamivir, oseltamivir

Ascletis, Gilead, AbbVie

See above; oseltamivir is a sialidase inhibitor approved for influenza

One trial (NCT04261270, 2/7/20)

Azvudine

Zhengzhou Granlen PharmaTech

Experimental reverse transcriptase inhibitor drug against HIV-1/AIDS

One trial (ChiCTR2000029853, 2/15/20)

Various combinations of baloxavir marboxil / favipiravir and lopinavir / ritonavir

Shionogi, Toyama Chemical

Baloxavir marboxil is a Cap-dependent endonuclease inhibitor and favipiravir is a guanine analog RNA-dependent RNA polymerase inhibitor approved for influenza A and B; see above

Two trials (ChiCTR2000029544, 2/3/20; ChiCTR2000029548, 2/4/20)

Various combinations of darunavir / cobicistat alone or with lopinavir / ritonavir and thymosin α1

Janssen, Gilead

Darunavir and cobicistat are, respectively, an HIV-1 protease inhibitor and inhibitor of cytochrome P450 (CYP)3A enzyme, approved as a combination against HIV-1/AIDS. Thymosin α1 is an immune response boosting agent

Two trials (NCT04252274, 2/5/20; ChiCTR2000029541, 2/3/20)

Remdesivir

Gilead

Phosphoramidate prodrug of an adenine analog used for Ebola and Marburg virus outbreaks (similar structure to approved HIV reverse transcriptase inhibitors)

Two trials (NCT04252664, 2/5/20; NCT04257656, 2/6/20)

Chloroquine or hydroxychloroquine

Shanghai Zhongxi Pharmaceutical, Shanghai Ziyuan Pharmaceutical, Wuhan Wuyao Pharmaceutical

Endosomal acidification fusion inhibitor

At least ten trials (e.g., ChiCTR2000029826, 2/2/20; NCT04261517, 2/14/20)

Methylprednisolone

Generic

Synthetic corticosteroid that binds to nuclear receptors to dampen proinflammatory cytokines

One trial (NCT04263402, 2/10/20)

Interferon alfa-2b alone or in combination with lopinavir / ritonavir and ribavirin

Biogen, Merck

Interferon alfa-2b is a recombinant cytokine with antiviral properties; ribavirin is a guanine derivative; as above

Two trials (NCT04254874, 2/5/20; ChiCTR2000029308, 1/23/20)

Camrelizumab and thymosin

Incyte, Shanghai Hengrui Pharmaceutical

Camrelizumab is a humanized monoclonal antibody (mAb) targeting PD-1

Two trials (ChiCTR2000029806, 2/14/20; NCT04268537, 2/14/20)

Tocilizumab

Chugai Pharmaceutical, Zhejiang Hisun Pharmaceutical, Jiangsu Qyun Bio-Pharmaceutical

Humanized mAb targeting interleukin-6

One trial (ChiCTR2000029765, 2/13/20)

Last search run on 15 February using https://clinicaltrials.gov and http://www.chictr.org.cn. Excludes traditional Chinese medicines and blood-derived products, such as serum from recovered patients and stem cells. All trials are being conducted in China.

Reproduced from: Harrison C. Coronavirus puts drug repurposing on the fast track. Nature Biotechnology. February 27, 2020.[19]

Supportive therapy and monitoring

Adapted from [20]

  • 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.[21]
  • Give empiric antimicrobials to treat all likely pathogens causing SARI within one hour of initial patient assessment for patients with sepsis.[22]
  • Do not routinely give systemic corticosteroids for treatment of viral pneumonia or ARDS outside of clinical trials unless they are indicated for another reason.[23],[24],[25],[26]
  • 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.[27],[28],[29]
  • Endotracheal intubation should be performed by a trained and experienced provider using airborne precautions.[30]
  • Implement mechanical ventilation using lower tidal volumes (4–8 ml/kg predicted body weight, PBW) and lower inspiratory pressures (plateau pressure < 30 cmH2O).[22],[31],[32]
  • In patients with severe ARDS, prone ventilation for >12 hours per day is recommended.[31],[32],[33]
  • Use a conservative fluid management strategy for ARDS patients without tissue hypoperfusion.[22],[34]
  • In patients with moderate or severe ARDS, higher PEEP instead of lower PEEP is suggested.[31],[35],[36]
  • In patients with moderate-severe ARDS (PaO2/FiO2 < 150), neuromuscular blockade by continuous infusion should not be routinely used.[37],[38]
  • In settings with access to expertise in extracorporeal life support (ECLS), consider referral of patients with refractory hypoxemia despite lung protective ventilation.[39],[40],[41],[42]
  • 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.[43],[22]
  • 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.[44]
  • 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.[22][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.

See Also

For health professionals

For the Public

References

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