COVID-19

Also known as coronavirus disease 2019, COVID, and SARS-CoV-2.

COVID-19 is a respiratory viral disease caused by the SARS-CoV-2 beta-coronavirus that:

Epidemiology and Risk Factors

Pandemic:

  • Disease first identified in Wuhan City, Hubei in November 2019
  • Global emergency declared 30 January 2020
  • Global pandemic declared 11 March 2020

Transmission:

  • Person-to-person
  • Via respiratory droplets, contact, and possible aerosols
    • Droplets may persist for up to 4 days
Viability of COVID-19 Aerosols on Different Surfaces

Pathophysiology

Viral characteristics:

  • Cellular entry effected via trans-membrane glycoproteins (“spike”) proteins
    • Bind to surface ACE2 receptors
      Found on:
      • Pneumocytes
      • Respiratory tract epithelium
      • Small bowel enterocyte
  • Hypoxaemia with normal lung compliance
  • Diffuse alveolar damage

Coronaviruses are named due to their characteristic halo under electron microscopy, and include:

  • Severe Acute Respiratory Syndrome
    SARS-CoV, in 2002.
  • Middle East Respiratory Syndrome
    MERS-CoV, in 2012.

Staging:

  1. Early Infection
    • Non-specific clinical features
    • Lymphopenia and pro-coagulant state
  2. Pulmonary phase
    • Dyspnoea and hypoxaemic respiratory failure
    • Abnormal chest imaging
  3. Hyper-inflammation phase
    • ARDS
    • Shock
    • ↑ Inflammatory markers

Clinical Features

Features are non-specific, and include:

  • Fever
    80-90%; typically high and persistent.
  • Dry cough
    60-70%.
  • Fatigue
    40%.
  • Dyspnoea
    Typically around day 6.
  • Myalgias
  • Sore throat
  • Headache
  • Chills
  • Nausea/vomiting
  • Anosmia
    ~30%.

Hypoxaemia may occur without breathlessness.

A substantial proportion (17-30%) of infected may never develop symptoms.

Assessment

Classification of COVID-19 Severity in Adults
Severity Characteristics
Mild

No features suggestive of a complicated course:

  • No symptoms
  • Mild URTI symptoms
  • No exertional dyspnoea
  • Normal radiography
Moderate

Stable but with evidence of lower respiratory disease, such as:

  • SpO2 >92%* with up to 4L/min nasal prong oxygen
  • Dyspnoea on mild exertion
  • Radiological abnormalities
Severe

Either:

  • Unstable (deteriorating) moderate disease
  • Any of:
    • RR ≥30 breaths/min
    • SpO2 ≤92% at rest
    • Lung infiltrates >50%
Critical

Any of:

  • P:F <200
  • ARDS
  • Deteriorating despite advanced respiratory support NIV, HFNO)
  • Requiring mechanical ventilation
  • Other signs of significant deterioration:
    • Hypotension or shock
    • Impairment of consciousness
    • Other organ failure

*Or above 90% for patients with chronic lung disease.

The PaO2:FiO2 (P:F) and SpO2:FiO2 and (S:F) ratios quantify the degree of hypoxia relative to the degree of oxygen supplementation.

They are calculated as:

  • \(P/F = {PaO_2 \over FiO_2}\)
  • \(S/F = {SpO_2 \over FiO_2} \times 1000\)

Where:

  • \(PaO_2\) is in mmHg
  • \(FiO_2\) is a decimal (0-1)

History

Exam

Investigations

Bedside:

  • Rapid antigen testing

Laboratory:

  • Blood
    • FBE
      • Leukopaenia or leukocytosis may occur
        Typically ↑ WCC in critically unwell.
      • Lymphopaenia
      • Thrombocytopaenia
    • LFT
      Monitor when using immunosuppressive agents, and consider ceasing if ↑ transaminases.
    • ↑ LDH
    • Coagulation studies
      • DIC
    • Antibody testing
      IgM or IgG antibodies:
      • Require up to 14 days to become positive
      • Detect presence of recent infection
    • Inflammatory markers
      Typically correlate with severity. Include:
      • CRP
        Rate of rise correlates with degree of inflammation and is a marker of future clinical deterioration.
      • Procalcitonin
      • IL-6
  • Respiratory sample
    • PCR
      • Sensitivity 60-95%
        Varies depending on quality of sample and amount of viral shedding.
      • The cycle time (or cycle threshold) is number of PCR cycles that must be performed before a result becomes positive
        • Provides an estimate of the viral load in the sample
          A lower cycle threshold indicates a higher viral load.
        • Can indicate the infectiveness of the patient
        • Does not correlate with severity of disease
        • The threshold for a significant cycle time varies depending on the test used

Bronchoalveolar lavage is more sensitive, but is aerosol generating.

Imaging:

Radiological changes develop between 2-5 days, and become maximal at day 13-15.

  • CXR
    • Bilateral alveolar opacities most common
    • Pleural effusions are uncommon
  • CT chest
    • Routine CT is not required
    • Typical appearance includes:
      • Peripheral, bilateral ground glass opacities
      • Multifocal ground glass opacities
      • Organising pneumonia in late disease
    • Non-specific features include:
      • Multifocal, diffuse, or unilateral ground glass opacitie
    • Indicating for investigating:
      • PE
      • Non-resolving disease for investigation of persistent pneumonic causes

Other:

Diagnostic Approach and DDx

Diagnostic criteria change overtime, however:

  • Confirmed case
    Positive:
    • NAA
    • Viral culture
  • Probable case
    All of:
    • Not tested
    • Febrile (>38°C) or symptomatic
    • Household contact of confirmed or probable case
  • Suspected case
    Meets both clinical and epidemiological criteria:
    • Clinical
      Febrile or symptomatic.
    • Epidemiological
      Significant risk factor in the last 14 days:
      • Close contact with confirmed or probable case
      • Travel
      • Cruise ship exposure
      • Healthcare exposure
      • High-risk community exposure

Management

  • Airborne precautions
  • Use appropriate PPE
  • Manage hypoxaemia
    • Prone positioning
    • Non-invasive ventilation is preferred to invasive ventilation where possible
    • Invasive ventilation should use a lung protective strategy
  • Immunosuppression
    Choice varies depending on disease severity.
Immunosuppression for COVID-19 by Disease Severity
Severity Immunosuppression Used
Mild
  • Remdesivir
Moderate
  • Dexamethasone
  • Baricitinib
Severe
  • Dexamethaxone
  • Tocilizumab
    If no baricitinib received.

Resuscitation:

  • A
    • Intubation
      Consider:
      • Aerosoliation
      • Rapid hypoxaemia on induction
      • Hypotension post-induction
        • Hypovolaemia
        • Effect of high PEEP
  • B
    • Correct hypoxaemia to SpO2 92-96%
      • High flow nasal oxygen
        • Titrate FiO2 to SpO2
        • Titrate flow to work of breathing
        • Minimal effect on recruitment
          Combine with proning to minimise atelectasis.
      • NIV
        • CPAP up to 15cmH2O
        • Assists recruitment and may be more beneficial in early disease
        • Significantly ↓ Rate of intubation
      • Invasive ventilation
      • Permissive hypercapnoea
    • Proning

Specific therapy:

Remdesivir Efficacy by Disease Severity

  • Pharmacological
    • Remdesivir 200mg IV load, then 100mg IV OD for a total of 5 days
      • Paediatric dosing: 5mg/kg load, then 2.5mg/kg on subsequent days
      • Indicated only for mild and moderate disease, within 7 days of symptom onset
        Limited utility in the hospital population.
      • ↓ Time to clinical recovery in mild cases
      • Contraindicated with:
        • Renal failure
        • Multi-organ failure
        • Neutropenia
    • Dexamethasone 6mg IV/PO daily for at least 10 days
      • Indicated for severe or critical disease
      • Methylprednisolone 32mg/day or prednisolone 40mg/day may be used if dexamethasone is unavailable
      • Consider ↑ to 12-20mg/day if tocilizumab or baricitinib are not available or are contraindicated
      • Significant ↓ in absolute mortality
    • Baricitinib 4mg PO daily for up to 14 days, or until hospital discharge
      • Janus kinase inhibitor, ↓ downstream effects of IL-6
      • Significant ↓ mortality in severe disease
      • Use 2mg PO daily if eGFR <30mL/min
      • Contraindicated in:
        • ESRD
        • Acute severe infection
        • Severe immune dysfunction
        • Neutropenia
        • Pregnancy
    • Tocilizumab 8mg/kg single dose
      • Indicated for patients requiring intubation and who have not received baricitinib
      • ↓ Mortality in combination with dexamethasone
      • Sarilumab may be used if tocilizumab is unavailable
  • Procedural
    • VV ECMO
  • Physical
    • Proning
      For all patients requiring more than low-flow oxygen support.
      • Can be performed awake
      • Side-to-side positioning for patients unwilling or unable to lie prone

Tocilizumab is indicated only for patients with evidence of systemic inflammation, defined as a CRP >75mg/L.

Supportive care:

  • D
    • RASS 0 to -2 in the intubated patient
  • F
    • Conservative fluid management
    • Avoid hypervolaemia
  • H
    • Thromboprophylaxis
      For all patients with moderate or worse disease.

Disposition:

Preventative:

  • Vaccination

Marginal and Ineffective Therapies

The following are not recommended:

  • Convalescent plasma
    Primary driver of severe disease is inflammation, not viral load.
  • Hydroxychloroquine
  • Famotidine
  • Ivermectin
  • Fluvoxamine
  • Colchicine

Anaesthetic Considerations

Complications

  • Death
    Mortality is highly age dependent:
    • <10: 0.002%
    • 10-25: 0.01%
    • 25-55: 0.4%
    • 55-65: 1.4%
    • 65-75: 4.6%
    • 75-85: 15%,
    • >90: >25%
  • B
    • Pulmonary fibrosis
    • Bacterial coinfection
      Uncommon outside of the intubated patient.
  • C
    • Myocarditis
      Up to 33% of critically ill patients.
    • Cardiomyopathy
  • F
    • AKI
      Multifactorial:
      • Diuresis
      • Renal microthrombi
  • H
    • Venous thromboembolism
  • I
    • Cytokine storm
      Similar to HLH.

Prognosis

Key Studies

References

  1. Zhu N, Zhang D, Wang W, et al. A Novel Coronavirus from Patients with Pneumonia in China, 2019. N Engl J Med. 2020;382(8):727-733. doi:10.1056/NEJMoa2001017
  2. Bhimraj A, Morgan RL, Shumaker AH, et al. Infectious Diseases Society of America Guidelines on the Treatment and Management of Patients With Coronavirus Disease 2019 (COVID-19). Clinical Infectious Diseases. Published online September 5, 2022:ciac724. doi:10.1093/cid/ciac724
  3. National Clinical Evidence Taskforce. Australian guidelines for the clinical care of people with COVID-19. 2023 [version 72].
  4. Perkins GD, Ji C, Connolly BA, et al. Effect of Noninvasive Respiratory Strategies on Intubation or Mortality Among Patients With Acute Hypoxemic Respiratory Failure and COVID-19: The RECOVERY-RS Randomized Clinical Trial. JAMA. 2022;327(6):546-558. doi:10.1001/jama.2022.0028
  5. Beigel JH, Tomashek KM, Dodd LE, et al. Remdesivir for the Treatment of Covid-19 — Final Report. N Engl J Med. 2020;383(19):1813-1826. doi:10.1056/NEJMoa2007764
  6. Marconi VC, Ramanan AV, Bono S de, et al. Efficacy and safety of baricitinib for the treatment of hospitalised adults with COVID-19 (COV-BARRIER): a randomised, double-blind, parallel-group, placebo-controlled phase 3 trial. The Lancet Respiratory Medicine. 2021;9(12):1407-1418. doi:10.1016/S2213-2600(21)00331-3
  7. Gorbalenya AE, Baker SC, Baric RS, et al. The species Severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2. Nat Microbiol. 2020;5(4):536-544. doi:10.1038/s41564-020-0695-z
  8. Lauer SA, Grantz KH, Bi Q, et al. The Incubation Period of Coronavirus Disease 2019 (COVID-19) From Publicly Reported Confirmed Cases: Estimation and Application. Ann Intern Med. 2020;172(9):577-582. doi:10.7326/M20-0504
  9. Bouadma L, Lescure FX, Lucet JC, Yazdanpanah Y, Timsit JF. Severe SARS-CoV-2 infections: practical considerations and management strategy for intensivists. Intensive Care Med. 2020;46(4):579-582. doi:10.1007/s00134-020-05967-x
  10. Guan W jie, Ni Z yi, Hu Y, et al. Clinical Characteristics of Coronavirus Disease 2019 in China. N Engl J Med. 2020;382(18):1708-1720. doi:10.1056/NEJMoa2002032
  11. van Doremalen N, Bushmaker T, Morris DH, et al. Aerosol and Surface Stability of SARS-CoV-2 as Compared with SARS-CoV-1. N Engl J Med. 2020;382(16):1564-1567. doi:10.1056/NEJMc2004973