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Covid-19

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  • Coronaviruses are large, enveloped, single-stranded RNA viruses
  • SARS-CoV-2 (Covid-19) is the 3rd coronavirus to cause serious outbreak after SARS and MERS
  • bats thought to be natural host but transmission thought to be via pangolin
  • Early in infection, SARS-CoV-2 targets cells via the viral structural spike (S) protein that binds to the angiotensin-converting enzyme 2 (ACE2) receptor
  • The type 2 transmembrane serine protease (TMPRSS2), present in the host cell, promotes viral uptake by cleaving ACE2 and activating the SARS-CoV-2 S protein, which mediates coronavirus entry into host cells.
  • viral replication accelerates and epithelial-endothelial barrier integrity is compromised and, in the lung, interstitial mononuclear inflammatory infiltrates and oedema develop
  • In severe COVID-19, fulminant activation of coagulation and consumption of clotting factors occur
  • Common laboratory abnormalities in hospitalised patients:
    • lymphopenia (83%)
    • elevated inflammatory markers (eg, erythrocyte sedimentation rate, C-reactive protein, ferritin, tumour necrosis factor-α, IL-1, IL-6)
    • abnormal coagulation parameters (eg, prolonged prothrombin time, thrombocytopenia, elevated D-dimer [46% of patients], low fibrinogen).
  • common CXR findings - ground glass appearance but pulmonary oedema and consolidation also occur

Clinical

  • Hospitalised patients presentation:
    • fever ~90%
    • Loss of taste & smell ~70%
    • dry cough ~75%
    • SOB ~70%
    • fatigue ~40%
    • nausea/vomiting or diarrhoea ~25%
    • myalgia ~30%
  • Patients can also present with non-classical symptoms, such as isolated gastrointestinal symptoms. Anosmia or ageusia may be the sole presenting symptom in approximately 3% of patients

deaths most commonly associated with co-morbidities:

  • patients dying in Italy, 3.6% patients presented with no co-morbidities, 14.4% with a single co-morbidity, 21.1% with two, and 60.9% with three or more co-morbidities.
  • Among these co-morbidities:
    • hypertension (69.1%)
    • ischaemic heart disease (27.5%)
    • chronic renal failure (21.1%)
    • atrial fibrillation (22%)
    • pulmonary diseases (17.1%)
    • heart failure (16.1%)
    • other co-morbidities with <15% incidence.
  • all these pathologies are characterized by a downregulation of ACE2 and a high ACE/ACE2 ratio

ACE2

Angiotensin-converting enzyme 2 (ACE2) is an amino-peptidase that converts Angiotensin (Ang) II into Ang (1-7). Coronavirus uses ACE2 as a cellular receptor to invade target cells.

  • Ang II, acting on AT1 receptors, exerts powerful vasoconstrictor, pro-fibrotic, and pro-inflammatory effects.
  • Ang (1-7), acting on Mas receptors (MasR), is a potent vasodilator, anti-apoptotic, and anti-proliferative agent (Figure 1).
  • Therefore, ACE2 is a negative regulator of classical ACE in the renin-angiotensin system (RAS).
  • ACE2 is largely expressed in lungs, liver, intestine, brain, heart, and kidneys, and also in testes.
  • In almost all the pathological conditions, especially those of the cardiovascular system, there is an increase in the ACE/ACE2 ratio within the organs and systems (5–9). This ACE/ACE2 imbalance is very often due to a downregulation of ACE2 levels.
  • initial investigations implied that SARS-CoV-2 uses angiotensin-converting enzyme 2 (ACE2) for cellular entry. There are other portals for entry also. Covid19 has 10x the affinity for the receptor compared with SARS

Pneumonia

  • Clinically, pneumonias have been subdivided into specific phenotypes: a spectrum from patchy ground-glass opacification to the oedematous lung with atypical acute respiratory distress syndrome features

Pulmonary embolism

  • d-Dimer values are frequently elevated in Covid-19 patients, with higher levels reflecting higher mortality
  • whilst the incidence of PE is higher in Covid-19 patients, a higher level of d-Dimer should probably be used as the cut-off before ordering CTPA. In the absence of other VTE risk factors, a d-Dimer of 1200 ng/ml has been suggested as a minimum.
  • Wells score has been reported as a poor marker for prediction of PE in patients with COVID-19

Management

  • O2 therapy - ranging from high flow O2 to mechanical ventilation with debates relating to timing of intervention for CPAP and/or intubation
  • fluid therapy - varying approaches with concerns by some to avoid fluid overload while others concerned that this approach encourages renal failure
  • dexamethasone - widely accepted to shorten illness
  • anti-virals -eg remdesivir (in the UK) is inhibitor of the viral RNA-dependent, RNA polymerase
  • casirivimab and imdevimab CUH Guideline for use
  • anti-coagulants - debatable -
References include:

ACE/ACE2 ratios in Covid
Euro Med J - Covid19 pathogenesis
JAMA Covid-19 pathogenesis etc
Emerg Rad. 2020. Higher dDimer to predict PE in Covid
Radiology 2020 PE in Thoracic imaging Covid
Eur Resp J. Elevated dDimer and anticoag predict PE
Apollos' Arrow - The Profound and Enduring Impact of Coronavirus on the Way We Live. Book by Prof Nicholas Christakis 2020
cuh_protocol_for_non_critical_care_management_of_covid_final_nov_2020.pdf
dDimer in Covid