Key Facts

COVID-19 emerged in late 2019 and became a global pandemic. Caused by SARS-CoV-2, it has resulted in over 200,000 deaths in the UK. Evidence-based treatments from the RECOVERY trial and vaccine rollout have dramatically reduced mortality.

Epidemiology

• UK: >24 million confirmed cases, >200,000 deaths (as of 2024)
• Global: >770 million cases, >6.9 million deaths (WHO)
• IFR varies by age: <0.01% (age <20) to >10% (age >80, unvaccinated)
• Now endemic with seasonal waves; predominantly Omicron sub-lineages
• Vaccination has reduced hospitalisation and death by >90%

Aetiology

• SARS-CoV-2: betacoronavirus, enveloped RNA virus
• Transmission: respiratory droplets, aerosols, fomites; incubation 2–14 days (median 5)
• Variants of concern: Alpha, Beta, Delta, Omicron (and sub-lineages)
• Spike protein mutations drive immune evasion and transmissibility changes

Pathophysiology

• Spike protein binds ACE2 receptor (lung, heart, kidney, endothelium, GI tract) → cell entry via TMPRSS2
• Phase 1 (viral replication): upper/lower respiratory tract — pyrexia, cough, anosmia
• Phase 2 (immune-mediated): cytokine storm (IL-6, TNF-α) → ARDS, multi-organ failure
• COVID-associated coagulopathy: endothelial damage + complement activation → VTE, microthrombi
• Post-acute sequelae (Long COVID): immune dysregulation, viral persistence, autoimmunity hypotheses

Mild Disease (80%)

• Fever, dry cough, fatigue
• Anosmia/ageusia (more common with earlier variants)
• Sore throat, headache, myalgia
• GI symptoms: nausea, diarrhoea

Moderate Disease (15%)

• Dyspnoea, SpO2 <94% on air
• Pneumonia on CXR (bilateral, peripheral, ground-glass opacities)
• Requiring supplemental oxygen

Severe/Critical Disease (5%)

• ARDS: PaO2/FiO2 <300, bilateral opacities
• Septic shock
• Multi-organ failure
• Requiring NIV, CPAP, or invasive ventilation

Complications

• VTE: PE and DVT — incidence 20–30% in ICU patients
• Myocarditis/pericarditis: troponin elevation, arrhythmias
• AKI: ~20–40% of hospitalised patients
• Secondary infections: bacterial pneumonia, invasive aspergillosis
• MIS-C (children): Kawasaki-like syndrome 2–6 weeks post-infection

Long COVID (>12 weeks)

• Fatigue (most common), breathlessness, brain fog, palpitations, joint pain, depression/anxiety
• Affects ~10% of infected individuals; may persist for months to years

Red Flags

• SpO2 <92% on air (or <94% if chronic lung disease)
• Silent hypoxia (low SpO2 without dyspnoea)
• RR >30, accessory muscle use
• Worsening on days 7–10 (immune-mediated phase)
• New confusion or drowsiness
• Haemoptysis
• Chest pain (PE or myocarditis)

Bedside

• SARS-CoV-2 PCR (RT-PCR on nasopharyngeal swab): gold standard
• Lateral flow test (LFT): rapid antigen detection — less sensitive, useful for screening
• SpO2: on air and on exertion (6-minute walk test desaturation)
• NEWS2: calculate and escalate
• ECG: myocarditis, PE

Bloods

• FBC: lymphopenia (prognostic), neutrophilia (secondary infection)
• CRP: significantly elevated in severe disease
• D-dimer: markedly elevated in COVID coagulopathy/PE
• Ferritin: very high in cytokine storm (often >1000)
• LDH: elevated — correlates with disease severity
• Troponin: myocardial injury
• IL-6: where available — guides tocilizumab use
• U&Es, LFTs: organ function
• Procalcitonin: distinguish bacterial co-infection (low in viral)
• Blood gas: respiratory failure assessment

Imaging

• CXR: bilateral peripheral ground-glass opacities, consolidation (later)
• CT chest: ground-glass opacities (GGO), crazy paving pattern, bilateral and peripheral predominance
• CTPA: if PE suspected (low threshold given high VTE risk)
• Echocardiography: RV strain (PE), myocarditis

Special Tests

• Genomic sequencing: variant identification
• Anti-spike antibody: post-vaccination response (research/monitoring)
• CT pulmonary angiography: VTE assessment

Non-pharmacological

• Oxygen therapy: target SpO2 92–96% (88–92% if COPD)
• Prone positioning: awake proning in non-intubated patients improves oxygenation
• CPAP/NIV: if SpO2 <92% despite 15L O2 via non-rebreathe mask
• Invasive ventilation: lung-protective strategy (Vt 6ml/kg IBW)
• Isolation: respiratory precautions (FFP3 mask for AGPs)
• VTE prophylaxis: all hospitalised COVID patients — LMWH at prophylactic dose (or therapeutic if ICU — REMAP-CAP, ATTACC trials)

Pharmacological

Hospitalised patients requiring oxygen:

• Dexamethasone 6mg OD (oral or IV) for 10 days — RECOVERY trial: reduces 28-day mortality by ~1/3 (ventilated) and ~1/5 (oxygen only); NO benefit if not requiring oxygen
• Tocilizumab 8mg/kg IV (single dose): for patients on oxygen with CRP ≥75 and within 48 hours of ICU admission — REMAP-CAP, RECOVERY trials
• Baricitinib 4mg OD (oral, 14 days): alternative to tocilizumab (COV-BARRIER trial)
• Remdesivir 200mg IV day 1, then 100mg OD for 5 days: modest benefit if early in disease course (ACTT-1 trial)

Non-hospitalised high-risk patients (within 5 days of symptoms):

• Nirmatrelvir/ritonavir (Paxlovid): 300mg/100mg BD for 5 days — EPIC-HR trial (89% reduction in hospitalisation). Check drug interactions (ritonavir is CYP3A4 inhibitor)
• Molnupiravir 800mg BD for 5 days: alternative if Paxlovid contraindicated

Anticoagulation:

• Prophylactic LMWH: all hospitalised patients
• Consider therapeutic LMWH: critically ill patients on ward (REMAP-CAP platform trial data)
• Post-discharge VTE prophylaxis: 14 days if high VTE risk

Landmark trials:

• RECOVERY: dexamethasone, tocilizumab, baricitinib, convalescent plasma (no benefit), hydroxychloroquine (no benefit), azithromycin (no benefit)
• REMAP-CAP: tocilizumab, therapeutic anticoagulation
• PANORAMIC: molnupiravir in community (modest benefit)

Referral Criteria

• Hospital admission: SpO2 <92%, severe symptoms, high-risk patient deteriorating
• ICU: requiring CPAP/NIV, intubation, vasopressors
• Long COVID clinic: symptoms >12 weeks affecting function

• Overall IFR: ~0.5–1% (pre-vaccine era); substantially lower now with vaccination
• ICU mortality (ventilated, pre-dexamethasone): ~40–50%; with dexamethasone + tocilizumab: ~25–30%
• Vaccinated hospitalised patients: mortality ~5–10%
• Long COVID: affects ~10% of all infections; ~2% have symptoms >1 year
• Post-COVID VTE risk: elevated for 6 months post-infection
• MIS-C: mortality <2% with treatment
• Post-COVID cognitive impairment: reported in ~10–20% of hospitalised patients
• Full recovery from acute infection: >95% in uncomplicated cases

RECOVERY Trial Key Results

COVID-19 Severity Classification