COVID-19

Introduction

COVID-19 is caused by SARS-CoV-2, a coronavirus first identified in late 2019 that produced a global pandemic through 2020-2022 and remains in ongoing circulation as an endemic respiratory pathogen. The virus's spike protein binds the ACE2 receptor, which is expressed on respiratory epithelium as well as vascular endothelium, cardiac and renal tissue - a distribution that explains both its primary respiratory tropism and its capacity to cause multisystem complications in severe disease.

It is examined heavily not because it is diagnostically difficult, but because it tests a body of practice-changing evidence generated at exceptional speed - most notably the UK's RECOVERY trial - and because it illustrates general principles of respiratory failure, thromboprophylaxis and vaccine safety that apply well beyond this one virus.

Transmission and pathophysiology

Spread is predominantly by respiratory droplets and aerosols, with a typical incubation period of around 5-6 days (range roughly 2-14 days). Viral replication in the upper and lower respiratory tract drives the initial illness; in a minority of patients, around 1-2 weeks after symptom onset, a hyperinflammatory phase develops, marked by a surge in inflammatory cytokines, endothelial dysfunction, and a strongly prothrombotic state - this second phase, rather than direct viral cytotoxicity alone, underlies most severe and critical disease.

Clinical features and severity

• Fever
• Dry cough
• Fatigue and myalgia
• Anosmia and ageusia (loss of smell and taste) - a distinctive early feature of the original strains, less consistently seen with more recent variants
• Sore throat, headache and coryzal symptoms
• Dyspnoea, in more significant disease, reflecting progression to pneumonia

Risk factors for severe disease

• Older age - the single strongest predictor
• Obesity
• Diabetes mellitus
• Cardiovascular disease
• Chronic respiratory disease
• Chronic kidney disease
• Immunosuppression
• Pregnancy
• Being unvaccinated or not up to date with vaccination
• UK surveillance data identified higher risk in some Black and South Asian populations, reflecting a combination of higher rates of relevant comorbidity, occupational exposure and socioeconomic factors rather than ethnicity as an independent biological risk factor in isolation

Investigations

• PCR (nasopharyngeal or throat swab) - the gold standard diagnostic test
• Lateral flow antigen testing - rapid, useful for triage and self-testing, but less sensitive than PCR, particularly early in infection or with a low viral load
• Pulse oximetry - essential in every assessment, given the risk of silent hypoxia
• Chest X-ray or CT - not required to make the diagnosis, but useful to assess the extent of pneumonia in more unwell patients; CT classically shows bilateral, peripheral ground-glass opacities
• Bloods in hospitalised patients - FBC (lymphopenia is common and associated with more severe disease), CRP, ferritin (a marker of the hyperinflammatory phase), D-dimer (frequently raised, reflecting the prothrombotic state), LDH, and troponin if cardiac involvement is suspected

Differential diagnosis

• Influenza and other respiratory viruses - clinically similar; co-circulation means testing is often needed to distinguish them
• Community-acquired bacterial pneumonia - can also complicate or follow COVID-19
• Pulmonary embolism - can present with similar breathlessness and hypoxia, and can coexist with COVID-19 given the shared prothrombotic tendency

Management

Mild disease

Supportive care - rest, fluids, antipyretics and analgesia - is sufficient for the great majority of cases, managed in the community.

Oxygen and respiratory support

Standard target saturations of 94-98% apply (88-92% in patients at risk of type 2 respiratory failure), escalating through standard oxygen, continuous positive airway pressure (CPAP) or high-flow nasal oxygen, and invasive ventilation according to the same principles used in any hypoxaemic respiratory failure. Proning (positioning the awake or ventilated patient prone) improves oxygenation in hypoxaemic COVID-19 pneumonia and is used at multiple points along this pathway.

Dexamethasone: the RECOVERY trial

The UK RECOVERY trial found that dexamethasone (6 mg once daily for up to 10 days) significantly reduced 28-day mortality in patients requiring supplemental oxygen or ventilation, with the greatest benefit seen in those on invasive mechanical ventilation.¹

Antivirals and immunomodulators

• Nirmatrelvir/ritonavir or molnupiravir - oral antivirals for selected high-risk outpatients, most effective when started early in the illness
• Remdesivir - an IV antiviral used in specific hospitalised patient groups, per current national guidance
• Tocilizumab or other IL-6 pathway inhibitors - considered in selected patients with severe, progressive hyperinflammatory disease, alongside dexamethasone
• Monoclonal antibodies (for example sotrovimab) for specific high-risk, non-hospitalised patients - efficacy has varied significantly with circulating variant, since these agents target the spike protein directly

Thromboprophylaxis

Hospitalised patients with COVID-19 have a substantially increased risk of venous thromboembolism and should receive prophylactic-dose anticoagulation unless contraindicated by active bleeding or another clear reason - this is standard practice across admissions, not an optional extra.

Vaccination

Vaccination substantially reduces the risk of severe disease, hospitalisation and death. UK programmes have used mRNA vaccines (Pfizer-BioNTech, Moderna) and, earlier in the pandemic, an adenoviral vector vaccine (Oxford-AstraZeneca, now largely discontinued in the UK).

Complications

• Venous thromboembolism - both PE and DVT, reflecting the virus's strongly prothrombotic effect
• ARDS - the dominant cause of death in critical disease
• Myocarditis and other cardiac complications
• Acute kidney injury
• Secondary bacterial pneumonia
• PIMS-TS (paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2), also called MIS-C - a delayed, Kawasaki-like hyperinflammatory syndrome in children, typically 2-6 weeks after infection, with persistent fever, rash, conjunctivitis, gastrointestinal symptoms and a risk of cardiac involvement including coronary artery aneurysms
• Long COVID - persistent symptoms beyond 12 weeks not explained by an alternative diagnosis, commonly fatigue, breathlessness, cognitive impairment ("brain fog"), and myalgia, now a well-recognised and often disabling condition in its own right

Red flags

Prognosis

Most infections are mild and self-limiting, particularly in vaccinated individuals and with more recent, generally less severe circulating variants. Severe and critical disease, and mortality, are concentrated in the risk groups above, and vaccination has been the single most effective intervention in reducing these outcomes at a population level. Long COVID represents a significant ongoing burden even after apparently mild acute illness, and its risk does not track neatly with the severity of the initial infection.