Medicine chapters
COVID-19
How SARS-CoV-2 causes disease, how to confirm it in the laboratory, how severity is graded and what the evidence-based treatments are for each stage.
- COVID-19 is caused by SARS-CoV-2, an enveloped positive-sense RNA coronavirus that enters cells through the ACE2 receptor (helped by the protease TMPRSS2).
- Severe disease is driven by an excessive inflammatory response and clotting, not just by the virus; it usually declares itself in the second week.
- RT-PCR on a nasopharyngeal swab confirms infection; dexamethasone helps only patients who need oxygen, while antivirals work best early.
On this page
Overview
COVID-19 (coronavirus disease 2019) is the illness caused by SARS-CoV-2, a coronavirus first identified in Wuhan, China, in December 2019. It spread worldwide as a pandemic.
Most infections are mild upper respiratory illnesses. A minority develop viral pneumonia, ARDS, clotting problems and multi-organ failure. Older age and chronic disease raise the risk.
For PGET you need the mechanism (ACE2, cytokine storm, clotting), the tests (PCR, antigen, CT, inflammatory markers) and the treatment by severity.
The virus
- Family Coronaviridae; an enveloped, positive-sense single-stranded RNA virus with a crown ("corona") of spike proteins.
- Related human coronaviruses: 229E, OC43, NL63, HKU1 (common colds), SARS-CoV (2002–03) and MERS-CoV (from dromedary camels, 2012).
- New variants arise by mutation of the spike protein (for example Delta and Omicron). Omicron spreads faster but tends to cause milder disease in vaccinated people.
Transmission
- Mainly respiratory droplets and aerosols; close contact and poorly ventilated rooms raise risk.
- Contaminated surfaces play a smaller role.
- People can spread the virus before symptoms start, which made control difficult.
- The incubation period is usually a few days and up to 14 days; this is why quarantine was 14 days early in the pandemic.
Pathophysiology
Cell entry
- The spike (S) protein binds the ACE2 receptor on host cells.
- The host protease TMPRSS2 cleaves the spike so the viral envelope can fuse with the cell.
- ACE2 is plentiful on type II pneumocytes, nasal epithelium, gut, kidney, heart and blood vessel lining. This explains why the disease affects many organs.
SARS-CoV-2 (like the original SARS-CoV) uses angiotensin-converting enzyme 2 (ACE2) as its receptor.
Stages of disease
| Stage | Timing | Main process | Clinical picture |
|---|---|---|---|
| Early infection | First week | Viral replication | Fever, cough, sore throat, fatigue, loss of smell or taste |
| Pulmonary phase | About days 7–10 | Viral pneumonia, falling oxygen levels | Breathlessness, hypoxia, bilateral infiltrates |
| Hyperinflammatory phase | Second week onwards | Cytokine storm (IL-6 and others), endothelial injury, clotting | ARDS, shock, thrombosis, multi-organ failure |
- Viral load is highest early, so antivirals help most then.
- Damage later is due mainly to the host immune response, which is why steroids and IL-6 blockers help in the later, oxygen-requiring stage.
- Endothelial damage and a hypercoagulable state cause venous thromboembolism, arterial clots and microthrombi in the lungs.
Loss of smell
- Sudden anosmia without a blocked nose is a typical early sign.
- The virus infects the supporting (sustentacular) cells of the olfactory epithelium, which carry ACE2, rather than the olfactory neurons themselves.
- When these support cells regenerate, smell usually returns over weeks.
Clinical features
- Common: fever, dry cough, fatigue, myalgia, sore throat, headache.
- Typical clues: sudden loss of smell or taste.
- Others: diarrhoea, conjunctivitis, rash.
- "Silent" or "happy" hypoxia: low oxygen saturation with surprisingly little breathlessness. Check pulse oximetry, not just symptoms.
Risk factors for severe disease
- Older age, diabetes, hypertension, obesity, chronic heart, lung or kidney disease.
- Immunosuppression, cancer, pregnancy.
- Being unvaccinated.
Investigations
Confirming infection
| Test | What it detects | Notes |
|---|---|---|
| RT-PCR (nasopharyngeal swab) | Viral RNA | Gold standard; most sensitive; may stay positive for weeks after recovery |
| Rapid antigen test | Viral nucleocapsid protein | Quick and cheap; less sensitive, best when viral load is high early on |
| Antibody (serology) | IgM/IgG | Shows past infection or vaccination; not used for acute diagnosis |
A positive antibody test does not mean active infection. Use PCR or antigen tests for diagnosis.
Blood tests: markers of severity
- Lymphopenia (low lymphocyte count) is typical.
- Raised D-dimer (clotting), ferritin, CRP, LDH, IL-6.
- Raised troponin suggests myocardial injury.
- Liver enzymes and creatinine may rise.
Lymphopenia with a high D-dimer, ferritin and LDH points to severe disease and a worse outcome.
Imaging
- Chest X-ray: bilateral, peripheral, lower-zone shadowing.
- HRCT chest: bilateral peripheral ground-glass opacities, later consolidation and a "crazy-paving" pattern.
- CT pulmonary angiogram if pulmonary embolism is suspected (sudden worsening, rising D-dimer).
Severity grading
Using the WHO approach (exact cut-offs vary between guidelines):
| Severity | Key features |
|---|---|
| Mild | Symptoms but no pneumonia or hypoxia |
| Moderate | Clinical pneumonia, but oxygen saturation acceptable on room air |
| Severe | Pneumonia with low oxygen saturation, fast breathing or severe distress |
| Critical | ARDS, sepsis, septic shock, need for ventilation |
Management
General measures
- Isolation and infection control (masks, hand hygiene, ventilation).
- Paracetamol for fever, fluids, rest.
- Home pulse oximetry for patients at higher risk.
Treatment by stage
| Patient group | Main treatment |
|---|---|
| Mild, high-risk, early (first few days) | Oral antiviral such as nirmatrelvir with ritonavir (watch drug interactions); remdesivir is an IV alternative |
| Needs oxygen | Dexamethasone 6 mg daily (up to 10 days); remdesivir in selected patients; prophylactic LMWH |
| Needs oxygen and has rising inflammation | Add an immunomodulator: tocilizumab (IL-6 receptor blocker) or baricitinib (JAK inhibitor) |
| Critical | ICU care, high-flow oxygen or ventilation, prone positioning, lung-protective ventilation |
Dexamethasone reduces deaths only in patients who need oxygen or ventilation. In mild disease without hypoxia it does not help and may cause harm.
Antibiotics do not treat COVID-19. Give them only if bacterial co-infection is suspected.
Hydroxychloroquine and ivermectin were widely used early in the pandemic, but good studies showed no benefit.
Oxygen and ventilation
- Give oxygen to keep saturation at a safe target (lower targets in COPD).
- Awake prone positioning improves oxygenation in non-intubated patients.
- High-flow nasal oxygen or CPAP before intubation where appropriate.
Thrombosis
- All admitted patients without a contraindication receive prophylactic low-molecular-weight heparin.
- Proven pulmonary embolism or DVT needs treatment-dose anticoagulation.
Complications
- ARDS and respiratory failure.
- Venous thromboembolism, stroke, myocardial infarction.
- Myocarditis, arrhythmias, acute kidney injury.
- Secondary infections, including mucormycosis in poorly controlled diabetics given steroids (a problem reported from South Asia).
- MIS-C (multisystem inflammatory syndrome in children): fever and inflammation weeks after infection, resembling Kawasaki disease.
- Long COVID (post-COVID condition): fatigue, breathlessness, poor concentration ("brain fog") lasting months.
Prevention
- Vaccination (mRNA, viral vector and inactivated vaccines) greatly reduces severe disease and death.
- Masks, distancing, ventilation, hand hygiene.
- Isolation of cases and testing of contacts.
ACE-2, Two weeks, Two killers: the virus binds ACE-2, the danger comes in week 2, and the two killers are inflammation and clots.
Expect: the receptor for SARS-CoV-2 (ACE2) and the role of TMPRSS2; RT-PCR as the gold-standard test versus antigen and antibody tests; lab markers of severity (lymphopenia, D-dimer, ferritin, CRP, LDH); typical HRCT findings (peripheral ground-glass, crazy-paving); dexamethasone only for patients needing oxygen; timing of antivirals; prone positioning; and complications such as thrombosis, mucormycosis, MIS-C and long COVID.
Quick revision
- SARS-CoV-2: enveloped, positive-sense RNA coronavirus.
- Entry via ACE2, spike primed by TMPRSS2.
- Week 1 viral; week 2 inflammation and clotting.
- Diagnosis: nasopharyngeal RT-PCR; antigen test is quicker but less sensitive.
- Severity markers: lymphopenia, high D-dimer, ferritin, CRP, LDH, troponin.
- CT: bilateral peripheral ground-glass opacities.
- Dexamethasone if oxygen needed; tocilizumab or baricitinib for rising inflammation.
- Antivirals early; LMWH for admitted patients; prone positioning for hypoxia.
Written by The House Job from standard references (Kumar and Clark's Clinical Medicine; Levinson's Review of Medical Microbiology and Immunology).
FAQ
What receptor does SARS-CoV-2 use?
It binds angiotensin-converting enzyme 2 (ACE2) through its spike protein; the host enzyme TMPRSS2 then primes the spike for entry.
Which test is best to diagnose COVID-19?
RT-PCR on a nasopharyngeal swab is the gold standard. Rapid antigen tests are quicker but miss more cases, and antibody tests show past exposure only.
Who should get dexamethasone?
Patients with COVID-19 who need supplemental oxygen or ventilation. It gives no benefit in mild disease without hypoxia.
Why does loss of smell in COVID-19 usually recover?
The virus damages the supporting cells of the olfactory lining rather than the smell neurons, and these support cells grow back over weeks.