covid 19

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# **1. Definition**

COVID-19 is an acute viral disease caused by **SARS-CoV-2**, an enveloped, positive-sense **RNA coronavirus**. It ranges from asymptomatic infection to severe viral pneumonia, ARDS, sepsis, and multi-organ dysfunction.

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# **2. Virology & Pathophysiology**

### **Virus**

* Betacoronavirus, 29–30 kb RNA genome.
* Structural proteins: **S (spike), E, M, N**.
* S-protein binds **ACE2** receptors + TMPRSS2 facilitates entry.

### **Host entry & organ tropism**

ACE2 found in:

* Type II alveolar cells
* Myocardium
* Endothelium
* GI mucosa
* Kidney proximal tubules
* CNS

### **Phases of disease**

1. **Early Viral Replication Phase** (Days 1–5)
→ Viral replication high; symptoms mild; antivirals useful.
2. **Pulmonary Phase** (Days 5–10)
→ Viral + immune injury → pneumonia → hypoxia.
3. **Hyper-inflammatory Phase / Cytokine storm** (Days 10–14)
→ IL-6, IL-1β, TNF-α surge → ARDS, shock, thrombosis.

### **Immune Pathogenesis**

* Dysregulated innate immunity
* Delayed interferon response
* Hyper-inflammation
* **Endothelialitis + microvascular thrombosis** (↑ D-dimer)
* **Hypercoagulable state**

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# **3. Modes of Transmission**

* Respiratory droplets, aerosols
* Fomites (less common)
* Close contact
* Vertical transmission rare
* Highest contagious period: **2 days before and 3 days after symptom onset**.

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# **4. Variants (Updated Classification)**

* **Alpha, Beta, Gamma** — earlier waves
* **Delta** — more severe, high hospitalization
* **Omicron (BA.1 → BA.5, XBB, BQ, JN.1)** — highly transmissible, less severe, immune evasion
* **Current dominant lineages (global): Omicron sublineages** with high reinfection capability.

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# **5. Clinical Features**

### **Asymptomatic:** ~30–40%

### **Mild (Upper respiratory)**

* Fever, dry cough
* Sore throat
* Anosmia/ageusia
* Rhinorrhea
* Myalgia, fatigue

### **Moderate**

* Pneumonia with **SpO₂ ≥ 94%**
* Dyspnea
* Persistent fever

### **Severe**

* **SpO₂ < 94%**
* RR ≥ 30/min
* Lung infiltrates > 50%
* Respiratory distress

### **Critical**

* ARDS
* Septic shock
* Multi-organ dysfunction
* Acute cardiac injury
* Acute kidney injury

### **Complications**

* ARDS
* Cytokine storm
* Microthrombosis, DVT, PE
* MIS-C (children)
* Myocarditis
* Acute liver injury
* Long COVID (fatigue, dyspnea, cognitive dysfunction)

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# **6. Investigations**

### **Baseline**

* CBC: lymphopenia
* CRP: ↑
* D-dimer: ↑
* Ferritin: ↑
* LDH: ↑
* LFT, RFT
* ABG (if hypoxic)

### **Radiology**

**HRCT chest findings**:

* Bilateral peripheral **ground-glass opacities**
* Crazy-paving pattern
* Patchy consolidation
* CT Severity Score (CSS) used for monitoring

### **Diagnostic Tests**

* **RT-PCR (gold standard)**

* Genes: RdRp, N, E
* Ct < 25 → high viral load
* **Rapid Antigen Test** (moderate sensitivity)
* **Serology IgM/IgG** (past infection)

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# **7. Differential Diagnosis**

* Influenza
* RSV
* Adenovirus pneumonia
* Bacterial pneumonia
* Pulmonary embolism
* Heart failure
* Other viral pneumonias (CMV, H1N1)

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# **8. Management (Stepwise)**

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# 🟢 **A. Mild COVID-19 (Home Care)**

* Paracetamol
* Hydration
* Pulse oximeter monitoring
* Zinc (optional)
* Avoid steroids
* **Antivirals only for high-risk** (elderly, comorbid, immunosuppressed):

* **Nirmatrelvir + Ritonavir (Paxlovid)**
* **Remdesivir (early 3-day outpatient regimen)**

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# 🟡 **B. Moderate (SpO₂ ≥ 94% but pneumonia present)**

* **Oxygen if required** (target 92–96%)
* **Steroids: Dexamethasone 6 mg/day**
* **Remdesivir**
* **Anticoagulation: Enoxaparin prophylactic dose**
* Monitor:

* CRP, D-dimer
* RR, SpO₂ trends
* Chest imaging if worsening

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# 🔴 **C. Severe / Critical COVID-19**

### **1. Respiratory**

* Oxygen: NRBM → HFNC → NIV
* Intubation for refractory hypoxia
* Proning (awake & ventilated)

### **2. Anti-inflammatory**

* Dexamethasone 6 mg IV/PO x 10 days
* **Tocilizumab** (IL-6 inhibitor) for cytokine storm
* Baricitinib (JAK inhibitor) when Tocilizumab unavailable

### **3. Anticoagulation**

* **Therapeutic enoxaparin** in high D-dimer or suspected thrombosis
* Avoid if bleeding risk

### **4. Antivirals**

* Remdesivir (if < 10 days from symptom onset)
* Paxlovid (early disease only)

### **5. Organ Support**

* Vasopressors
* Renal replacement therapy
* ECMO in selected cases

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# **9. Pharmacology of Key Drugs**

*(Indication, MOA, Dosage, PK, ADRs, Contra, Monitoring, Counselling)*

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## **A. Remdesivir**

**Indication:** Moderate–severe COVID (within 10 days of symptoms)
**MOA:** RNA-dependent RNA polymerase inhibitor
**Dose:**

* 200 mg IV day 1 → 100 mg IV daily × 5 days
**PK:** Hepatic metabolism; renal elimination
**ADRs:** LFT elevation, bradycardia
**Contra:** GFR < 30 ml/min
**Monitoring:** LFT, renal function
**Counselling:** Report palpitations, yellowing of eyes.

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## **B. Dexamethasone**

**Indication:** Hypoxic COVID
**MOA:** Corticosteroid → suppresses cytokine storm
**Dose:** 6 mg/day PO/IV (max 10 days)
**ADRs:** Hyperglycemia, secondary infection, GI bleed
**Contra:** Uncontrolled diabetes, active fungal infection
**Monitoring:** RBS, BP, sepsis signs
**Counselling:** Take with food, watch for fever/worsening cough.

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## **C. Tocilizumab**

**Indication:** Severe COVID with high IL-6/CRP
**MOA:** IL-6 receptor blocker
**Dose:** 8 mg/kg IV single dose (max 800 mg)
**ADRs:** Hepatitis, neutropenia, bowel perforation
**Contra:** Sepsis, TB
**Monitoring:** LFT, CBC, CRP
**Counselling:** Report abdominal pain, jaundice.

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## **D. Nirmatrelvir + Ritonavir (Paxlovid)**

**Indication:** High-risk mild/moderate COVID **within 5 days**
**MOA:** 3CL protease inhibition + ritonavir boosting
**Dose:** 300 mg/100 mg BID × 5 days
**PK:** CYP3A4 inhibition (many interactions!)
**ADRs:** Dysgeusia, diarrhea
**Contra:** Statins, antiarrhythmics, immunosuppressants
**Monitoring:** Drug interactions, renal function
**Counselling:** Bitter taste normal; keep hydration.

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## **E. Enoxaparin**

**Indication:** Hypercoagulability in COVID
**MOA:** Inhibits factor Xa
**Dose:**

* Prophylactic: 40 mg SC daily
* Therapeutic: 1 mg/kg SC BID
**ADRs:** Bleeding, HIT
**Contra:** Active bleeding
**Monitoring:** Platelets, PT/aPTT
**Counselling:** Look for bruising.

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# **10. MIS-C (Children)**

* Persistent fever
* Multisystem inflammation
* Rash, shock, myocarditis
**Treatment:** IVIG + steroids + aspirin.

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# **11. Long COVID**

Symptoms > 12 weeks:

* Fatigue
* Breathlessness
* Brain fog
* Autonomic dysfunction
* Depression/anxiety
**Management:**
Rehab, pulmonary exercises, sleep hygiene, CBT if needed.

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# **12. Prevention**

### **General**

* Masks
* Ventilation
* Hand hygiene
* Avoid crowded indoor spaces

### **Vaccination**

Approved platforms:

* mRNA (Pfizer, Moderna)
* Viral vector (Covishield, AstraZeneca, J&J)
* Inactivated (Covaxin, Sinopharm)
* Protein subunit (Novavax)

**Booster indicated** for elderly, comorbid, immunocompromised.

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# **13. Key Exam Pearls**

* **RT-PCR Ct value does NOT correlate with severity.**
* **Steroids only in hypoxia.**
* **Remdesivir not useful late (>10 days).**
* **Tocilizumab only with high inflammatory markers.**
* **High D-dimer is a poor prognostic marker.**
* **Omicron → less LRT disease but high reinfection rates.**

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