What are the current guidelines for managing Covid-19?

Current COVID-19 Management Guidelines

COVID-19 vaccination remains the cornerstone of prevention, with treatment stratified by disease severity and patient risk factors, emphasizing early antiviral therapy for high-risk patients and corticosteroids with immunomodulators for those requiring oxygen support. 1, 2, 3

Vaccination Strategy

General Population

• All eligible individuals should receive complete COVID-19 vaccination with the most immediately available locally approved vaccine 1
• Delaying the second dose is not recommended unless mandated by individual patient circumstances 1
• Third and fourth booster doses should be administered according to national guidelines, particularly for immunocompromised patients 1
• Household contacts of high-risk patients, including children (per age-appropriate approvals), should be vaccinated 1

Immunocompromised Patients

• Patients with hematological malignancies (HM) and hematopoietic stem cell transplant (HSCT) recipients should receive full vaccination programs 1
• Antibody response should be assessed 3-5 weeks after the last dose due to heterogeneous responses 1
• Patients with low antibody titers should be re-vaccinated 6 months after treatment completion 1
• HSCT recipients should initiate vaccination at least 6 months post-transplant when community transmission is low, though GVHD risk must be considered 1
• Previous COVID-19 infection does not eliminate the need for full vaccination 1

Treatment by Disease Severity

Mild COVID-19 (No Oxygen Requirement)

For high-risk patients, initiate antiviral therapy within 5 days of symptom onset: 2, 3

First-line options:

• Nirmatrelvir/ritonavir (Paxlovid): 300 mg nirmatrelvir with 100 mg ritonavir twice daily for 5 days 2

  • Critical caveat: Ritonavir is a strong CYP3A4 inhibitor with potentially life-threatening drug interactions 2
  • Must review all concomitant medications before prescribing 2
  • Contraindicated with drugs highly dependent on CYP3A clearance 2

• Remdesivir: 200 mg IV loading dose on Day 1, then 100 mg IV daily 3

  • Treatment duration: 5 days for non-hospitalized patients 3
  • Requires IV access but no significant drug interactions 3

Alternative therapies for immunocompromised patients (when antivirals unavailable): 1

• Anti-SARS-CoV-2 monoclonal antibodies (if active against circulating variants) 1
• High-titer convalescent plasma within 72 hours of symptom onset 1
• Inhaled interferon beta-1a 1
• Molnupiravir 1

Dexamethasone should NOT be used in mild COVID-19 1

Moderate COVID-19 (Oxygen Support, Saturation >90%)

Combination therapy is recommended: 1

1. Remdesivir: 200 mg IV loading dose, then 100 mg IV daily for up to 10 days 3
2. Dexamethasone 6 mg daily for 10 days 1
3. If patient is seronegative, add:
   • Casirivimab/imdevimab (if available and active against circulating variants) 1
   • OR convalescent plasma 1

If worsening despite dexamethasone with evidence of COVID-19-related inflammation, add second immunosuppressant: 1

• Anti-IL-6 agents (tocilizumab or sarilumab) 1
• Anti-IL-1 (anakinra) 1
• JAK inhibitors (baricitinib or tofacitinib) 1

Severe/Critical COVID-19 (Saturation <90%, RR >30/min, Mechanical Ventilation, or Vasopressor Therapy)

Intensive multimodal therapy: 1

1. Dexamethasone 6 mg daily for 10 days (proven mortality benefit) 1
2. Remdesivir: 200 mg IV loading dose, then 100 mg IV daily for up to 10 days 1, 3
3. If seronegative and on non-invasive ventilation (NIV), consider casirivimab/imdevimab (no data for invasive mechanical ventilation) 1
4. Add second immunosuppressant if COVID-19-related inflammation present:
   • Anti-IL-6 agents (tocilizumab or sarilumab) - preferred 1
   • Anti-IL-1 (anakinra) 1
   • JAK inhibitors 1

Prophylaxis Strategies

Pre-Exposure Prophylaxis

• Long-acting anti-SARS-CoV-2 monoclonal antibodies recommended for immunocompromised patients not immunized and at high risk for severe COVID-19 1
• Particularly important for vaccine non-responders or those not expected to respond to vaccination 1

Post-Exposure Prophylaxis

• Anti-SARS-CoV-2 monoclonal antibodies recommended for high-risk patients (unvaccinated, vaccine non-responders, or immunocompromised) 1

Infection Control for Healthcare Workers

For aerosol-generating procedures (intubation, bronchoscopy, suctioning, nebulization, proning, NIV, tracheostomy, CPR): 1

• Fitted N95 respirators, FFP2, or equivalent (not surgical masks) 1
• Plus full PPE: gloves, gown, and eye protection (face shield or goggles) 1
• Healthcare workers should be fit-tested for each respirator type 1

Diagnostic Testing

• Molecular assays (PCR/NAT) are the gold standard for acute diagnosis 1
• SARS-CoV-2 RNA testing in blood is NOT recommended for initial diagnosis 1
• Cycle threshold (Ct) values >30 indicate low/absent transmission risk (with adequate sampling quality) 1
• Antibody testing:
  • N-protein antibodies: assess previous SARS-CoV-2 exposure 1
  • S-protein antibodies: assess vaccine response or previous exposure 1
  • NOT recommended for acute diagnosis 1

Dose Adjustments for Renal Impairment (Nirmatrelvir/Ritonavir)

Moderate renal impairment (eGFR 30-59 mL/min): 2

• 150 mg nirmatrelvir with 100 mg ritonavir twice daily for 5 days

Severe renal impairment (eGFR <30 mL/min, including hemodialysis): 2

• Day 1: 300 mg nirmatrelvir with 100 mg ritonavir once
• Days 2-5: 150 mg nirmatrelvir with 100 mg ritonavir once daily
• Administer after hemodialysis on dialysis days

Symptom Management (Community/End-of-Life Care)

Cough Management 1

• Avoid supine positioning (makes coughing ineffective) 1
• Honey for patients >1 year old 1
• Short-term codeine linctus, codeine phosphate, or morphine sulfate oral solution for distressing cough 1

Fever Management 1

• Maintain adequate hydration (≤2 liters/day) 1
• Paracetamol preferred over NSAIDs for symptomatic relief 1
• Do not use antipyretics solely to reduce temperature 1

Breathlessness 1

• Controlled breathing techniques: pursed-lip breathing, positioning (sitting upright, leaning forward with arm support) 1
• For end-of-life moderate-to-severe breathlessness: morphine sulfate 2.5-5 mg every 2-4 hours as needed, with antiemetic and stimulant laxative 1

Critical Monitoring Requirements

• Hepatic function testing before and during treatment (particularly with remdesivir and ritonavir) 3
• Prothrombin time monitoring before and during treatment 3
• Strict glycemic control (especially for mucormycosis risk in corticosteroid-treated patients) 1