What is the recommended management for a patient with a confirmed Covid-19 diagnosis, considering severity of symptoms and underlying health conditions such as hypertension or diabetes?

Management of COVID-19 Positive Patients

For outpatient COVID-19 patients with mild-to-moderate disease who are at high risk for progression (including those with hypertension or diabetes), consider nirmatrelvir-ritonavir combination therapy within 5 days of symptom onset, with molnupiravir as an alternative when nirmatrelvir-ritonavir is unavailable. 1, 2

Risk Stratification

High-risk patients requiring treatment consideration include those with: 1

• Age >65 years 1
• Diabetes mellitus - associated with increased disease severity and mortality 1, 3
• Hypertension - positively associated with death (OR: 0.49), ICU care (OR: 0.42), and disease severity (OR: 2.69) 3
• Cardiovascular disease 1
• Chronic kidney disease 1
• Chronic lung disease 1
• Obesity 1
• Immunocompromising conditions 4

Outpatient Management (Mild-to-Moderate Disease)

Antiviral Therapy for High-Risk Patients

Within 5 days of symptom onset: 1, 5

• First-line: Nirmatrelvir-ritonavir combination therapy - reduces all-cause mortality, COVID-19 mortality, hospital admissions, and serious adverse events 1, 2, 6

• Second-line: Molnupiravir - reduces all-cause mortality, time to recovery, and hospital admissions when other options unavailable 1, 2, 6

• Alternative: Anti-SARS-CoV-2 monoclonal antibodies - especially for unvaccinated or immunocompromised patients with impaired vaccine response 2, 6

• High-titer convalescent plasma - within 72 hours of symptom onset if monoclonal antibodies unavailable 2, 6

Treatments NOT Recommended

• Do not use ivermectin - no evidence of benefit 1, 5
• Do not use sotrovimab - not effective against current variants 1, 5
• Do not use hydroxychloroquine/chloroquine combinations with azithromycin 2
• Do not use combinations of three or more antiviral drugs simultaneously 2

Hospitalized Patient Management

Non-Severe Disease (Not Requiring Oxygen)

• Remdesivir - 200 mg IV loading dose on Day 1, then 100 mg IV daily for 5 days total (may extend to 10 days if no clinical improvement) 7, 4, 8
• Supportive care with oxygen supplementation to maintain SpO2 >90-96% 2, 6
• Prophylactic anticoagulation to prevent venous thromboembolism 1, 2, 6

Moderate Disease (Requiring Supplemental Oxygen)

• Remdesivir - same dosing as above for 5-10 days 7, 4, 8
• Dexamethasone 6 mg daily for up to 10 days or until hospital discharge 2, 6
• Oxygen supplementation to maintain SpO2 >90-96% 2, 6
• Thromboprophylaxis 1, 2, 6

Severe/Critical Disease (Mechanical Ventilation/ECMO)

• Remdesivir - 200 mg IV loading dose on Day 1, then 100 mg IV daily for 10 days total 7
• Dexamethasone 6 mg daily for up to 10 days 2, 6
• Consider anti-IL-6 therapy (tocilizumab or sarilumab) if worsening despite dexamethasone 1, 9
• Therapeutic anticoagulation per institutional protocols 1
• Monitor for acute kidney injury - occurs in 31% of ventilated patients 1

Special Considerations for Diabetes and Hypertension

Diabetes Management 1

• Intensify glycemic control - check blood glucose every 2-4 hours or use continuous glucose monitoring 1
• Continue insulin therapy - never stop; expect dramatically increased insulin requirements disproportionate to typical critical illness 1
• Monitor for diabetic ketoacidosis - frequently presents at hospital admission with COVID-19 1
• Stop metformin if dehydration present due to lactic acidosis risk 1
• Stop SGLT-2 inhibitors due to dehydration and DKA risk 1
• Monitor renal function closely for acute kidney injury 1
• Continue DPP-4 inhibitors - generally well tolerated 1

Hypertension Management 1

• Continue ACE inhibitors and ARBs - no evidence to discontinue 1
• Maintain optimal fluid status - critical for reducing AKI incidence but challenging to achieve 1
• Monitor for volume depletion from fever and increased respiratory rate 1

Monitoring Requirements

Before and During Treatment 7

• Hepatic laboratory testing - before starting and during remdesivir therapy 7
• Prothrombin time - before starting and monitor during remdesivir 7
• Renal function - assess for AKI on admission and monitor serum urea, creatinine, electrolytes 1
• Fluid status - peripheral perfusion, capillary refill, pulse rate, blood pressure, urine output 1
• Potassium levels - manage hyperkalaemia per local protocols; consider patiromer or sodium zirconium cyclosilicate 1

Immunocompromised Patients 1, 2, 6

• Pre-exposure prophylaxis with long-acting monoclonal antibodies for unimmunized patients 2, 6
• Post-exposure prophylaxis with monoclonal antibodies for high-risk unvaccinated or vaccine non-responders 2, 6
• Consider longer antiviral treatment duration due to prolonged viral replication 1, 2, 6

Discharge Criteria 2

Patients may be discharged when:

• Two consecutive negative RT-PCR tests from respiratory samples 2
• Temperature normal for >3 days 2
• Respiratory symptoms significantly improved 2
• Significant absorption of pulmonary lesions on CT imaging 2

Critical Pitfalls to Avoid

• Do not delay antiviral therapy - must initiate within 5-7 days of symptom onset for outpatients 1, 7
• Do not use dexamethasone in patients not requiring oxygen - detrimental effect in early viral phase 1
• Do not underdose insulin - COVID-19 causes disproportionate insulin resistance 1
• Do not continue SGLT-2 inhibitors or metformin during acute illness - high risk of DKA and lactic acidosis 1
• Do not overlook AKI monitoring - occurs in 31% of ventilated patients and increases mortality 1