What erythropoiesis-stimulating agents (ESAs) are recommended for patients with long COVID and concurrent anemia?

Recommended Erythropoiesis-Stimulating Agents for Concurrent Anemia

For patients with long COVID and concurrent anemia, the recommended erythropoiesis-stimulating agents (ESAs) include epoetin alfa, epoetin beta, darbepoetin alfa, and biosimilar epoetin alfa products, all of which are considered equivalent in effectiveness and safety. 1

Selection of ESAs

The choice of ESA should follow these guidelines:

Available Options:

• Epoetin alfa: 150 IU/kg subcutaneously three times weekly or 450 IU/kg once weekly
• Epoetin beta: 30,000 IU subcutaneously once weekly
• Darbepoetin alfa: 2.25 μg/kg subcutaneously once weekly or 500 μg (6.75 μg/kg) once every 3 weeks 1, 2

Dosing Considerations:

• Initial dosing should follow FDA guidelines with adjustments based on hemoglobin response
• Dose increases should be considered if hemoglobin increases <1 g/dL after 4-6 weeks of therapy
• Dose reductions of 25-50% are recommended if hemoglobin rises >2 g/dL in a 4-week period or exceeds 12 g/dL 1
• Therapy should be temporarily discontinued if hemoglobin exceeds 13 g/dL until it falls below 12 g/dL 1

Clinical Decision Algorithm

Step 1: Determine Eligibility

• Confirm hemoglobin level is <10 g/dL (primary criterion for ESA initiation)
• Ensure treatment is not curative in intent (ESAs should not be used when cancer treatment is curative) 1
• Rule out other causes of anemia through appropriate testing (iron deficiency, vitamin deficiencies, etc.) 2

Step 2: Assess Risk Factors

• Evaluate for thromboembolism risk (ESAs significantly increase this risk) 1
• Consider comorbidities that might affect ESA response or safety
• Note that anemia is associated with more severe COVID-19 illness (OR 3.47,95% CI: 1.02-11.75) 3

Step 3: Implement Treatment

• Start with recommended initial dose based on selected ESA
• Monitor hemoglobin weekly until stable, then regularly throughout treatment 2
• Target hemoglobin level should be the lowest concentration needed to avoid transfusions (approximately 10-12 g/dL) 1

Step 4: Monitor Response and Adjust

• Evaluate hemoglobin response after 4-6 weeks
• Discontinue therapy if no response (increase of <1 g/dL) after 6-8 weeks 1
• For responders, continue treatment until completion of primary therapy course

Special Considerations for Long COVID Patients

Long COVID patients may have unique considerations:

• Higher risk of thrombotic events, which may be compounded by ESA use 4
• Potential for COVID-related anemia mechanisms including autoimmune hemolytic anemia 5
• Iron metabolism dysregulation in COVID-19 patients (elevated ferritin levels are common) 6

Important Caveats

• Thromboembolism risk: ESAs significantly increase thromboembolism risk; use with extreme caution in patients with history of thrombosis or other risk factors 1
• Treatment failure: If no response after 6-8 weeks, discontinue ESA and reevaluate for underlying causes 1
• Iron status: Monitor and supplement iron as needed to optimize ESA response 2
• Target hemoglobin: Do not exceed 12 g/dL due to increased cardiovascular risks with higher levels 1
• Administration route: Subcutaneous administration is 30-50% more efficient than intravenous administration 2

By following this structured approach, clinicians can appropriately select and manage ESA therapy for patients with long COVID and concurrent anemia, optimizing outcomes while minimizing risks.