How to manage a patient with elevated tryptase (a marker of mast cell activation) levels due to a viral infection such as Coronavirus Disease 2019 (COVID-19)?

Elevated Tryptase in Viral Infections Like COVID-19

Elevated tryptase in the context of COVID-19 is not a primary diagnostic concern and does not require specific mast cell-directed management unless there is clear evidence of anaphylaxis or systemic mastocytosis. The available evidence does not establish viral infections, including COVID-19, as a recognized cause of clinically significant tryptase elevation requiring intervention.

Understanding Tryptase Elevation

Tryptase is a neutral protease selectively concentrated in mast cell secretory granules and serves as a specific marker of mast cell activation and degranulation 1, 2. Elevated serum tryptase levels occur in two primary clinical contexts:

• Acute mast cell activation: Mature (beta) tryptase rises during systemic anaphylaxis, typically reaching 9-75 ng/mL during anaphylactic events 1
• Increased mast cell burden: Total tryptase elevation occurs in systemic mastocytosis and certain hematologic disorders 3

Importantly, viral infections including COVID-19 are not documented as causes of elevated tryptase in the available clinical literature. 1, 2, 3

COVID-19 and Biomarker Interpretation

When evaluating patients with COVID-19, focus should be on established inflammatory markers rather than tryptase:

Recognized COVID-19 Biomarkers

• Procalcitonin (PCT): Low PCT levels (<0.25 ng/mL) at presentation have high negative predictive value for bacterial coinfection and can guide antibiotic stewardship 4
• Cardiac troponin: Mild elevations (2-3 times upper limit of normal) commonly occur in COVID-19 due to myocardial injury from hypoxemia, cytokine storm, or type 2 MI, not requiring cardiac catheterization unless type 1 MI is suspected 4
• Inflammatory markers: Elevated CRP, ESR, D-dimer, and cytokines (IL-6, IL-1β, TNF-α) reflect the hyperinflammatory state 4

Clinical Approach to Elevated Tryptase

If tryptase is elevated in a patient with COVID-19, consider alternative explanations:

Differential Diagnosis

1. Anaphylaxis: Look for acute onset (minutes to hours) of hypotension, urticaria, angioedema, bronchospasm, or gastrointestinal symptoms 5, 1

   • Tryptase peaks 1-2 hours after symptom onset and remains elevated for several hours 2
   • Levels >5 ng/mL suggest mast cell activation 1

2. Systemic mastocytosis: Consider if baseline tryptase persistently elevated (>20 ng/mL typically) with symptoms of mast cell mediator release 3

3. Other causes: Acute myelocytic leukemia, myelodysplastic syndromes, end-stage renal failure 3

Management Algorithm

For patients with elevated tryptase during COVID-19:

• If acute symptoms of anaphylaxis present: Treat anaphylaxis immediately with intramuscular epinephrine, regardless of COVID-19 status 6, 2
• If no anaphylactic symptoms: Focus management on COVID-19 supportive care and monitoring for bacterial superinfection using PCT levels 4, 7
• Serial tryptase measurement: Not indicated for COVID-19 monitoring; reserve for suspected ongoing mast cell activation 5

COVID-19 Specific Management Priorities

Management should focus on established COVID-19 complications rather than tryptase levels:

• Monitor for respiratory deterioration requiring oxygen supplementation or mechanical ventilation 7
• Use PCT to guide antibiotic decisions, restricting antimicrobials when PCT <0.25 ng/mL 4
• Address cytokine storm with appropriate anti-inflammatory therapy when indicated 4
• Maintain immunosuppression in transplant or autoimmune patients unless severe deterioration occurs 7

Critical Pitfalls to Avoid

• Do not attribute tryptase elevation to COVID-19 without excluding anaphylaxis or mastocytosis 1, 2, 3
• Do not order tryptase routinely in COVID-19 patients—it is not part of standard COVID-19 laboratory evaluation 4
• Do not delay anaphylaxis treatment if clinical presentation suggests mast cell activation, even in COVID-19 patients 6
• Do not confuse troponin elevation (common in COVID-19) with tryptase elevation (not established in COVID-19) 4