Management of Elevated Tryptase in COVID-19 Patients
Do not routinely measure tryptase during acute COVID-19 illness unless there is clinical suspicion of concurrent anaphylaxis or acute mast cell degranulation. 1
Understanding the Pathophysiology
COVID-19 is strongly associated with mast cell activation and degranulation, though this occurs indirectly through the inflammatory response rather than direct viral activation. 2, 3 The evidence shows:
- Mast cell-derived proteases (tryptase, chymase, carboxypeptidase A3) are elevated in COVID-19 patient sera and correlate with clinical severity 2, 3, 4
- The density of degranulated mast cells in COVID-19 lung autopsies is significantly increased compared to control lungs 3
- Approximately 17% of the population may have underlying mast cell activation syndrome (MCAS), which could predispose to severe COVID-19 5
When to Measure Tryptase
Obtain timed tryptase samples only if the patient develops acute symptoms suggesting anaphylaxis or acute mast cell degranulation: 1
- Sudden cardiovascular collapse
- Acute bronchospasm
- Acute urticaria
- Multi-system symptoms suggesting anaphylaxis
Important caveat: Tryptase elevation in COVID-19 reflects the inflammatory cascade, not necessarily a primary mast cell disorder requiring specific intervention beyond standard COVID-19 management. 2, 3
Risk Stratification for Patients with Known Mast Cell Disorders
Patients with pre-existing mast cell disorders face elevated risk for severe COVID-19 if they have: 1
- Cardiovascular comorbidities
- Bronchopulmonary involvement
- Active chemotherapy or immunosuppressive therapy
Medication Management During COVID-19
Continue These Medications Without Interruption
For patients with known mast cell disorders, maintain all antimediator drugs throughout COVID-19 infection: 1
- H1 antihistamines
- H2 antihistamines
- Leukotriene receptor antagonists
- Cromolyn sodium (inhibits mast cell degranulation by preventing calcium entry) 1, 6
Corticosteroid Considerations
The American College of Rheumatology suggests corticosteroids may benefit severe COVID-19 with hyperinflammation, but routine escalation solely based on mastocytosis diagnosis is not warranted. 1 If initiated for COVID-19 management, expect a 2-3 week taper to avoid rebound inflammation. 1
Avoid Mast Cell Degranulators
In hospitalized patients, avoid direct mast cell degranulators: 1
- Morphine, meperidine (prefer fentanyl or sufentanil if opioids needed)
- Vancomycin
- Contrast media without premedication
Standard COVID-19 Management Applies
Implement standard COVID-19 protocols without modification for elevated tryptase alone: 1
- Standard anticoagulation protocols (COVID-19 creates a prothrombotic state independent of mast cell activation) 7
- Continue ACE inhibitors/ARBs if previously prescribed (no increased risk demonstrated) 7
- Supportive therapies based on disease severity 7
Emergency Preparedness for High-Risk Patients
All patients with confirmed mastocytosis or baseline tryptase >20 ng/mL must have: 1
- Two epinephrine auto-injectors available at all times
- Medic Alert identification
- Written emergency action plan
Critical recognition: Patients remain at risk for mast cell degranulation from fever, physical stress, hypoxia, certain COVID-19 medications, and emotional stress during acute illness. 1
Potential Therapeutic Implications
Emerging research suggests anti-Siglec-8 antibodies (which selectively inhibit mast cells and deplete eosinophils) reduced disease severity and airway inflammation in viral infection models, though this remains investigational. 2 Mast cell stabilizing drugs have been preliminarily observed to be helpful in COVID-19 patients. 5
Prognostic Value
The combined measurement of tryptase, CPA3, chymase, and prostaglandin D2 demonstrates enhanced predictive ability for severe COVID-19 outcomes and may serve as a biomarker for disease severity. 4 However, this is primarily useful for research and prognostication rather than altering acute management decisions.