Does a TPMT activity of 14 U (intermediate activity) in a patient with Behçet’s disease on azathioprine 150 mg daily increase the risk of severe COVID‑19?

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Last updated: October 2, 2026 • View editorial policy

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TPMT Activity of 14 U Does Not Increase COVID-19 Risk

A TPMT activity of 14 U (intermediate activity) does not place your patient at higher risk for severe COVID-19. The concern here relates to azathioprine toxicity risk, not COVID-19 severity.

Understanding the Actual Risks

TPMT and Azathioprine Toxicity (Not COVID-19)

Your patient's TPMT level of 14 U indicates intermediate enzyme activity (heterozygous deficiency), which creates a different clinical concern:

  • Patients with intermediate TPMT activity have a 4-fold increased risk of azathioprine-induced myelosuppression 1
  • This manifests as leukopenia, not increased COVID-19 susceptibility
  • The risk is for drug toxicity, particularly bone marrow suppression from the 150 mg daily azathioprine dose 2

Critical distinction: Low TPMT increases risk of azathioprine side effects, but does not independently increase COVID-19 infection risk or severity.

COVID-19 Risk in This Clinical Context

The actual COVID-19 risk factors for your patient are:

Azathioprine itself: Guidelines indicate no current evidence of increased risk of COVID-19 infection with immunomodulators including azathioprine 3. Studies in Behçet's disease patients on azathioprine showed:

  • No increased COVID-19 mortality 4
  • Relatively mild disease course 5
  • Hospital admission rates comparable to general population 4

The dose matters more than TPMT: At 150 mg daily, your patient is on a standard-to-high dose. Older patients (>60 years) or those with significant comorbidity on thiopurines may wish to consider stopping after discussion with their team 3.

Clinical Management Algorithm

For Azathioprine Dosing with Intermediate TPMT:

  1. Consider dose reduction: Patients with intermediate TPMT activity should receive azathioprine at the lower end of the dosing range 2
  2. Enhanced monitoring: More frequent CBC monitoring than standard (weekly initially, then at least monthly) 2, 6
  3. Alternative therapies should be considered for patients with low TPMT activity 2

For COVID-19 Risk Management:

Continue azathioprine unless the patient:

  • Is actively infected with COVID-19 (then temporarily withhold) 7
  • Is >60 years with significant comorbidity AND in sustained remission 3
  • Develops concerning cytopenias

Do not stop azathioprine solely due to COVID-19 concerns - the risk of Behçet's disease flare (potentially requiring high-dose steroids, which DO increase COVID-19 risk) outweighs theoretical infection concerns 3, 8.

Common Pitfall to Avoid

Do not conflate TPMT-related myelosuppression risk with COVID-19 susceptibility. The intermediate TPMT activity means your patient needs closer hematologic monitoring and possibly dose adjustment of azathioprine, but this pharmacogenetic finding does not place them in a higher COVID-19 risk category. The immunosuppression from azathioprine at therapeutic doses has not been shown to worsen COVID-19 outcomes in inflammatory disease patients 9, 4.

If myelosuppression develops (which is more likely with intermediate TPMT), this secondary neutropenia could theoretically increase infection susceptibility, but the primary concern remains azathioprine toxicity management, not an inherent COVID-19 risk from the TPMT level itself.

References

2
Guideline

guidelines for prescribing azathioprine in dermatology.

British Journal of Dermatology, 2004

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.