Lab Tests to Collect Shortly After Severe Allergic Reaction/Anaphylaxis Following COVID-19 Vaccination

For Healthcare Providers

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There are no specific lab tests that can definitively diagnose the cause of a severe allergic reaction (e.g., anaphylaxis) following COVID-19 vaccination. In the United States, two commercially available lab tests can be ordered by healthcare providers and processed through healthcare facilities to better characterize a severe allergic reaction.

This document provides an overview of the timing and procedure for collecting blood samples for these lab tests. These samples should only be collected after medically stabilizing a patient who has experienced a severe allergic reaction.

The two commercially available lab tests are:

  • Tryptase (a mast cell marker)
  • SC5b-9 (terminal complement complex)

Tryptase is released from mast cells during anaphylaxis. SC5b-9 (terminal complement complex) is a measurement of complement system activation. These lab tests can be transiently elevated shortly after a severe allergic reaction. Elevations in these test results can help characterize the severe allergic reaction. Therefore, the timing of the blood sample collection for these tests can affect interpretation of the results.

The ideal time window to collect blood for these two tests is between 30 minutes and 90 minutes after the reaction began. However, these blood tests might still remain elevated up to 6 hours after the reaction began.

  • Collecting blood earlier than 30 minutes after the reaction began could yield results that would be more difficult to interpret.
  • If unable to collect this blood within the ideal 30–90 minute time window after the reaction began, healthcare providers can collect the blood samples as soon as possible, up through 6 hours after the reaction.
  • These results are unlikely to be affected by epinephrine, antihistamines, and other treatments used to manage anaphylaxis.

Healthcare providers can consult with the laboratory in their healthcare facility to determine their site-specific practice for processing samples for tryptase and SC5b-9 tests. Typically, immediately flash-freezing the serum sample for SC5b-9 at -80 degrees C can maximize the accuracy of this test. The resources below provide more information about specimen processing requirements for some commercial laboratories. CDC does not endorse a particular laboratory.

A second sample for tryptase could be obtained 24 hours or more after the severe allergic reaction, or even weeks after the reaction. This tryptase level obtained 24 hours or more after the severe allergic reaction reflects the patient’s typical tryptase level and can aid in the assessment of the allergic reaction.

Interpreting test results

Interpretation of these test results can be challenging. Consultation with a specialist (e.g., allergist-immunologist) within the weeks after the severe allergic reaction can help healthcare providers further evaluate potential factors that might have contributed to the development of the allergic reaction in these individuals. Also, healthcare providers or health departments in the United States can request a consultation from CISA COVIDvax for a complex COVID-19 vaccine safety question that is (1) about an individual patient residing in the United States or vaccine safety issue and (2) not readily addressed by CDC or Advisory Committee on Immunization Practices (ACIP) guidelines. More information about how to request a CISA COVIDvax consultation is available here: Clinical Immunization Safety Assessment (CISA) Project.

Reporting errors and adverse events

Vaccination providers are required by the Food and Drug Administration to report vaccination administration errors, serious adverse events, cases of Multisystem Inflammatory Syndrome, and cases of COVID-19 that result in hospitalization or death following COVID-19 vaccination under Emergency Use Authorization. Reporting is encouraged for any other clinically significant adverse event even if it is uncertain whether the vaccine caused the event. For information on how to submit a report to the Vaccine Adverse Event Reporting System (VAERS) click here or call 1-800-822-7967.