Commentary on Macrotroponin Complex as a Cause for Cardiac Troponin Increase after COVID-19 Vaccination and Infection

Since the existence of potential macrotroponin complexes was first mooted in 2011 (1), further parallel work has highlighted a variety of possible causes of assay interference that may occur in a wide spectrum of clinical presentations where a troponin test request is clinically indicated. It remains unclear as to the precise mechanisms that lead to such interference and how troponins I versus T are affected, as well as the apparent increased involvement for certain assays, notably the high sensitivity troponins (2).

Clinically, any interference in a troponin assay measurement can produce spurious results that can lead to inappropriate diagnosis and subsequent management errors with suboptimal outcomes for the patient. Additional consequences for the patient’s recorded healthcare status and insurance risk may also be significant.

This series of cases focusing on patients following COVID-19 vaccination and infection adds a modern and relevant twist, so it would be important to publicize this at the present time given the significant burden that COVID-19 infection and possible vaccine reactions continue to impose on healthcare systems around the world. Acute presentations of potential acute coronary syndrome or myocarditis related to, or in the context of, COVID-19 infection or vaccination should, as suggested, consider assay interference when increased troponin levels are discordant with clinical or other investigations. Given that many emerging clinical guidance protocols may also suggest the use of tests such as troponin or natriuretic peptides in the assessment of patients with long COVID following the acute sequelae SARS-CoV-2 infection, then caution should also be observed in interpreting such test results in these patients.

Further work is now indicated to improve the knowledge surrounding interfering factors including prevalence in different clinical scenarios, clinical significance, and development of consistent, standardized approaches for identification and interpretation. Clarity around the prevalence and nature of immunoassay interference in these patient groups is crucial for their future management.

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Authors’ Disclosures or Potential Conflicts of Interest: No authors declared any potential conflicts of interest.