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

During the coronavirus disease 2019 (COVID-19) pandemic, there was renewed interest in infection, inflammation, and myocardial injury. Intriguingly, a publication from a decade ago looking at high-sensitivity cardiac troponin T (hs-cTnT) testing at 3 different biennial collection intervals in healthy children revealed that transient increases in hs-cTnT were more suggestive of an infective etiology as opposed to any cardiac disease (1). With the findings from Bularga and colleagues’ clinical case study on macrotroponin following COVID-19 vaccination or infection, another possible explanation, in hindsight, for the previous hs-cTn elevations in children may be due to macrocomplexes.

There are several analytical causes for increased cTn concentrations that are incongruent with ongoing myocardial injury (2), with one being immunoglobulin bound cTn, often called “macrotroponin.” Biochemical detection of macrocomplexes can be performed by either polyethylene glycol precipitation or immunoglobulin removal, as was performed in this case study. However, prior to performing such biochemical procedures, it is often helpful to assess whether the cTn elevations in serial sampling represent stable levels, where <20% change in concentrations is used for this stable designation. Intriguingly, 1 of the 3 patients in the case study exhibited a major decrease in hs-cTnI over 3–6 hours, from 280 000 ng/L to 180 000 ng/L (−36%), yet the paired hs-cTnT concentrations in these same samples were normal/unchanged at 8 ng/L and 6 ng/L, respectively.

When investigating possible macrocomplexes, testing with another hs-cTnI method may be beneficial, and here testing with hs-cTnT (another protein) further suggested an interference. However, macrocomplexes may yield different hs-cTn results on different manufacturer platforms and assay versions, with the findings from this case study also indicating that samples requiring dilutions (i.e. Abbott hs-cTnI >50 000 ng/L requires dilution) may also yield discrepant results. Careful collaboration between the clinical care and laboratory team is a necessity for these complex investigations.