Correlation between H eart fatty acid binding protein and severe COVID-19 :A case-control study

PONE-D-20-05567

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Reviewer #1: Yes

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Reviewer #1: This is a very timely, exciting and potentially transformative study of a potential blood biomarker for diagnosis of COVID-19 in symptomatic patients. The authors correctly state that currently severe COVID-19 is mainly diagnosed by clinical symptoms, and there is an urgent need for a serum marker that can be readily and rapidly performed. The study group patients were classified as mild or severe COVID according to the currently accepted pathological criteria. The focus on heart is justified because patients with heart disease are at higher risk for death and disability from the virus.

The novelty and high value of this study is that COVID patients were tested beginning with the day of admission for their serum level of heart fatty acid binding protein HFABP, an excellent choice for a candidate biomarker. H-FABP is an intracellular fatty acid binding protein found in high concentration in cardiac cells (myocytes). Its main function is to transport fatty acids inside the cell, and it does not normally leak though the cell membrane and enter the circulation. However, previous studies have extensively verified the discovery by the Glatz research group that after myocardial injury, damaged cells release HFABP. Is has been established as a marker for myocardial infarction, with higher sensitivity and specificity than the standard measure of troponin for an acute myocardial event and it is more rapidly released into the serum. The present study also measured troponin T in 40 patients, and only 6 showed elevated levels.

The current study is a milestone with its focus on the heart, and damage that can occur because of release of cytokines and by inflammatory responses. Moreover, previous studies have shown that the plasma concentration of HFABP has a prognostic value of death or MI after acute coronary syndrome one year. The current studies showed an association with higher levels of HFABP with severity of the COVID-19 in their patients. However, as a retrospective study, the elevated levels of HFABP cannot be a postulated to be a cause of the more rapid development.

Specific Comments:

Add refs below at top of p.3

Glatz JF, Kleine AH, van Nieuwenhoven FA, Hermens WT, van Dieijen-Visser MP, van der Vusse GJ (Feb 1994). "Fatty-acid-binding protein as a plasma marker for the estimation of myocardial infarct size in humans". British Heart Journal. 71 (2): 135–40. doi:10.1136/hrt.71.2.135. PMC 483632. PMID 8130020.

Kleine AH, Glatz JF, Van Nieuwenhoven FA, Van der Vusse GJ (Oct 1992). "Release of heart fatty acid-binding protein into plasma after acute myocardial infarction in man". Molecular and Cellular Biochemistry. 116 (1–2): 155–62. doi:10.1007/BF01270583. PMID 1480144.

Error in Table2: Table 2 has mislabeled the columns (HFABP negative should be positive)

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Reviewer #1: Yes: James A. Hamilton