Background
Cardiac fibrosis complicates SARS‐CoV‐2 infections and has been linked to arrhythmic complications in survivors. Accordingly, we sought evidence of increased HSP47 (heat shock protein 47), a stress‐inducible chaperone protein that regulates biosynthesis and secretion of procollagen in heart tissue, with the goal of elucidating molecular mechanisms underlying cardiac fibrosis in subjects with this viral infection.
Methods and Results
Using human autopsy tissue, immunofluorescence, and immunohistochemistry, we quantified Hsp47
+
cells and collagen α 1(l) in hearts from people with SARS‐CoV‐2 infections. Because macrophages are also linked to inflammation, we measured CD163
+
cells in the same tissues. We observed irregular groups of spindle‐shaped HSP47
+
and CD163
+
cells as well as increased collagen α 1(I) deposition, each proximate to one another in “hot spots” of ≈40% of hearts after SARS‐CoV‐2 infection (HSP47
+
P
<0.05 versus nonfibrotics and
P
<0.001 versus controls). Because HSP47
+
cells are consistent with myofibroblasts, subjects with hot spots are termed “profibrotic.” The remaining 60% of subjects dying with COVID‐19 without hot spots are referred to as “nonfibrotic.” No control subject exhibited hot spots.
Conclusions
Colocalization of myofibroblasts, M2(CD163
+
) macrophages, and collagen α 1(l) may be the first evidence of a COVID‐19–related “profibrotic phenotype” in human hearts in situ. The potential public health and diagnostic implications of these observations require follow‐up to further define mechanisms of viral‐mediated cardiac fibrosis.
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