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Our results highlight that the presence of CHIP may increase the susceptibility to hyperinflammation through the reorganization of chromatin architecture, establishing a novel subgroup of severe COVID-19 patients.In eukaryotic cells, DNA damage can occur at any time and at any chromatin locus, including loci at which active transcription is taking place. DNA double-strand breaks affect chromatin integrity and elicit a DNA damage response to facilitate repair of the DNA lesion. Actively transcribed genes near DNA lesions are transiently su