{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T16:12:54Z","timestamp":1753891974009,"version":"3.41.2"},"reference-count":24,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,5,1]],"date-time":"2025-05-01T00:00:00Z","timestamp":1746057600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pediatr."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>COVID-19 is known to induce cytokine storms and inappropriate cytotoxic immune responses. Hemophagocytic lymphohistiocytosis (HLH) is an underrecognized condition due to a hyperinflammatory syndrome characterized by fulminant hypercytokinemia with a high mortality burden. Cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induced secondary HLH during and post-infection have been sparsely reported in children. Inflammatory bowel disease (IBD) is a chronic, relapsing disorder of the gastrointestinal tract with a multifactorial etiology involving genetic, environmental, and immunological factors. To date, secondary HLH associated with COVID-19 in very early-onset inflammatory bowel disease (VEO-IBD) has not been reported. This case report aims to enhance understanding of the clinical manifestations of VEO-IBD and HLH, thereby facilitating the timely diagnosis and management of this rare condition.<\/jats:p><\/jats:sec><jats:sec><jats:title>Case presentation<\/jats:title><jats:p>We present the case of a 5-month-old Chinese female infant diagnosed with HLH following COVID-19 infection. The patient presented with hemophagocytic syndrome, which included recurrent fever, hepatosplenomegaly, cytopenia, hyperferritinemia, hypertriglyceridemia, and hypofibrinogenemia, after exposure to her mother, who had been diagnosed with COVID-19. Whole-exome sequencing(WES) identified heterozygous mutations in the IL-10RA gene: c.537 G\u2009&amp;gt;\u2009A (inherited from her mother) and c.301 C\u2009&amp;gt;\u2009T (inherited from her father), who was ultimately identified as having VEO-IBD. Despite receiving nutritional support, intravenous immunoglobulin (IVIG), and dexamethasone therapy, the patient continued to experience anemia, diarrhea, and refractory gastrointestinal bleeding. Following a brief improvement after interventional treatment, the parents declined further medical interventions, signed for discharge, and the infant sadly passed away three months later.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Rare genetic variants play a pivotal role in the pathogenesis of VEO-IBD, particularly in infants diagnosed before the age of one. These cases often demonstrate resistance to various immunosuppressive therapies and have a poor prognosis with conventional treatments. Our findings highlight the potential increased risk of severe HLH in patients with VEO-IBD and concurrent COVID-19, underscoring the need for comprehensive and vigilant differential diagnosis when patients exhibit symptoms suggestive of multi-organ damage.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fped.2025.1536066","type":"journal-article","created":{"date-parts":[[2025,5,1]],"date-time":"2025-05-01T05:38:57Z","timestamp":1746077937000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Secondary hemophagocytic lymphohistiocytosis in a 5-month-old infant with IBD post-COVID-19: a case 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