Interferon-lambda:New functions on intestinal symptoms in COVID-19

The tremendous public health and economic impact of coronavirus disease 2019(COVID-19), caused by severe acute respiratory syndrome coronavirus 2(SARSCoV-2), has become a huge challenge globally. There is increasing evidence that SARS-CoV-2 induces intestinal infections. Type Ⅲ interferon(IFN-λ) has an antiviral role in intestinal infection, with focused, long-lasting, and non-inflammatory characteristics. This review presents a summary of the structure of SARSCoV-2, including its invasion and immune escape mechanisms. Emphasis was placed on the gastrointestinal impact of SARS-CoV-2, including changes to the intestinal microbiome, activation of immune cells, and inflammatory responses.We also describe the comprehensive functions of IFN-λ in anti-enteric SARS-CoV-2 infection, and discuss the potential application of IFN-λ as a therapeutic agent for COVID-19 with intestinal symptoms.

Antibiotic and glucocorticoid-induced recapitulated hematological remission in acute myeloid leukemia:A case report and review of literature

BACKGROUND Leukemic hematopoietic cells acquire enhanced self-renewal capacity and impaired differentiation.The emergence of symptomatic leukemia also requires the acquisition of a clonal proliferative advantage.Untreated leukemia patients usually experience an aggressive process.However,spontaneous remission occasionally occurs in patients with acute myeloid leukemia(AML),most frequently after recovery from a febrile episode,and this is generally attributed to the triggering of antineoplastic immunity.There may be another explanation for the spontaneous remission as implicated in this paper.CASE SUMMARY A 63-year-old Chinese man presented with high fever,abdominal pain and urticaria-like skin lesions.He was diagnosed with AML-M4 with t(8;21)(q22;q22)/RUNX1-RUNX1T1 based on morphological,immunological,cytogenetic and molecular analyses.He had a complex chromosome rearrangement of 48,XY,t(8;21)(q22;q22),+13,+13[9]/49,idem,+mar[9]/49,idem,+8[2].He also had a mutated tyrosine kinase domain in fms-like tyrosine kinase 3 gene.He was treated with antibiotics and glucocorticoids for gastrointestinal infection and urticaria-like skin lesions.The infection and skin lesions were quickly resolved.Unexpectedly,he achieved hematological remission along with resolution of the febrile episode,gastrointestinal symptoms and skin lesions.Notably,after relapse,repeating these treatments resulted in a return to hematological remission.Unfortunately,he demonstrated strong resistance to antibiotic and glucocorticoid treatment after the second relapse and died of sepsis from bacterial infection with multidrug resistance.The main clinical feature of this patient was that symptomatic AML emerged with flaring of the gut inflammatory disorder and it subsided after resolution of the inflammation.Learning from the present case raises the possibility that in a subgroup of AML patients,the proliferative advantage of leukemia cells may critically require the presence of inflammatory stresses.CONCLUSION Inflammatory stresses,most likely arising from gastrointestinal infection,may sustain the growth and survival advantage of leukemic cells.

Acute suppurative oesophagitis with fever and cough: A case report

BACKGROUND Suppurative oesophagitis is a diffuse inflammation of the oesophagus characterized by suppurative exudate or pus formation.Suppurative infections can affect any part of the gastrointestinal tract,most commonly the stomach,with inflammation involving the entire gastric cavity.However,cases extending beyond the cardia or pylorus and involving the oesophagus,small intestine,and colon are rare.Usually such cases are discovered during surgery or autopsy.CASE SUMMARY We report a rare case of acute suppurative oesophagitis.A 57-year-old man presented at the Emergency Department of our hospital with fever and productive cough.The patient had a significant history of lower oesophageal mucosal frostbite.He was successfully diagnosed and treated with repeated gastroscopy,appropriate antibiotics,and innovative symptomatic treatment.CONCLUSION Early diagnosis and appropriate treatment of acute suppurative oesophagitis are critical.Nutritional support,postural drainage,and other symptomatic treatments must be considered.

SARS-CoV-2 induced intestinal responses with a biomimetic human gut-on-chip

Coronavirus disease 2019(COVID-19), caused by severe acute respiratory syndrome coronavirus 2(SARSCo V-2), has become a global pandemic. Clinical evidence suggests that the intestine is another high-risk organ for SARS-Co V-2 infection besides the lungs. However, a model that can accurately reflect the response of the human intestine to the virus is still lacking. Here, we created an intestinal infection model on a chip that allows the recapitulation of human relevant intestinal pathophysiology induced by SARSCo V-2 at organ level. This microengineered gut-on-chip reconstitutes the key features of the intestinal epithelium-vascular endothelium barrier through the three-dimensional(3 D) co-culture of human intestinal epithelial, mucin-secreting, and vascular endothelial cells under physiological fluid flow. The intestinal epithelium showed permissiveness for viral infection and obvious morphological changes with injury of intestinal villi, dispersed distribution of mucus-secreting cells, and reduced expression of tight junction(E-cadherin), indicating the destruction of the intestinal barrier integrity caused by virus.Moreover, the vascular endothelium exhibited abnormal cell morphology, with disrupted adherent junctions. Transcriptional analysis revealed abnormal RNA and protein metabolism, as well as activated immune responses in both epithelial and endothelial cells after viral infection(e.g., upregulated cytokine genes), which may contribute to the injury of the intestinal barrier associated with gastrointestinal symptoms. This human organ system can partially mirror intestinal barrier injury and the human response to viral infection, which is not possible in existing in vitro culture models. It provides a unique and rapid platform to accelerate COVID-19 research and develop novel therapies.