Clinical and immunological signatures of severe COVID-19 in previously healthy patients with clonal hematopoiesis

Identifying additional risk factors for COVID-19 severity in numerous previously healthy patients without canonical clinical risk factors remains challenging. In this study, we investigate whether clonal hematopoiesis of indeterminate potential (CHIP), a common aging-related process that predisposes various inflammatory responses, may exert COVID-19 severity. We examine the clinical impact of CHIP in 143 laboratory-confirmed COVID-19 patients. Both stratified analyses and logistic regression including the interaction between canonical risk factors and CHIP show that CHIP is an independent risk factor for severe COVID-19, especially in previously healthy patients. Analyses of 60,310 single-cell immune transcriptome profiles identify distinct immunological signatures for CHIP (+) severe COVID-19 patients, particularly in classical monocytes, with a marked increase in pro-inflammatory cytokine responses and potent IFN-{gamma} mediated hyperinflammation signature. We further demonstrate that the enhanced expression of CHIP (+) specific IFN-{gamma} response genes is attributed to the CHIP mutation-dependent epigenetic reprogramming of poised or bivalent cis-regulatory elements. Our results highlight a unique immunopathogenic mechanism of CHIP in the progression of severe COVID-19, which could be extended to elucidate how CHIP contributes to a variety of human infectious diseases.

Acute Suppurative Appendicitis Diagnosed by Acute Lower Gastrointestinal Hemorrhage / 대한소화기학회지

A 49-year-old man visited the emergency room of Korea University Ansan Hospital with hematochezia starting the day before the visit. Recently, he was on anti-platelet medication due to hypertension. The patient had no definite symptoms other than hematochezia. Digital rectal exam was positive and laboratory tests showed severe anemia. Sigmoidoscopy was initiated and almost no fecal material was observed in the intestinal tract, allowing insertion into the cecum. Active bleeding from the appendiceal opening was noted. On abdominal CT, contrast enhancement was observed at the tip of the appendix. Under suspicion of acute appendicitis, we consulted with a surgeon. The patient underwent appendectomy with partial cecal resection. Pathologic examination revealed a diagnosis of appendix bleeding due to acute suppurative appendicitis. The patient had no further bleeding after surgery and was discharged in a stable state. Careful observation by the endoscopist is necessary for accurate diagnosis of lower gastrointestinal hemorrhage. Appendiceal hemorrhage is very rarely reported, but it has various pathophysiologies. CT scan is useful when appendiceal hemorrhage is confirmed by endoscopic findings. Surgical treatment was needed in almost all cases reported worldwide. If bleeding from the appendix is confirmed, surgical treatment should be considered for both therapeutic and diagnostic purposes.

A Case of Tenofovir-associated Fanconi Syndrome in Patient with Chronic Hepatitis B / 대한소화기학회지

Tenofovir disoproxil fumarate (TDF) is one of the most widely used treatment options for human immunodeficiency virus (HIV) and HBV infections. Despite its efficacy and safety, some cases of nephrotoxicity have been reported in the treatment of HIV patients. Even more recently, very few cases of Fanconi syndrome associated with tenofovir therapy in HBV monoinfection have been reported. Herein, we report a case of a 47-year-old male with an HBV monoinfection, who developed Fanconi syndrome and a secondary osteomalacia with multiple bone pain. After TDF withdrawal and supplementation of calcitriol, his renal function was reverted. Although the overall risk of TDF-associated nephrotoxicity is very low, both glomerular and tubular function should be monitored in patients undergoing TDF treatment.