Human keratinocytes (KCs) express multiple EGF receptor (EGFR) ligands; however, their functions in specific cellular contexts remain largely undefined. To address this issue, first we measured mRNA and protein levels for multiple EGFR ligands in KCs and skin. Amphiregulin (AREG) was by far the most abundant EGFR ligand in cultured KCs, with > 19 times more mRNA and > 7.5 times more shed protein than any other family member. EGFR ligand expression in normal skin was low (< 8 ‰ of RPLP0/36B4); however, HB-EGF and AREG mRNAs were strongly induced in human skin organ culture. KC migration in scratch wound assays was highly metalloproteinase (MP)- and EGFR dependent, and markedly inhibited by EGFR ligand antibodies. However, lentivirus-mediated expression of soluble HB-EGF, but not soluble AREG, strongly enhanced KC migration, even in the presence of MP inhibitors. Lysophosphatidic acid (LPA)-induced ERK phosphorylation was also strongly EGFR and MP dependent and markedly inhibited by neutralization of HB-EGF. In contrast, autocrine KC proliferation and ERK phosphorylation were selectively blocked by neutralization of AREG. These data show that distinct EGFR ligands stimulate KC behavior in different cellular contexts, and in a MP-dependent fashion.

Objective Obesity has been found to be a risk factor for hospitalization with coronavirus disease (COVID‐19). This study investigated whether patients hospitalized with COVID‐19 differed in BMI at older versus younger ages and whether trends were independent of diabetes and hypertension. Methods A cross‐sectional analysis of patients hospitalized with moderate to severe COVID‐19 at Northwestern Memorial Hospital from March 19, 2020, until April 4, 2020, was performed. Patients hospitalized with COVID‐19 above and below the age of 50 were compared as well as those hospitalized without COVID‐19. Results Patients younger than 50 years of age hospitalized with COVID‐19 without diabetes or hypertension had mean BMI greater than those older than 50 years of age, with BMI 43.1 (95% CI: 34.5‐51.7) versus 30.1 (95% CI: 27.7‐32.5) (P = 0.02). Furthermore, BMI appeared to inversely correlate with increasing age among patients hospitalized with COVID‐19. We did not detect the same difference or trend for patients hospitalized without COVID‐19. Conclusions Younger patients (age < 50 years) with COVID‐19 had higher mean BMI than older patients with COVID‐19, with and without diabetes and hypertension. This trend did not exist in patients without COVID‐19 hospitalized during the same time period.

Background We present a yet to be described association of SARS-CoV-2 infection with Kikuchi-Fujimoto disease. Case presentation A 32-year-old physician with history of SARS-CoV-2 infection presented to the emergency department with 2 weeks of fever, chills, and right sided cervical lymphadenopathy. He was treated empirically for presumed folliculitis with worsening of symptoms leading to repeat presentation to the emergency department. Extensive workup was unrevealing of an infectious cause and needle biopsy of the lesion was unrevealing. An excisional lymph node biopsy revealed follicular hyperplasia with necrotic foci showing abundance of histiocytes at the edge of necrosis with CD8 predominance of T-cells. Final diagnosis was deemed to be Kikuchi-Fujimoto disease. Antibiotic therapy was discontinued, and the patient’s symptoms resolved with steroid therapy and expectant management. Conclusions This is the first report of a patient developing Kikuchi-Fujimoto disease following SARS-CoV-2 infection. Clinicians should be aware of Kikuchi-Fujimoto disease as a possibility when approaching patients with hyper-inflammatory states who present with cervical lymphadenopathy.

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