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Author(s): Deasy Natalia Adriana[sup.1], Titong Sugihartono[sup.2], Iswan Abbas Nusi[sup.2], Poernomo Boedi Setiawan[sup.2], Herry Purbayu[sup.2], Ummi Maimunah[sup.2], Ulfa Kholili[sup.2], Budi Widodo[sup.2], Husin Thamrin[sup.2], Amie Vidyani[sup.2], Hasan Maulahela[sup.3], Yoshio Yamaoka[sup.2,4,5,6] and Muhammad [...], Background Gastrointestinal manifestations of coronavirus disease 2019 (COVID-19) appear to be substantial. Fecal calprotectin is a promising biomarker in COVID-19 associated gastrointestinal inflammation; however, its role in the severity of COVID-19 remains limited. We conducted a study to analyze the relationship between the severity of COVID-19 and hypoxic intestinal damage. Methods We assessed the severity of 44 hospitalized COVID-19 pneumonia patients based on the PaO2/FiO2 (P/F) ratio. Inflammatory markers were measured from blood samples, and fecal calprotectin was obtained from stool samples. Results Median levels of fecal calprotectin in COVID-19 patients involved in this study (n = 44) were found to be markedly elevated along with the severity of hypoxemia, as seen in the non-acute respiratory distress syndrome (ARDS) group 21.4 [micro]g/g (5.2-120.9), mild ARDS 54.30 [micro]g/g (5.2-1393.7), moderate ARDS 169.6 [micro]g/g (43.4-640.5), and severe ARDS 451.6 [micro]g/g (364.5-538.6). We also found significant differences in fecal calprotectin levels based on the severity of ARDS (P < 0.001), and although the patients were divided into ARDS and non-ARDS groups (P < 0.001). Furthermore, we found a strong negative correlation between the P/F ratio and fecal calprotectin levels (r = - 0.697, P < 0.001). Conclusion Our findings support the potential role of fecal calprotectin as a biomarker of intestinal inflammation in COVID-19 as a consequence of hypoxic intestinal damage and as suggested by the reduced P/F ratio. Keywords: Fecal calprotectin, P/F ratio, COVID-19, Infectious disease

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.forsciint.2009.08.007 Byline: Jun-Ling An (a), Yuko Ishida (a), Akihiko Kimura (a), Michael Tsokos (b), Toshikazu Kondo (a) Keywords: Sepsis; Immunohistochemistry; Chemokines; CCR2; CX3CR1 Abstract: Sepsis is a systemic inflammatory disease with high mortality. In the present study, we immunohistochemically examined CCR2 and CX3CR1 expression in sepsis-induced lung injury, and discussed its availability for the postmortem diagnosis of sepsis. Lung samples were obtained from different lung lobes of nine sepsis and eight control cases with postmortem intervals between 12 and 48h. Immunohistochemically, mononuclear cells recruited into the lungs expressed CCR2 and CX3CR1 in both sepsis and non-septic groups. In double-color immunofluorescence analysis, CCR2- or CX3CR1-positive cells could be identified as CD68-positive macrophages. Moreover, most of CD68-positive macrophages expressed both CCR2 and CX3CR1. Morphometrically, the average of CCR2- and CX3CR1-positive macrophages was significantly increased in sepsis group, compared with control group (sepsis vs. control: 41.6[+ or -]1.3% vs. 8.0[+ or -]0.4% in CCR2; 36.2[+ or -]1.3% vs. 9.2[+ or -]0.4% in CX3CR1). These observations implied that CCR2- or CX3CR1-positive macrophages were recruited into the lungs under several pathological conditions. In particular, their recruitment might be more evident in sepsis. Moreover, from the forensic aspects, immunohistochemical detection of CCR2 and CX3CR1 expression in the lungs can be considered as valuable diagnostic tools for the postmortem diagnosis of sepsis. Author Affiliation: (a) Department of Forensic Medicine, Wakayama Medical University, 811-1 Kimiidera, Wakayama 641-8509, Japan (b) Institute of Legal Medicine and Forensic Sciences, Charite - University Medicine Berlin, Berlin, Germany Article History: Received 22 May 2009; Accepted 11 August 2009