Monocytes could be a bridge from inflammation to thrombosis on COVID-19 injury: A case report Antonino Mazzone a , Laura Castelnovo a, * , Antonio Tamburello a , Arianna Gatti b , Bruno Brando b , Paola Faggioli a , Nicola Mumoli a a Department of Internal Medicine - ASST Ovest Milanese, Italy b Transfusion Center Legnano Hospital - ASST Ovest Milanese, Italy ARTICLE INFO Keywords: COVID19 Thrombosis Inflammation Monocytes CD11B/CD18 SARS-Cov 2 infection is responsible for pandemic COVID19, a new viral illness causing acute respiratory syndrome and cardiovascular events [1] in which inflammation and thrombotic events are frequent. It’s also known that exacerbated inflammation ad immune system dys- regulation can cause severe clinical manifestations; in this process a crucial effector role is played by monocytes. Coronary thrombosis occurring during acute coronary syndromes, similarly, are due to an inflammatory storm with increased number of circulating activated monocytes/macrophages [2]. We know that monocytes are involved in infections: persistent activation of circulating monocytes/macrophages, induced by the release of cytokines, above all IL-6, has been postulated [1]; moreover IL-6 overexpression seems to be related with disease severity and pro-coagulant profile. Prior observa- tions documented that inflammation mediated by phagocytes in rat lungs is blocked by preincubation with anti-Mo1 monoclonal antibodies thus preventing pulmonary injury [3]; these antibodies react with CD11b/CD18 integrin complex, that represents a major adhesion on monocytes/macrophages and IL6 promotes interaction with ICAM, also acting on platelets, to favor thrombosis [4,5]. Our recent work [6] showed that, during the monitoring of patients infected by SARS-CoV-2 a reproducible decrease of peripheral Non-classical (NC) and intermediate (INT) monocyte was found in sub- jects with the most severe clinical status at admission suggesting that their decreasing may be considered prognostic indicators that may help in the early identification of patients with the worst and most rapid unfavorable outcome. Here we describe our investigations in expression levels of CD11b on peripheral blood CD14 þ monocytes, studied by flow cytometry, in a 64- year-old patient affected by COVID19 pneumonia who underwent to non -invasive ventilation (CPAP) then tracheal intubation due to an intersti- tial pneumonia conditioning acute respiratory failure. At admission the expression of CD11b was 8231 MFI (Mean Fluorescence Intensity) units. The patient was treated with enoxaparin and tocilizumab (in combina- tion with hydroxychloroquine and antibiotic therapy with ceftriaxone and azithromycin). No steroids were used. CD11b expression fell to 4582 MFI units over 7 days. In accordance with this, IL6 values were also hyper – expressed (IL6 243,4 pg/mL; L < 7 pg/mL) while value after 8 days was 18 pg/mL, showing a reduction in value, congruent with the improve- ment of the patient (Fig. 1, flow cytometric). Simultaneously with the improvement of data relating to the expression of IL6 and CD11b, as described in Fig. 2, we assisted to a normalization of inflammatory markers indices, improvement in lymphopenia values of and resolution of respiratory insufficiency. Asthenia improved and fever disappeared and the patient was progressively weaned from oxygen therapy. The relationship between inflammatory process and heart disease has been debated: monocytes/macrophages recruitment express the CD11b/ CD18 adhesion molecule, mediating their adhesion to the endothelial cells and leading to inflammation. Therefore, as reported in ischemic diseases and unstable angina, activated leukocytes and platelets poten- tiate each other’s effects, favoring the occurrence of thrombosis [1]. A * Corresponding author. E-mail address: laura.castelnovo@asst-ovestmi.it (L. Castelnovo). Contents lists available at ScienceDirect Thrombosis Update journal homepage: www.journals.elsevier.com/thrombosis-update https://doi.org/10.1016/j.tru.2020.100007 Received 7 June 2020; Received in revised form 17 August 2020; Accepted 22 August 2020 2666-5727/© 2020 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by- nc-nd/4.0/). Thrombosis Update 1 (2020) 100007