Archives of Academic Emergency Medicine. 2020; 8(1): e83 LE T T E R TO ED I TO R Superinfection by Trichomonas, a Second Reason to Add Metronidazole to COVID-19 Treatment; a Letter to Editor Christophe Duboucher1∗ 1. Laboratory of Pathology, C.H.I. de Poissy / Saint-Germain, Saint-Germain-en-Laye, France. Received: September 2020; Accepted: September 2020; Published online: 22 October 2020 Cite this article as: Duboucher C. Superinfection by Trichomonas, a Second Reason to Add Metronidazole to COVID-19 Treatment; a Letter to Editor. Arch Acad Emerg Med. 2020; 8(1): e83. Dear Editor, All countries are struggling against the COVID-19 pandemic. One million deaths have been recorded. Acute respiratory distress syndrome (ARDS) is the major complication. No an- tiviral therapy has been shown to be clearly effective for re- ducing the rate of mortality in published randomised con- trolled trials. In an article published in the last issue of Archives of Academic Emergency Medicine, metronidazole is suggested to be tested in clinical trials (1). In vitro and in vivo studies have revealed that metronidazole could decrease the levels of several cytokines. It could also decrease neutrophil- generated reactive oxygen species, and thus could counteract majority of the immunopathological manifestations of the COVID-19 infection. Metronidazole could be included in clinical trials for another reason. More than ten years ago we observed that lungs of patients diseased from ARDS, show superimposed infection by trichomonads (2). In this situation, local hypoxic condi- tions could be the main factor favoring trichomonad infec- tion development as alveolar lumens are obliterated by fibrin and cellular debris. If our observations show that trichomonads infection could develop during the late phase of ARDS, the deleterious action of trichomonads remains to be proven. Nevertheless, amoe- boid transformation argues for aggressiveness of trichomon- ads (3). When facing the current COVID-19 pandemic, the major medical complication of which is ARDS, the presence of tri- chomonads should not be overlooked or considered an anec- dotal event. It seems fair to assess the potential deleterious role of trichomonads in prospective clinical trials. The same observation of superimposed infection by tri- ∗Corresponding Author: Christophe Duboucher; 29 rue Raymond Queneau, 92500 Rueil Malmaison, France. Phone: +33.6.86.32.42.31, Fax: +33.9.57.39.78.12, Email: christophe.duboucher@trichomoniasis- pathology.org chomonads has been made during the course of Pneumocys- tis jirovecii pneumonia (PJP) (4). However, since our publication in 2005, observations of tri- chomonads in the course of PJP and of ARDS have not been made or commented on by other cytopathologists or parasitologists. Readers who are not observers may have doubts, but observers may see these unidentified cells in bronchoalveolar lavage fluids (BALF), and worry about their nature. Nevertheless, there is an explanation for this oc- cultation. In alveolar lumens, when adhering to epithelial cells of host, trichomonads evolve from a flagellated form to an amoeboid form. When transforming into amoeboid form, they develop pseudopods and lose their flagella. Thus, they look like anonymous cells that have lost their distinctive marks and can mimic human cells. So, on slides colored us- ing MGG, amoeboid trichomonads do not harbor a familiar appearance neither for parasitologists nor for cytopatholo- gists. It is difficult to find reports in the literature before 2005, when the word "trichomonad" was not used as keyword of indexation. The unique article we found, in which these "alien cells" are presented, was published in 2001 in Acta Cytologica by Jan Jacobs et al. (5). The authors described "non-identified cells" almost exclusively in BALF from hu- man immunodeficiency virus (HIV )-infected patients. Un- fortunately, the authors failed to ask themselves the follow- ing question: "are these cells human cells?". Parasitologists and cyto-pathologists need to be convinced by pictures. Mi- crophotographs from different cases of ARDS and PJP are vis- ible at https://www.trichomoniasis-pathology.org/ 1. Declarations 1.1. Acknowledgements None. This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: http://journals.sbmu.ac.ir/aaem C. Duboucher 2 1.2. Conflict of interest None. 1.3. Funding and support No financial support has been received. References 1. Gharebaghi R, Heidary F, Moradi M, Parvizi M. Metronida- zole; a potential novel addition to the COVID-19 treatment regimen. Archives of Academic Emergency Medicine. 2020;8(1). 2. Duboucher C, Barbier C, Beltramini A, Rona M, Ricome J- L, Morel G, et al. Pulmonary superinfection by trichomon- ads in the course of acute respiratory distress syndrome. Lung. 2007;185(5):295-301. 3. Duboucher C, Caby S, Pierce RJ, Capron M, DEI- CAS E, Viscogliosi E. Trichomonads as superinfecting agents in Pneumocystis pneumonia and acute respira- tory distress syndrome. Journal of Eukaryotic Microbiol- ogy. 2006;53:S95-S7. 4. Duboucher C, Gerbod D, Noel C, Durand-Joly I, Delgado- Viscogliosi P, Leclerc C, et al. Frequency of trichomonads as coinfecting agents in Pneumocystis pneumonia. Acta cytologica. 2005;49(3):273-7. 5. Jacobs JA, Dieleman MM, Cornelissen E, Groen E, Wage- naar SS, Drent M. Bronchoalveolar lavage fluid cytology in patients with Pneumocystis carinii pneumonia. Acta cyto- logica. 2001;45(3):317. This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: http://journals.sbmu.ac.ir/aaem Declarations References