SARS-CoV-2 and superimposed infection by trichomonads
Authors: Christophe Duboucher
Journal: Journal of Infection (2020)

•Until now, parasitic co-infections have not been noted in the course of COVID-19.•Trichomonads can be found in the lungs during acute respiratory distress syndrome.•Considering findings in ARDS, the detection of trichomonads in the lungs of SARS-CoV-2 can be relevant. Dear editor, We have read the interesting recently published review describing the evaluation of co-infections in patients with coronavirus disease 2019 (COVID-19).1Lansbury L. Lim B. Baskaran V. Lim W.S. Co-infections in people with COVID-19: a systematic review and meta-analysis.J Infect. Aug 2020; 81 (Epub 2020 May 27. PMID: 32473235; PMCID: PMC7255350): 266-275https://doi.org/10.1016/j.jinf.2020.05.046Abstract Full Text Full Text PDF PubMed Scopus (981) Google Scholar A letter to the editor has informed readers that fungal co-infections may be underestimated.2Alanio A. The presence of Pneumocystis jirovecii in critically ill patients with COVID-19.J Infect (in press 2020). 2020; https://doi.org/10.1016/j.jinf.2020.10.034Google Scholar The author of the letter reports an unexpected finding of a high proportion of critically ill COVID-19 patients detected as also being carrier of Pneumocystis jirovecii by RT-qPCR. Moreover, no parasitic co-infection was observed in the thirty studies collected in the review. With this letter, we wish to inform clinicians, pathologists and parasitologists of the occurrence of superimposed infections by trichomonads during "common" acute respiratory distress syndrome (ARDS) and probably also during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). More than ten years ago, in 2007, we reported frequent superimposed infection by trichomonads in ARDS.3Duboucher C. Barbier C. Beltramini A. Rona M. Ricome J.-L. Morel G. Capron M. Pierce R.J. Dei-Cas E. Viscogliosi E. Pulmonary superinfection by trichomonads in the course of acute respiratorydistress syndrome.Lung. Sep-Oct 2007; 185 (Epub 2007 Aug 15. PMID: 17701244): 295-301https://doi.org/10.1007/s00408-007-9022-1Crossref PubMed Scopus (22) Google Scholar Ninety consecutive bronchoalveolar lavage fluid (BALF) samples taken from 83 patients hospitalized in the same intensive care unit were retrospectively examined. Protists were detected in the BALF of 17/52 patients with ARDS. Only two of them also had P. jirovecii pneumonia (PjP). In ARDS, local hypoxic conditions could be the main factor favouring the multiplication of trichomonads because the alveolar lumens are filled with fibrin and cellular debris. The deleterious action of trichomonads remains hypothetical, but the amoeboid morphology of the parasite argues in favour of aggressiveness,4Hirt R.P. Trichomonas vaginalis virulence factors: an integrative overview.Sex Transm Infect. Sep 2013; 89 (Epub 2013 May 21. PMID: 23694938; PMCID: PMC3749517): 439-443https://doi.org/10.1136/sextrans-2013-051105Crossref PubMed Scopus (41) Google Scholar,5Salvador-Membreve D.M. Jacinto S.D. Rivera W.L. Trichomonas vaginalis induces cytopathic effect on human lung alveolar basal carcinoma epithelial cell line A549.Exp Parasitol. Dec 2014; 147 (Epub 2014 Oct 13. PMID: 25307688): 33-40https://doi.org/10.1016/j.exppara.2014.10.003Crossref PubMed Scopus (7) Google Scholar and the question of a role in the limitation of recovery is raised. SARS-CoV-2 offers the same local conditions favouring the development of trichomonads. Thus, the presence of trichomonads should be considered, and their potentially deleterious role in SARS-CoV-2 should be evaluated by clinical trials. Elsewhere, two years earlier, in 2005, we made the same observation of superimposed infection by trichomonads during PjP.6Duboucher C. Gerbod D. Noël C. Durand-Joly I. Delgado-Viscogliosi P. Leclerc C. Pham S. Capron M. Dei-Cas E. Viscogliosi E Frequency of trichomonads as coinfecting agents in Pneumocystis pneumonia.Acta Cytol. May-Jun 2005; 49 (PMID: 15966289): 273-277https://doi.org/10.1159/000326149Crossref PubMed Scopus (20) Google Scholar This observation was not made or commented on by others in the following years. Some readers even expressed doubt.7Duboucher C. Boggia R. Morel G. Capron M. Pierce R.J. Dei-Cas E. Viscogliosi E. Pneumocystis pneumonia: immunosuppression, Pneumocystis jirovecii... and the third man.Nat Rev Microbiol. Dec 2007; 5 (PMID: 19507333): 967https://doi.org/10.1038/nrmicro1621-c1Crossref Scopus (6) Google Scholar Nevertheless, this observation was also made earlier and was published in 2001.8Jacobs J.A. Dieleman M.M. Cornelissen E.I. Groen E.A. Wagenaar S.S. Drent M. Bronchoalveolar lavage fluid cytology in patients with Pneumocystis carinii pneumonia.Acta Cytol. May-Jun 2001; 45 (PMID: 11393061): 317-326https://doi.org/10.1159/000327625Crossref PubMed Scopus (34) Google Scholar The authors described "unidentified cells" almost exclusively in the BALF of patients infected with HIV. However, at that time, the cells described were considered human cells by the authors. The word "trichomonad" was not provided as an indexing keyword, and the report was forgotten. It is too early to consider superimposed trichomonas infection as a systematic event or threat to all patients with alveolar injury during ARDS, SARS-CoV-2, or PjP. Clinicians need confirmation from the cytopathologist or parasitologist examining the BALF. Parasitologists recognize the mobile flagellated form of trichomonad in liquid medium. Cytopathologists recognize trichomonads in Pap smears, not by their flagella – not stained – but by their calibrated shape and weakly stained elliptical nucleus. Thus, on BALF slides stained with May-Grünwald Giemsa (MGG), the parasite does not appear familiar to either cytopathologists or parasitologists. In addition, it is present in the amoeboid form. Strange cells can attract the eyes of cytopathologists accustomed to human cells, which can be regarded as "foreign cells" or more aptly as "parasitic cells" (Fig. 1). However, no one can assist the cytopathologists, including parasitologists. Apart from cases in which amoeboid forms of trichomonas are found under a microscope, mainly cases of PjP and ARDS, nested PCR is required. It should be noted that recent studies have shown that trichomonads colonize the lungs in other conditions and in healthy people.9Lin C. Ying F. Lai Y. Li X. Xue X. Zhou T. Hu D. Use of nested PCR for the detection of trichomonads in bronchoalveolar lavage fluid.BMC Infect Dis. Jun 2019; 19 (PMID: 31182037; PMCID: PMC6558733): 512https://doi.org/10.1186/s12879-019-4118-9Crossref PubMed Scopus (12) Google Scholar Unexpected or unknown species can also be found.10Maritz J.M. Land K.M. Carlton J.M. Hirt R.P. What is the importance of zoonotic trichomonads for human health?.Trends Parasitol. Jul 2014; 30 (Epub 2014 Jun 18. PMID: 24951156; PMCID: PMC7106558): 333-341https://doi.org/10.1016/j.pt.2014.05.005Abstract Full Text Full Text PDF PubMed Scopus (83) Google Scholar Struggling against the current COVID-19 pandemic, of which SARS is the major medical complication, the presence of trichomonas should not be overlooked or considered an anecdotal event. It seems fair to assess the potentially deleterious role of trichomonads in prospective clinical trials. Clinicians should inform their colleagues about this neglected parasite. Parasitologists and cytopathologists can only be convinced by pictures. It should be noted that routine MGG staining is the best way to identify amoeboid trichomonads and that even slides that are several years old can be examined retrospectively. The ideal way to convince observers is to show them pictures. Photomicrographs from different cases of P. jirovecii pneumonia and ARDS are provided as supplementary material in the online version of this letter (at http://dx.doi.org/10.17632/3b9bb9vsn8.1). None None No funding source is to be declared