Low-dose chest CT for diagnosing and assessing the extent of lung involvement of SARS-CoV-2 pneumonia using a semi quantitative score
Authors: Julie Finance
Maxime Castelli
Jean-Yves Gaubert
Alexis Jacquier
Matthieu Million
Axel Bartoli
Philippe Parola
Jean-Christophe Lagier
Paul Habert
Didier Raoult
Philippe Brouqui
Thomas Leger
Pierre-Antoine Barral
Journal: PLoS ONE (2020)
Discipline: Multidisciplinary
Keywords: low-dose CT; lung involvement; SARS-CoV-2 pneumonia; COVID19-LDCT severity score; ground-glass opacities
Affiliations: Department of Radiology, La Timone Hospital, Assistance Publique des Hôpitaux de Marseille, Marseille, France., Aix-Marseille Université, UMR 7339, CNRS, Centre de Résonance Magnétique Biologique et Médicale-Centre d'Exploration Métaboliques par Résonance Magnétique, Assistance Publique-Hôpitaux de Marseille, Marseille, France., IHU-Méditerranée Infection, Marseille, France., Aix Marseille Univ, IRD, APHM, MEPHI, Marseille, France., Aix Marseille Univ, IRD, APHM, SSA, VITROME, Marseille, France., Aix Marseille Univ, LIIE, Marseille, France., Aix Marseille Univ, CERIMED, Marseille, France.

Abstract:  Objectives: The purpose is to assess the ability of low-dose CT (LDCT) to determine lung involvement in SARS-CoV-2 pneumonia and to describe a COVID19-LDCT severity score. Materials and methods: Patients with SARS-CoV-2 infection confirmed by RT-PCR were retrospectively analysed. Clinical data, the National Early Warning Score (NEWS) and imaging features were recorded. Lung features included ground-glass opacities (GGO), areas of consolidation and crazy paving patterns. The COVID19-LDCT score was calculated by summing the score of each segment from 0 (no involvement) to 10 (severe impairment). Univariate analysis was performed to explore predictive factor of high COVID19-LDCT score. The nonparametric Mann-Whitney test was used to compare groups and a Spearman correlation used with p&lt;0.05 for significance. Results: Eighty patients with positive RT-PCR were analysed. The mean age was 55 years ± 16, with 42 males (53%). The most frequent symptoms were fever (60/80, 75%) and cough (59/80, 74%), the mean NEWS was 1.7±2.3. All LDCT could be analysed and 23/80 (28%) were normal. The major imaging finding was GGOs in 56 cases (67%). The COVID19-LDCT score (mean value = 19±29) was correlated with NEWS (r = 0.48, p&lt;0.0001). No symptoms were risk factor to have pulmonary involvement. Univariate analysis shown that dyspnea, high respiratory rate, hypertension and diabetes are associated to a COVID19-LDCT score superior to 50. Conclusions: COVID19-LDCT score did correlate with NEWS. It was significantly different in the clinical low-risk and high-risk groups. Further work is needed to validate the COVID19-LDCT score against patient prognosis. 

Retracted: No

PubPeer comments:
 This article mentions that  between the 13th and the 20th of March 2020 the first 80 patients with positive RT-PCR results for COVID-19 were enrolled in a single center. However, in a newspaper article [article] , a woman, who was part of this first 80 patients, testified she had symptoms on March 10th, 2020 and the CT scan on March 17th, 2020. Which is surprizing. In the supplementary data, no patients received a CT scan on March 17th, 2020. Is it an error in the dataset ? Furthermore, and it is the most disturbing point, the author mentioned this study was retrospective. But several evidence seems to indicate it was a prospective study. **Testimony of the participant** In the same newspaper article, the woman describes a prospective study where she had to signed an informed consent for a research protocol. * As soon as I arrived in the room, a nurse put the protocol on the bed explaining to me that it was in the state of research, hence the need to sign. In shock and fear, I didn t read anything, I didn t think, I signed. * This can not be considered as a retrospective study. It was clear for the patient that she participated to an experimentation in human. The woman also described the protocol which confirms it was a prospective research in human.  *When I arrived I had a blood test, an electrocardiogram, a nasal and rectal brush, and a urine analysis. I took the first plaquenil tablet (the drug whose active ingredient is hydrocychloroquine, editor s note) on Saturday evening with an antibiotic. Then I had one pill in the morning and one in the evening on the following days. With these renewed tests: nasal and rectal brushes, urinalysis. On Tuesday morning, **March 17, I was given a lung CT scan** to look for possible outbreaks of the virus and possible sequelae or lesions on the lungs.* Considering this testimony, the entire ethic approval process should be reviewed and investigated by the editor. This testimony covers also other articles with the same issue as mentionned in this [pubpeer comment] **The ethic approval document raises questions** The article provides the copy of the ethical approval. But we can note, by the remaining ink, that, at several places, several information were erased. Which is quite surprizing. It looks like this document might be not the original . Otherwise, there is only one signature. On other ethics approval from the same ethics committee, all the members of the ethics committee signed the approval. It is not the case here. Futhermore, the approval do not mention the investigator will use anonymized data from patient database but patient data. We can also note that the investigator did not mention to the ethics approval that the study will request the informed consent of patients. And the testimony of the participant showed that she signed an informed consent for the study, which is an evidence that this study was not retrospective but prospective. This ethics approval process raises serious concern which require to be investigated. If this study is prospective, this ethics committee approval was provided after the recruitment of the participant. Furthermore, this ethic committee did not have the ability to approve this study. Indeed, in France, prospective research in human MUST be approved by a Comitu00e9 de Protection des Personnes (CPP), the only IRBs which can approved a prospective research in humans in France. The article did not mention any approval from a CPP. This could be a serious violation to the french clinical trial regulation. **A similar study from the same author already under investigation** On February 21st, 2022, the [Insights into Imaging Journal] issued the following Editor s note relating to a similar study from the same authors: * The Editor-in-Chief is currently investigating this article as concerns have been raised about the ethics approval and potential errors in the presentation of the study type. Further editorial action will be taken as appropriate once the investigation into the concerns is complete and all parties have been given an opportunity to respond in full. * - This study is mentioned by the author as a prospective study in human. - This study has the same design as described in this article - There is an overlap in the recruitment period of both articles - This study did not obtain a CPP approval, which is mandatory for a prospective study in human. - This study obtain an ethic approval from the same ethic committee, after the recruitment period. Which is a violation of the Helsinki Declaration. Other evidences raises other serious ethical concerns. **The ethic committee of the institute is not independant** As required by the Helsinki Declaration, the ethic committee must be independant. It is not the case of the ethics committee of this institute. Indeed, one of the member of the ethics committee (PE Fournier) is a direct report of one of the author of the article (DR). As a consequence, the ethics committee can not be considered independant and the ethics approval must be rejected by Editor in this type of situation. **An investigation of the French Health Authority highlighted a possible falsification of the ethics approval documents from this institute** In November 2021, the French Health Authority (ANSM) did an inspection in the IHU Institute. As related by the newspaper Mediapart in this [article] , the ANSM preliminary reports found 8 critical findings and 7 major findings regarding the compliance to the Good Clinical Practices of this Institute. More concerning, the inspectors report describes a possible falsification of an ethics approval for a prospective study in human. Indeed, the Institute have provided to the inspectors a copy of ethics approval, obtained after the recruitment of the participants. But the person who had allegedly signed the document mentions to the inspectors it was a falsification and provided to the inspector the original. ANSM also mentioned several prospective studies from these institute did not get the proper ethics approval from a CPP and that the ethic committee of this institute can not deliver approval for prospective study in human. According to the newspaper, ANSM report mentions the sending of the dossier related to the falsification of the ethic approval to the French Criminal Prosecutor. We can also remind another article from Mediapart which mentions an internal investigation where several testimonies from the staff institute relates a case of falsification of the results. [French scientist who championed anti-malaria drug for Covid-19 accused of falsifying test results] In light of these recent events, Editors might consider to review all the articles from this institute in order to assess at least the ethics approval process and ensure that it was in compliance with the french law and the Helsinki Declaration. And retract the articles where it was not the case. , 
 Expression of Concern, 13 December 2022, found here: https: journals.plos.org plosone article?id=10.1371 journal.pone.0279045  This article [1] has been identified as one of a series of submissions for which we have concerns about the reported research ethics approval information and the articleu2019s adherence to PLOS research ethics policies. PLOS will be investigating these concerns in accordance with COPE guidance and journal policies. Meanwhile, the PLOS ONE Editors issue this Expression of Concern. ,