Rhino-orbital cerebral mycosis: a case series of non-mucorales in COVID patients

  1. Rajashri Patil
  2. Jyoti Ajagunde
  3. Sameena Khan
  4. Sriram Kannuri
  5. Nageswari Gandham
  6. Sahjid Mukhida

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Abstract

Introduction. Rhino-Orbito-cerebral mycoses are not only caused by Aspergillus spp. and Zygomycetes spp. but also can be associated with other rare species such as Neurospora spp. , Cladosporium spp. and Fusarium spp. Mucormycosis is associated causatively with immunocompromised states, for example patients with comorbidities such as diabetes mellitus. Clinical symptoms of coronavirus disease (COVID) and mucormycosis in tandem are critical and relentless, frequently with no life-saving treatment.

Case series. We report three patients with COVID-19 infection, who during the course of treatment developed rhino-orbital-cerebral mycosis including oral cavity involvement. Rhinocerebral mycosis along with oral cavity involvement was diagnosed by radiological investigations and preliminary screening for fungal infection (KOH mount) in all three cases. Empirical treatment was started but patients did not respond to treatment. All patients died even after debridement and maxillectomy. On culture, rare species of fungi were isolated in all three cases which, with the help of a reference laboratory, were identified as Neurospora , Cladosporium and Fusarium. Neurospora is considered nonpathogenic to humans. Cladosporium is a dematiaceous fungus found in soil in all climates, associated with disseminated or cerebral infections; and Fusarium , though considered a saprophytic colonizer of skin and respiratory mucosa along with other bacteria, is a common cause of mycotic keratitis worldwide.

Conclusion. Immune system modifications due to COVID-19 with/without other risk factors can result in fungal co-infections that prove to be fatal for the patients. It is vital to be aware that COVID-19 patients, particularly those who are critically ill, may acquire secondary fungal infections and early detection is critical.

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  1. Version published to 10.1099/acmi.0.000575.v4 on Access Microbiology
  3. Version published to 10.1099/acmi.0.000575.v3 on Access Microbiology
  4. Access Microbiology

    The language used is poor, which can cause ambiguity at times. Please carefully rewrite it. We offer a discounted translation service, Editage (https://www.editage.com/; see https://www.microbiologyresearch.org/prepare-an-article#13 for more information).

  5. Access Microbiology

    Comments to Author

    Although most of the requested modifications were made in the paper, there are still some grammatical and syntax errors in the text.

    Please rate the quality of the presentation and structure of the manuscript

    Good

    To what extent are the conclusions supported by the data?

    Partially support

    Do you have any concerns of possible image manipulation, plagiarism or any other unethical practices?

    No

    Is there a potential financial or other conflict of interest between yourself and the author(s)?

    No

    If this manuscript involves human and/or animal work, have the subjects been treated in an ethical manner and the authors complied with the appropriate guidelines?

    Yes

  6. Access Microbiology

    Comments to Author

    I thank the authors for their response to my comments. Regrettably, most of my primary concerns still stand after revision. I still consider it essential for this study to perform further analyses to taxonomically classify the isolates, along with susceptibility tests. Without this, the manuscript communicates incomplete cases.

    Please rate the quality of the presentation and structure of the manuscript

    Satisfactory

    To what extent are the conclusions supported by the data?

    Partially support

    Do you have any concerns of possible image manipulation, plagiarism or any other unethical practices?

    No

    Is there a potential financial or other conflict of interest between yourself and the author(s)?

    No

    If this manuscript involves human and/or animal work, have the subjects been treated in an ethical manner and the authors complied with the appropriate guidelines?

    Yes

  7. Version published to 10.1099/acmi.0.000575.v2 on Access Microbiology
  8. Access Microbiology

    The reviewers have highlighted major concerns with the work presented. Please ensure that you address their comments. The language used is poor, which can cause ambiguity at times. Please carefully rewrite it. We offer a discounted translation service, Editage (https://www.editage.com/; see https://www.microbiologyresearch.org/prepare-an-article#13 for more information).

  9. Access Microbiology

    Comments to Author

    This is an interesting report of three cases of rhino orbital cerebral mycosis caused by atypical fungal genera. The description of the cases is almost complete; the only gap I see is the lack of solid laboratory tests to assess immunological fitness before treatment. The main flaw of the presentation is the lack of details about the taxonomical identification of the putative causative agents. I think it is relevant to apply molecular taxonomical tests to the fungal isolates to have identification at a species level. Since these are atypical causative agents of this type of fungal infection, I consider this aspect essential. Along the same line, the antifungal susceptibility test should also be included. Finally, I do not agree with the following statement: "systemic immunological modifications caused by COVID-19 infection may result in secondary infections"... SARS-CoV-2 indeed modifies some immunological components during the infection, but the treatment based on steroidal antiinflammatories has a major impact on immunosuppression. So, it is both the infection and the treatment that open the door to secondary infections. This should be modified in the whole manuscript.

    Please rate the quality of the presentation and structure of the manuscript

    Satisfactory

    To what extent are the conclusions supported by the data?

    Partially support

    Do you have any concerns of possible image manipulation, plagiarism or any other unethical practices?

    No

    Is there a potential financial or other conflict of interest between yourself and the author(s)?

    No

    If this manuscript involves human and/or animal work, have the subjects been treated in an ethical manner and the authors complied with the appropriate guidelines?

    Yes

  10. Access Microbiology

    Comments to Author

    1. The manuscript under peer-review entitled, "Rhinoorbital cerebral mycosis: A case series of non-Mucorales in Covid patients" deals with uncommon presentations of a common fungi found among patients, particularly in the background of Covid-19 and emphasizes the importance of non-Mucorales fungi. 2. The drafting of the manuscript is very poor as far as the language is concerned. Moreover, the sentences are haphazard, which is not a feature of writing any manuscript. The authors are not very clear whether they want to deal with the fungal contaminants as significant fungi. 3. The study design is not proper on the basis of which the study should be based. 4. The names of the fungal isolates have been written up to the genus level only. There is no description of species of any of the isolate mentioned in the study. 5. There is mention of Fusarium but morphological description is of Aspergillus mentioning as vesicle, phialides, etc. the photograph also shows macro and micro conidia substantiating Fusarium but there is no vesicle or phialide as written in the text of the manuscript. 6. There is no clinical photograph of any of the patient, depicted in the manuscript. Moreover, there is no photomicrograph of the direct finding of KOH or CFW or HPE, any radiological finding, convincing photograph of the fungi isolated from the patients. This point is very crucial because the histopathological findings in a descriptive manner clearly and correctly mentioned the acute-angle branching of fungal hyphae. The textbook descriptions of fungi are very clear and decide their significance. 7. The entire discussion is also without any direction. The authors are trying to establish the nonpathogenic fungi as significant pathogen. They could have gone for molecular typing also when the fungus was grown in the pure form otherwise it may be similarly looking fungus, may be confusing with non-pathogenic fungi. Moreover, they are not identifying to the species level in any of the fungal isolates which is a major point in consideration of any publication. Moreover, the cultural description is related to Aspergillus whereas the final diagnosis in the of the same isolate is Fusarium. The authors have no idea what they are writing. 8. During the Covid-19 period about one-third of the patients of mucormycosis presented with mixed infection in India. Therefore, all these mixed infections are to be explored to maximum extent, which the authors have not done. In the entire manuscript it is not mentioned that any of the reported 3 cases were part of the mixed infection. They could have written that mucormycosis was ruled out in the prevailing circumstances of Covid-19. 9. The references are arranged without any specific pattern, definitely not the pattern of Access Microbiology. After writing the manuscript all the authors have not even read the manuscript otherwise how the reference No. 3 is again appearing at serial No. 11 and same is cited in the text also multiple times.

    Please rate the quality of the presentation and structure of the manuscript

    Very poor

    To what extent are the conclusions supported by the data?

    Not at all

    Do you have any concerns of possible image manipulation, plagiarism or any other unethical practices?

    No

    Is there a potential financial or other conflict of interest between yourself and the author(s)?

    No

    If this manuscript involves human and/or animal work, have the subjects been treated in an ethical manner and the authors complied with the appropriate guidelines?

    Yes

  11. Access Microbiology

    Comments to Author

    Dear authors, I read the manuscript in details. Here are some recommendations for improving the manuscript: Line 32: Instead of Zygomycetes group, you may be using Zygomycetes species. Lines 34-35: Define the primary risk factor for ROCM, whether it is COVID-19 or diabetes mellitus and reason it. Line 58: Correct the sentence. Mucoraceae are members of Zygomycetes. Lines 90-93: present the histopathological findings for all cases. Line 73- … Indicate the dates of all cases' admissions. The World Health Organization (WHO) issued a cautionary statement regarding remdesivir in late 2021. Are you still providing this medication? Lines 145-148: These sentences may not adequately represent Fusaria characteristics. The results can be revised, and their interpretation can be discussed with a mycologist.

    Please rate the quality of the presentation and structure of the manuscript

    Satisfactory

    To what extent are the conclusions supported by the data?

    Partially support

    Do you have any concerns of possible image manipulation, plagiarism or any other unethical practices?

    No

    Is there a potential financial or other conflict of interest between yourself and the author(s)?

    No

    If this manuscript involves human and/or animal work, have the subjects been treated in an ethical manner and the authors complied with the appropriate guidelines?

    Yes

  12. Version published to 10.1099/acmi.0.000575.v1 on Access Microbiology