Journal of Clinical and Diagnostic Research, ISSN - 0973 - 709X

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Dr Mohan Z Mani

"Thank you very much for having published my article in record time.I would like to compliment you and your entire staff for your promptness, courtesy, and willingness to be customer friendly, which is quite unusual.I was given your reference by a colleague in pathology,and was able to directly phone your editorial office for clarifications.I would particularly like to thank the publication managers and the Assistant Editor who were following up my article. I would also like to thank you for adjusting the money I paid initially into payment for my modified article,and refunding the balance.
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Dr Mohan Z Mani,
Professor & Head,
Department of Dermatolgy,
Believers Church Medical College,
Thiruvalla, Kerala
On Sep 2018




Prof. Somashekhar Nimbalkar

"Over the last few years, we have published our research regularly in Journal of Clinical and Diagnostic Research. Having published in more than 20 high impact journals over the last five years including several high impact ones and reviewing articles for even more journals across my fields of interest, we value our published work in JCDR for their high standards in publishing scientific articles. The ease of submission, the rapid reviews in under a month, the high quality of their reviewers and keen attention to the final process of proofs and publication, ensure that there are no mistakes in the final article. We have been asked clarifications on several occasions and have been happy to provide them and it exemplifies the commitment to quality of the team at JCDR."



Prof. Somashekhar Nimbalkar
Head, Department of Pediatrics, Pramukhswami Medical College, Karamsad
Chairman, Research Group, Charutar Arogya Mandal, Karamsad
National Joint Coordinator - Advanced IAP NNF NRP Program
Ex-Member, Governing Body, National Neonatology Forum, New Delhi
Ex-President - National Neonatology Forum Gujarat State Chapter
Department of Pediatrics, Pramukhswami Medical College, Karamsad, Anand, Gujarat.
On Sep 2018




Dr. Kalyani R

"Journal of Clinical and Diagnostic Research is at present a well-known Indian originated scientific journal which started with a humble beginning. I have been associated with this journal since many years. I appreciate the Editor, Dr. Hemant Jain, for his constant effort in bringing up this journal to the present status right from the scratch. The journal is multidisciplinary. It encourages in publishing the scientific articles from postgraduates and also the beginners who start their career. At the same time the journal also caters for the high quality articles from specialty and super-specialty researchers. Hence it provides a platform for the scientist and researchers to publish. The other aspect of it is, the readers get the information regarding the most recent developments in science which can be used for teaching, research, treating patients and to some extent take preventive measures against certain diseases. The journal is contributing immensely to the society at national and international level."



Dr Kalyani R
Professor and Head
Department of Pathology
Sri Devaraj Urs Medical College
Sri Devaraj Urs Academy of Higher Education and Research , Kolar, Karnataka
On Sep 2018




Dr. Saumya Navit

"As a peer-reviewed journal, the Journal of Clinical and Diagnostic Research provides an opportunity to researchers, scientists and budding professionals to explore the developments in the field of medicine and dentistry and their varied specialities, thus extending our view on biological diversities of living species in relation to medicine.
‘Knowledge is treasure of a wise man.’ The free access of this journal provides an immense scope of learning for the both the old and the young in field of medicine and dentistry as well. The multidisciplinary nature of the journal makes it a better platform to absorb all that is being researched and developed. The publication process is systematic and professional. Online submission, publication and peer reviewing makes it a user-friendly journal.
As an experienced dentist and an academician, I proudly recommend this journal to the dental fraternity as a good quality open access platform for rapid communication of their cutting-edge research progress and discovery.
I wish JCDR a great success and I hope that journal will soar higher with the passing time."



Dr Saumya Navit
Professor and Head
Department of Pediatric Dentistry
Saraswati Dental College
Lucknow
On Sep 2018




Dr. Arunava Biswas

"My sincere attachment with JCDR as an author as well as reviewer is a learning experience . Their systematic approach in publication of article in various categories is really praiseworthy.
Their prompt and timely response to review's query and the manner in which they have set the reviewing process helps in extracting the best possible scientific writings for publication.
It's a honour and pride to be a part of the JCDR team. My very best wishes to JCDR and hope it will sparkle up above the sky as a high indexed journal in near future."



Dr. Arunava Biswas
MD, DM (Clinical Pharmacology)
Assistant Professor
Department of Pharmacology
Calcutta National Medical College & Hospital , Kolkata




Dr. C.S. Ramesh Babu
" Journal of Clinical and Diagnostic Research (JCDR) is a multi-specialty medical and dental journal publishing high quality research articles in almost all branches of medicine. The quality of printing of figures and tables is excellent and comparable to any International journal. An added advantage is nominal publication charges and monthly issue of the journal and more chances of an article being accepted for publication. Moreover being a multi-specialty journal an article concerning a particular specialty has a wider reach of readers of other related specialties also. As an author and reviewer for several years I find this Journal most suitable and highly recommend this Journal."
Best regards,
C.S. Ramesh Babu,
Associate Professor of Anatomy,
Muzaffarnagar Medical College,
Muzaffarnagar.
On Aug 2018




Dr. Arundhathi. S
"Journal of Clinical and Diagnostic Research (JCDR) is a reputed peer reviewed journal and is constantly involved in publishing high quality research articles related to medicine. Its been a great pleasure to be associated with this esteemed journal as a reviewer and as an author for a couple of years. The editorial board consists of many dedicated and reputed experts as its members and they are doing an appreciable work in guiding budding researchers. JCDR is doing a commendable job in scientific research by promoting excellent quality research & review articles and case reports & series. The reviewers provide appropriate suggestions that improve the quality of articles. I strongly recommend my fraternity to encourage JCDR by contributing their valuable research work in this widely accepted, user friendly journal. I hope my collaboration with JCDR will continue for a long time".



Dr. Arundhathi. S
MBBS, MD (Pathology),
Sanjay Gandhi institute of trauma and orthopedics,
Bengaluru.
On Aug 2018




Dr. Mamta Gupta,
"It gives me great pleasure to be associated with JCDR, since last 2-3 years. Since then I have authored, co-authored and reviewed about 25 articles in JCDR. I thank JCDR for giving me an opportunity to improve my own skills as an author and a reviewer.
It 's a multispecialty journal, publishing high quality articles. It gives a platform to the authors to publish their research work which can be available for everyone across the globe to read. The best thing about JCDR is that the full articles of all medical specialties are available as pdf/html for reading free of cost or without institutional subscription, which is not there for other journals. For those who have problem in writing manuscript or do statistical work, JCDR comes for their rescue.
The journal has a monthly publication and the articles are published quite fast. In time compared to other journals. The on-line first publication is also a great advantage and facility to review one's own articles before going to print. The response to any query and permission if required, is quite fast; this is quite commendable. I have a very good experience about seeking quick permission for quoting a photograph (Fig.) from a JCDR article for my chapter authored in an E book. I never thought it would be so easy. No hassles.
Reviewing articles is no less a pain staking process and requires in depth perception, knowledge about the topic for review. It requires time and concentration, yet I enjoy doing it. The JCDR website especially for the reviewers is quite user friendly. My suggestions for improving the journal is, more strict review process, so that only high quality articles are published. I find a a good number of articles in Obst. Gynae, hence, a new journal for this specialty titled JCDR-OG can be started. May be a bimonthly or quarterly publication to begin with. Only selected articles should find a place in it.
An yearly reward for the best article authored can also incentivize the authors. Though the process of finding the best article will be not be very easy. I do not know how reviewing process can be improved. If an article is being reviewed by two reviewers, then opinion of one can be communicated to the other or the final opinion of the editor can be communicated to the reviewer if requested for. This will help one’s reviewing skills.
My best wishes to Dr. Hemant Jain and all the editorial staff of JCDR for their untiring efforts to bring out this journal. I strongly recommend medical fraternity to publish their valuable research work in this esteemed journal, JCDR".



Dr. Mamta Gupta
Consultant
(Ex HOD Obs &Gynae, Hindu Rao Hospital and associated NDMC Medical College, Delhi)
Aug 2018




Dr. Rajendra Kumar Ghritlaharey

"I wish to thank Dr. Hemant Jain, Editor-in-Chief Journal of Clinical and Diagnostic Research (JCDR), for asking me to write up few words.
Writing is the representation of language in a textual medium i e; into the words and sentences on paper. Quality medical manuscript writing in particular, demands not only a high-quality research, but also requires accurate and concise communication of findings and conclusions, with adherence to particular journal guidelines. In medical field whether working in teaching, private, or in corporate institution, everyone wants to excel in his / her own field and get recognised by making manuscripts publication.


Authors are the souls of any journal, and deserve much respect. To publish a journal manuscripts are needed from authors. Authors have a great responsibility for producing facts of their work in terms of number and results truthfully and an individual honesty is expected from authors in this regards. Both ways its true "No authors-No manuscripts-No journals" and "No journals–No manuscripts–No authors". Reviewing a manuscript is also a very responsible and important task of any peer-reviewed journal and to be taken seriously. It needs knowledge on the subject, sincerity, honesty and determination. Although the process of reviewing a manuscript is a time consuming task butit is expected to give one's best remarks within the time frame of the journal.
Salient features of the JCDR: It is a biomedical, multidisciplinary (including all medical and dental specialities), e-journal, with wide scope and extensive author support. At the same time, a free text of manuscript is available in HTML and PDF format. There is fast growing authorship and readership with JCDR as this can be judged by the number of articles published in it i e; in Feb 2007 of its first issue, it contained 5 articles only, and now in its recent volume published in April 2011, it contained 67 manuscripts. This e-journal is fulfilling the commitments and objectives sincerely, (as stated by Editor-in-chief in his preface to first edition) i e; to encourage physicians through the internet, especially from the developing countries who witness a spectrum of disease and acquire a wealth of knowledge to publish their experiences to benefit the medical community in patients care. I also feel that many of us have work of substance, newer ideas, adequate clinical materials but poor in medical writing and hesitation to submit the work and need help. JCDR provides authors help in this regards.
Timely publication of journal: Publication of manuscripts and bringing out the issue in time is one of the positive aspects of JCDR and is possible with strong support team in terms of peer reviewers, proof reading, language check, computer operators, etc. This is one of the great reasons for authors to submit their work with JCDR. Another best part of JCDR is "Online first Publications" facilities available for the authors. This facility not only provides the prompt publications of the manuscripts but at the same time also early availability of the manuscripts for the readers.
Indexation and online availability: Indexation transforms the journal in some sense from its local ownership to the worldwide professional community and to the public.JCDR is indexed with Embase & EMbiology, Google Scholar, Index Copernicus, Chemical Abstracts Service, Journal seek Database, Indian Science Abstracts, to name few of them. Manuscriptspublished in JCDR are available on major search engines ie; google, yahoo, msn.
In the era of fast growing newer technologies, and in computer and internet friendly environment the manuscripts preparation, submission, review, revision, etc and all can be done and checked with a click from all corer of the world, at any time. Of course there is always a scope for improvement in every field and none is perfect. To progress, one needs to identify the areas of one's weakness and to strengthen them.
It is well said that "happy beginning is half done" and it fits perfectly with JCDR. It has grown considerably and I feel it has already grown up from its infancy to adolescence, achieving the status of standard online e-journal form Indian continent since its inception in Feb 2007. This had been made possible due to the efforts and the hard work put in it. The way the JCDR is improving with every new volume, with good quality original manuscripts, makes it a quality journal for readers. I must thank and congratulate Dr Hemant Jain, Editor-in-Chief JCDR and his team for their sincere efforts, dedication, and determination for making JCDR a fast growing journal.
Every one of us: authors, reviewers, editors, and publisher are responsible for enhancing the stature of the journal. I wish for a great success for JCDR."



Thanking you
With sincere regards
Dr. Rajendra Kumar Ghritlaharey, M.S., M. Ch., FAIS
Associate Professor,
Department of Paediatric Surgery, Gandhi Medical College & Associated
Kamla Nehru & Hamidia Hospitals Bhopal, Madhya Pradesh 462 001 (India)
E-mail: drrajendrak1@rediffmail.com
On May 11,2011




Dr. Shankar P.R.

"On looking back through my Gmail archives after being requested by the journal to write a short editorial about my experiences of publishing with the Journal of Clinical and Diagnostic Research (JCDR), I came across an e-mail from Dr. Hemant Jain, Editor, in March 2007, which introduced the new electronic journal. The main features of the journal which were outlined in the e-mail were extensive author support, cash rewards, the peer review process, and other salient features of the journal.
Over a span of over four years, we (I and my colleagues) have published around 25 articles in the journal. In this editorial, I plan to briefly discuss my experiences of publishing with JCDR and the strengths of the journal and to finally address the areas for improvement.
My experiences of publishing with JCDR: Overall, my experiences of publishing withJCDR have been positive. The best point about the journal is that it responds to queries from the author. This may seem to be simple and not too much to ask for, but unfortunately, many journals in the subcontinent and from many developing countries do not respond or they respond with a long delay to the queries from the authors 1. The reasons could be many, including lack of optimal secretarial and other support. Another problem with many journals is the slowness of the review process. Editorial processing and peer review can take anywhere between a year to two years with some journals. Also, some journals do not keep the contributors informed about the progress of the review process. Due to the long review process, the articles can lose their relevance and topicality. A major benefit with JCDR is the timeliness and promptness of its response. In Dr Jain's e-mail which was sent to me in 2007, before the introduction of the Pre-publishing system, he had stated that he had received my submission and that he would get back to me within seven days and he did!
Most of the manuscripts are published within 3 to 4 months of their submission if they are found to be suitable after the review process. JCDR is published bimonthly and the accepted articles were usually published in the next issue. Recently, due to the increased volume of the submissions, the review process has become slower and it ?? Section can take from 4 to 6 months for the articles to be reviewed. The journal has an extensive author support system and it has recently introduced a paid expedited review process. The journal also mentions the average time for processing the manuscript under different submission systems - regular submission and expedited review.
Strengths of the journal: The journal has an online first facility in which the accepted manuscripts may be published on the website before being included in a regular issue of the journal. This cuts down the time between their acceptance and the publication. The journal is indexed in many databases, though not in PubMed. The editorial board should now take steps to index the journal in PubMed. The journal has a system of notifying readers through e-mail when a new issue is released. Also, the articles are available in both the HTML and the PDF formats. I especially like the new and colorful page format of the journal. Also, the access statistics of the articles are available. The prepublication and the manuscript tracking system are also helpful for the authors.
Areas for improvement: In certain cases, I felt that the peer review process of the manuscripts was not up to international standards and that it should be strengthened. Also, the number of manuscripts in an issue is high and it may be difficult for readers to go through all of them. The journal can consider tightening of the peer review process and increasing the quality standards for the acceptance of the manuscripts. I faced occasional problems with the online manuscript submission (Pre-publishing) system, which have to be addressed.
Overall, the publishing process with JCDR has been smooth, quick and relatively hassle free and I can recommend other authors to consider the journal as an outlet for their work."



Dr. P. Ravi Shankar
KIST Medical College, P.O. Box 14142, Kathmandu, Nepal.
E-mail: ravi.dr.shankar@gmail.com
On April 2011
Anuradha

Dear team JCDR, I would like to thank you for the very professional and polite service provided by everyone at JCDR. While i have been in the field of writing and editing for sometime, this has been my first attempt in publishing a scientific paper.Thank you for hand-holding me through the process.


Dr. Anuradha
E-mail: anuradha2nittur@gmail.com
On Jan 2020

Important Notice

Original article / research
Year : 2022 | Month : July | Volume : 16 | Issue : 7 | Page : TC01 - TC05 Full Version

Clinico-radiological Spectrum of COVID-19 Associated Rhino-cerebral Mucormycosis: A Retrospective Cohort Study from a Tertiary Care Hospital


Published: July 1, 2022 | DOI: https://doi.org/10.7860/JCDR/2022/56596.16621
Alka Agrawal, Neetu Kori, Yogita Dixit, Prakhar Nigam, Mrinal Choudhary, Silky Taya

1. Professor and Head, Department of Radiodiagnosis, M.G.M. Medical College and M.Y. Hospital, Indore, Madhya Pradesh, India. 2. Associate Professor, Department of Ophthalmology, M.G.M. Medical College and M.Y. Hospital, Indore, Madhya Pradesh, India. 3. Assistant Professor, Department of Otorhinolaryngology, M.G.M. Medical College and M.Y. Hospital, Indore, Madhya Pradesh, India. 4. Postgraduate Resident, Department of Radiodiagnosis, M.G.M. Medical College and M.Y. Hospital, Indore, Madhya Pradesh, India. 5. Postgraduate Resident, Department of Radiodiagnosis, M.G.M. Medical College and M.Y. Hospital, Indore, Madhya Pradesh, India. 6. Postgraduate Resident, Department of Radiodiagnosis, M.G.M. Medical College and M.Y. Hospital, Indore, Madhya Pradesh, India.

Correspondence Address :
Dr. Mrinal Choudhary,
Postgraduate Resident, Department of Radiodiagnosis, M.G.M. Medical College
and M.Y. Hospital, Indore-452001, Madhya Pradesh, India.
E-mail: choudharymrinal894@gmail.com

Abstract

Introduction: Rhino-cerebral Mucormycosis (RCM), in the pre-Coronavirus Disease-2019 (COVID-19) era, was thought to be solely associated with an immunocompromised state. However, an unforeseen outbreak in the number of mucormycosis cases was seen with the increase in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection.

Aim: To study and investigate the clinical characteristics, imaging findings, associated risk factors, and clinical outcomes in COVID-19 associated mucormycosis.

Materials and Methods: A retrospective cohort study was conducted comprising 480 cases of COVID-19 associated mucormycosis who presented to the institution between April 2020 and September 2020. The clinical and radiological data were studied and analysed.

Results: Out of a total of 480 cases, 443 (92.29%) were found to suffering from diabetes mellitus and 392 patients (81.66%) had a history of steroids intake in the studied population. Facial or per orbital swelling followed by pain were the most frequent presenting complaints found in 188 (39.16%) and 162 (33.75%) patients, respectively. Nasal septum and middle turbinate were the most common sites of disease involvement on nasal endoscopic examination. On radiological imaging, maxillary (438; 91.25%) was the most commonly involved sinus followed by ethmoids (395; 82.29%). Premaxillary/retroantral fat and orbits were the most common sites of extra sinonasal spread of infection found in 278 (57.91%) and 244 (50.83%) patients, respectively. About 238 (49.58%) patients showed bony erosion and dehiscence. Intracranial complications were seen in 73 (15.21%) patients. Glycated Haemoglobin (HbA1c) levels showed significant value with higher disease staging. Oxygen supplementation was frequently associated with extrasinus spread of infection. A total of 44 (9.17%) patients succumbed to death despite aggressive antifungal treatment.

Conclusion: COVID-19 associated RCM shows frequent and extensive spread to extrasinus regions, especially with uncontrolled diabetes mellitus, steroid administration, and oxygen supplementation. High clinical suspicion, early imaging, and prompt institution of antifungal therapy can aid in reducing mortality rate.

Keywords

Coronavirus disease-2019, Diabetes mellitus, Magnetic resonance imaging

Since the onset of the pandemic in 2020, the world has seen millions of people succumb to death due to COVID-19 and related complications (1). The complications of COVID-19 overwhelmed healthcare facilities worldwide and led to the re-emergence of many opportunistic infections. During the second wave of SARS-CoV-2 infection, India witnessed a dramatic increase in RCM (2). It is an invasive fungal infection that is known to cause high morbidity and mortality. Diabetic ketoacidosis, severe burns, steroid therapy, solid organ transplantation, prolonged corticosteroid therapy, haemochromatosis, patients with Human Immunodeficiency Virus (HIV), neutropenia, malnutrition, and haematologic malignancies predispose individuals for this opportunistic infection (3). India, home to more than 70 million diabetics, the second-highest globally, had an 80 times higher prevalence of mucormycosis in the pre-COVID era itself (4). The unholy trinity of high burden of diabetes, immunomodulation associated with COVID-19, and rampant use of steroids for treatment led to a rapid upsurge in the RCM cases.

The causative agent of the RCM is saprophytic fungi of the order Morales (5). Inhalation of spores followed by germination in the nasal cavity is the usual mode of infection. Rapid progression of the infection into surrounding soft tissue, orbit, and brain occurs due to its tendency to invade blood vessels (6). The extent of nasal and para nasal sinus involvement could be assessed by clinical and endoscopic examination. However, the extension into neck spaces, orbit, and brain remains a mystery unless the patient presents with overt features. Imaging plays a crucial role in the recognition of deeper extension of infection which is blind to clinicians’ eyes. The good prognosis of mucormycosis lies in early diagnosis and appropriate management. Early identification of disease is possible with the identification of associated clinical and radiological features in the setting of predisposing factors. The study of clinical characteristics, imaging findings, associated risk factors, and clinical outcomes help in a better understanding of the disease pathology. In our tertiary care hospital, authors conducted one of the largest single-centre studies on RCM using clinical and radiological data of 480 patients to describe the clinical features, risk factors and clinical outcome. The study also aimed to stage the patients on the basis of imaging findings and the association of disease severity with the clinical risk factors.

Material and Methods

A retrospective cohort study comprising of 480 consecutive patients who had a history of COVID-19 and were diagnosed with sinonasal mucormycosis was conducted after approval from the Institutional Ethics and Scientific Review Committee in M.Y. Hospital, Indore (IRB approval No. 03/22). Patients’ data including demography, clinical findings, blood investigations, endoscopic and imaging findings were assessed who presented to our tertiary care institution between April 2020 and September 2020. The analysis of the data was done from January 2022 to February 2022. Follow-up data was available till three months after the discharge from the hospital.

Inclusion criteria: A positive Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) test or COVID-19 reporting and data system (CO-RADS) grade 5 and histopathologically or microbiologically diagnosed cases with sinonasal mucormycosis were included in the study.

Exclusion criteria: Patients who did not undergo Magnetic Resonance Imaging (MRI) or whose follow-up details were not available were excluded.

Study Procedure

All documented microbiological and pathological investigations were carried out in the institutional laboratories. The stated co-morbidities, presenting complaints, clinical examination findings, laboratory parameters, past treatment history, and outcomes were thoroughly studied, compiled, tabulated, and analysed. Radiological imaging of all patients was performed in the institutional 3T MRI machine. Imaging data were acquired through hospital Picture Archiving and Communication System (PACS). Images were analysed at the workstation and reports were prepared using a dedicated format for RCM. Patients were segregated on the basis of the radiological staging of the disease. Stage I was defined as lesions confined to sinonasal cavities. Stage II represented the involvement of perinatal fat, neck spaces, pterygopalatine fossa, bone, and orbit. Patients with radiological evidence of intracranial spread of infection were labelled as stage III (7).

Statistical Analysis

All clinical and radiological imaging data were tabulated and comparisons were done using International Business Machines (IBM) Statistical Package for the Social Sciences (SPSS) software for Windows, Version 26.0. Armonk, NY: IBM Corp. The mean and Standard Deviation (SD) of the quantitative variables were calculated. A Chi-square test was used for the comparison of categorical variables. One-way Analysis of Variance (ANOVA) was used to find association between patients’ clinical parameters and the radiological stage of the disease. The p-values <0.05 were considered statistically significant.

Results

The most commonly affected patients belonged to the age group of 41-50 years. The mean age of the studied patients was 48.40 years, with a slight male preponderance (250;52%). The duration between COVID-19 and the appearance of symptoms related to RCM ranged from 2-8 weeks. Diabetes mellitus was the most commonly associated risk factor followed by the history of steroid therapy (Table/Fig 1).

The most common primary complaints were facial or periorbital swelling, seen in 188 patients (39.16%), followed by facial or periorbital pain in 162 patients (33.75%), nasal blockage in 50 (10.41%) patients, headache in 22 (4.58%), diminution of vision in 18 (3.75%), nasal discharge in 17 (3.54%), ptosis in 15 (3.12%), and others like proposes, epistaxis, toothache in 8 (1.67%) patients. The diminution of vision was associated with corneal haze, uveitis, optic disc edema, vitreous haemorrhage, retinal detachment, diabetic retinopathy, and central retinal artery occlusion as observed during ophthalmologic examination. Out of 480, 387 (80.62%) underwent diagnostic 2nasal endoscopy. Nasal septum and middle turbinate were the most common sites of disease pathology seen in 320 (82.68%) and 270 (69.76%) patients, respectively. The major endoscopic finding was mucosal discoloration (117;30.23%) with or without the presence of discharge. Nasal secretions with mucosal oedema were seen in 98 (25.32%) patients, while characteristic black scars were noted in 54 (13.95%) patients who underwent nasal endoscopy.

All 480 patients underwent combined MRI of the sinonasal, orbit, and brain. The most commonly involved sinuses on MRI were maxillary followed by ethmoid (Table/Fig 2). Bilateral involvement of sinuses was more common (330;68.75%) than unilateral disease (Table/Fig 3). Premaxillary/retroantral fat and orbits were the most common sites of extra sinonasal spread of infection found in 278 (57.91%) and 244 (50.83%) patients, respectively. Bone erosion or dehiscence was seen in 238 (49.58%) patients. The most common sites of erosion were lamina papyracea and posterior maxillary sinus walls. Intracranial signs (Table/Fig 4) of mucormycosis were seen in 73 (15.21%) patients, the most common being pachymeningitis (52;10.83%) and cavernous sinus thrombosis/thrombophlebitis (37;7.70%) (Table/Fig 5).

The stage I disease i.e. rhino mucormycosis without extra sinus spread was present in 190 (39.58%) patients while stage II and III were seen in 217 (45.21%) and 73 (15.20%) patients, respectively. Ninety-seven (44.70%) out of 217 patients diagnosed with stage II disease on 3MRI, had no specific signs or symptoms of ocular involvement during clinical assessment. There was a significant association between HbA1c levels and disease staging (Table/Fig 6). The patients who received steroids and oxygen supplementation during COVID-19 showed higher stages of fungal infection (Table/Fig 7).

All patients received intravenous liposomal amphotericin B for an average duration 19 days (10-32 days). The average duration of hospital stay was 18 days (14-40 days). All patients irrespective of the stage underwent nasal debridement with or without functional endoscopic sinus surgery and received liposomal amphotericin B. Patients with ocular involvement were given Transcutaneous Retro bulbar Amphotericin B (TRAMB) injections. Patients with MRI evidence of orbital involvement but with no ocular complaints were injected once in seven days while those with complaints were given daily injections. Out of a total of 244 patients with the orbital disease, 196 (80.33%) patients showed marked improvement in terms of ocular movement and visual acuity. Twenty (8.20%) patients showed minimal improvement while the rest 28 (11.47%) patients underwent orbital exoneration. Eighteen patients succumbed to death post exoneration. Overall, a total of 44 (9.17%) patients died despite aggressive antifungal therapy and surgical debridement.

Discussion

The order Mucorales are known for their aggressive angioinvasive nature in the presence of favorable host factors. Immunocompromised individuals are unable to mount a sufficient immune response to evade the fungal infection and therefore are at risk. The fungi begin their journey in the human body through germination and invasion of inhaled spores. The association of COVID-19 and RCM is now well known. COVID-19 causes a variety of immunological alterations such as decrease in number and impaired function of CD8+, CD4+, natural killer, and dendritic cells [8,9]. Recent literature suggests an increased expression of glucose-related protein 78 (GRP 78) in COVID-19 patients (10). Mucorales gain access to the epithelial and endothelial cells by binding to this receptor (11). Furthermore, high blood glucose levels and ketoacidosis in diabetic patients up regulate GRP-78 expression over the cell surface [11,12]. The corticosteroids widely used for the treatment of COVID-19 cause immunosuppression and hyperglycaemia, further compromising the host defense system. Thus, the triad of steroids, diabetes mellitus, and SARS-CoV-2 infection provides a perfect atmosphere for opportunistic fungal infections.

In present study, facial or per orbital swelling/pain and nasal blockage were the most common primary complaints. The metacentric Collaborative OPAI-IJO study on Mucormycosis In COVID-19 (COSMIC) study showed that orbital/facial pain (23%), orbital/facial oedema (21%), loss of vision (19%), ptosis (11%), and nasal block (9%) are presenting features among patients with COVID-19 associated mucormycosis (13). The study by Dubey S et al., revealed headache, ptosis/proptosis, retro-orbital pain, facial numbness in 81.81%, 78.18%, 61.82% and 56.36% of patients, respectively (14). Several studies including present study found maxillary and ethmoid sinuses as the most commonly affected paranasal sinuses (7),(15),(16).

The extra sinus spread of infection to per maxillary/retroantral fat and orbits was commonly observed in present study. Mangal R et al., also found fungal spread to retro maxillary fat and orbit in 50.74% and 40.25% of patients, respectively (15). The fungal invasion of blood vessels allows the perivascular spread of infection across the bony walls of sinuses (7). The invading hyphae also damages the endothelial lining of blood vessels leading to clot formation, which results in ischaemia and necrosis of the surrounding tissue (6). The ischaemia appeared as discoloration of nasal mucosa during endoscopy, which on complete devitalisation appeared as black necrotic eschar. Radiologically, ischaemic turbinate is described as black turbinate which is a non enhancement of turbinate on contrast-enhanced MR sequences (17).

Bony erosion or dehiscence is also a common phenomenon in mucor infection. In present study, it was seen in 238 out of 290 patients with extra sinus lesions. The lamina papyracea and inferior orbital wall were common sites of erosion allowing easy access to orbital soft tissue. Few cases with orbital infection also had lesions in the nasolacrimal duct suggesting ascend of infection through the duct. Cases with intact bony walls and normal duct probably had extension through perivascular/per neural routes.

Ophthalmoplegia was associated with the extraocular muscle involvement mainly along the floor and medial wall of the orbit. Orbital apex involvement in the form of fat stranding or soft tissue at the apex on MRI was clinically associated with complete ophthalmoplegia and variable loss of vision. However, in RCM, the clinical complaints do not necessarily correlate with the severity of the disease. Ninety-seven patients in present study had no specific ocular signs and symptoms but were detected with orbital lesions on MRI. Radiologically, lesions of extraocular muscles, retro-orbital fat, orbital apex, and cavernous sinus though infrequent but were seen without any diplopia or ophthalmoplegia. Similarly, pachymeningitis was not associated with any nuchal rigidity, probably due to focal meningeal involvement. A high index of suspicion and early radiological imaging allows timely detection of such complications.

Cavernous sinus thrombosis/thrombophlebitis was one of the most common intracranial manifestations in present study. Previous studies on radiological spectrum of COVID-19 associated mucormycosis also showed the involvement of cavernous sinus with an intracranial spread of infection [15,16,18]. Fungal hyphae can gain access to various nerves traversing the cavernous sinus and spread along the fibres to the brainstem or skull base (19). The trigeminal nerve was the most commonly affected nerve in present study. Abnormal enhancement on contrast-enhanced images and restriction on diffusion-weighted imaging suggested its involvement. Arteritis and thrombosis of the cavernous part of the internal carotid artery were common with cavernous sinus lesions. Consequently, with arterial access, cerebral infarct may occur. Cavernous sinus thrombophlebitis/thrombosis has a snowball effect with respect to intracranial complications and is an ominous sign. Therefore, it is prudent to identify clinical and radiological features of cavernous sinus involvement for better clinical outcomes.

In present study, 60.42% of patients presented with stage II/III lesions. The higher stages of disease were strongly associated with increased serum HbA1c levels (p<0.001). Yadav T et al., also found a significant correlation between HbA1c level and disease stage (p<0.005) (18). Hence, it is crucial to achieve adequate glycaemic control apart from administering standard antifungal regimens to limit fungal invasion, especially in diabetics.

In present study, 32.29% of patients had a history of oxygen supplementation during the treatment of COVID-19. It also showed a significant association with the disease severity. During the second wave of COVID-19 healthcare facilities were overwhelmed and there was a massive shortage of medical oxygen. The use of industrial oxygen as an alternative, possibly contaminated by rust (an iron-rich fungal growth-promoting substance) could be one of the possible reasons for increased infections (20). Additionally, damage to the nasal mucosa by repeated suctioning and reapplication and prolonged use of face masks especially in hot and humid Indian weather might have exacerbated the risk.

The overall mortality in the present study was 9.17%, which was far less than studies conducted in the pre-COVID era [21,22]. In COVID-19 associated RCM, the overall mortality has been estimated to be 31%. The lower mortality rate in present study was comparable to those stated by the COSMIC study group (14%) and could be attributed to increased awareness among the patients and, aggressive and early interventions by the clinicians (13). Furthermore, present study was conducted in a tertiary healthcare facility that had a dedicated hospital for COVID-19 and related complications. Specialists from otorhinolaryngology, ophthalmology, dentistry, neurology, radiology, pathology, and microbiology departments coordinated and were available round the clock for patient care. The study provides one of the largest single-centre data on clinical and radiological features along with the clinical outcomes of COVID-19 associated RCM.

Limitation(s)

First, a large percentage of patients in present study had extra sinonasal complications which could be due to selection bias as our institute is a tertiary referral centre. Second, due to the variation in the duration and the type of treatment provided, the correlation between clinical risk factors and disease outcome was not performed. Third, due to a lack of documentation and/or MR images, a large sum of patients were excluded from the study analysis. Lastly, present study included only those patients, who suffered from COVID-19. The patients without any history of COVID illness may show a different clinical picture and radiological features. Future prospective multicentric studies with serial assessment of clinical and imaging data as well as of long-term outcomes and complications of RCM are required for a better understanding of the disease process.

Conclusion

The clinical presentation of RCM has a broad spectrum. MRI being multiplanar imaging provides adequate information about the spread of disease. Orbits and fat surrounding the maxillary antrum, are frequent sites of disease spread. Orbital and intracranial lesions should be actively looked upon as they are associated with treatment measures used during COVID-19 and high glycaemic index. Judicious use of steroids, adequate glycaemic control, and standard hygiene measures during oxygen supplementation could reduce the risk of COVID-19 associated RCM. High clinical suspicion and prompt application of diagnostic methods remain fundamental for the identification of disease in its nascent stage. A robust multidisciplinary approach with a dedicated team of clinicians is vital for superior results in terms of morbidity and mortality associated with RCM.

References

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DOI and Others

DOI: 10.7860/JCDR/2022/56596.16621

Date of Submission: Mar 23, 2022
Date of Peer Review: Apr 24, 2022
Date of Acceptance: Jun 26, 2022
Date of Publishing: Jul 01, 2022

AUTHOR DECLARATION:
• Financial or Other Competing Interests: None
• Was Ethics Committee Approval obtained for this study? Yes
• Was informed consent obtained from the subjects involved in the study? Yes
• For any images presented appropriate consent has been obtained from the subjects. Yes

PLAGIARISM CHECKING METHODS:
• Plagiarism X-checker: Mar 29, 2022
• Manual Googling: May 30, 2022
• iThenticate Software: Jun 24, 2022 (5%)

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