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Sen, Mrittika; Honawal, Santosh G; Bansal, Rolica; Sengupta, Sabyasachi1; Rao, Raksha 2; Kim, Usha3; Sharma, Mukesh 4; Sachdev, Mahipal5; Gro Fu, Ashok K6; Survey, Abhidnya7; Budharapu, Abhishek8; Ramadan, Abhishek K9; Tripati, Abhishek Kumar 10; Gupta, Adit11; Bargava, Aditya12; Sahu, Animesh13 ;Khairnar, Anjali14; Kochar, Anju15; Madhavani, Ankita16; Shrivastava, Ankur K17; Desai, Anuja K18; Paul, Anujeet19; Ayyar, Anuradha20; Bhatnagar, Aparna21; Singhal, Aparna22; Nikose, Archana Sunil23; ; Tenagi, Arvind L24; Kambul, Ashish25; Nariani, Ashiyana26; Patel, Bhavin27; Kashyap, Bibbhuti28; Dhawan, Bodhraj29; Vohra, Busaraben30; Mandek, Chaluta 31; Thrishulamurthy, Chinmayee, 32; Sambarei Chitra 33; Sakar, Dipayan 34; Manghat, Devanshi Shirishbhai16; Maheshwari, Dhwani35; Larwani, Dilip 36; Kanani, Dipti16; Patel, Diti30; Manjandavida, Fairooz P37; Godhani, Frenali38; Agarwal, Garima Amol39; Ravulaparthi, Gayatri40; Shilpa, Gondhi Vijay41; Deshpande, Gunjan42; Thakkar, Hansa39; Shah, Hadik 43; Ojha, Hare Ram44; Jani, Harsha45; Gondia, Jyoti 46 ; Mishrikotkar, Jyotika P47; Likhari, Kamalpreet48; Prajapati, Kamini39; Povar, Kahuita 49; Koka, Kirthi50; Darawa, Kulver Singh 51; Ramamurthy, Lakshmi B52; Bhattacharyya, Mainak53; Saini, Manorama22; Christie, Marem C; Das, Mausumi19; Hatta, Maya 51; Panchal, Mehul54; Pandharpurkar, Modini 41; Ali, Muhammad Osman 41; Porvar, Mukesh 55; Gangashetappa, Nagaraju32; Mehrotra, Neelima56; Bijrani, Neha57; Gajendragadkar, Nidhi28; Nagaka, Nidin M58; Modi, Parak 39; Rewri, Parveen22; Sao , Piyushi59; Patil, Prajakta Salunkhe60; Giri, Prajakta Salunkhe60; Giri, Pramod42; Kapadia, Priti61; Yadav, Priti46; Bhagat, Purvi39; Parek, Rajni 62; Dyaberi, Rajashekhar52; Chauhan, Rajender Singh63; Kaur, Rajwinder64 Duvesh, Ram Kishan65; Murti, Ramesh66; Dandu, Ravi Varma67; Kathiara, Ravija39; Berry, Renu68; Pandit, Rinal69; Rani, Rita Hepsi70; Gupta, Roshmi2; Fewani, Ruchi71; Sapkal, Rujuta47; Meta, Rupa58; Tadpalli, Sameeksha72; Fatima, Samra 41; Karmarkar, Sandeep73; Patil, Sandeep Suresh 74; Shah, Sanjana30; Shah, Sankit75 ; Shah, Sapan18; Dubey, Sarika51; Gandhi, Solin 76; Karnakpur, Savita52; Mohan, Shalini 77; Bhomaj, Sharad78; Kerka, Shira 26; Jariwala, Shivani61; Sahu, Shivati46; Tower Ra, Shruthi79; Maru, Shruti Kochar49; Jawal, Shubah 80; Sharma, Shubhda81; Gupta, Shweta82; Kumari, Shwetha83; Das, Sima 84; Menon, Smita26; Bakule, Snehal85; Nisar, Sonam Poonam50; Kaliaperumal, Suba shini86; Rao, Subramanya87; Pakrasi, Sudipto81; Rathod, Sujatha32; Birada, Sunil G59; Kumar, Suresh 88; Dutt, Susheen87; Bansal, Svati81; Ravani, Swati Amulbhai39; Rosi Sveta 89; Rizvi, Syed Wajahat Ali90; Gokhale, Tanmay86; Lahane, Tatyarao P62; Vukkadala, Tejaswini91; Grover, Triveni92; Bhesaniya, Trupti61; Chawla, Urmil63; Singh, Usha 72; Une, Pi Sheli L14; Nandeka, Varsha 80; Subramaniam, Venkata93; Esvalam, Vidya 83; Chowdhury, Vidyanair 94; Langarayan, Viji95; Dehan, Vipin96; Sahasrabudhe , Vivek M85; Sowjanya, Yarra97; Tupkary, Yashaswini98; Phadke, Yogita47 and OPAI-IJO co-study COVID-19 mucormycosis (COSMIC) research group member
Vision Center, Hyderabad, Telangana, India
1Future Vision Eye Care and Research Center, Mumbai, Maharashtra, India
2Narayana Netralaya, Bangalore, Karnataka, India
3 Araven Eye Hospital, Madurai, Tamil Nadu, India
4 Vision Center, Jaipur, Rajasthan, India
5 Vision Center, New Delhi, India
6 Department of Ophthalmology, Sir Ganga Ram Hospital and Vision Eye Centres, New Delhi, India
7Ophthalmology, Dr. Hedgewar Rugnalaya, Aurangabad, Maharashtra, India
8 Head and Neck Surgery, Apollo Cancer Hospital, Hyderabad, Telangana, India
9 Department of Otolaryngology, Dr. Abhishek K. Ramadhin Hospital and Avyaan Research Center, Ranchi, Jharkhand, India
10Department of Ophthalmology, Bharati Vidyapeeth Hospital, Sangli, Maharashtra, India
11Mumbai Eye Plastic Surgery, Mumbai, Maharashtra, India
12Department of Otorhinolaryngology, Rohtak Graduate School of Medical Sciences, Haryana, India
13 Indore Retina Specialist Hospital, Madhya Pradesh, India
14 Department of Ophthalmology, Shree Bhausaheb Hire Government Medical School, Dhule, Maharashtra, India
15Department of Ophthalmology, Sardar Patel Medical College, Bikaner, Rajasthan, India
16 Ophthalmology, Pandit Deendayal Upadhyay School of Medicine, Rajkot, Gujarat, India
17 Ophthalmology, All India Institute of Medical Sciences, Raipur, Chhattisgarh, India
18 Department of Ophthalmology, Kusum Dhirajlal Hospital, Ahmedabad, Gujarat, India
19Department of Ophthalmology, Mahatma Gandhi Medical College and Research Institute, Pondicherry, India
20Oases Eye Care Centre, Thane, Maharashtra, India
21 Department of Ophthalmology, Apollo Specialist Hospital, Chennai, Tamil Nadu, India
22 Department of Ophthalmology, Agroha Maharaja Agrasen Medical College, Haryana, India
23 Department of Ophthalmology, NKP Salve Institute of Medical Sciences and Research Center, Nagpur, Maharashtra, India
24 Ophthalmology, Jawaharlal Nehru Medical College, Lingayat College of Higher Education and Research, Karnataka, Belagavi, Karnataka, India
25 Department of Ophthalmology, Kingsway Hospital, Nagpur, Maharashtra, India
26 Ophthalmology, King Edward Memorial Hospital and Seth Gordhandas Sunderdas Medical College, Mumbai, Maharashtra, India
27 Department of Otorhinolaryngology, Kiran Super Multispecialty Hospital, Surat, Gujarat, India
28 Kashyap Memorial Eye Hospital, Ranchi, Jharkhand, India
29 Department of Ophthalmology, Alexis Hospital, Nagpur, Maharashtra, India
30 Department of Ophthalmology and Sir Sayajirao General Hospital, Baroda Medical College, Gujarat, India
31 Ophthalmology, Hinduhridaysamrat Balasaheb Thackeray Medical College and Dr. RN Cooper Municipal Hospital, Mumbai, Maharashtra, India
32 Department of Ophthalmology, Bangalore School of Medicine and Research Institute, Bangalore, Karnataka, India
33 Department of Ophthalmology, Jehangir Hospital, Pune, Maharashtra, India
34 Department of Ophthalmology, All India Institute of Medical Sciences, Bhopal, Madhya Pradesh, India
35 Ophthalmology, Sayajirao Gaekwad Hospital, Vadodra, Gujarat, India
36Bhaskar Eye Care, Raipur, Chhattisgarh, India
37Horus Specialty Eye Care, Bangalore, Karnataka, India
38 Department of Ophthalmology, Jagjivan Ram Railway Hospital, Mumbai, Maharashtra, India
39M and J Western Regional Eye Institute, Byramjee Jeejeebhoy Medical College, Ahmedabad, Gujarat, India
40 Department of Ophthalmology, Mamata Academy of Medical Sciences, Hyderabad, Telangana, India
41 Sarojini Devi Eye Hospital, Hyderabad, Telangana, India
42Max Vision Eye Hospital, Nagpur, Maharashtra, India
43 Department of Otorhinolaryngology, Kusum Dhirajlal Hospital, Ahmedabad, Gujarat, India
44Raj Eye Hospital, Gorakhpur, Uttar Pradesh, India
45 Ophthalmology, Pramukh Swami School of Medicine, Karamsad, Gujarat, India
46 Ophthalmology, Maharaja Yeshwantrao Hospital, Mahatma Gandhi Memorial Medical College, Indore, Madhya Pradesh, India
47 Department of Ophthalmology, Mahatma Gandhi College and Hospital, Aurangabad, Maharashtra, India
48Ratan Jyoti Netralaya, Gwalior, Madhya Pradesh, India
49 Ophthalmology, Convenience Hospital Co., Ltd. (CHL)-Indore Hospital, Madhya Pradesh, India
50Sankara Nethralaya, Chennai, Tamil Nadu, India
51 Department of Ophthalmology, Sawai Man Singh Medical College, Jaipur, Rajasthan, India
52 Department of Ophthalmology, Karnataka Institute of Medical Sciences, Hubli, Karnataka, India
53Eye-Q and Max Group of Hospitals, New Delhi, India
54 Department of Microbiology, Kiran Super Multispecialty Hospital, Surat, Gujarat, India
55Porwal Eye Clinic, Rajkot, Gujarat, India
56 Ophthalmology, Shri Ram Murti Smarak Institute of Medical Sciences, Bareilly, Uttar Pradesh, India
57Vision Care & Research Centre, Bhopal, Madhya Pradesh, India
58 Department of Otolaryngology, All India Institute of Medical Sciences, Raipur, Chhattisgarh, India
59 Department of Ophthalmology, Shri Mallanagouda Basanagouda Patil School of Medicine, BLDE University, Vijayapura, Karnataka, India
60 Department of Ophthalmology, Karad Krishna Institute of Medical Sciences, Maharashtra, India
61 Department of Ophthalmology, Surat Government Medical College, Gujarat, India
62 Ophthalmology, Grant School of Medicine and Jamshedjee Jeejeebhoy Hospital Group, Mumbai, Maharashtra, India
63 Regional Institute of Ophthalmology, Graduate School of Medical Sciences, Rohtak, Haryana, India
64 Ophthalmology, Adesh Institute of Medical Sciences, Batinda, Punjab, India
65 Department of Ophthalmology, Vardhaman Mahavir School of Medicine and Safdarjung Hospital, New Delhi, India
66Axis Eye Clinic, Pune, Maharashtra, India
67Department of Neuroradiology, Citi Neuro Centre, Hyderabad, Telangana, India
68 Department of Ophthalmology, Ambala Cantonment Civil Hospital, Haryana, India
69 Department of Ophthalmology, Choithram Hospital and Research Center, Indore, Madhya Pradesh, India
70 Ophthalmology, Tirunelveli Medical College, Tirunelveli, Tamil Nadu, India
71 Department of Ophthalmology, SMBT Medical Science Research Center, Nashik, Maharashtra, India
72 Advanced Eye Center, Graduate School of Medical Education and Research, Chandigarh, India
73 Otolaryngology, Ruby Hall Clinic, Pune, Maharashtra, India
74 Ophthalmology, Sakra World Hospital, Bangalore, Karnataka, India
75 Ophthalmology, Kiran Super Multispecialty Hospital, Surat, Gujarat, India
76Eye Plasty Centre, Surat, Gujarat, India
77 Department of Ophthalmology, Ganesh Shankar Vidyarthi Memorial Medical College, Kanpur, Uttar Pradesh, India
78Shanti Saroj Netralaya, Miraj, Maharashtra, India
79Sankara Eye Hospital, Coimbatore, Tamil Nadu, India
80 Department of Ophthalmology, Aurangabad Government Medical College, Maharashtra, India
81Department of Ophthalmology, Medanta-The Medicity, Gurugram, Haryana, India
82Sankara Eye Foundation, Indore, Madhya Pradesh, India
83 Ophthalmology, Bowring and Lady Curzon Hospital, Bangalore Medical College and Research Institute, Bangalore, Karnataka, India
Dr. 84 Shroff Charity Eye Hospital, New Delhi, India
85 Department of Ophthalmology, Dr. Shankarrao Chavan Government Medical College, Nanded, Maharashtra, India
86 Department of Ophthalmology, Jawaharlal Graduate School of Medical Education and Research, Pondicherry, India
87 Department of Otolaryngology, Langador Memorial Hospital, Bangalore, Karnataka, India
88 Department of Ophthalmology, Government Medical College of Chandigarh, India
89 Department of Otorhinolaryngology, Kingsway Hospital, Nagpur, Maharashtra, India
90 Department of Ophthalmology, Jawaharlal Nehru Medical College, Aligarh Muslim University, Uttar Pradesh, India
91 Ophthalmology, Virinchi Hospital, Hyderabad, Telangana, India
92 Department of Ophthalmology, Fortis Hospital, Shalimar Bagh, New Delhi, India
93Rangalakshmi Netralaya, Bangalore, Karnataka, India
94 Ophthalmology, Aakash Healthcare Super Specialty Hospital, New Delhi, India
95Aravind Eye Hospital, Coimbatore, Tamil Nadu, India
96 Oral and Maxillofacial Surgery, Kingsway Hospital, Nagpur, Maharashtra, India
97Sankara Eye Hospital, Guntur, Andhra Pradesh, India
98 Ministry of Medicine, Dr. Hedgewar Rugnalaya, Aurangabad, Maharashtra, India
Corresponding author: Dr. Santosh G Honavar, Director of Ophthalmology Plastic Surgery and Eye Oncology, Vision Center, Ashoka Capitol, Road No 2, Banjara Hills, Hyderabad-500 034, Telangana, India. Email: [Email Protection]
The collaborative OPAI-IJO study of mucormycosis in the COVID-19 (COSMIC) research group includes all the authors listed on page 1670 and the following (listed in alphabetical order): Abhilasha Maheshwari, Greek Super Specialty Hospital, Mohali Akruti Desai, Khan Bahadur Bhabha Hospital, Mumbai Municipal Corporation, Mumbai; Alay Banker, Banker's Retina Clinic and Laser Center, Ahemdabad; Amit Kumar Deb, Pondicherry Jawaharlal Graduate Medical Education and Research Institute; Anagha A Heroor, Mumbai Anil Eye Hospital; Anil Jain, Roop Jeevan Hospital, Raipur; Anita Kumari, Railway Hospital, Ambala Cantonment, Haryana; Anuj Mehta, Vardhaman Mahavir Medical College and Safdarjung Hospital, New Delhi; Arpitha K, Sarojini Devi Eye Hospital, Hyderabad; Arun Alexander, Pondicherry Jawaharlal Graduate School of Medical Education and Research; Arundhati Malviya, Babasaheb Ambedkar Memorial Hospital, Mumbai Central Railway; Ashwini Ghodse, Bowring and Lady Curzon Hospital, Bangalore Medical College and Research Institute, Bangalore; Avriel Gudkar, Anil Eye Hospital, Mumbai; Babu MS, Langadore Memorial Hospital, Bangalore; Beena Viramgama, Rajkot Pandit Deendayal Upadhyay Medical School; Biswarup Ray, Bankura Sammilani School of Medicine and Hospital, Bankura ; Chirag Pujara, Pandit Deendayal Upadhyay School of Medicine, Rajkot; Dhaivat Shah, Choithram Hospital and Research Center, Indore; Dharmesh P Pandavadara, Pandavadara, Pandit Deendayal Upadhyay School of Medicine, Rajkot; Deepali Gawai, Shree Bhausaheb Hire Government Medicine Hospital, Dhule; Dheeraj Kumar Jonnalagadda, Virinchi Hospital, Hyderabad; Dhwani Mehta, Pramukh Swami Medical College, Karamsad; Divya Khandelwal, Maha of Mahatma Gandhi Memorial Medical College, Indore Department of Ophthalmology, Raja Yeshwantrao Hospital; Divyalakshmi Kaiyoor Surya, Yenepoa Medical College and Hospital, Mangalore; Ekta Singh Sahu, Indore Retina Specialist Hospital; Elika Gupta, Sawai Man Singh Medical College, Jaipur; Faraz Ali, Division Zekod Aster Malabar Institute of Medical Sciences; Gajendra Chawla, Bhopal Vision Care and Research Center; Grace Budhiraja, Ades Institute of Medical Sciences, Batinda; Gunjan Tank, M and J Western Regional Institute of Ophthalmology, Byramjee Jeejeebhoy School of Medicine, Ahmedabad; Harshit Vaidya, PhD, Vaidya Eye Hospital, Mumbai; Hiral Bhalodia, Rajkot Pandit Deendayal Upadhyay School of Medicine; Jay Rathod, M and J Western Region Eye Institute, Byramjee Jeejeebhoy School of Medicine, Ahmedabad; Jignesh Jethva, M and J Western Region Eye Research Institute, Byramjee Jeejeebhoy Medical College, Ahmedabad; K. Kiran Kumar, Bangalore Medical College and Research Institute, Bangalore; Karthik Shamanna, Bangalore Medicine Institute and Research Institute, Bangalore; Keya Chakraborty, Sum Ultimate Medicare, Bhubaneswar; Memuna Bahadur, Babasaheb Ambedkar Memorial Hospital, Mumbai Central Railway; Miti Shah, Rajkot Pandit Deendayal Upadhyay Medical College; Neebha Anand, Regional Ophthalmology Research Institute, Institute of Medical Sciences, Rohtak; Neeti Rushit Sheth, Pandit Deendayal Upadhyay School of Medicine, Rajkot; Nidhi Pandey, Lucknow Indira Gandhi Eye Hospital and Research Center; Niharika Chaurasia, Ratan Jyoti Netralaya, Gwalior; Nitin Kumar, Columbia Asian Hospital, Patiala; PS Kohli, Columbia Asian Hospital, Patiala; Piyush Bajaj, Dhir Hospital and Eye Institute, Bhiwani; Poonam Jain, Shalimar Bagh Fortis Hospital, New Delhi; Preet Kanwar Singh Sodhi , Columbia Asia Hospital, Patiala; Rashmi S, Yenepoa Medical College and Hospital, Mangalore; Ravishankar Chandrashekhar, Bowring and Lady Curzon Hospital, Bangalore Medical College and Research Institute; Rekha Khandelwal, Nagpur NKP Salve Medical Science Research Center and Research Center; Ricky Vinay, Axon Eye Care, Mumbai; Ruddi Joshi, M and J Western Regional Eye Institute, Byramjee Jeejeebhoy Medical College, Ahmedabad; Rukmendra PS Warkade, Sadguru Netra Chikitsalaya, Chitrakoot; Saloni Gupta, New Delhi Northern Railway Central Hospital; Nagpur Max Vision Eye Hospital Sameer Choudhary; Sangita Basantaray, Bhubaneswar High-Tech Medical College and Hospital; Sanket Oza, M and J Western Region Eye Institute, Byramjee Jeejeebhoy School of Medicine, Ahmedabad; Santanu Das, Bengaluru Sankara Eye Hospital; Saptagirish Rambhatla, Bangalore Sankara Eye Hospital; Satish Reddy S, Bankura Sammilani School of Medicine and Hospital, Bankura; Saurabh Singh Jareda, Institute of Medical Sciences and ESI Model Hospital, Basaidarapur, New Delhi; Shagil Khan, Jawaharlal Nehru Medical College, Aligarh Muslim University, Aligarh; Shailender Kumar Choudhary, Northern Railway Central Hospital, New Delhi; Shaunak Mokadam, Anjani Eye Care, Nagpur Hospital; Shikha Jain, Indore Mahatma Gandhi Memorial Medical College; Shivanand Bubanale, Jawaharlal Nehru Medical College, Karnataka College of Higher Education and Research, Belagavi; Nagpur Drishti Eye Clinic and Strabismus Center Shubhangi Bhave; Smitha KS, Jawaharlal Nehru Medical College, Karnataka College of Higher Education and Research, Belagavi; Soumya Ray, Bankura Sammilani School of Medicine and Hospital, Bankura; Sruthi Rao, Rungta College of Dental Science and Research Cent re, Raipur; Subhashini V, Klariti Eye Care Hospital, Chennai; Subina Narang, Chandigarh Government School of Medicine; Sujithra Haridas, Amrita Institute of Medical Sciences, Kochi; Sumeet Lahane, Grant School of Medicine and Jamshedjee Jeejeebhoy Hospital Group, Mumbai; Sunaina Chandana, Indira Gandhi Eye Hospital and Research Center, Lucknow; Sunitha Mathew, Aster Malabar Institute of Medical Sciences, Kozhikode; Surbhi Joshi Kapadia, Sunayana Eye Care Center and Venus Super Specialty Hospital, Vadodara; Supriya Khare, Indochina Department of Ophthalmology, Maharaja Yeshwantrao Hospital, Mahatma Gandhi Memorial Medical College; Swathi YK, Sakra World Hospital, Bangalore; Swati Samant, Sum Ultimate Medicare, Bhubaneswar; TN Ezhilvathani, Indira Gandhi Medical College and Research Institute, Pondicherry ; Umanath Nayak, Head and Neck Surgery, Apollo Cancer Hospital, Hyderabad; Vaibhavi Patel, M and J Western Regional Eye Institute, Byramjee Jeejeebhoy Medical College, Ahmedabad; Varsha Backiavathy, Sankara Nethralaya, Chennai; Vernon Miranda, Brahma Kumaris Global Hospital and Research Center, Mumbai; Vinay Prasad, Axon Eye Care, Mumbai; Vishal Sharma, Apex Super Professional Eye Care, Dehradun; Vishwanatha Borlingegowda, Bangalore School of Medicine and Research Institute, Bangalore; Yamini Sahu, Vardhaman, New Delhi, India Mahavir Medical College and Safdarjung Hospital
Received in revised form on June 6, 2021
During the second wave of COVID-19 pandemic in India, COVID-19-related rhinoorbital mucormycosis (ROCM) has reached epidemic proportions, and its pathogenesis involves several risk factors. This study aims to determine the patient’s demographics, risk factors including comorbidities, drugs used to treat COVID-19, symptoms and signs present, and treatment outcomes.
This is a retrospective observational study of COVID-19-related ROCM patients who were managed or co-managed by ophthalmologists in India from January 1, 2020 to May 26, 2021.
Among the 2826 patients, Gujarat (22%) and Maharashtra (21%) reported the highest number of ROCMs. The average age of the patients was 51.9 years old, with males predominantly (71%). Although 57% of patients needed oxygen support due to COVID-19 infection, 87% of patients received corticosteroid therapy (21% of patients lasted> 10 days). 78% of patients have diabetes (DM). Most cases developed ROCM symptoms between the 10th and 15th days after the diagnosis of COVID-19, 56% of the cases developed within 14 days after the diagnosis of COVID-19, and 44% of the cases delayed onset by more than 14 days. Orbit is involved in 72% of patients, of which stage 3c forms the majority (27%). The overall treatment includes 73% intravenous amphotericin B, 56% functional endoscopic sinus surgery (FESS)/paranasal sinus (PNS) debridement, 15% orbital debridement, and 17% FESS/ PNS debridement and orbital debridement. 22% of amphotericin B was administered by intraorbital injection. At the last follow-up, the mortality rate was 14%. Disease stage> 3b has a poor prognosis. Paranasal sinus debridement and intraorbital resection reduced the mortality of patients with stage 4 intracranial disease from 52% to 39% (p <0.05).
Corticosteroids and DM are the most important predisposing factors in the development of COVID-19-related ROCM. COVID-19 patients must be followed up after recovery. Awareness of red flag symptoms and signs, high clinical suspicion, rapid diagnosis and early initiation of treatment with amphotericin B, aggressive PNS surgical debridement and orbitectomy (if indicated) are indispensable for successful results Less.
India is currently responding to a fierce second wave of COVID-19. Only 3% of the population is fully vaccinated, and the third wave has been predicted. [1] In this case, the country is also plagued by a previously unknown but well-known deadly disease, rhino-orbito-cerebral mucormycosis (ROCM). A review of the existing literature shows that India accounts for 81% of COVID-19-related ROCM cases. [2] During the first wave of pandemics, few ROCM case reports related to COVID-19 were published. The first series in India was reported in February 2021. [3] Since then, with the surge in the second wave of COVID-19, the incidence in India has increased exponentially. [45]
No research has been conducted to determine large-scale epidemiology, disease characteristics, and outcomes nationwide. There is no formal staging system for this disease, and there is no evidence-based agreement to manage this disease, which makes the medical team struggle in an uncharted territory. Cooperative efforts are essential to obtain real-world information and baseline epidemiological data, identify at-risk patients, countless manifestations, and results of investigation and management at different stages of the disease.
The purpose of this multi-center collaborative study is to determine the patient's demographics and risk population, symptoms and signs, comorbidities, and the role of drugs used to treat COVID-19, and management results. The information provided by such studies may help medical professionals to identify the early clinical features of ROCM, high suspicion in the presence of typical symptoms and signs, and appropriately classify patients who may develop ROCM to confirm the diagnosis, determine the staging, and initiate based Early multidisciplinary management of the agreement. At the national level, this research can help decision makers in the healthcare sector estimate the severity of the problem, optimize COVID-19 care guidelines to minimize risk exposure, establish follow-up agreements after COVID-19, and establish regional multi-specialty centers And ROCM care team, and increase the availability of antifungal drugs.
We conducted a retrospective, multi-center, non-interventional, observational study on ROCM and patients with a history of COVID-19 infection at the same time or in the past. The study was approved by the ethics committee. Ophthalmologists across the country were invited to participate in this study, and entered their anonymous data on ROCM patients managed or co-managed by them between January 1, 2020 and May 26, 2021 into a public database (Attachment 1. Online content). The diagnosis of COVID-19 is based on any of the following: reverse transcription polymerase chain reaction (RT-PCR) test of nasopharyngeal or oropharyngeal swabs, rapid antigen test, or computed tomography (CT) chest score, but there is no positive result. RT-PCR detection in clinically symptomatic cases. In a clinical setting with concurrent or recently treated COVID-19, patients with symptoms and signs of ROCM are considered probable ROCM. If the clinical features are supported by diagnostic nasal endoscopy, contrast-enhanced magnetic resonance imaging (MRI), or CT scan, then a possible ROCM is diagnosed. A proven ROCM is defined as the microbiological confirmation of clinical radiological features and direct microscopic examination and/or culture or histopathology with special staining or molecular diagnosis. [Table 1] [6] Patients with non-COVID-19 related ROCM or patients with confirmed non-Mucor infection were excluded from the study. The patient is defined as recovering from COVID-19 if it tests negative in repeated RT-PCR, or two weeks have passed since the diagnosis.
A work staging system has been proposed to help classify these patients and customize their care [Figure. 1].[6] The system is very simple, following the general anatomical progress of ROCM from entry point (nasal mucosa) to paranasal sinus (PNS), orbit and central nervous system (CNS), and each of these anatomical locations Severity. Try to list the symptoms, signs, and preferred diagnostic tools for each stage. [6] In this study, all patients were retrospectively classified into the recommended staging system. SPSS (IBM SPSS Statistics 20, SPSS Inc., Chicago, IL, USA) and Microsoft Excel (version 16.49) were used to analyze the data. Chi-square test and Fisher's exact test are used to compare results. For all tests, a p-value ≤ 0.05 was defined as statistically significant.
Data of 2826 COVID-19-related ROCM patients from 102 treatment centers, 22 states and federal territories in India were analyzed. The percentage and number of cases in each state are shown in Table 2. It is closely followed by Gujarat in Maharashtra, which accounts for the majority of cases, with 22% (609) and 21% (603) respectively. Figure 2 shows the distribution of COVID-19 and ROCM drawn by each state and Union territory based on our data and the COVID-19-related mucormycosis data released by the Indian government. [7] The average age is 51.9 (range, 12-88) years old, with males predominantly (71% in 1993).
The average cycle thresholds for RT-PCR and high-resolution CT chest scores were 15.9 ± 6.5 (n = 286) and 12.2 ± 5 (n = 893), respectively. Table 3 shows the severity of COVID-19 and the details of its management. Although 2% (54) of patients were asymptomatic and cared for at home, and 26% (735) were symptomatic and cared for at home, 72% (2029) required hospitalization. Among hospitalized patients, 79% (1602) require oxygen support. Overall, only 57% (1602) of all patients require oxygen support. 10% (285) of the patients used remdesivir.
87% (2073 of 2371) patients used systemic corticosteroids (oral or intravenous or both), while 13% (298) did not receive any form of corticosteroids. [Table 3] 78% (1476 of 1902) patients received intravenous corticosteroids, intravenous methylprednisolone 51% (749) and dexamethasone 48% (704) were the most commonly used types, with a median persistent The time is 6 days. 64% (1185 out of 1865) used oral corticosteroids, with a median duration of 8 days. 42% (426 out of 1014) patients received oral corticosteroid therapy only, and the remaining patients also received intravenous corticosteroid therapy. Table 4 shows that corticosteroid use is the most common risk factor, and its use is directly proportional to the severity of COVID-19. Of the 789 (28%) home-care patients, 73% (361 of 492) received corticosteroid therapy. Of the 2029 people hospitalized, 80% (314 out of 393) did not need oxygen, 93% (1061 out of 1143) needed oxygen through a fork/mask, and 99% (226 out of 229) Oxygen-pressure non-invasive ventilation was required, and 97% (108 of 111) of the patients who received mechanical ventilation received corticosteroid therapy. Of the 631 non-diabetic patients, 89% (393 of 440) received corticosteroid therapy. Of the 174 non-diabetic patients who did not receive oxygen therapy, 81% (141 people) received corticosteroid therapy. Only 2% (58) use tocilizumab.
In systemic comorbidities, DM status, regardless of control, is a risk factor. Although 2194 patients (78%) had diabetes, 972 (44%) were uncontrolled or had diabetic ketoacidosis (DKA). Among 859 patients with other comorbidities, 80% (690) had hypertension, and 10% (88) had acute or chronic renal failure [Table 2].
The proportion of patients with ROCM who had neither diabetes nor corticosteroid therapy was 2% (47). In the outpatient and home isolation group, 6% (22) had no potential risk factors.
Figure 3 shows the timeline from the diagnosis of COVID-19 to the onset of ROCM symptoms. The average interval was 14.5 ± 10 days (n = 2285, median was 13, 0-90 days), and 56% of patients developed within 14 days. 44% of patients experienced delayed performance after 14 days. Figure 4 shows the frequency of the most common main symptoms of ROCM-orbital/facial pain (23%), orbital/facial edema (21%), vision loss (19%), ptosis (11%), and nasal block (9%). Other symptoms include prominent eyeballs, runny nose, diplopia, headache, discoloration of the eye sockets and face, toothache, loose teeth, epistaxis and facial deviations. Figure 5 shows the frequency of the most common main symptoms of ROCM-eye/face edema (33%), vision loss (21%), ptosis (12%), exophthalmos (11%) and nasal discharge (10%) ). Other signs include nasal ulcers or eschars, diplopia/restricted eye movements, discoloration around the eyes or face, decreased sensation around the eyes, oral/palatal ulcers/eschars, facial paralysis, and sensory center changes. Table 5 shows the cumulative incidence of ROCM clinical manifestations. Vision loss is the most common sign (63%), followed by ocular or facial edema (61%) and ptosis (54%). 38% of patients have exophthalmos. Among the 397 patients who can be measured for exophthalmos, the average measured exophthalmos was 3.1 (range 1-8) mm.
79% (1921 out of 2445) patients underwent diagnostic nasal endoscopy. Of the 752 patients with stage 1 and stage 2 disease, 85% (569 of 672) had surgery. For diagnostic evaluation, 43% (1016 of 2362) had deep nasal swabs, while 48% (1131 of 2362) samples were collected during sinus debridement. Microbiological evidence was obtained in 2175 patients-89% (1931) of the cases were directly examined with KOH/calcofluor white, 6% (121) were smears, and 19% (432) were cultured. 239 patients were diagnosed by rapid histopathology, 54% (130) were diagnosed early by frozen section, and 46% (109) were diagnosed by extrusion or imprinting technique. At the time of analysis, 39% (1090 out of 2795) patients had histopathological confirmation. 27% (670 out of 2,533) had a CT scan, 58% (1472) had MRI, and 15% (391) had both CT and MRI.
Table 5 shows the clinical and radiological involvement of PNS, orbit and CNS. Diffuse PNS involvement accounted for 58% (1413 out of 2428), and bilateral PNS involvement accounted for 40% (1050 out of 2669). In the orbit, diffuse involvement accounted for 40% (674 out of 1731), followed by medial orbital involvement, which accounted for 27% (469 people). 21% (371) of the patients involved the orbital apex. In the CNS, the cavernous sinus is most commonly involved in 53% (285 out of 539 people). Bilateral CNS involvement was documented in 5% (133 out of 2669) cases, and cavernous sinus was the most common route of transmission (70%, 299 out of 430 cases).
The staging of ROCM is based on the available information of 2669 patients. For 157 patients, this is impossible. Classification of patients according to the proposed ROCM staging system [6] [Figure. Figure 1 shows that 49% (1302) of patients have a disease severity of 3b or less, and 27% (724) of patients have stage 3c [Figure 1]. 6-17].
Figure 18 shows the main management performed on the COVID-19 related ROCM. 52% (1257 of 2437) preferred medical treatment of Amphotericin B, 21% (522) preferred functional endoscopic sinus surgery (FESS)/PNS debridement, and 9% (217) performed concurrently. Table 6 shows the overall patient management data as of the date of analysis. Of the 2066 (73%) patients who received intravenous amphotericin B for an average duration of 9.1 (range, 1-60) days, 73% (1512) provided liposomal amphotericin B, and 25% (516) Amphotericin B deoxycholate is provided, and both account for 2% (38). 23% (657) provided a combination therapy of amphotericin B and posaconazole or isaconazole. 26% (732) of patients received oral posaconazole or isaconazole for antihypertensive therapy (after stopping intravenous amphotericin B). A total of 67% (1585 out of 2358 people) underwent FESS/PNS debridement, of which 27% (346 out of 1286 people) received multiple treatments to eliminate residual/recurrent disease, and 15% (out of 2327 people) received FESS/PNS debridement. Of 339 people) underwent orbital resection, FESS/PNS debridement and orbital debridement both accounted for 17% (367 out of 2186), and intraorbital amphotericin B injection accounted for 22% (511 out of 2332) ), the median of two (range, 1-9) injections.
Of the 2218 patients, as of the date of data collection, we have the result data, the average follow-up time was 14.4 ± 21.3 days (n = 872, range, 1–-270), 41% (909) survived and recovered well in ROCM , 32% (717) were alive and had a clinically radiologically stable ROCM, 13% (287) had progressed on treatment, and 14% (305) had expired. Among the alive patients, eye results were available in 1838 patients, 16% (289 people) had an orbitectomy, and 84% (1549 people) had eye salvage. Of these, 55% (845) reported sight saving (visual acuity better than 20/200). [Table 7] Among 511 people who received intraorbital amphotericin B treatment, 88% (377 of 381 people were alive and the results were available) received eye salvation, and 38% (126 of 330 people) received Vision saving. Achieved 100% in phase 3a (50 out of 50), 98% in 3b (81 out of 83), 83% in 3c (97 out of 117), and in 3d 77% (10 out of 13), 71% (24 34) in 4a, 79% (11 out of 14) in 4b, 82% (22 out of 27) in 4c, 67% (8 out of 12) are in 4d.
Table 8 shows the results of patients at the last follow-up based on disease stage and surgical intervention. For stages 1 and 2, of the 382 patients who underwent PNS debridement, 366 (96%) had stable residue or regression (p <0.05) compared with patients who had not undergone any surgery. Of the 375 ROCM stage 3a and 3b patients, 25 underwent orbitectomy, and 84% (21) had stable residual or degenerative disease, similar to 370 patients who did not undergo orbitectomy (p = 0.96) . PNS debridement in ROCM patients at stage 3a and 3b reduced disease progression and mortality from 35% to 11% (p <0.05). Once the disease progresses to stage 3c or worse, the prognosis is poor, with 39% (451 out of 1145) patients experiencing mortality and disease progression, while 12% of patients with stage 3b or better (119 out of 1027) Name) (p <0.05). For diffuse intraorbital disease (stage 3c, 3d), both intraorbital resection and PNS debridement seem to be beneficial. Mortality and disease progression occurred in 47% (74 of 158) of patients who did not undergo PNS debridement, while 22% of patients who received debridement (90 of 410) (p <0.05) . Mortality and disease progression after intraorbital resection were also significantly reduced, 22% (36 out of 164) compared with 33% (134 out of 405) who did not undergo orbital resection (p = 0.008) . For stage 4, surgical intervention improved the prognosis. The mortality and disease progression after PNS debridement decreased from 67% (96 out of 143) to 39% (115 out of 297), and the mortality and disease progression after orbital debridement decreased from 52% (out of 314) 164 people) to 39% (48 out of 124 people).
A total of 137 patients were followed up for more than 3 weeks (average 45.6 days, 21-270 days). Of these, 6% (8) have expired, in addition, 6% (8) have disease progression, 24% (32) have stable residual disease, and 65% (88) have resolved. 66% (83 out of 125 people) achieved eye salvation, and 67% (56 out of 83 people) had vision> 20/200. Table 9 shows the staging results of these patients. Of the 20 patients with stage 2 disease, 17 underwent PNS debridement, and the lesions in all patients had resolved or stabilized. PNS debridement was performed on all 30 patients with stages 3a and 3b, and orbitectomy was performed in two cases. Mortality and disease progression occurred in 17% (15 of 86) patients with stage 3c or more severe, and 2% (1 in 50) of patients with stage 3b or better (p = <0.05 ). Orbitectomy did not significantly change the prognosis of patients with disease stages 3c and 3d (p = 0.24). PNS debridement in the 3c and 3d stages reduced disease progression and mortality from 33% (1 of 3) to 13% (5 of 38), but the results were not statistically significant. All 16 patients with stage 4 disease treated with orbitectomy survived with stable or regressive lesions (p = 0.03).
Mucormycosis is an opportunistic, potentially fatal, vascular invasive fungal infection, susceptible to uncontrolled DM, corticosteroids, immunosuppressive therapy, primary or secondary immunodeficiency, hematological malignancies, Blood stem cell transplantation, solid organ malignancies, solid organ transplantation and iron overload [3]. Other less common risk factors include intravenous drugs, human immunodeficiency virus infection, kidney failure, liver disease and chronic alcoholism, as well as child malnutrition and low birth weight. According to a study of the Indian population, tuberculosis and chronic kidney disease were found to be newly emerging risk factors. [89] It can affect the nose, sinuses, orbits, central nervous system, lungs, gastrointestinal tract, skin, jaws, heart, kidneys, and mediastinum. ROCM is the most common manifestation, accounting for approximately two-thirds of all mucormycosis cases. [1011] The spores were inhaled into the nasopharynx, tissue infiltration, thrombosis, and necrosis progressed from the nose to the PNS, orbits, and CNS. It is estimated that before the pandemic, the worldwide prevalence rate was 0.005-1.7 per million people. The prevalence in India has always been much higher, almost 80 times that of other parts of the world, at 0.14 per 1,000 people. [21213] In terms of the number of diabetic patients, India also ranks second in the world. [14]
For COVID-19, the incidence of secondary bacterial or fungal infections is 8%, of which aspergillosis and Candida are the most common fungi. [1516] In the current wave of COVID-19, mucormycosis has surged. Due to the immunosuppression of the virus itself and corticosteroids used in management, COVID-19 produces a hypoxic environment with high glucose levels, high levels of ferritin, and reduced phagocytic activity of white blood cells. This environment is very conducive to the germination and proliferation of fungal spores. [2] Unsanitary practices, prolonged hospital stays that may occur nosocomial infections, the use of immunosuppressants such as tocilizumab, and related comorbidities are other risk factors that lead to an increase in the incidence of COVID-19-related ROCM. [2] This study aims to improve the understanding of ROCM among COVID-19 patients in order to ultimately improve management and results.
In the Indian population, the average age of COVID-19 patients admitted to the hospital is 45-50.7 years, and 56-93% of patients are male. [171819] In a review of global cases by the European Medical Mycology Federation and the International Society of Human and Animal Mycology, it is reported that the median age of disease in patients with COVID-19-related ROCM is 55 years (range 10-86 years) . [20] Among the reported COVID-19-related ROCM cases, men prefer (79%). [2] The demographics in our series are consistent with these studies, with an average age of 51.9 years and 71% of male patients. Men have also been found to be associated with more severe COVID-19. More outdoor exposure, therefore, fungal spores may be the possible cause of this majority.
In a study in India, among the first wave of 235 patients who were infected with SARS-CoV-2 and required hospitalization, 77% required any form of oxygen support, 22% required high-flow nasal catheters, and 26% required hospitalization. Create mechanical ventilation. [17] In a larger study in Mumbai, 11% of people needed mask/cannula oxygen, 0.7% needed non-invasive ventilation, and only 0.2% needed ventilator support. [21] In this study, 57% (1602 out of 2818 people) observed oxygen demand, of which 78% used a mask/nose clip, 15% used non-invasive ventilation, and 7% required mechanical ventilation. Our data on COVID-19-related ROCM patients shows that 43% (1216 of 2,818) do not require oxygen support during COVID-19 treatment. However, most of these people have DM and most have received some form of corticosteroids, which suggests that contaminated oxygen may not be a driving factor for infection. Of the 47 non-diabetic patients with COVID-19-related ROCM who were not treated with corticosteroids, 51% (24) required hospitalization and 30% (14) required oxygen. Since there are no large published studies on hospitalized COVID-19 patients in India, it is difficult to understand whether patients with ROCM have a higher need for oxygen support than patients without ROCM. In 2.5% (10) of patients without any other identifiable risk factors, it can be speculated that they may have developed a nosocomial infection.
Remdesivir and tocilizumab have specific indications for use. Remdesivir has been authorized for emergency use of COVID-19, while tocilizumab is an off-label use. [twenty two]
Tocilizumab was only used in 6 cases of mucormycosis reported in the literature. [20] In our series, 10% of patients received remdesivir, and only 2.1% of patients received tocilizumab, and may not increase the risk of ROCM.
Corticosteroids are slandered for their role in increasing susceptibility to mucormycosis, and this accusation is not entirely unfounded. It has been found that cumulative doses of prednisone exceeding 600 mg and 2-7 grams of methylprednisolone can make immunocompromised patients susceptible to mucormycosis. [23] Long-term,> 3 weeks high-dose systemic corticosteroids are considered a risk factor for mucormycosis in non-COVID-19 patients. [24] In addition to COVID-19, corticosteroids have been used to treat many diseases and have become part of the guidelines even in the first wave of treatment. The RECOVERY trial shows that corticosteroids can reduce the mortality of patients with moderate to severe COVID-19. [25] The updated national guidelines recommend the use of intravenous methylprednisolone (or equivalent dexamethasone 0.1-0.2 mg/kg) at a dose of 0.5-1 mg/kg, twice for moderate disease , 1-2 mg/kg divided into two doses (dexamethasone 0.2-0.4 mg/kg) to treat serious diseases, lasting 5-10 days. [22] According to published literature, 76% of COVID-19-related ROCM patients have a history of systemic corticosteroids. [2] In India, this percentage is even higher, at 88%. [26] Our data show that 87% of patients use systemic corticosteroids. Although the average duration of oral and intravenous corticosteroids was within the prescribed recommended range, 21% (373 of 1775) patients received systemic corticosteroids for more than 10 days. Of the 789 mild COVID-19 cases that did not require hospitalization, 73% used corticosteroids. Unreasonable or unwise use of corticosteroids may be a possible cause of ROCM.
Among COVID-19 patients in India, 11-23% of hospitalized patients have DM. [1718] 20.6% of patients with mild to moderate COVID-19 have new DM. [27] It is said that the virus destroys pancreatic islet cells, produces new DM, and worsens the original DM or DKA. Cytokine storms indirectly exacerbate this situation by causing insulin resistance. [262829] Corticosteroids can also cause hyperglycemia and DKA. Hyperglycemia causes glycosylation of transferrin and ferritin and reduces iron binding. By reducing the ability of transferrin to sequester iron, acidosis exhibits an additive effect, leading to an overall increase in free iron levels, allowing Mucor to thrive. DM has been identified as an independent risk factor for mucormycosis. [8] In a series of mucormycosis cases that occurred in India before COVID-19, 74% of patients were diabetic. [10] The risk of mucormycosis in diabetic patients is 7.5 times that of the general population. [30] When we look at the current situation of COVID-19-related ROCM in India, in a series of 41 cases by John et al., [26] 93% are diabetic patients. A literature review of existing global data by Singh et al. [2] and Hoenigl et al. [20] showed that diabetic patients accounted for 80% of cases, and concomitant DKA was found in 15-41% of patients. Among them, 90-97% of cases are type 2 and 80.3% are not controlled. [220] Our data showed similar results, but we did not distinguish between type 1 and type 2. Of the 210 patients who did not receive corticosteroid therapy or needed oxygen, 84% (173) were diabetic.
Except in rare cases, it is not known that ROCM affects healthy individuals. Hypertension was found in 19% of the cases, while only 5% of the reported COVID-19-related ROCM cases did not record related comorbidities. [20] In our 2826 people series, 24% (690) people have high blood pressure and 3% (88) people have kidney disease. Similar to previous studies on ROCM and ROCM in COVID-19, in our series, 18% (506 out of 2826) patients had no systemic comorbidities other than COVID-19. This is important because patients with signs and symptoms of ROCM in the context of COVID-19 should be thoroughly investigated and highly suspected even if there are no potential comorbidities. Among patients in home isolation, 5% of patients do not require corticosteroids or diabetes, but still have ROCM. They do not have any known risk factors. Although the proportion is small, the absolute number of 23 is still shocking. It is necessary to further study the interaction between the virus and the host and look for other potential risk factors. Mucor is a known symbiotic bacteria in the gastrointestinal tract, but it also exists in the nasopharynx and PNS. The rupture of the mucosal barrier may cause endogenous infection. [31]
The etiology of COVID-19-related ROCM appears to be multifactorial. Pre-existing DM; new COVID-19-related hyperglycemia; mucosal immune impairment, mechanical rupture of the nasal mucosa and mucosal necrosis, hypoxia, and elevated ferritin levels are all attributable to COVID-19; systemic corticosteroids; Nosocomial infections of hospitalized patients, especially those in the intensive care unit, seem to be reminiscent of a malignant combination of risk factors. In a large study of 5,428 COVID-19 hospitalized patients from March 2020 to May 2021, 1027 were in the intensive care unit (915 out of 1027 received corticosteroid treatment, and 417 had diabetes ), no cases of ROCM have been reported. [32] The authors attribute this to compliance with low-dose corticosteroid regimens and strict blood sugar control. [32] Future research can solve these problems and regard the air quality of the hospital as a possible influencing factor. In addition to all these predisposing factors, the tropical Indian climate itself may also make susceptible patients susceptible to ROCM. [17182631323334]
ROCM coincides with COVID-19 and after recovery. In the comments of Hoenigl et al., 93% of 80 ROCMs were hospitalized and received active treatment for COVID-19. [20] The median time for the diagnosis of mucormycosis is 10 days from the date of diagnosis of COVID-19. For patients who showed signs of mucormycosis after being diagnosed with COVID-19, the duration was 14.5 days. [20] In the literature review by Singh et al., the deviation of this ratio is small. [2] 60% of cases occurred in the active phase, and 40% of cases occurred in recovered COVID-19 patients. Both series include mucormycosis in all anatomical parts, not just ROCM. In our series, the peak occurred on day 10, 10% (230 out of 2285 people) had ROCM symptoms, and 56% of patients had ROCM symptoms within 14 days of being diagnosed with COVID-19. On day 15 and day 20, 10% (227) and 7% (162) of patients had additional peaks, respectively. The development of ROCM while patients are still receiving active treatment for moderate or severe COVID-19 may present major management challenges—especially the termination of corticosteroids and surgery under general anesthesia. In our series, 44% of patients developed ROCM after recovering from COVID-19. A three-month delay in ROCM after COVID-19 was noted in 7 patients. Smaller peaks can also be seen in the charts around the 30th, 45th, and 60th day. This makes it necessary to follow up COVID-19 patients within three months of recovery. It is possible to provide a symptom list, helpline for problems, and follow-up clinics to educate patients and their families for patients recovering from COVID-19.
Compared with mucormycosis in other anatomical parts, ROCM has obvious signs and symptoms and can be diagnosed early. All ophthalmologists should be aware of red flags/warning signs. According to our research, the most common signs and symptoms reported are vision loss, orbital/face pain, peri-eye/face edema, ptosis, and nasal discharge. All of this is obvious only at the time of inspection, and no additional skills or equipment are required.
The left and right PNS, orbits and brain are affected equally. Interestingly, 40% of patients have bilateral PNS involvement. Unless diagnosed and controlled, this increases the imminent risk of the two eye sockets. The most common is the diffuse involvement of PNS, and even the structures in the orbit. In 27% of cases, the medial orbit is mainly affected. This can be through the nasolacrimal duct or papyrus. The orbital apex is involved in 21% of patients. The apex of the heart may be affected without fulminant signs and symptoms. Although the eyes may be white and the exophthalmos may be mild, ptosis, other cranial nerve palsies, and local hypoesthesia and vision loss may be early signs of orbital apex involvement. Early diagnosis of orbital apex involvement may help minimize the risk of progression to cavernous sinus.
CNS involvement has been documented in 37% of COVID-19-related ROCM cases. [20] In our study, 21% (573 of 2669) patients had CNS involvement. Information about the main site of involvement was available to 539 patients, and 53% (285) had focal or diffuse cavernous sinus involvement or thrombosis. PNS and brain involvement were noted in three patients who did not involve the orbit. The proposed staging system allows patients to be assigned to the most severe stage based on the anatomical location and severity within it, so it can be extended to classify discontinuously affected cases.
Contrast-enhanced MRI is the preferred imaging method. It can describe soft tissue involvement earlier and is better than CT scan, especially in the case of orbital and brain involvement. Contrast-enhanced CT scans are relatively fast and can be used for patients where MRI is not feasible. Mucormycosis causes tissue necrosis, and bone erosion is not common, so CT scans may not support early diagnosis. In our series, 58% of patients preferred MRI, and 27% of patients received CT scans. In patients who cannot be given contrast agents, even plain CT still needs to assess the extent of the disease. PET-CT is a useful tool for detecting and evaluating treatment response, limited by the cost of repeated imaging. [3536]
Diagnostic nasal endoscopy allows rapid inspection and sampling from the nasal cavity. It is a simple, bedside but powerful tool that can diagnose stage 1 and early stage 2 suspected cases before clinical and radiological signs are obvious. Encouragingly, it did in 78.6% of the cases. Swabs of secretions, nasal mucosal inflammation, ulcers, necrosis, or eschar areas guided by a nasal endoscope may produce a better representative sample for direct microscopic examination, rather than random, blind nasal swabs.
The rapid diagnosis of mucormycosis can be achieved by direct microscopy using KOH wet patches, with or without fluorescent whitening agents such as matting agents and calcofluor white, which was done in 88.8% of the cases we analyzed. Microbiopsy from abnormal nasal mucosa or turbinate under the guidance of nasal endoscope can be performed in clinic or bedside. In addition to routine microbiology and histopathology, it can also provide rapid and representative samples for rapid diagnostic tests. [37] Frozen section, squeeze and imprint diagnosis can be performed on any fresh tissue, and it can also help determine a clear surgical margin during the operation. In our series, rapid histopathological tests were performed on only 239 cases, and its potential does not seem to be exploited, although further research is needed to determine the sensitivity and specificity of these tests.
Culture is required to identify the genus, species, and antifungal properties. However, 50% of cases may have false negative results due to improper sampling, tissue processing, and ongoing antifungal treatment. [3839] Histopathology of biopsy tissue may be necessary for the diagnosis of mucormycosis, detection of vascular infiltration, and differentiation of infection and contaminants. It can also reveal co-infections. The use of monoclonal antibodies for immunohistochemistry can be helpful, especially if the culture is negative. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry is a relatively new method, but it needs further verification. [37] Compared with histopathology and culture, PCR is also a rapid test that can be performed on serum and paraffin-embedded tissue. [3740] They can also be used to monitor treatment. In ROCM, early diagnosis is the key to survival, and these resources should be utilized and made more widely available.
The treatment of mucormycosis mainly includes the control of high blood sugar or any other risk factors, optimal surgical debridement and antifungal drug treatment. A large-scale review of 929 cases showed that the survival rate without intervention was only 3%, the survival rate with surgery alone was 57%, the survival rate with amphotericin deoxycholate was 61%, and the use of amphotericin and surgery at the same time The survival rate of debridement treatment is 70%. [11] Figure 19 shows the proposed management guidelines for COVID-19 related ROCM. [6]
Amphotericin B is the antifungal drug of choice for mucormycosis. It has been used in 88% of COVID-19-related ROCM patients. [20] Even in our series, 73% of patients received amphotericin B at the time of analysis. Induction should be a full dose (5 mg/kg body weight for stage 1a-3d, up to 10 mg/kg body weight for stage 4a)-4d) use liposomal amphotericin B. In the case of limited resources, amphotericin B deoxycholate or amphotericin B lipid complex can be used. The liposome form is preferred because of its less nephrotoxicity, so higher doses can be given over a longer period of time. Our data shows that 73% of patients received the liposome form. For logical reasons, some patients receive both liposome and deoxycholate types. For patients with impaired renal function, posaconazole and isaconazole have been found to be effective alternatives, but amphotericin B is still the treatment of choice. Some patients also receive these drugs as the main treatment, possibly because amphotericin B is not available.
Long-term antihypertensive oral antifungal treatment is required for 3-6 months. [374142] Isaconazole has been used in combination with amphotericin B or as a salvage therapy and monotherapy for mucormycosis. Isaconazole was approved in 2015 for the treatment of invasive aspergillosis and mucormycosis. VITAL studies have shown that in refractory cases and patients who are toxic to other antifungal drugs, isaconazole is not inferior to amphotericin B in combating mucormycosis as the main treatment method. It is safer and can be taken orally and intravenously (loading dose of 200 mg TDS on day 1 and day 2, then 200 mg per day). Although liver toxicity is less than other azoles, liver function should be monitored. It is also well tolerated for long-term use for more than six months. [4344] 26% of patients received antihypertensive therapy, and 95% of patients received posaconazole. With longer follow-up, these numbers are expected to rise.
A study from India showed that posaconazole is very effective as a rescue therapy for ROCM, and 67% of patients can save lives and completely disappear. [45] However, there is no data to support the use of combination therapy, nor is it recommended in any major treatment guidelines. [374142] Few retrospective clinical studies have concluded that echinocandin (caspofungin) and polyene (liposomal amphotericin B) are superior in combination therapy. [46] However, a phase III randomized placebo-controlled trial is needed to determine the benefit. [47] In our series, 23% of patients received the combination therapy with posaconazole, which is the drug of choice to add to amphotericin B.
In some case reports, intraorbital injection of amphotericin B deoxycholate at a concentration of 3.5 mg/mL has proven to be effective in saving lives and eyes. [484950] There is little data on its safety and vision saving potential. However, for diseases with such a high mortality rate and relatively small eyesight, it is increasingly used as an adjunct to medical treatment and surgical debridement.
In our series of cases, 21% of cases use PNS debridement as the main treatment. This is used for diagnostic and therapeutic purposes. 67% of patients underwent PNS debridement. 15% of patients underwent intraorbital resection, and 17% of patients underwent both PNS debridement and intraorbital resection. In a review of 80 ROCM cases published in COVID-19, 37% of patients required orbital resection. Orbital resection is usually performed in the absence of visual potential and diffuse orbital involvement, but the disease is limited to the orbit, and there is no or only a small amount of extension to the cavernous sinus. The decision is up to the attending physician, because there is no clear consensus on the indications and timing of endoorbital resection. There was no significant difference in survival rates with or without orbitectomy. [5152] Some case reports have described the treatment of intraorbital mucormycosis without intraorbital resection. Some series even found that orbital resection is not conducive to survival and allows the disease to spread further. A retrospective case series showed that for localized sinus diseases, the success rate of nasal cavity and paranasal sinus debridement was 94%. On the other hand, patients with orbital disease who received orbital dissection and sinus debridement treatment failed treatment and progressed/death in 89% of cases, although the systemic disease was more serious and more serious. [51525354] Analysis of our data indicates that in patients with limited intraorbital disease (3a, 3b), intraorbital resection does not significantly change the outcome. However, when it progresses to stages 3c and worse, intraorbital resection seems to help improve the outcome. The mortality and disease progression of patients with stage 3c and 3d ROCM who received endoorbital resection (33%) was compared with patients who did not receive endoorbital resection (22%) (p = 0.008). For patients with central nervous system involvement, contrary to standard understanding, our study found that orbitectomy is beneficial. Among patients treated with orbitectomy, 39% of patients experienced mortality and disease progression, compared with 52% of patients who did not undergo orbitectomy. Ideally, an orbitectomy should be performed after histopathological confirmation of the diagnosis. However, in the absence of prior histopathological confirmation, but with clinical-radiological-microbiological evidence to support the diagnosis of ROCM and record the disease progression, the treatment multi-specialty medical team and family members can decide to perform orbitectomy to save lives as a priority. Good counseling on the necessity and availability of cosmetic rehabilitation may help patients undergo this radical but potentially life-saving procedure.
The literature shows that ROCM patients without central nervous system involvement have better outcomes when they undergo surgical intervention than those who receive medication alone (mortality rate 14% vs. 63%, p = 0.01). Surgery had no effect on the survival of patients with CNS involvement (fatality 71% vs. 57%, p = 0.66). [20] The first part is supported by our data, in which patients without CNS involvement received PNS debridement, and the mortality and disease progression decreased from 32% to 13%. However, an analysis of patients with CNS involvement shows that PNS debridement is associated with better outcomes than no surgical intervention at all. Death and disease progression after surgery decreased from 67% to 39%. Among patients followed up for at least 3 weeks, 100% of patients with stage 4 ROCM who underwent endoorbital resection had stable residual or regressing disease (p = 0.03). Therefore, surgery may not be a contraindication for patients with CNS involvement, and it can indeed improve survival. These findings suggest that orbitectomy may play an important role in advanced disease, and patients with stage 3b or better disease may prefer a more conservative approach. Readers are reminded that these are preliminary results and follow-up of patients is not sufficient to provide convincing evidence.
ROCM is a rapidly progressing disease with a mortality rate of 30-90% in cases of brain involvement. [2033] For COVID-19-related cases, the overall mortality rate is estimated to be 31%. [2] The median time to death from the disease is 75 days. [20] The results of our series show that overall, the mortality rate of COVID-19-related ROCM is 14%, and disease progression occurs in 13% of cases. As patients follow up, these results may change over time. During the 3-week follow-up, 88% (120 out of 136) patients were in stable/resolving condition. Based on our results, it is clear that the proposed staging corresponds to the severity of the disease and the outcome of survival. Although prospective studies are needed to verify it, it is a breakthrough for diseases for which there was no logical classification or staging system based on the anatomical progress and severity of each anatomical location.
The data includes only those cases submitted for the study and may not represent the actual incidence of COVID-19-related ROCM in India. The follow-up of patients is limited and most of them are still under active treatment. Therefore, the result analysis should be interpreted with caution. However, we believe that these data are urgently needed to classify and guide management. Further study of these data over time will give a better understanding of the true survival outcomes. There are no large-scale data on COVID-19 patients who have not developed ROCM as a control group, which limits the scope for determining risk factors. Most of the contributors are ophthalmology institutions. Since these data are collected retrospectively, and most cases are jointly managed by different departments, whether in the same institution or separately, it is impossible to obtain all the information of each patient at the time of collection. However, in the future, it will allow the treatment team to gather information in a more unified way based on the understanding of important factors. As information changes very quickly, this is the most comprehensive data we currently have. Information on vaccination, RT-PCR status at the time of diagnosis of mucormycosis, other surgical procedures (such as pterygopalatine fossa removal, maxillectomy, palatectomy, and orbital resection) and the timing of intervention were not collected. This information may be useful Future research is very important.
COVID-19-related ROCM mainly affects middle-aged and elderly men, and most patients develop ROCM symptoms between the 10th and 15th days after the diagnosis of COVID-19. Delays in submission can occur up to three months. A three-month post-COVID-19 follow-up is recommended, and may be carried out at an official post-COVID-19 follow-up clinic. DM and corticosteroids are consistent, important and independent risk factors for COVID-19-related ROCM. Blood sugar control is very important for COVID-19 patients. Corticosteroids are part of the fight against COVID-19, but they must be used with caution only in patients with moderate to severe disease in accordance with the recommended dosage and duration. In the absence of DM, corticosteroids, and hospitalization, the risk of obtaining ROCM is very low. Future research should address ROCM issues related to healthcare, including violations of aseptic precautions during hospitalization and hospital air quality control as potential risk factors.
Periorbital and facial pain and edema, runny nose, ptosis, and vision loss are common symptoms and signs. Most patients are diagnosed at stage 3, when the orbit is already affected. The common clinical symptoms and signs should be identified in time, and then the diagnostic nasal endoscopy and endoscopic-guided nasal swabs should be used for microbiological evaluation and nasal cavity microbiopsy for rapid histopathological rapid diagnosis. Contrast-enhanced MRI is the preferred imaging method. If not, CT scan is recommended. ROCM should be staged and classified by a team consisting of intensive care physicians, infectious disease specialists, ophthalmologists/eye plastic surgeons, otolaryngologists, maxillofacial surgeons, neurosurgeons, radiologists, microbiologists, and pathologists And management.
In a COVID-19 environment waiting for culture and histopathological confirmation, antifungal treatment should be initiated empirically based on clinical or clinical radiology relevance. Liposome amphotericin B is the drug of choice, and every effort must be made to ensure its availability. PNS debridement should be thorough and can be repeated as needed. For patients with limited orbital involvement (stage 3a and b), intraorbital injection of amphotericin B may be a promising option. Patients with diffuse orbital involvement require orbitectomy. When PNS debridement and orbitectomy are included in its management, patients with CNS involvement seem to be better off. Longer follow-up is critical to the final prognosis, but the analysis of our largest series of real-world data does provide some insightful information that may help plan the management of COVID-19-related ROCM.
With the joint efforts of the multidisciplinary medical team and the government, it is necessary to actively respond to the ROCM related to COVID-19 like the disease itself. Accepting the fact that Indians are born with a high prevalence of DM, tropical climates are susceptible to mucormycosis, and moderate to severe COVID-19 cases require corticosteroids to save lives. We can look forward to seeing ROCM in the coming days. The logistical preparation to ensure adequate supply of amphotericin B and the creation of well-equipped and dedicated multidisciplinary ROCM management center regional centers, each of which is connected to the spokes of COVID-19 treatment facilities, may help save the lives and lives of these patients. Eye.
There is no conflict of interest.
Corticosteroids; COVID-19 related ROCM; diabetes; mucormycosis; intraorbital resection; sinus debridement; rhino-orbital-cerebral mucormycosis; staging of rhino-orbital-cerebral mucormycosis
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Corticosteroids COVID-19 COVID-19-related ROCM Diabetic Orbital Mucormycosis Orbital Debridement Sinus Debridement Rhinocorbital-Cerebral Mucormycosis Staging of Rhino-orbital-Cerebral Mucormycosis
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