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A retrospective clinicopathological analysis of rhino-orbital mucormycosis in second wave of COVID-19


 Department of Pathology, Shri Guru Ram Rai Institute of Medical and Health Sciences, Dehradun, Uttarakhand, India

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Date of Submission18-Jul-2021
Date of Decision10-Nov-2021
Date of Acceptance30-Dec-2021
Date of Web Publication13-Jan-2023
 

   Abstract 


Background: During the present surge of COVID-19 positive cases, concurrent multifold increase in the incidence of mucormycosis cases has resulted into significant morbidity and mortality. We retrospectively evaluated the clinicopathological features along with microbiological examination findings in histologically diagnosed cases of rhino-orbital mucormycosis. Material and Methods: All the H and E and special stained slides of included mucormycosis cases were retrieved from the records and were evaluated with microbiological findings including screening KOH mount examination and culture results. Results: Out of 16 cases with available details, 10 cases had the previous history of diabetes mellitus. The most frequent single site of involvement was maxillary sinus (7/25) followed by nasal cavity, orbit, ethmoid and sphenoid sinuses. While comparing the histological diagnosis with KOH mount findings and culture results, 15 cases revealed consistent results. Conclusion: A high clinical suspicion, monitoring, early diagnosis, and timely management can improve the morbidity and mortality of this life-threatening complication.

Keywords: COVID-19, culture, KOH, mucormycosis, rhino-orbital


How to cite this URL:
Thakur B, Ahuja S, Acharya S, Kaushik S. A retrospective clinicopathological analysis of rhino-orbital mucormycosis in second wave of COVID-19. Indian J Pathol Microbiol [Epub ahead of print] [cited 2023 Feb 2]. Available from: https://www.ijpmonline.org/preprintarticle.asp?id=367703





   Introduction Top


India is experiencing a second wave of COVID-19, with total 3,07,52,950 cases and total 4,05,939 deaths reported as of this writing.[1] During the surge of COVID-19 positive cases, lack of oxygen supply or hospital beds or medicines of critical use or injudicious use of drugs has increased the burden on the health care system. This syndemic of invasive mucormycosis in the present crisis has given rise to higher morbidity and mortality rates despite surgical debridement and antifungal therapy. That is why early diagnosis, prompt and judicious treatment of mucormycosis are a need of hour for improved outcome.

Therefore, in the present study, we retrospectively analyzed the 25 cases of rhino-orbital mucormycosis in the second wave of current pandemic. We evaluated the clinicopathological features along with microbiological examination findings in these cases.


   Material and Methods Top


In the present study, we included 25 histomorphologically diagnosed cases of mucormycosis involving paranasal sinuses, nasal cavity, ocular structures or orbital soft tissue, from the records of last 3 months in histopathology section. Relevant available demographic or clinicoradiological details were recorded from the histopathology requisition forms. All of the included patients were either COVID-19 positive or had recovered from the infection.

The tissue samples including resected or debridement tissue or exenteration specimens were received in 10% neutral buffered formalin and grossed as per standard laboratory protocol. Sections of 3–5 μm were prepared from paraffin-embedded blocks using embedding station (Leica EG1150 H + C) and stained with Hematoxylin and Eosin (H and E). Additional sections were taken for special histochemical stains to highlight fungal element, i.e., Periodic Acid Schiff (PAS) and Gomori's silver methanamine stain (GMS).

All the H and E as well as special stained slides were retrieved from the records and were evaluated independently by two pathologists for histomorphological aspects. Final diagnosis was considered with consensus. Additionally, microbiological findings including screening KOH mount examination and culture results were also documented and tabulated.


   Results Top


Out of 25 cases, the majority of patients (68%) belonged to 40–60 years of age group.

The clinicopathological findings have been summarized in [Table 1].
Table 1: Comparative analysis of various clinicopathological features of Mucomycosis cases in present study

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Multiple paranasal sinuses involvement was more commonly seen (32%; 8/25) including 06 male and 02 female patients, while the most frequent single site of involvement was maxillary sinus (28%; 7/25). Bilateral sinuses were involved in 07 cases.

Histomorphologically, 03 cases were considered as mixed fungal infection, while the rest of cases were reported as mucormycosis or invasive mucormycosis [Figure 1] and [Figure 2]. Necrosis and fibrinoinflammatory exudates were noted in all the tissue specimens. Evidence of angioinvasion and adjacent soft tissue (muscle bundles or adipose tissue) is noted in 14 and 07 cases, respectively [Figure 1]d. Foreign body granuloma formation [Figure 1]f is noted 11 cases, including 09 male and 02 female patients [Table 1].
Figure 1: (a) Broad aseptate fungal hyphae of Mucormycosis in necrotic debris (H and E, 100×). (b and c) Highlighted broad aseptate fungal hyphae of Mucormycosis [GMS (b) and PAS (c) 100 ×]. (d) Broad aseptate fungal hyphae infiltration in vessel and muscle bundles (H and E, 100×). (e) GMS stain highlighting the angioinvasion by mucormycosis hyphae (GMS, 100×). (f) Foreign body giant cell reaction around fungal hyphae (H and E, 400×)

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Figure 2: (a–c) Mixed infection showing broad aseptate and septate filamentous fungal hyphae in H and E (a), GMS (b), and PAS (c) stain (100×). (d and e) Broad aseptate fungal hyphae of Mucormycosis with evidence of bone infiltration [H and E (e) and GMS (f) 100×]

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While comparing the histological diagnosis with KOH mount findings and culture results, 15 cases revealed consistent results and 08 cases showed comparable results with KOH preparation alone but not with culture. In 03 cases with histological suspicion of mixed fungal infection, one case was consistent with mixed infection and the rest 02 cases were consistent with mucormycosis with culture results. Four cases revealed no growth, while four cases showed growth of aspergillus species in culture findings. No details regarding microbiological examination were available in 02 cases [Table 2].
Table 2: Comparison of histological diagnosis with KOH mount and culture results in present study

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Taking culture growth as a gold standard, the diagnostic accuracy of histomorphological diagnosis was 78.9%.


   Discussion Top


Mucormycosis infection is caused by the family of Mucoraceae of the class of Phygomycetes or Zygomycetes, and characterized by rapid infarction or necrosis of host tissues due to angioinvasion by fungal hyphae.[2] The prevalence of mucormycosis is nearly 80 times higher (0.14 per 1000) in India as compared to developed countries.[3] Unfortunately, higher prevalence of poorly controlled diabetes mellitus, widespread or injudicious use of steroids, and hot and humid environment in India are likely to have a major contribution to several folds increase in superadded bacterial or fungal infections, particularly of rhino-orbital mucormycosis.

Host defense is primarily through macrophages inhibiting the germination of spores and neutrophils using the oxidative burst to kill proliferating hyphal elements. In addition to defective function of these cells, the cytokine storm seen in COVID-19 along with impaired cell-mediated immunity in the form of reduced CD4+ and CD8+ T cell counts and extensive use of corticosteroids may predispose to increased incidence of the superadded infections.[4] Critically ill patients in intensive care units, mechanical ventilation, prolonged hospitalization, immunosuppressive states especially in uncontrolled diabetes mellitus or acquired immunodeficiency syndrome or hematological malignancies or patients who underwent organ transplantation are the known contributory risk factors for opportunistic fungal infections.

Similar to our findings, a few case reports and case series observed patients of 40–60 years age group with rhinocerebral mucormycosis infection.[2],[5],[6],[7] Similarly, the most common presentation was noted sinusitis or pansinusitis as well as adjacent bony erosion or intracranial extension in a significant proportion of the patients in the literature searched.[2],[8],[9],[10] Moorthy et al.[2] also reported majority of the mucormycosis and COVID-19 positive patients with poorly controlled diabetes mellitus (DM, 16/18) in their case series. We observed 10 patients with history of DM with known status of 16 patients.

We observed various histological findings including necrosis, fibrinoinflammatory exudates, foreign body giant cell reaction, granuloma formation, angioinvasion, and soft tissue infiltration in a variable number of patients, which reflect variable host reaction to the invasive disease. Radiological evidence consistent with mucormycosis has been described in the majority of the patients previously similar to our findings.[5],[10],[11],[12]

In our experience, morphological diagnosis of mucormycosis from tissue specimens and KOH mount examination showed 100% concordance; however, comparing the culture growth results with histomorphology, four cases revealed discordant results exhibiting growth of aspergillus species. This discordance may be related to technical issues like type of specimen, inoculation error, mixed infection with one type of fungal overgrowth, or interpretation error or morphological changes during tissue processing. Airborne spores of Mucorales genera can cause contamination of laboratory media. That is why positive clinical culture result for these molds has to be correlated with the patient's history and clinical findings to consider as the cause of disease. In case of diagnostic dilemma, additional specific tests including polymerase chain reaction or immunohistochemistry (monoclonal antibodies against Aspergillus galactomannan) may help to resolve the issue.


   Conclusion Top


To the best of the authors' knowledge, this is the first evaluation including clinicopathological as well as microbiological findings in more than 20 histologically mucormycosis cases from India. In view of the manifold increase in the incidence of mucormycosis during the second wave of COVID-19, all patients should be monitored for this life-threatening complication resulting from post-covid or post-treatment immunosuppression. A high clinical suspicion, early diagnosis, and timely management can improve the morbidity and mortality.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
WHO COVID-19 Dashboard. Geneva: World Health Organization; 2020. Available from: https://covid19.who.int/. [Last accessed on 2021 Jul 09].  Back to cited text no. 1
    
2.
Moorthy A, Gaikwad R, Krishna S, Hegde R, Tripathi KK, Kale PG, et al. SARS-CoV-2, uncontrolled diabetes and corticosteroids—An unholy trinity in invasive fungal infections of the maxillofacial region? A retrospective, multi-centric analysis. J. Maxillofac. Oral Surg 2021;20:1-8.  Back to cited text no. 2
    
3.
Singh AK, Singh R, Joshi SR, Misra A. Mucormycosis in COVID-19: A systematic review of cases reported worldwide and in India. Diabetes Metab Syndr 2021;15:102146.  Back to cited text no. 3
    
4.
Sharma S, Grover M, Bhargava S, Samdani S, Kataria T. Post corona virus disease mucormycosis: A deadly addition to the pandemic spectrum. J Laryngol Otol 2021;135:442-7.  Back to cited text no. 4
    
5.
Mishra N, Mutya VSS, Thomas A, Rai G, Reddy B, Mohanan AA, et al. A case series of invasive mucormycosis in patients with COVID-19 infection. Int J Otorhinolaryngol Head Neck Surg 2021;7:867-70.  Back to cited text no. 5
    
6.
Garg D, Muthu V, Sehgal IS, Ramachandran R, Kaur H, Bhalla A, et al. Coronavirus disease (Covid-19) associated mucormycosis (CAM): Case report and systematic review of literature. Mycopathologia 2021;186:289-98.  Back to cited text no. 6
    
7.
Mekonnen ZK, Ashraf DC, Jankowski T, Grob SR, Vagefi MR, Kersten RC. Acute invasive rhino-orbital mucormycosis in a patient with COVID-19-associated acute respiratory distress syndrome. Ophthalmic Plast Reconstr Surg 2021;37:40-2.  Back to cited text no. 7
    
8.
Werthman-Ehrenreich A. Mucormycosis with orbital compartment syndrome in a patient with COVID-19. Am J Emerg Med 2021;42:264.e5-8.  Back to cited text no. 8
    
9.
Revannavar SM, Supriya PS, Samaga L, Vineeth VK. COVID-19 triggering mucormycosis in a susceptiblepatient: A new phenomenon in the developing world? BMJ Case Rep 2021;14:e241663.  Back to cited text no. 9
    
10.
Veisi A, Bagheri A, Eshaghi M, Rikhtehgar MH, Kanavi MR, Farjad R. Rhino-orbital mucormycosis during steroid therapy in COVID-19. Eur J Ophthalmol 2021:11206721211009450. doi: 10.1177/11206721211009450.  Back to cited text no. 10
    
11.
Satish D, Joy D, Ross A, Balasubramanya. Mucormycosis coinfection associated with global COVID-19: A case series from India. Int J Otorhinolaryngol Head Neck Surg 2021;7:815-20.  Back to cited text no. 11
    
12.
Mehta S, Pandey A. Rhino-orbital mucormycosis associated with COVID-19. Cureus 2020;12:e10726.  Back to cited text no. 12
    

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Correspondence Address:
Brijesh Thakur,
Department of Pathology, SGRRIM&HS, Patel Nagar, Dehradun - 248001, Uttarakhand
India
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijpm.ijpm_732_21



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    Tables

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    -  Ahuja S
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