| Abstract|| |
Context: Coinfection and superadded infections in patients with coronavirus disease 2019 (COVID-19) has been reported on multiple series. The emerging second wave of the pandemic has come with a lot of changes, especially in developing countries like India. One of such changes is sudden, significant rise in mucormycosis cases. Aims: To find out clinicopathological association of invasive mucormycosis with COVID-19 infection status and immunocompromised state. Settings and Design: A cross-sectional study done at a tertiary care centre. Methods and Material: All cases admitted in the dedicated mucormycosis ward between 1-06-2021 and 15-06-2021 were included in the study. The cases were admitted with suspicion of mucormycosis. The histopathological results were correlated with KOH mount and radiological reports. The clinicopathological association of occurrence of mucormycosis in post-covid and non-COVID patients along with other risk factors. Statistical Analysis Used: Odds ratio, chi square test were used to find the association using MS Excel 2010 and SPSS. Results: Thirty-six (81.82%) cases were of the post-COVID status, and 8 cases were non-COVID status. Out of 36 post-COVID patients, 33 (91.67%) showed evidence of invasive mucormycosis and of 8 non-COVIDpatients, 7 had evidence of mucormycosis (odds ratio = 1.57). Out of the total diagnosed cases of mucormycosis, 21 (52.5%) patients were known cases of diabetes mellitus (DM), and 7 (17.5%) cases of newly diagnosed hyperglycemia. Thirty (75%) patients out of 40 had some form of immunocompromised state. This shows statistically significant association of DM and immunocompromised state with the occurrence of mucormycosis in post-COVID patients (chi square value2 = 6.891, P value = 0.008). Twenty-five patients had the history of steroid use during the treatment of COVID-19. Conclusions: The infection with COVID-19 definitely increases the odds of contracting mucormycosis, but most of the cases had diabetes mellitus. So, it is possible that COVID-19 virus predisposes individuals to invasive fungal infection by precipitating DM.
Keywords: COVID19, diabetes mellitus, invasive fungal infection, mucormycosis
|How to cite this article:|
Varshney M, Saxena A, Binnani N, Kumar V, Vyas S P. Clinicopathological association of mucormycosis in COVID 19 pandemic. Indian J Pathol Microbiol 2023;66:101-5
|How to cite this URL:|
Varshney M, Saxena A, Binnani N, Kumar V, Vyas S P. Clinicopathological association of mucormycosis in COVID 19 pandemic. Indian J Pathol Microbiol [serial online] 2023 [cited 2023 Feb 2];66:101-5. Available from: https://www.ijpmonline.org/text.asp?2023/66/1/101/367973
| Introduction|| |
Coronavirus disease 2019 (COVID-19) syndrome caused by the 2019 novel coronavirus (2019-nCoV) or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) evolved as a global pandemic since December 2019 when it was first reported in Wuhan, China. Since its inception, the COVID-19 pandemic presented with surprises and challenges to the world and to the whole medical community. Coinfection and superadded infections in patients with COVID-19 have been reported on multiple series, being bacterial in origin the most frequent; and fungal infection being reported only in severe cases.,
The emerging second wave of the pandemic has come with a lot of changes, especially in developing countries like India. One of such changes is a sudden, significant rise in mucormycosis cases. Mucormycosis is an opportunistic fungal infection caused by fungi classified within Phygomycetes, subclass Zygomycetes, order Mucorales, family Mucoraceae. The rhino-orbital-cerebral localization is the most frequent form (44%–49%), followed by the pulmonary and cutaneous localizations (10%), then the gastrointestinal localization and the disseminated form. The incidence rate of mucormycosis globally varies from 0.005 to 1.7 per million population. Whereas, in the Indian population, its prevalence is 0.14 per 1000, which is about 80 times higher than in developed countries. The main reason is the second-largest population and an increasing number of cases of diabetes mellitus (DM). Importantly, DM has been the most common risk factor linked with mucormycosis in India although hematological malignancies and organ transplant take the lead in Europe and the USA.
This study aims at finding the clinicopathological association of mucormycosis with COVID- 19 status, immunocompromised state of the patient, and the histopathological variations seen in the COVID pandemic.
| Subjects and Methods|| |
This was a cross-sectional study conducted at our department at a tertiary care center. All cases admitted in the dedicated mucormycosis ward and their biopsies sent for examination to the pathology department between 1st June 2021 and 15th June 2021 were included in the study. The cases were admitted with clinical and radiological suspicion of mucormycosis. The patients were then investigated with KOH mount, culture, and histopathological examination of involved tissue. The COVID status was ascertained by RT-PCR test and HRCT chest score of the patients. All the biopsies were fixed in 10% buffered formalin and grossed as per protocol. Sections are stained with Haematoxylin and Eosin stain and examined under a light microscope. Special stains like Periodic Acid Schiff and Gomori methenamine silver (GMS) were done for confirmation. The histopathological results were correlated with KOH mount and radiological reports. The clinicopathological association of occurrence of mucormycosis in post-COVID and non-COVID patients along with other risk factors like diabetes mellitus, immunocompromised state, and long-term steroid use was done using statistical methods. The approval has been taken dated 1/6/2021.
| Results|| |
We received total of 44 samples during the study period with clinical suspicion and radiological evidence of invasive mucormycosis. Of these cases, 34 were male patients and 10 were female patients with a male: Female ratio of 3.4. The age range being between 16 years of age and 80 years of age with a mean age of 48 years. The maximum number of patients was in the sixth decade of life with 11 (24.44%) cases followed by the fourth and seventh decade with 9 (20.00%) cases each, respectively [Figure 1]. We received nasal biopsies, cutaneous tissue, eye (excision), and maxillary tissue. Nasal biopsies (n = 38) were the most common tissue received.
Out of the 44 cases, most of the patients (n = 27) presented with complaints of swelling and pain in the cheek with nasal stuffiness. Eight patients presented with redness and swelling of the eye with sudden onset of pain in movement of eyes, three patients presented with blackish discoloration of molar teeth with swelling and pain in the jaw, and two patients presented with blackish discoloration and ulceration over the skin. Few patients showed a combination of symptoms of pain and swelling of the cheek and eye redness and pain. With COVID status and clinical findings and suspicion of invasive mucormycosis, radiological investigations (Contrast-enhanced CT and MRI) were done initially. The patients were admitted to dedicated mucor ward on radiological suspicions of invasive fungal infection (? mucormycosis). Further on KOH mount and histopathological examination, a total of 40 (90.91%) cases showed evidence of mucormycosis. A total of 34 cases were reported positive for fungal hyphae on KOH mount, and 10 cases were reported negative. On histopathological examination, 40 cases showed evidence of invasive mucormycosis, and 8 cases which were negative on KOH mount showed histopathological evidence of invasive fungal infection. Of four cases reported negative for mucormycosis on histopathological examination, one case was diagnosed as candida spp. infection, two cases of the nasal polyp with acute chronic inflammation, and one case of nonspecific inflammation on bronchial biopsy.
A total of 36 (81.82%) cases were post-COVID status, and 8 cases were non-COVID status. Out of 36 post-COVID patients, 33 (91.67%) showed evidence of invasive mucormycosis and of 8 non-COVID patients, 7 had evidence of mucormycosis (odds ratio = 1.57).
Out of the total diagnosed cases of mucormycosis, 21 (52.5%) patients were known cases of diabetes mellitus and 7 (17.5%) cases of newly diagnosed hyperglycemia. Thirty (75%) patients out of 40 had some form of immunocompromised state. [Table 1] This shows statistically significant association of DM and immunocompromised state with the occurrence of mucormycosis in post-COVID patients (∑2 = 6.891, P value = 0.008). Twenty-five patients had a history of steroid use during the treatment of COVID-19.
On pathological examination, the most common specimen was of rhino-ocular mucormycosis with 38 cases, two specimens of cutaneous mucor, and one of suspected bronchial mucormycosis. On gross examination of exenteration of eye specimens (n = 6), there was grey-black discoloration on the outer surface with a variable amount of necrosis. Two cases of cutaneous mucormycosis showed black discoloration of the skin with ulceration and necrotic material. [Figure 2] Four cases of unilateral maxillectomy showed necrotic bone with grey-black discoloration of adherent soft tissue. On microscopic examination, all 40 cases with clinical and microbiological evidence of mucormycosis showed common findings of the presence of necrosis and acute inflammation. Necrosis was seen ranging from 30% to 85%. Twenty-eight (70%) cases showed the presence of several broad aseptate or sparsely septated fungal hyphae suggestive of Mucorale spp. [Figure 3]a and [Figure 3]b It was observed that the density of fungal colonies was more in the necrotic debris. [Figure 4]a, [Figure 4]b, [Figure 4]c Foreign body giant cell reaction was seen in 9 cases. [Figure 3]c Chronic inflammatory infiltrate in form of lymphocytes and plasma cells were seen in 27 cases. Two cases showed clear evidence of vascular invasion. [Figure 4]d [Table 2] Of four negative cases, one case was reported as candida infection, one nasal polyp without fungal involvement, and the other 2 cases showed only inflammatory infiltrate.
|Figure 2: (a) showing gross appearance of cutaneous mucor mycosis involving the anterior abdominal wall. (b) showing specimen of exentration of the eye with blackish discoloration on the outer surface|
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|Figure 3: Showing fungal hyphae (a) hyphae branching at right angle with inflammation, H and E 40 × (b) colony of fungal hyphae in acute inflammation and necrosis, H and E 40 × (c) Showing giant cell reaction with chronic inflammation, H and E 40 ×|
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|Figure 4: Showing fungal colony within necrosis GMS (a) on magnification 10 × (b) on 40 ×. (c) Showing broad aseptate fungal hyphae with branching, GMS 40 ×. (d) Showing vascular invasion by fungal hyphae, GMS 40 ×|
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On follow up of patients till the time of writing this paper, most of the patients (n = 37) were in postoperative treatment with amphotericin B or posaconazole. Three patients (6.8%) expired due to complications of multiple comorbidities during treatment.
| Discussion|| |
Mucormycosis is an acute and potentially fatal fungal infection caused by fungi related to the Mucoraceae family. It is categorized in rhinocerebral, cutaneous, disseminated, gastrointestinal, or pulmonary regions. It is most commonly encountered in immuno-compromise patients. Diabetes Mellitus is one of the most common risk factors documented in thethe literature. Invasive mucormycosis is a rare entity but with the second wave of COVID-19 pandemic, we saw a steep surge in mucormycosis cases in our OPDs. A similar increase in mucormycosis cases has been reported from various other parts of India and other parts of the world. In a recent systematic review conducted until April 9, 2021 by John et al. that reported the findings of 41 confirmed mucormycosis cases in people with COVID-19, DM was reported in 93% of cases, whereas 88% were receiving corticosteroids. We reported similar findings with around 70% COVID-positive cases had previously diagnosed or newly detected DM. This shows that the presence of DM in COVID patients definitely increases the odds of contracting mucormycosis, but most patients with invasive mucormycosis had previous or new diabetes mellitus.
The term “rhino-orbito-cerebral zygomycosis (ROCM)” refers to the spectrum of the disease, which starts in the sino-nasal tissue (nasal cavity and paranasal sinuses) (limited sino-nasal disease), progresses to the orbits (limited rhino-orbital disease), and finally affects the central nervous system (rhino-cerebral disease). Rhino-orbital mucormycosis was the most common type of infection found in our study with 95% cases followed by cutaneous, which is consistent with the study done by Prakash H, et al. who published reports of different studies with rhino-orbital mucormycosis as the most common clinical form of invasive mucormycosis followed by cutaneous mucormycosis.
In our study, out of the total 40 cases which showed histopathological evidence of mucormycosis, eight cases were negative on KOH mount study. Similar observations were reported by Satish, Deepthi et al. in their study where seven patients who tested negative on KOH mount, tested positive for zygomycetes on histopathological examination. The possible reason for this difference may be cases of deep infection like maxillary sinus, inadequate superficial sample for KOH mount, and or presence of excessive inflammation at the site of sampling.
Out of the two cases of cutaneous mucormycosis, one patient had a history of trauma followed by incision and drainage procedure. Prakash H, et al. also reported that the majority of the patients present with cutaneous mucormycosis after trauma, burns, and nosocomial infections at the surgery or injection site.
Ashina Goel et al. reported 33 cases of zygomycosis, all the cases of zygomycosis showed varying amounts of necrosis, and the density of fungal organisms was higher in necrotic tissues. The percentage of necrosis varied from 2% to 95%, and the density of fungal organisms was highest in necrotic tissues. Angioinvasion was seen in 17 (51%) of a total of 33 patients. We observed similar results in terms of necrosis and acute with chronic inflammation, but angioinvasion was reported in only two cases in our study. This variation may be due to the reason that most of the tissue samples in our study are tiny biopsies. We did not observe any significant difference in histopathological features of mucormycosis in cases of post-covid patients as compared to non-covid patients.
| Conclusion|| |
COVID-19 pandemic has brought multiple challenges to the medical community. With emerging pandemic, causing immune-compromised state, precipitating diabetes mellitus along with rampant use of immunosuppressant, there is a rise in occurrence of coinfection with fungal etiology causing a sudden rise in cases of invasive mucormycosis, esspecially in the second wave of this pandemic. The infection with COVID-19 definitely increases the odds of contracting mucormycosis but most of the cases had diabetes mellitus. So, it is possible that COVID-19 virus predisposes individuals to invasive fungal infection by precipitating DM.
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Conflicts of interest
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] [Full text]
Department of Pathology, SP Medical College, Bikaner, Rajasthan
Source of Support: None, Conflict of Interest: None
[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1], [Table 2]