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| ORIGINAL ARTICLE |
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| Year : 2022 | Volume
: 9
| Issue : 2 | Page : 127-131 |
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Mucormycosis in COVID-19 patients: A tertiary care experience
Sarandeep Singh Puri1, Jyoti Mishra1, Monal Trisal1, Ashish Kumar Mandal1, Suparna Dubey2
1 Department of Pathology, School of Medical Sciences and Research, Sharda University, Greater Noida, Uttar Pradesh, India
2 Department of Pathology, Andaman and Nicobar Islands Institute of Medical Sciences, Port Blair, India
| Date of Submission | 28-Jul-2022 |
| Date of Decision | 13-Aug-2022 |
| Date of Acceptance | 26-Sep-2022 |
| Date of Web Publication | 29-Dec-2022 |
Correspondence Address:
Dr. Ashish Kumar Mandal
Department of Pathology, School of Medical Sciences and Research, Sharda University, Plot No. 32-34, Knowledge Park III, Greater Noida - 201 306, Uttar Pradesh
India
 Source of Support: None, Conflict of Interest: None
DOI: 10.4103/amit.amit_66_22
Introduction: Zygomycetes consisting of Mucorales order is a group of fungal infections. These species cause life threatening opportunistic fungal infections mucormycosis. This infection is highly prevalent in immunocompromised. During the 2nd wave of Covid 19 pandemic corticosteroid treatment was used which has been linked to development of Mucormycosis. In our tertiary care teaching hospital we saw that patients suffering from Covid-19 infections developed mucormycosis. We present these cases in our study. To study the clinical, demographical,and Laboratory parameters in Covid-19 patients with Mucormycosis. Material and Methods: Retrospective Study. All biopsy proven cases of Mucormycosis (which developed after Covid-19 infection) were included. Relevant Clinical Demographics and Laboratory data was retrieved from the available case sheets. The data was tabulated in Excel sheet and further reviewed. Results: A total of 22 patients were diagnosed as suffering from mucormycosis majority were unvaccinated. 11 patients out of 22 (50%) started manifesting mucormycosis within one week of COVID infection. All the patients who had only single comorbidity (22.72%) suffered from mild disease and patient who had more than one comorbidity suffered from moderate (27.27%) to severe (50%) COVID infection. Conclusion: It is suggested that patients with Covid-19 infection are at risk for development of opportunistic fungal infections like Mucormycosis. Hence the physicians who are involved in treating such patients must be mindful of the fact that mucormycosis can develop in them. Histopathology helps in establishing a concrete diagnosis of Mucormycosis.
Keywords: COVID-19, fungal, mucormycosis
How to cite this article:
Puri SS, Mishra J, Trisal M, Mandal AK, Dubey S. Mucormycosis in COVID-19 patients: A tertiary care experience. Acta Med Int 2022;9:127-31 |
| Introduction | |  |
Zygomycetes consisting of Mucorales order is a group of fungal infections. These species cause life-threatening opportunistic fungal infections and mucormycosis. This infection is highly prevalent in immunocompromised.[1] During the second wave of the COVID-19 pandemic, corticosteroid treatment was used which has been linked to the development of mucormycosis. The steroids affect the activity of macrophages due to which macrophages are not able to stop the germination of these fungal spores.[2] The clinical spectrum of its presentation progresses systemically in an aggressive fashion in the human body and affects multiple organs.[3],[4]
In our tertiary care teaching hospital, we saw that patients suffering from COVID-19 infections developed mucormycosis. We present these cases in our study. This study aims to study the clinical, demographical, and laboratory parameters in COVID patients with mucormycosis.
| Materials and Methods | | |
Study design
This study was a retrospective study.
Duration of study
This study was conducted from April 2021 to September 2021.
Sample size
The sample size of this study is 22 cases.
Inclusion criteria
All biopsy-proven cases of mucormycosis (which developed after COVID-19 infection) were included in the study.
Method of collection of data
Relevant clinical, demographics, and laboratory data were retrieved from the available case sheets. The data were tabulated in an Excel sheet and further reviewed.
Statistical analysis
Statistical analysis will be done with student t-test and ANOVA using the SPSS version 26 (IBM Corp. IBM SPSS Statistics for Windows, Version 26.0. Armonk, NY: IBM Corp).
Ethical consideration
Complete confidentiality regarding the subject's information was maintained.
| Results | | |
Twenty-two patients were diagnosed as suffering from mucormycosis, and the majority were unvaccinated. Eleven patients out of 22 (50%) started manifesting mucormycosis within 1 week of COVID infection [Table 1].
Patients who had comorbidity such as diabetes mellitus (DM) (n = 6), chronic kidney disease (CKD) (n = 4), chronic obstructive pulmonary disease (COPD) (n = 3), and hypertension (n = 3) suffered from mucormycosis with in 1st week of admission [Table 2]a, [Table 2]b, [Table 2]c, [Table 2]d.
All the patients who had only single comorbidity (22.72%) suffered from mild disease, and patients who had more than one comorbidity suffered from moderate (27.27%)-to-severe (50%) COVID infection.
Three/five (60%) patients with single comorbidity required steroids, whereas 14/17 (82.35%) patients with greater than one comorbidity required steroids.
About 92.3% of DM, 100% cases of CKD, 100% cases of COPD, and 100% cases of hypertension were on continuous oxygen [Table 5].
Seven/ten (70%) cases with computed tomography (CT) value of reverse transcription-polymerase chain reaction (RT-PCR) test <20 showed a severe degree of COVID-19 infection [Table 6]a.
Majority of cases in 12/13 (92.30%) who showed CT value of RT-PCR test <20 were on steroids [Table 6]b.
Thirteen/seventeen (76.47%) cases who had CT value <20 needed oxygen [Table 6]c.
Total leukocyte count (TLC) count was higher in 21/22 (95.45%) cases who had the onset of mucormycosis in <5 weeks [Table 7]. | Table 7: Relation of total leukocyte count with the onset of mucormycosis
Click here to view |
Low lymphocyte count was seen in 21/22 (95.45%) cases who had onset of mucormycosis in <5 weeks [Table 8].
About 10/21 (47.61%) cases with severe degree of COVID-19 infection showed higher values of interleukin (IL)-6 as compared to 11/21 cases (52.38%) who had lesser IL-6 levels and were mild to moderate in severity [Table 9]a.
IL-6 levels were more in 17/21 (80.95%) cases who required oxygen therapy [Table 9]b.
IL-6 levels were higher in 11/21 (52.38%) cases with the onset of mucormycosis <1 week [Table 9]c.
D-dimer levels were higher in 10/18 (55.55%) cases with the onset of mucormycosis <1 week [Table 10] C-reactive protein (CRP) levels were highest in 10/19 (52.63%) cases who were severe in the severity of COVID 19 infection followed by 5/19 (26.31%) cases who were moderate in severity and were lowest in 4/19 (21.05%) cases [Table 11].
Thirteen/twenty-two (59.09%) patients were blood group A positive.
Positive patients suffered from severe COVID infection (8/13, i.e., 61.53%) [Table 12]a.
Positive patients suffered from severe COVID infection, 8/13 (61.53%) needed steroids [Table 12]b.
Positive patients suffered from severe COVID infection, 10/13 (76.92%) needed oxygen [Table 12]c.
Non-A blood group showed higher CRP, IL-6, and prothrombin time (PT) value compared to A blood group though D-dimer was more in blood group A [Table 13]. | Table 13: Mean values of prothrombin time, interleukin-6, D-dimer, and C-reactive protein in A versus non-A blood groups
Click here to view |
| Discussion | | |
Diabetes, hypertension, smoking, and another comorbidity status single/multiple have been existing for decades. Out of this, DM is known to develop superadded bacterial and fungal infections. However, none of them had the extent of mucormycosis that had been reported worldwide, particularly in India. This article makes an attempt to bring out precipitating factors and the possible reason as to why and what changes were brought about by COVID-19 that suddenly led to an increased number of mucormycosis cases at unprecedented levels.
A total of 22 patients were diagnosed as suffering from mucormycosis and the majority were unvaccinated. Only three patients who received vaccination but had multiple comorbidities such as DM and COPD also developed superadded mucor infection. A reduction in CD4+ T-lymphocytes has been observed which is responsible for opportunistic fungal infections in these cases.[5],[6],[7],[8]
It was also found that 11 patients out of 22 (50%) started manifesting mucormycosis within 1 week of COVID infection. None of the patients had any mucormycosis beyond 5 weeks of recovery. However, patients who had comorbidities such as DM (six cases), CKD (four), COPD (three), and hypertension (three) suffered from mucormycosis within 1st week of admission. It was also pertinent to find that all these patients were on steroids and oxygen. The treatment plan included steroids for critical COVID patients. The steroids were responsible for hyperglycemia and the development of invasive fungal infections.[9],[10],[11]
All the patients who had only single comorbidity (22.72%) suffered from mild disease and patients who had more than one comorbidity suffered from moderate (27.27%)-to-severe (50%) COVID infection [Table 3]. Three/five (60%) patients with single comorbidity required steroids, whereas 14/17 (82.35%) patients with greater than one comorbidity required steroids [Table 4]. About 92.3% of DM, 100% cases of CKD, 100% cases of COPD, and 100% cases of hypertension were on continuous oxygen [Table 5]a, [Table 5]b, [Table 5]c, [Table 5]d. Significant angiotensin-converting enzyme (ACE)-2 receptor expression has been seen in such groups of patients with single or multiple comorbidities and helps in viral entry into the host cells.[12]
CT values of the RT-PCR test were also compared with different parameters. CT value had no relation with clinical manifestations such as fever slurred speech, numbness, pain, nasal blockage, or nasal ulceration. Seventy percent of patients who had a severe form of COVID-19 had CT values <20. 92.20% were on steroids and 76.47% needed oxygen. Such low values have been directly linked to the possibility of a flared disease. It has been observed and documented that the test of choice for making a prompt definitive diagnosis is the RT-PCR test. The amount of viral load can be ascertained by measuring CT value which has an inverse relationship with each other.[13],[14],[15]
It was also interesting to note that total leukocyte count was higher in 95.45% of cases whose onset of mucormycosis was <5 weeks. Increased leukocyte count in such patients is responsible for the activation of the cellular phase of acute inflammation which finally culminates in massive production of cytokines and extensive damage to organs.[16],[17]
In spite of this high TLC count, 95.45% of patients had lymphocytopenia. The steroids, on the one hand, led to an increase in white blood cell count in particular neutrophilia, and on the other hand, also cause lymphopenia. Since T lymphocyte is the backbone of cell-mediated immunity, any disruption in their levels will lead to decreased immune response and complications in the disease process.[18],[19]
About 47.61% of cases who had a mean IL-6 level of 42.09 pg/ml had a severe degree of COVID infection; 52.38% had a lesser level of IL-6 rise and were mild to moderate in severity. COVID-19 infection causes severe inflammation which leads to cytokine storm. IL-6 plays multiple roles which include proinflammatory which results in cytokine storm and also has a role in tumorigenesis.[20]
It was also found that 80.95% of mucor cases had high IL-6 and were dependent on oxygen. IL-6 levels were also very high in 52.38% of mucormycosis cases who developed mucormycosis within 1 week. Only one case who had the lowest rise of IL-6 developed mucormycosis after 5 weeks. All the patients who developed mucormycosis within 1 week also had higher D-dimer levels (55.5%). Similarly, the CRP level was high in severe COVID cases (52.63%) followed by 26.3% of cases who had a moderate-to-severe disease. CRP values rise significantly in active inflammatory processes like COVID-19 which acts as a perfect soil for the development of mucormycosis.[21]
When we analyzed the blood group, we found that majority of cases 59.09% were in blood group A. Out of this, 61.53% suffered from severe COVID infection and 76.92% were dependent on oxygen and 61.53% needed steroids. No study could be found in the literature which could depict the relationship between blood group and mucormycosis infection. ACE is specifically inhibited by human natural anti-A antibodies in respiratory tissue due to which out of all blood groups, A blood group patients are most prone to this infection. Angiotensin II stimulates an inflammatory cascade in the alveoli which in turn destroys the alveolar cells and is responsible for the development of hypoxia.[22]
The clinical signs and symptoms have no relation to the blood group. It was interesting to note that non-A blood group showed higher CRP, IL-6, and PT values compared to A blood group though D-dimer was more in blood group A. It has been documented that due to a higher level of von Willebrand factor in patients with blood group A as compared to non-A blood groups; the A blood group subset is prone to develop more defects in hemostasis and thrombosis.[23],[24],[25]
| Conclusion | | |
The multidisciplinary team of doctors who are involved in treating COVID patients must be mindful of the fact that mucormycosis can develop in them. Since it is a life-threatening angioinvasive disease, timely diagnosis and management of the patient can reduce the mortality rate. It is imperative that one must adhere to strict guidelines while administering steroids to such group of patients and prevent the development of such deadly infections.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8], [Table 9], [Table 10], [Table 11], [Table 12], [Table 13]
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