Clinical profile and outcome of COVID-19 associated mucormycosis in Shiraz, South Iran: a longitudinal study
-
Pariya Kouhi
,
Seyed Alireza Mirhosseini
,
Maryam Ranjbar
,
Mohammadreza Akbari
,
Zeinab Mehrabi
,
Rojan Javaheri
,
Mahsa Moosavi
,
Mohammad Alishahi
,
Kamran Rasekh
,
Nazanin Fathi
,
Yasaman Mansoori
Abstract
Background and Objectives: Numerous cases of mucormycosis appeared among COVID-19 patients, predominantly in Asian countries. This study aimed to investigate the clinical profile, in-hospital outcome, and one-year prognosis of COVID-19-associated mucormycosis (CAM).
Materials and Methods: All patients who developed CAM in Shiraz, South Iran, between July and October 2021 were included in this study. We collected data on presentations, comorbidities, risk factors, and outcomes.
Results: Sixty-two patients with CAM were analyzed; the mean age was 59.3 years, and 58.1% were male. Diabetes mellitus was present in 80.6% (11.2% uncontrolled), hypertension in 54.8%, and chronic kidney disease in 11.3%. All patients had sinonasal involvement; ophthalmic, cutaneous, cerebral, gastrointestinal, pulmonary, and renal involvement occurred in 41.9%, 8.1%, 6.4%, 6.4%, 1.6%, and 1.6%, respectively. In-hospital and one-year mortality were 40.3% and 48.3%. Concurrent CAM and COVID-19, hypertension, older age, and radiologically severe COVID-19 lung involvement were associated with higher mortality. In multivariable analysis, age ≥60 years predicted in-hospital (OR: 5.47; 95% CI: 1.53-19.56) and one-year mortality (OR: 7.65; 95% CI: 1.90-30.84). Long-term mortality was also associated with ≥3 risk factors (OR: 4.12; 95% CI: 1.09-15.52) and lung severity index >30 (OR: 9.35; 95% CI: 1.01-86.63).
Conclusion: These findings emphasize the critical role of age in immune responses to opportunistic infections and highlight the impact of multiple comorbidities and severe lung damage on long-term prognosis in CAM.
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2. 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.
3. Saadi MHG, Hosseini SA, Khodamoradi Z, Mokhtaryan M, Omidifar N, Moghadami M. Comparison of mucormycosis infection between patients with and without a history of COVID-19 infection: a retrospective cohort study. Trans R Soc Trop Med Hyg 2023; 117:174-178.
4. Pasquier G. COVID-19-associated mucormycosis in India: Why such an outbreak? J Mycol Med 2023; 33:101393.
5. Stemler J, Hamed K, Salmanton-García J, Rezaei-Matehkolaei A, Gräfe SK, Sal E, et al. Mucormycosis in the Middle East and North Africa: Analysis of the FungiScope® registry and cases from the literature. Mycoses 2020; 63:1060-1068.
6. Pourazizi M, Hakamifard A, Peyman A, Mohammadi R, Dehghani S, Tavousi N, et al. COVID-19 associated mucormycosis surge: A review on multi-pathway mechanisms. Parasite Immunol 2024; 46(1):e13016.
7. Hoenigl M, Seidel D, Carvalho A, Rudramurthy SM, Arastehfar A, Gangneux JP, et al. The emergence of COVID-19 associated mucormycosis: a review of cases from 18 countries. Lancet Microbe 2022; 3(7):e543-e552.
8. Eshraghi B, Khademi B, Mirmohammadkhani M, Khataminia G, Ghahvehchian H, Kiarudi MY, et al. Risk Factors of COVID-19 associated mucormycosis in Iranian patients: a multicenter study. BMC Infect Dis 2024; 24:852.
9. Hussain S, Baxi H, Riad A, Klugarová J, Pokorná A, Slezáková S, et al. COVID-19-Associated Mucormycosis (CAM): An Updated Evidence Mapping. Int J Environ Res Public Health 2021; 18:10340.
10. Kwee TC, Kwee RM. Chest CT in COVID-19: What the Radiologist Needs to Know. Radiographics 2020; 40:1848-1865.
11. Honavar SG. Code Mucor: Guidelines for the Diagnosis, Staging and Management of Rhino-Orbito-Cerebral Mucormycosis in the Setting of COVID-19. Indian J Ophthalmol 2021; 69:1361-1365.
12. American Diabetes Association Professional Practice Committee. 6. Glycemic Targets: Standards of Medical Care in Diabetes-2022. Diabetes Care 2022; 45(Suppl 1):S83-S96.
13. Elmokadem AH, Mounir AM, Ramadan ZA, Elsedeiq M, Saleh GA. Comparison of chest CT severity scoring systems for COVID-19. Eur Radio 2022; 32:3501-3512.
14. Mishra N, Mutya VS, 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; 7:867-870.
15. Sarkar S, Gokhale T, Choudhury SS, Deb AK. COVID-19 and orbital mucormycosis. Indian J Ophthalmol 2021; 69:1002-1004.
16. Satish D, Joy D, Ross A, Balasubramanya B. Mucormycosis coinfection associated with global COVID-19: a case series from India. Int J Otorhinolaryngol Head Neck Surg 2021; 7:815-820.
17. Pakdel F, Ahmadikia K, Salehi M, Tabari A, Jafari R, Mehrparvar G, et al. Mucormycosis in patients with COVID-19: A cross-sectional descriptive multicentre study from Iran. Mycoses 2021; 64:1238-1252.
18. Rudrabhatla PK, Reghukumar A, Thomas SV. Mucormycosis in COVID-19 patients: predisposing factors, prevention and management. Acta Neurol Belg 2022; 122:273-280.
19. Kumar R, Misra AK, Dutta S, Gupta A, Kumar B, Charan J. A systematic review of mucormycosis cases in COVID-19: Is it an unholy trilogy of COVID-19, diabetes mellitus, and corticosteroids? J Family Med Prim Care 2022; 11:2573-2580.
20. Bhattacharyya A, Sarma P, Sharma DJ, Das KK, Kaur H, Prajapat M, et al. Rhino-orbital-cerebral-mucormycosis in COVID-19: A systematic review. Indian J Pharmacol 2021; 53:317-327.
21. John TM, Jacob CN, Kontoyiannis DP. When uncontrolled diabetes mellitus and severe COVID-19 converge: the perfect storm for Mucormycosis. J Fungi (Basel) 2021; 7:298.
22. Petrikkos G, Skiada A, Lortholary O, Roilides E, Walsh TJ, Kontoyiannis DP. Epidemiology and clinical manifestations of mucormycosis. Clin Infect Dis 2012; 54 Suppl 1:S23-34.
23. Nagalli S, Kikkeri NS. Mucormycosis in COVID-19: A systematic review of literature. Infez Med 2021; 29:504-512.
24. Ponnaiah M, Ganesan S, Bhatnagar T, Thulasingam M, Majella MG, Karuppiah M, et al. Hyperglycemia and steroid use increase the risk of rhino-orbito-cerebral mucormycosis regardless of COVID-19 hospitalization: Case-control study, India. PLoS One 2022; 17(8):e0272042.
25. Mulakavalupil B, Vaity C, Joshi S, Misra A, Pandit RA. Absence of Case of Mucormycosis (March 2020-May 2021) under strict protocol driven management care in a COVID-19 specific tertiary care intensive care unit. Diabetes Metab Syndr 2021; 15:102169.
26. Prakash H, Chakrabarti A. Global Epidemiology of Mucormycosis. J Fungi (Basel) 2019; 5:26.
27. Kaur H, Ghosh A, Rudramurthy SM, Chakrabarti A. Gastrointestinal mucormycosis in apparently immunocompetent hosts-A review. Mycoses 2018; 61:898-908.
28. Nath S, Baidya DK. Mucormycosis in COVID-19: Is Zinc a Silent Killer in India? Indian J Crit Care Med 2021; 25:1079-1080.
29. Muthu V, Kumar M, Paul RA, Zohmangaihi D, Choudhary H, Rudramurthy SM, et al. Is there an association between zinc and COVID-19-associated mucormycosis? Results of an experimental and clinical study. Mycoses 2021; 64:1291-1297.
30. Pongas GN, Lewis RE, Samonis G, Kontoyiannis DP. Voriconazole-associated zygomycosis: a significant consequence of evolving antifungal prophylaxis and immunosuppression practices? Clin Microbiol Infect 2009; 15 Suppl 5:93-97.
31. Horiguchi T, Tsukamoto T, Toyama Y, Sasaki T, Nakamura T, Sakurai A, et al. Fatal disseminated mucormycosis associated with COVID-19. Respirol Case Rep 2022; 10(3):e0912.
32. Campbell L, Chen C, Bhagat SS, Parker RA, Östör AJ. Risk of adverse events including serious infections in rheumatoid arthritis patients treated with tocilizumab: a systematic literature review and meta-analysis of randomized controlled trials. Rheumatology (Oxford) 2011; 50:552-562.
33. Bhattacharyya A, Sarma P, Kaur H, Kumar S, Bhattacharyya J, Prajapat M, et al. COVID-19-associated rhino-orbital-cerebral mucormycosis: A systematic review, meta-analysis, and meta-regression analysis. Indian J Pharmacol 2021; 53:499-510.
34. Sahu RK, Salem-Bekhit MM, Bhattacharjee B, Almoshari Y, Ikbal AMA, Alshamrani M, et al. Mucormycosis in Indian COVID-19 patients: insight into its Patho-Genesis, clinical manifestation, and management strategies. Antibiotics (Basel) 2021; 10:1079.
35. La Fauci V, Costa GB, Facciolà A, Conti A, Riso R, Squeri R. Humidifiers for oxygen therapy: what risk for reusable and disposable devices? J Prev Med Hyg 2017; 58(2):E161-E165.
36. Duffy J, Harris J, Gade L, Sehulster L, Newhouse E, O'Connell H, et al. Mucormycosis outbreak associated with hospital linens. Pediatr Infect Dis J 2014; 33:472-476.
37. Dave TV, Gopinathan Nair A, Hegde R, Vithalani N, Desai S, Adulkar N, et al. Clinical presentations, management and outcomes of Rhino-Orbital-Cerebral Mucormycosis (ROCM) following COVID-19: A multi-centric study. Ophthalmic Plast Reconstr Surg 2021; 37:488-495.
2. 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.
3. Saadi MHG, Hosseini SA, Khodamoradi Z, Mokhtaryan M, Omidifar N, Moghadami M. Comparison of mucormycosis infection between patients with and without a history of COVID-19 infection: a retrospective cohort study. Trans R Soc Trop Med Hyg 2023; 117:174-178.
4. Pasquier G. COVID-19-associated mucormycosis in India: Why such an outbreak? J Mycol Med 2023; 33:101393.
5. Stemler J, Hamed K, Salmanton-García J, Rezaei-Matehkolaei A, Gräfe SK, Sal E, et al. Mucormycosis in the Middle East and North Africa: Analysis of the FungiScope® registry and cases from the literature. Mycoses 2020; 63:1060-1068.
6. Pourazizi M, Hakamifard A, Peyman A, Mohammadi R, Dehghani S, Tavousi N, et al. COVID-19 associated mucormycosis surge: A review on multi-pathway mechanisms. Parasite Immunol 2024; 46(1):e13016.
7. Hoenigl M, Seidel D, Carvalho A, Rudramurthy SM, Arastehfar A, Gangneux JP, et al. The emergence of COVID-19 associated mucormycosis: a review of cases from 18 countries. Lancet Microbe 2022; 3(7):e543-e552.
8. Eshraghi B, Khademi B, Mirmohammadkhani M, Khataminia G, Ghahvehchian H, Kiarudi MY, et al. Risk Factors of COVID-19 associated mucormycosis in Iranian patients: a multicenter study. BMC Infect Dis 2024; 24:852.
9. Hussain S, Baxi H, Riad A, Klugarová J, Pokorná A, Slezáková S, et al. COVID-19-Associated Mucormycosis (CAM): An Updated Evidence Mapping. Int J Environ Res Public Health 2021; 18:10340.
10. Kwee TC, Kwee RM. Chest CT in COVID-19: What the Radiologist Needs to Know. Radiographics 2020; 40:1848-1865.
11. Honavar SG. Code Mucor: Guidelines for the Diagnosis, Staging and Management of Rhino-Orbito-Cerebral Mucormycosis in the Setting of COVID-19. Indian J Ophthalmol 2021; 69:1361-1365.
12. American Diabetes Association Professional Practice Committee. 6. Glycemic Targets: Standards of Medical Care in Diabetes-2022. Diabetes Care 2022; 45(Suppl 1):S83-S96.
13. Elmokadem AH, Mounir AM, Ramadan ZA, Elsedeiq M, Saleh GA. Comparison of chest CT severity scoring systems for COVID-19. Eur Radio 2022; 32:3501-3512.
14. Mishra N, Mutya VS, 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; 7:867-870.
15. Sarkar S, Gokhale T, Choudhury SS, Deb AK. COVID-19 and orbital mucormycosis. Indian J Ophthalmol 2021; 69:1002-1004.
16. Satish D, Joy D, Ross A, Balasubramanya B. Mucormycosis coinfection associated with global COVID-19: a case series from India. Int J Otorhinolaryngol Head Neck Surg 2021; 7:815-820.
17. Pakdel F, Ahmadikia K, Salehi M, Tabari A, Jafari R, Mehrparvar G, et al. Mucormycosis in patients with COVID-19: A cross-sectional descriptive multicentre study from Iran. Mycoses 2021; 64:1238-1252.
18. Rudrabhatla PK, Reghukumar A, Thomas SV. Mucormycosis in COVID-19 patients: predisposing factors, prevention and management. Acta Neurol Belg 2022; 122:273-280.
19. Kumar R, Misra AK, Dutta S, Gupta A, Kumar B, Charan J. A systematic review of mucormycosis cases in COVID-19: Is it an unholy trilogy of COVID-19, diabetes mellitus, and corticosteroids? J Family Med Prim Care 2022; 11:2573-2580.
20. Bhattacharyya A, Sarma P, Sharma DJ, Das KK, Kaur H, Prajapat M, et al. Rhino-orbital-cerebral-mucormycosis in COVID-19: A systematic review. Indian J Pharmacol 2021; 53:317-327.
21. John TM, Jacob CN, Kontoyiannis DP. When uncontrolled diabetes mellitus and severe COVID-19 converge: the perfect storm for Mucormycosis. J Fungi (Basel) 2021; 7:298.
22. Petrikkos G, Skiada A, Lortholary O, Roilides E, Walsh TJ, Kontoyiannis DP. Epidemiology and clinical manifestations of mucormycosis. Clin Infect Dis 2012; 54 Suppl 1:S23-34.
23. Nagalli S, Kikkeri NS. Mucormycosis in COVID-19: A systematic review of literature. Infez Med 2021; 29:504-512.
24. Ponnaiah M, Ganesan S, Bhatnagar T, Thulasingam M, Majella MG, Karuppiah M, et al. Hyperglycemia and steroid use increase the risk of rhino-orbito-cerebral mucormycosis regardless of COVID-19 hospitalization: Case-control study, India. PLoS One 2022; 17(8):e0272042.
25. Mulakavalupil B, Vaity C, Joshi S, Misra A, Pandit RA. Absence of Case of Mucormycosis (March 2020-May 2021) under strict protocol driven management care in a COVID-19 specific tertiary care intensive care unit. Diabetes Metab Syndr 2021; 15:102169.
26. Prakash H, Chakrabarti A. Global Epidemiology of Mucormycosis. J Fungi (Basel) 2019; 5:26.
27. Kaur H, Ghosh A, Rudramurthy SM, Chakrabarti A. Gastrointestinal mucormycosis in apparently immunocompetent hosts-A review. Mycoses 2018; 61:898-908.
28. Nath S, Baidya DK. Mucormycosis in COVID-19: Is Zinc a Silent Killer in India? Indian J Crit Care Med 2021; 25:1079-1080.
29. Muthu V, Kumar M, Paul RA, Zohmangaihi D, Choudhary H, Rudramurthy SM, et al. Is there an association between zinc and COVID-19-associated mucormycosis? Results of an experimental and clinical study. Mycoses 2021; 64:1291-1297.
30. Pongas GN, Lewis RE, Samonis G, Kontoyiannis DP. Voriconazole-associated zygomycosis: a significant consequence of evolving antifungal prophylaxis and immunosuppression practices? Clin Microbiol Infect 2009; 15 Suppl 5:93-97.
31. Horiguchi T, Tsukamoto T, Toyama Y, Sasaki T, Nakamura T, Sakurai A, et al. Fatal disseminated mucormycosis associated with COVID-19. Respirol Case Rep 2022; 10(3):e0912.
32. Campbell L, Chen C, Bhagat SS, Parker RA, Östör AJ. Risk of adverse events including serious infections in rheumatoid arthritis patients treated with tocilizumab: a systematic literature review and meta-analysis of randomized controlled trials. Rheumatology (Oxford) 2011; 50:552-562.
33. Bhattacharyya A, Sarma P, Kaur H, Kumar S, Bhattacharyya J, Prajapat M, et al. COVID-19-associated rhino-orbital-cerebral mucormycosis: A systematic review, meta-analysis, and meta-regression analysis. Indian J Pharmacol 2021; 53:499-510.
34. Sahu RK, Salem-Bekhit MM, Bhattacharjee B, Almoshari Y, Ikbal AMA, Alshamrani M, et al. Mucormycosis in Indian COVID-19 patients: insight into its Patho-Genesis, clinical manifestation, and management strategies. Antibiotics (Basel) 2021; 10:1079.
35. La Fauci V, Costa GB, Facciolà A, Conti A, Riso R, Squeri R. Humidifiers for oxygen therapy: what risk for reusable and disposable devices? J Prev Med Hyg 2017; 58(2):E161-E165.
36. Duffy J, Harris J, Gade L, Sehulster L, Newhouse E, O'Connell H, et al. Mucormycosis outbreak associated with hospital linens. Pediatr Infect Dis J 2014; 33:472-476.
37. Dave TV, Gopinathan Nair A, Hegde R, Vithalani N, Desai S, Adulkar N, et al. Clinical presentations, management and outcomes of Rhino-Orbital-Cerebral Mucormycosis (ROCM) following COVID-19: A multi-centric study. Ophthalmic Plast Reconstr Surg 2021; 37:488-495.
| Files | ||
| Issue | Vol 18 No 1 (2026) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijm.v18i1.20940 | |
| Keywords | ||
| COVID-19 Mucormycosis Risk factors Comorbidity Treatment outcome Prognosis | ||
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How to Cite
1.
Kouhi P, Mirhosseini SA, Ranjbar M, Akbari M, Mehrabi Z, Javaheri R, Moosavi M, Alishahi M, Rasekh K, Fathi N, Mansoori Y. Clinical profile and outcome of COVID-19 associated mucormycosis in Shiraz, South Iran: a longitudinal study. Iran J Microbiol. 2026;18(1):147-156.
