Clinical characteristics of patients with Coronavirus Disease 2019-associated pulmonary mucormycosis_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

ZHANG Renwen , LIU Yongzhe , LIU Jun , LI Ran ,  GU Li

Department of Infectious Diseases and Clinical Microbiology, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100020, China;

Corresponding author：

GU Li, Email: didcm2006@mail.ccmu.edu.cn

Keywords：

Coronavirus disease 2019; mucormycosis; coronavirus disease 2019-associated pulmonary mucormycosis; pulmonary aspergillosis; clinical characteristics

DOI：

10.7507/1671-6205.202411038

Video：

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Objective To analyze the clinical characteristics, prognosis and predisposing factors of coronavirus disease 2019 (COVID-19) associated pulmonary mucormycosis (CAPM), so as to improve people's understanding of the disease.Methods From from September 1, 2021 to July 31, 2024, 11 patients with CAPM who were hospitalized in Beijing Chaoyang Hospital affiliated to Capital Medical University were retrospectively collected, and 22 patients with non-CAPM were included after matching according to the ratio of 1:2. The clinical manifestations, laboratory examinations, imaging features, tracheoscopy, treatment and prognosis of the two groups were analyzed. Results The average age of patients in CAPM group was 59.5 ± 10.6 years, with 81.8% of males; diabetes mellitus (90.9%) was the most common complication. In CAPM group, the median time after the occurrence of mucor after COVID-19 was 13.0 (10.0, 24.0) days. The utilization rate of glucocorticoids in the CAPM group was 63.6% (7/11), which was significantly higher than that in non-CAPM group (13.6% (3/22)), and the difference between the groups was statistically significant (P=0.006). The C-reactive protein level in CAPM group was significantly higher at 93.90 (75.00, 129.00) mg/L than that in non-CAPM group at 26.10 (4.83,114.03) mg/L, with a statistically significant difference (P=0.040). The CD4+T lymphocyte counts and B lymphocyte counts in CAPM group were 223.00 (66.75,336.75)/µL and 32.00 (21.75,55.25)/µL, respectively, which were significantly lower than those in the non-CAPM group (394.00 (206.00, 610.00)/µL and 112.50 (56.00,159.25)/µL, with statistical differences between the groups (P=0.040, P=0.040). In terms of imaging, the main imaging findings were the involvement of multiple lobes in both groups. 63.6% (7/11) of patients with pulmonary aspergillosis in CAPM group were significantly higher than those(4/22,18.2%) in non-CAPM group (P=0.017). The incidence of dyspnea in CAPM group was significantly higher than that in non-CAPM group (90.9% vs. 50.0%, 0.027%).Conclusion The proportion of glucocorticoid use and the proportion of pulmonary aspergillosis in CAPM group are significantly higher, and they are in a more serious state of immunosuppression. Once combined with pulmonary aspergillus , the mortality rate is higher.

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2.	Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet, 2020, 395(10223): 497-506.
3.	Song G, Liang G, Liu W. Fungal Co-infections associated with global COVID-19 pandemic: a clinical and diagnostic perspective from China. Mycopathologia, 2020, 185(4): 599-606.
4.	Prattes J, Wauters J, Giacobbe DR, et al. Risk factors and outcome of pulmonary aspergillosis in critically ill coronavirus disease 2019 patients-a multinational observational study by the European Confederation of Medical Mycology. Clin Microbiol Infect, 2022, 28(4): 580-587.
5.	Singh AK, Singh R, Joshi SR, et al. Mucormycosis in COVID-19: a systematic review of cases reported worldwide and in India. Diabetes Metab Syndr, 2021, 15(4): 102146.
6.	Cornely OA, Alastruey-Izquierdo A, Arenz D, et al. Global guideline for the diagnosis and management of mucormycosis: an initiative of the European Confederation of Medical Mycology in cooperation with the Mycoses Study Group Education and Research Consortium. Lancet Infect Dis, 2019, 19(12): e405-e421.
7.	中国医师协会呼吸医师分会危重症学组, 中华医学会呼吸病学分会. 重症新型冠状病毒感染合并侵袭性肺曲霉病和肺毛霉病诊治专家共识. 中华结核和呼吸杂志, 2024, 47(1): 10-23.
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10.	White PL, Dhillon R, Cordey A, et al. A national strategy to diagnose coronavirus disease 2019-associated invasive fungal disease in the intensive care unit. Clin Infect Dis, 2021, 73(7): e1634-e1644.
11.	Rajapakse N, Dixit D. Human and novel coronavirus infections in children: a review. Paediatr Int Child Health, 2021, 41(1): 36-55.
12.	Sasani E, Pakdel F, Khodavaisy S, et al. Mixed aspergillosis and mucormycosis infections in patients with COVID-19: case series and literature review. Mycopathologia, 2024, 189(1): 10.
13.	中华人民共和国国家卫生健康委员会办公厅, 中华人民共和国国家中医药管理局综合司. 新型冠状病毒感染诊疗方案(试行第十版). 中国医药, 2023, 18(2): 161-166.
14.	中国医药教育协会真菌病专业委员会, 中国毛霉病专家共识工作组. 中国毛霉病临床诊疗专家共识(2022) .中华内科杂志, 2023, 62(6): 597-605.
15.	Muthu V, Agarwal R, Patel A, et al. Definition, diagnosis, and management of COVID-19-associated pulmonary mucormycosis: Delphi consensus statement from the Fungal Infection Study Forum and Academy of Pulmonary Sciences, India. Lancet Infect Dis, 2022, 22(9): e240-e253.
16.	中国医师协会呼吸医师分会危重症学组. 中华医学会呼吸病学分会. 重症新型冠状病毒感染合并侵袭性肺曲霉菌和肺毛霉病诊治专家共识. 中华结核和呼吸杂志, 2024, 47(1): 10-23.
17.	Koehler P, Bassetti M, Chakrabarti A, et al. Defining and managing COVID-19-associated pulmonary aspergillosis: the 2020 ECMM/ISHAM consensus criteria for research and clinical guidance. Lancet Infect Dis, 2021, 21(6): e149-e162.
18.	李俏, 雷伟, 张晓辉, 等. 新型冠状病毒肺炎相关性肺曲霉病的临床特征分析. 中国呼吸与危重监护杂志, 2023, 22(10): 710-715.
19.	Anand VK, Alemar G, Griswold JA Jr. Intracranial complications of mucormycosis: an experimental model and clinical review. Laryngoscope, 1992, 102(6): 656-662.
20.	Moorthy A, Gaikwad R, Krishna S, 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(3): 418-425.
21.	Patsouris D, Neels JG, Fan W, et al. Glucocorticoids and thiazolidinediones interfere with adipocyte-mediated macrophage chemotaxis and recruitment. J Biol Chem, 2009, 284(45): 31223-31235.
22.	Gregory MH, Spec A, Stwalley D, et al. Corticosteroids increase the risk of invasive fungal infections more than tumor necrosis factor-alpha inhibitors in patients with inflammatory bowel disease. Crohns Colitis 360, 2023, 5(2): otad010.
23.	Casadevall A, Pirofski LA. Immunoglobulins in defense, pathogenesis, and therapy of fungal diseases. Cell Host Microbe, 2012, 11(5): 447-456.
24.	Soliman SSM, Baldin C, Gu Y, et al. Mucoricin is a ricin-like toxin that is critical for the pathogenesis of mucormycosis. Nat Microbiol, 2021, 6(3): 313-326.
25.	Donnelly JP, Chen SC, Kauffman CA, et al. Revision and update of the consensus definitions of invasive fungal disease from the european organization for research and treatment of cancer and the mycoses study group education and research consortium. Clin Infect Dis, 2020, 71(6): 1367-1376.
26.	Chougule A, Muthu V, Bal A, et al. Pulmonary gangrene due to rhizopus spp. , staphylococcus aureus, klebsiella pneumoniae and probable sarcina organisms. Mycopathologia, 2015, 180(1-2): 131-136.
27.	Muthu V, Agarwal R, Dhooria S, et al. Has the mortality from pulmonary mucormycosis changed over time? a systematic review and meta-analysis. Clin Microbiol Infect, 2021, 27(4): 538-549.
28.	Muthu V, Agarwal R, Rudramurthy SM, et al. Prevalence of co-existent COVID-19-associated pulmonary aspergillosis (CAPA) and its impact on early mortality in patients with COVID-19-associated pulmonary mucormycosis (CAPM). Mycoses, 2024, 67(5): e13745.
29.	Muthu V, Gandra RR, Dhooria S, et al. Role of flexible bronchoscopy in the diagnosis of invasive fungal infections. Mycoses, 2021, 64(6): 668-677.
30.	Lass-Flörl C. Zygomycosis: conventional laboratory diagnosis. Clin Microbiol Infect, 2009, 15 Suppl 5: 60-65.
31.	Aranjani JM, Manuel A, Abdul Razack HI, et al. COVID-19-associated mucormycosis: Evidence-based critical review of an emerging infection burden during the pandemic’s second wave in India. PLoS Negl Trop Dis, 2021, 15(11): e0009921.

1. Mahase E. Covid-19: WHO declares pandemic because of "alarming levels" of spread, severity, and inaction. BMJ, 2020, 368: m1036.
2. Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet, 2020, 395(10223): 497-506.
3. Song G, Liang G, Liu W. Fungal Co-infections associated with global COVID-19 pandemic: a clinical and diagnostic perspective from China. Mycopathologia, 2020, 185(4): 599-606.
4. Prattes J, Wauters J, Giacobbe DR, et al. Risk factors and outcome of pulmonary aspergillosis in critically ill coronavirus disease 2019 patients-a multinational observational study by the European Confederation of Medical Mycology. Clin Microbiol Infect, 2022, 28(4): 580-587.
5. Singh AK, Singh R, Joshi SR, et al. Mucormycosis in COVID-19: a systematic review of cases reported worldwide and in India. Diabetes Metab Syndr, 2021, 15(4): 102146.
6. Cornely OA, Alastruey-Izquierdo A, Arenz D, et al. Global guideline for the diagnosis and management of mucormycosis: an initiative of the European Confederation of Medical Mycology in cooperation with the Mycoses Study Group Education and Research Consortium. Lancet Infect Dis, 2019, 19(12): e405-e421.
7. 中国医师协会呼吸医师分会危重症学组, 中华医学会呼吸病学分会. 重症新型冠状病毒感染合并侵袭性肺曲霉病和肺毛霉病诊治专家共识. 中华结核和呼吸杂志, 2024, 47(1): 10-23.
8. Muthu V, Rudramurthy SM, Chakrabarti A, et al. Epidemiology and pathophysiology of COVID-19-associated mucormycosis: India versus the rest of the world. Mycopathologia, 2021, 186(6): 739-754.
9. Hoenigl M, Seidel D, Carvalho A, et al. The emergence of COVID-19 associated mucormycosis: a review of cases from 18 countries. Lancet Microbe, 2022, 3(7): e543-e552.
10. White PL, Dhillon R, Cordey A, et al. A national strategy to diagnose coronavirus disease 2019-associated invasive fungal disease in the intensive care unit. Clin Infect Dis, 2021, 73(7): e1634-e1644.
11. Rajapakse N, Dixit D. Human and novel coronavirus infections in children: a review. Paediatr Int Child Health, 2021, 41(1): 36-55.
12. Sasani E, Pakdel F, Khodavaisy S, et al. Mixed aspergillosis and mucormycosis infections in patients with COVID-19: case series and literature review. Mycopathologia, 2024, 189(1): 10.
13. 中华人民共和国国家卫生健康委员会办公厅, 中华人民共和国国家中医药管理局综合司. 新型冠状病毒感染诊疗方案(试行第十版). 中国医药, 2023, 18(2): 161-166.
14. 中国医药教育协会真菌病专业委员会, 中国毛霉病专家共识工作组. 中国毛霉病临床诊疗专家共识(2022) .中华内科杂志, 2023, 62(6): 597-605.
15. Muthu V, Agarwal R, Patel A, et al. Definition, diagnosis, and management of COVID-19-associated pulmonary mucormycosis: Delphi consensus statement from the Fungal Infection Study Forum and Academy of Pulmonary Sciences, India. Lancet Infect Dis, 2022, 22(9): e240-e253.
16. 中国医师协会呼吸医师分会危重症学组. 中华医学会呼吸病学分会. 重症新型冠状病毒感染合并侵袭性肺曲霉菌和肺毛霉病诊治专家共识. 中华结核和呼吸杂志, 2024, 47(1): 10-23.
17. Koehler P, Bassetti M, Chakrabarti A, et al. Defining and managing COVID-19-associated pulmonary aspergillosis: the 2020 ECMM/ISHAM consensus criteria for research and clinical guidance. Lancet Infect Dis, 2021, 21(6): e149-e162.
18. 李俏, 雷伟, 张晓辉, 等. 新型冠状病毒肺炎相关性肺曲霉病的临床特征分析. 中国呼吸与危重监护杂志, 2023, 22(10): 710-715.
19. Anand VK, Alemar G, Griswold JA Jr. Intracranial complications of mucormycosis: an experimental model and clinical review. Laryngoscope, 1992, 102(6): 656-662.
20. Moorthy A, Gaikwad R, Krishna S, 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(3): 418-425.
21. Patsouris D, Neels JG, Fan W, et al. Glucocorticoids and thiazolidinediones interfere with adipocyte-mediated macrophage chemotaxis and recruitment. J Biol Chem, 2009, 284(45): 31223-31235.
22. Gregory MH, Spec A, Stwalley D, et al. Corticosteroids increase the risk of invasive fungal infections more than tumor necrosis factor-alpha inhibitors in patients with inflammatory bowel disease. Crohns Colitis 360, 2023, 5(2): otad010.
23. Casadevall A, Pirofski LA. Immunoglobulins in defense, pathogenesis, and therapy of fungal diseases. Cell Host Microbe, 2012, 11(5): 447-456.
24. Soliman SSM, Baldin C, Gu Y, et al. Mucoricin is a ricin-like toxin that is critical for the pathogenesis of mucormycosis. Nat Microbiol, 2021, 6(3): 313-326.
25. Donnelly JP, Chen SC, Kauffman CA, et al. Revision and update of the consensus definitions of invasive fungal disease from the european organization for research and treatment of cancer and the mycoses study group education and research consortium. Clin Infect Dis, 2020, 71(6): 1367-1376.
26. Chougule A, Muthu V, Bal A, et al. Pulmonary gangrene due to rhizopus spp. , staphylococcus aureus, klebsiella pneumoniae and probable sarcina organisms. Mycopathologia, 2015, 180(1-2): 131-136.
27. Muthu V, Agarwal R, Dhooria S, et al. Has the mortality from pulmonary mucormycosis changed over time? a systematic review and meta-analysis. Clin Microbiol Infect, 2021, 27(4): 538-549.
28. Muthu V, Agarwal R, Rudramurthy SM, et al. Prevalence of co-existent COVID-19-associated pulmonary aspergillosis (CAPA) and its impact on early mortality in patients with COVID-19-associated pulmonary mucormycosis (CAPM). Mycoses, 2024, 67(5): e13745.
29. Muthu V, Gandra RR, Dhooria S, et al. Role of flexible bronchoscopy in the diagnosis of invasive fungal infections. Mycoses, 2021, 64(6): 668-677.
30. Lass-Flörl C. Zygomycosis: conventional laboratory diagnosis. Clin Microbiol Infect, 2009, 15 Suppl 5: 60-65.
31. Aranjani JM, Manuel A, Abdul Razack HI, et al. COVID-19-associated mucormycosis: Evidence-based critical review of an emerging infection burden during the pandemic’s second wave in India. PLoS Negl Trop Dis, 2021, 15(11): e0009921.

Chinese Journal of Respiratory and Critical Care Medicine

Latest ArticlesClinical characteristics of patients with Coronavirus Disease 2019-associated pulmonary mucormycosis

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