新型冠状病毒感染合并机会性感染6例临床病理特征分析

Clinicopathological characteristics of COVID⁃19 complicated with opportunistic infections in a case series of six patients

目的:总结分析6例新型冠状病毒感染(COVID⁃19)合并机会性感染的临床病理特征,以期为临床诊治提供帮助。方法:收集2020至2021年广州医科大学附属市八医院临床确诊COVID⁃19且病理提示合并机会性感染的患者6例,回顾分析其临床特征及病理组织学特征,特殊染色法(六胺银、PAS及抗酸染色)、免疫荧光染色法(真菌荧光及抗酸荧光染色)及病原宏基因组二代测序法(mNGS)进行病原体检测,并进行相关文献复习。结果:本研究中6例COVID⁃19患者均有基础疾病,有不同程度发热及咳嗽、咳痰等呼吸道症状,并出现肺部CT改变,主要表现为双肺斑片状或磨玻璃密度影。6例均出现C反应蛋白升高,并出现CD4^(+)及CD8^(+)T淋巴细胞计数降低。在6例标本中,从肺泡灌洗液标本中检出耶氏肺孢子菌2例(均为老年患者合并肺部基础疾病,CD4^(+)T细胞<150个/μl),从背部痂皮组织中检出毛霉菌1例(糖尿病患者出现皮肤破损),2例肺泡灌洗液和1例压疮组织检出真菌孢子(均合并基础疾病),其中病例6肺泡灌洗液标本经mNGS检测查见白色假丝酵母菌。结论:COVID⁃19患者特别是年龄较大合并基础疾病且未注射新冠疫苗,病程较长病情复杂,出现CD4^(+)及CD8^(+)T细胞计数降低,C反应蛋白升高时,要警惕真菌等机会性感染可能,避免漏诊延误治疗;如可疑肺孢子菌等真菌感染时建议行病理学检查,必要时行病原宏基因组检测,有助于病原学确诊。

Objective:To present a summary on the clinicopathological characteristics of novel coronavirus infection(COVID⁃19)complicated with opportunistic infections in a six⁃patient case series,in hope of adding to guidance for the clinical diagnosis and treatment.Methods:Included were 6 patients with clinically confirmed COVID⁃19 and pathologically⁃evidenced complicating opportunistic infections registered to Guangzhou Eighth People’s Hospital Affiliated to Guangzhou Medical University between 2020 and 2021.A retrospective analysis of these patients was performed on their clinical patterns,pathohistological characteristics,and detection yield for culprit pathogens with special staining(hexamine silver,PAS,and acid⁃fast staining),immunofluorescence staining(fungal fluorescence staining and acid⁃fast fluorescence staining)and metagenomic next⁃generation sequencing(mNGS).Relevant literature was reviewed.Results:The six COVID⁃19 patients in this study,all with underlying comorbidities,showed varying severity of fever and respiratory symptoms such as cough and expectoration,and presented with abnormal chest CT findings predominated by patchy or ground glass opacities in both lungs.Elevated C⁃reactive protein level and lowered counts of CD4^(+)and CD8^(+)T lymphocytes were noted in all patients.Of the specimens collected in these cases,we identified Pneumocystis jiroveci in bronchial alveolar lavage fluid(BALF)from two elderly patients with pulmonary comorbidites and CD4^(+)T cell counts below 150/μl,Mucor spp in crust tissue on the back of a diabetic patient with skin lesions,fungal spores in BALF from two patients and bedsore ulcers from another(all with underlying comorbidities).Of note,Candida albicans was detected by mNGS in BALF from the patient No.6.Conclusion:COVID⁃19 patients,particularly those with advanced age and underlying comorbidities,those who remain unvaccinated for COVID⁃19 and on persistently unresolved,complicated conditions,should prompt medical alerts for the probability of infections with fungi or other opportunistic microbes to avert missed diagnosis and delay treatment when they present with lowered CD4^(+)and CD8^(+)T⁃cell counts and an elevated C⁃reactive protein level.For patients suspected to have Pneumocystis pneumonia,pathological tests should be ordered.When necessary,mNGS should be considered to aid microbiological confirmation of the culprit pathogens.