13例重症新型冠状病毒肺炎患者临床特征及疾病发展规律分析

Analysis of clinical features and the law of disease development of 13 cases of severe COVID-19

目的:总结重症新型冠状病毒肺炎(coronavirus disease 2019,COVID-19)诊治的临床经验,探索疾病特点及发展规律。方法:回顾性分析13例重症COVID-19患者的流行病学资料,疾病特点,主要治疗情况,病情演变过程中临床指标、生化指标、影像学特征的变化。结果:重症COVID-19患者在病程早期淋巴细胞(lymphocytes,LYM)计数明显降低,进展期进一步下降,缓解期上升,但未完全恢复到正常值,各期均有统计学差异(F=15.396,P=0.000)。C反应蛋白(C-reactive protein,CRP)和白介素-6(interleukin-6,IL-6)在早期升高,进展期开始下降,缓解期明显下降,缓解期与早期、进展期均具有统计学差异(CRP:F=5.366,P=0.009;IL-6:F=5.367,P=0.009)。乳酸脱氢酶(lactate dehydrogenase,LDH)及肌红蛋白(myoglobin,Mb)在病程早期就明显升高,进展期稍有下降,缓解期下降明显,LDH在各期均有统计学差异(F=10.464,P=0.000),而Mb只在缓解期与早期有统计学差异(F=4.303,P=0.021)。肌酸激酶(creatine kinase,CK)早期升高,进展期明显下降,缓解期继续下降,早期与进展期、缓解期有统计学差异(F=3.782,P=0.032)。白蛋白(albumin,ALB)在疾病早期有下降趋势,进展期明显下降,与早期、缓解期有统计学差异(F=5.264,P=0.010),缓解期有所上升,但低于正常值下限。重症COVID-19患者氧合指数(oxygen index,OI)早期就有下降趋势,进展期进一步下降,缓解期上升,与早期、缓解期有统计学差异(F=59.334,P=0.000)。影像特征:早期见斑片或片状磨玻璃影,其内可见支气管血管束增粗,部分可见小叶间隔增厚和实变,以胸膜下分布为主。进展期以片状磨玻璃影与实变同时存在,以混合密度为主,并且实变范围增大,可见小叶间隔增厚及支气管充气征,部分病变内出现纤维灶,病变自外周向中央发展的趋势,少数患者合并少量胸腔积液。个别病例早期病灶吸收减少后又出现新发病灶。缓解期病变范围缩小、数目减少、密度减低,残留部分实变及纤维灶。结论:重症COVID-19患者最常见的实验室检测指标是OI降低、低ALB血症、LYM计数减少,CRP、IL-6、LDH、CK、Mb水平升高。CRP、IL-6、LDH、CK、Mb在早期明显升高,反应灵敏,进展期不但没有持续上升,反而较早期有所下降,提示早期糖皮质激素使用和综合治疗有效,虽然呼吸衰竭尚未被纠正,但炎症指标已经开始下降,疾病有向好发展趋势;缓解期以上指标持续下降,疾病好转。而ALB、LYM计数降低一直持续到进展期,呼吸衰竭纠正后才有所回升,恢复缓慢,反应滞后。胸部CT影像具有相对特征性的表现,早期以渗出、磨玻璃病变为主,进展期渗出进一步增多、实变,个别病例病灶有此消彼长现象,缓解期病变范围吸收减少,纤维化形成。

Objective:To summarize the clinical experience,characteristics and progression of severe coronavirus disease 2019(COVID-19).Methods:The epidemiological data,disease characteristics,treatment,clinical indexes,biochemical indexes and imaging characteristics of 13 patients with severe COVID-19 were retrospectively analyzed.Results:In severe COVID-19 patients,the lymphocyte(LYM)count was significantly decreased in the early stage and further decreased in the advanced stage,while was increased in the remission period,but did not completely return to the normal value,with statistical differences in each period(F=15.396,P=0.000).C-reactive protein(CRP)and interleukin-6(IL-6)were increased in the early stage,began to decrease in the progression stage,and significantly decreased in the remission stage,with statistical differences between the remission stage and the early stage and the progression stage(CRP:F=5.366,P=0.009;IL-6:F=5.367,P=0.009).Lactate dehydrogenase(LDH)and myoglobin(Mb)were significantly increased in the early stage,slightly decreased in the progressive stage and significantly decreased in the remission stage.LDH was statistically different in each stage(F=10.464,P=0.000),but Mb was only significantly different in the remission stage and early stage(F=4.303,P=0.021).Creatine kinase(CK)was increased in the early stage,and decreased significantly in the advanced stage,and continued to decline in the remission stage,with statistical differences between the early stage and the advanced stage and the remission stage(F=3.782,P=0.032).Albumin(ALB)was decreased in the early stage,and decreased obviously in the advanced stage,with a statistical difference between the early stage and the remission stage(F=5.264,P=0.010).Oxygen index(OI)decreased in the early stage,and further decreased in the advanced stage,which was significantly different from the early stage and the remission stage(F=59.334,P=0.000).Imaging features in the early stage,there were patches or flakes of ground glass shadow,thickening of bronchovascular bundle was able to be seen,partially thickening and consolidation of interlobular septum,which was mainly distributed under pleura.In the progressive stage:there are both patchy ground glass shadow and consolidation,mainly mixed density,and consolidation range was increased.Thickening of interlobular septum and bronchiectasis was able to be seen,partially fibrofocus;the development trend of lesions was from peripheral to central and a few patients had complications of a small amount of pleural effusion.Few patients had problems that new lesions appeared after the absorption or decrease of early lesions.In the remission stage:the scope,number and density of lesions were reduced and the remaining were solid and fibrous foci.Conclusion:The most common abnormal biochemical indicators in patients with severe COVID-19 are decreased OI,decreased hypo-albuminemia,decreased LYM count,and elevated CRP,IL-6,LDH,CK and Mb.CRP,IL-6,LDH,CK and Mb are increased significantly at an early stage,and are sensitive to response.Instead of continuing to increase during the progression phase,they are declined,suggesting that early glucocorticoid and intervention therapy are effective.Although respiratory failure has not been corrected,the inflammation index has begun to decline,and the disease may develop for the better.In the remission period,the above indicators continues to decline,and the disease is improved.While the ALB and LYM counts continues to decline until the progression period,after the correction of respiratory failure,the recovery is slow,and the response is delayed.CT images of the chest have relatively distinctive manifestations,with main characteristics of exudation and ground glass lesions in the early period,and further increase and consolidation of exudation in the progressive stage.Few lesions have the phenomenon of ebb and flow,and the absorption of lesions in the remission stage is reduced,and fibrosis is formed.