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入院中の COVID-19 患者 289 例の臨床的、放射線学的、検査学的特徴と重症度および死亡の危険因子
Clinical, radiological and laboratory characteristics and risk factors for severity and mortality of 289 hospitalized COVID-19 patients.
PMID: 32662525 DOI: 10.1111/all.14496.
抄録
背景:
コロナウイルス疾患2019（COVID-19）は世界的なパンデミックとなっており、重症患者の10～20％が発症し、全世界で50万8000人以上が死亡している。
BACKGROUND: The coronavirus disease 2019 (COVID-19) has become a global pandemic, with 10-20% of severe cases and over 508,000 deaths worldwide.
目的:
本研究では，COVID-19 患者の重症度および重症患者の死亡率に関連する危険因子を取り上げることを目的としている．
OBJECTIVE: This study aims to address the risk factors associated with the severity of COVID-19 patients and the mortality of severe patients.
方法:
本研究には、入院中の臨床検査でCOVID-19が確認された289人の患者が含まれた。患者の人口統計学、臨床症状、併存疾患、臨床検査結果、放射線学的資料を含む電子カルテを収集し、分析した。患者の重症度と転帰に応じて、非生存群（n=49）、重症生存群（n=78）、非重症群（n=162）の3つのグループに分けた。これらのグループ間で臨床データ、検査データおよび放射線学的データを比較した。次元を減らし、患者を低次元空間で可視化するために主成分分析（PCA）を適用した。臨床、放射線、検査項目間の相関関係を調査した。重症患者の死亡率に関連する危険因子を決定するために、一変量および多変量ロジスティック回帰法を用いた。また、入院中に生存した重症患者と非生存患者の臨床検査所見の縦断的変化も収集した。
METHODS: 289 hospitalized laboratory-confirmed COVID-19 patients were included in this study. Electronic medical records, including patient demographics, clinical manifestation, comorbidities, laboratory tests results, and radiological materials were collected and analyzed. According to the severity and outcomes of the patients, they were divided into three groups: non-survived (n=49), survived severe (n=78), and non-severe (n=162) groups. Clinical, laboratory and radiological data were compared among these groups. Principal component analysis (PCA) was applied to reduce the dimensionality and visualize the patients on a low-dimensional space. Correlations between clinical, radiological and laboratory parameters were investigated. Univariate and multivariate logistic regression methods were used to determine the risk factors associated with mortality in severe patients. Longitudinal changes of laboratory findings of survived severe cases and non-survived cases during hospital stay were also collected.
結果:
289名の患者のうち，年齢中央値は57歳（範囲，22～88歳），155名（53.4％）が男性であった。本研究の最終フォローアップ日の時点で、240人（83.0％）の患者が退院し、49人（17.0％）の患者が死亡した。高齢化、併存疾患、および入院時の白血球数、好中球数、好中球対リンパ球比（NLR）、C反応性蛋白（CRP）、プロカルシトニン（PCT）、Dダイマー、アラニンアミノトランスフェラーゼ（ALT）、アスパラギン酸アミノトランスフェラーゼ（AST）、血中尿素窒素（BUN）などの臨床検査値の上昇が、非重症例に比べて生存している重症例で認められた。多変量ロジスティック回帰分析によると、高齢、罹患葉数の増加、入院時のCRP値の上昇、胸部圧迫感/呼吸困難の有病率の増加、喫煙歴が重症患者の死亡の独立した危険因子であった。PCAでは、「非重症」から「重症で生存した」患者を経て「非生存」への軌跡が観察された。患者の年齢、罹患葉数、臨床検査値との間には強い相関関係が認められた。重症生存例と非生存例の入院中の臨床検査所見を動的に変化させたところ、白血球数と好中球数の増加の継続、リンパ球減少と好酸球減少の持続、血小板数の減少の進行、NLR、CRP、PCT、AST、BUN、血清クレアチニンの高値が院内死亡と関連していることが明らかになった。
RESULTS: Of the 289 patients, the median age was 57 years (range, 22 - 88) and 155 (53.4%) patients were male. As of the final follow-up date of this study, 240 (83.0%) patients were discharged from the hospital and 49 (17.0%) patients died. Elder age, underlying comorbidities, and increased laboratory variables, such as leucocyte count, neutrophil count, neutrophil-to-lymphocyte ratio (NLR), C-reactive protein (CRP), procalcitonin (PCT), D-dimer, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and blood urea nitrogen (BUN) on admission were found in survived severe cases compared to non-severe cases. According to the multivariate logistic regression analysis, elder age, a higher number of affected lobes, elevated CRP levels on admission, increased prevalence of chest tightness/dyspnea and smoking history were independent risk factors for death of severe patients. A trajectory in PCA was observed from "non-severe" towards "non-survived" via "severe and survived" patients. Strong correlations between the age of patients, the affected lobe numbers and laboratory variables were identified. Dynamic changes of laboratory findings of survived severe cases and non-survived cases during hospital stay showed that continuing increase of leucocytes and neutrophil count, sustained lymphopenia and eosinopenia, progressing decrease in platelet count, as well as high levels of NLR, CRP, PCT, AST, BUN, and serum creatinine were associated with in-hospital death.
結論:
重症COVID-19の生存患者と非生存患者では、臨床的・検査的特徴が異なっており、主成分分析によって分離された。高齢、罹患葉数の増加、血清CRPの高値、胸部圧迫感/呼吸困難、喫煙歴は重症COVID-19患者の死亡率の危険因子であった。臨床検査所見の縦断的変化は、重症患者の疾患進行や臨床転帰の予測に役立つ可能性がある。
CONCLUSIONS: Survived severe and non-survived COVID-19 patients had distinct clinical and laboratory characteristics, which were separated by principle component analysis. Elder age, increased number of affected lobes, higher levels of serum CRP, chest tightness/dyspnea, and smoking history were risk factors for mortality of severe COVID-19 patients. Longitudinal changes of laboratory findings may be helpful in predicting disease progression and clinical outcome of severe patients.
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