Research press release


Nature Medicine

Immunology: Analysis of respiratory immune responses in patients with COVID-19

COVID-19患者では、呼吸器系の免疫応答に異常が見られることがNature Medicine に報告された。9人のCOVID-19患者の気管支肺胞の免疫細胞が調べられたこの研究は、SARS-CoV-2(COVID-19を引き起こす新型コロナウイルス)に対する免疫応答の基盤となる仕組みを解明する助けとなりそうだ。


Z Zhangたちは、COVID-19患者9人の気管支肺胞洗浄液(BALF)から抽出した免疫細胞を、単一細胞RNA塩基配列解読法を使って解析した。気管支肺胞洗浄は診断手法の1つで、鼻あるいは口から肺内部へと管を挿入して、生理食塩水を肺へと注入し、これを回収して検査を行う。患者のうち6人は重症/重篤(severe/critical)に分類され、その大半は機械的人工換気を必要とした。3人は中等症(moderate)と診断され、発熱と肺炎が見られた。患者の年齢の中央値は57歳で、6人が男性、3人は女性である。著者たちは、対照として3人の健常者と公的に入手できたBALF試料1例についても調べた。



Abnormalities in the respiratory immune response of patients with COVID-19 are reported in a paper in Nature Medicine. The study, which analyzed bronchoalveolar immune cells of nine patients with COVID-19, may aid in the understanding of potential mechanisms underlying immune responses to SARS-CoV-2 (the coronavirus that causes COVID-19).

Abnormal immune responses to coronavirus infections have been shown in animal models. However, human respiratory immune responses to SARS-CoV-2 have remained unclear.

Zheng Zhang and colleagues used single-cell RNA sequencing to analyze samples of immune cells extracted from bronchoalveolar lavage fluid (BALF) from nine patients with COVID-19. Bronchoalveolar lavage is a diagnostic procedure in which a tube is inserted through the nose or mouth and is passed into the lungs. The tube is used to flush the lungs with fluid, which is then recollected for testing. Six of the patients were categorized as severe/critical, with most requiring mechanical ventilation, and three were categorized as moderate, with fever and pneumonia. The patients had a median age of 57 and included six males and three females. The authors also examined three healthy control subjects and a publicly available BALF sample.

The authors found that BALF samples from the patients with severe/critical disease contained higher concentrations of macrophages and neutrophils (types of white blood cell) than did those from the moderate and control groups. The patients with severe/critical disease also had higher levels of inflammatory cytokines and chemokines ― signaling proteins released by immune cells. From this the authors infer that an inflammatory macrophage microenvironment is present in the lungs of patients with severe/critical COVID-19. The authors also analyzed the diversity of T cells, another type of white blood cell, in these samples. They found that in patients with severe/critical disease, there were higher proportions of proliferating T cells. However, the proportion of CD8+ T cells, which serve an important role in anti-viral immune responses by killing infected cells, were lower than in patients with moderate disease.

The findings reveal potential irregular macrophage and T cell responses during COVID-19, but the authors caution that there are limitations to the study, including a limited sample size and lack of longitudinal samples collected before and after infection.

doi: 10.1038/s41591-020-0901-9

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