BACKGROUND:Viral infections can cause acute respiratory distress syndrome (ARDS), systemic inflammation, and secondary cardiovascular complications. Lung macrophage subsets change during ARDS, but the role of heart macrophages in cardiac injury during viral ARDS remains unknown. Here we investigate how immune signals typical for viral ARDS affect cardiac macrophage subsets, cardiovascular health, and systemic inflammation.METHODS:We assessed cardiac macrophage subsets using immunofluorescence histology of autopsy specimens from 21 patients with COVID-19 with SARS-CoV-2–associated ARDS and 33 patients who died from other causes. In mice, we compared cardiac immune cell dynamics after SARS-CoV-2 infection with ARDS induced by intratracheal instillation of Toll-like receptor ligands and an ACE2 (angiotensin-converting enzyme 2) inhibitor.RESULTS:In humans, SARS-CoV-2 increased total cardiac macrophage counts and led to a higher proportion of CCR2⁺ (C-C chemokine receptor type 2 positive) macrophages. In mice, SARS-CoV-2 and virus-free lung injury triggered profound remodeling of cardiac resident macrophages, recapitulating the clinical expansion of CCR2⁺ macrophages. Treating mice exposed to virus-like ARDS with a tumor necrosis factor α–neutralizing antibody reduced cardiac monocytes and inflammatory MHCII^lo CCR2⁺ macrophages while also preserving cardiac function. Virus-like ARDS elevated mortality in mice with pre-existing heart failure.CONCLUSIONS:Our data suggest that viral ARDS promotes cardiac inflammation by expanding the CCR2⁺ macrophage subset, and the associated cardiac phenotypes in mice can be elicited by activating the host immune system even without viral presence in the heart.

中文翻译：

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病毒引起的急性呼吸窘迫综合征通过引起心脏炎症反应导致心肌病

背景：病毒感染可引起急性呼吸窘迫综合征（ARDS）、全身炎症和继发性心血管并发症。肺巨噬细胞亚群在 ARDS 期间发生变化，但心脏巨噬细胞在病毒性 ARDS 期间心脏损伤中的作用仍不清楚。在此，我们研究病毒性 ARDS 的典型免疫信号如何影响心脏巨噬细胞亚群、心血管健康和全身炎症。 方法：我们使用 21 名 SARS-CoV-2 相关 COVID-19 患者尸检标本的免疫荧光组织学方法评估心脏巨噬细胞亚群ARDS 和 33 名死于其他原因的患者。在小鼠中，我们比较了 SARS-CoV-2 感染后的心脏免疫细胞动态与通过气管内滴注 Toll 样受体配体和 ACE2（血管紧张素转换酶 2）抑制剂诱导的 ARDS 后的心脏免疫细胞动态。 结果：在人类中，SARS-CoV-2心脏巨噬细胞总数增加，导致 CCR2 ⁺（CC 趋化因子受体 2 型阳性）巨噬细胞比例更高。在小鼠中，SARS-CoV-2 和无病毒肺损伤引发了心脏驻留巨噬细胞的深刻重塑，重现了 CCR2 ⁺巨噬细胞的临床扩张。用肿瘤坏死因子 α 中和抗体治疗暴露于病毒样 ARDS 的小鼠，可减少心脏单核细胞和炎症性 MHCII ^lo CCR2 ⁺巨噬细胞，同时保留心脏功能。病毒样 ARDS 会提高患有心力衰竭的小鼠的死亡率。结论：我们的数据表明，病毒 ARDS 通过扩大 CCR2 ⁺巨噬细胞亚群来促进心脏炎症，并且可以通过激活宿主免疫系统来引发小鼠中相关的心脏表型即使心脏中没有病毒存在。