The interest on the role of angiogenesis in the pathogenesis and progression of human interstitial lung diseases is growing, with conventional sprouting (SA) and non-sprouting intussusceptive angiogenesis (IA) being differently represented in specific pulmonary injury patterns. The role of viruses as key regulators of angiogenesis is known for several years. A significantly enhanced amount of new vessel growth, through a mechanism of IA, has been reported in lungs of patients who died from Covid-19; among the angiogenesis-related genes, fibroblast growth factor 2 (FGF2) was found to be upregulated. These findings are intriguing. FGF2 plays a role in some viral infections: the upregulation is involved in the MERS-CoV-induced strong apoptotic response crucial for its highly lytic replication cycle in lung cells, whereas FGF2 is protective against the acute lung injury induced by H1N1 influenza virus, improving the lung wet-to-dry weight ratio. FGF2 plays a role also in regulating IA, acting on pericytes (crucial for the formation of intraluminal pillars), and endothelium, and FGF2-induced angiogenesis may be promoted by inflammation and hypoxia. IA is a faster and probably more efficient process than SA, able to modulate vascular remodeling through pruning of redundant or inefficient blood vessels. We can speculate that IA might have the function of restoring a functional vascular plexus consequently to extensive endothelialitis and alveolar capillary micro-thrombosis observed in Covid-19. Anti-Vascular endothelial growth factor (anti-VEGF) strategies are currently investigated for treatment of severe and critically ill Covid-19 patients, but also FGF2, and its expression and/or signaling, might represent a promising target.

对血管生成在人类间质性肺疾病发病机制和进展中的作用的兴趣正在增长，常规发芽 (SA) 和非发芽肠套叠性血管生成 (IA) 在特定肺损伤模式中的表现不同。多年来，病毒作为血管生成的关键调节剂的作用是众所周知的。据报道，死于 Covid-19 的患者的肺部通过 IA 机制显着增加了新血管的生长量；在血管生成相关基因中，发现成纤维细胞生长因子 2 (FGF2) 上调。这些发现很有趣。FGF2 在一些病毒感染中发挥作用：上调参与 MERS-CoV 诱导的强烈凋亡反应，这对其在肺细胞中的高度裂解复制周期至关重要，而 FGF2 对 H1N1 流感病毒引起的急性肺损伤具有保护作用，可提高肺湿重比。FGF2 还在调节 IA、作用于周细胞（对于腔内柱的形成至关重要）和内皮中发挥作用，炎症和缺氧可促进 FGF2 诱导的血管生成。IA 是比 SA 更快且可能更有效的过程，能够通过修剪多余或低效的血管来调节血管重塑。我们可以推测，IA 可能具有恢复功能性血管丛的功能，从而导致在 Covid-19 中观察到的广泛内皮炎和肺泡毛细血管微血栓形成。目前正在研究抗血管内皮生长因子 (anti-VEGF) 策略用于治疗重症和危重 Covid-19 患者，以及 FGF2、