When surveying the current literature on COVID-19, the “cytokine storm” is considered to be pathogenetically involved in its severe outcomes such as acute respiratory distress syndrome, systemic inflammatory response syndrome, and eventually multiple organ failure. In this review, the similar role of DAMPs is addressed, that is, of those molecules, which operate upstream of the inflammatory pathway by activating those cells, which ultimately release the cytokines. Given the still limited reports on their role in COVID-19, the emerging topic is extended to respiratory viral infections with focus on influenza. At first, a brief introduction is given on the function of various classes of activating DAMPs and counterbalancing suppressing DAMPs (SAMPs) in initiating controlled inflammation-promoting and inflammation-resolving defense responses upon infectious and sterile insults. It is stressed that the excessive emission of DAMPs upon severe injury uncovers their fateful property in triggering dysregulated life-threatening hyperinflammatory responses. Such a scenario may happen when the viral load is too high, for example, in the respiratory tract, “forcing” many virus-infected host cells to decide to commit “suicidal” regulated cell death (e.g., necroptosis, pyroptosis) associated with release of large amounts of DAMPs: an important topic of this review. Ironically, although the aim of this “suicidal” cell death is to save and restore organismal homeostasis, the intrinsic release of excessive amounts of DAMPs leads to those dysregulated hyperinflammatory responses—as typically involved in the pathogenesis of acute respiratory distress syndrome and systemic inflammatory response syndrome in respiratory viral infections. Consequently, as briefly outlined in this review, these molecules can be considered valuable diagnostic and prognostic biomarkers to monitor and evaluate the course of the viral disorder, in particular, to grasp the eventual transition precociously from a controlled defense response as observed in mild/moderate cases to a dysregulated life-threatening hyperinflammatory response as seen, for example, in severe/fatal COVID-19. Moreover, the pathogenetic involvement of these molecules qualifies them as relevant future therapeutic targets to prevent severe/ fatal outcomes. Finally, a theory is presented proposing that the superimposition of coronavirus-induced DAMPs with non-virus-induced DAMPs from other origins such as air pollution or high age may contribute to severe and fatal courses of coronavirus pneumonia.

在调查当前有关 COVID-19 的文献时，“细胞因子风暴”被认为在发病机制上涉及其严重后果，例如急性呼吸窘迫综合征、全身炎症反应综合征以及最终的多器官衰竭。在这篇综述中，DAMP 的类似作用得到了解决，即这些分子通过激活这些细胞在炎症途径的上游发挥作用，最终释放细胞因子。鉴于有关其在 COVID-19 中的作用的报道仍然有限，这一新兴主题已扩展到呼吸道病毒感染，重点是流感。首先，简要介绍了各类激活 DAMP 和平衡抑制 DAMP (SAMP) 在感染性和无菌性损伤时启动受控炎症促进和炎症消解防御反应的功能。需要强调的是，严重损伤时 DAMP 的过度释放揭示了它们在引发失调的危及生命的高炎症反应方面的致命特性。当病毒载量过高时，例如在呼吸道中，“迫使”许多病毒感染的宿主细胞决定进行与释放相关的“自杀性”调节性细胞死亡（例如坏死性凋亡、细胞焦亡）时，可能会发生这种情况大量 DAMP 的处理：本次综述的一个重要主题。具有讽刺意味的是，尽管这种“自杀性”细胞死亡的目的是拯救和恢复机体稳态，但过量 DAMP 的内在释放会导致过度炎症反应失调，这通常与急性呼吸窘迫综合征和全身炎症反应的发病机制有关呼吸道病毒感染综合征。 因此，正如本综述中简要概述的那样，这些分子可以被认为是有价值的诊断和预后生物标志物，用于监测和评估病毒性疾病的进程，特别是提前掌握从轻度/中度观察到的受控防御反应的最终转变。危及生命的过度炎症反应失调的病例，例如严重/致命的 COVID-19。此外，这些分子的致病作用使它们有资格成为未来预防严重/致命结果的相关治疗靶点。最后，提出了一种理论，认为冠状病毒诱导的 DAMP 与空气污染或高龄等其他来源的非病毒诱导的 DAMP 叠加可能会导致冠状病毒肺炎的严重和致命病程。