SARS-CoV-2 infects lung epithelial cells and induces senescence and an inflammatory response in patients with severe COVID-19

Abstract

SARS-CoV-2 infection of the respiratory system can evolve to a multi-system disease. Excessive levels of proinflammatory cytokines, known as a "cytokine storm" are associated with high mortality rates especially in the elderly and in patients with age-related morbidities. Senescent cells, characterized by secretion of such cytokines (Senescence Associated Secretory Phenotype - SASP), are known to occur in this context as well as upon a variety of stressogenic insults. Applying both: i) a novel "in house" antibody against the spike protein of SARS-CoV-2 and ii) a unique senescence detecting methodology, we identified for the first time in lung tissue from COVID-19 patients alveolar cells acquiring senescent features harboring also SARS-CoV-2. Moreover, using the same detection workflow we demonstrated the inflammatory properties of these cells. Our findings justify the application of senotherapeutics for the treatment or prevention of COVID-19 patients.

OnTheFly2.0: a text-mining web application for automated biomedical entity recognition, document annotation, network and functional enrichment analysis

“…We note that predicted REACTOME pathways included "cellular senescence" despite the absence of specific references to this biological term in any of the six annotated meta-analysis reports under study. In line with this prediction, COVID-19 pneumonia has recently been associated with immunosenescence (64) and accelerated aging of pneumocytes (65). Overall, the aforementioned analyses underscore the practical utility of OnTheFly 2.0 to rapidly extract biological information from texts and hence assisting knowledge discovery (Figure 4).…”

COVID-19 Immunobiology: Lessons Learned, New Questions Arise

“…In parallel, viral infection of host cells activates both the innate and adaptive arms of the immune system, mounting an immune response against SARS-CoV-2. Robust aberrant cellular alterations, including cellular senescence (31), apoptosis, with emphasis in the inflammatory subtypes thereof [pyroptosis (32), necroptosis (33), PANoptosis (34)] and NETosis are implicated in the disease course and severity.…”

“…Cellular senescence is a stress response against a plethora of cellular insults, including effects of infectious agents through mechanisms of DNA damage, cell fusion and ER stress (31). It is characterized by 4 interconnected hallmarks of: cell cycle arrest, macromolecular damage, altered metabolism and proinflammatory features, called the senescence-associated secretory phenotype (SASP) (99).…”

SARS-CoV-2 Antigenemia as a Confounding Factor in Immunodiagnostic Assays: A Case Study

“…The specificity of the immunohistochemical signal was confirmed by (1) omitting the primary antibody and (2) performing competition with the corresponding S antigen (Supplementary Figure S1A). Tissues from a large cohort of non-COVID-19 patients served as negative controls, whereas viral particles were detected in archival material from lung tissues of COVID-19 patients [18,19].…”

“…Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the culprit of an ongoing pandemic, continues to engender detrimental effects on healthcare systems worldwide leading to serious socioeconomic consequences. Following an incubation period of 2-14 days infected individuals experience a heterogeneous clinical course of the so-called Coronavirus Disease-2019 (COVID- 19), ranging from asymptomatic infection to critical illness [1,2]. Similarly, symptomatic infection comprises of a wide array of clinical manifestations from localized disease affecting preferentially the respiratory and occasionally the gastrointestinal tract to multisystemic organ involvement [3,4].…”