Your browser doesn't support javascript.
A virus-free cellular model recapitulates several features of severe COVID-19.
Lavorgna, Giovanni; Cavalli, Giulio; Dagna, Lorenzo; Gregori, Silvia; Larcher, Alessandro; Landoni, Giovanni; Ciceri, Fabio; Montorsi, Francesco; Salonia, Andrea.
  • Lavorgna G; Division of Experimental Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy. lavorgna.giovanni@hsr.it.
  • Cavalli G; University Vita-Salute San Raffaele, Milan, Italy.
  • Dagna L; Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR), IRCCS San Raffaele Scientific Institute, Milan, Italy.
  • Gregori S; University Vita-Salute San Raffaele, Milan, Italy.
  • Larcher A; Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR), IRCCS San Raffaele Scientific Institute, Milan, Italy.
  • Landoni G; San Raffaele Telethon Institute for Gene Therapy (SR-TIGET), IRCCS Ospedale San Raffaele, Milan, Italy.
  • Ciceri F; Division of Experimental Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy.
  • Montorsi F; University Vita-Salute San Raffaele, Milan, Italy.
  • Salonia A; Anesthesia and Intensive Care Department, IRCCS Ospedale San Raffaele, Milan, Italy.
Sci Rep ; 11(1): 17473, 2021 09 01.
Article in English | MEDLINE | ID: covidwho-1392888
ABSTRACT
As for all newly-emergent pathogens, SARS-CoV-2 presents with a relative paucity of clinical information and experimental models, a situation hampering both the development of new effective treatments and the prediction of future outbreaks. Here, we find that a simple virus-free model, based on publicly available transcriptional data from human cell lines, is surprisingly able to recapitulate several features of the clinically relevant infections. By segregating cell lines (n = 1305) from the CCLE project on the base of their sole angiotensin-converting enzyme 2 (ACE2) mRNA content, we found that overexpressing cells present with molecular features resembling those of at-risk patients, including senescence, impairment of antibody production, epigenetic regulation, DNA repair and apoptosis, neutralization of the interferon response, proneness to an overemphasized innate immune activity, hyperinflammation by IL-1, diabetes, hypercoagulation and hypogonadism. Likewise, several pathways were found to display a differential expression between sexes, with males being in the least advantageous position, thus suggesting that the model could reproduce even the sex-related disparities observed in the clinical outcome of patients with COVID-19. Overall, besides validating a new disease model, our data suggest that, in patients with severe COVID-19, a baseline ground could be already present and, as a consequence, the viral infection might simply exacerbate a variety of latent (or inherent) pre-existing conditions, representing therefore a tipping point at which they become clinically significant.
Subject(s)

Full text: Available Collection: International databases Database: MEDLINE Main subject: Up-Regulation / Gene Expression Profiling / Angiotensin-Converting Enzyme 2 / COVID-19 Type of study: Prognostic study Limits: Female / Humans / Male Language: English Journal: Sci Rep Year: 2021 Document Type: Article Affiliation country: S41598-021-96875-7

Similar

MEDLINE

...
LILACS

LIS


Full text: Available Collection: International databases Database: MEDLINE Main subject: Up-Regulation / Gene Expression Profiling / Angiotensin-Converting Enzyme 2 / COVID-19 Type of study: Prognostic study Limits: Female / Humans / Male Language: English Journal: Sci Rep Year: 2021 Document Type: Article Affiliation country: S41598-021-96875-7