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The Activin/FLRG Pathway Associates with Poor COVID-19 Outcomes in Hospitalized Patients.
McAleavy, Megan; Zhang, Qian; Ehmann, Peter J; Xu, Jianing; Wipperman, Matthew F; Ajithdoss, Dharani; Pan, Li; Wakai, Matthew; Simonson, Raphael; Gadi, Abhilash; Oyejide, Adelekan; Hamon, Sara C; Boyapati, Anita; Morton, Lori G; Shavlakadze, Tea; Kyratsous, Christos A; Glass, David J.
  • McAleavy M; Regeneron Pharmaceuticals Inc., Tarrytown, New York, USA.
  • Zhang Q; Regeneron Pharmaceuticals Inc., Tarrytown, New York, USA.
  • Ehmann PJ; Regeneron Pharmaceuticals Inc., Tarrytown, New York, USA.
  • Xu J; Regeneron Pharmaceuticals Inc., Tarrytown, New York, USA.
  • Wipperman MF; Regeneron Pharmaceuticals Inc., Tarrytown, New York, USA.
  • Ajithdoss D; Regeneron Pharmaceuticals Inc., Tarrytown, New York, USA.
  • Pan L; Regeneron Pharmaceuticals Inc., Tarrytown, New York, USA.
  • Wakai M; Regeneron Pharmaceuticals Inc., Tarrytown, New York, USA.
  • Simonson R; Regeneron Pharmaceuticals Inc., Tarrytown, New York, USA.
  • Gadi A; Regeneron Pharmaceuticals Inc., Tarrytown, New York, USA.
  • Oyejide A; Regeneron Pharmaceuticals Inc., Tarrytown, New York, USA.
  • Hamon SC; Regeneron Pharmaceuticals Inc., Tarrytown, New York, USA.
  • Boyapati A; Regeneron Pharmaceuticals Inc., Tarrytown, New York, USA.
  • Morton LG; Regeneron Pharmaceuticals Inc., Tarrytown, New York, USA.
  • Shavlakadze T; Regeneron Pharmaceuticals Inc., Tarrytown, New York, USA.
  • Kyratsous CA; Regeneron Pharmaceuticals Inc., Tarrytown, New York, USA.
  • Glass DJ; Regeneron Pharmaceuticals Inc., Tarrytown, New York, USA.
Mol Cell Biol ; 42(1): e0046721, 2022 01 20.
Article in English | MEDLINE | ID: covidwho-1494978
ABSTRACT
A subset of hospitalized COVID-19 patients, particularly the aged and those with comorbidities, develop the most severe form of the disease, characterized by acute respiratory disease syndrome (ARDS), coincident with experiencing a "cytokine storm." Here, we demonstrate that cytokines which activate the NF-κB pathway can induce activin A. Patients with elevated activin A, activin B, and FLRG at hospital admission were associated with the most severe outcomes of COVID-19, including the requirement for mechanical ventilation, and all-cause mortality. A prior study showed that activin A could decrease viral load, which indicated there might be a risk to giving COVID-19 patients an inhibitor of activin. To evaluate this, the role for activin A was examined in a hamster model of SARS-CoV-2 infection, via blockade of activin A signaling. The hamster model demonstrated that use of an anti-activin A antibody did not worsen the disease and there was no evidence for increase in lung viral load and pathology. The study indicates blockade of activin signaling may be beneficial in treating COVID-19 patients experiencing ARDS.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Activins / Follistatin-Related Proteins / Antibodies, Monoclonal, Humanized / SARS-CoV-2 / COVID-19 Drug Treatment Type of study: Experimental Studies / Prognostic study / Randomized controlled trials Limits: Adult / Aged / Animals / Female / Humans / Male / Middle aged Language: English Journal: Mol Cell Biol Year: 2022 Document Type: Article Affiliation country: MCB.00467-21

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Activins / Follistatin-Related Proteins / Antibodies, Monoclonal, Humanized / SARS-CoV-2 / COVID-19 Drug Treatment Type of study: Experimental Studies / Prognostic study / Randomized controlled trials Limits: Adult / Aged / Animals / Female / Humans / Male / Middle aged Language: English Journal: Mol Cell Biol Year: 2022 Document Type: Article Affiliation country: MCB.00467-21