Activin A correlates with the worst outcomes in COVID-19 patients, and can be induced by cytokines via the IKK/NF-kappa B pathway

McAleavy, M.; Zhang, Q.; Xu, J.; Pan, L.; Wakai, M.; Ehmann, P. J.; Wipperman, M. F.; Shavlakadze, T.; Hamon, S. C.; Boyapati, A.; Morton, L. G.; Kyratsous, C. A.; Glass, D. J.

doi:10.1101/2021.02.04.429815

bioRxiv · 10.1101/2021.02.04.429815

Activin A correlates with the worst outcomes in COVID-19 patients, and can be induced by cytokines via the IKK/NF-kappa B pathway

McAleavy, M.·Zhang, Q.·Xu, J.·Pan, L.·Wakai, M.·Ehmann, P. J.·Wipperman, M. F.·Shavlakadze, T.·Hamon, S. C.·Boyapati, A.·Morton, L. G.·Kyratsous, C. A.·Glass, D. J.

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Abstract

A fraction of COVID-19 patients develop the most severe form, characterized by Acute Respiratory Disease Syndrome (ARDS). The molecular mechanisms causing COVID-19-induced ARDS have yet to be defined, though many studies have documented an increase in cytokines known as a "cytokine storm." Here, we demonstrate that cytokines that activate the NF-kappaB pathway can induce Activin A and its downstream marker, FLRG. In hospitalized COVID-19 patients elevated Activin A/FLRG at baseline were predictive of the most severe longitudinal outcomes of COVID-19, including the need for mechanical ventilation, lack of clinical improvement and all-cause mortality. Patients with Activin A/FLRG above the sample median were 2.6/2.9 times more likely to die, relative to patients with levels below the sample median, respectively. The study indicates high levels of Activin A and FLRG put patients at risk of ARDS, and blockade of Activin A may be beneficial in treating COVID-19 patients experiencing ARDS.

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McAleavy, M., Zhang, Q., Xu, J., Pan, L., Wakai, M., Ehmann, P. J., Wipperman, M. F., Shavlakadze, T., Hamon, S. C., Boyapati, A., Morton, L. G., Kyratsous, C. A., Glass, D. J.. 2021-02-08. Activin A correlates with the worst outcomes in COVID-19 patients, and can be induced by cytokines via the IKK/NF-kappa B pathway. https://doi.org/10.1101/2021.02.04.429815

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