There is an urgent need for new drugs for ARDS patients, including those with COVID-19. ARDS in influenza-infected mice is associated with reduced levels of liponucleotides (essential precursors for de novo phospholipid synthesis) in alveolar type II (ATII) epithelial cells.

Because surfactant phospholipid synthesis is a primary function of ATII cells, we hypothesized that disrupting this process could contribute significantly to the pathogenesis of influenza-induced ARDS. The goal of this study was to determine whether parenteral liponucleotide supplementation can attenuate ARDS.

C57BL/6 mice inoculated intranasally with 10,000 pfu/mouse of H1N1 influenza A/WSN/33 virus were treated with CDP-choline (100 μg/mouse, i.p.) +/- CDP-diacylglycerol 16:0/16:0 (10 μg/mouse, i.p.) once daily from 1-5 days post-inoculation (to model post-exposure influenza prophylaxis) or as a single dose on day 5 (to model treatment of patients with ongoing influenza-induced ARDS).

Daily post-exposure prophylaxis with CDP-choline attenuated influenza-induced hypoxemia, pulmonary edema, alterations in lung mechanics, impairment of alveolar fluid clearance, and pulmonary inflammation without altering viral replication.

These effects were not recapitulated by daily administration of CTP and/or choline.

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