Aviptadil Injection

Since the outbreak of the coronavirus disease 2019 (COVID‑19) pandemic, it has posed enormous challenges to global public health. Severe cases are often complicated by acute respiratory distress syndrome (ARDS), which has become one of the leading causes of death in patients. ARDS is a severe form of acute lung injury characterized by damage to the alveolar‑capillary barrier, interstitial and alveolar edema, and refractory hypoxemia. COVID‑19‑associated ARDS (COVID‑19‑ARDS) is characterized by more rapid disease progression and greater therapeutic difficulty due to the systemic inflammatory response and lung‑specific injury induced by viral infection. As a synthetic vasoactive intestinal peptide (VIP), aviptadil injection has demonstrated potential therapeutic value in the treatment of COVID‑19‑ARDS owing to its unique anti‑inflammatory, lung‑protective, and immunomodulatory effects.

The pathogenesis of COVID‑19‑ARDS is complex, with the core being excessive inflammatory response and lung injury triggered by severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) infection: the virus invades cells by binding its spike protein to the ACE2 receptor on the surface of alveolar type II (ATII) epithelial cells, causing ATII cell damage and subsequent reduction in pulmonary surfactant production and alveolar collapse. Meanwhile, the virus activates the host immune system, releasing large amounts of pro‑inflammatory cytokines (e.g., interleukin‑6, tumor necrosis factor‑α, etc.) and triggering a "cytokine storm", which exacerbates damage to the alveolar‑capillary barrier, leading to pulmonary interstitial and alveolar edema, and ultimately hypoxemia and respiratory failure. The product acts through multiple targets and pathways to specifically ameliorate the pathophysiological processes of COVID‑19‑ARDS, with detailed mechanisms as follows.

2.1 Anti‑Inflammatory and Anti‑Cytokine Storm Effects

Aviptadil can specifically bind to target cells in the lungs, inhibit the production and release of pro‑inflammatory cytokines, and alleviate pulmonary inflammation. Studies have shown that aviptadil suppresses the synthesis of key pro‑inflammatory factors such as interleukin‑6 (IL‑6) and tumor necrosis factor‑α (TNF‑α), blocking the formation of a cytokine storm, thereby reducing damage to the alveolar‑capillary barrier by inflammatory mediators and alleviating pulmonary interstitial edema and alveolar inflammation. Its mechanism is related to the inhibition of N‑methyl‑D‑aspartate (NMDA)‑induced caspase‑3 activation, which further protects lung cells from inflammatory injury and maintains normal pulmonary physiological functions. This anti‑inflammatory effect is not limited to the lungs; it also modulates systemic immune responses, preventing excessive inflammation from damaging other organs and supporting multi‑organ protection in patients with COVID‑19‑ARDS.

2.2 Protection of Alveolar Type II Epithelial Cells and Promotion of Surfactant Synthesis

ATII cells are the main target cells of SARS‑CoV‑2 infection. Their injury leads to reduced synthesis of pulmonary surfactant, followed by alveolar collapse and impaired gas exchange, which is a key step in the development and progression of COVID‑19‑ARDS. Aviptadil injection can specifically bind to receptors on the surface of ATII cells, exerting cytoprotective effects to reduce viral damage to ATII cells, while stimulating ATII cells to synthesize and secrete more pulmonary surfactant. Pulmonary surfactant coats the inner surface of alveoli, lowering alveolar surface tension, preventing alveolar collapse, and maintaining normal alveolar expansion and gas exchange, thereby improving hypoxemia and relieving respiratory distress in patients. This effect distinguishes aviptadil from other anti‑inflammatory drugs and is one of the core mechanisms underlying its efficacy in ARDS.

2.3 Repair of the Alveolar‑Capillary Barrier and Reduction of Pulmonary Edema

Damage to the alveolar‑capillary barrier is a typical pathological feature of ARDS. The inflammatory response induced by COVID‑19 further disrupts the integrity of this barrier, causing intravascular fluid leakage into the pulmonary interstitium and alveoli, forming pulmonary edema and worsening respiratory dysfunction. Aviptadil can repair the damaged alveolar‑capillary barrier by regulating the function of alveolar capillary endothelial and epithelial cells, reducing intravascular fluid leakage, thereby alleviating pulmonary edema and improving pulmonary gas exchange efficiency. In addition, aviptadil exerts mild vasodilatory effects, improving pulmonary blood circulation, increasing pulmonary oxygen supply, further relieving hypoxemia, and creating favorable conditions for the repair of lung injury.

2.4 Adjuvant Antiviral Effects

In addition to its anti‑inflammatory and lung‑protective effects, aviptadil also exhibits certain antiviral potential. Non‑clinical studies have shown that VIP can block the replication of SARS‑CoV‑2 in lung cells and reduce viral lung injury. Its antiviral mechanism may involve the regulation of intracellular signaling pathways and inhibition of viral invasion and replication. Meanwhile, by improving the pulmonary microenvironment and enhancing the host's innate antiviral capacity, aviptadil injection may exert synergistic effects when combined with antiviral agents (e.g., remdesivir), further enhancing therapeutic outcomes.