In this context, our study highlights the potential of PDE4 inhibitors (such as roflumilast which has been shown to provide clinical benefits in patients with chronic obstructive pulmonary disease), as a candidate treatment option for alleviating intracellular Cl− accumulation and mitigating inflammatory responses induced by SARS-CoV-2 E protein in COVID-19 cases. Here, PROS1 is linked to COVID-19.