The SARS-CoV-2 pandemic spread worldwide unabated. However, achieving protection from the virus in the whole respiratory tract, avoiding blood dissemination, and calming the subsequent cytokine storm remains a major challenge. Here, we develop an inhaled microfluidic microsphere using dual camouflaged methacrylate hyaluronic acid hydrogel microspheres with a genetically engineered membrane from angiotensin-converting enzyme II (ACE2) receptor-overexpressing cells and macrophages. By timely competing with the virus for ACE2 binding, the inhaled microspheres significantly reduce SARS-CoV-2 infective effectiveness over the whole course of the respiratory system in vitro and in vivo. Moreover, the inhaled microspheres efficiently neutralize proinflammatory cytokines, cause an alternative landscape of lung-infiltrated immune cells, and alleviate hyperinflammation of lymph nodes and spleen. In an acute pneumonia model, the inhaled microspheres show significant therapeutic efficacy by regulation of the multisystem inflammatory syndrome and reduce acute mortality, suggesting a powerful synergic strategy for the treatment of patients with severe COVID-19 via non-invasive administration.
Keyphrases
- sars cov
- angiotensin converting enzyme
- angiotensin ii
- hyaluronic acid
- cystic fibrosis
- respiratory tract
- coronavirus disease
- respiratory syndrome coronavirus
- liver failure
- molecularly imprinted
- lymph node
- respiratory failure
- single cell
- randomized controlled trial
- circulating tumor cells
- aortic dissection
- systematic review
- type diabetes
- oxidative stress
- drug delivery
- cardiovascular events
- risk factors
- binding protein
- early onset
- cell proliferation
- cardiovascular disease
- extracorporeal membrane oxygenation
- rectal cancer
- simultaneous determination
- acute respiratory distress syndrome
- replacement therapy
- dna binding
- smoking cessation
- neoadjuvant chemotherapy