Erratum: Inhaled ACE2-engineered microfluidic microsphere for intratracheal neutralization of COVID-19 and calming of the cytokine storm.

[This corrects the article DOI: 10.1016/j.matt.2021.09.022.].

Cover Picture: Nanoantidote for repression of acidosis pH promoting COVID-19 infection (View 4/2022)

Acidosis-related pH promotes SARS-CoV-2 pseudovirus infection by increasing cell membrane ACE2 expression. A CaCO3-NPs antacid nanoantidote restored the normal blood related pH 7.4, attenuating the SARS-CoV-2 pseudovirus infection. In article number 20220004, Wenguo Cui, Cheng Li, Siguang Li and their co-workers have suggested the existence of a positive feedback loop in which SARS-CoV-2 infection-induced acidosis enhances further SARS-CoV-2 infection. CaCO3-NPs nanoantidote may become an effective antacid.

Nanoantidote for repression of acidosis pH promoting COVID-19 infection.

Acidosis, such as respiratory acidosis and metabolic acidosis, can be induced by coronavirus disease 2019 (COVID-19) infection and is associated with increased mortality in critically ill COVID-19 patients. It remains unclear whether acidosis further promotes SARS-CoV-2 infection in patients, making virus removal difficult. For antacid therapy, sodium bicarbonate poses great risks caused by sodium overload, bicarbonate side effects, and hypocalcemia. Therefore, new antacid antidote is urgently needed. Our study showed that an acidosis-related pH of 6.8 increases SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2) expression on the cell membrane by regulating intracellular microfilament polymerization, promoting SARS-CoV-2 pseudovirus infection. Based on this, we synthesized polyglutamic acid-PEG materials, used complexation of calcium ions and carboxyl groups to form the core, and adopted biomineralization methods to form a calcium carbonate nanoparticles (CaCO3-NPs) nanoantidote to neutralize excess hydrogen ions (H+), and restored the pH from 6.8 to approximately 7.4 (normal blood pH). CaCO3-NPs effectively prevented the heightened SARS-CoV-2 infection efficiency due to pH 6.8. Our study reveals that acidosis-related pH promotes SARS-CoV-2 infection, which suggests the existence of a positive feedback loop in which SARS-CoV-2 infection-induced acidosis enhances SARS-CoV-2 infection. Therefore, antacid therapy for acidosis COVID-19 patients is necessary. CaCO3-NPs may become an effective antacid nanoantidote superior to sodium bicarbonate.

Inhaled ACE2-engineered microfluidic microsphere for intratracheal neutralization of COVID-19 and calming of the cytokine storm.

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.

CRISPR-Cas system for biomedical diagnostic platforms

Clustered short palindrome repeats with regular intervals, abbreviated as CRISPR, and functions as a self-defense system for prokaryotes, detecting particular pathogenic nucleic acid, interfering with the functions of exoteric DNA, and protecting them against foreign invaders. In recent years, CRISPR has attracted increasing interests in the in vitro diagnostic field because of its inherent allele specificity, which is one of the critical factors for the successful application of this technology in the development of high-precision treatment and diagnosis. Herein, this review article aims to provide an overview of CRISPR-CRISPR associated proteins (Cas) based biomedical diagnostics, including the biological mechanism, biomaterials, and applications. This paper first briefly introduces the development history and biological characteristics of the CRISPR-Cas system, and then summarizes the application status and development trend of the CRISPR-Cas system in the detection and identification of particular pathogens, specifically displaying a brilliant prospect in the most recent outbreak of novel coronavirus (formerly named 2019-nCoV). Moreover, its potential diagnostic power in oncogene mutations and single nucleotide variations detecting are assembled. Finally, we discuss challenges and future prospects of CRISPR-Cas system based diagnostic platforms in biomedicine, hoping to further inspire the development of biomedical diagnostics.