iPSC-Derived Airway Epithelial Cells: Progress, Promise, and Challenges.

Induced pluripotent stem cells (iPSCs) generated from somatic cell sources are pluripotent and capable of indefinite expansion in vitro. They provide an unlimited source of cells that can be differentiated into lung progenitor cells for potential clinical use in pulmonary regenerative medicine. This review gives a comprehensive overview of recent progress toward the use of iPSCs to generate proximal and distal airway epithelial cells and mix lung organoids. Furthermore, their potential applications and future challenges for the field are discussed, with a focus on the technological hurdles that must be cleared before stem cell therapeutics can be used for clinical treatment.

Neuropilin-1-Mediated SARS-CoV-2 Infection in Bone Marrow-Derived Macrophages Inhibits Osteoclast Differentiation.

In humans, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can cause medical complications across various tissues and organs. Despite the advances to understanding the pathogenesis of SARS-CoV-2, its tissue tropism and interactions with host cells have not been fully understood. Existing clinical data have revealed disordered calcium and phosphorus metabolism in Coronavirus Disease 2019 (COVID-19) patients, suggesting possible infection or damage in the human skeleton system by SARS-CoV-2. Herein, SARS-CoV-2 infection in mouse models with wild-type and beta strain (B.1.351) viruses is investigated, and it is found that bone marrow-derived macrophages (BMMs) can be efficiently infected in vivo. Single-cell RNA sequencing (scRNA-Seq) analyses of infected BMMs identify distinct clusters of susceptible macrophages, including those related to osteoblast differentiation. Interestingly, SARS-CoV-2 entry on BMMs is dependent on the expression of neuropilin-1 (NRP1) rather than the widely recognized receptor angiotensin-converting enzyme 2 (ACE2). The loss of NRP1 expression during BMM-to-osteoclast differentiation or NRP1 neutralization and knockdown can significantly inhibit SARS-CoV-2 infection in BMMs. Importantly, it is found that authentic SARS-CoV-2 infection impedes BMM-to-osteoclast differentiation. Collectively, this study provides evidence for NRP1-mediated SARS-CoV-2 infection in BMMs and establishes a potential link between disturbed osteoclast differentiation and disordered skeleton metabolism in COVID-19 patients.

Detection of Anti-SARS-CoV-2-S2 IgG Is More Sensitive Than Anti-RBD IgG in Identifying Asymptomatic COVID-19 Patients.

Characterizing the serologic features of asymptomatic SARS-CoV-2 infection is imperative to improve diagnostics and control of SARS-CoV-2 transmission. In this study, we evaluated the antibody profiles in 272 plasma samples collected from 59 COVID-19 patients, consisting of 18 asymptomatic patients, 33 mildly ill patients and 8 severely ill patients. We measured the IgG against five viral structural proteins, different isotypes of immunoglobulins against the Receptor Binding Domain (RBD) protein, and neutralizing antibodies. The results showed that the overall antibody response was lower in asymptomatic infections than in symptomatic infections throughout the disease course. In contrast to symptomatic patients, asymptomatic patients showed a dominant IgG-response towards the RBD protein, but not IgM and IgA. Neutralizing antibody titers had linear correlations with IgA/IgM/IgG levels against SARS-CoV-2-RBD, as well as with IgG levels against multiple SARS-CoV-2 structural proteins, especially with anti-RBD or anti-S2 IgG. In addition, the sensitivity of anti-S2-IgG is better in identifying asymptomatic infections at early time post infection compared to anti-RBD-IgG. These data suggest that asymptomatic infections elicit weaker antibody responses, and primarily induce IgG antibody responses rather than IgA or IgM antibody responses. Detection of IgG against the S2 protein could supplement nucleic acid testing to identify asymptomatic patients. This study provides an antibody detection scheme for asymptomatic infections, which may contribute to epidemic prevention and control.