Insights Gained Into the Treatment of COVID19 by Pulmonary Surfactant and Its Components

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Abstract

Pulmonary surfactant constitutes an important barrier that pathogens must cross to gain access to the rest of the organism via the respiratory surface. The presence of pulmonary surfactant prevents the dissemination of pathogens, modulates immune responses, and optimizes lung biophysical activity. Thus, the application of pulmonary surfactant for the treatment of respiratory diseases provides an effective strategy. Currently, several clinical trials are investigating the use of surfactant preparations to treat patients with coronavirus disease 2019 (COVID-19). Some factors have been considered in the application of pulmonary surfactant for the treatment COVID-19, such as mechanical ventilation strategy, timing of treatment, dose delivered, method of delivery, and preparation utilized. This review supplements this list with two additional factors: accurate measurement of surfactants in patients and proper selection of pulmonary surfactant components. This review provides a reference for ongoing exogenous surfactant trials involving patients with COVID-19 and provides insight for the development of surfactant preparations for the treatment of viral respiratory infections.

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Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein

Alexandra C Walls, Young-Jun Park, M. Alejandra Tortorici … (2020)

Summary The emergence of SARS-CoV-2 has resulted in >90,000 infections and >3,000 deaths. Coronavirus spike (S) glycoproteins promote entry into cells and are the main target of antibodies. We show that SARS-CoV-2 S uses ACE2 to enter cells and that the receptor-binding domains of SARS-CoV-2 S and SARS-CoV S bind with similar affinities to human ACE2, correlating with the efficient spread of SARS-CoV-2 among humans. We found that the SARS-CoV-2 S glycoprotein harbors a furin cleavage site at the boundary between the S1/S2 subunits, which is processed during biogenesis and sets this virus apart from SARS-CoV and SARS-related CoVs. We determined cryo-EM structures of the SARS-CoV-2 S ectodomain trimer, providing a blueprint for the design of vaccines and inhibitors of viral entry. Finally, we demonstrate that SARS-CoV S murine polyclonal antibodies potently inhibited SARS-CoV-2 S mediated entry into cells, indicating that cross-neutralizing antibodies targeting conserved S epitopes can be elicited upon vaccination.

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Single-cell landscape of bronchoalveolar immune cells in patients with COVID-19

Mingfeng Liao, Yang Liu, Jing Yuan … (2020)

Respiratory immune characteristics associated with Coronavirus Disease 2019 (COVID-19) severity are currently unclear. We characterized bronchoalveolar lavage fluid immune cells from patients with varying severity of COVID-19 and from healthy people by using single-cell RNA sequencing. Proinflammatory monocyte-derived macrophages were abundant in the bronchoalveolar lavage fluid from patients with severe COVID-9. Moderate cases were characterized by the presence of highly clonally expanded CD8+ T cells. This atlas of the bronchoalveolar immune microenvironment suggests potential mechanisms underlying pathogenesis and recovery in COVID-19.

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Inborn errors of type I IFN immunity in patients with life-threatening COVID-19

Qian Zhang, Paul Bastard, Zhiyong Liu … (2021)

The genetics underlying severe COVID-19 The immune system is complex and involves many genes, including those that encode cytokines known as interferons (IFNs). Individuals that lack specific IFNs can be more susceptible to infectious diseases. Furthermore, the autoantibody system dampens IFN response to prevent damage from pathogen-induced inflammation. Two studies now examine the likelihood that genetics affects the risk of severe coronavirus disease 2019 (COVID-19) through components of this system (see the Perspective by Beck and Aksentijevich). Q. Zhang et al. used a candidate gene approach and identified patients with severe COVID-19 who have mutations in genes involved in the regulation of type I and III IFN immunity. They found enrichment of these genes in patients and conclude that genetics may determine the clinical course of the infection. Bastard et al. identified individuals with high titers of neutralizing autoantibodies against type I IFN-α2 and IFN-ω in about 10% of patients with severe COVID-19 pneumonia. These autoantibodies were not found either in infected people who were asymptomatic or had milder phenotype or in healthy individuals. Together, these studies identify a means by which individuals at highest risk of life-threatening COVID-19 can be identified. Science, this issue p. eabd4570, p. eabd4585; see also p. 404

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Contributors

Dan Li: URI : https://loop.frontiersin.org/people/1595132

Xianzheng Wang: URI : https://loop.frontiersin.org/people/1296776

Shouchuan Wang: URI : https://loop.frontiersin.org/people/1566628

Jinjun Shan: URI : https://loop.frontiersin.org/people/543945

Jianjian Ji: URI : https://loop.frontiersin.org/people/616900

Journal

Journal ID (nlm-ta): Front Immunol

Journal ID (iso-abbrev): Front Immunol

Journal ID (publisher-id): Front. Immunol.

Title: Frontiers in Immunology

Publisher: Frontiers Media S.A.

ISSN (Electronic): 1664-3224

Publication date (Electronic): 03 May 2022

Publication date Collection: 2022

Publication date PMC-release: 03 May 2022

Volume: 13

Electronic Location Identifier: 842453

Affiliations

[1] ¹ Jiangsu Key Laboratory of Pediatric Respiratory Disease, Institute of Pediatrics, Nanjing University of Chinese Medicine , Nanjing, China

[2] ² Department of Immunology, Nanjing University of Chinese Medicine , Nanjing, China

[3] ³ Pediatrics of Traditional Chinese Medicine, Shenzhen Traditional Chinese Medicine Hospital , Shenzhen, China

Author notes

Edited by: Taruna Madan, National Institute for Research in Reproductive Health (ICMR), India

Reviewed by: Shantibhusan Senapati, Institute of Life Sciences (ILS), India; Hrishikesh Pandit, National Cancer Institute at Frederick (NIH), United States

*Correspondence: Shouchuan Wang, wscnj@ 123456njucm.edu.cn ; Jianjian Ji, jijj@ 123456njucm.edu.cn ; Jinjun Shan, jshan@ 123456njucm.edu.cn

This article was submitted to Viral Immunology, a section of the journal Frontiers in Immunology

†These authors have contributed equally to this work

Article

DOI: 10.3389/fimmu.2022.842453

PMC ID: 9110697

PubMed ID: 35592339

SO-VID: 7461996c-d48d-4f43-aeb0-1bd35ba92d08

License:

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

History

Date received : 23 December 2021

Date accepted : 11 April 2022

Page count

Figures: 1, Tables: 2, Equations: 0, References: 74, Pages: 8, Words: 4127

Funding

Funded by: National Natural Science Foundation of China , doi 10.13039/501100001809;

Funded by: Qinglan Project of Jiangsu Province of China , doi 10.13039/501100013088;

Insights Gained Into the Treatment of COVID19 by Pulmonary Surfactant and Its Components

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Novel Coronavirus Disease COVID-19

Most cited references 73

Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein

Single-cell landscape of bronchoalveolar immune cells in patients with COVID-19

Inborn errors of type I IFN immunity in patients with life-threatening COVID-19

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