Elevated MUC1 and MUC5AC mucin protein levels in airway mucus of critical ill COVID‐19 patients

Lu, Wenju; Liu, Xiaoqing; Wang, Tao; Liu, Fei; Zhu, Airu; Lin, Yongping; Luo, Jieping; Ye, Feng; He, Jianxing; Zhao, Jincun; Li, Yiming; Zhong, Nanshan

doi:10.1002/jmv.26406

Cited by 94 publications

(101 citation statements)

References 10 publications

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“…Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) exhibited by a subset of patients suffering from COVID-19 and other respiratory ailments have been linked to the elevated circulating levels of mucin-1 ( KL-6/MUC1 ) and MUC5AC [ 105 , 106 ]. As a transmembrane protein of the mucosal epithelial cells, MUC1 plays a critical role in the lining of the airway lumen.…”

Section: Pharmacological Therapiesmentioning

confidence: 99%

COVID-19: A review of therapeutic strategies and vaccine candidates

Izda

Jeffries

Sawalha

2021

Clinical Immunology

219

208

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The world is engulfed by one of the most widespread and significant public health crises in decades as COVID-19 has become among the leading causes of death internationally. The novel SARS-CoV-2 coronavirus which causes COVID-19 has unified the scientific community in search of therapeutic and preventative solutions. The top priorities at the moment are twofold: first, to repurpose already-approved pharmacologic agents or develop novel therapies to reduce the morbidity and mortality associated with the ever-spreading virus. Secondly, the scientific and larger pharmaceutical community have been tasked with the development, testing, and production of a safe and effective vaccine as a longer-term solution to prevent further spread and recurrence throughout the populace. The purpose of this article is to review the most up-to-date published data regarding both the leading pharmacological therapies undergoing clinical trials and vaccine candidates in development to stem the threat of COVID-19.

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Section: Pharmacological Therapiesmentioning

confidence: 99%

COVID-19: A review of therapeutic strategies and vaccine candidates

Izda

Jeffries

Sawalha

2021

Clinical Immunology

219

208

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“…It is currently not known if and how SARS-CoV-2 interacts with human respiratory mucin and mucin glycans. However, a recent study indicated the presence of elevated levels of secreted MUC1 and MUC5AC in the sputum aspirated from the trachea of COVID-19 patients ( 62 ). COVID-19 patients also have a lower allelic frequency of the MUC5B genetic variant rs35705950 than healthy controls, which is associated with a higher level of expression of MUC5B, suggesting a protective role for MUC5B ( 63 ).…”

Section: Mucosal Defense Against Sars-cov-2mentioning

confidence: 99%

Defensive Properties of Mucin Glycoproteins during Respiratory Infections—Relevance for SARS-CoV-2

Chatterjee

Putten

Strijbis

2020

mBio

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Mucus plays a pivotal role in protecting the respiratory tract against microbial infections. It acts as a primary contact site to entrap microbes and facilitates their removal from the respiratory tract via the coordinated beating of motile cilia. The major components of airway mucus are heavily O-glycosylated mucin glycoproteins, divided into gel-forming mucins and transmembrane mucins. The gel-forming mucins MUC5AC and MUC5B are the primary structural components of airway mucus, and they enable efficient clearance of pathogens by mucociliary clearance. MUC5B is constitutively expressed in the healthy airway, whereas MUC5AC is upregulated in response to inflammatory challenge. MUC1, MUC4, and MUC16 are the three major transmembrane mucins of the respiratory tracts which prevent microbial invasion, can act as releasable decoy receptors, and activate intracellular signal transduction pathways. Pathogens have evolved virulence factors such as adhesins that facilitate interaction with specific mucins and mucin glycans, for example, terminal sialic acids. Mucin expression and glycosylation are dependent on the inflammatory state of the respiratory tract and are directly regulated by proinflammatory cytokines and microbial ligands. Gender and age also impact mucin glycosylation and expression through the female sex hormone estradiol and age-related downregulation of mucin production. Here, we discuss what is currently known about the role of respiratory mucins and their glycans during bacterial and viral infections of the airways and their relevance for the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Understanding the impact of microbe-mucin interaction in the respiratory tract could inspire the development of novel therapies to boost mucosal defense and combat respiratory infections.

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“…MUC1 binds directly to the DNA binding domain of ERα and stabilizes it by inhibiting its ubiquitination and subsequent degradation (Wei et al, 2006). A recent study reported markedly increased levels of MUC1 and MUC5AC in the sputum aspirated from the trachea of patients with severe COVID‐19 symptoms (Lu et al, 2020). All the 16 patients recruited in this study were admitted to the intensive care unit because of low oxygenation index, and most of them received mechanical ventilation.…”

Section: Connection Of Mucins To Covid‐19mentioning

confidence: 99%

“…High levels of the gel‐forming MUC4 dehydrates airway surfaces and leads to mucus adhesion, thus causing shortness of breath. All the 16 critically ill patients recovered owing to an aggressive clearance of the respiratory tract by the medical practitioners (Lu et al, 2020). Therefore, it is plausible that high levels of shed mucins correspond to worse outcome of the disease and this must be investigated.…”

Section: Connection Of Mucins To Covid‐19mentioning

confidence: 99%