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1.
Biomedicines ; 9(12)2021 Dec 17.
Article in English | MEDLINE | ID: covidwho-1591484

ABSTRACT

Lung macrophage iron levels are increased in COPD patients. Lung macrophage iron levels are thought to be increased by cigarette smoke, but the role of red blood cells (RBCs) as a source of iron has not been investigated. We investigate RBCs as a potential source of alveolar iron in COPD, and determine the effect of RBC-derived iron on macrophage function. We used lung tissue sections to assess RBC coverage of the alveolar space, iron and ferritin levels in 11 non-smokers (NS), 15 smokers (S) and 32 COPD patients. Lung macrophages were isolated from lung resections (n = 68) and treated with hemin or ferric ammonium citrate (50, 100 or 200 µM). Lung macrophage phenotype marker gene expression was measured by qPCR. The phagocytosis of Non-typeable Haemophilus influenzae (NTHi) was measured by flow cytometry. Cytokine production in response to NTHi in iron-treated macrophages was measured by ELISA. Lung macrophage iron levels were significantly correlated with RBC coverage of the alveolar space (r = 0.31, p = 0.02). Furthermore, RBC coverage and lung macrophage iron were significantly increased in COPD patients and correlated with airflow obstruction. Hemin treatment downregulated CD36, CD163, HLA-DR, CD38, TLR4, CD14 and MARCO gene expression. Hemin-treated macrophages also impaired production of pro-inflammatory cytokines in response to NTHi exposure, and decreased phagocytosis of NTHi (200 µM: 35% decrease; p = 0.03). RBCs are a plausible source of pulmonary iron overload in COPD. RBC-derived iron dysregulates macrophage phenotype and function.

2.
Curr Opin Pulm Med ; 28(2): 76-83, 2022 03 01.
Article in English | MEDLINE | ID: covidwho-1483670

ABSTRACT

PURPOSE OF REVIEW: Chronic obstructive pulmonary disease (COPD) and COVID-19 have many potentially negative interrelationships, which may influence the course of infection and clinical outcomes. The aim of this review is to provide clinicians with an up-to-date perspective of the complex interactions between COPD and COVID-19. RECENT FINDINGS: We consider mechanisms that could increase SARS-CoV-2 infection susceptibility in COPD, including increased ACE2 expression, reduced antiviral defence and dysfunctional immunity. We review evidence that COPD is associated with worse clinical outcomes from COVID-19 in analyses that have adjusted for confounding factors, and describe the mechanisms responsible. We discuss the use of inhaled corticosteroids in the context of susceptibility to COVID-19, and consider the impact of COVID-19 on the usual care of COPD patients. SUMMARY: The current review highlights the evidence that COPD patients have worse outcomes from COVID-19, and the multiple mechanisms responsible.


Subject(s)
COVID-19 , Pulmonary Disease, Chronic Obstructive , Adrenal Cortex Hormones/therapeutic use , Humans , Pulmonary Disease, Chronic Obstructive/drug therapy , Pulmonary Disease, Chronic Obstructive/epidemiology , SARS-CoV-2
3.
N Engl J Med ; 385(13): 1172-1183, 2021 09 23.
Article in English | MEDLINE | ID: covidwho-1287849

ABSTRACT

BACKGROUND: Early clinical data from studies of the NVX-CoV2373 vaccine (Novavax), a recombinant nanoparticle vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that contains the full-length spike glycoprotein of the prototype strain plus Matrix-M adjuvant, showed that the vaccine was safe and associated with a robust immune response in healthy adult participants. Additional data were needed regarding the efficacy, immunogenicity, and safety of this vaccine in a larger population. METHODS: In this phase 3, randomized, observer-blinded, placebo-controlled trial conducted at 33 sites in the United Kingdom, we assigned adults between the ages of 18 and 84 years in a 1:1 ratio to receive two intramuscular 5-µg doses of NVX-CoV2373 or placebo administered 21 days apart. The primary efficacy end point was virologically confirmed mild, moderate, or severe SARS-CoV-2 infection with an onset at least 7 days after the second injection in participants who were serologically negative at baseline. RESULTS: A total of 15,187 participants underwent randomization, and 14,039 were included in the per-protocol efficacy population. Of the participants, 27.9% were 65 years of age or older, and 44.6% had coexisting illnesses. Infections were reported in 10 participants in the vaccine group and in 96 in the placebo group, with a symptom onset of at least 7 days after the second injection, for a vaccine efficacy of 89.7% (95% confidence interval [CI], 80.2 to 94.6). No hospitalizations or deaths were reported among the 10 cases in the vaccine group. Five cases of severe infection were reported, all of which were in the placebo group. A post hoc analysis showed an efficacy of 86.3% (95% CI, 71.3 to 93.5) against the B.1.1.7 (or alpha) variant and 96.4% (95% CI, 73.8 to 99.5) against non-B.1.1.7 variants. Reactogenicity was generally mild and transient. The incidence of serious adverse events was low and similar in the two groups. CONCLUSIONS: A two-dose regimen of the NVX-CoV2373 vaccine administered to adult participants conferred 89.7% protection against SARS-CoV-2 infection and showed high efficacy against the B.1.1.7 variant. (Funded by Novavax; EudraCT number, 2020-004123-16.).


Subject(s)
COVID-19 Vaccines , COVID-19/prevention & control , Immunogenicity, Vaccine , Adolescent , Adult , Aged , Aged, 80 and over , COVID-19/epidemiology , COVID-19 Vaccines/administration & dosage , COVID-19 Vaccines/adverse effects , COVID-19 Vaccines/immunology , Humans , Injections, Intramuscular/adverse effects , Middle Aged , SARS-CoV-2 , Single-Blind Method , Vaccines, Synthetic/immunology , Young Adult
4.
Eur Respir Rev ; 29(158)2020 Dec 31.
Article in English | MEDLINE | ID: covidwho-1177704

ABSTRACT

The European Respiratory Society journals publish respiratory research and policy documents of the highest quality, offering a platform for the exchange and promotion of scientific knowledge. In this article, focusing on COPD, the third leading cause of death globally, we summarise novel research highlights focusing on the disease's underlying mechanisms, epidemiology and management, with the aim to inform and inspire respiratory clinicians and researchers.


Subject(s)
Pulmonary Disease, Chronic Obstructive , Humans , Pulmonary Disease, Chronic Obstructive/diagnosis , Pulmonary Disease, Chronic Obstructive/epidemiology , Pulmonary Disease, Chronic Obstructive/therapy
5.
Eur Respir Rev ; 29(158)2020 Dec 31.
Article in English | MEDLINE | ID: covidwho-914011

ABSTRACT

The 2019 coronavirus disease (COVID-19) pandemic is caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). Clinical outcomes, including mortality, are worse in males, older individuals and patients with comorbidities. COPD patients are included in shielding strategies due to their susceptibility to virus-induced exacerbations, compromised pulmonary function and high prevalence of associated comorbidities. Using evidence from basic science and cohort studies, this review addresses key questions concerning COVID-19 and COPD. First, are there mechanisms by which COPD patients are more susceptible to SARS-CoV-2 infection? Secondly, do inhaled corticosteroids offer protection against COVID-19? And, thirdly, what is the evidence regarding clinical outcomes from COVID-19 in COPD patients? This up-to-date review tackles some of the key issues which have significant impact on the long-term outlook for COPD patients in the context of COVID-19.


Subject(s)
Coronavirus Infections/diagnosis , Coronavirus Infections/epidemiology , Disease Progression , Disease Susceptibility , Pneumonia, Viral/diagnosis , Pneumonia, Viral/epidemiology , Pulmonary Disease, Chronic Obstructive/diagnosis , Pulmonary Disease, Chronic Obstructive/epidemiology , Adult , Age Factors , Aged , COVID-19 , Comorbidity , Coronavirus Infections/therapy , Evidence-Based Medicine , Humans , Incidence , Middle Aged , Pandemics/statistics & numerical data , Pneumonia, Viral/therapy , Prognosis , Pulmonary Disease, Chronic Obstructive/therapy , Respiratory Function Tests , Risk Assessment , Severe Acute Respiratory Syndrome/diagnosis , Severe Acute Respiratory Syndrome/epidemiology , Severity of Illness Index , Sex Factors
6.
Obesity (Silver Spring) ; 28(9): 1586-1589, 2020 09.
Article in English | MEDLINE | ID: covidwho-306140

ABSTRACT

OBJECTIVE: Mortality from coronavirus disease 2019 (COVID-19) is increased in patients with chronic obstructive pulmonary disease (COPD). Furthermore, higher BMI is related to severe disease. Severe acute respiratory syndrome coronavirus 2 utilizes angiotensin converting enzyme 2 (ACE2) to gain cellular entry. METHODS: Whether ACE2 bronchial epithelial expression is increased in COPD patients who have overweight compared with those who do not was investigated by RNA sequencing. RESULTS: Increased ACE2 expression was observed in patients with COPD with overweight (mean BMI, 29 kg/m2 ) compared with those without overweight (mean BMI, 21 kg/m2 ) (P = 0.004). CONCLUSIONS: Increased ACE2 expression may cause increased severe acute respiratory syndrome coronavirus 2 infection of the respiratory tract. Overweight COPD patients may be at greater risk for developing severe COVID-19.


Subject(s)
Bronchi , Epithelium/metabolism , Overweight/complications , Peptidyl-Dipeptidase A/genetics , Pulmonary Disease, Chronic Obstructive/genetics , Aged , Angiotensin-Converting Enzyme 2 , Betacoronavirus , COVID-19 , Coronavirus Infections , Female , Gene Expression Regulation , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral , Pulmonary Disease, Chronic Obstructive/complications , SARS-CoV-2
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