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Chronic Obstr Pulm Dis ; 9(2): 266-273, 2022 Apr 29.
Article in English | MEDLINE | ID: covidwho-1856402


Patients with severe alpha-1 antitrypsin deficiency (AATD) are at increased risk for the development of chronic obstructive pulmonary disease (COPD), particularly if they smoke. This, coupled with their predilection for dysregulated inflammation and autoimmunity, makes affected individuals priority candidates for vaccination against coronavirus disease 2019 (COVID-19). To promote vaccine uptake effectively, an understanding of the factors motivating people to proceed with vaccination is essential. The attitudes of patients with AATD towards COVID-19 vaccination have yet to be described. We prospectively studied 170 Pi*ZZ genotype AATD patients, 150 patients with nonhereditary (Pi*MM genotype) COPD and 140 Pi*MM genotype individuals without lung disease receiving first-dose vaccination with ChAdOx1 nCoV-19 (AstraZeneca). Patient attitudes towards vaccination and motivations for getting vaccinated were assessed at the time of the vaccine being offered. Following completion of the 2-dose vaccine series, Pi*ZZ patients were then re-assessed regarding their attitudes towards booster vaccination. The most common primary motivation for accepting vaccination in Pi*ZZ participants ≥50 years old was a fear of illness or death from COVID-19. In contrast, Pi*ZZ patients <50 years most often cited a desire to socialize. The motivation pattern of younger Pi*ZZ AATD patients was similar to that of non-deficient individuals of comparable age, whereas older Pi*ZZ individuals were more closely aligned with Pi*MM COPD and differed from age-matched controls without lung disease. When considering booster vaccination, Pi*ZZ patients were increasingly motivated by a desire to reacquire social freedoms. A desire to reduce the risk of transmission was not a prominent consideration in any of the groups studied. The most commonly cited reason for booster hesitancy was a lack of incentive, given that no additional social freedoms were available to triple-vaccinated individuals compared to those who were double-vaccinated at the time. Taken together, these data may inform policymakers attempting to promote vaccine uptake among patients with AATD.

Thorax ; 76(1): 86-88, 2021 01.
Article in English | MEDLINE | ID: covidwho-1066942


False negatives from nasopharyngeal swabs (NPS) using reverse transcriptase PCR (RT-PCR) in SARS-CoV-2 are high. Exhaled breath condensate (EBC) contains lower respiratory droplets that may improve detection. We performed EBC RT-PCR for SARS-CoV-2 genes (E, S, N, ORF1ab) on NPS-positive (n=16) and NPS-negative/clinically positive COVID-19 patients (n=15) using two commercial assays. EBC detected SARS-CoV-2 in 93.5% (29/31) using the four genes. Pre-SARS-CoV-2 era controls (n=14) were negative. EBC was positive in NPS negative/clinically positive patients in 66.6% (10/15) using the identical E and S (E/S) gene assay used for NPS, 73.3% (11/15) using the N/ORF1ab assay and 14/15 (93.3%) combined.

Breath Tests/methods , COVID-19 Testing/methods , COVID-19/diagnosis , Exhalation , RNA, Viral/analysis , SARS-CoV-2/genetics , Adult , Aged , Aged, 80 and over , COVID-19/epidemiology , Female , Humans , Male , Middle Aged , Prospective Studies , Reproducibility of Results
Am J Respir Crit Care Med ; 202(6): 812-821, 2020 09 15.
Article in English | MEDLINE | ID: covidwho-614625


Rationale: Coronavirus disease (COVID-19) is a global threat to health. Its inflammatory characteristics are incompletely understood.Objectives: To define the cytokine profile of COVID-19 and to identify evidence of immunometabolic alterations in those with severe illness.Methods: Levels of IL-1ß, IL-6, IL-8, IL-10, and sTNFR1 (soluble tumor necrosis factor receptor 1) were assessed in plasma from healthy volunteers, hospitalized but stable patients with COVID-19 (COVIDstable patients), patients with COVID-19 requiring ICU admission (COVIDICU patients), and patients with severe community-acquired pneumonia requiring ICU support (CAPICU patients). Immunometabolic markers were measured in circulating neutrophils from patients with severe COVID-19. The acute phase response of AAT (alpha-1 antitrypsin) to COVID-19 was also evaluated.Measurements and Main Results: IL-1ß, IL-6, IL-8, and sTNFR1 were all increased in patients with COVID-19. COVIDICU patients could be clearly differentiated from COVIDstable patients, and demonstrated higher levels of IL-1ß, IL-6, and sTNFR1 but lower IL-10 than CAPICU patients. COVID-19 neutrophils displayed altered immunometabolism, with increased cytosolic PKM2 (pyruvate kinase M2), phosphorylated PKM2, HIF-1α (hypoxia-inducible factor-1α), and lactate. The production and sialylation of AAT increased in COVID-19, but this antiinflammatory response was overwhelmed in severe illness, with the IL-6:AAT ratio markedly higher in patients requiring ICU admission (P < 0.0001). In critically unwell patients with COVID-19, increases in IL-6:AAT predicted prolonged ICU stay and mortality, whereas improvement in IL-6:AAT was associated with clinical resolution (P < 0.0001).Conclusions: The COVID-19 cytokinemia is distinct from that of other types of pneumonia, leading to organ failure and ICU need. Neutrophils undergo immunometabolic reprogramming in severe COVID-19 illness. Cytokine ratios may predict outcomes in this population.

Acute-Phase Reaction/immunology , Carrier Proteins/metabolism , Coronavirus Infections/immunology , Coronavirus Infections/metabolism , Cytokines/immunology , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Lactic Acid/metabolism , Membrane Proteins/metabolism , Pneumonia, Viral/immunology , Pneumonia, Viral/metabolism , Thyroid Hormones/metabolism , alpha 1-Antitrypsin/immunology , Acute-Phase Reaction/metabolism , Adult , Aged , Betacoronavirus , Blotting, Western , COVID-19 , Case-Control Studies , Community-Acquired Infections/immunology , Community-Acquired Infections/metabolism , Coronavirus Infections/mortality , Coronavirus Infections/physiopathology , Critical Illness , Electrophoresis, Polyacrylamide Gel , Enzyme-Linked Immunosorbent Assay , Female , Hospitalization , Humans , Intensive Care Units , Interleukin-10/immunology , Interleukin-1beta/immunology , Interleukin-6/immunology , Interleukin-8/immunology , Length of Stay , Male , Middle Aged , Neutrophils/immunology , Neutrophils/metabolism , Pandemics , Phosphorylation , Pneumonia/immunology , Pneumonia/metabolism , Pneumonia, Viral/mortality , Pneumonia, Viral/physiopathology , Receptors, Tumor Necrosis Factor, Type I/immunology , SARS-CoV-2 , Severity of Illness Index , alpha 1-Antitrypsin/metabolism