Detection of SARS-CoV-2 antibodies formed in response to the BNT162b2 and mRNA-1237 mRNA vaccine by commercial antibody tests.

BACKGROUND: With rapid approval of SARS-CoV-2 vaccines, the ability of clinical laboratories to detect vaccine-induced antibodies with available high-throughput commercial assays is unknown. We aimed to determine if commercial serology assays can detect vaccine-induced antibodies (VIAs) and understand the vaccination response. METHODS: This cohort study recruited healthcare workers and residents of long-term care facilities (receiving the BNT162b2 and mRNA-1273 products, respectively) who underwent serum collection pre-vaccination (BNT162b2 group), 2-weeks post vaccination (both groups), and pre-2nd dose (both groups). Sera were tested for the presence of SARS-CoV-2 IgG using four commercial assays (Abbott SARS-CoV-2 IgG, Abbott SARS-CoV-2 IgG II Quant, DiaSorin Trimeric S IgG, and GenScript cPASS) to detect VIAs. Secondary outcomes included description of post-vaccination antibody response and correlation with neutralizing titers. RESULTS: 225 participants (177 receiving BNT162b2 and 48 receiving mRNA-1273) were included (median age 41 years; 66-78% female). Nucleocapsid IgG was found in 4.1% and 21.9% of the BNT162b2 (baseline) and mRNA-1273 (2-weeks post first dose). All anti-spike assays detected antibodies post-vaccination, with an average increase of 87.2% (range 73.8-94.3%; BNT162b2), and 25.2% (range 23.8-26.7%; mRNA-1273) between the first and last sampling time points (all p < 0.05). Neutralizing antibodies were detected at all post-vaccine timepoints for both vaccine arms, with increasing titers over time (all p < 0.05). CONCLUSIONS: Anti-spike vaccine-induced SARS-CoV-2 IgG are detectable by commercially available high-throughput assays and increases over time. Prior to second dose of vaccination, neutralizing antibodies are detectable in 73-89% of individuals, suggesting most individuals would have some degree of protection from subsequent infection.

The association between small airway obstruction and emphysema phenotypes in COPD.

BACKGROUND: Airflow limitation in COPD is due to a variable combination of small airway obstruction and centrilobular emphysema (CLE) and/or panlobular emphysema (PLE), but the relationship between these three different phenotypes is poorly understood. This study compares the severity of small airway obstruction in both forms of emphysema and determines its relationship with FEV(1). METHODS: We compared the lung histology of nonsmoking control subjects without emphysema (n = 10) to that of patients with CLE (n = 30) and PLE with (n = 8) and without alpha(1)-antitrypsin (AAT) deficiency (n = 11). The degree of airspace enlargement was measured using the mean interalveolar wall distance (IAWD) [mean linear intercept, Lm], and the evenness of airspace destruction was assessed by the coefficient of variation (CV) of the IAWD. The severity of small airway obstruction was determined by dividing total wall area by the length of the basement membrane to obtain wall thickness. RESULTS: Lm was greater in all three subgroups of emphysema than in control subjects, and in AAT deficiency than in PLE or CLE. The CV of IAWD was greater in AAT deficiency and CLE than in control subjects and in CLE than in AAT deficiency or PLE. Although small airway wall thickness was greater in CLE and PLE with AAT deficiency than in control subjects, the association between wall thickness and both Lm and FEV(1) was observed only in CLE. CONCLUSIONS: Small airway wall thickening occurs in CLE and PLE with AAT deficiency but is more closely associated with degree of emphysema and airflow limitation in CLE.

Effects of a switch from tenofovir- to abacavir-based antiretroviral therapy, with or without atazanavir, on renal function.

INTRODUCTION: Tenofovir disoproxil fumarate (TDF)-associated renal dysfunction may abate when TDF is replaced with abacavir (ABC). The extent to which the third drug atazanavir contributes to renal dysfunction is unclear. METHODS: A retrospective analysis was conducted on adults who had plasma viral load (pVL)<200 copies/mL for≥six months while receiving TDF/lamivudine (3TC) - or TDF/emtricitabine (FTC)-based antiretroviral therapy (ART), then switched to ABC/3TC while retaining the third drug in the ART regimen. CD4, pVL, creatinine, estimated glomerular filtration rate (eGFR), serum phosphorus, urine albumin to creatinine ratio and serum lipids were compared between pre-switch baseline and 3, 6 and 12 months after the switch to ABC. RESULTS: A total of 286 patients switched from TDF to ABC between 2004 and 2014: 232 (81%) male, median age 48 years (interquartile range (IQR) 42, 56). The third drug was atazanavir (± ritonavir) in 141 (49%) cases. The pVL was<50 copies/mL in 93 to 96% at all time points. Median serum creatinine was 93 µmol/L (IQR 80-111) at baseline and decreased to 88 µmol/L (IQR 78-98) at 12 months after the switch to ABC. Median eGFR increased from 74 (IQR 60-88) mL/min at baseline to 80 mL/min (IQR 69-89) at 12 months. Results were not significantly different between patients on atazanavir versus those on another third drug. CONCLUSIONS: Viral suppression was maintained among patients who switched from TDF/3TC or TDF/FTC to ABC/3TC. Serum creatinine and eGFR improved up to 12 months after switching to ABC/3TC, irrespective of whether or not patients were also receiving atazanavir±ritonavir.

Patterns of retention of particulate matter in lung tissues of patients with COPD: potential role in disease progression.

BACKGROUND: Particulate matter (PM) is present in lung tissues of smokers and urban dwellers. This study was designed to quantify the burden of PM in different lung tissues of subjects with COPD and determine its relationship to disease severity. METHODS: Surgical lung tissue samples from nonsmokers (control subjects) were compared with those from smokers with normal spirometry and subjects in the four other categories of the GOLD (Global Initiative for Obstructive Lung Disease) classification of COPD severity using quantitative histologic techniques. RESULTS: PM was present in the lung parenchyma, blood vessel walls, airways, lymphoid follicles, and alveolar macrophages. The total burden of PM (volume fraction [Vv]) in all tissues of the lung was higher in smokers than nonsmokers (P < .001) and also in smokers with airflow obstruction compared with the smokers with normal spirometry (P < .01). There was an incremental increase in total PM burden with increased COPD severity that peaked in GOLD II and then trended downward in GOLD III and IV COPD. This same pattern of PM retention was also observed in alveolar walls. The total burden of PM in lung tissues correlated with a decline in FEV(1)/FVC as well as pack-years smoking. mRNA expression of fibrinogen (γ chain) correlated with total lung burden of PM and burden of PM in lung parenchyma (r(2) = 0.22, P < .001). CONCLUSIONS: We conclude that retained PM is widely distributed in lung tissues of subjects with COPD and that cigarette smoke exposure and airflow obstruction are associated with retention of PM in lung tissues. We attribute the downward trend in PM burden in severe COPD to either less deposition and retention or selective removal of PM containing tissues by emphysematous destruction.

Particulate matter air pollution exposure: role in the development and exacerbation of chronic obstructive pulmonary disease.

Due to the rapid urbanization of the world population, a better understanding of the detrimental effects of exposure to urban air pollution on chronic lung disease is necessary. Strong epidemiological evidence suggests that exposure to particulate matter (PM) air pollution causes exacerbations of pre-existing lung conditions, such as, chronic obstructive pulmonary disease (COPD) resulting in increased morbidity and mortality. However, little is known whether a chronic, low-grade exposure to ambient PM can cause the development and progression of COPD. The deposition of PM in the respiratory tract depends predominantly on the size of the particles, with larger particles deposited in the upper and larger airways and smaller particles penetrating deep into the alveolar spaces. Ineffective clearance of this PM from the airways could cause particle retention in lung tissues, resulting in a chronic, low-grade inflammatory response that may be pathogenetically important in both the exacerbation, as well as, the progression of lung disease. This review focuses on the adverse effects of exposure to ambient PM air pollution on the exacerbation, progression, and development of COPD.