Respiratory manifestations of long COVID

As we near the third year of the COVID-19 pandemic, greater attention is now being paid to the potential long-term consequences of SARS-CoV-2 in the hundreds of millions of people infected globally. A syndrome termed "long COVID" has emerged, which predominantly manifests as persistent fatigue, dyspnea, chest pain, and cognitive dysfunction following acute infection. The incidence of long COVID is in the range of 15% based on current best evidence, and symptoms are likely a result of several different pathophysiological mechanisms including multi-organ injury from acute infection, systemic viral persistence, immune dysregulation, and/or autoimmunity. Pulmonary symptoms represent a significant component of long COVID, and there is a growing body of research describing the epidemiology, risk factors, physiology, and radiology of the respiratory manifestations of long COVID. In this clinical review, we examine the most recent evidence relating to "respiratory long COVID," discuss how innovative technologies such as Xenon-129 gas transfer magnetic resonance imaging (MRI) and respiratory oscillometry are helping to elucidate its unique pathophysiology, and consider the role of preventative strategies and possible treatments such as adapted pulmonary rehabilitation. The burden of respiratory long COVID is likely to continue to grow, and all healthcare professionals who care for patients with respiratory disease must prepare for this emerging chronic condition. This will require increased resources from healthcare decision makers, inventive approaches to healthcare delivery, further research, and the same spirit of collaboration that has enabled the many success stories to date in the global effort against COVID-19.Copyright © 2023 Canadian Thoracic Society.

Longitudinal lung function assessment of patients hospitalised with COVID-19 using 1H and 129Xe lung MRI

Introduction: The progression of pathophysiological pulmonary changes in patients following acute COVID-19 is not well established. Method(s): Patients hospitalised with COVID-19 pneumonia without signs of ILD, had MRI exams at a median of 6 (n=9), 12 (n=9), 25 (n=7), and 52 (n=3) weeks. MRI sequences included: dynamic contrast enhanced (DCE) lung perfusion,129 Xe diffusion weighted (DW-MRI), 129Xe ventilation and 129Xe 3D dissolved phase imaging. Result(s): 9 patients (age 56+/-9 years;7 male;1 required treatment in an ICU) were recruited. Median RBC:TP was abnormally low at all visits compared to reference age and sex matched data. An individual's RBC:TP was significantly and positively associated with an increase in their pulmonary blood volume (p=0.026). For patients with 52 week data available, one showed a continued increase in RBC:TP, 2 patients maintained a low RBC:TP (Figure 1). Ventilation defect percentage, and ventilation heterogeneity significantly decreased at 25 weeks compared to 6 129 129 129 weeks (p=0.010 and p=0.048). DW-MRI was normal at all visits. Dissolved phase xenon imaging showed RBC:TP significantly increased at 12 and 25 weeks compared to 6 weeks (p=0.048). Conclusion(s): In patients recovering after COVID-19, poor gas transfer is reflected by impaired xenon transfer, which improves alongside pulmonary blood volume.

Longitudinal Lung Function Assessment of Patients Hospitalized With COVID-19 Using 1H and 129Xe Lung MRI.

BACKGROUND: Microvascular abnormalities and impaired gas transfer have been observed in patients with COVID-19. The progression of pulmonary changes in these patients remains unclear. RESEARCH QUESTION: Do patients hospitalized with COVID-19 without evidence of architectural distortion on structural imaging exhibit longitudinal improvements in lung function measured by using 1H and 129Xe MRI between 6 and 52 weeks following hospitalization? STUDY DESIGN AND METHODS: Patients who were hospitalized with COVID-19 pneumonia underwent a pulmonary 1H and 129Xe MRI protocol at 6, 12, 25, and 51 weeks following hospital admission in a prospective cohort study between November 2020 and February 2022. The imaging protocol was as follows: 1H ultra-short echo time, contrast-enhanced lung perfusion, 129Xe ventilation, 129Xe diffusion-weighted, and 129Xe spectroscopic imaging of gas exchange. RESULTS: Nine patients were recruited (age 57 ± 14 [median ± interquartile range] years; six of nine patients were male). Patients underwent MRI at 6 (n = 9), 12 (n = 9), 25 (n = 6), and 51 (n = 8) weeks following hospital admission. Patients with signs of interstitial lung damage were excluded. At 6 weeks, patients exhibited impaired 129Xe gas transfer (RBC to membrane fraction), but lung microstructure was not increased (apparent diffusion coefficient and mean acinar airway dimensions). Minor ventilation abnormalities present in four patients were largely resolved in the 6- to 25-week period. At 12 weeks, all patients with lung perfusion data (n = 6) showed an increase in both pulmonary blood volume and flow compared with 6 weeks, although this was not statistically significant. At 12 weeks, significant improvements in 129Xe gas transfer were observed compared with 6-week examinations; however, 129Xe gas transfer remained abnormally low at weeks 12, 25, and 51. INTERPRETATION: 129Xe gas transfer was impaired up to 1 year following hospitalization in patients who were hospitalized with COVID-19 pneumonia, without evidence of architectural distortion on structural imaging, whereas lung ventilation was normal at 52 weeks.

Respiratory manifestations of long COVID

As we near the third year of the COVID-19 pandemic, greater attention is now being paid to the potential long-term consequences of SARS-CoV-2 in the hundreds of millions of people infected globally. A syndrome termed "long COVID" has emerged, which predominantly manifests as persistent fatigue, dyspnea, chest pain, and cognitive dysfunction following acute infection. The incidence of long COVID is in the range of 15% based on current best evidence, and symptoms are likely a result of several different pathophysiological mechanisms including multi-organ injury from acute infection, systemic viral persistence, immune dysregulation, and/or autoimmunity. Pulmonary symptoms represent a significant component of long COVID, and there is a growing body of research describing the epidemiology, risk factors, physiology, and radiology of the respiratory manifestations of long COVID. In this clinical review, we examine the most recent evidence relating to "respiratory long COVID," discuss how innovative technologies such as Xenon-129 gas transfer magnetic resonance imaging (MRI) and respiratory oscillometry are helping to elucidate its unique pathophysiology, and consider the role of preventative strategies and possible treatments such as adapted pulmonary rehabilitation. The burden of respiratory long COVID is likely to continue to grow, and all healthcare professionals who care for patients with respiratory disease must prepare for this emerging chronic condition. This will require increased resources from healthcare decision makers, inventive approaches to healthcare delivery, further research, and the same spirit of collaboration that has enabled the many success stories to date in the global effort against COVID-19. Copyright © 2023 Canadian Thoracic Society.

Pulsed-Xenon Ultraviolet Light Highly Inactivates Human Coronaviruses on Solid Surfaces, Particularly SARS-CoV-2.

In the context of ongoing and future pandemics, non-pharmaceutical interventions are critical in reducing viral infections and the emergence of new antigenic variants while the population reaches immunity to limit viral transmission. This study provides information on efficient and fast methods of disinfecting surfaces contaminated with different human coronaviruses (CoVs) in healthcare settings. The ability to disinfect three different human coronaviruses (HCoV-229E, MERS-CoV, and SARS-CoV-2) on dried surfaces with light was determined for a fully characterized pulsed-xenon ultraviolet (PX-UV) source. Thereafter, the effectiveness of this treatment to inactivate SARS-CoV-2 was compared to that of conventional low-pressure mercury UVC lamps by using equivalent irradiances of UVC wavelengths. Under the experimental conditions of this research, PX-UV light completely inactivated the CoVs tested on solid surfaces since the infectivity of the three CoVs was reduced up to 4 orders of magnitude by PX-UV irradiation, with a cumulated dose of as much as 21.162 mJ/cm2 when considering all UV wavelengths (5.402 mJ/cm2 of just UVC light). Furthermore, continuous irradiation with UVC light was less efficient in inactivating SARS-CoV-2 than treatment with PX-UV light. Therefore, PX-UV light postulates as a promising decontamination measure to tackle the propagation of future outbreaks of CoVs.

Significant Fragmentation of Disposable Surgical Masks—Enormous Source for Problematic Micro/Nanoplastics Pollution in the Environment

The pandemic of COVID-19 disease has brought many challenges in the field of personal protective equipment. The amount of disposable surgical masks (DSMs) consumed increased dramatically, and much of it was improperly disposed of, i.e., it entered the environment. For this reason, it is crucial to accurately analyze the waste and identify all the hazards it poses. Therefore, in the present work, a DSM was disassembled, and gravimetric analysis of representative DSM waste was performed, along with detailed infrared spectroscopy of the individual parts and in-depth analysis of the waste. Due to the potential water contamination by micro/nanoplastics and also by other harmful components of DSMs generated during the leaching and photodegradation process, the xenon test and toxicity characteristic leaching procedure were used to analyze and evaluate the leaching of micro/nanoplastics. Micro/nanoplastic particles were leached from all five components of the mask in an aqueous medium. Exposed to natural conditions, a DSM loses up to 30% of its mass in just 1 month, while micro/nanoplastic particles are formed by the process of photodegradation. Improperly treated DSMs pose a potential hazardous risk to the environment due to the release of micro/nanoparticles and chloride ion content.

MR Imaging for the Evaluation of Diffuse Lung Disease: Where Are We?

Patients with diffuse lung diseases require thorough medical and social history and physical examinations, coupled with a multitude of laboratory tests, pulmonary function tests, and radiologic imaging to discern and manage the specific disease. This review summarizes the current state of imaging of various diffuse lung diseases by hyperpolarized MR imaging. The potential of hyperpolarized MR imaging as a clinical tool is outlined as a novel imaging approach that enables further understanding of the cause of diffuse lung diseases, permits earlier detection of disease progression before that found with pulmonary function tests, and can delineate physiologic response to lung therapies.

Hyperpolarized 129Xe Ventilation and Gas Exchange Imaging in a Single, Clinically Feasible Breath-Hold

Hyperpolarized 129Xe MRI (Xe-MRI) is eliciting increasing interest as an outcome measure in clinical trials, and, with FDA approval expected in 2022, for clinical application. This technique can provide 3D images of pulmonary structure and function non-invasively and with no ionizing radiation. In particular, Xe-MRI can be used to map regional ventilation and gas exchange, both of which have proven effective at identifying structure and function abnormalities in a variety of pulmonary diseases. However, multiple breath-holds are required to collect ventilation and gas exchange images, which increases patient burden and the time/cost of imaging. Building on recent advances to Xe-MRI, namely 3D spiral imaging and flip angle/TR equivalence, we have developed an imaging sequence that can acquire high quality ventilation and gas exchange images within a single, clinically feasible (∼10 s) breath-hold. This sequence uses an interleaved 3D spiral/3D radial 1- point Dixon approach to simultaneously acquire ventilation and gas exchange images. In postprocessing, images are generated of ventilation (voxel size 4 x 4 x 4 mm3) and gas exchange, including xenon dissolved in tissues (“Barrier”) and red blood cells (RBCs) (voxel size 6.25 x 6.25 x 6.25 mm3). This sequence has been used to acquire images in 8 subjects, including 4 healthy volunteers, 1 patient with scleroderma associated ILD (SSc-ILD), and 3 patients experiencing respiratory post-acute sequelae of COVID-19 (PASC). Of these, 7 subjects had a dedicated breath-hold for imaging ventilation, and 5 subjects had a dedicated gas exchange image. In all cases, image signal to noise ratio was equal or superior to dedicated breath-hold images. Qualitative agreement between ventilation/gas exchange images in dedicated breath-holds (Figure A, B) and single-breath images (Figure C) was excellent, and quantitative biomarkers, including ventilation defect percentage (VDP) (ICC = 0.90, p = 0.006), mean barrier signal (ICC = .99, p = 0.001), mean RBC signal (ICC = 0.93, p < 0.001), global RBC oscillation (ICC = 0.984, p = 0.001), percent of the lungs with low barrier (ICC = .98, p = 0.001), and percent with low RBC signal (ICC = 0.92, p = 0.006) were closely correlated. Single-breath imaging was able to identify ventilation defects (Figure C), elevated barrier (in SSc-ILD), and RBC defects (in SSc-ILD, PASC). These data show that hyperpolarized 129Xe ventilation and gas exchange images can effectively be acquired within a single, clinically manageable breath-hold, which may help to pave the way for increased clinical utilization of hyperpolarized 129Xe MRI. (Figure Presented).

Evaluating the impact of ultraviolet C exposure conditions on coliphage MS2 inactivation on surfaces.

The COVID-19 pandemic has raised interest in using devices that generate ultraviolet C (UVC) radiation as an alternative approach for reducing or eliminating microorganisms on surfaces. Studies investigating the efficacy of UVC radiation against pathogens use a wide range of laboratory methods and experimental conditions that can make cross-comparison of results and extrapolation of findings to real-world settings difficult. Here, we use three different UVC-generating sources - a broad-spectrum pulsed xenon light, a continuous light-emitting diode (LED), and a low-pressure mercury vapour lamp - to evaluate the impact of different experimental conditions on UVC efficacy against the coliphage MS2 on surfaces. We find that a nonlinear dose-response relationship exists for all three light sources, meaning that linear extrapolation of doses resulting in a 1-log10 (90%) reduction does not accurately predict the dose required for higher (e.g. 3-log10 or 99.9%) log10 reductions. In addition, our results show that the inoculum characteristics and underlying substrate play an important role in determining UVC efficacy. Variations in microscopic surface topography may shield MS2 from UVC radiation to different degrees, which impacts UVC device efficacy. These findings are important to consider in comparing results from different UVC studies and in estimating device performance in field conditions.

Advances in magnetic resonance tomography

This chapter sets out the most promising modern directions of research in the field of magnetic resonance imaging. These include multinuclear studies aimed at the exploration of magnetic resonance (MR) image contrast induced by exogeneous (fluorine-19, hyperpolarized noble gases) and “built-in” (phosphorus-31, sodium-23) contrast agents for potential clinical benefits. The chapter covers electrodynamic elements of MR scanners that increase signal-to-noise ratio in low-field magnetic resonance imaging (MRI), hyperpolarization techniques that allow several orders of magnitude improved sensitivity in low-field MRI, as well as MRI methods to study dynamics of pharmaceuticals introduced into the body. Special attention is given to MRI methods based upon magnetization transfer aimed at the detection of myelination defects of axons in the brain and functional MRI characterizing brain dynamic response to external stimuli. © 2022 Elsevier Ltd All rights reserved.

A case of xenon inhalation therapy for respiratory failure and neuropsychiatric disorders associated with COVID-19.

Acute respiratory distress syndrome (ARDS) is the main danger to the life of patients with pneumonia caused by SARS-CoV-2. At the same time, respiratory failure (RF) after ARDS can persist for a long time despite intensive therapy. Therefore, it is important to develop new effective approaches for restoring the ventilation function of the lungs after COVID-19. Here, we present a case report of effective application of short-term inhalations of xenon-oxygen (Xe/O2) gas mixture for treatment of RF and neuropsychiatric disorders (NPD) associated with COVID-19. The patient inhaled a gas mixture of 70 % Xe and 30 % O2. We used multispiral computed tomography, evaluated psychometry, studied hematological and biochemical blood parameters, and applied some other methods of clinical studies to assess the therapeutic effectiveness of Xe inhalation. Also, we studied the mechanism of action of xenon with computer modeling. The clinical case showed the high efficacy of Xe/O2 mixture for treating severe RF and NPD after SARS-CoV-2 infection. Xenon inhalations dramatically increased oxygen saturation and the degree of pneumatization of the lungs. We found out that in coronavirus pneumonia, saturated phospholipids of surfactant are transferred to the solid-ordered phase, which disrupts the surface tension of the alveoli and alveolar gas exchange. Using molecular modeling methods, we demonstrated that the xenon atom increases the distance between the acyl chains of phospholipids due to the van der Waals dispersion interaction. These changes allow for the phase transition of phospholipids from the solid-ordered phase to the liquid phase and restore the functional activity of the surfactant. The findings suggest the feasibility of conducting studies on the effectiveness of Xe/O2 inhalations for treating ARDS in SARS-CoV-2 infection.

129Xe MRI as a measure of clinical disease severity for pediatric asthma.

BACKGROUND: Measurement of regional lung ventilation with hyperpolarized 129Xe magnetic resonance imaging (129Xe MRI) in pediatric asthma is poised to advance our understanding of disease mechanisms and pathophysiology in a disorder with diverse clinical phenotypes. 129Xe MRI has not been investigated in a pediatric asthma cohort. OBJECTIVE: We hypothesized that 129Xe MRI is feasible and can demonstrate ventilation defects that relate to and predict clinical severity in a pediatric asthma cohort. METHODS: Thirty-seven children (13 with severe asthma, 8 with mild/moderate asthma, 16 age-matched healthy controls) aged 6 to 17 years old were imaged with 129Xe MRI. Ventilation defect percentage (VDP) and image reader score were calculated and compared with clinical measures at baseline and at follow-up. RESULTS: Children with asthma had higher VDP (P = .002) and number of defects per image slice (defects/slice) (P = .0001) than children without asthma. Children with clinically severe asthma had significantly higher VDP and number of defects/slice than healthy controls. Children with asthma who had a higher number of defects/slice had a higher rate of health care utilization (r = 0.48; P = .03) and oral corticosteroid use (r = 0.43; P = .05) at baseline. Receiver-operating characteristic analysis demonstrated that the VDP and number of defects/slice were predictive of increased health care utilization, asthma, and severe asthma. VDP correlated with FEV1 (r = -0.35; P = .04) and FEV1/forced vital capacity ratio (r = -0.41; P = .01). CONCLUSIONS: 129Xe MRI correlates with asthma severity, health care utilization, and oral corticosteroid use. Because delineation of clinical severity is often difficult in children, 129Xe MRI may be an important biomarker for severity, with potential to identify children at higher risk for exacerbations and improve outcomes.