The identification of an optimal body size parameter to adjust skeletal muscle area on chest CT in COVID-19 patients.

Objectives: The most efficient way to adjust skeletal muscle area (SMA) derived from chest CT to body size remains unclear. We hypothesized that vertebral body area (VBA) measurement would allow such efficient adjustment. Methods: We conducted a retrospective observational study of chest CT imaging in a cohort of critically ill COVID-19 patients. We measured paravertebral SMA at T5 level and T5 vertebral body anteroposterior length, width, and area. We used linear regression and multivariable modelling to assess the association of VBA with SMA. Results: In 48 COVID-19 patients in ICU, T5 VBA could be easily derived from simple width and anteroposterior length linear measurements. T5 VBA (measured manually or estimated from width and length) performed similarly to height (R2 of 0.22) as an adjustment variable for SMA, with R2 of 0.23 and 0.22, respectively. Gender had the strongest correlation with SMA (R2 = 0.28). Adding height or age to a model using gender and VBA did not improve correlation. Conclusions: Gender and estimated VBA from simple linear measurements at T5 level on CT images can be utilized for adjustment of SMA without the need for height. Validation of these findings in larger cohorts of critically ill patients is now needed.

SARS-CoV-2 infection results in immune responses in the respiratory tract and peripheral blood that suggest mechanisms of disease severity.

Respiratory tract infection with SARS-CoV-2 results in varying immunopathology underlying COVID-19. We examine cellular, humoral and cytokine responses covering 382 immune components in longitudinal blood and respiratory samples from hospitalized COVID-19 patients. SARS-CoV-2-specific IgM, IgG, IgA are detected in respiratory tract and blood, however, receptor-binding domain (RBD)-specific IgM and IgG seroconversion is enhanced in respiratory specimens. SARS-CoV-2 neutralization activity in respiratory samples correlates with RBD-specific IgM and IgG levels. Cytokines/chemokines vary between respiratory samples and plasma, indicating that inflammation should be assessed in respiratory specimens to understand immunopathology. IFN-α2 and IL-12p70 in endotracheal aspirate and neutralization in sputum negatively correlate with duration of hospital stay. Diverse immune subsets are detected in respiratory samples, dominated by neutrophils. Importantly, dexamethasone treatment does not affect humoral responses in blood of COVID-19 patients. Our study unveils differential immune responses between respiratory samples and blood, and shows how drug therapy affects immune responses during COVID-19.

Immune responses in COVID-19 respiratory tract and blood reveal mechanisms of disease severity.

Although the respiratory tract is the primary site of SARS-CoV-2 infection and the ensuing immunopathology, respiratory immune responses are understudied and urgently needed to understand mechanisms underlying COVID-19 disease pathogenesis. We collected paired longitudinal blood and respiratory tract samples (endotracheal aspirate, sputum or pleural fluid) from hospitalized COVID-19 patients and non-COVID-19 controls. Cellular, humoral and cytokine responses were analysed and correlated with clinical data. SARS-CoV-2-specific IgM, IgG and IgA antibodies were detected using ELISA and multiplex assay in both the respiratory tract and blood of COVID-19 patients, although a higher receptor binding domain (RBD)-specific IgM and IgG seroconversion level was found in respiratory specimens. SARS-CoV-2 neutralization activity in respiratory samples was detected only when high levels of RBD-specific antibodies were present. Strikingly, cytokine/chemokine levels and profiles greatly differed between respiratory samples and plasma, indicating that inflammation needs to be assessed in respiratory specimens for the accurate assessment of SARS-CoV-2 immunopathology. Diverse immune cell subsets were detected in respiratory samples, albeit dominated by neutrophils. Importantly, we also showed that dexamethasone and/or remdesivir treatment did not affect humoral responses in blood of COVID-19 patients. Overall, our study unveils stark differences in innate and adaptive immune responses between respiratory samples and blood and provides important insights into effect of drug therapy on immune responses in COVID-19 patients.

Agreement and mortality prediction in high-resolution CT of diffuse fibrotic lung disease.

INTRODUCTION: The prognosis of diffuse fibrotic lung disease (DFLD) is known to be variable, but there is a paucity of literature on prognostic markers independent of precise clinical diagnosis. This study aimed to assess the mortality prediction of three high-resolution computed tomography (HRCT) scores in a heterogeneous population of patients with DFLD. A large radiologist and physician reader group was used to determine agreement among readers of varying background in applying these scores. METHODS: Institutional review board approval was obtained. Informed consent was waived for this retrospective study. Eighty HRCTs in 68 patients with DFLD (35 men, mean age 72.9 years) were evaluated retrospectively by 18 readers. Readers included thoracic and general radiologists, respiratory physicians and radiology trainees. Features scored were honeycombing, extent of disease and traction bronchiectasis. Demographics, diagnosis and pulmonary function data were collected. Patients were categorised as having either idiopathic pulmonary fibrosis, fibrosis relating to connective tissue disease, 'miscellaneous' DFLD or 'undefined', where no single entity was felt entirely or confidently to explain the pulmonary disease. Agreement was assessed using the kappa statistic. Associations with mortality were analysed using the Cox marginal model. RESULTS: Agreement was better for honeycombing (kappa = 0.44) and disease extent (kappa = 0.47) than traction bronchiectasis (kappa = 0.24). Honeycombing presence (P < 0.0005) and disease extent >30% (P = 0.002) predicted increased mortality independent of clinical diagnosis. Traction bronchiectasis was non-predictive. Clinical diagnosis was not an independent predictor, but age was independently associated with mortality (P = 0.004). Pulmonary function data were only available for 43 patients, but in a limited subanalysis, the diffusion capacity of carbon monoxide was independently predictive of increased mortality (P = 0.005). CONCLUSIONS: The presence of honeycombing and a greater extent of fibrotic lung disease predict increased mortality independent of clinical diagnosis. Our large, mixed-expertise reader group shows moderate interobserver agreement, comparable with agreement values for these scores in the literature.

Diagnostic challenges and pitfalls in MR imaging with hepatocyte-specific contrast agents.

The use of gadolinium-based hepatocyte-specific contrast agents (HSCAs) has increased markedly since their introduction, and hepatocellular phase imaging performed with an HSCA is now a key part of the standard magnetic resonance (MR) imaging work-up for focal liver lesions. An understanding of the mechanisms of action of HSCAs helps ensure their effective use. The optimal delay for hepatocellular phase image acquisition differs between the two currently available HSCAs, gadoxetic acid and gadobenate dimeglumine, and MR imaging protocols must be adjusted accordingly. In addition, familiarity with typical and atypical appearances of benign and malignant focal liver lesions at HSCA-enhanced hepatocellular phase MR imaging, along with knowledge of the processes that are most likely to produce atypical appearances, is required to achieve optimal diagnostic accuracy.