Casirivimab-imdevimab neutralizing SARS-CoV-2: post-infusion clinical events and their risk factors

Background Casirivimab-imdevimab has been developed to neutralize SARS-CoV-2. The global clinical trials in outpatients documented several adverse effects (AE), which mandate caution in Japan where part of patients return home. To investigate post-infusion clinical events and their risk factors, we attempted a retrospective study. Main body Subjects were a consecutive series of inpatients with COVID-19 undergoing an infusion of casirivimab-imdevimab in our institute. The criteria for administration were in accordance with previous clinical trials, e.g., exclusion of patients necessitating oxygen supply. In Japan, however, SARS-CoV-2 vaccinees were eligible. Methods were review of background factors of status, imaging, and laboratory findings for the outcome of post-infusion events such as temperature increase (Temp+), pulse oximetry below 94%, and other events. Also, we documented the drug efficacy. Of a total of 96 patients with a median follow-up of 54 days, one (1.0%) died who alone was an exception demanding oxygen supply. Other 95 patients (99.0%) recovered from fever and hypoxia by Day 4 and later had no worsening of COVID-19. Median increase of body temperature was 1.0 degrees Celsius, which was used for computation of Temp+. Multivariate analysis showed that for Temp+ (n = 47), white blood cell counts more than 4.3 × 103/microliter (Odds Ratio [OR] 2.593, 95% Confidence Interval [CI] 1.060–6.338, P = 0.037) was at risk, whereas 2-time vaccination for SARS-CoV-2 (OR 0.128, 95% CI 0.026–0.636, P = 0.012) was a preventing factor. Likewise for lowered oximetry (n = 21), CT showing bilateral ground glass attenuation (OR 5.544, CI 1.599–19.228, P = 0.007) was a significant risk factor. Two patients (2.1%) showed bradycardia (asymptomatic, intervention not indicated) on Day 3 and recovery on Day 5. Limitations for this study included the difficulty distinguishing AE from worsening of COVID-19, thus we documented as clinical events. Conclusions For 24 h after infusion of casirivimab-imdevimab, COVID-19 patients with increased white blood cell counts may be predisposed to temperature elevation more than 1.0 degrees centigrade, as may bilateral ground glass opacity to lowered oximetry. Thus, patients with leukocytosis and bilateral ground glass attenuation may need precaution for transient fever and hypoxia, respectively.

Chest computed tomography findings of adult patients with antimelanoma differentiation-associated protein 5 antibody-positive interstitial lung disease

ABSTRACT Objectives Interstitial lung disease (ILD) associated with the antimelanoma differentiation-associated protein 5 (anti-MDA5) antibody is a rapidly progressive disease that requires timely, aggressive treatment. However, prompt diagnosis is difficult due to the longer time required for antibody detection. This study described the computed tomography (CT) findings of anti-MDA5 antibody-positive ILD (anti-MDA5-ILD). Methods CT findings of 20 patients (7 men, 13 women; mean age, 53.6 ± 13.5 years) with anti-MDA5-ILD were retrospectively reviewed. All patients had clinical diagnoses of dermatomyositis, and 14 patients presented with amyopathic findings. Results Bilateral ground-glass attenuation, air-space consolidation, and reticular shadows were observed in 20 (100%), 15 (75%), and 3 (15%) patients, respectively. The spread of air-space consolidation was 6.0 ± 5.6% (mean ± standard deviation). Univariate analysis revealed that high Krebs von den Lungen-6, high spread of consolidation, low partial pressure of oxygen, and low forced vital capacity were significant predictors for poor survival. The final radiological diagnoses were nonspecific interstitial pneumonia and organising pneumonia (OP) in 2 (10%) and 16 (80%) patients, respectively. Further, 30% of OP patients showed fibrosis. Conclusion The characteristic CT findings of patients with anti-MDA5-ILD were ground-glass attenuation, air-space consolidation, and less reticulation. These CT findings were compatible with those of OP.

Differentiation of pulmonary complications with extensive ground-glass attenuation on high-resolution CT in immunocompromised patients

Purpose The purpose of this study was to compare the high-resolution CT (HRCT) findings of pulmonary infectious and noninfectious complications with extensive ground-glass attenuation (GGA) in immunocompromised patients. Materials and methods One hundred fifty-two immunocompromised patients with pulmonary complications that showed extensive GGA (> 50% of the whole lung on HRCT) were included in this study. The diagnoses of the 152 patients were as follows: pneumocystis pneumonia (PCP), n = 82; drug-induced pneumonia, n = 38; bacterial pneumonia, n = 9; cytomegalovirus pneumonia, n = 6; idiopathic pneumonia syndrome, n = 6; diffuse alveolar hemorrhage (DAH), n = 4; fungal infection, n = 3; tuberculosis, n = 2 and pulmonary edema, n = 2. Two chest radiologists retrospectively evaluated the CT criteria, which consisted of 12 findings. Results The nodule (p = 0.015), the bronchovascular bundle (BVB) thickening (p = 0.001), and the interlobular septum (ILS) thickening (p = 0.002) were significantly infrequent in PCP. The ILS thickening was significantly frequent in drug-induced pneumonia (p < 0.001) though it was also frequent in other noninfectious and infectious diseases. The BVB thickening was significantly frequent in bacterial pneumonia (p = 0.005). The nodule was significantly frequent in DAH (p = 0.049). Conclusion Nodules, BVB thickening, and ILS thickening could be useful HRCT findings for the differential diagnosis of pulmonary complications in immunocompromised patients with extensive GGA.

Uncommon radiologic computed tomography appearances of the chest in patients with lymphangioleiomyomatosis

Lymphangioleiomyomatosis (LAM) is a rare destructive lung disease characterized by multiple thin-walled pulmonary cysts. The currently proposed diagnostic algorithm emphasizes the characteristic cystic appearance on high-resolution computed tomography (HRCT) so uncommon HRCT appearances present challenges to establishing the proper LAM diagnosis. The objective of this study is to accrue uncommon chest HRCT appearances, determine frequencies in both tuberous sclerosis complex (TSC)-associated LAM (TSC-LAM) and sporadic LAM (S-LAM) patients. 311 females referred to our hospital, including 272 S-LAM patients (mean age 39.2 years) and 39 TSC-LAM patients (mean age 38.3 years), were retrospectively evaluated. We found 2 types of radiologic findings likely to make HRCT cyst appearance atypical: characteristics of the cyst itself and uncommon findings in addition to cysts. We found that approximately 80% of LAM patients, whether TSC-associated or sporadic, showed typical HRCT appearance with mild to severe cystic destruction. The remaining 20% displayed unusual profiles in cyst appearance as well as additional findings aside from cyst: the former includes large cyst, thickened walls, and irregularly shaped whereas the latter includes ground glass attenuation and diffuse noncalcified nodules. It is important to be aware of various radiologic findings that make HRCT cystic appearance atypical of LAM.

Comparison of initial thin-section CT features in coronavirus disease 2019 pneumonia and other community-acquired pneumonia

Background Coronavirus disease 2019 (COVID-19) pneumonia caused similar symptoms to other community-acquired pneumonia (CAP). It is important to early quarantine suspected patients with COVID-19 pneumonia from patients with other CAP to reduce cross infection. The purpose of the study is to review and compare initial thin-section computed tomography (CT) features in patients with coronavirus disease 2019 (COVID-19) pneumonia and other community-acquired pneumonia (CAP). Methods 24 cases of COVID-19 pneumonia (14 males and 10 females; age range, 14-87 years; mean age, 48.0 years) and 28 cases of CAP caused by other pathogens (13 males and 15 females; age range, 24-85 years; mean age, 49.5 years) were included. Thin-section CT features of the lungs for all patients were retrospectively reviewed by two independent radiologists. Results There were no significant differences for the shape of main lesions, pure ground glass attenuation (GGA), mixed GGA with consolidation, air bronchogram, linear opacities, halo sign/reversed halo sign, cavitation and lymphadenopathy between the group of COVID-19 pneumonia and the group of other CAP. However, the frequency of crazy-paving appearance, vessel dilatation, bilaterally involvement and peripherally distribution were significantly higher in patients with COVID-19 compared with other CAP ( p =0.031, p =0.000, p =0.029 and p =0.009, respectively). Conversely, the frequencies of pure consolidation, tree-in-bud sign and pleural effusion were significantly higher in patients with CAP than in patients with COVID-19 pneumonia ( p =0.002, p =0.000 and p =0.048, respectively). Conclusion There are considerable overlaps in thin-section CT features between COVID-19 pneumonia and other CAP. However, the presence of crazy paving pattern, vessel dilation, bilateral involvement and peripheral distribution contributes to the diagnosis of COVID-19 pneumonia. While the presence of pure consolidation tree-in-bud sign, pleural effusion can be assisting in exclusive the diagnosis of COVID-19 pneumonia.

Taxane induced pulmonary toxicity in breast cancer.

e15522 Background: Taxanes are an integral part of chemotherapy for a broad range of tumor types. The usual toxicities associated with Taxane use are peripheral neuropathy, myelosuppression and musculoskeletal adverse effects. Very few studies have reported taxane induced pulmonary toxicity objectively. In our study we explored Taxane induced pulmonary toxicity based on discrete CT findings. Methods: 40 non-smokers diagnosed with Her-2 negative breast cancer who received Taxane monotherapy from 2017 to 2018 were retrospectively analyzed for pre and post therapy CT changes. Following CT findings were considered significant as pulmonary toxicity; (a) Nonspecific area with ground-glass attenuation, (b) multifocal areas of airspace consolidation, (c) patchy distribution of ground-glass attenuation accompanied by interlobular septal thickening and (d) extensive bilateral ground-glass attenuation or airspace consolidations with traction bronchiectasis. The CT findings were assessed independently by two radiologists and one pulmonologist. Results: Our study showed that 5 patients (12.5%) developed pulmonary changes on chest CT post Taxane therapy as summarized in Table. Conclusions: Our study shows that taxane has more potential to induce pulmonary toxicity than reported in present literature. Given that taxanes are the most widely used chemotherapy, it is of utmost necessity to be cognizant of this under-reported potentially fatal adverse effect in a large population. Further studies should be conducted to better understand the true potential, mechanisms and patterns of taxanes induced pulmonary toxicity. [Table: see text]

Pulmonary Metastases

Pulmonary metastases represent spread of malignancy to the lung parenchyma. Patients with metastatic disease may present with dyspnea, cough, or hemoptysis. Alternatively, affected patients may be asymptomatic. The lungs are a common site for metastatic disease. Relatively common primary malignancies (breast, colon, lung, and kidney cancers) are the most common causes of pulmonary metastases. However, less common primary malignancies (choriocarcinoma, testicular cancers, melanoma, and sarcomas) have a higher likelihood to produce lung metastases. The vast majority of pulmonary metastases spread via the bloodstream. Hematogenous metastases are typically basilar predominant lung nodules. Metastatic nodules may be very small (miliary, < 3mm), or very large (cannonball), and may rarely be solitary. The presence of surrounding ground-glass attenuation (CT-Halo sign) often indicates surrounding hemorrhage. Some metastases may be cavitary or calcified. Pulmonary metastases may spread via the lymphatics. Asymmetric smooth or nodular interlobular septal thickening should raise concern for lymphangitic carcinomatosis. An uncommon mechanism is spread within the airways, which may result in an endobronchial lesion or post obstructive atelectasis.

Mycoplasma and Viral Pneumonia

Mycoplasma pneumoniae and viruses remain among the most common causes of community acquired pneumonia (CAP), and account for approximately 30% or more of all cases. M. pneumoniae is a bacterium that lacks a cell wall, which results in certain microbiologic features absent in other bacteria. The combination of centrilobular nodules, peribronchial thickening and lobular ground-glass attenuation on CT is the most suggestive pattern identified in patients with M. pneumoniae pneumonia. Although cellular bronchiolitis is a non-specific finding, a patchy or clustered distribution should raise the possibility of infectious etiology, with the most likely causative agents being M. pneumoniae, tuberculosis and viral bronchiolitis. The radiologic findings of adult viral and M. pneumoniae pneumonias are variable and depend on the host and the virulence of the pathogen. The imaging findings in this chapter overlap with those found in in pneumonias caused by atypical microorganisms (e.g. virus, PCP pneumonia, etc.). CT imaging of immunocompetent patients with suspected viral or mycoplasma pneumonia is not indicated unless there is suspicion of complications. CT may be performed in patients with normal, equivocal, or nonspecific radiographic findings. Conversely, CT is often indicated in immunocompromised patients with a normal chest radiograph and suspected pulmonary infection.

A Morphological and Quantitative Analysis of Lung CT Scan in Patients With Acute Respiratory Distress Syndrome and in Cardiogenic Pulmonary Edema

Background: The acute respiratory distress syndrome (ARDS) and cardiogenic pulmonary edema (CPE) are both characterized by an increase in lung edema that can be measured by computed tomography (CT). The aim of this study was to compare possible differences between patients with ARDS and CPE in the morphologic pattern, the aeration, and the amount and distribution of edema within the lung. Methods: Lung CT was performed at a mean positive end-expiratory pressure level of 5 cm H2O in both groups. The morphological evaluation was performed by two radiologists, while the quantitative evaluation was performed by a dedicated software. Results: A total of 60 patients with ARDS (20 mild, 20 moderate, 20 severe) and 20 patients with CPE were enrolled. The ground-glass attenuation regions were similarly present among the groups, 8 (40%), 8 (40%), 14 (70%), and 10 (50%), while the airspace consolidations were significantly more present in ARDS. The lung gas volume was significantly lower in severe ARDS compared to CPE (830 [462] vs 1120 [832] mL). Moving from the nondependent to the dependent lung regions, the not inflated lung tissue significantly increased, while the well inflated tissue decreased (ρ = 0.96-1.00, P < .0001). Significant differences were found between ARDS and CPE mostly in dependent regions. In severe ARDS, the estimated edema was significantly higher, compared to CPE (757 [740] vs 532 [637] g). Conclusions: Both ARDS and CPE are characterized by a similar presence of ground-glass attenuation and different airspace consolidation regions. Acute respiratory distress syndrome has a higher amount of not inflated tissue and lower amount of well inflated tissue. However, the overall regional distribution is similar within the lung.