Detection of Post-COVID-19 Lung Abnormalities: Photon-counting CT versus Same-Day Energy-integrating Detector CT.

Background Photon-counting detector (PCD) CT enables ultra-high-resolution lung imaging and may shed light on morphologic correlates of persistent symptoms after COVID-19. Purpose To compare PCD CT with energy-integrating detector (EID) CT for noninvasive assessment of post-COVID-19 lung abnormalities. Materials and Methods For this prospective study, adult participants with one or more COVID-19-related persisting symptoms (resting or exertional dyspnea, cough, fatigue) underwent same-day EID and PCD CT between April 2022 and June 2022. The 1.0-mm EID CT images and, subsequently, 1.0-, 0.4-, and 0.2-mm PCD CT images were reviewed for the presence of lung abnormalities. Subjective and objective EID and PCD CT image quality were evaluated using a five-point Likert scale (-2 to 2) and lung signal-to-noise ratios (SNRs). Results Twenty participants (mean age, 54 years ± 16 [SD]; 10 men) were included. EID CT showed post-COVID-19 lung abnormalities in 15 of 20 (75%) participants, with a median involvement of 10% of lung volume [IQR, 0%-45%] and 3.5 lobes [IQR, 0-5]. Ground-glass opacities and linear bands (10 of 20 participants [50%] for both) were the most frequent findings at EID CT. PCD CT revealed additional lung abnormalities in 10 of 20 (50%) participants, with the most common being bronchiectasis (10 of 20 [50%]). Subjective image quality was improved for 1.0-mm PCD versus 1.0-mm EID CT images (median, 1; IQR, 1-2; P < .001) and 0.4-mm versus 1.0-mm PCD CT images (median, 1; IQR, 1-1; P < .001) but not for 0.4-mm versus 0.2-mm PCD CT images (median, 0; IQR, 0-0.5; P = .26). PCD CT delivered higher lung SNR versus EID CT for 1.0-mm images (mean difference, 0.53 ± 0.96; P = .03) but lower SNR for 0.4-mm versus 1.0-mm images and 0.2-mm vs 0.4-mm images (-1.52 ± 0.68 [P < .001] and -1.15 ± 0.43 [P < .001], respectively). Conclusion Photon-counting detector CT outperformed energy-integrating detector CT in the visualization of subtle post-COVID-19 lung abnormalities and image quality. © RSNA, 2023 Supplemental material is available for this article.

Comparison of pulmonary function test, diffusion capacity, blood gas analysis and CT scan in patients with and without persistent respiratory symptoms following COVID-19.

BACKGROUND: Long-lasting symptoms following SARS-CoV2-infection have been described in several studies. However, there is only limited knowledge about the ongoing pathophysiology and the association with pathological findings in medical examinations. METHODS: In this post hoc analysis of a prospective trial, 135 patients following COVID-19 were enrolled and grouped with respect to the presence or absence of respiratory ongoing symptoms following COVID-19. Pulmonary function test (PFT), diffusion capacity measurement (TLCO SB and TLCO/VA), blood gas analysis (BGA), laboratory tests and high-resolution computed tomography (HRCT) of patients with persistent respiratory symptoms were compared to those of asymptomatic patients. RESULTS: In this analysis, 71% (96/135) of all patients (mean age 49 years; range 20-91 years) reported long-lasting symptoms after a median (IQR) of 85 days (60-116) following COVID-19 whereby 57.8% (78/135) complained about persistent pulmonary symptoms. Pathological findings in blood test, PFT, TLCO, BGA and/or HRCT were found in 71.8% and 64.1% of patients with and without long-lasting respiratory symptoms respectively. Patients with persistent respiratory symptoms were significantly younger and presented a significant lower FVC (%), TLC (L), and TLCO SB compared to asymptomatic patients (p < 0.05). The multiple logistic regression results in a significant effect of age (p = 0.004) and TLCO SB (p = 0.042). CONCLUSION: Following COVID-19, a large proportion of patients experience ongoing symptoms, whereby the respiratory symptoms are the predominant complaints. Compared to asymptomatic patients, patients with ongoing symptoms were younger and presented a significant lower FVC, TLC and TLCO SB. The multiple logistic regression demonstrated only a significant association between the TLCO SB as the only PFT parameter and the perceived symptoms.

Comparison of heart rates at fixed percentages and the ventilatory thresholds in patients with interstitial lung disease.

Heart rate (HR) responses to maximal exercise are commonly used for the prescription of training intensities in pulmonary rehabilitation. Those intensities are usually based on fixed percentages of peak HR (HRpeak), heart rate reserve (HRR), or peak work load (Wpeak), and rarely on HRs at the individual ventilatory thresholds (VT1 and VT2) derived from cardiopulmonary exercise testing (CPET). For patients suffering from interstitial lung disease (ILD), data on cardiorespiratory responses to CPET are scarce. Thus, the aim of this study was to record cardiorespiratory responses to CPET and to compare fixed HR percentages with HRs at VT1 and VT2 in ILD patients. A total of 120 subjects, 80 ILD patients and 40 healthy controls, underwent a symptom-limited CPET. From the ILD patient, 32 suffered from idiopathic pulmonary fibrosis (IPF), 37 from connective tissue disease (CTD), and 11 from sarcoidosis. HRs at fixed percentages, that is, at 70%HRpeak, at 70%Wpeak, and at 60%HRR were significantly lower in the ILD patients compared with the control group (p-values: 0.001, 0.044, and 0.011). Large percentages of HR values at 70%Wpeak and 60%HRR ranged between the HRs at VT1 and VT2 in ILD subgroups and controls as well. HRs at 70%HRpeak were lower than HRs at VT1 in 66% of the IPF patients, 54% of the CTD patients, and 55% of patients with sarcoidosis compared with 18% in the control group. Our findings demonstrate a considerable scattering of fixed HR percentages compared with HRs at the individual VTs derived from CPET in ILD patients. These findings may provide valuable information for the prescription of exercise intensity in pulmonary rehabilitation of ILD patients.

Impact of persistent D-dimer elevation following recovery from COVID-19.

BACKGROUND: Elevated D-dimer is known as predictor for severity of SARS-CoV2-infection. Increased D-dimer is associated with thromboembolic complications, but it is also a direct consequence of the acute lung injury seen in COVID-19 pneumonia. OBJECTIVES: To evaluate the rate of persistent elevated D-dimer and its association with thromboembolic complications and persistent ground glass opacities (GGO) after recovery from COVID-19. METHODS: In this post hoc analysis of a prospective multicenter trial, patients underwent blood sampling, measurement of diffusion capacity, blood gas analysis, and multidetector computed tomography (MDCT) scan following COVID-19. In case of increased D-dimer (>0,5 µg/ml), an additional contrast medium-enhanced CT was performed in absence of contraindications. Results were compared between patients with persistent D-dimer elevation and patients with normal D-dimer level. RESULTS: 129 patients (median age 48.8 years; range 19-91 years) underwent D-Dimer assessment after a median (IQR) of 94 days (64-130) following COVID-19. D-dimer elevation was found in 15% (19/129) and was significantly more common in patients who had experienced a severe SARS-CoV2 infection that had required hospitalisation compared to patients with mild disease (p = 0.049). Contrast-medium CT (n = 15) revealed an acute pulmonary embolism in one patient and CTEPH in another patient. A significant lower mean pO2 (p = 0.015) and AaDO2 (p = 0.043) were observed in patients with persistent D-Dimer elevation, but the rate of GGO were similar in both patient groups (p = 0.33). CONCLUSION: In 15% of the patients recovered from COVID-19, persistent D-dimer elevation was observed after a median of 3 months following COVID-19. These patients had experienced a more severe COVID and still presented more frequently a lower mean pO2 and AaDO2.

Predictors of Prolonged Cardiopulmonary Exercise Impairment After COVID-19 Infection: A Prospective Observational Study.

Objectives: Coronavirus disease 2019 (COVID-19) is a global pandemic affecting individuals to varying degrees. There is emerging evidence that even patients with mild symptoms will suffer from prolonged physical impairment. Methods: In this prospective observational study, lung function, and cardiopulmonary exercise testing have been performed in 100 patients for 3-6 months after COVID-19 diagnosis (post-CoVG). Depending on the severity of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection, patients were divided into asymptomatic, or mild to moderate (mild post-CoVG), and severe post-CoVG [hospitalization with or without intensive care unit/non-invasive ventilation (ICU/NIV)]. Results have been compared with age, sex, and body mass index (BMI) matched control group (CG, N = 50). Results: Both lung function (resting) and exercise capacity (peak workload, Wpeak and peak oxygen uptake, VO2 peak - % predicted) were considerably affected in patients with severe post-CoV (81.7 ± 27.6 and 86.1 ± 20.6%), compared to the mild post-CoVG (104.8 ± 24.0%, p = 0.001 and 100.4 ± 24.8; p = 0.003). In addition, also the submaximal exercise performance was significantly reduced in the severe post-CoVG (predicted VT1/VO2 peak; p = 0.013 and VT2/VO2 peak; p = 0.001). Multiple linear regression analyses revealed that 74 % (adjusted R 2) of the variance in relative VO2 peak of patients who had CoV could be explained by the following variables: lower age, male sex, lower BMI, higher DLCO, higher predicted heart rate (HR) peak, lower breathing reserve (BR), and lower SaO2 peak, which were related to higher relative VO2 peak values. Higher NT-proBNP and lower creatinine kinase (CK) values were seen in severe cases compared to patients who experienced mild CoV. Discussion: Maximal and submaximal exercise performance in patients recovering from severe COVID-19 remain negatively affected for 3-6 months after COVID-19 diagnosis. The presented findings reveal that impaired pulmonary, cardiac, and skeletal muscle function contributed to the limitation of VO2 peak in those patients, which may have important implications on rehabilitation programs.

Daptomycin plus fosfomycin, a synergistic combination in experimental implant-associated osteomyelitis due to methicillin-resistant Staphylococcus aureus in rats.

The aim of this study was to evaluate the combination of daptomycin and fosfomycin in experimental chronic implant-associated osteomyelitis due to methicillin-resistant Staphylococcus aureus (MRSA). Infection was induced in the tibiae of rats by the insertion of a bacterial inoculum (1 to 5×10(8) CFU/ml) of a clinical MRSA isolate and a titanium wire. Four weeks after infection, each animal was assigned to a treatment group: daptomycin monotherapy at 60 mg/kg of body weight once daily (n=10), fosfomycin monotherapy at 40 mg/kg once daily (n=10), or daptomycin and fosfomycin combined at 60 mg/kg and 40 mg/kg, respectively, once daily (n=9). Ten animals were left untreated. After a 3-week treatment period, the animals were euthanized, and the infected tibiae and implants were processed for quantitative bacterial cultures. The bacterial cultures from bones were positive for MRSA in all animals in the untreated group, the daptomycin group, and the fosfomycin group, with median bacterial counts of 2.34×10(6) CFU/g bone, 1.57×10(6) CFU/g bone, and 3.48×10(2) CFU/g bone, respectively. In the daptomycin-fosfomycin group, 6 out of 9 animals were positive for MRSA, with a median count of 7.92 CFU/g bone. Bacterial cultures derived from the titanium wires were negative in the fosfomycin- and daptomycin-fosfomycin-treated groups. Based on bacterial counts in bones, treatment with daptomycin-fosfomycin was statistically significantly superior to all that of the other groups (P≤0.003). Fosfomycin was superior to daptomycin and no treatment (P<0.0001). No development of resistance was observed in any treatment arm. The combination of daptomycin and fosfomycin demonstrated synergism against MRSA in experimental implant-associated osteomyelitis.

Efficacy of fosfomycin compared to vancomycin in treatment of implant-associated chronic methicillin-resistant Staphylococcus aureus osteomyelitis in rats.

Fosfomycin monotherapy was compared to therapy with vancomycin for the treatment of implant-associated methicillin-resistant Staphylococcus aureus (MRSA) osteomyelitis in an experimental rat model. The proximal tibiae were inoculated with 15 µl of a suspension containing 1×10(8) to 5×10(8) CFU/ml of a clinical isolate of MRSA with simultaneous insertion of a titanium wire. Four weeks later, treatment was started for 28 days with either 50 mg/kg of body weight vancomycin intraperitoneally twice daily (n=11) or 75 mg/kg fosfomycin intraperitoneally once daily (n=10). Eleven animals were left untreated. After treatment, quantitative cultures from bone were found to be positive for MRSA in all animals in the untreated group (median, 3.29×10(6) CFU/g of bone) and the vancomycin group (median, 3.03×10(5) CFU/g of bone). In the fosfomycin group, MRSA was detectable in 2 out of 10 (20%) animals (3.42×10(2) and 1.51×10(3) CFU/g of bone). Vancomycin was superior to the no-drug control (P=0.002), and fosfomycin was superior to the no-drug control and vancomycin (P<0.001). The cultures from the wires were positive in all untreated animals (median, 2.5×10(3) CFU/implant), in 10 animals in the vancomycin group (median, 1.15×10(3) CFU/implant), and negative in all animals in the fosfomycin group. Based on the bacterial counts from the implants, vancomycin was not superior to the no-drug control (P=0.324), and fosfomycin was superior to the no-drug control and vancomycin (P<0.001). No emergence of resistance was observed. In conclusion, it was demonstrated that fosfomycin monotherapy is highly effective for the treatment of experimental implant-associated MRSA osteomyelitis.

Assessing pharmacokinetics of different doses of fosfomycin in laboratory rats enables adequate exposure for pharmacodynamic models.

Fosfomycin has been the subject of numerous pharmacodynamic in vivo models in recent years. The present study set out to determine fosfomycin pharmacokinetics in laboratory rats to enable adequate dosing regimens in future rodent models. Fosfomycin was given intraperitoneally as single doses of 75, 200 and 500 mg/kg bodyweight to 4 Sprague-Dawley rats per dose group. Blood samples were collected over 8 h and fosfomycin concentrations were determined by HPLC-mass spectrometry. Fosfomycin showed a dose-proportional pharmacokinetic profile indicated by a correlation of 0.99 for maximum concentration and area under the concentration-time curve (AUC). The mean AUC0-8 after intraperitoneal administration of 75, 200 or 500 mg/kg bodyweight fosfomycin were 109.4, 387.0 and 829.1 µg·h/ml, respectively. In conclusion, a dosing regimen of 200-500 mg/kg 3 times daily is appropriate to obtain serum concentrations in laboratory rats, closely mimicking human serum concentrations over time.