Lung perfusion disturbances in nonhospitalized post-COVID with dyspnea-A magnetic resonance imaging feasibility study.

BACKGROUND: Dyspnea is common after COVID-19. Though the underlying mechanisms are largely unknown, lung perfusion abnormalities could contribute to lingering dyspnea. OBJECTIVES: To detect pulmonary perfusion disturbances in nonhospitalized individuals with the post-COVID condition and persistent dyspnea 4-13 months after the disease onset. METHODS: Individuals with dyspnea and matched healthy controls were recruited for dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), a 6-min walk test, and an assessment of dyspnea. The DCE-MRI was quantified using two parametric values: mean time to peak (TTP) and TTP ratio, reflecting the total lung perfusion resistance and the fraction of lung with delayed perfusion, respectively. RESULTS: Twenty-eight persons with persistent dyspnea (mean age 46.5 ± 8.0 years, 75% women) and 22 controls (mean age 44.1 ± 10.8 years, 73% women) were included. There was no systematic sex difference in dyspnea. The post-COVID group had no focal perfusion deficits but had higher mean pulmonary TTP (0.43 ± 0.04 vs. 0.41 ± 0.03, p = 0.011) and TTP ratio (0.096 ± 0.052 vs. 0.068 ± 0.027, p = 0.032). Post-COVID males had the highest mean TTP of 0.47 ± 0.02 and TTP ratio of 0.160 ± 0.039 compared to male controls and post-COVID females (p = 0.001 and p < 0.001, respectively). Correlations between dyspnea and perfusion parameters were demonstrated in males (r = 0.83, p < 0.001 for mean TTP; r = 0.76, p = 0.003 for TTP ratio), but not in females. CONCLUSIONS: DCE-MRI demonstrated late contrast bolus arrival in males with post-COVID dyspnea, suggestive of primary vascular lesions or secondary effects of hypoxic vasoconstriction. Since this effect was not regularly observed in female patients, our findings suggest sex differences in the mechanisms underlying post-COVID dyspnea, which warrants further investigation in dedicated trials.

Negative effects of iodine-based contrast agent on renal function in patients with moderate reduced renal function hospitalized for COVID-19.

BACKGROUND: Kidney disease and renal failure are associated with hospital deaths in patients with COVID - 19. We aimed to test if contrast enhancement affects short-term renal function in hospitalized COVID - 19 patients. METHODS: Plasma creatinine (P-creatinine) was measured on the day of computed tomography (CT) and 24 h, 48 h, and 4-10 days after CT. Contrast-enhanced (n = 142) and unenhanced (n = 24) groups were subdivided, based on estimated glomerular filtration rates (eGFR), > 60 and ≤ 60 ml/min/1.73 m2. Contrast-induced acute renal failure (CI-AKI) was defined as ≥27 µmol/L increase or a > 50% rise in P-creatinine from CT or initiation of renal replacement therapy during follow-up. Patients with renal replacement therapy were studied separately. We evaluated factors associated with a > 50% rise in P-creatinine at 48 h and at 4-10 days after contrast-enhanced CT. RESULTS: Median P-creatinine at 24-48 h and days 4-10 post-CT in patients with eGFR> 60 and eGFR≥30-60 in contrast-enhanced and unenhanced groups did not differ from basal values. CI-AKI was observed at 48 h and at 4-10 days post contrast administration in 24 and 36% (n = 5/14) of patients with eGFR≥30-60. Corresponding figures in the eGFR> 60 contrast-enhanced CT group were 5 and 5% respectively, (p < 0.037 and p < 0.001, Pearson χ2 test). In the former group, four of the five patients died within 30 days. Odds ratio analysis showed that an eGFR≥30-60 and 30-day mortality were associated with CK-AKI both at 48 h and 4-10 days after contrast-enhanced CT. CONCLUSION: Patients with COVID - 19 and eGFR≥30-60 had a high frequency of CK-AKI at 48 h and at 4-10 days after contrast administration, which was associated with increased 30-day mortality. For patients with eGFR≥30-60, we recommend strict indications are practiced for contrast-enhanced CT. Contrast-enhanced CT had a modest effect in patients with eGFR> 60.

Widespread Parenchymal Abnormalities and Pulmonary Embolism on Contrast-Enhanced CT Predict Disease Severity and Mortality in Hospitalized COVID-19 Patients.

Purpose: Severe COVID-19 is associated with inflammation, thromboembolic disease, and high mortality. We studied factors associated with fatal outcomes in consecutive COVID-19 patients examined by computed tomography pulmonary angiogram (CTPA). Methods: This retrospective, single-center cohort analysis included 130 PCR-positive patients hospitalized for COVID-19 [35 women and 95 men, median age 57 years (interquartile range 51-64)] with suspected pulmonary embolism based on clinical suspicion. The presence and extent of embolism and parenchymal abnormalities on CTPA were recorded. The severity of pulmonary parenchymal involvement was stratified by two experienced radiologists into two groups: lesions affecting ≤50% or >50% of the parenchyma. Patient characteristics, radiological aspects, laboratory parameters, and 60-day mortality data were collected. Results: Pulmonary embolism was present in 26% of the patients. Most emboli were small and peripheral. Patients with widespread parenchymal abnormalities, with or without pulmonary embolism, had increased main pulmonary artery diameter (p < 0.05) and higher C-reactive protein (p < 0.01), D-dimer (p < 0.01), and troponin T (p < 0.001) and lower hemoglobin (p < 0.001). A wider main pulmonary artery diameter correlated positively with C-reactive protein (r = 0.28, p = 0.001, and n = 130) and procalcitonin. In a multivariant analysis, D-dimer >7.2 mg/L [odds ratio (±95% confidence interval) 4.1 (1.4-12.0)] and ICU stay were significantly associated with embolism (p < 0.001). The highest 60-day mortality was found in patients with widespread parenchymal abnormalities combined with pulmonary embolism (36%), followed by patients with widespread parenchymal abnormalities without pulmonary embolism (26%). In multivariate analysis, high troponin T, D-dimer, and plasma creatinine and widespread parenchymal abnormalities on CT were associated with 60-day mortality. Conclusions: Pulmonary embolism combined with widespread parenchymal abnormalities contributed to mortality risk in COVID-19. Elevated C-reactive protein, D-dimer, troponin-T, P-creatinine, and enlarged pulmonary artery were associated with a worse outcome and may mirror a more severe systemic disease. A liberal approach to radiological investigation should be recommended at clinical deterioration, when the situation allows it. Computed tomography imaging, even without intravenous contrast to assess the severity of pulmonary infiltrates, are of value to predict outcome in COVID-19. Better radiological techniques with higher resolution could potentially improve the detection of microthromboses. This could influence anticoagulant treatment strategies, preventing clinical detoriation.

Randomised, controlled, open label, multicentre clinical trial to explore safety and efficacy of hyperbaric oxygen for preventing ICU admission, morbidity and mortality in adult patients with COVID-19.

INTRODUCTION: COVID-19 may cause severe pneumonitis and trigger a massive inflammatory response that requires ventilatory support. The intensive care unit (ICU)-mortality has been reported to be as high as 62%. Dexamethasone is the only of all anti-inflammatory drugs that have been tested to date that has shown a positive effect on mortality. We aim to explore if treatment with hyperbaric oxygen (HBO) is safe and effective for patients with severe COVID-19. Our hypothesis is that HBO can prevent ICU admission, morbidity and mortality by attenuating the inflammatory response. The primary objective is to evaluate if HBO reduces the number of ICU admissions compared with best practice treatment for COVID-19, main secondary objectives are to evaluate if HBO reduces the load on ICU resources, morbidity and mortality and to evaluate if HBO mitigates the inflammatory reaction in COVID-19. METHODS AND ANALYSIS: A randomised, controlled, phase II, open label, multicentre trial. 200 subjects with severe COVID-19 and at least two risk factors for mortality will be included. Baseline clinical data and blood samples will be collected before randomisation and repeated daily for 7 days, at days 14 and 30. Subjects will be randomised with a computer-based system to HBO, maximum five times during the first 7 days plus best practice treatment or only best practice treatment. The primary endpoint, ICU admission, is defined by criteria for selection for ICU. We will evaluate if HBO mitigates the inflammatory reaction in COVID-19 using molecular analyses. All parameters are recorded in an electronic case report form. An independent Data Safety Monitoring Board will review the safety parameters. ETHICS AND DISSEMINATION: The trial is approved by The National Institutional Review Board in Sweden (2020-01705) and the Swedish Medical Product Agency (5.1-2020-36673). Positive, negative and any inconclusive results will be published in peer-reviewed scientific journals with open access. TRIAL REGISTRATION: NCT04327505. EudraCT number: 2020-001349-37.