COVID-19 patients treated with convalescent plasma. / Covid-19-pasienter behandlet med rekonvalesensplasma.

BACKGROUND: In Norway, treatment with COVID-19 convalescent plasma has been given through the NORPLASMA project. The treatment was initially offered to critically ill patients after an individual assessment, but from December 2020, the indication was limited to critically ill, immunocompromised patients. In this article we describe clinical characteristics, comorbidity and mortality in patients who received convalescent plasma in these two periods. MATERIAL AND METHOD: From 22 April 2020 to 30 March 2022, a total of 79 patients were included in the observational studies NORPLASMA MONITOR and the Norwegian SARS-CoV-2 study. The patients had received a total of 193 units of convalescent plasma at 15 Norwegian hospitals/nursing homes; 62 in South-Eastern Norway Regional Health Authority, 8 in Western Norway Regional Health Authority and 9 in Central Norway Regional Health Authority. Information on immune status, comorbidity and course of infection was retrieved from the patient records after informed written consent was obtained. RESULTS: Of 79 patients with a median age of 65 years (interquartile range 51-⁠73) who were treated with convalescent plasma, 31 (39 %) died during hospitalisation. A total of 59 patients were immunocompromised, and of these, 20 died in hospital compared to 11 of 20 who were assumed to be immunocompetent. Median number of comorbidities was 2 (interquartile range 1-4). The patients received a median of two plasma units (min.-max. 1-21). Two of the patients developed mild allergic skin reactions. INTERPRETATION: Convalescent plasma was well tolerated by patients with COVID-19. Immunocompromised patients may have benefitted from the treatment, with lower mortality than for those assumed to be immunocompetent.

Raised Serum Markers of T Cell Activation and Exhaustion in Granulomatous-Lymphocytic Interstitial Lung Disease in Common Variable Immunodeficiency.

PURPOSE: About 20-30% of patients with common variable immunodeficiency (CVID) develop granulomatous-lymphocytic interstitial lung disease (GLILD) as one of several non-infectious complications to their immunodeficiency. The purpose of this study was to identify biomarkers that could distinguish GLILD from other non-infectious complications in CVID. METHODS: We analyzed serum biomarkers related to inflammation, pulmonary epithelium injury, fibrogenesis, and extracellular matrix (ECM) remodeling, and compared three subgroups of CVID: GLILD patients (n = 16), patients with other non-infectious complications (n = 37), and patients with infections only (n = 20). RESULTS: We found that GLILD patients had higher levels of sCD25, sTIM-3, IFN-γ, and TNF, reflecting T cell activation and exhaustion, compared to both CVID patients with other inflammatory complications and CVID with infections only. GLILD patients also had higher levels of SP-D and CC16, proteins related to pulmonary epithelium injury, as well as the ECM remodeling marker MMP-7, than patients with other non-infectious complications. CONCLUSION: GLILD patients have elevated serum markers of T cell activation and exhaustion, pulmonary epithelium injury, and ECM remodeling, pointing to potentially important pathways in GLILD pathogenesis, novel targets for therapy, and promising biomarkers for clinical evaluation of these patients.

Granulomatous-Lymphocytic Interstitial Lung Disease in Common Variable Immunodeficiency-Features of CT and 18F-FDG Positron Emission Tomography/CT in Clinically Progressive Disease.

Common variable immunodeficiency (CVID) is characterized not only by recurrent bacterial infections, but also autoimmune and inflammatory complications including interstitial lung disease (ILD), referred to as granulomatous-lymphocytic interstitial lung disease (GLILD). Some patients with GLILD have waxing and waning radiologic findings, but preserved pulmonary function, while others progress to end-stage respiratory failure. We reviewed 32 patients with radiological features of GLILD from our Norwegian cohort of CVID patients, including four patients with possible monogenic defects. Nineteen had deteriorating lung function over time, and 13 had stable lung function, as determined by pulmonary function testing of forced vital capacity (FVC), and diffusion capacity of carbon monoxide (DLCO). The overall co-existence of other non-infectious complications was high in our cohort, but the prevalence of these was similar in the two groups. Laboratory findings such as immunoglobulin levels and T- and B-cell subpopulations were also similar in the progressive and stable GLILD patients. Thoracic computer tomography (CT) scans were systematically evaluated and scored for radiologic features of GLILD in all pulmonary segments. Pathologic features were seen in all pulmonary segments, with traction bronchiectasis as the most prominent finding. Patients with progressive disease had significantly higher overall score of pathologic features compared to patients with stable disease, most notably traction bronchiectasis and interlobular septal thickening. 18F-2-fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography/CT (PET/CT) was performed in 17 (11 with progressive and six with stable clinical disease) of the 32 patients and analyzed by quantitative evaluation. Patients with progressive disease had significantly higher mean standardized uptake value (SUVmean), metabolic lung volume (MLV) and total lung glycolysis (TLG) as compared to patients with stable disease. Nine patients had received treatment with rituximab for GLILD. There was significant improvement in pathologic features on CT-scans after treatment while there was a variable effect on FVC and DLCO. Conclusion: Patients with progressive GLILD as defined by deteriorating pulmonary function had significantly greater pathology on pulmonary CT and FDG-PET CT scans as compared to patients with stable disease, with traction bronchiectasis and interlobular septal thickening as prominent features.