ABSTRACT
The role of autoimmunity in post-acute sequelae of COVID-19 (PASC) is not well explored, although clinicians observe a growing population of convalescent COVID-19 patients with manifestation of post-acute sequelae of COVID-19. We analyzed the immune response in 40 post-acute sequelae of COVID-19 patients with non-specific PASC manifestation and 15 COVID-19 convalescent healthy donors. The phenotyping of lymphocytes showed a significantly higher number of CD8+ T cells expressing the Epstein-Barr virus induced G protein coupled receptor 2, chemokine receptor CXCR3 and C-C chemokine receptor type 5 playing an important role in inflammation and migration in PASC patients compared to controls. Additionally, a stronger, SARS-CoV-2 reactive CD8+ T cell response, characterized by IFN{gamma} production and predominant TEMRA phenotype but low SARS-CoV-2 avidity was detected in PASC patients compared to controls. Furthermore, higher titers of several autoantibodies were detected among PASC patients. Our data suggest that a persistent inflammatory response triggered by SARS-CoV-2 might be responsible for the observed sequelae in PASC patients. These results may have implications on future therapeutic strategies.
ABSTRACT
BackgroundWhen patients with chronic kidney disease are infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) they can face two specific problems: Virus-specific immune responses may be impaired and remdesivir, an antiviral drug described to shorten the time to recovery, is contraindicated. Antiviral treatment with convalescent plasma could be an alternative treatment option. MethodsIn this case series we present two kidney transplant recipients and two patients dependent on haemodialysis who were infected with SARS-CoV-2 and received convalescent plasma. Antibodies against the spike 1 protein of SARS-CoV-2 were determined sequentially by IgG ELISA and neutralization assay and specific T cell responses by interferon-gamma ELISpot. ResultsPrior to treatment, in three patients antibodies were undetectable by ELISA (ratio < 1.1), corresponding to low neutralizing antibody titers ([≤] 1:40). One patient was also negative to the ELISpot and two showed weak responses. After convalescent plasma treatment we observed an increase of SARS-CoV-2-specific antibodies (IgG ratio and neutralization titer) and of specific T cell responses. After intermittent clinical improvement one kidney transplant recipient again developed typical symptoms at day 12 after treatment and received a second cycle of convalescent plasma treatment. Altogether, three patients clinically improved and could be discharged from hospital. However, one multimorbid female in her early eighties deceased. ConclusionsOur data suggest that the success of convalescent plasma therapy may only be temporary in patients with chronic kidney disease; which requires an adaptation of the treatment regimen. Close monitoring after treatment is needed for this patient group.
ABSTRACT
Purpose@#To study the value of 2-deoxy-2-[18F]fluoro-D-glucose([18F]FDG) positron emission tomography/computed tomography(PET/CT) and [18F]FDG positron emission tomography/magnetic resonance imaging (PET/MRI) in assessing immunocompromisedpatients with suspected malignancy or infection. @*Methods@#[18F]FDG-PET/CT and [18F]FDG-PET/MRI examinations of patients who were immunocompromised after receivinglung, heart, pancreas, kidney, liver, or combined kidney-liver transplants were analyzed in this retrospective study. Patientsunderwent whole-body hybrid-imaging because of clinical signs of malignancy and/or infection. Findings were assessed bymolecular features ([18F]FDG-uptake) and morphological changes. The final diagnosis, which was arrived at after review ofclinical, laboratory, and histopathologic analyses and follow-up imaging studies, served as the reference standard. @*Results@#Altogether, (i) 28 contrast-enhanced [18F]FDG-PET/CT scans (CE-PET/CT), (ii) 33 non-contrast [18F]FDG-PET/CTscans (NC-PET/CT), and (iii) 18 [18F]FDG-PET/MRI scans were included. Additionally, 12/62 patients underwent follow-upPET imaging to rule out vital tumor ormetabolic active inflammatory processes. CE-PET/CT exhibited 94.4%sensitivity, 80.0%specificity, 89.5% positive predictive value (PPV), 88.9% negative predictive value (NPV), and 89.3% accuracy with regard tothe reference standard. NC-PET/CT exhibited 91.3% sensitivity, 80.0% specificity, 91.3% PPV, 80.0% NPV, and 87.9% accuracy. PET/MRI exhibited 88.6% sensitivity, 99.2% specificity, 99.6% PPV, 81.3% NPV, and 94.4% accuracy. ExactMcNemar statistical test (one-sided) showed significant difference between the CT-/MR-component alone and the integratedPET/CT and PET/MRI for diagnosis of malignancy or infection (p value < 0.001). Radiation exposure was 4- to 7-fold higherwith PET/CT than with PET/MRI. @*Conclusion@#For immunocompromised patients with clinically unresolved symptoms, to rule out vital tumor manifestations ormetabolic active inflammation, [18F]FDG-PET/MRI, CE-[18F]FDG-PET/CT, and NC-[18F]FDG-PET/CT exhibit excellent performancein diagnosing malignancy or infection. The main strength of PET/MRI is its considerably lower level of radiationexposure than that associated with PET/CT.
