Nocardia cyriacigeorgica bacteraemia presenting with cytomegalovirus disease and rapidly fatal pneumonia in a renal transplant patient: a case report

INTRODUCTION: Nocardia cyriacigeorgica bacteraemia has been described in the setting of profound immunodeficiency in only two previous case reports. In both instances, diagnosis was rapidly facilitated by 16S rRNA gene sequencing of blood culture isolates. To the best of our knowledge, we believe that our case is the first presentation of N. cyriacigeorgica bacteraemia associated with acute cytomegalovirus disease in a kidney transplant recipient, which was then followed by severe and fatal pneumonia only seven days later. CASE PRESENTATION: We present the case of a 73-year-old Caucasian woman, a renal transplant recipient, with peripheral vascular disease, hypertension, osteoporosis and vascular dementia who was diagnosed with septicemia and pneumonia. In spite of appropriate anti-microbial therapy for nocardial sepsis, she developed severe pneumonia and acute renal failure. CONCLUSION: This case illustrates a potential for disseminated nocardial infection to produce clinical syndromes that may be indistinguishable from acute cytomegalovirus disease. An atypical presentation (pneumonia and renal failure) of a rare disease (nocardial septicemia) in the setting of renal transplantation is discussed. This case illustrates that the possibility of severe cytomegalovirus disease should be considered in renal transplanted patients diagnosed with nocardial septicemia who subsequently develop severe sepsis, pneumonia, and renal failure. Molecular diagnosis should readily be available to assist with the prompt diagnosis and treatment of these infections in renal transplant patients

Functional immune responses against SARS-CoV-2 variants of concern after fourth COVID-19 vaccine dose or infection in patients with blood cancer

Summary Patients with blood cancer continue to have a greater risk of inadequate immune responses following three COVID-19 vaccine doses and risk of severe COVID-19 disease. In the context of the CAPTURE study (NCT03226886) we report immune responses in 80 patients with blood cancer who received a fourth dose of BNT162b2. We measured neutralising antibody titres (NAbT) using a live virus microneutralization assay against wild-type (WT), Delta, Omicron BA.1 and BA.2 and T cell responses against WT and Omicron BA.1 using an activation-induced marker (AIM) assay. The proportion of patients with detectable NAb titres and T cell responses after the fourth vaccine dose increases compared to those after the third vaccine dose. Patients who received B cell-depleting therapies within 12 months before vaccination have the greatest risk of not having detectable NAbT. In addition, we report immune responses in 57 patients with breakthrough infections after vaccination

Functional antibody and T-cell immunity following SARS-CoV-2 infection, including by variants of concern, in patients with cancer: the CAPTURE study

Patients with cancer have higher COVID-19 morbidity and mortality. Here we present the prospective CAPTURE study (NCT03226886) integrating longitudinal immune profiling with clinical annotation. Of 357 patients with cancer, 118 were SARS-CoV-2-positive, 94 were symptomatic and 2 patients died of COVID-19. In this cohort, 83% patients had S1-reactive antibodies, 82% had neutralizing antibodies against WT, whereas neutralizing antibody titers (NAbT) against the Alpha, Beta, and Delta variants were substantially reduced. Whereas S1-reactive antibody levels decreased in 13% of patients, NAbT remained stable up to 329 days. Patients also had detectable SARS-CoV-2-specific T cells and CD4+ responses correlating with S1-reactive antibody levels, although patients with hematological malignancies had impaired immune responses that were disease and treatment-specific, but presented compensatory cellular responses, further supported by clinical. Overall, these findings advance the understanding of the nature and duration of immune response to SARS-CoV-2 in patients with cancer

<it>Nocardia cyriacigeorgica</it> bacteraemia presenting with cytomegalovirus disease and rapidly fatal pneumonia in a renal transplant patient: a case report

Abstract Introduction Nocardia cyriacigeorgica bacteraemia has been described in the setting of profound immunodeficiency in only two previous case reports. In both instances, diagnosis was rapidly facilitated by 16S rRNA gene sequencing of blood culture isolates. To the best of our knowledge, we believe that our case is the first presentation of N. cyriacigeorgica bacteraemia associated with acute cytomegalovirus disease in a kidney transplant recipient, which was then followed by severe and fatal pneumonia only seven days later. Case presentation We present the case of a 73-year-old Caucasian woman, a renal transplant recipient, with peripheral vascular disease, hypertension, osteoporosis and vascular dementia who was diagnosed with septicemia and pneumonia. In spite of appropriate anti-microbial therapy for nocardial sepsis, she developed severe pneumonia and acute renal failure. Conclusion This case illustrates a potential for disseminated nocardial infection to produce clinical syndromes that may be indistinguishable from acute cytomegalovirus disease. An atypical presentation (pneumonia and renal failure) of a rare disease (nocardial septicemia) in the setting of renal transplantation is discussed. This case illustrates that the possibility of severe cytomegalovirus disease should be considered in renal transplanted patients diagnosed with nocardial septicemia who subsequently develop severe sepsis, pneumonia, and renal failure. Molecular diagnosis should readily be available to assist with the prompt diagnosis and treatment of these infections in renal transplant patients.</p

Coherent pipeline for biomarker discovery using mass spectrometry and bioinformatics

Abstract Background Robust biomarkers are needed to improve microbial identification and diagnostics. Proteomics methods based on mass spectrometry can be used for the discovery of novel biomarkers through their high sensitivity and specificity. However, there has been a lack of a coherent pipeline connecting biomarker discovery with established approaches for evaluation and validation. We propose such a pipeline that uses in silico methods for refined biomarker discovery and confirmation. Results The pipeline has four main stages: Sample preparation, mass spectrometry analysis, database searching and biomarker validation. Using the pathogen Clostridium botulinum as a model, we show that the robustness of candidate biomarkers increases with each stage of the pipeline. This is enhanced by the concordance shown between various database search algorithms for peptide identification. Further validation was done by focusing on the peptides that are unique to C. botulinum strains and absent in phylogenetically related Clostridium species. From a list of 143 peptides, 8 candidate biomarkers were reliably identified as conserved across C. botulinum strains. To avoid discarding other unique peptides, a confidence scale has been implemented in the pipeline giving priority to unique peptides that are identified by a union of algorithms. Conclusions This study demonstrates that implementing a coherent pipeline which includes intensive bioinformatics validation steps is vital for discovery of robust biomarkers. It also emphasises the importance of proteomics based methods in biomarker discovery.</p