Epidemiological characteristics and outcome of viral respiratory tract infections in the first year after allogeneic hematopoietic cell transplantation.

Adverse outcomes of viral respiratory tract infections (RTI) have been reported in recipients of allogeneic hematopoietic cell transplantation. Using a laboratory-developed multiparameter PCR in a consecutive series of 242 patients, we found the highest incidence of viral RTI in the pre-engraftment phase. The occurrence of multiple episodes of viral RTI or viral pneumonia was significantly associated with a higher hazard of non-relapse mortality in the first year after transplantation. We observed a 90-day mortality of 19.7% after viral RTI, which was significantly different between patient groups stratified according to the ISI score.

Dynamics of the Cellular and Humoral Immune Response After BNT162b2 Messenger Ribonucleic Acid Coronavirus Disease 2019 (COVID-19) Vaccination in COVID-19-Naive Nursing Home Residents.

Short-term humoral and cellular immune responses are diminished after BNT162b2 messenger ribonucleic acid coronavirus disease 2019 (COVID-19) vaccination in COVID-19-naive nursing home residents, a population particularly vulnerable to the disease. We found both responses to decline after 4 weeks and remain lower than those of healthcare workers after 24 weeks, with an estimated half-life of the antibody response of 47 days. At 4 weeks, older age was significantly associated with a decreased humoral response, and diabetes mellitus and active malignancy were associated with a decreased cellular response. Our results imply that COVID-19-naive nursing home residents are a target group for booster vaccination trials.

Comparison of four commercial SARS-CoV-2 IgG immuno-assays in RT-PCR negative patients with suspect CT findings.

A subset of patients with Covid-19 presents with negative RT-PCR screening but suspect CT findings. Using four commercially available anti-SARS-CoV-2 IgG immuno-assays, we found this subset constituted 9.2% of all consecutively admitted outpatients with Covid-19 in our hospital. Clinical specificity for Covid-19 of some N protein-based immuno-assays was suboptimal, as positive results were observed in control patients with recent common human coronavirus, influenza B and adenovirus infections.

Commensal microbiota influence systemic autoimmune responses.

Antinuclear antibodies are a hallmark feature of generalized autoimmune diseases, including systemic lupus erythematosus and systemic sclerosis. However, the processes underlying the loss of tolerance against nuclear self-constituents remain largely unresolved. Using mice deficient in lymphotoxin and Hox11, we report that approximately 25% of mice lacking secondary lymphoid organs spontaneously develop specific antinuclear antibodies. Interestingly, we find this phenotype is not caused by a defect in central tolerance. Rather, cell-specific deletion and in vivo lymphotoxin blockade link these systemic autoimmune responses to the formation of gut-associated lymphoid tissue in the neonatal period of life. We further demonstrate antinuclear antibody production is influenced by the presence of commensal gut flora, in particular increased colonization with segmented filamentous bacteria, and IL-17 receptor signaling. Together, these data indicate that neonatal colonization of gut microbiota influences generalized autoimmunity in adult life.

Belgian 2024 guidance on the use of pre-exposure prophylaxis.

OBJECTIVES: We aimed to develop a guidance on the use of pre-exposure prophylaxis (PrEP) for HIV tailored to the Belgian context. METHODS: Different aspects of PrEP care were judged by an expert group of nine Belgian clinicians, seeking consensus for areas of controversies. RESULTS: PrEP should be considered in HIV negative patients at high risk of acquiring HIV. Currently, only oral tenofovir/emtricitabine is available in Belgium for PrEP, which can be used daily, or also event-driven in cisgender men and trans women who are not taking exogenous estradiol-based hormones. Personal counselling directed at medication adherence and sexual health should have a central role in PrEP care. At the initial assessment clinicians should give attention to symptoms of an acute HIV infection, the patients' immunization status and renal function. A regular follow-up must be set up to diagnose HIV seroconversion, treat sexually transmitted infections, and manage side effects of PrEP. CONCLUSION: The Belgian guidance on the use of PrEP provides a point of reference for standard PrEP care in Belgium and will be periodically updated.

Infections caused by hypervirulent Klebsiella pneumoniae in non-endemic countries: three case reports and review of the literature.

OBJECTIVES: Spontaneous liver abscess caused by a hypervirulent Klebsiella pneumoniae strain was first described several decades ago in Taiwan and has been an emerging clinical entity worldwide ever since. We aimed to describe the clinical and microbiological characteristics of this infection in a non-endemic setting. METHODS: A narrative literature review was conducted in PubMed for European case reports of hypervirulent Klebsiella pneumoniae from 2016 to 2021. RESULTS: Forty case reports were retrieved. Mean age of the patients was 59 years and 72% were male. Diabetes mellitus was present in 33%. Twenty percent of the patients originated from an endemic region. A liver abscess and bacteremia were observed in, respectively, 83% and 80% of the cases. The most frequent metastatic infections were found in the eye (28%) and the lungs (28%). The sensitivity of molecular capsular antigen detection and the string test was 87% and 92%, respectively. Sixty-three percent of the strains had a wildtype resistance. CONCLUSION: Hypervirulent Klebsiella pneumoniae infections in non-endemic countries are most frequently observed in middle-aged males. Clinicians should be vigilant for metastatic infections.

Infectious diarrhea after allogeneic hematopoietic cell transplantation assessed by a multiplex polymerase chain reaction assay.

OBJECTIVES: To determine the incidence of infectious diarrhea after allogeneic hematopoietic cell transplantation (HCT) using a multiplex polymerase chain reaction assay and assess risk factors for developing infectious diarrhea. METHODS: This was a single-center retrospective study of 140 consecutive allogeneic HCT recipients. Infectious diarrhea was assessed using a laboratory-developed multiplex polymerase chain reaction the first year after transplantation. RESULTS: The incidence rate of infectious diarrhea episodes was 47 per 100 person-years, with the highest rate observed in the pre-engraftment phase. Most episodes were seen as nosocomial infections (38%) and most affected patients (82%) had only one episode of infectious diarrhea. The cumulative incidence of at least one episode of infectious diarrhea was 32% after 1 year. Nonrelapse mortality was higher in transplant recipients with at least one episode of infectious diarrhea (hazard ratio (HR) 2.02, 95% CI = 1.07-3.80). The most frequently observed pathogens were Clostridium difficile, adenovirus, Enteropathogenic Escherichia coli, and Campylobacter jejuni. Patients with acute lower gastrointestinal graft-vs-host disease stage 3 or 4 (HR 3.68, 95% CI = 1.57-8.63) conferred a higher risk for a first infectious diarrhea episode. CONCLUSION: Infectious diarrhea after allogeneic HCT was seen in about one-third of the patients, mostly as nosocomial infection in the pre-engraftment phase.

Immune Senescence Markers Predict the Cellular Immune Response to BNT162b2 Vaccination in Hemodialysis Patients.

Background: Chronic kidney disease is associated with increased risk of frailty and accelerated immune senescence, potentially affecting the immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. Methods: Humoral and cellular responses against the spike protein of SARS-CoV-2 were determined in 189 COVID-naive hemodialysis patients at week 4 and 8 after vaccination with 2 doses of BNT162b2. Frailty indicators and immune senescence markers were determined at baseline to identify predictors of the immune response. Results: Controlling for age, activities of daily living (ADLs), instrumental ADLs, walking pace, and the clinical frailty score correlated negatively and hand grip strength positively with the humoral response. Controlling for age, the proportions of memory CD4+ T cells, memory CD8+ T cells, CD28null T cells, and CD57+CD8+ T cells correlated negatively with the humoral response, whereas the proportions of memory CD4+ T cells and CD28null T cells correlated negatively and the CD4/CD8 ratio positively with the cellular response. In a multivariate model, only the proportions of memory CD4+ T cells and CD28null T cells independently predicted the cellular response. Conclusions: Markers of immune senescence, but not frailty indicators, independently predict the cellular immune response after vaccination in hemodialysis patients, overruling the effect of chronological age.

Nailfold capillaroscopy for day-to-day clinical use: construction of a simple scoring modality as a clinical prognostic index for digital trophic lesions.

OBJECTIVE: Construction of a simple nailfold videocapillaroscopic (NVC) scoring modality as a prognostic index for digital trophic lesions for day-to-day clinical use. METHODS: An association with a single simple (semi)-quantitatively scored NVC parameter, mean score of capillary loss, was explored in 71 consecutive patients with systemic sclerosis (SSc), and reliable reduction in the number of investigated fields (F32-F16-F8-F4). The cut-off value of the prognostic index (mean score of capillary loss calculated over a reduced number of fields) for present/future digital trophic lesions was selected by receiver operating curve (ROC) analysis. RESULTS: Reduction in the number of fields for mean score of capillary loss was reliable from F32 to F8 (intraclass correlation coefficient of F16/F32: 0.97; F8/F32: 0.90). Based on ROC analysis, a prognostic index (mean score of capillary loss as calculated over F8) with a cut-off value of 1.67 is proposed. This value has a sensitivity of 72.22/70.00, specificity of 70.59/69.77, positive likelihood ratio of 2.46/2.32 and a negative likelihood ratio of 0.39/0.43 for present/future digital trophic lesions. CONCLUSIONS: A simple prognostic index for digital trophic lesions for daily use in SSc clinics is proposed, limited to the mean score of capillary loss as calculated over eight fields (8 fingers, 1 field per finger).

Specific anti-nuclear antibodies in systemic sclerosis patients with and without skin involvement: an extended methodological approach.

OBJECTIVES: To determine how sensitively SSc-associated ANAs are detected by a standard identification algorithm compared with an extensive panel of ANA identification assays, and to assess the distribution of SSc-associated ANAs and SSc organ system involvement in patients without skin involvement (limited SSc). METHODS: Serum samples from 145 consecutive monocentric SSc patients fulfilling LeRoy and Medgser's criteria for early SSc were studied. ANAs were detected by IIF on HEp-2000 cells and identified by western blotting, protein radio-immunoprecipitation, RNA immunoprecipitation and line immunoassay (LIA). SSc organ involvement was assessed according to a modification of Medsger's disease severity scale. RESULTS: At least one specific ANA reactivity was present in 88% of the patients. The standard algorithm (IIF and LIA) found at least one specific ANA in 74% of the patients. The main reactivities missed by this algorithm were anti-RNA polymerase III, anti-PM/Scl and anti-Th/To. Eighty-three percent of the patients with limited SSc had at least one ANA. ACAs and anti-Th/To antibodies were significantly associated with limited SSc, whereas anti-topoisomerase I and anti-RNA polymerase III were observed less frequently. SSc organ system involvement was present in 63% of the patients with limited SSc, most of whom had lung involvement. CONCLUSIONS: Standard algorithms for ANA identification lack sensitivity for the detection of SSc-associated ANA and should be supplemented with additional assays, especially in a clinical environment that has particular interest in SSc. The spectrum of SSc-associated ANA differs according to the presence or absence of skin involvement.

Hospital mortality in COVID-19 patients in Belgium treated with statins, ACE inhibitors and/or ARBs.

The COVID-19 pandemic has disrupted life throughout the world. Newly developed vaccines promise relief to people who live in high-income countries, although vaccines and expensive new treatments are unlikely to arrive in time to help people who live in low-and middle-income countries. The pathogenesis of COVID-19 is characterized by endothelial dysfunction. Several widely available drugs like statins, ACE inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) have immunometabolic activities that (among other things) maintain or restore endothelial cell function. For this reason, we undertook an observational study in four Belgian hospitals to determine whether in-hospital treatment with these drugs could improve survival in 959 COVID-19 patients. We found that treatment with statins and ACEIs/ARBs reduced 28-day mortality in hospitalized COVID-19 patients. Moreover, combination treatment with these drugs resulted in a 3-fold reduction in the odds of hospital mortality (OR = 0.33; 95% CI 0.17-0.69). These findings were in general agreement with other published studies. Additional observational studies and clinical trials are needed to convincingly show that in-hospital treatment with statins, ACEIs/ARBs, and especially their combination saves lives.

Reliability of the qualitative and semiquantitative nailfold videocapillaroscopy assessment in a systemic sclerosis cohort: a two-centre study.

OBJECTIVE: Investigation of the reliability of the qualitative and semiquantitative scoring of nailfold videocapillaroscopy (NVC) assessment between two raters in a systemic sclerosis (SSc) cohort. METHODS: Two raters from different centres blindly assessed the NVC images of 71 consecutive patients with SSc qualitatively as belonging to the scleroderma spectrum (SDS) category ('early', 'active', 'late' scleroderma pattern or 'scleroderma-like' pattern) or to the 'normal' category and semiquantitatively by calculating the mean score for capillary loss, giant capillaries, microhaemorrhages and capillary ramifications. Inter-rater/intrarater agreement was assessed by calculation of the proportion of agreement and by kappa coefficients. Rater agreement of mean score values of hallmark parameters was assessed by intraclass correlation coefficients. RESULTS: The inter-rater/intrarater proportion of agreement to qualitatively assess an image as belonging to the SDS category or not was 90% and 96%, whereas the agreement to distinguish between only 'early', 'active' and 'late' scleroderma NVC patterns was 62% and 81%. The agreement of the semiquantitative scoring, as assessed by intraclass correlation coefficient, was 0.96 and 0.95 for capillary loss, 0.84 and 0.95 for giant capillaries, 0.90 and 0.95 for microhaemorrhages and 0.64 and 0.95 for capillary ramifications. CONCLUSIONS: This is the first study to demonstrate reliability of the qualitative and semiquantitative NVC assessment in an SSc cohort between raters at different centres. Reliability of NVC assessment is essential for use of this tool in multicentre SSc trials.

How the microbiota shapes rheumatic diseases.

The human gut harbours a tremendously diverse and abundant microbial community that correlates with, and even modulates, many health-related processes. The mucosal interfaces are particularly active sites of microorganism-host interplay. Growing insight into the characteristic composition and functionality of the mucosal microbiota has revealed that the microbiota is involved in mucosal barrier integrity and immune function. This involvement affects proinflammatory and anti-inflammatory processes not only at the epithelial level, but also at remote sites such as the joints. Here, we review the role of the gut microbiota in shaping local and systemic immune responses and how disturbances in the host-microorganism interplay can potentially affect the development and progression of rheumatic diseases. Increasing our understanding of how to promote host-microorganism homeostasis could therefore reveal novel strategies for the prevention or alleviation of rheumatic disease.