Inborn errors of immunity are associated with increased COVID-19-related hospitalization and intensive care compared to the general population.

Background: It is thought that patients with inborn errors of immunity (IEI) are more susceptible to severe coronavirus disease 2019 (COVID-19) than the general population, but a quantification of this potential risk is largely missing.

Objective: We assessed the impact of COVID-19 on patients with IEI.

Methods: A nationwide cohort study was performed to estimate the relative risk (RR) for hospitalization, intensive care, and death within 30 days after a positive severe acute respiratory syndrome coronavirus 2 test result in an IEI population (n = 2392) compared to the general population (n = 8,270,705) using data from Swedish national registries.

Risk of COVID-19 hospitalisation by HIV-status and SARS-CoV-2 vaccination status during pre- and post-Omicron era in a national register-based cohort study in Sweden.

Background: Data on the outcomes of COVID-19 in people living with HIV (PLHIV), specifically in relation to vaccination status, are lacking during the Omicron era.

Methods: This nationwide registry-based study included all resident in Sweden ≥18 years with a positive SARS-CoV-2 PCR test during January 2021-February 2023. We estimated adjusted odds ratios (adjOR) for COVID-19 hospitalisation and severe COVID-19 (ICU admission and 90-day mortality), categorised by SARS-CoV-2 vaccination status (0-1, 2, and ≥3 doses), and HIV-status.

Immunological characterization of IgG subclass deficiency reveals decreased Tregs and increased circulating costimulatory and regulatory immune checkpoints.

Background: Immunoglobulin G subclass deficiencies (IgGsd) comprise a wide clinical spectrum from no symptoms to repeated respiratory infections and risk for the development of lung damage. Our aims were to investigate whether the immunological phenotype of IgGsd patients on and off immunoglobulin replacement therapy (IgRT) was reflected in the clinical features of IgGsd.

Method: Thirty patients with IgGsd were included in this prospective study of 18 months of IgRT, followed by 7-18 months of IgRT discontinuation.

Plasma Levels of mir-34a-5p Correlate with Systemic Inflammation and Low Naïve CD4 T Cells in Common Variable Immunodeficiency.

Purpose: Common variable immunodeficiency (CVID) is a primary antibody deficiency that commonly manifests as recurrent infections. Many CVID patients also suffer from immune dysregulation, an inflammatory condition characterized by polyclonal lymphocytic tissue infiltration and associated with increased morbidity and mortality. The genetic cause is unknown in most CVID patients and epigenetic alterations may contribute to the broad range of clinical manifestations.

In-depth immune profiling reveals advanced B- and T-cell differentiation to be associated with Th1-driven immune dysregulation in common variable immunodeficiency.

Common variable immunodeficiency (CVID) is an inborn error of immunity characterized by low levels of antibodies. In addition to infections, many patients also suffer from T-helper 1-driven immune dysregulation, which is associated with increased mortality. The aim of this study was to perform in-depth characterization of the T and the B cell compartments in a well-defined cohort of patients affected by CVID and correlate the findings to the level of clinical immune dysregulation.

Pentameric C-reactive protein is a better prognostic biomarker and remains elevated for longer than monomeric CRP in hospitalized patients with COVID-19.

The differing roles of the pentameric (p) and monomeric (m) C-reactive protein (CRP) isoforms in viral diseases are not fully understood, which was apparent during the COVID-19 pandemic regarding the clinical course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Herein, we investigated the predictive value of the pCRP and mCRP isoforms for COVID-19 severity in hospitalized patients and evaluated how the levels of the protein isoforms changed over time during and after acute illness. This study utilized samples from a well-characterized cohort of Swedish patients with SARS-CoV-2 infection, the majority of whom had known risk factors for severe COVID-19 and required hospitalization.

Major alterations to monocyte and dendritic cell subsets lasting more than 6 months after hospitalization for COVID-19.

Introduction: After more than two years the Coronavirus disease-19 (COVID-19) pandemic continues to burden healthcare systems and economies worldwide, and it is evident that the effects on the immune system can persist for months post-infection. The activity of myeloid cells such as monocytes and dendritic cells (DC) is essential for correct mobilization of the innate and adaptive responses to a pathogen. Impaired levels and responses of monocytes and DC to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is likely to be a driving force behind the immune dysregulation that characterizes severe COVID-19.

Long Term Norovirus Infection in a Patient with Severe Common Variable Immunodeficiency.

Norovirus is the most common cause of acute non-bacterial gastroenteritis. Immunocompromised patients can become chronically infected, with or without symptoms. In Europe, common variable immunodeficiency (CVID) is one of the most common inborn errors of immunity.

T cell perturbations persist for at least 6 months following hospitalization for COVID-19.

COVID-19 is being extensively studied, and much remains unknown regarding the long-term consequences of the disease on immune cells. The different arms of the immune system are interlinked, with humoral responses and the production of high-affinity antibodies being largely dependent on T cell immunity. Here, we longitudinally explored the effect COVID-19 has on T cell populations and the virus-specific T cells, as well as neutralizing antibody responses, for 6-7 months following hospitalization.

SARS-CoV-2 Specific Antibody Response and T Cell-Immunity in Immunocompromised Patients up to Six Months Post COVID: A Pilot Study.

COVID-19 generates SARS-CoV-2-specific antibodies in immunocompetent individuals. However, in immunocompromised patients, the humoral immunity following infection may be impaired or absent. Recently, the assessment of cellular immunity to SARS-CoV-2, both following natural infection and vaccination, has contributed new knowledge regarding patients with low or no antibody responses.

Specific T-cell responses for guiding treatment with convalescent plasma in severe COVID-19 and humoral immunodeficiency: a case report.

Background: The immune response to SARS-CoV-2 virus, the cause of COVID-19, is complex. Antibody mediated responses are important for viral clearance but may also drive hyperinflammation in severe COVID-19. We present a case of an individual with a genetic inability to produce antibodies and severe COVID-19, receiving no other specific anti-viral treatment than convalescent COVID-19 plasma, illustrating that hyperinflammation can occur in the absence of a humoral anti-viral response.

Evaluation of SARS-CoV-2 rapid antigen diagnostic tests for saliva samples.

Using saliva samples would facilitate sample collection, diagnostic feasibility, and mass screening of SARS-CoV-2. We tested two rapid antigen (RAD) immunochromatographic tests designed for detection of SARS-CoV-2 in saliva: Rapid Response™ COVID-19 Antigen Rapid Test Cassette for oral fluids and DIAGNOS™ COVID-19 Antigen Saliva Test. Evaluation of detection limit was performed with purified SARS-CoV-2 nucleocapsid protein and live SARS-CoV-2 virus.

Fatigue Is Common in Immunoglobulin G Subclass Deficiency and Correlates With Inflammatory Response and Need for Immunoglobulin Replacement Therapy.

Purpose: Individuals with immunoglobulin G deficiency (IgGsd) often complain of fatigue. The correlation between systemic inflammation and fatigue is unknown. In this study perceived quality of life (QoL) and fatigue in individuals with IgGsd, on and off immunoglobulin replacement therapy (IgRT) were correlated to inflammatory markers in plasma to identify the subgroup that benefits from IgRT.

Soluble Urokinase Plasminogen Activator Receptor (suPAR) Independently Predicts Severity and Length of Hospitalisation in Patients With COVID-19.

Efficient healthcare based on prognostic variables in hospitalised patients with COVID-19 could reduce the risk of complications and death. Recently, soluble urokinase Plasminogen Activator Receptor (suPAR) was shown to predict respiratory failure, kidney injury, and clinical outcome in patients with SARS-CoV-2 infection. The aim of this study was to investigate the value of suPAR as a prognostic tool, in comparison with other variables, regarding disease severity and length of hospital stay in patients with COVID-19.

Methicillin-Resistant Lineages in the Nasal and Skin Microbiota of Patients Planned for Arthroplasty Surgery.

, ubiquitous in the human nasal and skin microbiota, is a common causative microorganism in prosthetic joint infections (PJIs). A high proportion of PJI isolates have been shown to harbor genetic traits associated with resistance to/tolerance of agents used for antimicrobial prophylaxis in joint arthroplasties. These traits were found within multidrug-resistant (MDRSE) lineages of multiple genetic backgrounds.

Comparative genomics of from prosthetic-joint infections and nares highlights genetic traits associated with antimicrobial resistance, not virulence.

There is increased awareness of the worldwide spread of specific epidemic multidrug-resistant (MDR) lineages of the human commensal . Here, using bioinformatic analyses accounting for population structure, we determined genomic traits (genes, SNPs and mers) that distinguish causing prosthetic-joint infections (PJIs) from commensal isolates from nares, by analysing whole-genome sequencing data from from PJIs prospectively collected over 10 years in Sweden, and contemporary from the nares of patients scheduled for arthroplasty surgery. Previously suggested virulence determinants and the presence of genes and mutations linked to antimicrobial resistance (AMR) were also investigated.

Presence of the neonatal Staphylococcus capitis outbreak clone (NRCS-A) in prosthetic joint infections.

Staphylococcus capitis is a coagulase-negative staphylococcus that has been described primarily as causing bloodstream infections in neonatal intensive care units (NICUs), but has also recently been described in prosthetic joint infections (PJIs). The multidrug-resistant S. capitis subsp.

Alteration of Bacterial Communities in Anterior Nares and Skin Sites of Patients Undergoing Arthroplasty Surgery: Analysis by 16S rRNA and Staphylococcal-Specific Gene Sequencing.

The aim was to study alterations of bacterial communities in patients undergoing hip or knee arthroplasty to assess the impact of chlorhexidine gluconate soap decolonisation and systemic antibiotic prophylaxis. A Swedish multicentre, prospective collection of samples obtained from elective arthroplasty patients (n = 83) by swabbing anterior nares, skin sites in the groin and the site of planned surgery, before and after arthroplasty surgery, was analysed by 16S rRNA (V3-V4) gene sequencing and a complementary targeted gene sequencing approach to comprehensively characterise alterations in staphylococcal communities. Significant reductions in alpha diversity was detected for both bacterial ( = 0.

Plasma protein profiling reflects T1-driven immune dysregulation in common variable immunodeficiency.

Background: Common variable immunodeficiency (CVID) is a disorder characterized by antibody deficiency. A significant fraction of the patients suffer from immune dysregulation, which leads to increased morbidity and mortality. The pathogenesis of this condition is poorly understood.

Optimization of 16S rRNA gene analysis for use in the diagnostic clinical microbiology service.

Broad-range amplification and sequencing of the 16S rRNA gene, directly from clinical samples, is a method that potentially allows detection of any cultivable or non-cultivable bacteria. However, the method is prone to false positive results due to PCR contamination. Another concern is the human DNA abundance compared to bacterial DNA in samples from sterile sites.

[Treatment of orthopedic implant-associated infections].

The Swedish National Guidelines for Bone and Joint Infections were revised during 2018. The work was carried out on behalf of the Swedish Society for Infectious Diseases. The study group consists of senior consultants in infectious diseases, supported by specialists in orthopedic surgery, clinical microbiology and allergology when needed.

Same Organism, Different Phenotype - Are Phenotypic Criteria Adequate In Coagulase-Negative Staphylococcal Orthopaedic Implant-Associated Infections?

In current diagnostic criteria for implant-associated bone- and joint infections, phenotypically identical low-virulence bacteria in two intraoperative cultures are usually required. Using whole-genome sequencing, we have further characterized three phenotypically different isolated from one prosthetic joint infection, highlighting the challenges in defining microbiological criteria for low-virulence prosthetic joint infections.

Fcγ-receptor polymorphisms associated with clinical symptoms in patients with immunoglobulin G subclass deficiency.

Background: Immunoglobulin G subclass deficiencies (IgGsd) are associated with recurrent respiratory tract infections. Immunoglobulin substitution therapy may be needed to prevent chronic lung tissue damage but tools for identifying the patients that will benefit from this treatment are still insufficient. Some FcγR polymorphisms seem to predispose for an increased risk for infections.

Staphylococcus epidermidis from prosthetic joint infections induces lower IL-1β release from human neutrophils than isolates from normal flora.

The aim of this study was to test the hypothesis that Staphylococcus epidermidis isolated from prosthetic joint infections (PJIs) differs from S. epidermidis isolated from normal flora in terms of its capacity to induce activation of caspase-1 and release of IL-1β in human neutrophils. The amount of active caspase-1 was determined over 6 h by detecting Ac-YVAD-AMC fluorescence in human neutrophils incubated with S.