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 tuf gene sequencing approach to comprehensively characterise alterations in staphylococcal communities. Significant reductions in alpha diversity was detected for both bacterial (p = 0.04) and staphylococcal (p = 0.03) groin communities after arthroplasty surgery with significant reductions in relative Corynebacterium (p = 0.001) abundance and Staphylococcus hominis (p = 0.01) relative staphylococcal abundance. In nares, significant reductions occurred for Staphylococcus hominis (p = 0.02), Staphylococcus haemolyticus (p = 0.02), and Staphylococcus pasteuri (p = 0.003) relative to other staphylococci. Staphylococcus aureus colonised 35% of anterior nares before and 26% after arthroplasty surgery. Staphylococcus epidermidis was the most abundant staphylococcal species at all sampling sites. No bacterial genus or staphylococcal species increased significantly after arthroplasty surgery. Application of a targeted tuf gene sequencing approach provided auxiliary staphylococcal community profiles and allowed species-level characterisation directly from low biomass clinical samples.

Staphylococcus epidermidis, 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 S. epidermidis (MDRSE) lineages of multiple genetic backgrounds. In this study, the aim was to study whether MDRSE lineages previously associated with PJIs are present in the nasal and skin microbiota of patients planned for arthroplasty surgery but before hospitalization. We cultured samples from nares, inguinal creases, and skin over the hip or knee (dependent on the planned procedure) taken two weeks (median) prior to admittance to the hospital for total joint arthroplasty from 66 patients on agar plates selecting for methicillin resistance. S. epidermidis colonies were identified and tested for the presence of mecA. Methicillin-resistant S. epidermidis (MRSE) were characterized by Illumina-based whole-genome sequencing. Using this method, we found that 30/66 (45%) of patients were colonized with MRSE at 1–3 body sites. A subset of patients, 10/66 (15%), were colonized with MDRSE lineages associated with PJIs. The qacA gene was identified in MRSE isolates from 19/30 (63%) of MRSE colonized patients, whereas genes associated with aminoglycoside resistance were less common, found in 11/30 (37%). We found that MDRSE lineages previously associated with PJIs were present in a subset of patients’ pre-admission microbiota, plausibly in low relative abundance, and may be selected for by the current prophylaxis regimen comprising whole-body cleansing with chlorhexidine-gluconate containing soap. To further lower the rate of S. epidermidis PJIs, the current prophylaxis may need to be modified, but it is important for possible perioperative MDRSE transmission events and specific risk factors for MDRSE PJIs to be investigated before reevaluating antimicrobial prophylaxis.

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. A potentially severe complication is CVID-associated enteropathy, a disorder with similar histopathology to celiac disease. Studies suggest that chronic norovirus infection may be a contributor to CVID enteropathy, and that the antiviral drug ribavirin can be effective against norovirus. Here, a patient with CVID-like disease with combined B- and T-cell deficiency, had chronic norovirus infection and enteropathy. The patient was routinely administered subcutaneous and intravenous immunoglobulin replacement therapy (SCIg and IVIg). The patient was also administered ribavirin for ~7.5 months to clear the infection. Stool samples (collected 2013–2016) and archived paraffin embedded duodenal biopsies were screened for norovirus by qPCR, confirming a chronic infection. Norovirus genotyping was done in 25 stool samples. For evolutionary analysis, the capsid (VP1) and polymerase (RdRp) genes were sequenced in 10 and 12 stool samples, respectively, collected before, during, and after ribavirin treatment. Secretor phenotyping was done in saliva, and serum was analyzed for histo-blood group antigen (HBGA) blocking titers. The chronic norovirus strain formed a unique variant subcluster, with GII.4 Den Haag [P4] variant, circulating around 2009, as the most recent common ancestor. This corresponded to the documented debut of symptoms. The patient was a secretor and had HBGA blocking titers associated with protection in immunocompetent individuals. Several unique amino acid substitutions were detected in immunodominant epitopes of VP1. However, HBGA binding sites were conserved. Ribavirin failed in treating the infection and no clear association between ribavirin-levels and quantity of norovirus shedding was observed. In conclusion, long term infection with norovirus in a patient with severe CVID led to the evolution of a unique norovirus strain with amino acid substitutions in immunodominant epitopes, but conservation within HBGA binding pockets. Regularly administered SCIg, IVIg, and ~7.5-month ribavirin treatment failed to clear the infection.

Staphylococcus epidermidis infections are usually nosocomial and involve colonization of biomaterials. The immune defense system cannot efficiently c

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. In addition, the case illustrates that the assessment of SARS-CoV-2 T cell responses can facilitate clinical decision making in patients with COVID-19 and weak or absent humoral immune responses. Case presentation: A male with X-linked agammaglobulinemia on regular immunoglobulin replacement therapy, hospitalized for 35 days due to severe COVID-19. Systemic inflammatory parameters were highly elevated. After treatment with convalescent COVID-19 plasma he became afebrile and the fatigue diminished. He was discharged on day 42 and nasopharyngeal SARS-CoV-2 PCR eventually was negative on day 49. Evidence of SARS-CoV-2 specific T cells prior to administration of plasma therapy suggested that antibodies were crucial for viral clearance. Regular assessment showed robust and persistent SARS-CoV-2 specific T-cell responses after recovery suggested that prophylactic administration of convalescent COVID-19 plasma was unnecessary. Conclusion: Assessment of SARS-CoV-2T-cell responses can facilitate the clinical management of COVID-19 patients with humoral immunodeficiencies.

Individuals with chronic lymphocytic leukemia (CLL) face an increased risk for severe COVID-19. This study from Sweden, a country that only had a few mandatory restrictions at the onset of the pandemic, used 10 nationwide registers to compare the risks for severe COVID-19 outcomes of polymerase chain reaction–verified severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections through February 2023 in individuals with and those without CLL. From a population of 8 275 839 (6653 CLL) individuals born between 1930 and 2003, 2 088 163 first infections (1289 CLL) were included. The 90-day all-cause mortality rate and adjusted relative risk (aRR; 95% confidence interval) for individuals with CLL vs the general population was 24.8% (1.95; 1.58-2.41) during wild-type, 17.2% (2.38; 1.58-3.57) during Alpha, 4.1% (0.71; 0.24-2.08) during Delta, and 12.6% (1.49; 1.24-1.78) during Omicron infections. Their mortality during Omicron was 0.6% (<65 years), 5.4% (65-74 years), and 19.7% (≥75 years). Small molecule inhibitors (1.56; 1.03-2.37) and corticosteroid usage (1.45; 1.04-2.02) was associated with increased mortality. Next, we analyzed the all-cause mortality in the capital (Stockholm), widely affected by SARS-CoV-2 at the onset of the pandemic. Mortality in individuals with CLL increased by 55% during the first 6 months of 2020 vs 2019, and the age- and sex-aRR by 30 June was 1.53 (1.09-2.15) for individuals with CLL (P = .02) and 1.29 (1.25-1.33) for the general population (P < .001). Collectively, a significantly increased risk for severe COVID-19 and death was observed among individuals with CLL in Sweden, particularly at the onset of the pandemic when few national protective measures were introduced and also after Omicron emerged, emphasizing the need for a more pro-active pandemic strategy for CLL.