Background. Recent population-based cohort studies have questioned the role of pneumococci as the most frequent pathogen causing severe infection in patients after splenectomy. The aim of the study ...was to define the causative pathogens and clinical presentation of patients with overwhelming postsplenectomy infection (OPSI). Methods. In a prospective cohort study in 173 German intensive care units, we searched for patients with and without asplenia and community-acquired severe sepsis/septic shock. Clinical and laboratory variables and survival of patients were assessed. Results. Fifty-two patients with severe sepsis or septic shock with asplenia and 52 without asplenia were included. OPSI patients more often had a history of malignancy (38% vs 17%; P= 0.16) and had a lower body mass index (24 kg/m2 vs 28 kg/m2; P= .004). Streptococcus pneumoniae was detected more frequently in OPSI patients (42% vs 12% without asplenia; P< .001) and more frequently manifested as bloodstream infection (31% vs 6%; P= .002). Gram-negative infection was similar in both groups (12% vs 19%; P = .157). Pneumococcal vaccine coverage of OPSI patients was low overall (42% vs 8% among patients without asplenia; P < .001). Purpura fulminans was a frequent complication, developing in 19% of OPSI patients vs 5% of patients without asplenia (P = .038). The interval between splenectomy and OPSI was 6 years (range, 1 month-50 years). On multivariable Poisson regression, asplenia was the only predictive variable independently associated with pneumococcal sepsis (adjusted relative risk, 2.53 95% confidence interval, 1.06-6.08). Conclusions. Pneumococcal infections remain the most important cause of severe sepsis and septic shock following splenectomy.
SARS-CoV-2 antibody assays are used for epidemiological studies and for the assessment of vaccine responses in highly vulnerable patients. So far, data on cross-reactivity of SARS-CoV-2 antibody ...assays is limited. Here, we compared four enzyme-linked immunosorbent assays (ELISAs; Vircell SARS-CoV-2 IgM/IgA and IgG, Euroimmun SARS-CoV-2 IgA and IgG) for detection of anti-SARS-CoV-2 antibodies in 207 patients with COVID-19, 178 patients with serological evidence of different bacterial infections, 107 patients with confirmed viral respiratory disease, and 80 controls from the pre-COVID-19 era. In COVID-19 patients, the assays showed highest sensitivity in week 3 (Vircell-IgM/A and Euroimmun-IgA: 78.9% each) and after week 7 (Vircell-IgG: 97.9%; Euroimmun-IgG: 92.1%). The antibody indices were higher in patients with fatal disease. In general, IgM/IgA assays had only limited or no benefit over IgG assays. In patients with non-SARS-CoV-2 respiratory infections, IgG assays were more specific than IgM/IgA assays, and bacterial infections were associated with more false-positive results than viral infections. The specificities in bacterial and viral infections were 68.0 and 81.3% (Vircell-IgM/IgA), 84.8 and 96.3% (Euroimmun-IgA), 97.8 and 86.0% (Vircell-IgG), and 97.8 and 99.1% (Euroimmun-IgG), respectively. Sera from patients positive for antibodies against
Mycoplasma pneumoniae
,
Chlamydia psittaci
, and
Legionella pneumophila
yielded particularly high rates of unspecific false-positive results in the IgM/IgA assays, which was revealed by applying a highly specific flow-cytometric assay using HEK 293 T cells expressing the SARS-CoV-2 spike protein. Positive results obtained with anti-SARS-CoV-2 IgM/IgA ELISAs require careful interpretation, especially if there is evidence for prior bacterial respiratory infections.
mRNA vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), such as BNT162b2 (Comirnaty®), have proven to be highly immunogenic and efficient but also show marked ...reactogenicity, leading to adverse effects (AEs). Here, we analyzed whether the severity of AEs predicts the antibody response against the SARS-CoV-2 spike protein. Healthcare workers without prior SARS-CoV-2 infection, who received a prime-boost vaccination with BNT162b2, completed a standardized electronic questionnaire on the duration and severity of AEs. Serum specimens were collected two to four weeks after the boost vaccination and tested with the COVID-19 ELISA IgG (Vircell-IgG), the LIAISON® SARS-CoV-2 S1/S2 IgG CLIA (DiaSorin-IgG) and the iFlash-2019-nCoV NAb surrogate neutralization assay (Yhlo-NAb). A penalized linear regression model fitted by machine learning was used to correlate AEs with antibody levels. Eighty subjects were enrolled in the study. Systemic, but not local, AEs occurred more frequently after the boost vaccination. Elevated SARS-CoV-2 IgG antibody levels were measured in 92.5% of subjects with Vircell-IgG and in all subjects with DiaSorin-IgG and Yhlo-NAb. Gender, age and BMI showed no association with the antibody levels or with the AEs. The linear regression model identified headache, malaise and nausea as AEs with the greatest variable importance for higher antibody levels (Vircell-IgG and DiaSorin-IgG). However, the model performance for predicting antibody levels from AEs was very low for Vircell-IgG (squared correlation coefficient r2 = 0.04) and DiaSorin-IgG (r2 = 0.06). AEs did not predict the surrogate neutralization (Yhlo-NAb) results. In conclusion, AEs correlate only weakly with the SARS-CoV-2 spike protein antibody levels after COVID-19 vaccination with BNT162b2 mRNA.
At the start of the SARS-CoV-2 pandemic, healthcare workers had an increased risk of acquiring coronavirus disease (COVID)-19. As tertiary care hospitals are critical for the treatment of severely ...ill patients, the University Hospital Erlangen offered BNT162b2 mRNA vaccination against COVID-19 to all employees when the vaccine became available in Germany. Here, we performed a survey to assess the age- and sex-dependent reactogenicity and safety of BNT162b2 in a real-life setting with a special emphasis on the rate of vaccine-related incapacity to work amongst the employees. All vaccinated employees were invited to participate in the survey and received access to an electronic questionnaire between 31 March and 14 June 2021, which allowed them to report local and systemic adverse effects after the first or second vaccine dose. A total of 2372 employees completed the survey. After both the first and second dose, women had a higher risk than men for vaccine-related systemic side effects (odds ratio (OR) 1.48 (1.24-1.77) and 1.49 (1.23-1.81), respectively) and for inability to work (OR 1.63 (1.14-2.34) and 1.85 (1.52-2.25), respectively). Compared to employees ≥ 56 years of age, younger vaccinated participants had a higher risk of systemic reactions after the first (OR 1.35 (1.07-1.70)) and second vaccination (OR 2.08 (1.64-2.63)) and were more often unable to work after dose 2 (OR 2.20 (1.67-2.88)). We also recorded four anaphylactic reactions and received two reports of severe adverse effects indicative of vaccine complications. After the first and second vaccination, 7.9% and 34.7% of the survey participants, respectively, were temporarily unable to work, which added up to 1700 days of sick leave in this cohort. These real-life data extend previous results on the reactogenicity and safety of BNT162b2. Loss of working time due to vaccine-related adverse effects was substantial, but was outweighed by the potential benefit of prevented cases of COVID-19.
The proportion of VREfm among all
isolated from blood cultures in German hospitals has increased in the period 2015-2020 from 11.9% to 22.3% with a country-wide spread of the clonal lineage ...ST117/CT71
. In this study, we provided useful information about the genetic diversity of invasive strains of
. Moreover, our findings confirm the nosocomial spread of novel ST1299
lineages, which recently had a rapid expansion in Austria and the south-eastern part of Germany.
Hyper-IgE syndromes (HIES) are a group of inborn errors of immunity (IEI) caused by monogenic defects such as in the gene
STAT3
(STAT3-HIES). Patients suffering from HIES show an increased ...susceptibility to
Staphylococcus aureus
(
S. aureus
) including skin abscesses and pulmonary infections. To assess if the underlying immune defect of STAT3-HIES patients influences the resistance patterns, pathogenicity factors or strain types of
S. aureus
. We characterized eleven
S. aureus
strains isolated from STAT3-HIES patients (
n
= 4) by whole genome sequencing (WGS) to determine presence of resistance and virulence genes. Additionally, we used multi-locus sequence typing (MLST) and protein A (
spa
) typing to classify these isolates. Bacterial isolates collected from this cohort of STAT3-HIES patients were identified as common
spa
types in Germany. Only one of the isolates was classified as methicillin-resistant
S. aureus
(MRSA). For one STAT3 patient WGS illustrated that infection and colonization occurred with different
S. aureus
isolates rather than one particular clone. The identified
S. aureus
carriage profile on a molecular level suggests that
S. aureus
strain type in STAT3-HIES patients is determined by local epidemiology rather than the underlying immune defect highlighting the importance of microbiological assessment prior to antibiotic treatment.