Morphologic and molecular analysis of liver injury after SARS-CoV-2 vaccination reveals distinct characteristics.

BACKGROUND & AIMS: Liver injury after COVID-19 vaccination is very rare and shows clinical and histomorphological similarities with autoimmune hepatitis (AIH). Little is known about the pathophysiology of COVID-19 vaccine-induced liver injury (VILI) and its relationship to AIH. Therefore, we compared VILI with AIH. METHODS: Formalin-fixed and paraffin-embedded liver biopsy samples from patients with VILI (n = 6) and from patients with an initial diagnosis of AIH (n = 9) were included. Both cohorts were compared by histomorphological evaluation, whole-transcriptome and spatial transcriptome sequencing, multiplex immunofluorescence, and immune repertoire sequencing. RESULTS: Histomorphology was similar in both cohorts but showed more pronounced centrilobular necrosis in VILI. Gene expression profiling showed that mitochondrial metabolism and oxidative stress-related pathways were more and interferon response pathways were less enriched in VILI. Multiplex analysis revealed that inflammation in VILI was dominated by CD8+ effector T cells, similar to drug-induced autoimmune-like hepatitis. In contrast, AIH showed a dominance of CD4+ effector T cells and CD79a+ B and plasma cells. T-cell receptor (TCR) and B-cell receptor sequencing showed that T and B cell clones were more dominant in VILI than in AIH. In addition, many T cell clones detected in the liver were also found in the blood. Interestingly, analysis of TCR beta chain and Ig heavy chain variable-joining gene usage further showed that TRBV6-1, TRBV5-1, TRBV7-6, and IgHV1-24 genes are used differently in VILI than in AIH. CONCLUSIONS: Our analyses support that SARS-CoV-2 VILI is related to AIH but also shows distinct differences from AIH in histomorphology, pathway activation, cellular immune infiltrates, and TCR usage. Therefore, VILI may be a separate entity, which is distinct from AIH and more closely related to drug-induced autoimmune-like hepatitis. IMPACT AND IMPLICATIONS: Little is known about the pathophysiology of COVID-19 vaccine-induced liver injury (VILI). Our analysis shows that COVID-19 VILI shares some similarities with autoimmune hepatitis, but also has distinct differences such as increased activation of metabolic pathways, a more prominent CD8+ T cell infiltrate, and an oligoclonal T and B cell response. Our findings suggest that VILI is a distinct disease entity. Therefore, there is a good chance that many patients with COVID-19 VILI will recover completely and will not develop long-term autoimmune hepatitis.

Preventing Implant-Associated Infections by Silver Coating.

Implant-associated infections (IAIs) are a dreaded complication mainly caused by biofilm-forming staphylococci. Implant surfaces preventing microbial colonization would be desirable. We examined the preventive effect of a silver-coated titanium-aluminum-niobium (TiAlNb) alloy. The surface elicited a strong, inoculum-dependent activity againstStaphylococcus epidermidisandStaphylococcus aureusin an agar inhibition assay. Gamma sterilization and alcohol disinfection did not alter the effect. In a tissue cage mouse model, silver coating of TiAlNb cages prevented perioperative infections in an inoculum-dependent manner and led to a 100% prevention rate after challenge with 2 × 10(6)CFU ofS. epidermidisper cage. InS. aureusinfections, silver coating had only limited effect. Similarly, daptomycin or vancomycin prophylaxis alone did not preventS. aureusinfections. However, silver coating combined with daptomycin or vancomycin prophylaxis thwarted methicillin-resistantS. aureusinfections at a prevention rate of 100% or 33%, respectively. Moreover, silver release from the surface was independent of infection and occurred rapidly after implantation. On day 2, a peak of 82 µg Ag/ml was reached in the cage fluid, corresponding to almost 6× the MIC of the staphylococci. Cytotoxicity toward leukocytes in the cage was low and temporary. Surrounding tissue did not reveal histological signs of silver toxicity.In vitro, no emergence of silver resistance was observed in several clinical strains of staphylococci upon serial subinhibitory silver exposures. In conclusion, our data demonstrate that silver-coated TiAlNb is potent for prevention of IAIs and thus can be considered for clinical application.

First case of infective endocarditis caused by Helicobacter cinaedi.

BACKGROUND: Up to 20% of all infective endocarditis are blood culture-negative and therefore a diagnostic challenge. Here we present the case of an infective endocarditis due to Helicobacter cinaedi finally diagnosed using different molecular methods. This highly fastidious gram-negative spiral rod is increasingly recognized as a human pathogen, above all in immunocompromised patients. So far H. cinaedi has been associated with bacteremia, cellulitis, arthritis and meningitis. CASE PRESENTATION: A 71-year-old man presented with fever and progressive dyspnea for weeks. He was immunocompromised by long-term steroid therapy. As one major and two minor Duke's criteria (vegetation, fever and aortic valve stenosis as predisposition) were present, an infective endocarditis was suspected and an empiric therapy with amoxicillin/clavulanic acid and gentamicin was established. The persistent severe aortic regurgitation resulted in a valve replacement. Histological evaluation of the aortic valve showed a polypous-ulcerative endocarditis. Gram stain and culture remained negative. Broad-range bacterial PCR targeting the 16S rRNA gene on the biopsy of the aortic valve identified H. cinaedi as the causative agent. The antibiotic therapy was simplified accordingly to ceftriaxone and gentamicin with a recommended duration of 6 weeks. Ten days after valve replacement the patient was discharged. To complete our molecular finding, we sequenced nearly the complete 16S rRNA gene (accession number KF914917) resulting in 99.9% identity with H. cinaedi reference sequences. Based on this result, 2 species-specific PCR tests amplifying part of the ctd gene were established and applied to the valve specimen. The 2 PCRs confirmed H. cinaedi. In addition, we analyzed stool, urine and saliva from the patient using H. cinaedi PCR. The fecal and urine specimen showed a positive signal, saliva was PCR-negative. CONCLUSION: We identified H. cinaedi as causative agent of a culture-negative endocarditis in an immunocompromised patient using broad-range and specific PCR. In addition to 2 cases from Japan presented on international meetings in 2010 and 2013, our case report shows that H. cinaedi should be recognized as additional causative organism of infective endocarditis. The use of molecular diagnostic techniques proved to be a powerful complement for the detection of blood culture-negative infective endocarditis.