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

BACKGROUND AND 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 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 (DI-AILH). 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 (BCR) 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 vaccination-induced liver injury is related to AIH but also shows distinct differences from AIH in histomorphology, pathway activation, cellular immune infiltrates, and TCR usage. VILI may be a separate entity, which is distinct from AIH and more closely related to DI-AILH. IMPACT AND IMPLICATIONS: Little is known about the pathophysiology of COVID-19 vaccine-induced liver injury. Our analysis shows that COVID-19 vaccine-induced liver injury 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 vaccine-induced liver injury is a distinct disease entity. Therefore, there is a good chance that many patients with COVID-19 vaccine-induced liver injury will recover completely and do not develop long-term autoimmune hepatitis.

Severe Neuro-COVID is associated with peripheral immune signatures, autoimmunity and neurodegeneration: a prospective cross-sectional study.

Growing evidence links COVID-19 with acute and long-term neurological dysfunction. However, the pathophysiological mechanisms resulting in central nervous system involvement remain unclear, posing both diagnostic and therapeutic challenges. Here we show outcomes of a cross-sectional clinical study (NCT04472013) including clinical and imaging data and corresponding multidimensional characterization of immune mediators in the cerebrospinal fluid (CSF) and plasma of patients belonging to different Neuro-COVID severity classes. The most prominent signs of severe Neuro-COVID are blood-brain barrier (BBB) impairment, elevated microglia activation markers and a polyclonal B cell response targeting self-antigens and non-self-antigens. COVID-19 patients show decreased regional brain volumes associating with specific CSF parameters, however, COVID-19 patients characterized by plasma cytokine storm are presenting with a non-inflammatory CSF profile. Post-acute COVID-19 syndrome strongly associates with a distinctive set of CSF and plasma mediators. Collectively, we identify several potentially actionable targets to prevent or intervene with the neurological consequences of SARS-CoV-2 infection.

Impact of COVID-19 on eating habits, sleeping behaviour and physical activity status of final-year medical students in Ankara, Turkey.

OBJECTIVE: The massive increase in COVID-19 cases led to the implementation of nationwide lockdown in Turkey. While enforced lockdown is an effective strategy to abate the transmission of the virus, it causes significant lifestyle changes in every part of the community. This study aims to assess the changes in eating habits, sleeping behaviour and physical activity status of final-year medical students (interns) whose education was suspended during the pandemic. DESIGN: In this cross-sectional epidemiological study, an online questionnaire was created. Interns were asked questions regarding socio-demographic status, eating habits, sleeping behaviour and physical activity status before and during COVID-19 pandemic. Changes in dietary habits and sleep quality were evaluated under the guidance of Turkey Dietary Guidelines, Determination of Nutritional Status Report, Turkey National Nutrition and Health Survey and Pittsburgh Sleep Quality Index. SETTING: Hacettepe University Faculty of Medicine - Ankara, Turkey. PARTICIPANTS: Among 536 students, a total of 340 students (63·4 %) answered the questionnaire. RESULTS: After the beginning of lockdown, an increase in BMI was observed in both female (P = 0·002) and male students (P = 0·013). Students having healthy dietary habits increased by 18·8 % and unhealthy dietary habits decreased by 3·2 % during lockdown (P < 0·001). Overall, 63·2 % of students reported a decrease in physical activity, and 33·6 % reported a reduction in sleep quality, whereas 38·6 % reported an improvement in sleep quality. There was no significant difference in sleep quality between genders (P = 0·075). CONCLUSIONS: This study indicated that medical school suspension and enforced lockdown led to significant changes in interns' eating behaviour, physical activity and sleeping habits.