Long COVID (LC) describes the clinical phenotype of symptoms after infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Diagnostic and therapeutic options are limited, as the pathomechanism of LC is elusive. As the number of acute SARS-CoV-2 infections was and is large, LC will be a challenge for the healthcare system. Previous studies revealed an impaired blood flow, the formation of microclots, and autoimmune mechanisms as potential factors in this complex interplay. Since functionally active autoantibodies against G-protein-coupled receptors (GPCR-AAbs) were observed in patients after SARS-CoV-2 infection, this study aimed to correlate the appearance of GPCR-AAbs with capillary microcirculation. The seropositivity of GPCR-AAbs was measured by an established cardiomyocyte bioassay in 42 patients with LC and 6 controls. Retinal microcirculation was measured by OCT–angiography and quantified as macula and peripapillary vessel density (VD) by the Erlangen-Angio Tool. A statistical analysis yielded impaired VD in patients with LC compared to the controls, which was accentuated in female persons. A significant decrease in macula and peripapillary VD for AAbs targeting adrenergic β2-receptor, MAS-receptor angiotensin-II-type-1 receptor, and adrenergic α1-receptor were observed. The present study might suggest that a seropositivity of GPCR-AAbs can be linked to an impaired retinal capillary microcirculation, potentially mirroring the systemic microcirculation with consecutive clinical symptoms.

Post-COVID-19 syndrome (PCS) is characterized by persisting sequelae after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). PCS can affect patients with all COVID-19 disease severities. As previous studies have revealed impaired blood flow as a provoking factor triggering PCS, it was the aim of the present study to investigate the potential association between self-reported chronic fatigue and retinal microcirculation in patients with PCS, potentially indicating an objective biomarker. A prospective study was performed, including 201 subjects: 173 patients with PCS and 28 controls. Retinal microcirculation was visualized by OCT angiography (OCT-A) and quantified using the Erlangen-Angio-Tool as macula and peripapillary vessel density (VD). Chronic fatigue (CF) was assessed according to the variables of Bell’s score, age and gender. VDs in the superficial vascular plexus (SVP), intermediate capillary plexus (ICP) and deep capillary plexus (DCP) were analyzed, considering the repetitions (12 times). Seropositivity for autoantibodies targeting G protein-coupled receptors (GPCR-AAbs) was determined by an established cardiomyocyte bioassay. Taking account of the repetitions, a mixed model was performed to detect possible differences in the least square means between the different groups included in the analysis. An age effect in relation to VD was observed between patients and controls (p < 0.0001). Gender analysis showed that women with PCS showed lower VD levels in the SVP compared to male patients (p = 0.0015). The PCS patients showed significantly lower VDs in the ICP as compared to the controls (p = 0.0001 (CI: 0.32; 1)). Moreover, considering PCS patients, the mixed model revealed a significant difference between those with chronic fatigue (CF) and those without CF with respect to VDs in the SVP (p = 0.0033 (CI: −4.5; −0.92)). The model included variables of age, gender and Bell’s score, representing a subjective marker for CF. Consequently, retinal microcirculation might serve as an objective biomarker in subjectively reported chronic fatigue in patients with PCS.

PRINCIPLES: The incidence of hepatocellular carcinoma is rising. However, this is occurring not only in developing nations, but in industrial countries as well. Surveillance programmes, classification systems and therapeutic options have improved, but there is a lack of data regarding their impact on the prognosis of this difficult-to-treat cancer. MATERIALS AND METHODS: We evaluated 484 patients and reported on disease stage, therapeutic procedures and survival time. Data were compared with a historical cohort treated in the same centre 10 years before. RESULTS: In this cohort, the main reason for liver disease was alcoholism, although hepatitis B remains the leading cause of hepatocellular carcinoma worldwide. Now, most patients have compensated liver function and hepatocellular carcinoma is diagnosed in the early tumour stages (it was diagnosed in the advanced disease stages in the previous cohort). Overall, median survival time was 62.4 weeks, 1-year survival was 58.6% and 3-year survival was 23.2%. Survival time correlated with the stage of liver disease, tumour stage and with therapeutic options. CONCLUSION: Surveillance programmes lead to diagnosis in earlier tumour stages. Differentiated classification systems allow individualised therapeutic approaches. Earlier cancer stage and compensated liver function allow combination or sequential therapy, which was nearly impossible some years ago but is an option for most now. Primary liver cancer remains a difficult-to-treat malignancy, but the prognosis has improved remarkably, at least in the western world.

Long-COVID (LC) is characterized by diverse and persistent symptoms, potentially mirroring different molecular pathways. Recent data might offer that one of them is mediated by functional autoantibodies (fAAb) targeting G protein-coupled receptors (GPCR). Thus, the aim of this study was to investigate the clinical phenotype of patients with LC in relation to their GPCR-fAAb seropositivity. The present study recruited 194 patients with LC and profiled them based on self-reported symptoms. GPCR-fAAb seropositivity was identified by using a cardiomyocyte bioassay, testing the presence and functionality of the AAbs. Logistic regression, clustering, and decision tree analyses were applied to examine associations between GPCR-fAAb profiles and self-reported symptoms considering age and gender. The most prevalent GPCR-fAAbs in patients with LC were fAAB targeting the β2 adrenergic receptor (β2-fAAb, 92.8%), the muscarinergic M2 receptor (M2-fAAb, 87.1%), the Angiotensin II type 1 receptor (AT1-fAAb, 85.6%), and angiotensin (1–7) Mas receptor (MAS-fAAb, 85.6%). β2-fAAb showed a significant relation with dizziness, lack of concentration, and POTS, while Endothelin Type A receptor functional autoantibody (ET-A-fAAb) was significantly related to deterioration of pre-existing neurological disorders. Statistical analysis indicated a strong positive correlation between M2- and β2-fAAb; as in addition, an association of β2-fAAb and gender was observed to one of the major clinical symptoms (fatigue/PEM), a critical impact of GPCR-fAAb on LC-pathogenesis can be assumed. Summing up, the present data show that specific GPCR-fAAb are associated with distinct clinical phenotypes. Especially, the combination of M2- and β2-fAAb seemed to be essential for the LC-phenotype with a combination of fatigue/PEM and lack of concentration as major clinical symptoms.

The cumulative dosage of ribavirin per kilogram of body-weight prevents relapse and thus is a significant predictor of sustained virological response (SVR). Comparison of peginterferon (peg-IFN) alfa-2b/ribavirin and peg-IFN alfa-2a/ribavirin shows that the rates of SVR are similar, but the rates of relapse are significantly lower under the peg-IFN alfa-2b regimen. Depending on the weight-based ribavirin dose, patients with >105 kg reach a maximum of 13.2 mg/kg body-weight ribavirin in the peg-IFN alfa-2b regimen as opposed to only 11.3 mg/kg in the peg-IFN alfa-2a regimen. The aim of these investigations was to determine relapse rates in a retrospective analysis of 98 patients chronically infected with hepatitis C virus (HCV) genotype (GT) 1 in relation to the weight-based ribavirin dose.All patients completed treatment with peg-IFN alfa-2a/ribavirin (1000 mg/d or 1200 mg/d for patients weighing or =75 kg) for 48 weeks. Classification of a low ribavirin dose with or =13.2 mg/kg were compared with those with a dose or = 13.2 mg/kg (n=84) showed a relapse rate of 19.0% in contrast to 71.4% in patients with a ribavirin dose of or =13.2 mg/kg ribavirin dosed group (59.5% versus 28.6%).Weight-adapted ribavirin dosing in combination with peg-IFN alfa-2a to avoid giving low doses of ribavirin should be evaluated. This will minimize relapse, especially in HCV GT 1 patients.