Objectives Patients under rituximab therapy are at high risk for a severe COVID-19 disease course. Humoral immune responses to SARS-CoV-2 vaccination are vastly diminished in B-cell-depleted patients, even after a third vaccine dose. However, it remains unclear whether these patients benefit from a fourth vaccination and whether continued rituximab therapy affects antibody development. Methods In this open-label extension trial, 37 rituximab-treated patients who received a third dose with either a vector or mRNA-based vaccine were vaccinated a fourth time with an mRNA-based vaccine (mRNA-1273 or BNT162b2). Key endpoints included the humoral and cellular immune response as well as safety after a fourth vaccination. Results The number of patients who seroconverted increased from 12/36 (33%) to 21/36 (58%) following the fourth COVID-19 vaccination. In patients with detectable antibodies to the spike protein’s receptor-binding domain (median: 8.0 binding antibody units (BAU)/mL (quartiles: 0.4; 13.8)), elevated levels were observed after the fourth vaccination (134.0 BAU/mL (quartiles: 25.5; 1026.0)). Seroconversion and antibody increase were strongly diminished in patients who received rituximab treatment between the third and the fourth vaccination. The cellular immune response declined 12 weeks after the third vaccination, but could only be slightly enhanced by a fourth vaccination. No unexpected safety signals were detected, one serious adverse event not related to vaccination occurred. Conclusions A fourth vaccine dose is immunogenic in a fraction of rituximab-treated patients. Continuation of rituximab treatment reduced humoral immune response, suggesting that rituximab affects a second booster vaccination. It might therefore be considered to postpone rituximab treatment in clinically stable patients. Trial registration number 2021-002348-57.

Background: Dirofilariosis is a vector-borne parasitosis caused by filarial nematodes of the genus Dirofilaria. In humans, who represent accidental hosts, dirofilariosis is mostly caused by Dirofilaria repens and Dirofilaria immitis. In Austria, the first reported case occurred in 1978. Since then, several (case) reports have been published. Methods: A systematic and retrospective review of collected published cases and new, unpublished confirmed cases of human dirofilariosis occurring in Austria was performed. A nematode was extracted from the eyelid of a previously unreported case and subsequently characterized histologically and using molecular biology techniques. Results: Data on a total of 39 cases of human dirofilariosis in Austria occurring between 1978 and 2020 are summarized. Over the past four decades the incidence has markedly increased, in particular after 1998. Of the 39 patients, men and women were equally affected, and the mean age was 47.1 years. The area most frequently affected was the head (38.5% of cases). Confined ocular involvement was observed in 23.1% of cases, and nematodes were isolated from the neck/trunk, extremities and the genito-inguinal area in 25.6, 15.4 and 15.4% of patients, respectively. Microfilariae were detected in two cases. Of the 39 patients, only 73.9% tested positive for anti-filarial antibodies and 56.3% for eosinophilia, despite successful isolation of a nematode; consequently, these measures did not represent reliable markers for dirofilariosis. Most patients had a travel history to countries endemic for Dirofilaria species. One patient who had not traveled abroad represented the only autochthonous case recorded to date. Dirofilaria repens was the predominant species, identified in 89.7% of cases. In the newly reported case of subcutaneous dirofilariosis, a live non-gravid Dirofilaria repens adult female of 12 cm length was isolated from the eyelid of the patient, and a video of the extraction is provided. Conclusions: The incidence of human dirofilariosis cases has increased strikingly over the last four decades in Austria. More cases can be expected in the foreseeable future due to changes in human behavior and (travel) activities as well as climate changes and the associated alterations in the availability of the natural reservoir, the vectors and the intrinsic characteristics of the parasite. Graphical

Objectives A third COVID-19 vaccination is recommended for immunosuppressed patients. However, data on immunogenicity and safety of a third COVID-19 vaccination in patients with immune-mediated inflammatory diseases (IMIDs) are sparse and therefore addressed within this clinical trial. Methods 60 immunosuppressed patients and 48 healthy controls (HCs) received a third vaccination with an mRNA vaccine. The primary endpoint was defined as the presence of antibody levels against the receptor-binding domain (RBD)>1500 BAU/mL in patients with IMIDs versus HCs. Further endpoints included differences in neutralising antibodies and cellular immune responses after the third vaccination. Reactogenicity was recorded for 7 days, and safety was evaluated until week 4. Results Rate of individuals with anti-RBD antibodies>1500 BAU/mL was not significantly different after the third vaccination between patients with IMIDs and HCs (91% vs 100% p=0.101). Anti-RBD and neutralising antibody levels were significantly lower in patients with IMIDs after the third vaccination than in HCs (p=0.002 and p=0.016, respectively). In contrast, fold increase in antibody levels between week 0 and 4 was higher in patients with IMIDs. Treatment with biological (b) disease-modifying anti-rheumatic drugs (DMARD) or combination of bDMARDs and conventional synthetic DMARDs was associated with reduced antibody levels. Enhanced cellular immune response to wild type and Omicron peptide stimulation was observed after the third vaccination. No serious adverse event was attributed to the third vaccination. Conclusion Our clinical trial data support the immunogenicity and safety of a third COVID-19 vaccination in patients with IMIDs. However, effects of DMARD therapy on immunogenicity should be considered. Trial registration number EudraCT No: 2021-002693-10.

Background: Severe falciparum malaria is associated with considerable rates of mortality, despite the administration of appropriate anti-malarial treatment. Since overall survival is associated with total parasite biomass, blood exchange transfusion has been proposed as a potential method to rapidly reduce peripheral parasitaemia. However, current evidence suggests that this treatment modality may not improve outcome. Automated red blood cell exchange (also referred to as “erythrocytapheresis”) has been advocated as an alternative method to rapidly remove parasites from circulating blood without affecting patients’ volume and electrolyte status. However, only limited evidence from case reports and case series is available for this adjunctive treatment. This retrospective cohort study describes the use of automated red blood cell exchange for the treatment of severe malaria at the Medical University of Vienna. Methods: Epidemiologic data for imported malaria cases in Austria are reported and data of patients treated for malaria at the General Hospital/Medical University of Vienna were extracted from electronic hospital records. Results: Between 2000 and 2010, 146 patients were hospitalized at the Medical University of Vienna due to malaria and 16 of those were classified as severe malaria cases. Eleven patients of this cohort were potentially eligible for an adjunctive treatment with automated red blood cell exchange. Five patients eventually underwent this procedure within a period of seven hours (range: 3–19 hours) after hospital admission. Six patients did not undergo this adjunctive treatment following the decision of the treating physician. The procedure was well tolerated in all cases and rapid reduction in parasite counts was achieved without occurrence of haemodynamic complications. One patient died within seven days, whereas four patients survived without any sequelae. Discussion and conclusion: Automated red blood cell exchange was a safe and efficient procedure to rapidly clear peripheral parasitaemia. Whether the fast reduction in parasite biomass may ultimately improve patient survival remains however unclear. Randomized controlled trials are needed to conclusively appreciate the value of this adjunctive treatment.