SARS-CoV-2 mRNA Vaccination in People with Multiple Sclerosis Treated with Fingolimod: Protective Humoral Immune Responses May Develop after the Preferred Third Shot.

Evidence suggests limited development of protective IgG responses to mRNA-based vaccines in sphingosine-1-phosphate receptor (S1PR)-modulator treated individuals with multiple sclerosis (MS). We studied the extent of the humoral immune response after the preferred third mRNA SARS-CoV-2 vaccine in S1PR-modulator treated people with MS (pwMS) and insufficient IgG responses after the standard immunization scheme. Eight pwMS that were treated with fingolimod received a third homologous SARS-CoV-2 mRNA vaccine dose, either the Moderna's mRNA-1273 or Pfizer-BioNTech's BNT162b2 vaccine. We quantified the serum levels of IgG antibodies against the receptor-binding domain of SARS-CoV-2 four weeks later. An antibody titer of 100 AU/mL or more was considered protective. After the third vaccination, we found clinically relevant IgG titers in four out of eight individuals (50%). We conclude that the humoral immune response may reach protective levels after the third preferred dose of the homologous SARS-CoV-2 mRNA vaccine. Vaccine shots in S1PR-modulator treated pwMS ahead of schedule may be a strategy to overcome insufficient humoral immune responses following the standard vaccination scheme

Humoral Immune Response after the Third SARS-CoV-2 mRNA Vaccination in CD20 Depleted People with Multiple Sclerosis.

CD20 depletion is a risk factor for unfavorable outcomes of COVID-19 in people with MS (pwMS). Evidence suggests that protective IgG response to mRNA-based vaccines in B cell-depleted individuals is limited. We studied the seroconversion after the third mRNA SARS-CoV-2 vaccine in B cell-depleted pwMS with limited or no IgG response after the standard immunization. Sixteen pwMS treated with ocrelizumab or rituximab received a third homologous SARS-CoV-2 mRNA vaccine, either the Moderna mRNA-1273 or Pfizer-BioNTech's BNT162b2 vaccine. We quantified the response of IgG antibodies against the spike receptor-binding domain of SARS-CoV-2 four weeks later. An antibody titer of 100 AU/mL or more was considered clinically relevant. The median time between the last infusion of the anti-CD20 treatment and the third vaccination was 22.9 weeks (range 15.1-31.3). After the third vaccination, one out of 16 patients showed an IgG titer deemed clinically relevant. Only the seroconverted patient had measurable B-cell counts at the time of the third vaccination. The development of a humoral immune response remains rare in pwMS on anti-CD20 therapy, even after third dose of the homologous SARS-CoV-2 mRNA vaccine. It remains to be determined whether T-cell responses can compensate for the lack of seroconversion and provide sufficient protection against CoV-2 infections

Travellers returning from the island of Zanzibar colonized with MDR Escherichia coli strains: assessing the impact of local people and other sources.

OBJECTIVES Many travellers to low-income countries return home colonized at the intestinal level with extended-spectrum cephalosporin-resistant (ESC-R) and/or colistin-resistant (CST-R) Escherichia coli (Ec) strains. However, nothing is known about the local sources responsible for the transmission of these pathogens to the travellers. METHODS We compared the ESC-R- and CST-R-Ec strains found in the pre- (n = 23) and post-trip (n = 37) rectal swabs of 37 travellers from Switzerland to Zanzibar with those (i) contemporarily isolated from local people, poultry, retailed chicken meat (n = 31), and (ii) from other sources studied in the recent past (n = 47). WGS and core-genome analyses were implemented. RESULTS Twenty-four travellers returned colonized with ESC-R- (n = 29) and/or CST-R- (n = 8) Ec strains. Almost all ESC-R-Ec were CTX-M-15 producers and belonged to heterogeneous STs/core-genome STs (cgSTs), while mcr-positive strains were not found. Based on the strains' STs/cgSTs, only 20 subjects were colonized with ESC-R- and/or CST-R-Ec that were not present in their gut before the journey. Single nucleotide variant (SNV) analysis showed that three of these 20 travellers carried ESC-R-Ec (ST3489, ST3580, ST361) identical (0-20 SNVs) to those found in local people, chicken meat, or poultry. Three further subjects carried ESC-R-Ec (ST394, ST648, ST5173) identical or highly related (15-55 SNVs) to those previously reported in local people, fish, or water. CONCLUSIONS This is the first known study comparing the ESC-R- and/or CST-R-Ec strains obtained from travellers and local sources using solid molecular methods. We showed that for at least one-third of the returning travellers the acquired antibiotic-resistant Ec had a corresponding strain among resident people, food, animal and/or environmental sources