Long term persistence of SARS-CoV-2 humoral response in multiple sclerosis subjects.

BACKGROUND & OBJECTIVES: The persistence of the severe acute respiratory syndrome coronavirus (SARS-CoV)-2 pandemic, partly due to the appearance of highly infectious variants, has made booster vaccinations necessary for vulnerable groups. Here, we present data regarding the decline of the SARS-CoV-2 BNT162b2 mRNA vaccine-induced humoral immune response in a monocentric cohort of MS patients. METHODS: 96 MS patients undergoing eight different DMTs, all without previous SARS-CoV-2 infection, were evaluated for anti-Spike IgG levels, 21 days (T1) and 5-6 months (T2) after the second SARS-CoV-2 BNT162b2 mRNA vaccine dose. The anti-Spike IgG titre from MS subjects was compared with 21 age- and sex-matched healthy controls (HC). RESULTS: When compared with SARS-CoV-2 IgG levels at T2 in HC, we observed comparable levels in interferon-ß 1a-, dimethyl fumarate-, teriflunomide- and natalizumab-treated MS subjects, but an impaired humoral response in MS subjects undergoing glatiramer acetate-, cladribine-, fingolimod- and ocrelizumab-treatments. Moreover, comparison between SARS-CoV-2 IgG Spike titre at T1 and T2 revealed a faster decline of the humoral response in patients undergoing dimethyl fumarate-, interferon-ß 1a- and glatiramer acetate-therapies, while those receiving teriflunomide and natalizumab showed higher persistence compared to healthy controls. CONCLUSION: The prominent decline in humoral response in MS subjects undergoing dimethyl fumarate-, interferon-ß 1a- and glatiramer acetate-therapies should be considered when formulating booster regimens as these subjects would benefit of early booster vaccinations.

Interferon Beta-1a treatment promotes SARS-CoV-2 mRNA vaccine response in multiple sclerosis subjects.

BACKGROUND: Several concerns exist on the immunogenicity of SARS-CoV-2 vaccines in multiple sclerosis (MS) subjects due to their immunomodulating disease modifying therapies (DMTs). Here we report a comparison of the humoral response to BNT162b2-mRNA coronavirus (COVID)-19 vaccine and the immunological phenotype in a cohort of 125 MS subjects undergoing different DMTs, with no history of SARS-CoV-2 infection. METHODS: We collected serum and blood samples at the first day of vaccine (T0) and 21 days after the second vaccine dose (T1) from 125 MS subjects, undergoing eight different DMTs. Sera were tested using the Elecsys anti-SARS-CoV-2-IgG assay for the detection of IgG antibodies to SARS-CoV-2 spike protein. The anti-spike IgG titres from MS subjects were compared with 24 age- and sex-matched healthy controls (HC). Percentage and absolute number of B and T lymphocytes were evaluated by cytofluorimetric analysis in the same study cohort. RESULTS: When compared with SARS-CoV-2 IgG levels in HC (n = 24, median 1089 (IQR 652.5-1625) U/mL), we observed an increased secretion of SARS-CoV-2 IgG in interferon-beta 1a (IFN)-treated MS subjects (n = 22, median 1916 (IQR 1024-2879) U/mL) and an impaired humoral response in MS subjects undergoing cladribine (CLAD) (n = 10, median 396.9 (IQR 37.52-790.9) U/mL), fingolimod (FTY) (n = 19, median 7.9 (IQR 4.8-147.6) U/mL) and ocrelizumab (OCRE) (n = 15, median 0.67 (IQR 0.4-5.9) U/mL) treatment. Moreover, analysis of geometric mean titre ratio (GMTR) between different DMT's groups of MS subjects revealed that, when compared with IFN-treated MS subjects, intrinsic antibody production was impaired in teriflunomide (TERI)-, natalizumab (NAT)-, CLAD-, FTY- and OCRE-, while preserved in DMF- and GA-treated MS subjects. CONCLUSION: Humoral response to BNT162b2-mRNA-vaccine was increased in IFN-treated MS subjects while clearly blunted in those under CLAD, FTY and OCRE treatment. This suggests that the DMTs could have a key role in the protection from SARS-CoV-2 related disease and complication in MS subjects, underlying a novel aspect that should be considered in the selection of the most appropriate therapy under COVID-19 pandemic.

Risk Factors for Varicella Susceptibility Among Refugees to Toronto, Canada.

Several outbreaks of varicella have occurred among refugees. We aimed to estimate the prevalence of varicella susceptibility among refugees, and identify risk factors for varicella susceptibility. All refugees rostered at Crossroads Clinic in Toronto, Canada in 2011-2014 were included in our study. Varicella serology was assessed at the initial visit. Refugees' age, sex, education, time since arrival, and climate and population density of birth country were abstracted from the chart. Multivariate logistic regression was used to identify risk factors for varicella susceptibility. 1063 refugees were rostered at Crossroads Clinic during the study; 7.9 % (95 % CI 6.1, 9.7) were susceptible to varicella. Tropical climate (OR 3.20, 95 % CI 1.53, 6.69) and younger age (ORper year of age 0.92, 95 % CI 0.88-0.96) were associated with increased varicella susceptibility. These risk factors for varicella susceptibility should be taken into account to maximize the cost-effectiveness of varicella prevention strategies among refugees.

Health status of newly arrived refugees in Toronto, Ont: Part 1: infectious diseases.

OBJECTIVE: To determine the prevalence of selected infectious diseases among newly arrived refugee patients and whether there is variation by key demographic factors. DESIGN: Retrospective chart review. SETTING: Primary care clinic for refugee patients in Toronto, Ont. PARTICIPANTS: A total of 1063 refugee patients rostered at the clinic from December 2011 to June 2014. MAIN OUTCOME MEASURES: Demographic information (age, sex, and region of birth); prevalence of HIV, hepatitis B, hepatitis C, Strongyloides, Schistosoma, intestinal parasites, gonorrhea, chlamydia, and syphilis infections; and varicella immune status. RESULTS: The median age of patients was 29 years and 56% were female. Refugees were born in 87 different countries. Approximately 33% of patients were from Africa, 28% were from Europe, 14% were from the Eastern Mediterranean Region, 14% were from Asia, and 8% were from the Americas (excluding 4% born in Canada or the United States). The overall rate of HIV infection was 2%. The prevalence of hepatitis B infection was 4%, with a higher rate among refugees from Asia (12%, P < .001). Hepatitis B immunity was 39%, with higher rates among Asian refugees (64%, P < .001) and children younger than 5 years (68%, P < .001). The rate of hepatitis C infection was less than 1%. Strongyloides infection was found in 3% of tested patients, with higher rates among refugees from Africa (6%, P = .003). Schistosoma infection was identified in 15% of patients from Africa. Intestinal parasites were identified in 16% of patients who submitted stool samples. Approximately 8% of patients were varicella nonimmune, with higher rates in patients from the Americas (21%, P < .001). CONCLUSION: This study highlights the importance of screening for infectious diseases among refugee patients to provide timely preventive and curative care. Our data also point to possible policy and clinical implications, such as targeted screening approaches and improved access to vaccinations and therapeutics.

Health status of newly arrived refugees in Toronto, Ont: Part 2: chronic diseases.

OBJECTIVE: To determine the prevalence of selected chronic diseases among newly arrived refugee patients and to explore associations with key demographic factors. DESIGN: Retrospective chart review. SETTING: Primary care clinic for refugee patients in Toronto, Ont. PARTICIPANTS: A total of 1063 refugee patients rostered at the clinic from December 2011 to June 2014. MAIN OUTCOME MEASURES: Demographic information (age, sex, and region of birth) and prevalence of abnormal Papanicolaou test results, anemia, elevated blood pressure (BP), and markers of prediabetes or diabetes (elevated random glucose, fasting glucose, or hemoglobin A1c levels). RESULTS: More than half of our patients were female (56%) and the median age was 29 years. Patients originated from 87 different countries of birth. Top source countries were Hungary (210 patients), North Korea (119 patients), and Nigeria (93 patients). Most patients were refugee claimants (92%), as opposed to government-assisted refugees (5%). Overall, 11% of female patients who underwent Pap tests had abnormal cervical cytology findings, with the highest rates among women from Asia (26%, P = .028). The prevalence of anemia among children younger than 15 years was 11%; for children younger than 5 years the prevalence was 14%. Approximately 25% of women older than 15 years had anemia, with the highest rates among African women (37%, P < .001). Elevated BP was observed in 30% of adult patients older than 15 years, with higher prevalence among male patients (38%, P < .001) and patients from Europe (42%, P < .001). Laboratory markers of prediabetes or diabetes were identified in 8% of patients older than 15 years, with higher rates among patients from Europe (15%, P = .026). CONCLUSION: This study found a notable burden of chronic diseases among refugee patients, including anemia, elevated BP, and impaired glycemic control, as well as abnormal cervical cytology findings. These results underscore the importance of accessible, comprehensive primary care for refugees, with attention to prevention and management of chronic diseases in addition to management of infectious disease.

Presence of FLT3 mutations does not impair stem cell mobilization and feasibility of autologous peripheral blood stem cell transplantation in acute myeloid leukemia.

Fetal liver tyrosine kinase 3 (FLT3) mutations represent a powerful prognostic indicator in acute myeloid leukemia (AML). Further, interaction between FLT3 and its ligand plays a role in normal hematopoiesis. Accordingly, FLT3 mutations may affect mobilization of peripheral blood stem cells (PBSCs) and feasibility of autologous stem cell transplantation (ASCT) in AML. We analyzed the effect of FLT3 mutations on mobilization of CD34(+) cells and on PBASCT feasibility from 111 patients with AML, with a median age of 58 years and normal karyotype. Overall, 23 patients (21%) had FLT3 mutations. The complete remission rate was 74% and was not influenced by FLT3 mutations (73% for patients with FLT3(-) and 78% for those with FLT3(+); P= .78). The successful mobilization rate was 79% and was comparable for patients with FLT3(-) and with FLT3(+) (P = .42). Median numbers of CD34(+) cells collected were 7.6 x 10(6)/kg and 7.1 x 10(6)/kg for patients with FLT3(-) and those with FLT3(+), respectively (P = .64). Among 73 patients evaluated for mobilization, feasibility of ASCT was 71%, and there was no difference between patients with FLT3(-) (74%) and those with FLT3(+) (61%), P = .43. We conclude that the FLT3 mutations have no influence on mobilization of CD34(+) cells or on feasibility of PBASCT in patients with AML and normal karyotype.