HLA polymorphism can complicate the design and development of vaccines, especially those that contain a selected number of epitopes and are directed at pathogens prevalent worldwide. Because of HLA class I restricted antigen recognition and ethnic variation in HLA distribution, such vaccines may not be uniformly effective across populations. We, therefore, considered whether it is possible to assemble a panel of HLA‐A and/or HLA‐B alleles that would allow the formulation of a single vaccine for a set of Caucasian, Black, or Asian populations. In applying an algorithm to predict levels of favorable response, we identified predominant alleles in 15 representative populations. Approximately 80% of the individuals in one African Black population and five Asian populations were positive for at least one of three HLA‐A alleles. Eighty percent coverage was also theoretically possible in five Caucasian populations with only five HLA‐A alleles. Four of five Black populations analyzed also required five alleles, but the allelic combinations differed. Our findings suggest that HLA‐A alleles may be preferred targets because of the increased heterogeneity at HLA‐B, although addition of a single HLA‐B allele to a set of HLA‐A alleles improved coverage. This approach provides for the identification of combinations of alleles that represent a desired percentage of a population and that could be targeted in designing vaccines. For vaccines with known HLA‐restricted epitopes, it allows a prediction of theoretical levels of “responder” and “non‐responder” status. Finally, these results might be used in the analysis of protein sequences to identify potential CD8+ T‐cell epitopes in populations of interest. Biologic variables that may have further relevance are discussed. Genet. Epidemiol. 20:87–106, 2001. © 2001 Wiley‐Liss, Inc.
Background:Since its inception, the COVID-19 outbreak has been carefully monitored both by the patients using DMARDs and their physicians. There is no data that patients with rheumatic and musculoskeletal diseases (RMD) are at a higher risk of contracting COVID-19 disease than those without RMD (1). COVID-19-related death in people with RMD has been associated with older age, male gender, concomitant cardiovascular and pulmonary diseases, moderate/high disease activity, and certain treatments (rituximab (RTX), sulfasalazine (SSZ) and some immunosuppressants) (2).Objectives:To determine the conditions of getting and being affected poorly by COVID-19 and related factors of RMD patients followed in our outpatient clinic.Methods:160 patients over 18 years of age who applied to our outpatient clinic between July 2020-January 2021; who used DMARDs for rheumatic diseases and agreed to participate were included in the study. The patients’s demographic data, RMDs, csDMARDs and b/tsDMARDs usage, comorbid diseases and smoking status were recorded. The data of the patients on COVID-19 disease between March 2020 and January 2021 were questioned at each visit.Results:Patient characteristics are presented in Table 1. 57 (36%) of all patients had COVID-19 PCR test, 23 (14%) were positive, and 1 patient was diagnosed with COVID-19 because the CT findings were positive, although the PCR test was negative.Table 1.Patient characteristicsAll Patients n=160COVID-19 Patients n=24Male61 (38%)6 (25%)Female99 (62%)18 (75%)Mean age49.549.5Ever smoker88 (55%)8 (33,3%)Obesity51 (32%)9 (37,5%)Hypertension (HT)46 (29%)7 (29%)Diabetes (DM)22 (14%)2 (8%)Cardiovascular disease (CVD)26 (16%)5 (20%)Chronic lung disease (CLD)12 (7,5%)4 (16%)SpA71 (44,3%)9 (37,5%)RA71 (44,3%)14 (58,3%)PsA14 (8,8%)1 (4,2%)SLE2 (1,25%)-PMR2 (1,25%)-cDMARD only82 (51,2%)14 (58,3%)b/tsDMARD only55 (34,4%)8 (33.3%)Combined DMARD23 (14,4%)2 (8.4%)The rate of getting COVID-19 infection was 15% in all patients. This rate was 18% in all obese patients, 19% in those with at least one comorbid disease (HT, DM, CVD, CLD), and 22% in those who were obese and had at least one comorbid disease. 16% of non-smokers and 9% of those who ever smoked got COVID-19. Among patients over the age of 65 (n=17), 2 patients (%12) had COVID-19. Treatments of RMDs of patients with COVID-19 were as follows: bDMARD=8 [(Etanercept(ETN) n=2, adalimumab (ADA) n=2, certolizumab pegol (CTZ) n=1, infliximab (IFX) n=1, golimumab (GOL) n=1, RTX n=1)], csDMARD=14 [(methotrexate (MTX) n=4, leflunomid (LEF) n=4, SSZ n=3, HCQ n=2, MTX+SSZ+HCQ n=1)], combined=2 [tofacitinib (TOF)+MTX n=1, TCZ+LEF n=1)], none of them was using glucocorticoids. Overall 17% of patients using csDMARD, 14,5% of patients using b/tsDMARD as monotherapy and 9% of patients using combination treatment had COVID-19. Of the patients using HCQ (n=14), 3 (21%) were diagnosed with COVID-19 disease. 18 of the patients received COVID-19 treatment at home, 6 were hospitalized and 1 of them (RA patient, LEF user) needed intensive care unit. None of them died.Conclusion:Preliminary results regarding the health status associated with COVID-19 of our patients with RMD are presented. Biologic drugs seems not to increase COVID-19 but final results will be presented after the completion of statistical analysis of all data.References:[1]Landewé RB, Machado PM, Kroon F, et al. EULAR provisional recommendations for the management of rheumatic and musculoskeletal diseases in the context of SARS-CoV-2. Ann Rheum Dis. 2020;79(7):851-858. doi:10.1136/annrheumdis-2020-217877[2]Strangfeld A, Schäfer M, Gianfrancesco MA, et al. Factors associated with COVID-19-related death in people with rheumatic diseases: results from the COVID-19 Global Rheumatology Alliance physician-reported registry [published online ahead of print, 2021 Jan 27]. Ann Rheum Dis. 2021;annrheumdis-2020-219498. doi:10.1136/annrheumdis-2020-219498Disclosure of Interests:None declared
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