RESUMO
BACKGROUND: One hundred fifty million contagions, more than 3 million deaths and little more than 1 year of COVID-19 have changed our lives and our health management systems forever. Ageing is known to be one of the significant determinants for COVID-19 severity. Two main reasons underlie this: immunosenescence and age correlation with main COVID-19 comorbidities such as hypertension or dyslipidaemia. This study has two aims. The first is to obtain cut-off points for laboratory parameters that can help us in clinical decision-making. The second one is to analyse the effect of pandemic lockdown on epidemiological, clinical, and laboratory parameters concerning the severity of the COVID-19. For these purposes, 257 of SARSCoV2 inpatients during pandemic confinement were included in this study. Moreover, 584 case records from a previously analysed series, were compared with the present study data. RESULTS: Concerning the characteristics of lockdown series, mild cases accounted for 14.4, 54.1% were moderate and 31.5%, severe. There were 32.5% of home contagions, 26.3% community transmissions, 22.5% nursing home contagions, and 8.8% corresponding to frontline worker contagions regarding epidemiological features. Age > 60 and male sex are hereby confirmed as severity determinants. Equally, higher severity was significantly associated with higher IL6, CRP, ferritin, LDH, and leukocyte counts, and a lower percentage of lymphocyte, CD4 and CD8 count. Comparing this cohort with a previous 584-cases series, mild cases were less than those analysed in the first moment of the pandemic and dyslipidaemia became more frequent than before. IL-6, CRP and LDH values above 69 pg/mL, 97 mg/L and 328 U/L respectively, as well as a CD4 T-cell count below 535 cells/µL, were the best cut-offs predicting severity since these parameters offered reliable areas under the curve. CONCLUSION: Age and sex together with selected laboratory parameters on admission can help us predict COVID-19 severity and, therefore, make clinical and resource management decisions. Demographic features associated with lockdown might affect the homogeneity of the data and the robustness of the results.
RESUMO
BACKGROUND: The SARS-CoV-2 infection has widely spread to become the greatest public health challenge to date, the COVID-19 pandemic. Different fatality rates among countries are probably due to non-standardized records being carried out by local health authorities. The Spanish case-fatality rate is 11.22%, far higher than those reported in Asia or by other European countries. A multicentre retrospective study of demographic, clinical, laboratory and immunological features of 584 Spanish COVID-19 hospitalized patients and their outcomes was performed. The use of renin-angiotensin system blockers was also analysed as a risk factor. RESULTS: In this study, 27.4% of cases presented a mild course, 42.1% a moderate one and for 30.5% of cases, the course was severe. Ages ranged from 18 to 98 (average 63). Almost 60 % (59.8%) of patients were male. Interleukin 6 was higher as severity increased. On the other hand, CD8 lymphocyte count was significantly lower as severity grew and subpopulations CD4, CD8, CD19, and NK showed concordant lowering trends. Severity-related natural killer percent descents were evidenced just within aged cases. A significant severity-related decrease of CD4 lymphocytes was found in males. The use of angiotensin-converting enzyme inhibitors was associated with a better prognosis. The angiotensin II receptor blocker use was associated with a more severe course. CONCLUSIONS: Age and age-related comorbidities, such as dyslipidaemia, hypertension or diabetes, determined more frequent severe forms of the disease in this study than in previous literature cohorts. Our cases are older than those so far reported and the clinical course of the disease is found to be impaired by age. Immunosenescence might be therefore a suitable explanation for the hampering of immune system effectors. The adaptive immunity would become exhausted and a strong but ineffective and almost deleterious innate response would account for COVID-19 severity. Angiotensin-converting enzyme inhibitors used by hypertensive patients have a protective effect in regards to COVID-19 severity in our series. Conversely, patients on angiotensin II receptor blockers showed a severer disease.
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Characterization of HLA-DQB1*06:472, -DQB1*06:02:01:34 and -DQB1*06:04:01:06 alleles in Spanish individuals.
Assuntos
Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Alelos , Cadeias beta de HLA-DQ/genéticaRESUMO
Genomic sequence of HLA-DQB1*03:01:01:60, -DQB1*03:01:01:61, -DQB1*03:01:01:62, -DQB1*03:01:01:63, -DQB1*03:02:01:23, -DQB1*03:02:01:24, -DQB1*03:02:01:25 and -DQB1*03:03:02:14 alleles in Spanish individuals.
Assuntos
Alelos , Cadeias beta de HLA-DQ , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Cadeias beta de HLA-DQ/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Teste de Histocompatibilidade/métodos , Éxons , Espanha , Análise de Sequência de DNA/métodos , Variação GenéticaRESUMO
Genomic sequence of HLA-DPA1*01:03:01:73, -DPA1*01:03:01:80, DPA1*01:03:01:82, -DPA1*01:155:01:02, -DPA1*02:02:02:16 alleles in Spanish individuals.
Assuntos
Alelos , Cadeias alfa de HLA-DP , Humanos , Cadeias alfa de HLA-DP/genética , Éxons , Espanha , Teste de Histocompatibilidade , Análise de Sequência de DNA , Sequência de Bases , Alinhamento de SequênciaRESUMO
Characterisation of HLA-DQA1*01:02:01:30, HLA-DQA1*01:03:01:14, HLA-DQA1*03:03:01:20, HLA-DQA1*04:01:01:13, HLA-DQA1*05:05:01:40 alleles in Spanish individuals.
Assuntos
Alelos , Cadeias alfa de HLA-DQ , Humanos , Cadeias alfa de HLA-DQ/genética , Teste de Histocompatibilidade , Espanha , Análise de Sequência de DNA/métodos , Éxons , Sequência de BasesRESUMO
Characterization of HLA-DQB1*02:02:01:18, -DQB1*02:02:01:19, -DQB1*03:02:01:20 and -DQB1*05:03:01:10 alleles in Spanish individuals.
Assuntos
Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Alelos , Cadeias beta de HLA-DQ/genética , MutaçãoRESUMO
Characterization of HLA-B*40:01:02:61, -B*48:01:01:14, and -C*01:02:01:69 alleles in Spanish individuals.
Assuntos
Genes MHC Classe I , Antígenos HLA-B , Humanos , Alelos , Antígenos HLA-B/genética , Genômica , Sequenciamento de Nucleotídeos em Larga EscalaRESUMO
BACKGROUND: In 2015, the Spanish National Transplant Organization developed a prioritization system (Program for Access to Transplantation for Highly Sensitized Patients [PATHI]) to increase transplant options for patients with calculated panel-reactive antibodies (cPRAs) ≥98%, based on virtual crossmatch. We describe the experience with the implementation of PATHI and assess its efficacy. METHODS: PATHI registry was used to collect characteristics of donors and patients between June 15, 2015, and March 1, 2018. One-year graft and patient survival and acute rejection were also measured. A Cox model was used to identify factors related to patient death and graft loss and logistical regression for those associated with rejection. RESULTS: One thousand eighty-nine patients were included, and 272 (25%) were transplanted. Transplant rate by cPRA was 54.9%, 40.5%, and 12.8% in patients with cPRA98%, cPRA99%, and cPRA100%, respectively. One-year patient survival was 92.5%. Recipient age ≥60, time under dialysis >7 y, and delayed graft function were mortality risk factors. One-year graft survival was 88.7%. The factor related to graft loss was delayed graft function. The rejection rate was 22%. Factors related to rejection were sex, older recipients, and posttransplant donor-specific antibodies. CONCLUSIONS: A prioritization approach increases transplant options for highly sensitized patients with appropriate short-term postransplant outcomes. Along with other programs, PATHI may inspire other countries to adopt strategies to meet transplant needs of these patients.
Assuntos
Transplante de Rim , Humanos , Transplante de Rim/efeitos adversos , Função Retardada do Enxerto/etiologia , Rejeição de Enxerto/prevenção & controle , Doadores de Tecidos , Sobrevivência de Enxerto , Anticorpos , Teste de Histocompatibilidade , Antígenos HLARESUMO
The DQA1*05:01:11 allele shows the TAA (UAA) stop codon instead of the common DQA1 TGA (UGA) stop codon.
Assuntos
Códon de Terminação , Humanos , Alelos , Éxons , Cadeias alfa de HLA-DQ/genéticaRESUMO
Three novel HLA Class I alleles, -B*15:640, -B*18:01:01:71 and -C*05:275, characterized in Spanish individuals.
Assuntos
Antígenos HLA-B , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Alelos , Antígenos HLA-B/genética , Genes MHC Classe I , Teste de HistocompatibilidadeRESUMO
Four novel HLA Class II alleles, HLA-DPA1*01:03:01:68, -DPA1*01:03:01:71, -DQA1*02:01:01:06, and -DQB1*06:03:01:19, characterized in Spanish individuals.
Assuntos
Cadeias alfa de HLA-DP , Humanos , Alelos , Cadeias alfa de HLA-DP/genética , Cadeias beta de HLA-DQ/genética , Haplótipos , Cadeias alfa de HLA-DQ/genética , Frequência do GeneRESUMO
Three novel HLA Class I alleles, -A*02:1092, -A*29:01:01:11 and -B*44:03:01:58, characterized in Spanish individuals.
Assuntos
Antígenos HLA-A , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Alelos , Antígenos HLA-A/genética , Antígenos HLA-B/genéticaRESUMO
Four novel HLA-DQA1 alleles, -DQA1*01:01:02:04, -DQA1*01:04:01:05, -DQA1*03:03:01:19 and -DQA1*05:01:01:08, characterized in Spanish individuals.
Assuntos
Alelos , Humanos , Cadeias alfa de HLA-DQ/genéticaRESUMO
Three novel HLA Class II alleles, -DQA1*02:28, -DQA1*05:01:08:02 and -DQB1*03:02:01:13, characterized in Spanish individuals.
Assuntos
Antígenos HLA-DQ , Humanos , Antígenos HLA-DQ/genética , Frequência do Gene , Alelos , Cadeias beta de HLA-DQ/genética , Cadeias HLA-DRB1 , Haplótipos , Cadeias alfa de HLA-DQ/genéticaRESUMO
Background: After exposure to SARS-CoV-2 and/or vaccination there is an increase in serum antibody titers followed by a non-linear waning. Our aim was to find out if this waning of antibody titers would fit to a mathematical model. Methods: We analyzed anti-RBD (receptor binding domain) IgG antibody titers and the breakthrough infections over a ten-month period following the second dose of the mRNA BNT162b2 (Pfizer-BioNtech.) vaccine, in a cohort of 54 health-care workers (HCWs) who were either never infected with SARS-CoV-2 (naïve, nHCW group, n=27) or previously infected with the virus (experienced, eHCW group, n=27). Two mathematical models, exponential and power law, were used to quantify antibody waning kinetics, and we compared the relative quality of the goodness of fit to the data between both models was compared using the Akaik Information Criterion. Results: We found that the waning slopes were significantly more pronounced for the naïve when compared to the experienced HCWs in exponential (p-value: 1.801E-9) and power law (p-value: 9.399E-13) models. The waning of anti-RBD IgG antibody levels fitted significantly to both exponential (average-R2: 0.957 for nHCW and 0.954 for eHCW) and power law (average-R2: 0.991 for nHCW and 0.988 for eHCW) models, with a better fit to the power law model. In the nHCW group, titers would descend below an arbitrary 1000-units threshold at a median of 210.6 days (IQ range: 74.2). For the eHCW group, the same risk threshold would be reached at 440.0 days (IQ range: 135.2) post-vaccination. Conclusion: Two parsimonious models can explain the anti-RBD IgG antibody titer waning after vaccination. Regardless of the model used, eHCWs have lower waning slopes and longer persistence of antibody titers than nHCWs. Consequently, personalized vaccination booster schedules should be implemented according to the individual persistence of antibody levels.
Assuntos
Vacina BNT162 , COVID-19 , Humanos , SARS-CoV-2 , COVID-19/prevenção & controle , Anticorpos Antivirais , Vacinação , RNA Mensageiro , Convulsões , Imunoglobulina GRESUMO
Four novel HLA-DPA1 alleles, -DPA1*01:03:01:59, -DPA1*01:03:01:60, -DPA1*02:01:01:30, and -DPA1*02:01:01:31, characterized in Spanish individuals.
Assuntos
Cadeias alfa de HLA-DP , Sequenciamento de Nucleotídeos em Larga Escala , Alelos , Cadeias alfa de HLA-DP/genética , Humanos , Íntrons/genéticaRESUMO
Four novel HLA-DQB1 alleles, -DQB1*02:02:01:08, -DQB1*02:01:01:11, -DQB1*03:01:01:30 and -DQB1*03:01:01:36, characterized in Spanish individuals.
Assuntos
Sequenciamento de Nucleotídeos em Larga Escala , Alelos , Cadeias beta de HLA-DQ/genética , Humanos , ÍntronsRESUMO
The characterization of the expression profile of HLA questionable alleles (Q) is clinically relevant in allogeneic hematopoietic stem cell transplantation (HSTC) because an aberrant expression of these alleles could lead to transplantation-related complications. HLA-DQB1*03:01:01:21Q shows a substitution at the donor splice site of intron 3 that potentially could affect the expression of this allele. In order to determine their expression profile at RNA and protein level, we analyzed the presence of the HLA-DQ7 molecule by complement-dependent cytotoxicity test (CDC) and flow cytometry, and their RNA processing by cDNA analyses and sequencing by Sanger methods. Our results reveal that HLA-DQ7 is not detectable by serological methods, this is confirmed by cDNA methods demonstrating the absence of specific HLA-DQB1*03:01:01:21Q mRNA, probably due to an intron 3 retention that creates a premature TGA stop codon, leading to mRNA degradation via nonsense-mediated decay (NMD). These findings demonstrate that the HLA-DQB1*03:01:01:21Q allele is nonexpressed, thus it has been renamed as DQB1*03:01:01:21N.
Assuntos
RNA , Alelos , DNA Complementar/genética , Cadeias beta de HLA-DQ/genética , HumanosRESUMO
Four novel HLA alleles, HLA-B*40:02:01:26, HLA-DQB1*03:01:01:29, HLA-DQB1*04:02:01:12 and HLA-DPB1*1195:01, detected in Spanish individuals.