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1.
Clin Cancer Res ; 2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39264275

RESUMEN

PURPOSE: Antibodies to select Epstein-Barr virus (EBV) proteins can diagnose early-stage nasopharyngeal carcinoma (NPC). We have previously shown that IgA against EBV nuclear antigen 1 (EBNA1) can predict incident NPC in high- and intermediate-risk cohorts 4 years pre-diagnosis. Here, we tested EBNA1 variants, with mutants, to define the sequence requirements for an NPC risk assay. DESIGN: Mammalian-expressed constructs were developed to represent EBNA1 variants 487V and 487A which can differ by ≥15 amino acids in the N- and C-termini. Denatured lysates were evaluated by a refined IgA and IgG immunoblot assay in a case-control study using pre-diagnostic NPC sera from two independent cohorts in Singapore and Shanghai, P.R. China. RESULTS: At 95% sensitivity, 487V yielded a 94.9% specificity compared to 86.1% for 487A. EBNA1 deleted for the conserved glycine-alanine repeats (GAr) reduced false positives by 22.8%. NPC sera reacted more strongly to the C-terminus than healthy controls, but the C-terminal construct (a.a. 390-641) showed lower specificity (84.8%) than the EBNA1 GAr deleted construct (92.4%) at 95% sensitivity. CONCLUSION: Although EBNA1 IgA was present in healthy sera, most epitopes localized to the immunodominant GAr. We conclude that a refined EBNA1 antigen deleted for the GAr but with residues consistently detected in Southeast Asian NPC tumors is optimal for risk prediction with an extended sojourn time of 7.5 years. Furthermore, distinct EBNA1 serologic profiles enhanced the utility of the EBNA1 IgA assay for risk stratification. This illustrates the importance of serologically relevant EBNA1 sequences for NPC risk prediction and early detection.

2.
J Med Life ; 16(5): 782-793, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-37520491

RESUMEN

Healthcare workers (HCWs) are at high risk of COVID-19 infection despite vaccination. Limited data exist on COVID-19 cases among vaccinated HCWs. This study aimed to describe the clinical characteristics and outcomes of RT PCR-confirmed COVID-19 cases in vaccinated HCWs, at a COVID clinic in a medical college hospital. This single-center, prospective cohort study included HCWs who received at least one dose of the COVID-19 vaccine and tested positive for COVID-19 within 6 months. Data on demographics, symptoms, work category, COVID-19 vaccination interval, and infection severity were collected. Of 2381 vaccinated HCWs, 105 tested positive and were categorized as mild, moderate, or severe cases. Among vaccinated HCWs, 4.41% had post-vaccine COVID-19 infections. All 105 cases received the first dose, and 79 received the second dose. Of the cases, 47.6% were partially vaccinated, and 53.3% were breakthrough cases. The mean age was 30.90±8.69 years, with 63.8% male and 36.2% female cases. Most cases (85.7%) acquired infection in the hospital, and 47.6% had direct contact with COVID-19 patients. Common symptoms included fatigue (85.7%), fever (82.9%), and cough (64.8%). Among cases, 93.3% were mild, 5.7% were moderate, and 0.9% were severe. Hospital admission and supplemental oxygen therapy were required for moderate and severe cases. No mortality was reported. Certain variables were associated with age, preventive measures, workplace type, symptoms, and comorbidities. Breakthrough infections can occur among fully vaccinated HCWs but with reduced severity and mortality. Monitoring and infection control measures remain crucial even in vaccinated individuals. This study provides insights into clinical presentations, oxygen therapy requirements, and outcomes of post-vaccine COVID-19 cases among HCWs. The data will inform strategies for booster doses to prevent COVID-19.


Asunto(s)
COVID-19 , Vacunas , Humanos , Femenino , Masculino , Adulto Joven , Adulto , Vacunas contra la COVID-19 , COVID-19/epidemiología , COVID-19/prevención & control , Estudios Prospectivos , Hospitales Universitarios , India/epidemiología , Personal de Salud , Oxígeno
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