Background COVID-19, the pandemic disease caused by infection with SARS-CoV-2, may take highly variable clinical courses, ranging from symptom-free and pauci-symptomatic to fatal disease. The goal of the current study was to assess the association of COVID-19 clinical courses controlled by patients’ adaptive immune responses without progression to severe disease with patients’ Human Leukocyte Antigen (HLA) genetics, AB0 blood group antigens, and the presence or absence of near-loss-of-function delta 32 deletion mutant of the C–C chemokine receptor type 5 (CCR5). Patient and methods An exploratory observational study including 157 adult COVID-19 convalescent patients was performed with a median follow-up of 250 days. The impact of different HLA genotypes, AB0 blood group antigens, and the CCR5 mutant CD195 were investigated for their role in the clinical course of COVID-19. In addition, this study addressed levels of severity and morbidity of COVID-19. The association of the immunogenetic background parameters were further related to patients’ humoral antiviral immune response patterns by longitudinal observation. Results Univariate HLA analyses identified putatively protective HLA alleles (HLA class II DRB1*01:01 and HLA class I B*35:01, with a trend for DRB1*03:01). They were associated with reduced durations of disease instead decreased (rather than increased) total anti-S IgG levels. They had a higher virus neutralizing capacity compared to non-carriers. Conversely, analyses also identified HLA alleles (HLA class II DQB1*03:02 und HLA class I B*15:01) not associated with such benefit in the patient cohort of this study. Hierarchical testing by Cox regression analyses confirmed the significance of the protective effect of the HLA alleles identified (when assessed in composite) in terms of disease duration, whereas AB0 blood group antigen heterozygosity was found to be significantly associated with disease severity (rather than duration) in our cohort. A suggestive association of a heterozygous CCR5 delta 32 mutation status with prolonged disease duration was implied by univariate analyses but could not be confirmed by hierarchical multivariate testing. Conclusion The current study shows that the presence of HLA class II DRB1*01:01 and HLA class I B*35:01 is of even stronger association with reduced disease duration in mild and moderate COVID-19 than age or any other potential risk factor assessed. Prospective studies in larger patient populations also including novel SARS-CoV-2 variants will be required to assess the impact of HLA genetics on the capacity of mounting protective vaccination responses in the future.
BackgroundAdjuvant radiotherapy in advanced head and neck squamous cell cancer (HNSCC) reduces the risk of local-regional failure and most likely increases the survival rate. Patients at high risk for tumor recurrence may benefit from more aggressive altered fractionation schedules in order to reduce the overall time from surgery to completion of radiotherapy. Here, we reviewed the results of six randomized trials addressing the above hypothesis.MethodsIn the six trials of interest, a total of 988 patients with locally advanced HNSCC were randomly assigned to receive either accelerated or conventionally fractionated adjuvant radiotherapy. Hazard ratios (HR) were extracted from available publications for local-regional control, distant metastasis as well as overall-, cancer specific- and disease-free survival. Meta-analysis of the effect sizes was performed using fixed and random effect models. Acute and late side effects were categorized and summarized for comparison.ResultsAccelerated radiotherapy did not improve the loco-regional control (n = 988, HR = 0.740, CI = 0.48–1.13, p = 0.162), progression-free survival (HR = 0.89, CI = 0.76–1.04, p = 0.132) or overall survival (HR = 0.88, CI = 0.75–1.04, p = 0.148) significantly. Acute confluent mucositis occurred with significant higher frequency with accelerated radiotherapy. Late side effects did not differ significantly in either group.ConclusionAccelerated radiotherapy does not result in a significant improvement of loco-regional control or overall survival in high-risk patients. Acute but not late radiation toxicity were more frequent with the accelerated RT technique. In clinical practice accelerated postoperative radiation therapy might be a suitable option only for a subset of patients.
All patients presented with restricted cervical mobility and all patients had CT and/or MRI scan on admission. The mean abscess volume was 9.4 cm(3). Surgical intervention was performed in all cases, including transoral (n=5), transcervical (n=3) or combined transoral and transcervical (n=2) drainage. In one patient RPA close to the skull base was drained by an MRI-guided transnasal approach. All patients recovered; however, there was one recurrence and in one case surgical tracheotomy was unavoidable during the course of disease. Growth of streptococcal species was verified in six of the examined abscesses. Abscessing lymphadenitis, infection of a cervical cyst, and previous ganglionar local opioid analgesia treatment were identified as causative factors.
The frequently performed determination of routine coagulation parameters (aPTT, PT, PLC) is not able to reliably identify relevant coagulation disorders or to predict the risk for postoperative hemorrhagic complications after adenoidectomy or tonsillectomy.
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