Association of COVID-19 mortality with COVID-19 vaccination rates in Rhineland-Palatinate (Germany) from calendar week 1 to 20 in the year 2021: a registry-based analysis.

Vaccination is among the measures implemented by authorities to control the spread of the COVID-19 pandemic. However, real-world evidence of population-level effects of vaccination campaigns against COVID-19 are required to confirm that positive results from clinical trials translate into positive public health outcomes. Since the age group 80 + years is most at risk for severe COVID-19 disease progression, this group was prioritized during vaccine rollout in Germany. Based on comprehensive vaccination data from the German federal state of Rhineland-Palatinate for calendar week 1-20 in the year 2021, we calculated sex- and age-specific vaccination coverage. Furthermore, we calculated the proportion of weekly COVID-19 fatalities and reported SARS-CoV-2 infections formed by each age group. Vaccination coverage in the age group 80 + years increased to a level of 80% (men) and 75% (women). Increasing vaccination coverage coincided with a reduction in the age group's proportion of COVID-19 fatalities. In multivariable logistic regression, vaccination coverage was associated both with a reduction in an age-group's proportion of COVID-19 fatalities [odds ratio (OR) per 5 percentage points = 0.89, 95% confidence interval (CI) = 0.82-0.96, p = 0.0013] and of reported SARS-CoV-2 infections (OR per 5 percentage points = 0.82, 95% CI 0.76-0.88, p < 0.0001). The results are consistent with a protective effect afforded by the vaccination campaign against severe COVID-19 disease in the oldest age group.

An efficient and comprehensive strategy for genetic diagnostics of polycystic kidney disease.

Renal cysts are clinically and genetically heterogeneous conditions. Autosomal dominant polycystic kidney disease (ADPKD) is the most frequent life-threatening genetic disease and mainly caused by mutations in PKD1. The presence of six PKD1 pseudogenes and tremendous allelic heterogeneity make molecular genetic testing challenging requiring laborious locus-specific amplification. Increasing evidence suggests a major role for PKD1 in early and severe cases of ADPKD and some patients with a recessive form. Furthermore it is becoming obvious that clinical manifestations can be mimicked by mutations in a number of other genes with the necessity for broader genetic testing. We established and validated a sequence capture based NGS testing approach for all genes known for cystic and polycystic kidney disease including PKD1. Thereby, we demonstrate that the applied standard mapping algorithm specifically aligns reads to the PKD1 locus and overcomes the complication of unspecific capture of pseudogenes. Employing careful and experienced assessment of NGS data, the method is shown to be very specific and equally sensitive as established methods. An additional advantage over conventional Sanger sequencing is the detection of copy number variations (CNVs). Sophisticated bioinformatic read simulation increased the high analytical depth of the validation study and further demonstrated the strength of the approach. We further raise some awareness of limitations and pitfalls of common NGS workflows when applied in complex regions like PKD1 demonstrating that quality of NGS needs more than high coverage of the target region. By this, we propose a time- and cost-efficient diagnostic strategy for comprehensive molecular genetic testing of polycystic kidney disease which is highly automatable and will be of particular value when therapeutic options for PKD emerge and genetic testing is needed for larger numbers of patients.