Exploring the Spatial Distribution of Persistent SARS-CoV-2 Mutations - Leveraging mobility data for targeted sampling (preprint)

Given the rapid cross-country spread of SARS-CoV-2 and the resulting difficulty in tracking lineage spread, we investigated the potential of combining mobile service data and fine-granular metadata (such as postal codes and genomic data) to advance integrated genomic surveillance of the pandemic in the federal state of Thuringia, Germany. We sequenced over 6,500 SARS-CoV-2 Alpha genomes (B.1.1.7) across seven months within Thuringia while collecting patients' isolation dates and postal codes. Our dataset is complemented by over 66,000 publicly available German Alpha genomes and mobile service data for Thuringia. We identified the existence and spread of nine persistent mutation variants within the Alpha lineage, seven of which formed separate phylogenetic clusters with different spreading patterns in Thuringia. The remaining two are sub-clusters. Mobile service data can indicate these clusters' spread and highlight a potential sampling bias, especially of low-prevalence variants. Thereby, mobile service data can be used either retrospectively to assess surveillance coverage and efficiency from already collected data or to actively guide part of a surveillance sampling process to districts where these variants are expected to emerge. The latter concept proved successful as we introduced a mobility-guided sampling strategy for the surveillance of Omicron sublineage BQ.1.1. The combination of mobile service data and SARS-CoV-2 surveillance by genome sequencing is a valuable tool for more targeted and responsive surveillance.

Molecular epidemiology of SARS-CoV-2 - a regional to global perspective (preprint)

Background: After a year of the global SARS-CoV-2 pandemic, a highly dynamic genetic diversity is surfacing. Among nearly 1000 reported virus lineages, dominant lineages such as B.1.1.7 or B.1.351 attract media attention with questions regarding vaccine efficiency and transmission potential. In response to the pandemic, the Jena University Hospital began sequencing SARS-CoV-2 samples in Thuringia in early 2020. Methods: Viral RNA was sequenced in tiled amplicons using Nanopore sequencing. Subsequently, bioinformatic workflows were used to process the generated data. As a genomic background, 9,642 representative SARS-CoV-2 genomes (1,917 of German origin) were extracted from more than 300.000 genomes. Results: In a comprehensive bioinformatics analysis, we have set Thuringian isolates in the German, European and global context. In Thuringia, a largely rural German region without an international airport and a population density below the German average, we discovered many of the common "EU lineages". German samples are scattered across eight major clades, and Thuringian samples occupy four of them. Conclusion: The rapid emergence and spread of novel variants are of great concern as these lineages could transmit more efficiently, evade current vaccine efforts or undermine diagnostic test accuracy. To anticipate and mitigate these threats, a continuous molecular surveillance is essential.

SARS-CoV-2 causes severe alveolar inflammation and barrier dysfunction (preprint)

Infections with SARS-CoV-2 lead to mild to severe coronavirus disease-19 (COVID-19) with systemic symptoms. Although the viral infection originates in the respiratory system, it is unclear how the virus can overcome the alveolar barrier, which is observed in severe COVID-19 disease courses. To elucidate the viral effects on the barrier integrity and immune reactions, we used mono-cell culture systems and a complex human alveolus-on-a-chip model composed of epithelial, endothelial, and mononuclear cells. Our data show that SARS-CoV-2 efficiently infected epithelial cells with high viral loads and inflammatory response, including the interferon expression. By contrast, the adjacent endothelial layer was no infected and did neither show productive virus replication or interferon release. With prolonged infection, both cell types are damaged, and the barrier function is deteriorated, allowing the viral particles to overbear. In our study, we demonstrate that although SARS-CoV-2 is dependent on the epithelium for efficient replication, the neighboring endothelial cells are affected, e.g., by the epithelial cytokine release, which results in the damage of the alveolar barrier function and viral dissemination.