New subtype of Omicron on the rise
The coronavirus is constantly mutating. After Alpha and Beta came Delta, but also Gamma, Lambda, Epsilon and Iota are circulating in parts of the world. Since Omicron came on the scene, Delta has almost completely disappeared from Germany. There are two known subvariants of Omicron: BA.1 and BA.2. So far BA.1 has been dominant in Berlin, but scientists from the Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), the Berliner Wasserbetriebe (BWB), and the laboratory company amedes have now been able to detect the Omicron subvariant BA.2 in Berlin wastewater: There was hardly a trace of BA.2 in early January, but the new subvariant accounted for six percent by around January 13, and its share grew to about twelve percent by January 20. So it is spreading rapidly.
It is possible that BA.2 may be prolonging the current Omicron wave somewhat.
BA.2 has about 20 mutations that set it apart from BA.1. It has almost displaced the BA.1 subvariant in Denmark and South Africa, and since early January the share of BA.2 has also been growing rapidly in the United Kingdom. A study by Danish researchers shows that BA.2 appears to be spreading even faster than BA.1. “It is possible that BA.2 may be prolonging the current Omicron wave somewhat,” says MDC molecular biologist Dr. Emanuel Wyler from Professor Markus Landthaler’s RNA Biology and Posttranscriptional Regulation Lab. “Yet data so far from the UK and Denmark tend to suggest that BA.1 and BA.2 are comparable in terms of disease severity and vaccine effectiveness.”
Computer tool predicts whether cases will rise or fall
Predictions like this can be done using a computer-based tool developed by Dr. Altuna Akalin’s Bioinformatics and Omics Data Science Platform at the MDC’s Berlin Institute of Medical Systems Biology (BIMSB), along with other colleagues. The tool, a data analysis pipeline called PiGx SARS-CoV-2, allows them to detect the spread of SARS-CoV-2 as well as determine the frequency of mutations or virus variants. The analysis is not dependent on people taking COVID-19 tests or developing symptoms.
Proportion of ten different BA.2-specific mutations in the Berlin wastewater. A and B are independent samples analyzed on the same day at different times.
The findings are consistent with those of the Berliner Wasserbetriebe, the local water supply company, which has teamed up with the Berlin laboratory of the amedes Group, led by Dr. Martin Meixner, to develop a detection model that includes variant sequencing and a data visualization app. The MDC and the Berliner Wasserbetriebe have split up the various tasks: While the BWB focuses on rapidly determining the viral load and passing on this information, the MDC primarily conducts analyses of subvariants and mutations.
For more than a year, the researchers have been searching for the genome of the coronavirus in Berlin’s wastewater. Once a week the Berliner Wasserbetriebe, which is currently setting up its own virus sequencing capabilities in its laboratory, prepares wastewater samples and sends them to BIMSB and amedes. The scientists enrich the virus particles and amplify the virus genome with a method called PCR. In the next step they can use high-throughput sequencing to determine what individual virus variants are among the found coronavirus specimens and in what proportion. The wastewater sequencing at BIMSB is mainly the responsibility of Markus Landthaler’s lab and the Genomics Platform headed by Dr. Janine Altmüller.
Such analysis can provide an early warning, as it indicates which variant is circulating with a few days lead time.
Sequencing performed on throat samples has so far not distinguished between individual variants. Wastewater analysis makes this easier: “To get meaningful results on the spread of new virus variants, significantly fewer samples need to be analyzed in comparison with nasopharyngeal swabs,” Landthaler says. “Such analysis can also provide an early warning, as it indicates which variant is circulating with a few days lead time. The data on BA.2 show how sensitive and efficient wastewater monitoring is in identifying pathogens. This is also useful beyond the context of SARS-CoV-2.”
Wastewater testing is not yet an established part of Germany’s Covid-19 early warning system – for either known or new variants. That could now change: Berlin is one of 20 pilot sites in the wastewater monitoring program that the German Ministries for the Environment, Nature Conservation, Nuclear Safety and Consumer Protection (BMUV), of Health (BMG), and of Education and Research (BMBF) are supporting in conjunction with EU funding. Project partners include the Berliner Wasserbetriebe and the Berlin State Office for Health and Social Affairs (LaGeSo). The goal is to create a national wastewater surveillance system that will collect data on the presence of SARS‐CoV‐2 and its variants in wastewater and transmit these data to the competent health authorities and to a European exchange platform.
Text: Jana Ehrhardt-Joswig
Further information
Literature
Vic-Fabienne Schumann, Rafael Ricardo de Castro Cuadrat, Emanuel Wyler et al. (2021): „COVID-19 infection dynamics revealed by SARS-CoV-2 wastewater sequencing analysis and deconvolution“. MedRxiv, DOI: 10.1101/2021.11.30.21266952
Please note: This manuscript and the preliminary findings it contains are being made available to the scientific community on a preprint server. It has not yet been certified by peer review. As the authors may have to edit or make additions to the manuscript, it may take some time until journal publication occurs. Notwithstanding this, the MDC is presenting the research here as the subject matter is of high urgency due to the rapid spread of the Omicron variant of concern.
Contacts
Dr. Emanuel Wyler
Landthaler Lab, RNA Biology and Posttranscriptional Regulation
Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC)
+49 30 9406-3009
emanuel.wyler@mdc-berlin.de
Jana Schlütter
Editor, Communications Department
Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC)
+49-(0)30-9406-2121
jana.schluetter@mdc-berlin.de or presse@mdc-berlin.de
Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC)
The Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC) is one of the world’s leading biomedical research institutions. Max Delbrück, a Berlin native, was a Nobel laureate and one of the founders of molecular biology. At the MDC’s locations in Berlin-Buch and Mitte, researchers from some 60 countries analyze the human system – investigating the biological foundations of life from its most elementary building blocks to systems-wide mechanisms. By understanding what regulates or disrupts the dynamic equilibrium in a cell, an organ, or the entire body, we can prevent diseases, diagnose them earlier, and stop their progression with tailored therapies. Patients should benefit as soon as possible from basic research discoveries. The MDC therefore supports spin-off creation and participates in collaborative networks. It works in close partnership with Charité – Universitätsmedizin Berlin in the jointly run Experimental and Clinical Research Center (ECRC), the Berlin Institute of Health (BIH) at Charité, and the German Center for Cardiovascular Research (DZHK). Founded in 1992, the MDC today employs 1,600 people and is funded 90 percent by the German federal government and 10 percent by the State of Berlin.
