Biosecurity Poland
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Bartosz Gonsior

Shotgun metagenomics in pandemic surveillance

The last pandemic proved that sequencing a pathogen’s genome is not an academic curiosity but a useful tool for monitoring pathogens. In 2021 Poland set up a team to study the genome and mutations of SARS-CoV-2, based on whole genome sequencing (WGS) of the virus. Like the polymerase chain reaction, this type of test has a limitation: it detects only what we are looking for.

This is usually where the first question comes up: how do we look for new threats? Can we build a system that detects such microorganisms? The answer appears to be shotgun metagenomic sequencing1 (MGS).

1. What is MGS and how does it differ from PCR?

The polymerase chain reaction (PCR) works by targeted searching: primers are designed to hybridise (bind) only to the sequence of a specific, known-in-advance pathogen’s genetic material and amplify it many times over. That makes PCR a fast, cheap and very sensitive tool, provided you know what you are looking for.

Shotgun metagenomics drops that assumption. Instead of amplifying one chosen fragment, it sequences all of the genetic material present in a sample — human, bacterial, viral, fungal — without a primer-based selection step. The sample (e.g. wastewater, bronchoalveolar lavage, nasal swabs) goes straight to library preparation, and the resulting reads are then classified bioinformatically by comparison with reference databases and, for environmental studies, with earlier results.

In one published validation study2 in the diagnosis of respiratory tract infections, MGS achieved sensitivity and specificity comparable to the gold standard, multiplex reverse-transcription PCR (RT-PCR): 93.6% and 93.8%. After discrepancy analysis it reached even higher overall agreement (97.9% vs. 95.0% for RT-PCR), while retaining the ability to detect pathogens outside the panel. This is, however, the result of a single validation, not a meta-analysis of the whole method. I look forward to further publications comparing these tests.

2. Why I think MGS has an edge in pandemic prevention

PCR-based surveillance is “blind” to two categories of threat:

  • natural pathogens that have not yet been characterised;
  • deliberately engineered and chimeric pathogens (a chimeric construct combines genetic material from different organisms). In a diagnostic context, such microorganisms may be modified by changing the regions that commercial primers target.

MGS approaches this problem differently from PCR: instead of asking “is pathogen X here?”, it asks “is there anything in this sample that deviates from the expected background?”. The idea behind projects such as SecureBio Detection (formerly the Nucleic Acid Observatory) is to monitor differences relative to a historical baseline of environmental sequences, detecting any organism whose share of a sample grows unusually, whether or not science has described it before. The approach also works for sequences with an unusual, “unnatural” architecture (e.g. chimeric gene fusions).

One issue that deserves scrutiny follows from the ability to read all genetic material without a filter. We need to think about how the resulting data are handled3: who has access to raw environmental sequencing reads, how they should be secured, and how to prevent a situation in which such data would make it easier for someone to design a threat. At present there are no clear guidelines on what steps to take if a potential threat is detected. This is not an argument against MGS, but a feature of a new method and a real part of the risk discussion that should be addressed in Polish law before deployment.

3. Where has MGS been deployed?

  • United States4. CDC Traveler-based Genomic Surveillance (a project of the Centers for Disease Control and Prevention and SecureBio Detection, formerly the Nucleic Acid Observatory) combines voluntary nasal swabs from travellers with sequencing of airport wastewater at nine locations. In parallel, SecureBio Detection runs a pilot of metagenomic sequencing of municipal wastewater from large metropolitan areas; more on their website.
  • United Kingdom5. mSCAPE: the NHS has deployed MGS for diagnosing respiratory tract infections in 30 hospitals6.
  • European Union7. GLOWACON: a consortium set up in cooperation with the Health Emergency Preparedness and Response Authority (HERA) and the Joint Research Centre (JRC), developing a global wastewater and environmental surveillance network that includes pandemic prevention using MGS.

4. Place in Polish and European law

Directive (EU) 2024/3019 on urban wastewater requires member states to monitor the following pathogens in wastewater:

  • SARS-CoV-2 and its variants
  • poliovirus
  • influenza virus
  • new pathogens

as well as any other public health parameters that the competent authorities consider relevant enough to monitor.

At a meeting of the Climate and Environment Committee on 21 January 2025 these EU rules were presented, but their implementation was not presented at later committee meetings. Wastewater surveillance covering more than 70% of Poland’s population is required. Although the deadline passed on 1 January 2025, I see an opportunity to bring MGS into this monitoring.

5. ProtectEU

It is worth placing the above in one more, broader legal framework, because it concerns Poland directly as an EU member state and signals the direction of change for the coming years.

On 1 April 2025 the European Commission presented ProtectEU, the European internal security strategy. It covers, among other things, resilience to hybrid threats, cybersecurity, protection of critical infrastructure and the fight against organised crime. One of the announced elements of the strategy is an action plan on chemical, biological, radiological and nuclear threats, complementing the EU action plan in place since 2017 and the Preparedness Union Strategy adopted in 2025.

ProtectEU places biological threats (including deliberate ones, not only natural ones) within the framework of the EU’s internal security, not solely public health. This potentially creates an additional channel and source of funding, independent of HERA, for developing pathogen detection capabilities, including metagenomic ones.

A new EU Chemical, Biological, Radiological and Nuclear (CBRN) Preparedness and Response Action Plan is due to be published in 2026, including an examination of ways to counter the misuse of new technologies; nucleic acid synthesis and AI-supported biotechnology are mentioned explicitly. In parallel, an EU Stockpiling Strategy and a Medical Countermeasures Strategy were announced as elements of health preparedness for CBRN threats.

6. Development of sequencing in Poland

Genomics for Poland (Genomika dla Polski, G4PL) is a project launched in January 2026 to build a nationwide network of genomic laboratories. It is run by a consortium of 12 institutions led by the Institute of Bioorganic Chemistry of the Polish Academy of Sciences and funded with PLN 248.3 million from the FENG programme (European Funds for a Modern Economy). The project includes the purchase of long-read sequencers, collecting and sequencing DNA from Polish donors (partly as a contribution to the European Genome of Europe project), and building a central data repository.

G4PL is a population genomics and personalised medicine project, aimed mainly at diagnosing rare, oncological and cardiological diseases; unfortunately it does not include pandemic surveillance. Still, the equipment purchases indirectly contribute to the development of sequencing in Poland and, in the future, a shorter path to introducing MGS.

What lies ahead? Implementation of the One Health strategy8, which in my opinion is key to pandemic preparedness. Combining broad metagenomic diagnostics at many levels with integrated international cooperation and data sharing will become possible by jointly breaking down technological and legal barriers.

If you are interested in developing your own project or joining an existing one, see https://blueprintbiosecurity.org/biosurveillance-rfp-2026/

This is an English translation of an article first published in Polish.

Footnotes

  1. Russell T, Formiconi E, Casey M, McElroy M, Mallon P, Gautier VW. Viral Metagenomic Next-Generation Sequencing for One Health Discovery and Surveillance of (Re)Emerging Viruses: A Deep Review. International Journal of Molecular Sciences. 2025;26. doi:10.3390/ijms26199831 ↩

  2. Tan JK, Servellita V, Stryke D, et al. Laboratory validation of a clinical metagenomic next-generation sequencing assay for respiratory virus detection and discovery. Nat Commun. 2024;15(1):9016. Published 2024 Nov 12. doi:10.1038/s41467-024-51470-y ↩

  3. Liang C, Wagstaff J, Aharony N, Schmit V, Manheim D. Managing the Transition to Widespread Metagenomic Monitoring: Policy Considerations for Future Biosurveillance. Health Security. 2023;21:34–45. doi:10.1089/hs.2022.0029 ↩

  4. https://www.cdc.gov/traveler-genomic-surveillance/about/index.html ↩

  5. https://mscape.climb.ac.uk/ ↩

  6. Venkatesan P. UK launch metagenomic pathogen surveillance programme. Lancet Microbe. Published online April 9, 2025. doi:10.1016/j.lanmic.2025.101143 ↩

  7. https://glowacon.org/ ↩

  8. Aarestrup FM, Bonten M, Koopmans M. Pandemics — One Health preparedness for the next. Lancet Reg Health Eur. 2021;9:100210. doi:10.1016/j.lanepe.2021.100210 ↩