The overarching goal of Dave O’Connor’s lab is to contribute meaningfully to the global response to viral infections impacting human health. Along with Marc Johnson and Shelby O’Connor, I lead Lungfish, a program to collect innovative samples including wastewater and air to understand how pathogens spread through time and space. We and our partners gather samples from around the world and test them for pathogens using molecular assays such as PCR and sequencing. Long-term, we believe this will provide an affordable way for low-and-medium income countries to strengthen their public health systems, provide early warning when new pathogens arrive in communities, and create “pathogen weather forecasts” that make people safer and healthier.
Related to Lungfish, Shelby and I also have a National Institutes of Health-funded project to implement air sampling in Dane County, Wisconsin schools and a project from the Centers of Excellence for Influenza Research and Response to determine whether air sampling in hospital emergency rooms can detect bovine H5N1 influenza infections. Marc and I also have a project funded by Heart of Racing to find highly divergent SARS-CoV-2 viruses that arise when people are persistently infected for years.
Before I started working on respiratory viruses, I studied HIV/AIDS in monkeys to understand how to make more effective vaccines. The cluster of major histocompatibility complex (MHC) genes that bind and present peptides to T cells influence susceptibility and resistance to HIV, as well as mediating transplant rejection. I continue to develop tools and assays to understand MHC genes in monkeys to improve the reproducibility of experiments and, ultimately, reduce the number of animals needed in experiments.
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Recent research manuscripts
Here are some recent projects we’ve completed with our collaborators:
- Showed that more than 98% of air samples collected in international airports contain SARS-CoV-2 genetic material. Medrxiv.
- Described improved methods for multiplex viral testing of air samples. Medrxiv.
- Deep sequenced wastewater from Columbia, Missouri every week for more than a year and found several viruses including H5N1 influenza and hepatitis A virus could be detected in wastewater even though they had not been found in clinical cases. Medrxiv.
- Comprehensive review of how primate models accelerated Zika virus research, enabling rapid understanding of pregnancy complications and development of countermeasures. PMID 40024258
- Developed methods to detect unusual SARS-CoV-2 variants in publicly available wastewater sequencing data, identifying 18 cryptic lineages likely arising from chronic infections. PMC12176291
- Demonstrated that transplant recipients shed SARS-CoV-2 far longer than typical—40% still positive at 28 days—highlighting the need for extended monitoring in immunocompromised patients. PMID 40335381
- Partnered with libraries and public health clinics to collect home COVID tests from community members, establishing a practical model for genomic surveillance after the end of widespread laboratory testing. PMC12078534
- Traced a mysterious SARS-CoV-2 variant in Wisconsin wastewater to a single building, revealing that one person’s year-long chronic infection generated Omicron-like mutations—showing how new variants can emerge from persistent infections. PMC11049544
- Proposed a clearer framework for defining and classifying persistent SARS-CoV-2 infections, arguing these underrecognized cases may be an important source of new variants. PMID 38340735
- Found evidence that “COVID toes”—the skin lesions that surged during the pandemic—result from a strong interferon response that blocks virus before it spreads, explaining why affected patients often never developed antibodies. PMC11326933
Innovative research data
Manuscripts are a 20th century method for communicating scientific information. We are excited about communicating our science using tools that are faster and more interactive.
- Do densoviruses infect humans and mammals more frequently than currently appreciated? [GitHub]
- What SARS-CoV-2 variants are increasing and decreasing in frequency? [Dashboard]
- Which pathogens are being detected in wastewater collected from sites around the country? [Dashboard]
- Which viruses are being detected in the air of school cafeterias in Dane County, Wisconsin? [Dashboard]. We are proud to collaborate with Public Health Madison Dane County who makes this air data available as part of their Respiratory Illness Dashboard.





