Dr. Michael Peluso

(Medford MA, October 28, 2023) – PolyBio’s LongCovid Research Consortium is proud to have contributed support to a new preprint published by Dr. Michael Peluso and team at the University of California San Francisco. The study titled “Plasma-based antigen persistence in the post-acute phase of SARS-CoV-2 infection” was performed as part of a collaboration with Dr. David Walt’s team at Harvard Medical School. The team to used a sensitive assay called SIMOA to search for SARS-CoV-2 proteins in Long COVID blood.

In comparison to samples obtained from healthy individuals collected before the COVID-19 pandemic, the team identified increased prevalence of SARS-CoV-2 proteins in Long COVID blood for up to 14 months following confirmed SARS-CoV-2 infection. The findings build on earlier LongCovid studies – including by Walt’s team – that previously found SARS-CoV-2 protein in Long COVID blood. Taken together the research “provides strong evidence that SARS-CoV-2 should be added to the list of RNA viruses whose components may persist beyond the period of acute illness.”

Overall, SARS-CoV-2 proteins identified in Long COVID blood are likely derived from persistent virus in tissue reservoir sites, but “leak” into patient blood where they can be measured. In the most recent SIMOA UCSF study, more that 10% of plasma samples collected for over a year following initial SARS-CoV-2 infection contained SARS-CoV-2 proteins, which can potentially provoke the immune response.

While a failure to identify SARS-CoV-2 protein in the blood of a study participant could be interpreted to mean that the person does not harbor a SARS-CoV-2 reservoir, multiple factors must be considered. Some Long COVID patients may harbor a SARS-CoV-2 tissue reservoir in body sites such as the brain where viral protein does not leak into the blood. Protein in blood could also be trapped inside immune cells or be bound by antibodies – and thus fail to measured by the SIMOA assay used in the study.

A chart showing SARS-CoV-2 S1 protein identified at multiple timepoints in the blood of a Long COVID patient

In addition, while the SIMOA assay is highly sensitive, it is possible that more sensitive assays will be needed to identify viral protein in Long COVID blood. Indeed, the study team found that multiple participants in the study had viral protein levels detected near the SIMOA assay limit. David Walt’s team is consequently developing a new assay – MOSAIC – that should be able to identify even more tiny amounts of SARS-CoV-2 proteins in samples.

Overall, the study findings provide additional rationale for interventions meant to reduce or eliminate SARS-CoV-2 reservoirs or persistent protein in Long COVID patients. These interventions include antiviral drugs (if viral replication is present) or other drugs that could neutralize protein, clear infected cells, and/or modulate the immune response to these antigens (e.g., monoclonal antibodies).