medRxiv : the preprint server for health sciencesOct 24, 2026

Strong Protein Responses to Infection Help Control Overall and COVID-19-Related Brain Symptoms After Illness

Updated Oct 25, 2026

Abstract

Analysis of 173 saliva samples identified 44 proteins linked to responses from acute viral infections.

Persistent symptoms after severe infections, known as Post-Acute Infection Syndromes (PAIS), include neurocognitive dysfunction, cardiopulmonary instabilities, and fatigue.
Rates of post-acute syndromes were similar across different viral infections, but the specific types of symptoms varied by virus.
High levels of 19 identified proteins are associated with lower rates of general post-acute symptoms across all viruses.
High expression of 23 overlapping proteins is linked to lower rates of neurocognitive symptoms specifically in SARS-CoV-2 infections.
Low expression of these proteins, which are involved in controlling viral replication and immune responses, may contribute to the development of PAIS and PASC.

Simplified

After serious infections, many survivors fully recover while others face persistent symptoms including neurocognitive dysfunction, cardiopulmonary instabilities and disabling fatigue, classified broadly as Post-Acute Infection Syndromes (PAIS). Post-Acute Sequelae of COVID19 (PASC) is one special case. To test whether acute infection initiates PAIS, we analyzed proteins in 173 saliva samples collected during severe respiratory viral infections and tracked patient outcomes for five years. We discovered 44 proteins, all derived from interferon stimulated genes, that respond strongly to acute infection. Rates of post-acute syndromes were similar regardless of infection, but the types of Sequelae differed by virus. High expression of 19 proteins predict low General Sequelae rates across all viruses. High expression of 23 overlapping proteins predict low Neurocognitive Sequelae rates only with SARS-CoV-2 infections. We propose that low expressions of these proteins, which control viral replication, innate immunity, and secondary autoimmunity, combine to precipitate PAIS and PASC.

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Strong Protein Responses to Infection Help Control Overall and COVID-19-Related Brain Symptoms After Illness

Abstract

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