Strong Protein Responses to Acute Infection Control General Post-Viral Sequelae and SARS-CoV-2-specific Neurocognitive Sequelae
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.
HIGHLIGHTS
Acute viral infections elicit interferon stimulated gene (ISG) protein responses.
23 ISG proteins prevent post-infection General Sequelae for all viral infections.
19 ISG proteins prevent post-infection Neurocognitive Sequelae only with SARS-CoV-2.
Poor protein responses induce distinct post-viral syndromes with or without COVID19.
Web | DOI | PDF | Preprint: MedRxiv | Open Access
Theodore G Liou; Ryan J Andrews; Heather S Battey; Brenda L Bass; Luis G Vargas Buonfiglio; Barbara C Cahill; James E Cox; Scott Gibson; Stephen C Hartsell; Nathan Hatton; Mark W Hazel; My N Helms; Judy L Jensen; Christiana Kartsonaki; Jesse Kupfer; Yanping Li; Filipa Blasco Tavares Pereira Lopes; Allison Manuel; Marco Marchetti; James E Marvin; Elizabeth A Middleton; Patrice Mimche; Kristyn A Packer; Robert Paine; Rhonda D Szczesniak; Anne B Sturrock; Anwar Tandar; E Bart Tarbet; Andrew Ulrich; Derek Warner; Kristi Jo Warren; Allison M Weis; Elizabeth Zimmerman; Sarang K Yoon; Micah G Ownbey; Scott T Youngquist; Frederick R Adler
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.
HIGHLIGHTS
Acute viral infections elicit interferon stimulated gene (ISG) protein responses.
23 ISG proteins prevent post-infection General Sequelae for all viral infections.
19 ISG proteins prevent post-infection Neurocognitive Sequelae only with SARS-CoV-2.
Poor protein responses induce distinct post-viral syndromes with or without COVID19.
Web | DOI | PDF | Preprint: MedRxiv | Open Access