Alterations in the plasma proteome persist ten months after recovery from mild to moderate SARS-CoV-2 infection, 2024, Huapaya et al.

SNT Gatchaman

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Alterations in the plasma proteome persist ten months after recovery from mild to moderate SARS-CoV-2 infection
Huapaya, Julio A.; Gairhe, Salina; Kanth, Shreya; Tian, Xin; Demirkale, Cumhur Y.; Regenold, David; Sun, Jian; Lynch, Nicolas F.; Luo, Renjie; Forsberg, Alisa; Dewar, Robin; Rehman, Tauseef; Li, Willy; Krack, Janell; Kuruppu, Janaki; Aboye, Etsubdink A.; Barnett, Christopher; Strich, Jeffrey R.; Davey, Richard; Childs, Richard; Chertow, Daniel; Kovacs, Joseph A.; Torabi-Parizi, Parizad; Suffredini, Anthony F.

Limited data are available describing the effects of SARS-CoV-2 breakthrough infections on the plasma proteome.

PCR-positive SARS-CoV-2 patients, enrolled in a natural history study, underwent analysis of the plasma proteome. A prospective cohort of 66 unvaccinated and 24 vaccinated persons with different degrees of infection severity were evaluated acutely (within 40 days of symptom onset), and at three and ten months. Comparisons based on vaccination status alone and unsupervised hierarchical clustering were performed. A second cohort of vaccinated Omicron patients were evaluated acutely and at ten months.

Acutely, unvaccinated patients manifested overexpression of proteins involved in immune and inflammatory responses, while vaccinated patients exhibited adaptive immune responses without significant inflammation. At three and ten months, only unvaccinated patients had diminished but sustained inflammatory (C3b, CCL15, IL17RE) and immune responses (DEFA5,TREM1). Both groups had underexpression of pathways essential for cellular function, signaling, and angiogenesis (AKT1, MAPK14, HSPB1) across phases. Unsupervised clustering, based on protein expression, identified four groups of patients with variable vaccination rates demonstrating that additional clinical factors influence the plasma proteome. The proteome of vaccinated Omicron patients did not differ from vaccinated pre-Omicron patients.

Vaccination attenuates the inflammatory response to SARS-CoV-2 infection across phases. However, at ten months after symptom onset, changes in the plasma proteome persist in both vaccinated and unvaccinated individuals, which may be relevant to post-acute sequelae of SARS-CoV-2 and other viral infections associated with post-acute infection syndromes.


Link | PDF (Frontiers in Immunology) [Open Access]
 
Thirty-six patients had symptoms data reported at ten months post-infection. Eighteen patients met clinical criteria for post-acute sequelae of SARS-CoV-2 (PASC), 8 with cardiovascular symptoms, 9 with musculoskeletal symptoms, and 15 with neurological symptoms. Random forest showed that FKBP7, COMMD7, POLR3F, CRELD1, and AGRD1 had the highest variable importance that was associated with PASC symptoms.

Proteins associated with any persistent symptom attributed to long COVID at ten months postinfection included FKBP7, which accelerates the folding of proteins during protein synthesis, and COMMD7, which associates with the NF-kappa-B complex and suppresses its transcriptional activity.

Notably, NXPH1, which may play a role in the modulation of synaptic transmission, was the top protein associated with neurological symptoms. Larger validation studies are warranted to confirm these results.
 
It is such a pity that nowadays authors feel the need to 'explain' each bit of data as 'inflammatory' or 'immune'. What matter are the specifics of the data. C3b comes up again - or at least we have had related members of the pathway (C3b, C3d,g, CR2) coming up. This pathway is not specifically inflammatory. It is a pivot point for all sorts of things. It is relevant to the 'writing on the wall' idea since one protein written on the matrix is CD55, which affects the forks of the C3b pathway.
 
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