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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Viral Immunology
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1448780
This article is part of the Research Topic Community Series in the Regulation of the Host Immune Activation in Respiratory Virus Infections: Volume II View all articles

Alterations in the Plasma Proteome Persist Ten Months after Recovery from Mild to Moderate SARS-CoV-2 Infection

Provisionally accepted
Julio Huapaya Julio Huapaya 1*Salina Gairhe Salina Gairhe 1Shreya Kanth Shreya Kanth 1Xin Tian Xin Tian 2*Cumhur Y. Demirkale Cumhur Y. Demirkale 1*David Regenold David Regenold 3*Jian Sun Jian Sun 3*Nicolas F. Lynch Nicolas F. Lynch 3*Renjie Luo Renjie Luo 2*Alisa Forsberg Alisa Forsberg 3*Robin Dewar Robin Dewar 4*Tauseef Rehman Tauseef Rehman 4*Willy Li Willy Li 1*Janell Krack Janell Krack 1*Janaki Kuruppu Janaki Kuruppu 1*Etsubdink A. Aboye Etsubdink A. Aboye 5*Christopher Barnett Christopher Barnett 6*Jeffrey R. Strich Jeffrey R. Strich 1Richard Davey Richard Davey 3*Richard Childs Richard Childs 2Daniel Chertow Daniel Chertow 1Joseph A. Kovacs Joseph A. Kovacs 1Parizad Torabi-Parizi Parizad Torabi-Parizi 2*Anthony F. Suffredini Anthony F. Suffredini 1*
  • 1 Clinical Center (NIH), Bethesda, Maryland, United States
  • 2 National Heart, Lung, and Blood Institute (NIH), Bethesda, Maryland, United States
  • 3 National Institute of Allergy and Infectious Diseases (NIH), Bethesda, Maryland, United States
  • 4 Frederick National Laboratory for Cancer Research, National Cancer Institute at Frederick (NIH), Frederick, Maryland, United States
  • 5 MedStar Washington Hospital Center, Washington D.C., District of Columbia, United States
  • 6 Division of Cardiology, School of Medicine, University of California San Francisco, San Francisco, United States

The final, formatted version of the article will be published soon.

    Background: Limited data are available describing the effects of SARS-CoV-2 breakthrough infections on the plasma proteome. Methods: 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. Results: 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. Conclusions: 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.

    Keywords: SARS-CoV-2, Proteomics, Vaccination, Breakthrough infections, post-acute sequelae, Inflammation

    Received: 13 Jun 2024; Accepted: 23 Aug 2024.

    Copyright: © 2024 Huapaya, Gairhe, Kanth, Tian, Demirkale, Regenold, Sun, Lynch, Luo, Forsberg, Dewar, Rehman, Li, Krack, Kuruppu, Aboye, Barnett, Strich, Davey, Childs, Chertow, Kovacs, Torabi-Parizi and Suffredini. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Julio Huapaya, Clinical Center (NIH), Bethesda, 20892, Maryland, United States
    Xin Tian, National Heart, Lung, and Blood Institute (NIH), Bethesda, MD 20892, Maryland, United States
    Cumhur Y. Demirkale, Clinical Center (NIH), Bethesda, 20892, Maryland, United States
    David Regenold, National Institute of Allergy and Infectious Diseases (NIH), Bethesda, MD 20892-9807, Maryland, United States
    Jian Sun, National Institute of Allergy and Infectious Diseases (NIH), Bethesda, MD 20892-9807, Maryland, United States
    Nicolas F. Lynch, National Institute of Allergy and Infectious Diseases (NIH), Bethesda, MD 20892-9807, Maryland, United States
    Renjie Luo, National Heart, Lung, and Blood Institute (NIH), Bethesda, MD 20892, Maryland, United States
    Alisa Forsberg, National Institute of Allergy and Infectious Diseases (NIH), Bethesda, MD 20892-9807, Maryland, United States
    Robin Dewar, Frederick National Laboratory for Cancer Research, National Cancer Institute at Frederick (NIH), Frederick, 21702-1201, Maryland, United States
    Tauseef Rehman, Frederick National Laboratory for Cancer Research, National Cancer Institute at Frederick (NIH), Frederick, 21702-1201, Maryland, United States
    Willy Li, Clinical Center (NIH), Bethesda, 20892, Maryland, United States
    Janell Krack, Clinical Center (NIH), Bethesda, 20892, Maryland, United States
    Janaki Kuruppu, Clinical Center (NIH), Bethesda, 20892, Maryland, United States
    Etsubdink A. Aboye, MedStar Washington Hospital Center, Washington D.C., District of Columbia, United States
    Christopher Barnett, Division of Cardiology, School of Medicine, University of California San Francisco, San Francisco, 94143, United States
    Richard Davey, National Institute of Allergy and Infectious Diseases (NIH), Bethesda, MD 20892-9807, Maryland, United States
    Parizad Torabi-Parizi, National Heart, Lung, and Blood Institute (NIH), Bethesda, MD 20892, Maryland, United States
    Anthony F. Suffredini, Clinical Center (NIH), Bethesda, 20892, Maryland, United States

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