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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- 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
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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