Evidence map›Paper›PMID 41542038›Full record

ArticleResearch square2026

Persistent Immune Dysregulation during Long COVID is Manifested in Antibodies Targeting Envelope and Nucleocapsid Proteins.

Marcin Kwissa, Manikannan Mathayan, Satyajeet S Salunkhe, Velavan Bakthavachalam, Zijing Ye, Mark A Sanborn, Samantha Condo, Aditi Upadhye, Athulith Nemakal, Haoyang Wang and 20 more

Abstract readPreprint
In one paragraph

Article in Research square, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

30 authors.

Marcin KwissaDepartment of Biochemistry and Molecular Genetics, University of Illinois, College of Medicine, Chicago, IL, USA.
Manikannan MathayanIllinois Research Network (ILLInet) RECOVER Hub, Chicago, IL.
Satyajeet S SalunkheIllinois Research Network (ILLInet) RECOVER Hub, Chicago, IL.
Velavan BakthavachalamIllinois Research Network (ILLInet) RECOVER Hub, Chicago, IL.
Zijing YeDepartment of Biochemistry and Molecular Genetics, University of Illinois, College of Medicine, Chicago, IL, USA.ORCID https://orcid.org/0000-0003-4983-2329
Mark A SanbornDepartment of Biochemistry and Molecular Genetics, University of Illinois, College of Medicine, Chicago, IL, USA.
Samantha CondoDepartment of Biochemistry and Molecular Genetics, University of Illinois, College of Medicine, Chicago, IL, USA.
Aditi UpadhyeDepartment of Biochemistry and Molecular Genetics, University of Illinois, College of Medicine, Chicago, IL, USA.
Athulith NemakalIllinois Research Network (ILLInet) RECOVER Hub, Chicago, IL.
Haoyang WangMassachusetts General Hospital Biostatistics, Boston, MA, USA.
James ChanMassachusetts General Hospital Biostatistics, Boston, MA, USA.
Justin M RichnerIllinois Research Network (ILLInet) RECOVER Hub, Chicago, IL.ORCID https://orcid.org/0000-0002-5344-118X
Sanjib BasuIllinois Research Network (ILLInet) RECOVER Hub, Chicago, IL.
Richard M NovakIllinois Research Network (ILLInet) RECOVER Hub, Chicago, IL.
Jeffrey R JacobsonIllinois Research Network (ILLInet) RECOVER Hub, Chicago, IL.
Balaji B GaneshIllinois Research Network (ILLInet) RECOVER Hub, Chicago, IL.
Martha CerdaIllinois Research Network (ILLInet) RECOVER Hub, Chicago, IL.
Hassan BrimDepartment of Medicine, Pathology, Surgery, and Cancer Center, Howard University College of Medicine, Washington, DC, USA.
Nathaniel B ErdmannDivision of Infectious Diseases, Department of Medicine, University of Alabama at Birmingham, USA.
Bruce D LevyPulmonary and Critical Care Medicine, Department of Internal Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Mass, USA.
Gailen D MarshallThe University of Mississippi Medical Center, Department of Internal Medicine, Division of Clinical Immunology, Jackson, Mississippi, USA.
Grace A McComseyCase Western Reserve University School of Medicine, Cleveland, Ohio.ORCID https://orcid.org/0000-0003-2690-8888
Torri D MetzDepartment of Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, University of Utah Health, Salt Lake City, UT, USA.
Megumi J OkumuraDepartment of Medicine, University of California San Francisco, CA, USA.
Michael J PelusoDivision of HIV, Infectious Diseases, and Global Medicine University of California, San Francisco, San Francisco, CA, USA.ORCID https://orcid.org/0000-0003-0585-6230
Tiffany WalkerDepartment of Medicine, Emory University, Atlanta, Georgia, USA.
Paul J UtzDivision of Immunology and Rheumatology, Department of Medicine, Stanford, CA, USA.ORCID https://orcid.org/0000-0003-1181-1565
Jerry A KrishnanIllinois Research Network (ILLInet) RECOVER Hub, Chicago, IL.
Bellur S PrabhakarIllinois Research Network (ILLInet) RECOVER Hub, Chicago, IL.ORCID https://orcid.org/0000-0001-9815-9850
Jalees RehmanDepartment of Biochemistry and Molecular Genetics, University of Illinois, College of Medicine, Chicago, IL, USA.ORCID https://orcid.org/0000-0002-2787-9292

Funding

OTA-21-015A Post-Acute Sequelae of SARS-CoV-2 Infection Initiative: NYU Langone Health Clinical Science Core, Data Resource Core, and PASC Biorepository CoreOT2HL161847 · NHLBI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI GROSS, RACHEL SHARON, HORWITZ, LEORA · 2021 to 2025
$651.0M
Clinical and Translational Science Collaborative of Northern Ohio, Catalyzing Linkages to Equity in Health (CLE Health)UM1TR004528 · NCATS · CASE WESTERN RESERVE UNIVERSITY · PI GRACE A MCCOMSEY · 2023 to 2026
$32.1M
NCATS NIH HHS UM1 TR004528NHLBI NIH HHS OT2 HL161847
6 · The paper itself

Abstract

Long COVID (LC) or Post-Acute Sequelae of SARS-CoV-2 infection (PASC) syndrome represents a widespread health challenge that necessitates the development of novel diagnostic approaches and targeted therapies that can be readily deployed. Immune dysregulation has been reported as one of the hallmarks of LC, but the extent of LC immune dysregulation in patients over time remains unclear. We therefore assessed SARS-CoV-2-specific antibody responses, peripheral immune cell profiles, autoantibody profiles and circulating cytokines for up to 6 months in participants with a SARS-CoV-2 infection who either convalesced or developed LC. Compared to convalescent, LC participants with a broad range of LC phenotypes exhibited persistently elevated IgG titers for SARS-CoV-2 Envelope and Nucleocapsid proteins over the 6 months of study duration. In contrast, the IgG responses to Spike protein were significantly lower in the LC cohort with predominantly IgG1 and IgG3 class-switched bias. Using CyTOF analysis we show elevated numbers of circulating T follicular helper cells (cTFH) and mucosa-associated invariant T cells (MAIT), which also correlated with high anti-Envelope IgG titers. Persistent immune activation was accompanied by augmented serum cytokine profiles with LIF, IL-11, Eotaxin-3, and HMGB-1 in LC participants, who also demonstrated significantly higher rates of autoantibodies. These findings highlight the persistence of immune dysregulation in LC, underscoring the need to explore targeted therapies addressing viral persistence, dysregulated antibody production, and autoimmunity.

Identifiers

PMID41542038
PMCPMC12803341

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.