Precision symptom phenotyping identifies early clinical and proteomic predictors of distinct COVID-19 sequelae DOI Creative Commons
Nusrat J Epsi, Josh Chenoweth, Paul W. Blair

et al.

The Journal of Infectious Diseases, Journal Year: 2024, Volume and Issue: unknown

Published: June 25, 2024

Abstract Background Post-COVID conditions (PCC) are difficult to characterize, diagnose, predict, and treat due overlapping symptoms poorly understood pathology. Identifying inflammatory profiles may improve clinical prognostication trial endpoints. Methods This analysis included 1988 SARS-CoV-2 positive U.S. Military Health System beneficiaries who had quantitative post–COVID symptom scores. Among participants reported moderate-to-severe on surveys collected 6 months post-SARS-CoV-2 infection, principal component followed by k-means clustering identified distinct clusters of symptoms. Results Three symptom-based were identified: a sensory cluster (loss smell and/or taste), fatigue/difficulty thinking cluster, difficulty breathing/exercise intolerance cluster. Individuals within the all outpatients during their initial COVID-19 presentation. The breathing higher likelihood obesity hospitalization than those with no/mild at post-infection. Multinomial regression linked early post-infection D-dimer IL-1RA elevation elevated ICAM-1 concentrations Conclusions We three PCC phenotypes specific risk factors predictors. With further validation characterization, this framework allow more precise classification cases potentially diagnosis, prognostication, treatment PCC.

Language: Английский

Blood–brain barrier disruption and sustained systemic inflammation in individuals with long COVID-associated cognitive impairment DOI Creative Commons
Chris Greene, Ruairi Connolly,

Declan Brennan

et al.

Nature Neuroscience, Journal Year: 2024, Volume and Issue: 27(3), P. 421 - 432

Published: Feb. 22, 2024

Abstract Vascular disruption has been implicated in coronavirus disease 2019 (COVID-19) pathogenesis and may predispose to the neurological sequelae associated with long COVID, yet it is unclear how blood–brain barrier (BBB) function affected these conditions. Here we show that BBB evident during acute infection patients COVID cognitive impairment, commonly referred as brain fog. Using dynamic contrast-enhanced magnetic resonance imaging, COVID-associated Transcriptomic analysis of peripheral blood mononuclear cells revealed dysregulation coagulation system a dampened adaptive immune response individuals Accordingly, showed increased adhesion human endothelial vitro, while exposure serum from induced expression inflammatory markers. Together, our data suggest sustained systemic inflammation persistent localized dysfunction key feature

Language: Английский

Citations

159
Large-scale phenotyping of patients with long COVID post-hospitalization reveals mechanistic subtypes of disease DOI Creative Commons
Felicity Liew, Claudia Efstathiou, Sara Fontanella

et al.

Nature Immunology, Journal Year: 2024, Volume and Issue: 25(4), P. 607 - 621

Published: April 1, 2024

One in ten severe acute respiratory syndrome coronavirus 2 infections result prolonged symptoms termed long disease (COVID), yet phenotypes and mechanisms are poorly understood

Language: Английский

Citations

41
Mechanisms of long COVID and the path toward therapeutics DOI Creative Commons

Michael J. Peluso,

Steven G. Deeks

Cell, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 1, 2024

Language: Английский

Citations

32
Fibrin drives thromboinflammation and neuropathology in COVID-19 DOI Creative Commons
Jae Kyu Ryu, Zhaoqi Yan, Mauricio Montaño

et al.

Nature, Journal Year: 2024, Volume and Issue: 633(8031), P. 905 - 913

Published: Aug. 28, 2024

Abstract Life-threatening thrombotic events and neurological symptoms are prevalent in COVID-19 persistent patients with long COVID experiencing post-acute sequelae of SARS-CoV-2 infection 1–4 . Despite the clinical evidence 1,5–7 , underlying mechanisms coagulopathy its consequences inflammation neuropathology remain poorly understood treatment options insufficient. Fibrinogen, central structural component blood clots, is abundantly deposited lungs brains COVID-19, correlates disease severity a predictive biomarker for post-COVID-19 cognitive deficits 1,5,8–10 Here we show that fibrin binds to spike protein, forming proinflammatory clots drive systemic thromboinflammation COVID-19. Fibrin, acting through inflammatory domain, required oxidative stress macrophage activation lungs, whereas it suppresses natural killer cells, after infection. Fibrin promotes neuroinflammation neuronal loss infection, as well innate immune brain independently active A monoclonal antibody targeting domain provides protection from microglial injury, lung Thus, drives fibrin-targeting immunotherapy may represent therapeutic intervention acute COVID.

Language: Английский

Citations

24
The knowns and unknowns of long COVID-19: from mechanisms to therapeutical approaches DOI Creative Commons
Roxana Gheorghiţă, Iuliana Șoldănescu, Andrei Lobiuc

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: March 4, 2024

The coronavirus disease 2019 (COVID-19) pandemic caused by SARS-CoV-2 has been defined as the greatest global health and socioeconomic crisis of modern times. While most people recover after being infected with virus, a significant proportion them continue to experience issues weeks, months even years acute infection SARS-CoV-2. This persistence clinical symptoms in individuals for at least three onset or emergence new lasting more than two months, without any other explanation alternative diagnosis have named long COVID, long-haul post-COVID-19 conditions, chronic post-acute sequelae (PASC). Long COVID characterized constellation disorders that vary widely their manifestations. Further, mechanisms underlying are not fully understood, which hamper efficient treatment options. review describes predictors common related COVID's effects on central peripheral nervous system organs tissues. Furthermore, transcriptional markers, molecular signaling pathways risk factors such sex, age, pre-existing condition, hospitalization during phase COVID-19, vaccination, lifestyle presented. Finally, recommendations patient rehabilitation management, well therapeutical approaches discussed. Understanding complexity this disease, its across multiple organ systems overlapping pathologies possible paramount developing diagnostic tools treatments.

Language: Английский

Citations

23
Sepsis-trained macrophages promote antitumoral tissue-resident T cells DOI

Alexis Broquet,

Victor Gourain, Thomas Goronflot

et al.

Nature Immunology, Journal Year: 2024, Volume and Issue: 25(5), P. 802 - 819

Published: April 29, 2024

Language: Английский

Citations

18
Cognitive and psychiatric symptom trajectories 2–3 years after hospital admission for COVID-19: a longitudinal, prospective cohort study in the UK DOI Creative Commons
Maxime Taquet,

Zuzanna Skórniewska,

Thomas De Deyn

et al.

The Lancet Psychiatry, Journal Year: 2024, Volume and Issue: 11(9), P. 696 - 708

Published: July 31, 2024

Language: Английский

Citations

18
Early biological markers of post-acute sequelae of SARS-CoV-2 infection DOI Creative Commons

Scott Lu,

Michael J. Peluso, David V. Glidden

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Aug. 29, 2024

To understand the roles of acute-phase viral dynamics and host immune responses in post-acute sequelae SARS-CoV-2 infection (PASC), we enrolled 136 participants within 5 days their first positive real-time PCR test. Participants self-collected up to 21 nasal specimens 28 post-symptom onset; interviewer-administered questionnaires blood samples were collected at enrollment, 9, 14, 21, 28, month 4 8 onset. Defining PASC as presence any COVID-associated symptom 4-month visit, compared markers (quantity duration RNA load, infectious plasma N-antigen level) (IL-6, IL-10, TNF-α, IFN-α, IFN-γ, MCP, IP-10, Spike IgG) over acute period. Compared those who fully recovered, reporting demonstrated significantly higher maximum levels N-antigen, burden shedding, lower Spike-specific IgG 9 post-illness No significant differences identified among a panel markers. Our results suggest early associated play role pathogenesis PASC, highlighting importance understanding biological natural history PASC.

Language: Английский

Citations

13
Prolonged exposure to lung-derived cytokines is associated with activation of microglia in patients with COVID-19 DOI Creative Commons
Rogan A. Grant, Taylor A. Poor, Lango Sichizya

et al.

JCI Insight, Journal Year: 2024, Volume and Issue: unknown

Published: March 19, 2024

BACKGROUNDSurvivors of pneumonia, including SARS-CoV-2 are at increased risk for cognitive dysfunction and dementia. In rodent models, following pneumonia has been linked to the systemic release lung-derived pro-inflammatory cytokines. Microglia poised respond inflammatory signals from circulation, their impairment in murine models dementia humans.METHODSWe measured levels 55 cytokines chemokines bronchoalveolar lavage fluid plasma 341 patients with respiratory failure 13 healthy controls, 93 unvaccinated COVID-19 203 other causes pneumonia. We used flow cytometry sort neuroimmune cells postmortem brain tissue 5 who died 3 single-cell RNA-sequencing.RESULTSMicroglia exhibited a transcriptomic signature suggestive activation by circulating Peak were similar irrespective etiology, but cumulative cytokine exposure was higher COVID-19. Treatment corticosteroids reduced expression COVID-19-specific cytokines.CONCLUSIONProlonged lung inflammation results sustained elevations compared those secondary pathogens. exhibit transcriptional responses These findings support data causally linking further investigation into role microglia pneumonia-related dysfunction.FUNDINGSCRIPT U19AI135964, UL1TR001422, P01AG049665, P01HL154998, R01HL149883, R01LM013337, R01HL153122, R01HL147290, R01HL147575, R01HL158139, R01ES034350, R01ES027574, I01CX001777, U01TR003528, R21AG075423, T32AG020506, F31AG071225, T32HL076139.

Language: Английский

Citations

12
Unraveling Links between Chronic Inflammation and Long COVID: Workshop Report DOI Open Access
Pushpa Tandon, Natalie Abrams, Leela Rani Avula

et al.

The Journal of Immunology, Journal Year: 2024, Volume and Issue: 212(4), P. 505 - 512

Published: Feb. 5, 2024

As COVID-19 continues, an increasing number of patients develop long COVID symptoms varying in severity that last for weeks, months, or longer. Symptoms commonly include lingering loss smell and taste, hearing loss, extreme fatigue, "brain fog." Still, persistent cardiovascular respiratory problems, muscle weakness, neurologic issues have also been documented. A major problem is the lack clear guidelines diagnosing COVID. Although some studies suggest due to prolonged inflammation after SARS-CoV-2 infection, underlying mechanisms remain unclear. The broad range COVID-19's bodily effects responses initial viral infection are poorly understood. This workshop brought together multidisciplinary experts showcase discuss latest research on chronic might be associated with sequelae following infection.

Language: Английский

Citations

11