The immunology of long COVID

Nature reviews. Immunology, Journal Year: 2023, Volume and Issue: 23(10), P. 618 - 634

Published: July 11, 2023

Language: Английский

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SARS-CoV-2 reservoir in post-acute sequelae of COVID-19 (PASC)

Nature Immunology, Journal Year: 2023, Volume and Issue: 24(10), P. 1616 - 1627

Published: Sept. 4, 2023

Language: Английский

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Multimodal Molecular Imaging Reveals Tissue-Based T Cell Activation and Viral RNA Persistence for Up to 2 Years Following COVID-19

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: July 31, 2023

ABSTRACT The etiologic mechanisms of post-acute medical morbidities and unexplained symptoms (Long COVID) following SARS-CoV-2 infection are incompletely understood. There is growing evidence that viral persistence immune dysregulation may play a major role. We performed whole-body positron emission tomography (PET) imaging in cohort 24 participants at time points ranging from 27 to 910 days acute using novel radiopharmaceutical agent, [ 18 F]F-AraG, highly selective tracer allows for anatomical quantitation activated T lymphocytes. Tracer uptake the COVID group, which included those with without Long symptoms, was significantly higher compared pre-pandemic controls many regions, including brain stem, spinal cord, bone marrow, nasopharyngeal hilar lymphoid tissue, cardiopulmonary tissues, gut wall. Although cell activation tended be imaged closer illness, increased up 2.5 years infection. observed cord wall associated presence symptoms. In addition, lung tissue persistent pulmonary Notably, these tissues also individuals COVID. Given high F]F-AraG detected gut, we obtained colorectal situ hybridization RNA immunohistochemical studies subset identified cellular rectosigmoid lamina propria all participants, 158 676 initial COVID-19 suggesting could long-term immunological perturbations.

Language: Английский

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Long COVID or Post-COVID-19 Condition: Past, Present and Future Research Directions

Microorganisms, Journal Year: 2023, Volume and Issue: 11(12), P. 2959 - 2959

Published: Dec. 11, 2023

The presence of symptoms after an acute SARS-CoV-2 infection (long-COVID) has become a worldwide healthcare emergency but remains underestimated and undertreated due to lack recognition the condition knowledge underlying mechanisms. In fact, prevalence post-COVID ranges from 50% during first months up 20% two-years after. This perspective review aimed map existing literature on identify gaps in guide global effort toward improved understanding long-COVID suggest future research directions. There is plethora symptomatology that can be COVID-19; however, today, there no clear classification definition this condition, termed or post-COVID-19 condition. heterogeneity led groups/clusters patients, which could exhibit different risk factors Viral persistence, long-lasting inflammation, immune dysregulation, autoimmune reactions, reactivation latent infections, endothelial dysfunction alteration gut microbiota have been proposed as potential mechanisms explaining complexity long-COVID. such equation, viral biology (e.g., re-infections, variants), host genetics, epigenetics) external vaccination) should also considered. These various will discussed current directions suggested.

Language: Английский

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Persistent symptoms after COVID-19 are not associated with differential SARS-CoV-2 antibody or T cell immunity

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Aug. 23, 2023

Among the unknowns in decoding pathogenesis of SARS-CoV-2 persistent symptoms Long Covid is whether there a contributory role abnormal immunity during acute infection. It has been proposed that consequence either an excessive or inadequate initial immune response. Here, we analyze humoral and cellular 86 healthcare workers with laboratory confirmed mild asymptomatic infection first wave. Symptom questionnaires allow stratification into those without for comparison. During period up to 18-weeks post-infection, observe no difference antibody responses spike RBD nucleoprotein, virus neutralization, T cell responses. Also, profile waning. Analysis at 1-year, after two vaccine doses, comparing without, again shows similar immunity. Thus, quantitative differences these measured parameters adaptive following are unlikely have contributed causality. ClinicalTrials.gov (NCT04318314).

Language: Английский

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Divergent adaptive immune responses define two types of long COVID

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: July 20, 2023

Background The role of adaptive immune responses in long COVID remains poorly understood, with contrasting hypotheses suggesting either an insufficient antiviral response or excessive associated inflammatory damage. To address this issue, we set to characterize humoral and CD4+ T cell patients prior SARS-CoV-2 vaccination. Methods Long who were seropositive (LC+, n=28) seronegative (LC-, n=23) by spike ELISA assay recruited based on (i) initial infection documented PCR the conjunction three major signs COVID-19 (ii) persistence resurgence at least 3 symptoms for over months. They compared resolved (RE, n=29) uninfected control individuals (HD, n=29). Results spectrum persistent proved similar both groups, a trend higher number group (median=6 vs 4.5; P=0.01). use highly sensitive S-flow enabled detection low levels spike-specific IgG 22.7% ELISA-seronegative (LC-) patients. In contrast, uniformly high LC+ RE groups. Multiplexed antibody analyses 30 different viral antigens showed that LC- had defective all proteins tested but most cases preserved other viruses. A primary line revealed detectable SARS-CoV-2-specific CD4 39.1% patients, while frequencies Correlation overall strong associations between cellular responses, exceptions group. Conclusions These findings provide evidence two types COVID. Seropositive coordinated as those recovered specific cells and/or antibodies close half (52.2%). divergent sharing comparable raise possibility multiple etiologies

Language: Английский

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Inflammation and Epstein–Barr Virus at the Crossroads of Multiple Sclerosis and Post-Acute Sequelae of COVID-19 Infection

Viruses, Journal Year: 2023, Volume and Issue: 15(4), P. 949 - 949

Published: April 12, 2023

Recent studies have strengthened the evidence for Epstein-Barr Virus (EBV) as an important contributing factor in development of multiple sclerosis (MS). Chronic inflammation is a key feature MS. EBV

Language: Английский

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A pilot study on the immune cell proteome of long COVID patients shows changes to physiological pathways similar to those in myalgic encephalomyelitis/chronic fatigue syndrome

Scientific Reports, Journal Year: 2023, Volume and Issue: 13(1)

Published: Dec. 12, 2023

Of those infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), ~ 10% develop the chronic post-viral debilitating condition, long COVID (LC). Although LC is a heterogeneous about half of cases have typical fatigue onset and symptoms that are very similar to myalgic encephalomyelitis/chronic (ME/CFS). A key question whether these conditions closely related. ME/CFS post-stressor condition arises from multiple triggers. To investigate pathophysiology LC, pilot study patients (n = 6) healthy controls 5) has used quantitative proteomics discover changes in peripheral blood mononuclear cell (PBMC) proteins. principal component analysis separated all controls. Analysis 3131 proteins identified 162 differentially regulated, which 37 were related immune functions, 21 mitochondrial functions. Markov cluster clusters involved system processes, two aspects gene expression-spliceosome transcription. These results compared an earlier dataset 346 regulated PBMC's 9) analysed by same methodology. There overlapping protein enriched molecular pathways particularly suggesting as prominent feature, functions energy production affected both conditions.

Language: Английский

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Systemic immune profiling of Omicron-infected subjects inoculated with different doses of inactivated virus vaccine

Cell, Journal Year: 2023, Volume and Issue: 186(21), P. 4615 - 4631.e16

Published: Sept. 27, 2023

SARS-CoV-2 primary strain-based vaccination exerts a protective effect against Omicron variants-initiated infection, symptom occurrence, and disease severity in booster-dependent manner. Yet, the underlying mechanisms remain unclear. During 2022 outbreak Shanghai, we enrolled 122 infected adults 50 uninfected controls who had been unvaccinated or vaccinated with two three doses of COVID-19 inactive vaccines performed integrative analysis 41-plex CyTOF, RNA-seq, Olink on their peripheral blood samples. The frequencies HLA-DRhi classical monocytes, non-classical Th1-like Tem tended to increase, whereas frequency Treg was reduced by booster vaccine, they influenced occurrence vaccine dose-dependent Intercorrelation mechanistic suggested that induced monocytic training, which would prime activation maturation rather than differentiating into myeloid-derived suppressive cells upon infections. Overall, our study provides insights how elaborates immunity across variants.

Language: Английский

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Long COVID: Molecular Mechanisms and Detection Techniques

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 25(1), P. 408 - 408

Published: Dec. 28, 2023

Long COVID, also known as post-acute sequelae of SARS-CoV-2 infection (PASC), has emerged a significant health concern following the COVID-19 pandemic. Molecular mechanisms underlying occurrence and progression long COVID include viral persistence, immune dysregulation, endothelial dysfunction, neurological involvement, highlight need for further research to develop targeted therapies this condition. While clearer picture clinical symptomatology is shaping, many molecular are yet be unraveled, given their complexity high level interaction with other metabolic pathways. This review summarizes some most important symptoms associated that occur in well relevant techniques can used understanding pathogen, its affinity towards host, possible outcomes host-pathogen interaction.

Language: Английский

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