Multiple early factors anticipate post-acute COVID-19 sequelae

Cell, Journal Year: 2022, Volume and Issue: 185(5), P. 881 - 895.e20

Published: Jan. 25, 2022

Post-acute sequelae of COVID-19 (PASC) represent an emerging global crisis. However, quantifiable risk factors for PASC and their biological associations are poorly resolved. We executed a deep multi-omic, longitudinal investigation 309 patients from initial diagnosis to convalescence (2-3 months later), integrated with clinical data patient-reported symptoms. resolved four PASC-anticipating at the time diagnosis: type 2 diabetes, SARS-CoV-2 RNAemia, Epstein-Barr virus viremia, specific auto-antibodies. In gastrointestinal PASC, SARS-CoV-2-specific CMV-specific CD8+ T cells exhibited unique dynamics during recovery COVID-19. Analysis symptom-associated immunological signatures revealed coordinated immunity polarization into endotypes, exhibiting divergent acute severity PASC. find that between diminish over time, leading distinct convalescent immune states. Detectability most emphasizes importance early disease measurements understanding emergent chronic conditions suggests treatment strategies.

Language: Английский

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SARS-CoV-2 infection in hamsters and humans results in lasting and unique systemic perturbations after recovery

Science Translational Medicine, Journal Year: 2022, Volume and Issue: 14(664)

Published: June 7, 2022

The host response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can result in prolonged pathologies collectively referred as post-acute sequalae of COVID-19 (PASC) or long COVID. To better understand the mechanism underlying COVID biology, we compared short- and long-term systemic responses golden hamster after either SARS-CoV-2 influenza A virus (IAV) infection. Results demonstrated that exceeded IAV its capacity cause permanent injury lung kidney uniquely affected olfactory bulb (OB) epithelium (OE). Despite a lack detectable infectious virus, OB OE myeloid T cell activation, proinflammatory cytokine production, an interferon correlated with behavioral changes extending month viral clearance. These sustained transcriptional could also be corroborated from tissue isolated individuals who recovered COVID-19. data highlight molecular for persistent symptomology provide small animal model explore future therapeutics.

Language: Английский

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Effect of Convalescent Plasma on Organ Support–Free Days in Critically Ill Patients With COVID-19

JAMA, Journal Year: 2021, Volume and Issue: 326(17), P. 1690 - 1690

Published: Oct. 5, 2021

Importance

The evidence for benefit of convalescent plasma critically ill patients with COVID-19 is inconclusive.

Objective

To determine whether would improve outcomes adults COVID-19.

Design, Setting, and Participants

ongoing Randomized, Embedded, Multifactorial, Adaptive Platform Trial Community-Acquired Pneumonia (REMAP-CAP) enrolled randomized 4763 suspected or confirmed between March 9, 2020, January 18, 2021, within at least 1 domain; 2011 were to open-label interventions in the immunoglobulin domain 129 sites 4 countries. Follow-up ended on April 19, 2021.

Interventions

participants receive 2 units high-titer, ABO-compatible (total volume 550 mL ± 150 mL) 48 hours randomization (n = 1084) no 916).

Main Outcomes Measures

primary ordinal end point was organ support–free days (days alive free intensive care unit–based support) up day 21 (range, −1 days; who died assigned –1 day). analysis an adjusted bayesian cumulative logistic model. Superiority defined as posterior probability odds ratio (OR) greater than (threshold trial conclusion superiority >99%). Futility OR less 1.2 futility >95%). An represented improved survival, more days, both. prespecified secondary included in-hospital survival; 28-day 90-day respiratory cardiovascular progression invasive mechanical ventilation, extracorporeal oxygenation, death; unit length stay; hospital World Health Organization scale score 14; venous thromboembolic events 90 serious adverse events.

Results

Among (median age, 61 [IQR, 52 70] years 645/1998 [32.3%] women), 1990 (99%) completed trial. intervention stopped after criterion met. median number 0 (IQR, 16) group 3 group. mortality rate 37.3% (401/1075) 38.4% (347/904) support 14 18) 7 18), respectively. median-adjusted 0.97 (95% credible interval, 0.83 1.15) (OR <1.2) 99.4% compared treatment effects consistent across outcome 11 outcomes. Serious reported 3.0% (32/1075) 1.3% (12/905)

Conclusions Relevance

COVID-19, had a low likelihood providing improvement days.

Trial Registration

ClinicalTrials.gov Identifier:NCT02735707

Language: Английский

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Humoral Innate Immunity and Acute-Phase Proteins

New England Journal of Medicine, Journal Year: 2023, Volume and Issue: 388(5), P. 439 - 452

Published: Feb. 1, 2023

Language: Английский

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SARS-CoV-2-specific T cells in infection and vaccination

Cellular and Molecular Immunology, Journal Year: 2021, Volume and Issue: 18(10), P. 2307 - 2312

Published: Sept. 1, 2021

During viral infections, antibodies and T cells act together to prevent pathogen spread remove virus-infected cells. Virus-specific adaptive immunity can, however, also trigger pathological processes characterized by localized or systemic inflammatory events. The protective and/or role of virus-specific in SARS-CoV-2 infection has been the focus many studies COVID-19 patients vaccinated individuals. Here, we review works that have elucidated function SARS-CoV-2-specific Understanding whether are more linked protection pathogenesis is pivotal define future therapeutic prophylactic strategies manage current pandemic.

Language: Английский

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Post-acute sequelae of COVID-19: understanding and addressing the burden of multisystem manifestations

The Lancet Respiratory Medicine, Journal Year: 2023, Volume and Issue: 11(8), P. 739 - 754

Published: July 17, 2023

Individuals with SARS-CoV-2 infection can develop symptoms that persist well beyond the acute phase of COVID-19 or emerge after phase, lasting for weeks months initial illness. The post-acute sequelae COVID-19, which include physical, cognitive, and mental health impairments, are known collectively as long COVID post-COVID-19 condition. substantial burden this multisystem condition is felt at individual, health-care system, socioeconomic levels, on an unprecedented scale. Survivors COVID-19-related critical illness risk respiratory distress syndrome, sepsis, chronic illness, these multidimensional morbidities might be difficult to differentiate from specific effects COVID-19. We provide overview manifestations in adults. explore various organ systems, describe potential pathophysiological mechanisms, consider challenges providing clinical care support survivors manifestations. Research needed reduce incidence optimise therapeutic rehabilitative patients.

Language: Английский

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Severe Acute Respiratory Syndrome Coronavirus 2 Viremia Is Associated With Coronavirus Disease 2019 Severity and Predicts Clinical Outcomes

Clinical Infectious Diseases, Journal Year: 2021, Volume and Issue: 74(9), P. 1525 - 1533

Published: Aug. 9, 2021

Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral RNA (vRNA) is detected in the bloodstream of some patients with disease 2019 (COVID-19), but it not clear whether this RNAemia reflects viremia (ie, virus particles) and how relates to host immune responses outcomes. Methods SARS-CoV-2 vRNA was quantified plasma samples from observational cohorts 51 COVID-19 including 9 outpatients, 19 hospitalized (non–intensive care unit [ICU]), 23 ICU patients. levels were compared cross-sectional indices severity prospective clinical We used multiple imaging methods visualize virions plasma. Results 100%, 52.6%, 11.1% ICU, non-ICU, respectively. Virions pellets using electron tomography immunostaining. Plasma significantly higher &gt; non-ICU outpatients (P &lt; .0001); for inpatients, strongly associated World Health Organization (WHO) score at admission = .01), maximum WHO .002), discharge disposition .004). A level &gt;6000 copies/mL mortality (hazard ratio, 10.7). Levels several inflammatory biomarkers .01) neutralizing antibody titers .8). Conclusions Visualization particles indicates that due, least part, viremia. The correlate severity, patient outcome, specific titers.

Language: Английский

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Immune response in COVID-19: what is next?

Cell Death and Differentiation, Journal Year: 2022, Volume and Issue: 29(6), P. 1107 - 1122

Published: May 17, 2022

Abstract The coronavirus disease 2019 (COVID-19) has been a global pandemic for more than 2 years and it still impacts our daily lifestyle quality in unprecedented ways. A better understanding of immunity its regulation response to SARS-CoV-2 infection is urgently needed. Based on the current literature, we review here various virus mutations evolving manifestations along with alterations immune responses specific focuses innate response, neutrophil extracellular traps, humoral immunity, cellular immunity. Different types vaccines were compared analyzed based their unique properties elicit Various therapeutic strategies such as antibody, anti-viral medications inflammation control discussed. We predict that available continuously emerging new technologies, powerful administration schedules, effective public health measures, COVID-19 will be under near future.

Language: Английский

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SARS-CoV-2 viremia is associated with distinct proteomic pathways and predicts COVID-19 outcomes

Journal of Clinical Investigation, Journal Year: 2021, Volume and Issue: 131(13)

Published: June 30, 2021

BACKGROUND. SARS-CoV-2 plasma viremia has been associated with severe disease and death in COVID-19 small-scale cohort studies. The mechanisms behind this association remain elusive.

Language: Английский

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Persistent post–COVID-19 smell loss is associated with immune cell infiltration and altered gene expression in olfactory epithelium

Science Translational Medicine, Journal Year: 2022, Volume and Issue: 14(676)

Published: Dec. 21, 2022

SARS-CoV-2 causes profound changes in the sense of smell, including total smell loss. Although these alterations are often transient, many patients with COVID-19 exhibit olfactory dysfunction that lasts months to years. animal and human autopsy studies have suggested mechanisms driving acute anosmia, it remains unclear how persistent loss a subset patients. To address this question, we analyzed epithelial samples collected from 24 biopsies, nine objectively quantified long-term after COVID-19. This biopsy-based approach revealed diffuse infiltrate T cells expressing interferon-γ shift myeloid cell population composition, enrichment CD207+ dendritic depletion anti-inflammatory M2 macrophages. Despite absence detectable RNA or protein, gene expression barrier supporting epithelium, termed sustentacular cells, appeared reflect response ongoing inflammatory signaling, which was accompanied by reduction number sensory neurons relative cells. These findings indicate cell-mediated inflammation persists epithelium long has been eliminated tissue, suggesting mechanism for post-COVID-19

Language: Английский

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