Nirmatrelvir-Ritonavir and Symptoms in Adults With Postacute Sequelae of SARS-CoV-2 Infection

JAMA Internal Medicine, Journal Year: 2024, Volume and Issue: 184(9), P. 1024 - 1024

Published: June 7, 2024

Importance There is an urgent need to identify treatments for postacute sequelae of SARS-CoV-2 infection (PASC). Objective To assess the efficacy a 15-day course nirmatrelvir-ritonavir in reducing severity select PASC symptoms. Design, Setting, and Participants This was 15-week blinded, placebo-controlled, randomized clinical trial conducted from November 2022 September 2023 at Stanford University (California). The participants were adults with moderate severe symptoms 3 months or longer duration. Interventions 2:1 treatment oral (NMV/r, 300 mg 100 mg) placebo-ritonavir (PBO/r) twice daily 15 days. Main Outcomes Measures Primary outcome pooled 6 (fatigue, brain fog, shortness breath, body aches, gastrointestinal symptoms, cardiovascular symptoms) based on Likert scale score 10 weeks. Secondary outcomes included symptom different time points, burden relief, patient global measures, Patient-Reported Measurement Information System (PROMIS) orthostatic vital signs, sit-to-stand test change baseline. Results Of 155 (median [IQR] age, 43 [34-54] years; 92 [59%] females), 102 NMV/r group 53 PBO/r group. Nearly all (n = 153) had received primary series COVID-19 vaccination. Mean (SD) between index randomization 17.5 (9.1) months. no statistically significant difference model-derived across core weeks groups. No between-group differences found Patient Global Impression Severity Change scores, summative baseline PROMIS fatigue, dyspnea, cognitive function, physical function measures. Adverse event rates similar groups mostly low grade. Conclusions Relevance results this showed that population patients generally safe but did not demonstrate benefit improving vaccinated cohort protracted Further studies are needed determine role antivirals PASC. Trial Registration ClinicalTrials.gov Identifier: NCT05576662

Language: Английский

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Characterizing Long COVID in Children and Adolescents

JAMA, Journal Year: 2024, Volume and Issue: 332(14), P. 1174 - 1174

Published: Aug. 21, 2024

Most research to understand postacute sequelae of SARS-CoV-2 infection (PASC), or long COVID, has focused on adults, with less known about this complex condition in children. Research is needed characterize pediatric PASC enable studies underlying mechanisms that will guide future treatment.

Language: Английский

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Long COVID in pediatrics—epidemiology, diagnosis, and management

European Journal of Pediatrics, Journal Year: 2024, Volume and Issue: 183(4), P. 1543 - 1553

Published: Jan. 27, 2024

Abstract This review summarizes current knowledge on post-acute sequelae of COVID-19 (PASC) and post-COVID-19 condition (PCC) in children adolescents. A literature was performed to synthesize information from clinical studies, expert opinions, guidelines. PASC also termed Long COVID — at any age comprise a plethora unspecific symptoms present later than 4 weeks after confirmed or probable infection with severe respiratory syndrome corona virus type 2 (SARS-CoV-2), without another medical explanation. PCC adolescents defined by the WHO as occurring within 3 months acute coronavirus disease 2019 (COVID-19), lasting least months, limiting daily activities. Pediatric mostly manifest mild courses majority cases remit few months. However, can last for more 1 year may result significant disability. Frequent include fatigue, exertion intolerance, anxiety. Some patients postural tachycardia (PoTS), small number fulfill criteria myalgic encephalomyelitis/chronic fatigue (ME/CFS). To date, no diagnostic marker has been established, differential diagnostics remains challenging. Therapeutic approaches appropriate self-management well palliation non-pharmaceutical pharmaceutical strategies. Conclusion : pediatrics heterogenous severity duration. stepped, interdisciplinary, individualized approach is essential management. Current health care structures have be adapted, research extended meet psychosocial needs young people similar conditions. What Known: • Post-acute (COVID-19) lead activity limitation reduced quality life. belongs large group syndromes (PAIS). Specific biomarkers causal treatment options are not yet available. New: In February 2023, case definition post provided World Health Organization (WHO), indicating duration Interdisciplinary collaborations necessary established worldwide offer harmonized, multimodal diagnosis management PASC/PCC

Language: Английский

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Differentiation of Prior SARS-CoV-2 Infection and Postacute Sequelae by Standard Clinical Laboratory Measurements in the RECOVER Cohort

Annals of Internal Medicine, Journal Year: 2024, Volume and Issue: 177(9), P. 1209 - 1221

Published: Aug. 12, 2024

There are currently no validated clinical biomarkers of postacute sequelae SARS-CoV-2 infection (PASC).

Language: Английский

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COVID-19 influenced gut dysbiosis, post-acute sequelae, immune regulation, and therapeutic regimens

Frontiers in Cellular and Infection Microbiology, Journal Year: 2024, Volume and Issue: 14

Published: May 28, 2024

The novel coronavirus disease 2019 (COVID-19) pandemic outbreak caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has garnered unprecedented global attention. It over 2.47 million deaths through various syndromes such as distress, hypercoagulability, and multiple organ failure. viral invasion proceeds the ACE2 receptor, expressed in cell types, some patients serious damage to tissues, organs, immune cells, microbes that colonize gastrointestinal tract (GIT). Some who survived SARS-CoV-2 infection have developed months of persistent long-COVID-19 symptoms or post-acute sequelae COVID-19 (PASC). Diagnosis these revealed biological effects, none which are mutually exclusive. However, severity also depends on numerous comorbidities obesity, age, diabetes, hypertension care must be taken with respect other morbidities, host immunity. Gut microbiota relation immunopathology is considered evolve progression via mechanisms biochemical metabolism, exacerbation inflammation, intestinal mucosal secretion, cytokine storm, immunity regulation. Therefore, modulation gut microbiome equilibrium food supplements probiotics remains a hot topic current research debate. In this review, we discuss complications physio-pathological effects infection, GIT response, therapeutic pharmacological strategies. We summarize targets probiotics, their limitations, efficacy preclinical clinical drugs effectively inhibit spread SARS-CoV-2.

Language: Английский

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Identification of an immunological signature of long COVID syndrome

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 8, 2025

Acute COVID-19 infection causes significant alterations in the innate and adaptive immune systems. While most individuals recover naturally, some develop long COVID (LC) syndrome, marked by persistent or new symptoms weeks to months after SARS-CoV-2 infection. Despite its prevalence, there are no clinical tests distinguish LC patients from those fully recovered. Understanding immunological basis of is essential for improving diagnostic treatment approaches. We performed deep immunophenotyping functional assays examine profiles patients, with active COVID-19, recovered healthy donors. This analysis assessed both features, identifying potential biomarkers syndrome. A Binomial Generalized Linear Model (BGLM) was used pinpoint features characterizing LC. exhibited depletion cell subsets, including plasmacytoid conventional dendritic cells, classical, non-classical, intermediate monocytes, monocyte-derived inflammatory cells. Elevated basal inflammation observed compared whose were closer donors individuals. However, displayed alterations, reduced T subsets (CD4, CD8, Tregs) switched memory B similar patients. Through BGLM, a unique signature identified, featuring CD8 gd cells low proliferative capacity diminished expression activation homing receptors. The findings highlight associated characterized dysregulation. recovery comparable Recovered individuals, deficits populations evident, differentiating full recovery. These provide insights into pathogenesis may support development tools targeted therapies.

Language: Английский

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Neutrophil extracellular traps and long COVID

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

Published: Sept. 27, 2023

Post-acute COVID-19 sequelae, commonly known as long COVID, encompasses a range of systemic symptoms experienced by significant number survivors. The underlying pathophysiology COVID has become topic intense research discussion. While chronic inflammation in received considerable attention, the role neutrophils, which are most abundant all immune cells and primary responders to inflammation, been unfortunately overlooked, perhaps due their short lifespan. In this review, we discuss emerging neutrophil extracellular traps (NETs) persistent inflammatory response observed patients. We present early evidence linking persistence NETs pulmonary fibrosis, cardiovascular abnormalities, neurological dysfunction COVID. Several uncertainties require investigation future studies. These include mechanisms SARS-CoV-2 brings about sustained activation phenotypes after infection resolution; whether heterogeneity neutrophils seen acute persists into phase; presence autoantibodies can induce protect them from degradation; exert differential, organ-specific effects; specifically NET components contribute pathologies, such fibrosis; senescent drive formation through pro-inflammatory secretome Answering these questions may pave way for development clinically applicable strategies targeting NETs, providing relief health crisis.

Language: Английский

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Early immune factors associated with the development of post-acute sequelae of SARS-CoV-2 infection in hospitalized and non-hospitalized individuals

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

Published: Jan. 22, 2024

Infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can lead to post-acute sequelae of SARS-CoV-2 (PASC) that persist for weeks years following initial viral infection. Clinical manifestations PASC are heterogeneous and often involve multiple organs. While many hypotheses have been made on the mechanisms its associated symptoms, biological drivers still unknown. We enrolled 494 patients with COVID-19 at their presentation a hospital or clinic followed them longitudinally determine development PASC. From 341 patients, we conducted multi-omic profiling peripheral blood samples collected shortly after study enrollment investigate early immune signatures During first week COVID-19, observed large number differences in profile individuals who were hospitalized compared those not hospitalized. Differences between did later develop were, comparison, more limited, but included significant autoantibodies epigenetic transcriptional double-negative 1 B cells, particular. found indicators incident nuanced, molecular signals manifesting predominantly robust hospitalization during COVID-19. The emerging cell phenotypes, especially highlight potentially important role these cells

Language: Английский

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Coronavirus disease 2019 (COVID-19) pandemic and autoimmune rheumatic diseases: Outcomes and prospects

Rheumatology Science and Practice, Journal Year: 2024, Volume and Issue: 62(1), P. 32 - 54

Published: Feb. 29, 2024

The pandemic of coronavirus disease 2019 (COVID-19), etiologically related to the SARS-CoV-2 virus (severe acute respiratory syndrome coronavirus-2), has drawn attention new clinical and fundamental problems in immunopathology human diseases associated with virus-induced autoimmunity autoinflammation. provision that “the experience gained rheumatology process studying pathogenetic mechanisms pharmacotherapy immunoinflammatory rheumatic as most common severe forms autoimmune autoinflammatory pathology humans will be demand for deciphering nature pathological processes underlying COVID-19 developing approaches effective pharmacotherapy” was confirmed numerous studies conducted over next 3 years midst pandemic. main focus on a critical analysis data regarding role inflammation, which basis pathogenesis immune-mediated context COVID-19.

Language: Английский

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Navigating the Post-COVID-19 Immunological Era: Understanding Long COVID-19 and Immune Response

Life, Journal Year: 2023, Volume and Issue: 13(11), P. 2121 - 2121

Published: Oct. 26, 2023

The COVID-19 pandemic has affected the world unprecedentedly, with both positive and negative impacts. significantly impacted immune system, understanding immunological consequences of is essential for developing effective treatment strategies. purpose this review to comprehensively explore provide insights into aspects long COVID-19, a phenomenon where individuals continue experience range symptoms complications, even after acute phase infection subsided. system responds initial by producing various cells molecules, including antibodies, T cells, cytokines. However, in some patients, response becomes dysregulated, leading chronic inflammation persistent symptoms. Long encompasses diverse affecting multiple organ systems, respiratory, cardiovascular, neurological, gastrointestinal systems. In post-COVID-19 era, its impact on have become significant concern. Post-COVID-19 pathology, autoimmunity immune-mediated disorders, also been reported patients. This provides an overview current relationship responses, pathology patient outcomes. Additionally, addresses potential treatments immunomodulatory therapies, rehabilitation programs, mental health support, all which aim improve quality life COVID-19. Understanding complex interplay between crucial targeted therapeutic strategies providing optimal care era.

Language: Английский

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