Nirmatrelvir-Ritonavir and Symptoms in Adults With Postacute Sequelae of SARS-CoV-2 Infection DOI Creative Commons
Linda N. Geng, Hector Bonilla, Haley Hedlin

et al.

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

Long COVID: major findings, mechanisms and recommendations DOI Open Access
Hannah Davis, Lisa McCorkell, Julia Moore Vogel

et al.

Nature Reviews Microbiology, Journal Year: 2023, Volume and Issue: 21(3), P. 133 - 146

Published: Jan. 13, 2023

Language: Английский

Citations

2794
Distinguishing features of long COVID identified through immune profiling DOI Creative Commons
Jon Klein, Jamie Wood, Jillian R. Jaycox

et al.

Nature, Journal Year: 2023, Volume and Issue: 623(7985), P. 139 - 148

Published: Sept. 25, 2023

Abstract Post-acute infection syndromes may develop after acute viral disease 1 . Infection with SARS-CoV-2 can result in the development of a post-acute syndrome known as long COVID. Individuals COVID frequently report unremitting fatigue, post-exertional malaise, and variety cognitive autonomic dysfunctions 2–4 However, biological processes that are associated persistence these symptoms unclear. Here 275 individuals or without were enrolled cross-sectional study included multidimensional immune phenotyping unbiased machine learning methods to identify features Marked differences noted circulating myeloid lymphocyte populations relative matched controls, well evidence exaggerated humoral responses directed against among participants Furthermore, higher antibody non-SARS-CoV-2 pathogens observed COVID, particularly Epstein–Barr virus. Levels soluble mediators hormones varied groups, cortisol levels being lower Integration data into models identified key most strongly status. Collectively, findings help guide future studies pathobiology developing relevant biomarkers.

Language: Английский

Citations

458
The neurobiology of long COVID DOI Creative Commons
Michelle Monje, Akiko Iwasaki

Neuron, Journal Year: 2022, Volume and Issue: 110(21), P. 3484 - 3496

Published: Oct. 7, 2022

Persistent neurological and neuropsychiatric symptoms affect a substantial fraction of people after COVID-19 represent major component the post-acute syndrome, also known as long COVID. Here, we review what is understood about pathobiology impact on CNS discuss possible neurobiological underpinnings cognitive affecting survivors. We propose chief mechanisms that may contribute to this emerging health crisis.

Language: Английский

Citations

299
The immunology of long COVID DOI Open Access
Daniel M. Altmann, Emily M. Whettlock, Siyi Liu

et al.

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

Published: July 11, 2023

Language: Английский

Citations

265
Serotonin reduction in post-acute sequelae of viral infection DOI Creative Commons
Andrea C. Wong, Ashwarya S. Devason,

Iboro C. Umana

et al.

Cell, Journal Year: 2023, Volume and Issue: 186(22), P. 4851 - 4867.e20

Published: Oct. 1, 2023

Post-acute sequelae of COVID-19 (PASC, "Long COVID") pose a significant global health challenge. The pathophysiology is unknown, and no effective treatments have been found to date. Several hypotheses formulated explain the etiology PASC, including viral persistence, chronic inflammation, hypercoagulability, autonomic dysfunction. Here, we propose mechanism that links all four in single pathway provides actionable insights for therapeutic interventions. We find PASC are associated with serotonin reduction. Viral infection type I interferon-driven inflammation reduce through three mechanisms: diminished intestinal absorption precursor tryptophan; platelet hyperactivation thrombocytopenia, which impacts storage; enhanced MAO-mediated turnover. Peripheral reduction, turn, impedes activity vagus nerve thereby impairs hippocampal responses memory. These findings provide possible explanation neurocognitive symptoms persistence Long COVID, may extend other post-viral syndromes.

Language: Английский

Citations

222
SARS-CoV-2 reservoir in post-acute sequelae of COVID-19 (PASC) DOI Open Access
Amy D. Proal, Michael B. VanElzakker, Soo Aleman

et al.

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

Published: Sept. 4, 2023

Language: Английский

Citations

183
ME/CFS and Long COVID share similar symptoms and biological abnormalities: road map to the literature DOI Creative Commons
Anthony L. Komaroff, W. Ian Lipkin

Frontiers in Medicine, Journal Year: 2023, Volume and Issue: 10

Published: June 2, 2023

Some patients remain unwell for months after "recovering" from acute COVID-19. They develop persistent fatigue, cognitive problems, headaches, disrupted sleep, myalgias and arthralgias, post-exertional malaise, orthostatic intolerance other symptoms that greatly interfere with their ability to function can leave some people housebound disabled. The illness (Long COVID) is similar myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) as well persisting illnesses follow a wide variety of infectious agents following major traumatic injury. Together, these are projected cost the U.S. trillions dollars. In this review, we first compare ME/CFS Long COVID, noting considerable similarities few differences. We then in extensive detail underlying pathophysiology two conditions, focusing on abnormalities central autonomic nervous system, lungs, heart, vasculature, immune gut microbiome, energy metabolism redox balance. This comparison highlights how strong evidence each abnormality, illness, helps set priorities future investigation. review provides current road map literature biology both illnesses.

Language: Английский

Citations

180
Muscle abnormalities worsen after post-exertional malaise in long COVID DOI Creative Commons
Brent Appelman, Braeden T. Charlton, Richie P. Goulding

et al.

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

Published: Jan. 4, 2024

A subgroup of patients infected with SARS-CoV-2 remain symptomatic over three months after infection. distinctive symptom long COVID is post-exertional malaise, which associated a worsening fatigue- and pain-related symptoms acute mental or physical exercise, but its underlying pathophysiology unclear. With this longitudinal case-control study (NCT05225688), we provide new insights into the malaise in COVID. We show that skeletal muscle structure lower exercise capacity patients, local systemic metabolic disturbances, severe exercise-induced myopathy tissue infiltration amyloid-containing deposits muscles worsen induction malaise. This highlights novel pathways help to understand suffering from other post-infectious diseases.

Language: Английский

Citations

164
Viral persistence, reactivation, and mechanisms of long COVID DOI Creative Commons
Benjamin K. Chen,

Boris Jülg,

Sindhu Mohandas

et al.

eLife, Journal Year: 2023, Volume and Issue: 12

Published: May 4, 2023

The COVID-19 global pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has infected hundreds of millions individuals. Following infection, a subset can develop wide range chronic symptoms affecting diverse organ systems referred to as post-acute sequelae SARS-CoV-2 (PASC), also known long COVID. A National Institutes Health-sponsored initiative, RECOVER: Researching COVID Enhance Recovery, sought understand basis in large cohort. Given that occur COVID, mechanisms may underlie these be diverse. In this review, we focus on emerging literature supporting role(s) viral persistence or reactivation viruses play PASC. Persistence RNA antigens is reported some organs, yet mechanism which they do so and how associated with pathogenic immune responses unclear. Understanding RNA, antigen other reactivated relate specific inflammatory drive PASC provide rationale for treatment.

Language: Английский

Citations

144
SARS-CoV-2 Spike protein induces TLR4-mediated long-term cognitive dysfunction recapitulating post-COVID-19 syndrome in mice DOI Creative Commons
Fabrícia Lima Fontes-Dantas, Gabriel Gripp Fernandes,

Elisa Gouvea Gutman

et al.

Cell Reports, Journal Year: 2023, Volume and Issue: 42(3), P. 112189 - 112189

Published: Feb. 17, 2023

Cognitive dysfunction is often reported in patients with post-coronavirus disease 2019 (COVID-19) syndrome, but its underlying mechanisms are not completely understood. Evidence suggests that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Spike protein or fragments released from cells during infection, reaching different tissues, including the CNS, irrespective of presence viral RNA. Here, we demonstrate brain infusion mice has a late impact on cognitive function, recapitulating post-COVID-19 syndrome. We also show neuroinflammation and hippocampal microgliosis mediate Spike-induced memory via complement-dependent engulfment synapses. Genetic pharmacological blockage Toll-like receptor 4 (TLR4) signaling protects animals against synapse elimination induced by infusion. Accordingly, cohort 86 who recovered mild COVID-19, genotype GG TLR4-2604G>A (rs10759931) associated poor outcome. These results identify TLR4 as key target to investigate long-term after COVID-19 infection humans rodents.

Language: Английский

Citations

109