SARS-CoV-2 airway infection results in the development of somatosensory abnormalities in a hamster model DOI Creative Commons
Randal A. Serafini, Justin J. Frere, Jeffrey Zimering

et al.

Science Signaling, Journal Year: 2023, Volume and Issue: 16(784)

Published: May 9, 2023

Although largely confined to the airways, SARS-CoV-2 infection has been associated with sensory abnormalities that manifest in both acute and chronic phenotypes. To gain insight on molecular basis of these abnormalities, we used golden hamster model characterize compare effects influenza A virus (IAV) nervous system. We detected transcripts but no infectious material cervical thoracic spinal cord dorsal root ganglia (DRGs) within first 24 hours intranasal infection. SARS-CoV-2–infected hamsters exhibited mechanical hypersensitivity was milder prolonged compared observed IAV-infected hamsters. RNA sequencing analysis DRGs 1 4 days after suggested perturbations predominantly neuronal signaling animals as opposed type I interferon animals. Later, 31 infection, a neuropathic transcriptome emerged from animals, which coincided SARS-CoV-2–specific hypersensitivity. These data revealed potential targets for pain management, including binding protein ILF3, validated murine models. This work elucidates transcriptomic signatures triggered by may underlie short- long-term abnormalities.

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
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
Non-cell-autonomous disruption of nuclear architecture as a potential cause of COVID-19-induced anosmia DOI Creative Commons
Marianna Zazhytska, Albana Kodra, Daisy A. Hoagland

et al.

Cell, Journal Year: 2022, Volume and Issue: 185(6), P. 1052 - 1064.e12

Published: Feb. 2, 2022

Language: Английский

Citations

213
The neuroinvasiveness, neurotropism, and neurovirulence of SARS-CoV-2 DOI
Lisa Bauer, Brigitta M. Laksono, Femke M.S. de Vrij

et al.

Trends in Neurosciences, Journal Year: 2022, Volume and Issue: 45(5), P. 358 - 368

Published: March 3, 2022

Language: Английский

Citations

191
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

183
Innate immune evasion strategies of SARS-CoV-2 DOI Open Access
Judith M. Minkoff, Benjamin R. tenOever

Nature Reviews Microbiology, Journal Year: 2023, Volume and Issue: unknown

Published: Jan. 11, 2023

Language: Английский

Citations

167
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
Pathogenic mechanisms of post-acute sequelae of SARS-CoV-2 infection (PASC) DOI Creative Commons
Zaki A. Sherif, Christian R. Gómez, Thomas J. Connors

et al.

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

Published: March 22, 2023

COVID-19, with persistent and new onset of symptoms such as fatigue, post-exertional malaise, cognitive dysfunction that last for months impact everyday functioning, is referred to Long COVID under the general category post-acute sequelae SARS-CoV-2 infection (PASC). PASC highly heterogenous may be associated multisystem tissue damage/dysfunction including acute encephalitis, cardiopulmonary syndromes, fibrosis, hepatobiliary damages, gastrointestinal dysregulation, myocardial infarction, neuromuscular neuropsychiatric disorders, pulmonary damage, renal failure, stroke, vascular endothelial dysregulation. A better understanding pathophysiologic mechanisms underlying essential guide prevention treatment. This review addresses potential hypotheses connect long-term health consequences. Comparisons between other virus-initiated chronic syndromes myalgic encephalomyelitis/chronic fatigue syndrome postural orthostatic tachycardia will addressed. Aligning identifying potentially regulated common underlining pathways necessary true nature PASC. The discussed contributors include from injury one or more organs, reservoirs replicating virus its remnants in several tissues, re-activation latent pathogens Epstein-Barr herpes viruses COVID-19 immune-dysregulated environment, interactions host microbiome/virome communities, clotting/coagulation dysfunctional brainstem/vagus nerve signaling, dysautonomia autonomic dysfunction, ongoing activity primed immune cells, autoimmunity due molecular mimicry pathogen proteins. individualized suggests different therapeutic approaches required best manage specific patients.

Language: Английский

Citations

154
Core mitochondrial genes are down-regulated during SARS-CoV-2 infection of rodent and human hosts DOI
Joseph W. Guarnieri, Joseph M. Dybas,

Hossein Fazelinia

et al.

Science Translational Medicine, Journal Year: 2023, Volume and Issue: 15(708)

Published: Aug. 9, 2023

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral proteins bind to host mitochondrial proteins, likely inhibiting oxidative phosphorylation (OXPHOS) and stimulating glycolysis. We analyzed gene expression in nasopharyngeal autopsy tissues from patients with disease 2019 (COVID-19). In samples declining titers, the virus blocked transcription of a subset nuclear DNA (nDNA)–encoded OXPHOS genes, induced microRNA 2392, activated HIF-1α induce glycolysis, immune defenses including integrated stress response. COVID-19, SARS-CoV-2 was no longer present, had recovered lungs. However, nDNA remained suppressed tissue heart and, lesser extent, kidney, liver, whereas host-immune defense pathways were activated. During early infection hamsters peak lung load, minimally perturbed but down-regulated cerebellum up-regulated striatum even though detected brain. mid-phase mice, starting recover mouse These data suggest that when titer first peaks, there is systemic response followed by suppression induction glycolysis leading deployment antiviral defenses. Even cleared function recovered, heart, lymph nodes impaired, potentially severe COVID-19 pathology.

Language: Английский

Citations

112
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

111