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

Persistent post–COVID-19 smell loss is associated with immune cell infiltration and altered gene expression in olfactory epithelium DOI Creative Commons
John B. Finlay, David H. Brann, Ralph Abi Hachem

et al.

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

Citations

104
Acute blood biomarker profiles predict cognitive deficits 6 and 12 months after COVID-19 hospitalization DOI Creative Commons
Maxime Taquet,

Zuzanna Skórniewska,

Adam Hampshire

et al.

Nature Medicine, Journal Year: 2023, Volume and Issue: 29(10), P. 2498 - 2508

Published: Aug. 31, 2023

Post-COVID cognitive deficits, including 'brain fog', are clinically complex, with both objective and subjective components. They common debilitating, can affect the ability to work, yet their biological underpinnings remain unknown. In this prospective cohort study of 1,837 adults hospitalized COVID-19, we identified two distinct biomarker profiles measured during acute admission, which predict outcomes 6 12 months after COVID-19. A first profile links elevated fibrinogen relative C-reactive protein deficits. second D-dimer deficits occupational impact. This was mediated by fatigue shortness breath. Neither significantly depression or anxiety. Results were robust across secondary analyses. replicated, specificity COVID-19 tested, in a large-scale electronic health records dataset. These findings provide insights into heterogeneous biology post-COVID

Language: Английский

Citations

66
The long-term health outcomes, pathophysiological mechanisms and multidisciplinary management of long COVID DOI Creative Commons
Jingwei Li, Yun Zhou, Jiechao Ma

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Nov. 1, 2023

Abstract There have been hundreds of millions cases coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome 2 (SARS-CoV-2). With the growing population recovered patients, it crucial to understand long-term consequences and management strategies. Although COVID-19 was initially considered an illness, recent evidence suggests that manifestations including but not limited those cardiovascular, respiratory, neuropsychiatric, gastrointestinal, reproductive, musculoskeletal systems may persist long after phase. These persistent manifestations, also referred as COVID, could impact all patients with across full spectrum illness severity. Herein, we comprehensively review current literature on highlighting its epidemiological understanding, vaccinations, organ-specific sequelae, pathophysiological mechanisms, multidisciplinary In addition, psychological psychosomatic factors underscored. Despite these findings diagnostic therapeutic strategies based previous experience pilot studies remain inadequate, well-designed clinical trials should be prioritized validate existing hypotheses. Thus, propose primary challenges concerning biological knowledge gaps efficient remedies well discuss corresponding recommendations.

Language: Английский

Citations

65
Human SARS-CoV-2 challenge uncovers local and systemic response dynamics DOI Creative Commons
Rik G.H. Lindeboom, Kaylee B. Worlock, Lisa M. Dratva

et al.

Nature, Journal Year: 2024, Volume and Issue: 631(8019), P. 189 - 198

Published: June 19, 2024

The COVID-19 pandemic is an ongoing global health threat, yet our understanding of the dynamics early cellular responses to this disease remains limited

Language: Английский

Citations

53
Thromboinflammation in long COVID—the elusive key to postinfection sequelae? DOI Creative Commons
Leo Nicolai, Rainer Kaiser, Konstantin Stark

et al.

Journal of Thrombosis and Haemostasis, Journal Year: 2023, Volume and Issue: 21(8), P. 2020 - 2031

Published: May 11, 2023

Language: Английский

Citations

52
Neuroinvasion and anosmia are independent phenomena upon infection with SARS-CoV-2 and its variants DOI Creative Commons
Guilherme Dias de Melo, Victoire Perraud, Flavio Alvarez

et al.

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

Published: July 26, 2023

Abstract Anosmia was identified as a hallmark of COVID-19 early in the pandemic, however, with emergence variants concern, clinical profile induced by SARS-CoV-2 infection has changed, anosmia being less frequent. Here, we assessed clinical, olfactory and neuroinflammatory conditions golden hamsters infected original Wuhan strain, its isogenic ORF7-deletion mutant three variants: Gamma, Delta, Omicron/BA.1. We show that animals develop variant-dependent disease including anosmia, ORF7 contributes to induction dysfunction. Conversely, all are neuroinvasive, regardless presentation they induce. Taken together, this confirms neuroinvasion independent phenomena upon infection. Using newly generated nanoluciferase-expressing SARS-CoV-2, validate pathway major entry point into brain vivo demonstrate vitro travels retrogradely anterogradely along axons microfluidic neuron-epithelial networks.

Language: Английский

Citations

43
SARS-CoV-2 immunity in animal models DOI Creative Commons
Chen Zhao,

Yaochang Yuan,

Qing‐Tao Hu

et al.

Cellular and Molecular Immunology, Journal Year: 2024, Volume and Issue: 21(2), P. 119 - 133

Published: Jan. 18, 2024

The COVID-19 pandemic, which was caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a worldwide health crisis due to its transmissibility. SARS-CoV-2 infection results in illness and can lead significant complications affected individuals. These encompass symptoms such as coughing, distress, fever, infectious shock, distress (ARDS), even multiple-organ failure. Animal models serve crucial tools for investigating pathogenic mechanisms, immune responses, escape antiviral drug development, vaccines against SARS-CoV-2. Currently, various animal infection, nonhuman primates (NHPs), ferrets, hamsters, many different mouse models, have been developed. Each model possesses distinctive features applications. In this review, we elucidate the response elicited patients provide an overview of characteristics mainly used well corresponding responses applications these models. A comparative analysis transcriptomic alterations lungs from revealed that K18-hACE2 mouse-adapted virus exhibited highest similarity with deceased patients. Finally, highlighted current gaps related research between studies clinical investigations, underscoring lingering scientific questions demand further clarification.

Language: Английский

Citations

18
The Host Response to Influenza A Virus Interferes with SARS-CoV-2 Replication during Coinfection DOI
Kohei Oishi, Shu Horiuchi, Judith M. Minkoff

et al.

Journal of Virology, Journal Year: 2022, Volume and Issue: 96(15)

Published: July 12, 2022

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza A virus (IAV) represent two highly transmissible airborne pathogens with pandemic capabilities. Although these viruses belong to separate families-SARS-CoV-2 is a member of the family Coronaviridae, while IAV Orthomyxoviridae-both have shown zoonotic potential, significant animal reservoirs in species close contact humans. The are similar their capacity infect human airways, coinfections resulting morbidity mortality been documented. Here, we investigate interaction between SARS-CoV-2 USA-WA1/2020 H1N1 A/California/04/2009 during coinfection. Competition assays vitro were performed susceptible cells that either interferon type I/III (IFN-I/-III) nonresponsive or IFN-I/-III responsive, addition an vivo golden hamster model. We find infection does not interfere biology vivo, regardless timing infections. In contrast, observe loss replication following infection. latter phenotype correlates increased levels immune priming interferes kinetics replication. Together, data suggest cocirculation unlikely result severity disease. IMPORTANCE population now has circulating RNA high namely, virus. As both airways can mortality, it imperative also understand consequences getting coinfected. demonstrate host response uniquely although inverse relationship evident. Overall, comparable alone.

Language: Английский

Citations

50
In vitro and in vivo differences in neurovirulence between D614G, Delta And Omicron BA.1 SARS-CoV-2 variants DOI Creative Commons
Lisa Bauer, Melanie Rissmann, Feline F. W. Benavides

et al.

Acta Neuropathologica Communications, Journal Year: 2022, Volume and Issue: 10(1)

Published: Sept. 4, 2022

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with various neurological complications. Although the mechanism not fully understood, several studies have shown that neuroinflammation occurs in and post-acute phase. As these predominantly been performed isolates from 2020, it unknown if there are differences among SARS-CoV-2 variants their ability to cause neuroinflammation. Here, we compared neuroinvasiveness, neurotropism neurovirulence of ancestral strain D614G, Delta (B.1.617.2) Omicron BA.1 (B.1.1.529) using vitro vivo models. The variant showed reduced D614G human induced pluripotent stem cell (hiPSC)-derived cortical neurons co-cultured astrocytes. Similar were obtained Syrian hamsters inoculated 5 days post infection. Replication olfactory mucosa was observed all hamsters, but most prominently hamsters. Furthermore, neuroinvasion into CNS via nerve or bulb D614G. Altogether, our findings suggest neuroinvasive, neurotropic neurovirulent potential between hiPSC-derived neural cultures during phase

Language: Английский

Citations

46
Mechanisms of SARS-CoV-2-associated anosmia DOI
Tatsuya Tsukahara, David H. Brann, Sandeep Robert Datta

et al.

Physiological Reviews, Journal Year: 2023, Volume and Issue: 103(4), P. 2759 - 2766

Published: June 21, 2023

Anosmia, the loss of sense smell, is one main neurological manifestations COVID-19. Although SARS-CoV-2 virus targets nasal olfactory epithelium, current evidence suggests that neuronal infection extremely rare in both periphery and brain, prompting need for mechanistic models can explain widespread anosmia COVID-19 patients. Starting from work identifying non-neuronal cell types are infected by system, we review effects these supportive cells epithelium brain posit downstream mechanisms through which smell impaired We propose indirect contribute to altered system function COVID-19-associated anosmia, as opposed or neuroinvasion into brain. Such include tissue damage, inflammatory responses immune infiltration systemic circulation cytokines, downregulation odorant receptor genes sensory neurons response local signals. also highlight key unresolved questions raised recent findings.

Language: Английский

Citations

34