Long-Term Sequelae of COVID-19 in Experimental Mice

Paidas, Michael J.; Cosio, Daniela; Saad, Ali; Kenyon, Norma S.; Jayakumar, Arumugam R.

doi:10.1007/s12035-022-02932-1

Cited by 27 publications

(49 citation statements)

References 66 publications

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“…These mice exhibit pronounced lung injury with mortality rates ranging from 40% to 60% between days 7 and 12 post-infection [ 14 ]. Upon examination at the time of death, the lungs display severe interstitial pneumonitis characterized by interstitial inflammatory reactions, along with substantial infiltrations of lymphocytes and macrophages [ 15 , 16 , 17 , 18 ]. Additionally, investigations into the livers of MHV-1-infected A/J mice disclose evidence of severe hepatic congestion, mirroring observations in humans infected with SARS-CoV-2 [ 16 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

Dermatologic Changes in Experimental Model of Long COVID

Hussain,

Paidas,

Rajalakshmi

et al. 2024

Microorganisms

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The coronavirus disease-19 (COVID-19) pandemic, declared in early 2020, has left an indelible mark on global health, with over 7.0 million deaths and persistent challenges. While the pharmaceutical industry raced to develop vaccines, the emergence of mutant severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) strains continues to pose a significant threat. Beyond the immediate concerns, the long-term health repercussions of COVID-19 survivors are garnering attention, particularly due to documented cases of cardiovascular issues, liver dysfunction, pulmonary complications, kidney impairments, and notable neurocognitive deficits. Recent studies have delved into the pathophysiological changes in various organs following post-acute infection with murine hepatitis virus-1 (MHV-1), a coronavirus, in mice. One aspect that stands out is the impact on the skin, a previously underexplored facet of long-term COVID-19 effects. The research reveals significant cutaneous findings during both the acute and long-term phases post-MHV-1 infection, mirroring certain alterations observed in humans post-SARS-CoV-2 infection. In the acute stages, mice exhibited destruction of the epidermal layer, increased hair follicles, extensive collagen deposition in the dermal layer, and hyperplasticity of sebaceous glands. Moreover, the thinning of the panniculus carnosus and adventitial layer was noted, consistent with human studies. A long-term investigation revealed the absence of hair follicles, destruction of adipose tissues, and further damage to the epidermal layer. Remarkably, treatment with a synthetic peptide, SPIKENET (SPK), designed to prevent Spike glycoprotein-1 binding with host receptors and elicit a potent anti-inflammatory response, showed protection against MHV-1 infection. Precisely, SPK treatment restored hair follicle loss in MHV-1 infection, re-architected the epidermal and dermal layers, and successfully overhauled fatty tissue destruction. These promising findings underscore the potential of SPK as a therapeutic intervention to prevent long-term skin alterations initiated by SARS-CoV-2, providing a glimmer of hope in the battle against the lingering effects of the pandemic.

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Section: Introductionmentioning

confidence: 99%

Dermatologic Changes in Experimental Model of Long COVID

Hussain,

Paidas,

Rajalakshmi

et al. 2024

Microorganisms

Self Cite

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“… 31 Mucin inhibits coronavirus infection via its glycan in an organoid in vitro model. 32 , 33 Mucin mRNA in the blood or respiratory tissue could be a marker for SARS-CoV-2 infection and COVID-19 severity. 34 Our previous study showed that the number of mucin-secreting cells decreases in some GI tract fragments at the early stage of SARS-CoV-2 infection, but gradually increases at the late stage of infection in the NHP model, indicating that mucin correlates with the recovery of the disease caused by SARS-CoV-2 infection.…”

Section: Discussionmentioning

confidence: 99%

Gastrointestinal microbiota and metabolites possibly contribute to distinct pathogenicity of SARS-CoV-2 proto or its variants in rhesus monkeys

Chen,

Wang,

Ding

et al. 2024

Gut Microbes

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Gastrointestinal (GI) infection is evidenced with involvement in COVID-19 pathogenesis caused by SARS-CoV-2. However, the correlation between GI microbiota and the distinct pathogenicity of SARS-CoV-2 Proto and its emerging variants remains unclear. In this study, we aimed to determine if GI microbiota impacted COVID-19 pathogenesis and if the effect varied between SARS-CoV-2 Proto and its variants. We performed an integrative analysis of histopathology, microbiomics, and transcriptomics on the GI tract fragments from rhesus monkeys infected with SARS-CoV-2 proto or its variants. Based on the degree of pathological damage and microbiota profile in the GI tract, five of SARS-CoV-2 strains were classified into two distinct clusters, namely, the clusters of Alpha, Beta and Delta (ABD), and Proto and Omicron (PO). Notably, the abundance of potentially pathogenic microorganisms increased in ABD but not in the PO-infected rhesus monkeys. Specifically, the high abundance of UCG-002 , UCG-005 , and Treponema in ABD virus-infected animals positively correlated with interleukin, integrins, and antiviral genes. Overall, this study revealed that infection-induced alteration of GI microbiota and metabolites could increase the systemic burdens of inflammation or pathological injury in infected animals, especially in those infected with ABD viruses. Distinct GI microbiota and metabolite profiles may be responsible for the differential pathological phenotypes of PO and ABD virus-infected animals. These findings improve our understanding the roles of the GI microbiota in SARS-CoV-2 infection and provide important information for the precise prevention, control, and treatment of COVID-19.

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“…Another study reported increased reactive astrocytes and microglia, hyperphosphorylated TDP-43 and tau, and decrease in synaptic protein synaptophysin-1 and defective neuronal integrity in A/J mice 12 months post-infection. Although the study recapitulates long-term sequelae of COVID-19, a mouse hepatitis virus 1 (MHV-1) was used in this study 48,49 .…”

Section: Discussionmentioning

confidence: 99%

A Murine Model of Post-acute Neurological Sequelae Following SARS-CoV-2 Variant Infection

Singh,

Adam,

Aditi

et al. 2024

Preprint

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Viral variant is one known risk factor associated with post-acute sequelae of COVID-19 (PASC), yet the pathogenesis is largely unknown. Here, we studied SARS-CoV-2 Delta variant-induced PASC in K18-hACE2 mice. The virus replicated productively, induced robust inflammatory responses in lung and brain tissues, and caused weight loss and mortality during the acute infection. Longitudinal behavior studies in surviving mice up to 4 months post-acute infection revealed persistent abnormalities in neuropsychiatric state and motor behaviors, while reflex and sensory functions recovered over time. Surviving mice showed no detectable viral RNA in the brain and minimal neuroinflammation post-acute infection. Transcriptome analysis revealed persistent activation of immune pathways, including humoral responses, complement, and phagocytosis, and reduced levels of genes associated with ataxia telangiectasia, impaired cognitive function and memory recall, and neuronal dysfunction and degeneration. Furthermore, surviving mice maintained potent T helper 1 prone cellular immune responses and high neutralizing antibodies against Delta and Omicron variants in the periphery for months post-acute infection. Overall, infection in K18-hACE2 mice recapitulates the persistent clinical symptoms reported in long COVID patients and may be useful for future assessment of the efficacy of vaccines and therapeutics against SARS-CoV-2 variants.

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Long-Term Sequelae of COVID-19 in Experimental Mice

Cited by 27 publications

References 66 publications

Dermatologic Changes in Experimental Model of Long COVID

Dermatologic Changes in Experimental Model of Long COVID

Gastrointestinal microbiota and metabolites possibly contribute to distinct pathogenicity of SARS-CoV-2 proto or its variants in rhesus monkeys

A Murine Model of Post-acute Neurological Sequelae Following SARS-CoV-2 Variant Infection

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