Neuroinvasion and Neurotropism by SARS-CoV-2 Variants in the K18-hACE2 Mouse

Letter Medicine, General & Internal

Reduced neutralisation of SARS-CoV-2 omicron B.1.1.529 variant by post-immunisation serum

Wanwisa Dejnirattisai et al.

LANCET (2022)

Article Multidisciplinary Sciences

SARS-CoV-2 Omicron virus causes attenuated disease in mice and hamsters

Peter J. Halfmann et al.

Summary: The recent study by the SAVE/NIAID network shows that the B.1.1.529 Omicron variant causes milder lung disease in rodents, which is consistent with preliminary human clinical data.

NATURE (2022)

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Article Pathology

Chronological brain lesions after SARS-CoV-2 infection in hACE2-transgenic mice

Enric Vidal et al.

Summary: This study chronologically characterized the neuroinvasion and neuropathology of SARS-CoV-2 in a mouse model. The virus was found to enter the brain early through the olfactory mucosa and rapidly spread between neurons, causing acute encephalitis and neuronal damage.

VETERINARY PATHOLOGY (2022)

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Article Microbiology

SARS-CoV-2 Infects Primary Neurons from Human ACE2 Expressing Mice and Upregulates Genes Involved in the Inflammatory and Necroptotic Pathways

Hussin A. Rothan et al.

Summary: This study investigates the neuropathogenesis of SARS-CoV-2 infection in transgenic K18-hACE2 mice. The researchers found that neurons obtained from K18-hACE2 mice are susceptible to SARS-CoV-2 infection and support virus replication. Additionally, SARS-CoV-2 infection upregulates the expression of genes involved in innate immunity and inflammation in neurons and mouse brains. The study also reveals activation of the ZBP1/pMLKL-regulated necroptosis pathway in SARS-CoV-2-infected neurons and mouse brains.

PATHOGENS (2022)

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Article Virology

Fatal Neurodissemination and SARS-CoV-2 Tropism in K18-hACE2 Mice Is Only Partially Dependent on hACE2 Expression

Mariano Carossino et al.

Summary: This study evaluated the pathogenesis and clinical dynamics of SARS-CoV-2 infection in a transgenic mouse model. The results suggest that the model has limitations in replicating the pathological processes, neuroinvasion, and neurodissemination observed in humans.

VIRUSES-BASEL (2022)

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Article Microbiology

Update on SARS-CoV-2 Omicron Variant of Concern and Its Peculiar Mutational Profile

Mohammad Alkhatib et al.

Summary: This study provides a comprehensive definition and functional characterization of mutations characterizing the Omicron variant of concern (VOC), shedding light on its mutational profile and clinical implications. The study highlights the importance of understanding the unique spectrum of mutations in the Omicron variant, particularly in the spike glycoprotein, and their potential impact on infectivity, antibody recognition, and diagnostic assays.

MICROBIOLOGY SPECTRUM (2022)

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Review Cell Biology

COVID-19 and olfactory dysfunction: A possible associative approach towards neurodegenerative diseases

Iyer Mahalaxmi et al.

Summary: The emergence of SARS-CoV-2 has caused global concern due to its severe life-threatening conditions. COVID-19 symptoms like fever, sore throat, and shortness of breath are common, and anecdotal reports suggest potential effects on the central nervous system, including neuroinflammation and neurodegenerative disorders like anosmia and hyposmia. Further research is needed to understand the full extent of the virus's impact on the brain and potential long-term consequences.

JOURNAL OF CELLULAR PHYSIOLOGY (2021)

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Letter Clinical Neurology

Brain ischemic injury in COVID-19-infected patients: a series of 10 post-mortem cases

Viscardo P. Fabbri et al.

BRAIN PATHOLOGY (2021)

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Article Pharmacology & Pharmacy

Dose prediction for repurposing nitazoxanide in SARS-CoV-2 treatment or chemoprophylaxis

Rajith K. R. Rajoli et al.

Summary: The study utilized PBPK modeling to determine optimal doses of nitazoxanide to maintain its concentration in the body at effective antiviral levels. The validated model successfully predicted human pharmacokinetics, providing a rational basis for designing clinical trials with nitazoxanide for the treatment or prevention of SARS-CoV-2 infection.

BRITISH JOURNAL OF CLINICAL PHARMACOLOGY (2021)

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Review Clinical Neurology

Invited Review: The spectrum of neuropathology in COVID-19

S. Al-Sarraj et al.

Summary: Patients with COVID-19 show a range of neurological and psychiatric symptoms, with potential involvement of the central nervous system directly through viral invasion or indirectly through other mechanisms. Further pathological studies are needed to clarify the relationship between neuropathological changes and clinical features observed in COVID-19 patients.

NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY (2021)

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Article Biochemistry & Molecular Biology

Article Visualizing in deceased COVID-19 patients how SARS-CoV-2 attacks the respiratory and olfactory mucosae but spares the olfactory bulb

Mona Khan et al.

Summary: Anosmia, the loss of smell, is a common symptom of COVID-19, but it is caused by the virus attacking sustentacular cells in the olfactory mucosa rather than infecting olfactory sensory neurons. This suggests that SARS-CoV-2 is not a neurotropic virus.

CELL (2021)

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Article Immunology

Neuroinvasion of SARS-CoV-2 in human and mouse brain

Eric Song et al.

Summary: The study showed through three approaches that SARS-CoV-2 is capable of infecting brain neurons, leading to metabolic changes and pathological features without triggering type I interferon responses. These results provide evidence for the neuroinvasive capacity of SARS-CoV-2 and the unexpected consequence of direct infection of neurons by the virus.

JOURNAL OF EXPERIMENTAL MEDICINE (2021)

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Article Biochemistry & Molecular Biology

Immune determinants of COVID-19 disease presentation and severity

Petter Brodin

Summary: The severity of COVID-19 varies by sex and age, and is linked to comorbidities. Differences in immune reactions may go some way to explain this.

NATURE MEDICINE (2021)

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Article Neurosciences

Olfactory transmucosal SARS-CoV-2 invasion as a port of central nervous system entry in individuals with COVID-19

Jenny Meinhardt et al.

Summary: The study demonstrates the presence of SARS-CoV-2 in the nasopharynx and brain, suggesting the virus may enter the CNS through the olfactory mucosa. The virus utilizes the neural-mucosal interface in the olfactory mucosa to penetrate the nervous system, affecting various neuroanatomical areas, including the primary respiratory and cardiovascular control center.

NATURE NEUROSCIENCE (2021)

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Article Neurosciences

The S1 protein of SARS-CoV-2 crosses the blood-brain barrier in mice

Elizabeth M. Rhea et al.

Summary: The study demonstrates that the SARS-CoV-2 spike 1 protein can cross the mouse blood-brain barrier and be taken up by both the brain and peripheral tissues. Intravenous injection results in higher levels of protein uptake in the brain compared to intranasal administration. Genetic factors and sex have varying effects on the uptake of the spike protein in different tissues.

NATURE NEUROSCIENCE (2021)

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Article Pathology

Sheep-Associated Malignant Catarrhal Fever: Role of Latent Virus and Macrophages in Vasculitis

Helena Saura-Martinez et al.

Summary: The study suggests that the vasculitis in MCF originates from the interaction between infected cells and immune cells, leading to infiltration of inflammatory cells and recruitment of white blood cells in the blood vessels, resulting in structural changes in the vasculature. Macrophages and T cells are the main infiltrating cells, capable of proliferating locally, and the process is accompanied by widespread viral infection.

VETERINARY PATHOLOGY (2021)

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Article Virology

Neuroinvasion and Encephalitis Following Intranasal Inoculation of SARS-CoV-2 in K18-hACE2 Mice

Pratima Kumari et al.

Summary: The study demonstrated that SARS-CoV-2 infection can lead to neuroinvasion and encephalitis in K18-hACE2 mice, resulting in mortality. While the highest virus titers were observed in the lungs, high levels of infectious virus were also found in the brains of the infected mice. The severity of the disease in infected mice correlated with peak viral levels in the brain.

VIRUSES-BASEL (2021)

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Article Microbiology

K18-hACE2 mice develop respiratory disease resembling severe COVID-19

Claude Kwe Yinda et al.

Summary: The study demonstrates that humanized transgenic mice developed dose-dependent disease when inoculated with SARS-CoV-2, showing upper and lower respiratory tract infection with viral replication also in the brain. The pathological and immunological manifestations observed in these mice resemble human COVID-19, suggesting the model's usefulness in elucidating COVID-19 pathogenesis and testing countermeasures.

PLOS PATHOGENS (2021)

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Article Infectious Diseases

SARS-CoV-2 RNA in plasma samples of COVID-19 affected individuals: a cross-sectional proof-of-concept study

Luna Colagrossi et al.

Summary: This proof-of-concept study of 41 SARS-CoV-2-positive adult individuals revealed that patients with viremia had a higher mortality rate, were more frequently affected by haematological malignancies, and had higher viral loads in respiratory samples. This highlights the importance of early identification of high-risk patients for severe COVID-19, particularly among haematologic patients.

BMC INFECTIOUS DISEASES (2021)

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Article Cell Biology

Coinfection with influenza A virus enhances SARS-CoV-2 infectivity

Lei Bai et al.

Summary: The upcoming flu season in the Northern Hemisphere coinciding with the COVID-19 pandemic poses a potential threat to public health. Research shows that influenza A virus infection significantly enhances the infectivity of SARS-CoV-2, leading to increased viral load and more severe lung damage in coinfected individuals. Preventing influenza A infection is crucial in controlling the spread of COVID-19.

CELL RESEARCH (2021)

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Article Multidisciplinary Sciences

Comparison of rhesus and cynomolgus macaques as an infection model for COVID-19

Francisco J. Salguero et al.

Summary: This study demonstrates that SARS-CoV-2 replicates in the upper and lower respiratory tract of both rhesus and cynomolgus macaques, causing pulmonary lesions. Immune responses against SARS-CoV-2 are similar in both species, suggesting that both macaque species authentically represent mild to moderate forms of COVID-19. The findings provide valuable insights for evaluating interventions against SARS-CoV-2.

NATURE COMMUNICATIONS (2021)

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Article Biochemistry & Molecular Biology

COVID-19 induces a hyperactive phenotype in circulating platelets

Shane P. Comer et al.

Summary: This study found distinct differences in routine full blood count and other clinical laboratory parameters between patients with severe and nonsevere COVID-19. It also determined that all COVID-19 patients possess hyperactive circulating platelets, suggesting abnormal platelet reactivity may contribute to hypercoagulability in COVID-19, influencing the severity of the disease and recovery path complexity.

PLOS BIOLOGY (2021)

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Article Multidisciplinary Sciences

Co-infection of SARS-CoV-2 and influenza virus causes more severe and prolonged pneumonia in hamsters

Takaaki Kinoshita et al.

Summary: Co-infection with influenza A virus and SARS-CoV-2 in hamsters can result in more severe health risks, including greater body weight loss, more severe and prolonged pneumonia, and potentially abnormal immune responses.

SCIENTIFIC REPORTS (2021)

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Article Multidisciplinary Sciences

Escape of SARS-CoV-2 501Y.V2 from neutralization by convalescent plasma

Sandile Cele et al.

Summary: The study compared the neutralization of non-VOC and 501Y.V2 VOC variants using plasma from COVID-19 patients in South Africa. It found that plasma from individuals infected during the first wave effectively neutralized the first-wave virus variant, while plasma from those infected in the second wave effectively neutralized the 501Y.V2 variant.

NATURE (2021)

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Article Biochemistry & Molecular Biology

Single-dose immunisation with a multimerised SARS-CoV-2 receptor binding domain (RBD) induces an enhanced and protective response in mice

Ralf Salzer et al.

Summary: The study identified a stable multivalent dodecameric vaccine nanoparticles covalently coupled with SARS-CoV-2 antigens, which induced higher antibody titers and neutralizing antibody responses in mice immunization experiments. The vaccine provided protection against serious illness and viral clearance in the lungs upon SARS-CoV-2 infection, highlighting the efficacy of multimerized SARS-CoV-2 subunit vaccines when combined with an ultra-stable scaffold.

FEBS LETTERS (2021)

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Article Cell Biology

SARS-CoV-2 infection in the mouse olfactory system

Qing Ye et al.

Summary: The study reveals that SARS-CoV-2 infection causes olfactory dysfunction, with its mechanism unclear, but replicable in a mouse model and providing critical clues to understanding extrapulmonary manifestations of COVID-19. These findings suggest a direct impact on olfactory structures and gene expression, triggering immune responses and cell death.

CELL DISCOVERY (2021)

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Article Pharmacology & Pharmacy

A mechanism-based pharmacokinetic model of remdesivir leveraging interspecies scaling to simulate COVID-19 treatment in humans

Patrick O. Hanafin et al.

Summary: The outbreak of SARS-CoV-2 led to the COVID-19 pandemic with millions of confirmed infections and deaths worldwide. Remdesivir has shown effectiveness against coronaviruses, but its distribution to the site of lung infection in humans is unknown. Alternative dosing strategies may be needed to achieve more efficacious concentrations in human lungs.

CPT-PHARMACOMETRICS & SYSTEMS PHARMACOLOGY (2021)

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COVID-19 treatments and pathogenesis including anosmia in K18-hACE2 mice

Jian Zheng et al.

Summary: The COVID-19 pandemic is associated with significant morbidity and mortality. Experimental studies in animals infected with SARS-CoV-2 have revealed severe lung and brain damage, as well as early onset anosmia in mice. Excitingly, infusion of convalescent plasma from recovered patients has shown to protect against lethal disease, though it does not prevent anosmia.

NATURE (2021)

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Letter Clinical Neurology

Neuropathology of COVID-19: a spectrum of vascular and acute disseminated encephalomyelitis (ADEM)-like pathology

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ACTA NEUROPATHOLOGICA (2020)

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SARS-CoV-2 Detected in Cerebrospinal Fluid by PCR in a Case of COVID-19 Encephalitis

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SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor

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High risk of thrombosis in patients with severe SARS-CoV-2 infection: a multicenter prospective cohort study

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A first case of meningitis/encephalitis associated with SARS-Coronavirus-2

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Microvascular injury and hypoxic damage: emerging neuropathological signatures in COVID-19

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Neuroinvasion and Neurotropism by SARS-CoV-2 Variants in the K18-hACE2 Mouse

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