SARS-CoV-2-Mediated Neuropathogenesis, Deterioration of Hippocampal Neurogenesis and Dementia

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Abstract

A significant portion of COVID-19 patients and survivors display marked clinical signs of neurocognitive impairments. SARS-CoV-2-mediated peripheral cytokine storm and its neurotropism appear to elicit the activation of glial cells in the brain proceeding to neuroinflammation. While adult neurogenesis has been identified as a key cellular basis of cognitive functions, neuroinflammation-induced aberrant neuroregenerative plasticity in the hippocampus has been implicated in progressive memory loss in ageing and brain disorders. Notably, recent histological studies of post-mortem human and experimental animal brains indicate that SARS-CoV-2 infection impairs neurogenic process in the hippocampus of the brain due to neuroinflammation. Considering the facts, this article describes the prominent neuropathogenic characteristics and neurocognitive impairments in COVID-19 and emphasizes a viewpoint that neuroinflammation-mediated deterioration of hippocampal neurogenesis could contribute to the onset and progression of dementia in COVID-19. Thus, it necessitates the unmet need for regenerative medicine for the effective management of neurocognitive deficits in COVID-19.

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Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China

Chaolin Huang, Yeming Wang, Xingwang Li … (2020)

Summary Background A recent cluster of pneumonia cases in Wuhan, China, was caused by a novel betacoronavirus, the 2019 novel coronavirus (2019-nCoV). We report the epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of these patients. Methods All patients with suspected 2019-nCoV were admitted to a designated hospital in Wuhan. We prospectively collected and analysed data on patients with laboratory-confirmed 2019-nCoV infection by real-time RT-PCR and next-generation sequencing. Data were obtained with standardised data collection forms shared by WHO and the International Severe Acute Respiratory and Emerging Infection Consortium from electronic medical records. Researchers also directly communicated with patients or their families to ascertain epidemiological and symptom data. Outcomes were also compared between patients who had been admitted to the intensive care unit (ICU) and those who had not. Findings By Jan 2, 2020, 41 admitted hospital patients had been identified as having laboratory-confirmed 2019-nCoV infection. Most of the infected patients were men (30 [73%] of 41); less than half had underlying diseases (13 [32%]), including diabetes (eight [20%]), hypertension (six [15%]), and cardiovascular disease (six [15%]). Median age was 49·0 years (IQR 41·0–58·0). 27 (66%) of 41 patients had been exposed to Huanan seafood market. One family cluster was found. Common symptoms at onset of illness were fever (40 [98%] of 41 patients), cough (31 [76%]), and myalgia or fatigue (18 [44%]); less common symptoms were sputum production (11 [28%] of 39), headache (three [8%] of 38), haemoptysis (two [5%] of 39), and diarrhoea (one [3%] of 38). Dyspnoea developed in 22 (55%) of 40 patients (median time from illness onset to dyspnoea 8·0 days [IQR 5·0–13·0]). 26 (63%) of 41 patients had lymphopenia. All 41 patients had pneumonia with abnormal findings on chest CT. Complications included acute respiratory distress syndrome (12 [29%]), RNAaemia (six [15%]), acute cardiac injury (five [12%]) and secondary infection (four [10%]). 13 (32%) patients were admitted to an ICU and six (15%) died. Compared with non-ICU patients, ICU patients had higher plasma levels of IL2, IL7, IL10, GSCF, IP10, MCP1, MIP1A, and TNFα. Interpretation The 2019-nCoV infection caused clusters of severe respiratory illness similar to severe acute respiratory syndrome coronavirus and was associated with ICU admission and high mortality. Major gaps in our knowledge of the origin, epidemiology, duration of human transmission, and clinical spectrum of disease need fulfilment by future studies. Funding Ministry of Science and Technology, Chinese Academy of Medical Sciences, National Natural Science Foundation of China, and Beijing Municipal Science and Technology Commission.

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

Markus Hoffmann, Hannah Kleine-Weber, Simon Schroeder … (2020)

Summary The recent emergence of the novel, pathogenic SARS-coronavirus 2 (SARS-CoV-2) in China and its rapid national and international spread pose a global health emergency. Cell entry of coronaviruses depends on binding of the viral spike (S) proteins to cellular receptors and on S protein priming by host cell proteases. Unravelling which cellular factors are used by SARS-CoV-2 for entry might provide insights into viral transmission and reveal therapeutic targets. Here, we demonstrate that SARS-CoV-2 uses the SARS-CoV receptor ACE2 for entry and the serine protease TMPRSS2 for S protein priming. A TMPRSS2 inhibitor approved for clinical use blocked entry and might constitute a treatment option. Finally, we show that the sera from convalescent SARS patients cross-neutralized SARS-2-S-driven entry. Our results reveal important commonalities between SARS-CoV-2 and SARS-CoV infection and identify a potential target for antiviral intervention.

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Neurologic Manifestations of Hospitalized Patients With Coronavirus Disease 2019 in Wuhan, China

Ling Mao, Huijuan Jin, Mengdie Wang … (2020)

The outbreak of coronavirus disease 2019 (COVID-19) in Wuhan, China, is serious and has the potential to become an epidemic worldwide. Several studies have described typical clinical manifestations including fever, cough, diarrhea, and fatigue. However, to our knowledge, it has not been reported that patients with COVID-19 had any neurologic manifestations.

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Journal

Journal ID (nlm-ta): Am J Alzheimers Dis Other Demen

Journal ID (iso-abbrev): Am J Alzheimers Dis Other Demen

Journal ID (hwp): spaja

Journal ID (publisher-id): AJA

Title: American Journal of Alzheimer's Disease and Other Dementias

Publisher: SAGE Publications (Sage CA: Los Angeles, CA )

ISSN (Print): 1533-3175

ISSN (Electronic): 1938-2731

Publication date (Electronic): 8 February 2022

Publication date Collection: Jan-Dec 2022

Volume: 37

Electronic Location Identifier: 15333175221078418

Affiliations

[1 ]Laboratory of Stem Cells and Neuroregeneration, Department of Animal Science, School of Life Sciences, Ringgold 30011, universityBharathidasan University; , Tiruchirappalli, India

[2 ]Faculty Recharge Programme, Ringgold 30011, universityUniversity Grants Commission (UGC-FRP); , New Delhi, India

Author notes

[*]Mahesh Kandasamy, PhD, UGC-Assistant Professor, Department of Animal Science, School of Life Sciences, Bharathidasan University, Tiruchirappalli, Tamilnadu 620024, India. Email: mahesh.kandasamy@ 123456bdu.ac.in

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Mahesh Kandasamy https://orcid.org/0000-0002-6720-9082

Article

Publisher ID: 10.1177_15333175221078418

DOI: 10.1177/15333175221078418

PMC ID: 10581113

PubMed ID: 35133907

SO-VID: 186b0b50-9c2f-408c-9fa8-e763c5219947

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This article is distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 License ( https://creativecommons.org/licenses/by-nc-nd/4.0/) which permits non-commercial use, reproduction and distribution of the work as published without adaptation or alteration, without further permission provided the original work is attributed as specified on the SAGE and Open Access pages ( https://us.sagepub.com/en-us/nam/open-access-at-sage).

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Funding

Funded by: Faculty Recharge Programme, University Grants Commission (UGC-FRP);

Award ID: SERB-EEQ/2016/000639

Award ID: SERB-ECR/2016/000741

Funded by: RUSA2.0, Biological Sciences, Bharathidasan University;

Funded by: JRF;

Award ID: ECR/2016/000741, SERB

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typesetter ts10

cover-date January-December 2022

Keywords: covid-19,cytokine storm,neuroinflammation,hippocampal neurogenesis,dementia

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Keywords: covid-19, cytokine storm, neuroinflammation, hippocampal neurogenesis, dementia

SARS-CoV-2-Mediated Neuropathogenesis, Deterioration of Hippocampal Neurogenesis and Dementia

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Novel Coronavirus Disease COVID-19

Most cited references 137

Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China

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

Neurologic Manifestations of Hospitalized Patients With Coronavirus Disease 2019 in Wuhan, China

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