SARS-CoV2 entry and spread in the lymphatic drainage system of the brain

Bostancıklıoğlu, Mehmet

doi:10.1016/j.bbi.2020.04.080

Cited by 61 publications

(60 citation statements)

References 11 publications

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“…Furthermore, brain endothelial and smooth muscle cells of the blood vessels express ACE-2 [7]. The virus may enter into the CNS through the hematogenic pathway, subsequently crossing the BBB [91]. A post-mortem study of the frontal lobe of a COVID-19 patient reports virus presence in neurons and capillary endothelial cells [92].…”

Section: Ace-2 Dependent and Independent Infection Of The Nervous Sysmentioning

confidence: 99%

SARS-CoV-2, an Underestimated Pathogen of the Nervous System

Jakhmola

Indari

Chatterjee

et al. 2020

SN Compr. Clin. Med.

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Numerous clinical studies have reported neurological symptoms in COVID-19 patients since the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), apart from the atypical signs of pneumonia. Angiotensin-converting enzyme-2 (ACE-2), a potential receptor for SARS-CoV-2 entry, is expressed on various brain cells and cerebral parts, i.e., subfornical organ, paraventricular nucleus, nucleus of the tractus solitarius, and rostral ventrolateral medulla, as well as in non-cardiovascular areas such as the motor cortex and raphe. The resident CNS cells like astrocytes and microglia also express ACE-2, thus highlighting the vulnerability of the nervous system to SARS-CoV-2 infection. Additionally, transmembrane serine protease 2 (TMPRSS2) and furin facilitate virus entry into the host. Besides, the probable routes of virus entry into the nervous system include the hematogenic pathway, through the vagus, the olfactory nerve, or the enteric nervous system. However, the trajectory of SARS-CoV-2 to the brain needs investigation. Furthermore, a Th17-mediated cytokine storm is seen in COVID-19 cases with higher levels of IL-1β/2/7/8/9/ 10/17, GM-CSF, IFN-γ, TNF-α, CXCL-10, MCP1, and MIP1α/β. Some cytokines can cross the blood-brain barrier and activate the brain's immune cells to produce neural cytokines, leading to neuronal dysfunctions. Nonetheless, most of the neurological conditions developed due to viral infections may not have effective and registered treatments. Although, some antivirals may inhibit the virus-mediated pathogenesis and prove to be suitable in COVID-19 treatment. Therefore, clinicians' and researchers' collective expertise may unravel the potential of SARS-CoV-2 infection to prevent short-term and long-term CNS damage.

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Section: Ace-2 Dependent and Independent Infection Of The Nervous Sysmentioning

confidence: 99%

SARS-CoV-2, an Underestimated Pathogen of the Nervous System

Jakhmola

Indari

Chatterjee

et al. 2020

SN Compr. Clin. Med.

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“…Moreover, brain damage may occur upon disturbance of the drainage system due to viral infection, thus leading to the entrance of viruses into the CSF [176,180]. Interestingly, some positive COVID-19 patients have been reported to present paranasal sinusitis with the presence of lymph endothelial cells infected by SARS-CoV-2 [181,182]. This particular cell infection appears to be associated with the potential ability to infect by coronaviruses.…”

Section: Nervous Systemmentioning

confidence: 99%

Unpuzzling COVID-19: tissue-related signaling pathways associated with SARS-CoV-2 infection and transmission

et al. 2020

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The highly infective coronavirus disease 19 (COVID-19) is caused by a novel strain of coronaviruses – the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) – discovered in December 2019 in the city of Wuhan (Hubei Province, China). Remarkably, COVID-19 has rapidly spread across all continents and turned into a public health emergency, which was ultimately declared as a pandemic by the World Health Organization (WHO) in early 2020. SARS-CoV-2 presents similar aspects to other members of the coronavirus family, mainly regarding its genome, protein structure and intracellular mechanisms, that may translate into mild (or even asymptomatic) to severe infectious conditions. Although the mechanistic features underlying the COVID-19 progression have not been fully clarified, current evidence have suggested that SARS-CoV-2 may primarily behave as other β-coronavirus members. To better understand the development and transmission of COVID-19, unveiling the signaling pathways that may be impacted by SARS-CoV-2 infection, at the molecular and cellular levels, is of crucial importance. In this review, we present the main aspects related to the origin, classification, etiology and clinical impact of SARS-CoV-2. Specifically, here we describe the potential mechanisms of cellular interaction and signaling pathways, elicited by functional receptors, in major targeted tissues/organs from the respiratory, gastrointestinal (GI), cardiovascular, renal, and nervous systems. Furthermore, the potential involvement of these signaling pathways in evoking the onset and progression of COVID-19 symptoms in these organ systems are presently discussed. A brief description of future perspectives related to potential COVID-19 treatments is also highlighted.

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“…A third way SARS-CoV-2 can enter the CNS could be via the spreading of the virus in the lymphatic drainage system of the brain [177]. Although the glymphatic vessel structure mainly contains endothelial lining cell systems, this pathway is rather contradictory at the moment, and other researchers do not confirm lymphatic draining entry [2].…”

Section: Lymphatic Brain Drainage Routementioning

confidence: 99%

SARS-CoV-2 Infection Reaches the Human Nervous System: How?

Uversky¹,

Elrashdy²,

Aljadawi³

et al. 2020

Preprint

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Without protective and/or therapeutic agents the SARS-CoV-2 infection known as coronavirus disease 2019 (COVID-19) is quickly spreading worldwide. It has surprising transmissibility potential, since it could infect all ages, gender, and human sectors. It attacks respiratory, gastrointestinal, urinary, hepatic, and endovascular systems and can reach the peripheral nervous system (PNS) and central nervous system (CNS) through known and unknown mechanisms. The reports on the neurological manifestations and complications of the SARS-CoV-2 infection are increasing exponentially. Herein, we enumerate seven candidate routes, which the mature or immature SARS-CoV-2 components could use to reach the CNS and PNS, utilizing the within-body crosstalk between organs. The majority of SARS-CoV-2 infected patients suffer from some neurological manifestations (e.g., confusion, anosmia, and ageusia). It seems that although the mature virus did not reach the CNS or PNS of the majority of patients, its unassembled components and/or the accompanying immune-mediated responses may be responsible for the observed neurological symptoms. The viral particles and/or its components have been specifically documented in endothelial cells of lung, kidney, skin, and CNS. This means that the blood-endothelial-barrier may be considered as the main route for SARS-CoV-2 entry into the nervous system, with the barrier disruption being more logical than barrier permeability, as evidenced by postmortem analyses.

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SARS-CoV2 entry and spread in the lymphatic drainage system of the brain

Cited by 61 publications

References 11 publications

SARS-CoV-2, an Underestimated Pathogen of the Nervous System

SARS-CoV-2, an Underestimated Pathogen of the Nervous System

Unpuzzling COVID-19: tissue-related signaling pathways associated with SARS-CoV-2 infection and transmission

SARS-CoV-2 Infection Reaches the Human Nervous System: How?

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