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

Meinhardt, Jenny; Radke, Josefine; Dittmayer, Carsten; Franz, Jonas; Thomas, Carolina; Mothes, Ronja; Laue, Michael; Schneider, Julia; Brünink, Sebastian; Greuel, Selina; Lehmann, Malte; Hassan, Olga; Aschman, Tom; Schumann, Elisa; Chua, Robert Lorenz; Conrad, Christian; Eils, Roland; Stenzel, Werner; Windgassen, М.; Rößler, L.; Goebel, Hans‐Hilmar; Gelderblom, Hans R.; Martin, H; Nitsche, Andreas; Schulz‐Schaeffer, Walter; Hakroush, Samy; Winkler, Martin Sebastian; Tampe, Björn; Scheibe, Franziska; Körtvelyessy, Péter; Reinhold, Dirk; Siegmund, Britta; Kühl, Anja A.; Elezkurtaj, Sefer; Horst, David; Oesterhelweg, Lars; Tsokos, Michael; Ingold-Heppner, Barbara; Stadelmann, Christine; Drosten, Christian; Corman, Victor M.; Radbruch, Helena; Heppner, Frank L.

doi:10.1038/s41593-020-00758-5

Cited by 1,153 publications

(1,459 citation statements)

References 51 publications

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“…We showed evidence of SARS-CoV-2 RNA using qRT-PCR in a FFPT myocardial tissue although the exact anatomical location of viral RNA evidence could not be proven with ISH methodology, implying an indirect endothelial damage possibly triggered and enhanced by the inflammatory cellular reaction rather than the virus itself. On the other hand, IF labelled reaction products similar as recently described in central nervous vascular endothelium using the same methodology with qRT-PCR and IF labeling on FFPE autopsy tissue as in our cohort, further support a direct endothelial damage though the SARS-CoV-2 virus [ 60 , 64 ].…”

Section: Discussionsupporting

confidence: 86%

“…Direct endothelial viral damage has been documented in several previous studies using in vivo or in vitro samples [ 59 , 60 ]. Vascular organoids infected with SARS-CoV-2 were described earlier this year and the recently published study by Meinhardt et al.…”

Section: Discussionmentioning

confidence: 99%

“…Vascular organoids infected with SARS-CoV-2 were described earlier this year and the recently published study by Meinhardt et al. demonstrates endotheliitis and SARS-CoV S protein in the endothelial cells of small CNS vessels [ 59 , 60 ].…”

Section: Discussionmentioning

confidence: 99%

“…Discrepant viral evidence results between qRT-PCR, ISH and IF/IHC technologies have been the subject of several recent studies 60 , 61 , 62 , 63 . The presence of current viral load, the phase of disease course as well as the severity of COVID-19 all have impact on the detection rate of viral RNA or viral protein in a given sample 60 , 61 , 62 , 63 .…”

Section: Discussionmentioning

confidence: 99%

See 3 more Smart Citations

SARS-CoV-2 leads to a small vessel endotheliitis in the heart

et al. 2021

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Section: Discussionsupporting

confidence: 86%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

SARS-CoV-2 leads to a small vessel endotheliitis in the heart

et al. 2021

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“…A genomewide association study identified a kidney failure-related 3p21.31 gene cluster as a genetic susceptibility locus in patients with COVID-19 with respiratory 36 . Moreover, a latest study demonstrated the presence of SARS-CoV-2 RNA and protein in anatomically distinct regions of the nasopharynx and brain 37 . Cumulative evidence indicate that a heart-brain-kidney network 38 may be associated with SARS-CoV-2 infection.…”

Section: /14mentioning

confidence: 99%

Tea flavonoids blocking multiple SARS-CoV-2 protein targets judged from molecular docking

Wang¹,

Sang²,

Su³

et al. 2020

Preprint

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Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has caused Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic. Flavonoids derived Chinese patent medicines has outstanding curative effects for the improvement and treatment of COVID-19. There are numerous studies suggesting that flavonoids-rich tea have antiviral effects. However, bioactive compounds from tea flavonoids with anti-COVID-19 effect, and the potential molecular mechanisms are unclear. In this study, we performed a molecular docking of 468 tea flavonoids and its derivatives with main protease (Mpro), angiotensin-converting enzyme 2 (ACE2), RNA dependent RNA polymerase (RdRp), compared with the positive control drugs of each target. The results suggested that ACE2 and RdRp are the main targets inhibited by tea flavonoids.Q3G Isovitexin, and TF would be considered as the potential candidate compounds of RdRp and ACE2. Our study provides a theoretical basis for further drug design of anti-COVID-19.

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Viral Antigen and Inflammatory Biomarkers in Cerebrospinal Fluid in Patients With COVID-19 Infection and Neurologic Symptoms Compared With Control Participants Without Infection or Neurologic Symptoms

et al. 2022

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Key Points Question Are cerebrospinal fluid (CSF) SARS-CoV-2 antigens associated with central nervous system inflammation in patients with COVID-19? Findings Of 44 patients with COVID-19 (23 neurosymptomatic) included in this hospital-based cross-sectional study, CSF nucleocapsid antigen was detectable in 89% of patients with available data and was significantly correlated with immune activation markers (neopterin and interferon γ). Moreover, neurosymptomatic patients had a more pronounced inflammatory CSF profile compared with neuroasymptomatic patients that could not be attributed to differences in COVID-19 severity. Meaning These results suggest that viral components may contribute to central nervous system immune responses without direct viral invasion and highlight the clinical importance of neurologic symptoms.

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

Cited by 1,153 publications

References 51 publications

SARS-CoV-2 leads to a small vessel endotheliitis in the heart

SARS-CoV-2 leads to a small vessel endotheliitis in the heart

Tea flavonoids blocking multiple SARS-CoV-2 protein targets judged from molecular docking

Viral Antigen and Inflammatory Biomarkers in Cerebrospinal Fluid in Patients With COVID-19 Infection and Neurologic Symptoms Compared With Control Participants Without Infection or Neurologic Symptoms

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