Fibrin drives thromboinflammation and neuropathology in COVID-19.

Journal

Nature
ISSN: 1476-4687
Titre abrégé: Nature
Pays: England
ID NLM: 0410462

Informations de publication

Date de publication:
28 Aug 2024
Historique:
received: 13 02 2023
accepted: 24 07 2024
medline: 31 8 2024
pubmed: 31 8 2024
entrez: 28 8 2024
Statut: aheadofprint

Résumé

Life-threatening thrombotic events and neurological symptoms are prevalent in COVID-19 and are persistent in patients with long COVID experiencing post-acute sequelae of SARS-CoV-2 infection

Identifiants

DOI: 10.1038/s41586-024-07873-4 PMID: 39198643
pubmed: 39198643
doi: 10.1038/s41586-024-07873-4
pii: 10.1038/s41586-024-07873-4
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

© 2024. The Author(s).

Références

Conway, E. M. et al. Understanding COVID-19-associated coagulopathy. Nat. Rev. Immunol. 22, 639–649 (2022).
pubmed: 35931818 pmcid: 9362465 doi: 10.1038/s41577-022-00762-9
Monje, M. & Iwasaki, A. The neurobiology of long COVID. Neuron 110, 3484–3496 (2022).
Spudich, S. & Nath, A. Nervous system consequences of COVID-19. Science 375, 267–269 (2022).
pubmed: 35050660 doi: 10.1126/science.abm2052
Al-Aly, Z. & Topol, E. Solving the puzzle of Long Covid. Science 383, 830–832 (2024).
pubmed: 38386747 doi: 10.1126/science.adl0867
Taquet, M. et al. Acute blood biomarker profiles predict cognitive deficits 6 and 12 months after COVID-19 hospitalization. Nat. Med. 29, 2498–2508 (2023).
pubmed: 37653345 pmcid: 10579097 doi: 10.1038/s41591-023-02525-y
Greene, C. et al. Blood–brain barrier disruption and sustained systemic inflammation in individuals with long COVID-associated cognitive impairment. Nat. Neurosci. 27, 421–432 (2024).
pubmed: 38388736 pmcid: 10917679 doi: 10.1038/s41593-024-01576-9
Radke, J. et al. Proteomic and transcriptomic profiling of brainstem, cerebellum and olfactory tissues in early- and late-phase COVID-19. Nat. Neurosci. 27, 409–420 (2024).
pubmed: 38366144 doi: 10.1038/s41593-024-01573-y
Lee, M. H. et al. Microvascular injury in the brains of patients with Covid-19. N. Engl. J. Med. 384, 481–483 (2021).
pubmed: 33378608 doi: 10.1056/NEJMc2033369
Lee, M. H. et al. Neurovascular injury with complement activation and inflammation in COVID-19. Brain 145, 2555–2568 (2022).
pubmed: 35788639 doi: 10.1093/brain/awac151
Fox, S. E. et al. Pulmonary and cardiac pathology in African American patients with COVID-19: an autopsy series from New Orleans. Lancet Respir. Med. 8, 681–686 (2020).
pubmed: 32473124 pmcid: 7255143 doi: 10.1016/S2213-2600(20)30243-5
Douaud, G. et al. SARS-CoV-2 is associated with changes in brain structure in UK Biobank. Nature 604, 697–707 (2022).
pubmed: 35255491 pmcid: 9046077 doi: 10.1038/s41586-022-04569-5
Tu, T. M. et al. Acute ischemic stroke during the convalescent phase of asymptomatic COVID-2019 infection in men. JAMA Netw. Open 4, e217498 (2021).
pubmed: 33885771 pmcid: 8063067 doi: 10.1001/jamanetworkopen.2021.7498
Grobbelaar, L. M. et al. SARS-CoV-2 spike protein S1 induces fibrin(ogen) resistant to fibrinolysis: implications for microclot formation in COVID-19. Biosci. Rep. 41, BSR20210611 (2021).
pubmed: 34328172 pmcid: 8380922 doi: 10.1042/BSR20210611
Merad, M., Blish, C. A., Sallusto, F. & Iwasaki, A. The immunology and immunopathology of COVID-19. Science 375, 1122–1127 (2022).
pubmed: 35271343 doi: 10.1126/science.abm8108
Davalos, D. & Akassoglou, K. Fibrinogen as a key regulator of inflammation in disease. Semin. Immunopathol. 34, 43–62 (2012).
pubmed: 22037947 doi: 10.1007/s00281-011-0290-8
Doolittle, R. F., Yang, Z. & Mochalkin, I. Crystal structure studies on fibrinogen and fibrin. Ann. N. Y. Acad. Sci. 936, 31–43 (2001).
pubmed: 11460486 doi: 10.1111/j.1749-6632.2001.tb03492.x
Ryu, J. K. et al. Fibrin-targeting immunotherapy protects against neuroinflammation and neurodegeneration. Nat. Immunol. 19, 1212–1223 (2018).
pubmed: 30323343 pmcid: 6317891 doi: 10.1038/s41590-018-0232-x
Petersen, M. A., Ryu, J. K. & Akassoglou, K. Fibrinogen in neurological diseases: mechanisms, imaging and therapeutics. Nat. Rev. Neurosci. 19, 283–301 (2018).
pubmed: 29618808 pmcid: 6743980 doi: 10.1038/nrn.2018.13
Silva, L. M. et al. Fibrin is a critical regulator of neutrophil effector function at the oral mucosal barrier. Science 374, eabl5450 (2021).
pubmed: 34941394 doi: 10.1126/science.abl5450
Merlini, M. et al. Fibrinogen induces microglia-mediated spine elimination and cognitive impairment in an Alzheimer’s disease model. Neuron 101, 1099–1108 (2019).
pubmed: 30737131 pmcid: 6602536 doi: 10.1016/j.neuron.2019.01.014
Mendiola, A. S. et al. Defining blood-induced microglia functions in neurodegeneration through multiomic profiling. Nat. Immunol. 24, 1173–1187 (2023).
pubmed: 37291385 pmcid: 10307624 doi: 10.1038/s41590-023-01522-0
Long, W. et al. Abnormal fibrinogen level as a prognostic indicator in coronavirus disease patients: a retrospective cohort study. Front. Med. 8, 687220 (2021).
doi: 10.3389/fmed.2021.687220
Pretorius, E. et al. Persistent clotting protein pathology in long COVID/post-acute sequelae of COVID-19 (PASC) is accompanied by increased levels of antiplasmin. Cardiovasc. Diabetol. 20, 172 (2021).
pubmed: 34425843 pmcid: 8381139 doi: 10.1186/s12933-021-01359-7
Liu, Y. et al. The N501Y spike substitution enhances SARS-CoV-2 infection and transmission. Nature 602, 294–299 (2022).
pubmed: 34818667 doi: 10.1038/s41586-021-04245-0
Lijnen, H. R. Elements of the fibrinolytic system. Ann. N. Y. Acad. Sci. 936, 226–236 (2001).
pubmed: 11460480 doi: 10.1111/j.1749-6632.2001.tb03511.x
Ugarova, T. P. et al. Sequence γ377-395(P2), but not γ190-202(P1), is the binding site for the α
pubmed: 12899623 doi: 10.1021/bi034057k
Violi, F. et al. Nox2 activation in Covid-19. Redox Biol. 36, 101655 (2020).
pubmed: 32738789 pmcid: 7381406 doi: 10.1016/j.redox.2020.101655
Rendeiro, A. F. et al. The spatial landscape of lung pathology during COVID-19 progression. Nature 593, 564–569 (2021).
pubmed: 33780969 pmcid: 8204801 doi: 10.1038/s41586-021-03475-6
Gudowska-Sawczuk, M. & Mroczko, B. What is currently known about the role of CXCL10 in SARS-CoV-2 infection? Int. J. Mol. Sci. 23, 3673 (2022).
pubmed: 35409036 pmcid: 8998241 doi: 10.3390/ijms23073673
Osman, M. et al. Impaired natural killer cell counts and cytolytic activity in patients with severe COVID-19. Blood Adv. 4, 5035–5039 (2020).
pubmed: 33075136 pmcid: 7594380 doi: 10.1182/bloodadvances.2020002650
Liu, C. F. et al. Complement receptor 3 has negative impact on tumor surveillance through suppression of natural killer cell function. Front. Immunol. 8, 1602 (2017).
pubmed: 29209332 pmcid: 5702005 doi: 10.3389/fimmu.2017.01602
Bouhaddou, M. et al. The global phosphorylation landscape of SARS-CoV-2 infection. Cell 182, 685–712 (2020).
pubmed: 32645325 pmcid: 7321036 doi: 10.1016/j.cell.2020.06.034
Bjorkstrom, N. K., Strunz, B. & Ljunggren, H. G. Natural killer cells in antiviral immunity. Nat. Rev. Immunol. 22, 112–123 (2022).
pubmed: 34117484 doi: 10.1038/s41577-021-00558-3
Swank, Z. et al. Persistent circulating SARS-CoV-2 spike is associated with post-acute COVID-19 sequelae. Clin. Infect. Dis. 76, e487–e490 (2022).
pmcid: 10169416 doi: 10.1093/cid/ciac722
Ryu, J. K. et al. Blood coagulation protein fibrinogen promotes autoimmunity and demyelination via chemokine release and antigen presentation. Nat. Commun. 6, 8164 (2015).
pubmed: 26353940 doi: 10.1038/ncomms9164
Scully, M. et al. Pathologic antibodies to platelet factor 4 after ChAdOx1 nCoV-19 vaccination. N. Engl. J. Med. 384, 2202–2211 (2021).
pubmed: 33861525 doi: 10.1056/NEJMoa2105385
Ols, S. et al. Route of vaccine administration alters antigen trafficking but not innate or adaptive immunity. Cell Rep. 30, 3964–3971 e3967 (2020).
pubmed: 32209459 pmcid: 7198771 doi: 10.1016/j.celrep.2020.02.111
Mercade-Besora, N. et al. The role of COVID-19 vaccines in preventing post-COVID-19 thromboembolic and cardiovascular complications. Heart 110, 635–643 (2024).
pubmed: 38471729
Faksova, K. et al. COVID-19 vaccines and adverse events of special interest: a multinational Global Vaccine Data Network (GVDN) cohort study of 99 million vaccinated individuals. Vaccine 42, 2200–2211 (2024).
pubmed: 38350768 doi: 10.1016/j.vaccine.2024.01.100
Akassoglou, K. The immunology of blood: connecting the dots at the neurovascular interface. Nat. Immunol. 21, 710–712 (2020).
pubmed: 32577008 pmcid: 7394454 doi: 10.1038/s41590-020-0671-z
Stein, S. R. et al. SARS-CoV-2 infection and persistence in the human body and brain at autopsy. Nature 612, 758–763 (2022).
pubmed: 36517603 pmcid: 9749650 doi: 10.1038/s41586-022-05542-y
Tarres-Freixas, F. et al. Heterogeneous infectivity and pathogenesis of SARS-CoV-2 variants Beta, Delta and Omicron in transgenic K18-hACE2 and wildtype mice. Front. Microbiol. 13, 840757 (2022).
pubmed: 35602059 pmcid: 9114491 doi: 10.3389/fmicb.2022.840757
Soung, A. L. et al. COVID-19 induces CNS cytokine expression and loss of hippocampal neurogenesis. Brain 145, 4193–4201 (2022).
pubmed: 36004663 pmcid: 9452175 doi: 10.1093/brain/awac270
Fernandez-Castaneda, A. et al. Mild respiratory COVID can cause multi-lineage neural cell and myelin dysregulation. Cell 185, 2452–2468 (2022).
pubmed: 35768006 pmcid: 9189143 doi: 10.1016/j.cell.2022.06.008
Song, E. et al. Neuroinvasion of SARS-CoV-2 in human and mouse brain. J. Exp. Med. 218, e20202135 (2021).
pubmed: 33433624 pmcid: 7808299 doi: 10.1084/jem.20202135
Antonelli, M., Pujol, J. C., Spector, T. D., Ourselin, S. & Steves, C. J. Risk of long COVID associated with delta versus omicron variants of SARS-CoV-2. Lancet 399, 2263–2264 (2022).
pubmed: 35717982 pmcid: 9212672 doi: 10.1016/S0140-6736(22)00941-2
Suryawanshi, R. K. et al. Limited cross-variant immunity from SARS-CoV-2 Omicron without vaccination. Nature 607, 351–355 (2022).
pubmed: 35584773 pmcid: 9279157 doi: 10.1038/s41586-022-04865-0
Gunji, Y., Lewis, J. & Gorelik, E. Fibrin formation inhibits the in vitro cytotoxic activity of human natural and lymphokine-activated killer cells. Blood Coagul. Fibrinolysis 1, 663–672 (1990).
pubmed: 2133246
Cerwenka, A. & Lanier, L. L. Natural killer cell memory in infection, inflammation and cancer. Nat. Rev. Immunol. 16, 112–123 (2016).
pubmed: 26806484 doi: 10.1038/nri.2015.9
Muradashvili, N. et al. Fibrinogen-induced increased pial venular permeability in mice. J. Cereb. Blood Flow Metab. 32, 150–163 (2012).
pubmed: 21989482 doi: 10.1038/jcbfm.2011.144
Kantor, A. B., Akassoglou, K. & Stavenhagen, J. B. Fibrin-targeting immunotherapy for dementia. J. Prev. Alzheimers Dis. 10, 647–660 (2023).
pubmed: 37874085 pmcid: 11227370
Suh, T. T. et al. Resolution of spontaneous bleeding events but failure of pregnancy in fibrinogen-deficient mice. Genes Dev. 9, 2020–2033 (1995).
pubmed: 7649481 doi: 10.1101/gad.9.16.2020
Flick, M. J. et al. Leukocyte engagement of fibrin(ogen) via the integrin receptor α
pubmed: 15173886 pmcid: 419487 doi: 10.1172/JCI20741
Stadlbauer, D. et al. SARS-CoV-2 seroconversion in humans: a detailed protocol for a serological assay, antigen production, and test setup. Curr. Protoc. Microbiol. 57, e100 (2020).
pubmed: 32302069 pmcid: 7235504 doi: 10.1002/cpmc.100
Hotaling, N. A., Bharti, K., Kriel, H. & Simon, C. G. Jr. DiameterJ: a validated open source nanofiber diameter measurement tool. Biomaterials 61, 327–338 (2015).
pubmed: 26043061 pmcid: 4492344 doi: 10.1016/j.biomaterials.2015.05.015
Bates, D., Mächler, M., Bolker, B. & Walker, S. Fitting linear mixed-effects models using lme4. J. Stat. Softw. 67, 1–48 (2015).
doi: 10.18637/jss.v067.i01
Holm, S. A simple sequentially rejective multiple test procedure. Scand. J. Stat. 6, 65–70 (1979).
Pettersen, E. F. et al. UCSF Chimera—a visualization system for exploratory research and analysis. J. Comput. Chem. 25, 1605–1612 (2004).
pubmed: 15264254 doi: 10.1002/jcc.20084
Erturk, A. et al. Three-dimensional imaging of solvent-cleared organs using 3DISCO. Nat. Protoc. 7, 1983–1995 (2012).
pubmed: 23060243 doi: 10.1038/nprot.2012.119
Mendiola, A. S. et al. Transcriptional profiling and therapeutic targeting of oxidative stress in neuroinflammation. Nat. Immunol. 21, 513–524 (2020).
pubmed: 32284594 pmcid: 7523413 doi: 10.1038/s41590-020-0654-0
Stopak, K., de Noronha, C., Yonemoto, W. & Greene, W. C. HIV-1 Vif blocks the antiviral activity of APOBEC3G by impairing both its translation and intracellular stability. Mol. Cell 12, 591–601 (2003).
pubmed: 14527406 doi: 10.1016/S1097-2765(03)00353-8
Tegally, H. et al. Detection of a SARS-CoV-2 variant of concern in South Africa. Nature 592, 438–443 (2021).
pubmed: 33690265 doi: 10.1038/s41586-021-03402-9
Chong, Z. et al. Nasally delivered interferon-λ protects mice against infection by SARS-CoV-2 variants including Omicron. Cell Rep. 39, 110799 (2022).
pubmed: 35523172 pmcid: 9021357 doi: 10.1016/j.celrep.2022.110799
Chen, R. E. et al. In vivo monoclonal antibody efficacy against SARS-CoV-2 variant strains. Nature 596, 103–108 (2021).
pubmed: 34153975 pmcid: 8349859 doi: 10.1038/s41586-021-03720-y
Starr, T. N. et al. SARS-CoV-2 RBD antibodies that maximize breadth and resistance to escape. Nature 597, 97–102 (2021).
pubmed: 34261126 pmcid: 9282883 doi: 10.1038/s41586-021-03807-6
Sevigny, J. et al. The antibody aducanumab reduces Aβ plaques in Alzheimer’s disease. Nature 537, 50–56 (2016).
pubmed: 27582220 doi: 10.1038/nature19323
Sefik, E. et al. Inflammasome activation in infected macrophages drives COVID-19 pathology. Nature 606, 585–593 (2022).
pubmed: 35483404 pmcid: 9288243 doi: 10.1038/s41586-022-04802-1
Sachs, B. D. et al. p75 neurotrophin receptor regulates tissue fibrosis through inhibition of plasminogen activation via a PDE4/cAMP/PKA pathway. J. Cell Biol. 177, 1119–1132 (2007).
pubmed: 17576803 pmcid: 2064370 doi: 10.1083/jcb.200701040
Schachtrup, C. et al. Nuclear pore complex remodeling by p75
pubmed: 26120963 pmcid: 4878404 doi: 10.1038/nn.4054
Davalos, D. et al. Fibrinogen-induced perivascular microglial clustering is required for the development of axonal damage in neuroinflammation. Nat. Commun. 3, 1227 (2012).
pubmed: 23187627 doi: 10.1038/ncomms2230
Robinson, M. D. & Oshlack, A. A scaling normalization method for differential expression analysis of RNA-seq data. Genome Biol. 11, R25 (2010).
pubmed: 20196867 pmcid: 2864565 doi: 10.1186/gb-2010-11-3-r25
Shannon, P. et al. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res. 13, 2498–2504 (2003).
pubmed: 14597658 pmcid: 403769 doi: 10.1101/gr.1239303
Pollenus, E. et al. Aspecific binding of anti-NK1.1 antibodies on myeloid cells in an experimental model for malaria-associated acute respiratory distress syndrome. Malar. J. 23, 110 (2024).
pubmed: 38637828 pmcid: 11025177 doi: 10.1186/s12936-024-04944-9
Burrack, K. S. et al. Interleukin-15 complex treatment protects mice from cerebral malaria by inducing Interleukin-10-producing natural killer cells. Immunity 48, 760–772 (2018).
pubmed: 29625893 pmcid: 5906161 doi: 10.1016/j.immuni.2018.03.012
Wensveen, F. M. et al. NK cells link obesity-induced adipose stress to inflammation and insulin resistance. Nat. Immunol. 16, 376–385 (2015).
pubmed: 25729921 doi: 10.1038/ni.3120
Choi, M. et al. MSstats: an R package for statistical analysis of quantitative mass spectrometry-based proteomic experiments. Bioinformatics 30, 2524–2526 (2014).
pubmed: 24794931 doi: 10.1093/bioinformatics/btu305
Turei, D. et al. Integrated intra- and intercellular signaling knowledge for multicellular omics analysis. Mol. Syst. Biol. 17, e9923 (2021).
pubmed: 33749993 pmcid: 7983032 doi: 10.15252/msb.20209923
Tognatta, R. et al. In vivo two-photon microscopy protocol for imaging microglial responses and spine elimination at sites of fibrinogen deposition in mouse brain. STAR Protoc. 2, 100638 (2021).
pubmed: 34258598 pmcid: 8259313 doi: 10.1016/j.xpro.2021.100638
Shapiro, S. S. & Wilk, M. B. An analysis of variance test for normality (complete samples). Biometrica 52, 591–611 (1965).
doi: 10.1093/biomet/52.3-4.591
Brown, M. B. & Forsythe, A. B. Robust tests for the equality of variances. J. Am. Stat. Assoc. 69, 364–367 (1974).
doi: 10.1080/01621459.1974.10482955

Auteurs

Jae Kyu Ryu (JK)

Center for Neurovascular Brain Immunology at Gladstone and UCSF, San Francisco, CA, USA.
Gladstone Institute of Neurological Disease, San Francisco, CA, USA.
Department of Neurology, Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA, USA.
ORCID: 0000-0002-3992-4011

Zhaoqi Yan (Z)

Center for Neurovascular Brain Immunology at Gladstone and UCSF, San Francisco, CA, USA.
Gladstone Institute of Neurological Disease, San Francisco, CA, USA.
ORCID: 0000-0001-9326-2920

Mauricio Montano (M)

Gladstone Institute of Virology, San Francisco, CA, USA.
Michael Hulton Center for HIV Cure Research at Gladstone, San Francisco, CA, USA.
ORCID: 0000-0002-0353-0037

Elif G Sozmen (EG)

Center for Neurovascular Brain Immunology at Gladstone and UCSF, San Francisco, CA, USA.
Gladstone Institute of Neurological Disease, San Francisco, CA, USA.
Department of Neurology, Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA, USA.

Karuna Dixit (K)

Center for Neurovascular Brain Immunology at Gladstone and UCSF, San Francisco, CA, USA.
Gladstone Institute of Neurological Disease, San Francisco, CA, USA.
ORCID: 0000-0003-3583-2512

Rahul K Suryawanshi (RK)

Gladstone Institute of Virology, San Francisco, CA, USA.
ORCID: 0000-0001-8374-669X

Yusuke Matsui (Y)

Gladstone Institute of Virology, San Francisco, CA, USA.
Michael Hulton Center for HIV Cure Research at Gladstone, San Francisco, CA, USA.
ORCID: 0000-0002-6016-2867

Ekram Helmy (E)

Gladstone Institute of Virology, San Francisco, CA, USA.
Michael Hulton Center for HIV Cure Research at Gladstone, San Francisco, CA, USA.

Prashant Kaushal (P)

Department of Microbiology, Immunology and Molecular Genetics (MIMG), University of California Los Angeles, Los Angeles, CA, USA.
Institute for Quantitative and Computational Biosciences (QCBio), University of California Los Angeles, Los Angeles, CA, USA.

Sara K Makanani (SK)

Department of Microbiology, Immunology and Molecular Genetics (MIMG), University of California Los Angeles, Los Angeles, CA, USA.
Institute for Quantitative and Computational Biosciences (QCBio), University of California Los Angeles, Los Angeles, CA, USA.

Thomas J Deerinck (TJ)

National Center for Microscopy and Imaging Research, Center for Research on Biological Systems, University of California San Diego, La Jolla, CA, USA.

Anke Meyer-Franke (A)

Gladstone Institute of Neurological Disease, San Francisco, CA, USA.

Pamela E Rios Coronado (PE)

Department of Biology, Stanford University, Stanford, CA, USA.

Troy N Trevino (TN)

Center for Neurovascular Brain Immunology at Gladstone and UCSF, San Francisco, CA, USA.
Gladstone Institute of Neurological Disease, San Francisco, CA, USA.

Min-Gyoung Shin (MG)

Gladstone Institute of Data Science and Biotechnology, San Francisco, CA, USA.

Reshmi Tognatta (R)

Center for Neurovascular Brain Immunology at Gladstone and UCSF, San Francisco, CA, USA.
Gladstone Institute of Neurological Disease, San Francisco, CA, USA.
ORCID: 0000-0001-7460-1843

Yixin Liu (Y)

Center for Neurovascular Brain Immunology at Gladstone and UCSF, San Francisco, CA, USA.
Gladstone Institute of Neurological Disease, San Francisco, CA, USA.
ORCID: 0000-0003-1135-2805

Renaud Schuck (R)

Center for Neurovascular Brain Immunology at Gladstone and UCSF, San Francisco, CA, USA.
Gladstone Institute of Neurological Disease, San Francisco, CA, USA.

Lucas Le (L)

Center for Neurovascular Brain Immunology at Gladstone and UCSF, San Francisco, CA, USA.
Gladstone Institute of Neurological Disease, San Francisco, CA, USA.
ORCID: 0009-0005-7794-5736

Hisao Miyajima (H)

Center for Neurovascular Brain Immunology at Gladstone and UCSF, San Francisco, CA, USA.
Gladstone Institute of Neurological Disease, San Francisco, CA, USA.

Andrew S Mendiola (AS)

Center for Neurovascular Brain Immunology at Gladstone and UCSF, San Francisco, CA, USA.
Gladstone Institute of Neurological Disease, San Francisco, CA, USA.
ORCID: 0000-0002-2897-3299

Nikhita Arun (N)

Center for Neurovascular Brain Immunology at Gladstone and UCSF, San Francisco, CA, USA.
Gladstone Institute of Neurological Disease, San Francisco, CA, USA.

Brandon Guo (B)

Center for Neurovascular Brain Immunology at Gladstone and UCSF, San Francisco, CA, USA.
Gladstone Institute of Neurological Disease, San Francisco, CA, USA.

Taha Y Taha (TY)

Gladstone Institute of Virology, San Francisco, CA, USA.
Michael Hulton Center for HIV Cure Research at Gladstone, San Francisco, CA, USA.
ORCID: 0000-0002-7344-7490

Ayushi Agrawal (A)

Gladstone Institute of Data Science and Biotechnology, San Francisco, CA, USA.
ORCID: 0000-0003-2940-8926

Eilidh MacDonald (E)

Center for Neurovascular Brain Immunology at Gladstone and UCSF, San Francisco, CA, USA.
Gladstone Institute of Neurological Disease, San Francisco, CA, USA.

Oliver Aries (O)

Center for Neurovascular Brain Immunology at Gladstone and UCSF, San Francisco, CA, USA.
Gladstone Institute of Neurological Disease, San Francisco, CA, USA.

Aaron Yan (A)

Center for Neurovascular Brain Immunology at Gladstone and UCSF, San Francisco, CA, USA.
Gladstone Institute of Neurological Disease, San Francisco, CA, USA.

Olivia Weaver (O)

Center for Neurovascular Brain Immunology at Gladstone and UCSF, San Francisco, CA, USA.
Gladstone Institute of Neurological Disease, San Francisco, CA, USA.
Department of Pediatrics, University of California San Francisco, San Francisco, CA, USA.

Mark A Petersen (MA)

Center for Neurovascular Brain Immunology at Gladstone and UCSF, San Francisco, CA, USA.
Gladstone Institute of Neurological Disease, San Francisco, CA, USA.
Department of Pediatrics, University of California San Francisco, San Francisco, CA, USA.
ORCID: 0000-0003-1366-1353

Rosa Meza Acevedo (R)

Center for Neurovascular Brain Immunology at Gladstone and UCSF, San Francisco, CA, USA.
Gladstone Institute of Neurological Disease, San Francisco, CA, USA.

Maria Del Pilar S Alzamora (MDPS)

Center for Neurovascular Brain Immunology at Gladstone and UCSF, San Francisco, CA, USA.
Gladstone Institute of Neurological Disease, San Francisco, CA, USA.
ORCID: 0000-0001-8861-387X

Reuben Thomas (R)

Gladstone Institute of Data Science and Biotechnology, San Francisco, CA, USA.

Michela Traglia (M)

Gladstone Institute of Data Science and Biotechnology, San Francisco, CA, USA.

Valentina L Kouznetsova (VL)

San Diego Supercomputer Center, University of California San Diego, La Jolla, CA, USA.
CureScience Institute, San Diego, CA, USA.

Igor F Tsigelny (IF)

Center for Neurovascular Brain Immunology at Gladstone and UCSF, San Francisco, CA, USA.
San Diego Supercomputer Center, University of California San Diego, La Jolla, CA, USA.
CureScience Institute, San Diego, CA, USA.
Department of Neurosciences, University of California San Diego, La Jolla, CA, USA.

Alexander R Pico (AR)

Gladstone Institute of Data Science and Biotechnology, San Francisco, CA, USA.
ORCID: 0000-0001-5706-2163

Kristy Red-Horse (K)

Department of Biology, Stanford University, Stanford, CA, USA.
Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, USA.
Howard Hughes Medical Institute, Stanford University, Stanford, CA, USA.
ORCID: 0000-0003-1541-601X

Mark H Ellisman (MH)

National Center for Microscopy and Imaging Research, Center for Research on Biological Systems, University of California San Diego, La Jolla, CA, USA.
Department of Neurosciences, University of California San Diego, La Jolla, CA, USA.
ORCID: 0000-0001-8893-8455

Nevan J Krogan (NJ)

Gladstone Institute of Data Science and Biotechnology, San Francisco, CA, USA.
Department of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, CA, USA.
Quantitative Biosciences Institute (QBI), University of California San Francisco, San Francisco, CA, USA.
COVID-19 Research Group (QCRG), University of California San Francisco, San Francisco, CA, USA.

Mehdi Bouhaddou (M)

Department of Microbiology, Immunology and Molecular Genetics (MIMG), University of California Los Angeles, Los Angeles, CA, USA.
Institute for Quantitative and Computational Biosciences (QCBio), University of California Los Angeles, Los Angeles, CA, USA.

Melanie Ott (M)

Gladstone Institute of Virology, San Francisco, CA, USA.
Michael Hulton Center for HIV Cure Research at Gladstone, San Francisco, CA, USA.
COVID-19 Research Group (QCRG), University of California San Francisco, San Francisco, CA, USA.
Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
Chan Zuckerberg Biohub, San Francisco, CA, USA.
ORCID: 0000-0002-5697-1274

Warner C Greene (WC)

Gladstone Institute of Virology, San Francisco, CA, USA. warner.greene@gladstone.ucsf.edu.
Michael Hulton Center for HIV Cure Research at Gladstone, San Francisco, CA, USA. warner.greene@gladstone.ucsf.edu.
Department of Medicine, University of California, San Francisco, San Francisco, CA, USA. warner.greene@gladstone.ucsf.edu.
Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA. warner.greene@gladstone.ucsf.edu.
ORCID: 0000-0001-9896-8615

Katerina Akassoglou (K)

Center for Neurovascular Brain Immunology at Gladstone and UCSF, San Francisco, CA, USA. katerina.akassoglou@gladstone.ucsf.edu.
Gladstone Institute of Neurological Disease, San Francisco, CA, USA. katerina.akassoglou@gladstone.ucsf.edu.
Department of Neurology, Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA, USA. katerina.akassoglou@gladstone.ucsf.edu.
ORCID: 0000-0002-2632-1465

Classifications MeSH