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Article ; Online: Global Teleneurology.

Wechsler, Lawrence R / Koralnik, Igor J

2022 Volume 91, Issue 4, Page(s) 443–444

MeSH term(s)	COVID-19 ; Humans ; Neurology ; Pandemics ; Remote Consultation ; Zambia
Language	English
Publishing date	2022-03-08
Publishing country	United States
Document type	Journal Article ; Comment
ZDB-ID	80362-5
ISSN	1531-8249 ; 0364-5134
ISSN (online)	1531-8249
ISSN	0364-5134
DOI	10.1002/ana.26334
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Zs.MO 478: Show issues

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Article ; Online: Postacute Sequelae of SARS-CoV-2 Infection.

Batra, Ayush / Nath, Avindra / Koralnik, Igor J

JAMA

2023 Volume 330, Issue 15, Page(s) 1491–1492

MeSH term(s)	Humans ; COVID-19 ; SARS-CoV-2 ; Disease Progression
Language	English
Publishing date	2023-10-17
Publishing country	United States
Document type	Letter ; Comment
ZDB-ID	2958-0
ISSN	1538-3598 ; 0254-9077 ; 0002-9955 ; 0098-7484
ISSN (online)	1538-3598
ISSN	0254-9077 ; 0002-9955 ; 0098-7484
DOI	10.1001/jama.2023.15709
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Article ; Online: Can Immune Checkpoint Inhibitors Keep JC Virus in Check?

Koralnik, Igor J

The New England journal of medicine

2019 Volume 380, Issue 17, Page(s) 1667–1668

MeSH term(s)	Antibodies, Monoclonal, Humanized ; Humans ; JC Virus/immunology ; Leukoencephalopathy, Progressive Multifocal ; Natalizumab
Chemical Substances	Antibodies, Monoclonal, Humanized ; Natalizumab ; pembrolizumab (DPT0O3T46P)
Language	English
Publishing date	2019-04-10
Publishing country	United States
Document type	Editorial ; Comment
ZDB-ID	207154-x
ISSN	1533-4406 ; 0028-4793
ISSN (online)	1533-4406
ISSN	0028-4793
DOI	10.1056/NEJMe1904140
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Article ; Online: Characterization of the brain virome in human immunodeficiency virus infection and substance use disorder.

Dang, Xin / Hanson, Barbara A / Orban, Zachary S / Jimenez, Millenia / Suchy, Stephen / Koralnik, Igor J

PloS one

2024 Volume 19, Issue 4, Page(s) e0299891

Abstract: Viruses can infect the brain in individuals with and without HIV-infection: however, the brain virome is poorly characterized. Metabolic alterations have been identified which predispose people to substance use disorder (SUD), but whether these could be ... ...

Abstract	Viruses can infect the brain in individuals with and without HIV-infection: however, the brain virome is poorly characterized. Metabolic alterations have been identified which predispose people to substance use disorder (SUD), but whether these could be triggered by viral infection of the brain is unknown. We used a target-enrichment, deep sequencing platform and bioinformatic pipeline named "ViroFind", for the unbiased characterization of DNA and RNA viruses in brain samples obtained from the National Neuro-AIDS Tissue Consortium. We analyzed fresh frozen post-mortem prefrontal cortex from 72 individuals without known viral infection of the brain, including 16 HIV+/SUD+, 20 HIV+/SUD-, 16 HIV-/SUD+, and 20 HIV-/SUD-. The average age was 52.3 y and 62.5% were males. We identified sequences from 26 viruses belonging to 11 viral taxa. These included viruses with and without known pathogenic potential or tropism to the nervous system, with sequence coverage ranging from 0.03 to 99.73% of the viral genomes. In SUD+ people, HIV-infection was associated with a higher total number of viruses, and HIV+/SUD+ compared to HIV-/SUD+ individuals had an increased frequency of Adenovirus (68.8 vs 0%; p<0.001) and Epstein-Barr virus (EBV) (43.8 vs 6.3%; p=0.037) as well as an increase in Torque Teno virus (TTV) burden. Conversely, in HIV+ people, SUD was associated with an increase in frequency of Hepatitis C virus, (25 in HIV+/SUD+ vs 0% in HIV+/SUD-; p=0.031). Finally, HIV+/SUD- compared to HIV-/SUD- individuals had an increased frequency of EBV (50 vs 0%; p<0.001) and an increase in TTV viral burden, but a decreased Adenovirus viral burden. These data demonstrate an unexpectedly high variety in the human brain virome, identifying targets for future research into the impact of these taxa on the central nervous system. ViroFind could become a valuable tool for monitoring viral dynamics in various compartments, monitoring outbreaks, and informing vaccine development.
MeSH term(s)	Male ; Humans ; Middle Aged ; Female ; Virome ; Epstein-Barr Virus Infections/complications ; DNA Virus Infections ; DNA, Viral/genetics ; Herpesvirus 4, Human/genetics ; HIV Infections/epidemiology ; Virus Diseases/complications ; Torque teno virus/genetics ; Brain ; Hepacivirus/genetics ; Substance-Related Disorders/complications
Chemical Substances	DNA, Viral
Language	English
Publishing date	2024-04-17
Publishing country	United States
Document type	Journal Article
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0299891
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Article ; Online: Therapeutic Approaches to the Neurologic Manifestations of COVID-19.

Graham, Edith L / Koralnik, Igor J / Liotta, Eric M

Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics

2022 Volume 19, Issue 5, Page(s) 1435–1466

Abstract: As of May 2022, there have been more than 527 million infections with severe acute respiratory disease coronavirus type 2 (SARS-CoV-2) and over 6.2 million deaths from Coronavirus Disease 2019 (COVID-19) worldwide. COVID-19 is a multisystem illness with ... ...

Abstract	As of May 2022, there have been more than 527 million infections with severe acute respiratory disease coronavirus type 2 (SARS-CoV-2) and over 6.2 million deaths from Coronavirus Disease 2019 (COVID-19) worldwide. COVID-19 is a multisystem illness with important neurologic consequences that impact long-term morbidity and mortality. In the acutely ill, the neurologic manifestations of COVID-19 can include distressing but relatively benign symptoms such as headache, myalgias, and anosmia; however, entities such as encephalopathy, stroke, seizures, encephalitis, and Guillain-Barre Syndrome can cause neurologic injury and resulting disability that persists long after the acute pulmonary illness. Furthermore, as many as one-third of patients may experience persistent neurologic symptoms as part of a Post-Acute Sequelae of SARS-CoV-2 infection (Neuro-PASC) syndrome. This Neuro-PASC syndrome can affect patients who required hospitalization for COVID-19 or patients who did not require hospitalization and who may have had minor or no pulmonary symptoms. Given the large number of individuals affected and the ability of neurologic complications to impair quality of life and productivity, the neurologic manifestations of COVID-19 are likely to have major and long-lasting personal, public health, and economic consequences. While knowledge of disease mechanisms and therapies acquired prior to the pandemic can inform us on how to manage patients with the neurologic manifestations of COVID-19, there is a critical need for improved understanding of specific COVID-19 disease mechanisms and development of therapies that target the neurologic morbidities of COVID-19. This current perspective reviews evidence for proposed disease mechanisms as they inform the neurologic management of COVID-19 in adult patients while also identifying areas in need of further research.
MeSH term(s)	Adult ; Humans ; COVID-19/complications ; SARS-CoV-2 ; Quality of Life ; Stroke ; Seizures
Language	English
Publishing date	2022-07-21
Publishing country	United States
Document type	Journal Article
ZDB-ID	2316693-9
ISSN	1878-7479 ; 1933-7213
ISSN (online)	1878-7479
ISSN	1933-7213
DOI	10.1007/s13311-022-01267-y
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Article: Case report: Treatment of long COVID with a SARS-CoV-2 antiviral and IL-6 blockade in a patient with rheumatoid arthritis and SARS-CoV-2 antigen persistence.

Visvabharathy, Lavanya / Orban, Zachary S / Koralnik, Igor J

Frontiers in medicine

2022 Volume 9, Page(s) 1003103

Abstract: Introduction: Long COVID, or post-acute sequelae of SARS-CoV-2 infection (PASC) in ∼30% of all infected individuals. Here, we present a case of PASC in a patient with rheumatoid arthritis characterized by viral persistence in the nasopharynx for 6 ... ...

Abstract	Introduction: Long COVID, or post-acute sequelae of SARS-CoV-2 infection (PASC) in ∼30% of all infected individuals. Here, we present a case of PASC in a patient with rheumatoid arthritis characterized by viral persistence in the nasopharynx for 6 months after acute infection. We demonstrate transient disappearance of antigen persistence and decreased antiviral and autoimmune T cell responses after nirmatrelvir/ritonavir and tocilizumab treatment. Case presentation: A 37-year-old female with a 7-year history of rheumatoid arthritis enrolled in a COVID-19 research study was found to continuously test SARS-CoV-2 antigen positive in the nasopharynx for 6 months after acute infection. She simultaneously presented with new-onset PASC symptoms including chronic occipital headache and periods of intense fatigue 8 weeks after acute infection. The patient was prescribed nirmatrelvir/ritonavir to treat SARS-CoV-2 persistence at 3.5 months post-acute infection and observed a reduction in PASC symptoms 3 weeks after completing antiviral treatment. After resurgence of PASC symptoms, she stopped treatment with tocilizumab for rheumatoid arthritis to attempt complete SARS-CoV-2 viral clearance. The severity of the patient's PASC symptoms subsequently increased, and she developed new-onset brain fog in addition to previous symptoms, which resolved after resumption of tocilizumab treatment. Assessment of adaptive immune responses demonstrated that nirmatrelvir/ritonavir and tocilizumab treatment decreased antiviral and autoreactive T cell activation. After resuming tocilizumab treatment, the patient's PASC symptoms were significantly reduced, but nasopharyngeal antigen positivity remained. Conclusion: These data suggest that nirmatrelvir/ritonavir should be considered in the treatment of PASC in patients who have SARS-CoV-2 antigen persistence, though care must be taken to monitor the patient for symptom resurgence or viral reactivation. In addition, the IL-6 inhibitor tocilizumab may ameliorate PASC symptoms in patients with persistent headache, fatigue, and brain fog.
Language	English
Publishing date	2022-09-23
Publishing country	Switzerland
Document type	Case Reports
ZDB-ID	2775999-4
ISSN	2296-858X
ISSN	2296-858X
DOI	10.3389/fmed.2022.1003103
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Article ; Online: Reply to COVID-19 encephalopathy, Bayes rule, and a plea for case-control studies.

Liotta, Eric M / Batra, Ayush / Koralnik, Igor J

Annals of clinical and translational neurology

2021 Volume 8, Issue 3, Page(s) 726

MeSH term(s)	Bayes Theorem ; Brain Diseases ; COVID-19 ; Case-Control Studies ; Humans ; Morbidity ; SARS-CoV-2
Language	English
Publishing date	2021-01-29
Publishing country	United States
Document type	Letter ; Comment
ZDB-ID	2740696-9
ISSN	2328-9503 ; 2328-9503
ISSN (online)	2328-9503
ISSN	2328-9503
DOI	10.1002/acn3.51287
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Article ; Online: COVID-19: A Global Threat to the Nervous System.

Koralnik, Igor J / Tyler, Kenneth L

Annals of neurology

2020 Volume 88, Issue 1, Page(s) 1–11

Abstract: In less than 6 months, the severe acute respiratory syndrome-coronavirus type 2 (SARS-CoV-2) has spread worldwide infecting nearly 6 million people and killing over 350,000. Initially thought to be restricted to the respiratory system, we now understand ... ...

Abstract	In less than 6 months, the severe acute respiratory syndrome-coronavirus type 2 (SARS-CoV-2) has spread worldwide infecting nearly 6 million people and killing over 350,000. Initially thought to be restricted to the respiratory system, we now understand that coronavirus disease 2019 (COVID-19) also involves multiple other organs, including the central and peripheral nervous system. The number of recognized neurologic manifestations of SARS-CoV-2 infection is rapidly accumulating. These may result from a variety of mechanisms, including virus-induced hyperinflammatory and hypercoagulable states, direct virus infection of the central nervous system (CNS), and postinfectious immune mediated processes. Example of COVID-19 CNS disease include encephalopathy, encephalitis, acute disseminated encephalomyelitis, meningitis, ischemic and hemorrhagic stroke, venous sinus thrombosis, and endothelialitis. In the peripheral nervous system, COVID-19 is associated with dysfunction of smell and taste, muscle injury, the Guillain-Barre syndrome, and its variants. Due to its worldwide distribution and multifactorial pathogenic mechanisms, COVID-19 poses a global threat to the entire nervous system. Although our understanding of SARS-CoV-2 neuropathogenesis is still incomplete and our knowledge is evolving rapidly, we hope that this review will provide a useful framework and help neurologists in understanding the many neurologic facets of COVID-19. ANN NEUROL 2020;88:1-11 ANN NEUROL 2020;88:1-11.
MeSH term(s)	Betacoronavirus ; Brain Diseases/etiology ; Brain Diseases/physiopathology ; Brain Ischemia/etiology ; Brain Ischemia/physiopathology ; COVID-19 ; Coronavirus Infections/complications ; Coronavirus Infections/physiopathology ; Disseminated Intravascular Coagulation/etiology ; Disseminated Intravascular Coagulation/physiopathology ; Encephalitis/etiology ; Encephalitis/physiopathology ; Encephalomyelitis, Acute Disseminated/etiology ; Encephalomyelitis, Acute Disseminated/physiopathology ; Guillain-Barre Syndrome/etiology ; Guillain-Barre Syndrome/physiopathology ; Humans ; Inflammation ; Intracranial Hemorrhages/etiology ; Intracranial Hemorrhages/physiopathology ; Leukoencephalitis, Acute Hemorrhagic/etiology ; Leukoencephalitis, Acute Hemorrhagic/physiopathology ; Meningitis, Viral/etiology ; Meningitis, Viral/physiopathology ; Nervous System Diseases/etiology ; Nervous System Diseases/physiopathology ; Olfaction Disorders/etiology ; Olfaction Disorders/physiopathology ; Pandemics ; Pneumonia, Viral/complications ; Pneumonia, Viral/physiopathology ; SARS-CoV-2 ; Sinus Thrombosis, Intracranial/etiology ; Sinus Thrombosis, Intracranial/physiopathology ; Stroke/etiology ; Stroke/physiopathology ; Thrombophilia/etiology ; Thrombophilia/physiopathology
Keywords	covid19
Language	English
Publishing date	2020-06-07
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	80362-5
ISSN	1531-8249 ; 0364-5134
ISSN (online)	1531-8249
ISSN	0364-5134
DOI	10.1002/ana.25807
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Article ; Online: Reader Response: A Prospective Study of Neurologic Disorders in Hospitalized Patients With COVID-19 in New York City.

Liotta, Eric M / Batra, Ayush / Koralnik, Igor J

Neurology

2021 Volume 96, Issue 11, Page(s) 550

MeSH term(s)	COVID-19 ; Humans ; Nervous System Diseases/epidemiology ; Neuroimaging ; New York City/epidemiology ; Prospective Studies ; Retrospective Studies ; SARS-CoV-2
Language	English
Publishing date	2021-03-15
Publishing country	United States
Document type	Journal Article ; Comment
ZDB-ID	207147-2
ISSN	1526-632X ; 0028-3878
ISSN (online)	1526-632X
ISSN	0028-3878
DOI	10.1212/WNL.0000000000011613
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Article ; Online: SARS-CoV-2-Specific Immune Responses in Patients With Postviral Syndrome After Suspected COVID-19.

Orban, Zachary S / Visvabharathy, Lavanya / Perez Giraldo, Gina S / Jimenez, Millenia / Koralnik, Igor J

Neurology(R) neuroimmunology & neuroinflammation

2023 Volume 10, Issue 6

Abstract: Background and objectives: Millions of Americans were exposed to SARS-CoV-2 early in the pandemic but could not get diagnosed with COVID-19 due to testing limitations. Many have developed a postviral syndrome (PVS) including neurologic manifestations ... ...

Abstract	Background and objectives: Millions of Americans were exposed to SARS-CoV-2 early in the pandemic but could not get diagnosed with COVID-19 due to testing limitations. Many have developed a postviral syndrome (PVS) including neurologic manifestations similar to those with postacute sequelae of SARS-CoV-2 infection (Neuro-PASC). Owing to those circumstances, proof of SARS-CoV-2 infection was not required for evaluation at Northwestern Medicine's Neuro COVID-19 clinic. We sought to investigate clinical and immunologic findings suggestive of SARS-CoV-2 exposure in patients with PVS. Methods: We measured SARS-CoV-2-specific humoral and cell-mediated immune responses against Nucleocapsid and Spike proteins in 29 patients with PVS after suspected COVID-19, 32 confirmed age-matched/sex-matched Neuro-PASC (NP) patients, and 18 unexposed healthy controls. Neurologic symptoms and signs, comorbidities, quality of life, and cognitive testing data collected during clinic visits were studied retrospectively. Results: Of 29 patients with PVS, 12 (41%) had detectable humoral or cellular immune responses consistent with prior exposure to SARS-CoV-2. Of 12 PVS responders (PVS Discussion: Antibody and T-cell assays showed evidence of prior SARS-CoV-2 exposure in approximately 40% of the PVS group. Three-quarters of patients with PVS
MeSH term(s)	Humans ; SARS-CoV-2 ; COVID-19/complications ; COVID-19 Testing ; Quality of Life ; Retrospective Studies ; Immunity
Language	English
Publishing date	2023-08-23
Publishing country	United States
Document type	Journal Article
ZDB-ID	2767740-0
ISSN	2332-7812 ; 2332-7812
ISSN (online)	2332-7812
ISSN	2332-7812
DOI	10.1212/NXI.0000000000200159
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