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1.
Front Immunol ; 12: 782731, 2021.
Article in English | MEDLINE | ID: covidwho-1581325

ABSTRACT

The SARS-CoV-2 and its variants are still hitting the world. Ever since the outbreak, neurological involvements as headache, ageusia, and anosmia in COVID-19 patients have been emphasized and reported. But the pathogenesis of these new-onset neurological manifestations in COVID-19 patients is still obscure and controversial. As difficulty always lay in the diagnosis of neurological infection, current reports to validate the presence of SARS-CoV-2 in cerebrospinal fluid (CSF) almost relied on the basic methods and warranted improvement. Here we reported a case series of 8 patients with prominent new-onset neurological manifestations, who were screened out from a patch of 304 COVID-19 confirmed patients. Next-generation sequencing (NGS) and proteomics were conducted in the simultaneously obtained CSF and serum samples of the selected patients, with three non-COVID-19 patients with matched demographic features used as the controls for proteomic analysis. SARS-CoV-2 RNA was detected in the CSF of four COVID-19 patients and was suspicious in the rest four remaining patients by NGS, but was negative in all serum samples. Proteomic analysis revealed that 185 and 59 proteins were differentially expressed in CSF and serum samples, respectively, and that only 20 proteins were shared, indicating that the proteomic changes in CSF were highly specific. Further proteomic annotation highlighted the involvement of complement system, PI3K-Akt signaling pathway, enhanced cellular interaction, and macrophages in the CSF proteomic alterations. This study, equipped with NGS and proteomics, reported a high detection rate of SARS-CoV-2 in the CSF of COVID-19 patients and the proteomic alteration of CSF, which would provide insights into understanding the pathological mechanism of SARS-CoV-2 CNS infection.


Subject(s)
COVID-19/cerebrospinal fluid , Central Nervous System Diseases/virology , Cerebrospinal Fluid/metabolism , Cerebrospinal Fluid/virology , RNA, Viral/cerebrospinal fluid , Adult , Aged , Aged, 80 and over , Female , High-Throughput Nucleotide Sequencing , Humans , Male , Middle Aged , Proteomics , SARS-CoV-2 , Sequence Analysis, RNA
2.
J Stroke Cerebrovasc Dis ; 30(9): 105915, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1253282

ABSTRACT

We report the case of a 35-year-old male with COVID-19 encephalitis presenting as a stroke mimic with sudden-onset expressive and receptive dysphasia, mild confusion and right arm incoordination. The patient received thrombolysis for a suspected ischaemic stroke, but later became febrile and SARS-CoV-2 was detected in cerebrospinal fluid. Electroencephalography demonstrated excess in slow waves, but neuroimaging was reported as normal. Respiratory symptoms were absent throughout and nasopharyngeal swab was negative for SARS-CoV-2. At the most recent follow-up, the patient had made a full neurological recovery. Clinicians should therefore consider testing for SARS-CoV-2 in CSF in patients who present with acute focal neurology, confusion and fever during the pandemic, even when there is no evidence of respiratory infection.


Subject(s)
COVID-19 Nucleic Acid Testing , COVID-19/diagnosis , Encephalitis, Viral/diagnosis , Ischemic Stroke/diagnosis , RNA, Viral/cerebrospinal fluid , SARS-CoV-2/genetics , Adult , COVID-19/cerebrospinal fluid , COVID-19/virology , Diagnosis, Differential , Electroencephalography , Encephalitis, Viral/cerebrospinal fluid , Encephalitis, Viral/virology , Humans , Magnetic Resonance Imaging , Male , Predictive Value of Tests , Tomography, X-Ray Computed
3.
Pediatr Infect Dis J ; 40(7): e274-e276, 2021 07 01.
Article in English | MEDLINE | ID: covidwho-1228550

ABSTRACT

Underlying mechanisms on the association between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and neurologic complications are still poorly understood. Cases of Guillain-Barré Syndrome (GBS) have been linked to the SARS-CoV-2 infection as the result of dysregulated immune response with damage in neuronal tissues. In the current report, we present the first pediatric case of GBS with detection of SARS-CoV-2 in the cerebrospinal fluid (CFS). This unique case of COVID-19-associated GBS with detection of SARS-CoV-2 RNA in the CSF indicates direct viral involvement inducing peripheral nerve inflammation.


Subject(s)
COVID-19/cerebrospinal fluid , COVID-19/diagnosis , Guillain-Barre Syndrome/complications , RNA, Viral/cerebrospinal fluid , Adolescent , COVID-19/complications , Cauda Equina/diagnostic imaging , Cauda Equina/pathology , Cauda Equina/virology , Female , Guillain-Barre Syndrome/virology , Humans , Inflammation/virology , Magnetic Resonance Imaging , SARS-CoV-2/isolation & purification
4.
Neurology ; 95(10): 445-449, 2020 09 08.
Article in English | MEDLINE | ID: covidwho-999777

ABSTRACT

Here, we report a case of COVID-19-related acute necrotizing encephalopathy where SARS-CoV-2 RNA was found in CSF 19 days after symptom onset after testing negative twice. Although monocytes and protein levels in CSF were only marginally increased, and our patient never experienced a hyperinflammatory state, her neurologic function deteriorated into coma. MRI of the brain showed pathologic signal symmetrically in central thalami, subinsular regions, medial temporal lobes, and brain stem. Extremely high concentrations of the neuronal injury markers neurofilament light and tau, as well as an astrocytic activation marker, glial fibrillary acidic protein, were measured in CSF. Neuronal rescue proteins and other pathways were elevated in the in-depth proteomics analysis. The patient received IV immunoglobulins and plasma exchange. Her neurologic status improved, and she was extubated 4 weeks after symptom onset. This case report highlights the neurotropism of SARS-CoV-2 in selected patients and emphasizes the importance of repeated lumbar punctures and CSF analyses in patients with suspected COVID-19 and neurologic symptoms.


Subject(s)
Brain/diagnostic imaging , Coronavirus Infections/cerebrospinal fluid , Leukoencephalitis, Acute Hemorrhagic/cerebrospinal fluid , Pneumonia, Viral/cerebrospinal fluid , RNA, Viral/cerebrospinal fluid , Acyclovir/therapeutic use , Antiviral Agents/therapeutic use , Betacoronavirus/genetics , COVID-19 , Coronavirus Infections/diagnostic imaging , Coronavirus Infections/physiopathology , Coronavirus Infections/therapy , Female , Glial Fibrillary Acidic Protein/cerebrospinal fluid , Humans , Immunoglobulins, Intravenous/therapeutic use , Immunologic Factors/therapeutic use , Interleukin-6/cerebrospinal fluid , Leukoencephalitis, Acute Hemorrhagic/diagnostic imaging , Leukoencephalitis, Acute Hemorrhagic/physiopathology , Leukoencephalitis, Acute Hemorrhagic/therapy , Magnetic Resonance Imaging , Middle Aged , Neurofilament Proteins/cerebrospinal fluid , Pandemics , Plasma Exchange , Pneumonia, Viral/diagnostic imaging , Pneumonia, Viral/physiopathology , Pneumonia, Viral/therapy , Real-Time Polymerase Chain Reaction , SARS-CoV-2 , Tomography, X-Ray Computed , Viral Tropism , tau Proteins/cerebrospinal fluid
6.
Int J Infect Dis ; 96: 567-569, 2020 Jul.
Article in English | MEDLINE | ID: covidwho-526616

ABSTRACT

We report that patients with COVID-19 displaying distinct neurological disorders have undetectable or extremely low levels of SARS-CoV-2 RNA in the cerebrospinal fluid, indicating that viral clearance precede the neurological involvement. This finding points to the need for the development of more sensitive molecular tests and the investigation of other neurotropic pathogens to exclude concurrent neuroinfection.


Subject(s)
Coronavirus Infections/diagnosis , Coronavirus Infections/physiopathology , Nervous System Diseases/virology , Pneumonia, Viral/diagnosis , Pneumonia, Viral/physiopathology , RNA, Viral/cerebrospinal fluid , Betacoronavirus , COVID-19 , Coronavirus Infections/cerebrospinal fluid , Humans , Pandemics , Pneumonia, Viral/cerebrospinal fluid , SARS-CoV-2
7.
Biosci Trends ; 14(3): 209-211, 2020 Jul 17.
Article in English | MEDLINE | ID: covidwho-276162

ABSTRACT

Recently, an increasing number of reports have indicated that a few patients who were believed to have recovered from COVID-19 initially tested negative but later tested positive. Several hospitals in different countries have detected SARS-CoV-2 RNA in the semen and cerebrospinal fluid of patients with severe COVID-19. Given the fact that the testes and central nervous system are both immune privilege sites and the fact that Ebola virus and Zika virus can avoid immune clearance and continue proliferating and spreading by hiding in those sites, the question of whether SARS-CoV-2 is present in immune privilege sites, it attacks those sites, and it spreads again after proliferating in those sites needs to be investigated.


Subject(s)
Betacoronavirus/immunology , Coronavirus Infections/immunology , Pneumonia, Viral/immunology , RNA, Viral/cerebrospinal fluid , COVID-19 , Coronavirus Infections/cerebrospinal fluid , Humans , Immune Privilege , Pandemics , Pneumonia, Viral/cerebrospinal fluid , SARS-CoV-2 , Semen/virology
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