Brain injury in COVID-19 is associated with dysregulated innate and adaptive immune responses

Article Multidisciplinary Sciences

Persistent COVID-19 symptoms in a community study of 606,434 people in England

Matthew Whitaker et al.

Summary: This study characterizes Long COVID using data from the REACT-2 community-based study in England, estimating the prevalence of persistent symptoms and identifying risk factors. It also finds evidence of symptom clustering.

NATURE COMMUNICATIONS (2022)

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Article Clinical Neurology

Immune-mediated neurological syndromes in SARS-CoV-2-infected patients

Antoine Guilmot et al.

Summary: Evidence of immune-mediated neurological syndromes in COVID-19 patients is limited. However, this study found that in a small subset of patients with neurological manifestations, CSF pleocytosis and detection of anti-GD1b and anti-Caspr2 antibodies may suggest secondary autoimmunity potentially induced by SARS-CoV-2 infection.

JOURNAL OF NEUROLOGY (2021)

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Review Rheumatology

The role of antirheumatics in patients with COVID-19

Christoffer B. Nissen et al.

Summary: The COVID-19 pandemic has led to over 2 million deaths worldwide, with immune modulators and immunosuppressive drugs proposed as treatments. Further studies are needed to confirm the efficacy and safety, with potential for more clarity on the use of other anti-rheumatic drugs in the next 12 months.

LANCET RHEUMATOLOGY (2021)

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Article Clinical Neurology

Serum Neurofilament Light Chain Levels in the Intensive Care Unit: Comparison between Severely Ill Patients with and without Coronavirus Disease 2019

Raoul Sutter et al.

Summary: There is increasing evidence for various neurological manifestations of COVID-19, with higher sNfL concentrations observed in critically ill patients with COVID-19 compared to healthy controls and critically ill non-COVID-19 patients. Elevated sNfL levels were associated with unfavorable short-term outcomes, indicating common and pronounced neuronal injury in critically ill patients.

ANNALS OF NEUROLOGY (2021)

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Article Immunology

High frequency of cerebrospinal fluid autoantibodies in COVID-19 patients with neurological symptoms

Christiana Franke et al.

Summary: The study on critically ill COVID-19 patients presenting with unexplained neurological symptoms found that all patients showed anti-neuronal autoantibodies in serum or CSF, which may be related to clinical symptoms, particularly hyperexcitability. Several underlying autoantigens and their potential molecular mimicry with SARS-CoV-2 still need further identification.

BRAIN BEHAVIOR AND IMMUNITY (2021)

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Article Clinical Neurology

Biomarkers for central nervous system injury in cerebrospinal fluid are elevated in COVID-19 and associated with neurological symptoms and disease severity

Johan Virhammar et al.

Summary: This study analyzed CSF biomarkers of CNS injury in 19 patients with neurological symptoms of COVID-19, finding elevated levels of NfL protein, GFAp, and total tau. NfL protein was found to be associated with central neurological symptoms and disease severity in these patients.

EUROPEAN JOURNAL OF NEUROLOGY (2021)

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Article Clinical Neurology

Susceptibility-weighted imaging reveals cerebral microvascular injury in severe COVID-19

John Conklin et al.

Summary: In patients with severe COVID-19, microvascular brain lesions, characterized by punctate SWI lesions, are commonly found in the subcortical and deep white matter. These lesions are associated with widespread microvascular injury, indicating a risk for hemorrhagic and ischemic lesions in the brain.

JOURNAL OF THE NEUROLOGICAL SCIENCES (2021)

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Review Neurosciences

Neurofilament Proteins as Biomarkers to Monitor Neurological Diseases and the Efficacy of Therapies

Aidong Yuan et al.

Summary: Neurofilament proteins serve as important biomarkers of neurodegeneration and neuronal injury, reflecting neuronal damage and degeneration across various neurological diseases. Measuring NfP levels in cerebrospinal fluid and blood can track disease progression, assess treatment responses, and offer novel insights into a wide range of neurological disorders in the field of neurology.

FRONTIERS IN NEUROSCIENCE (2021)

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Article Immunology

Immunoglobulin G Immune Complexes May Contribute to Neutrophil Activation in the Course of Severe Coronavirus Disease 2019

Ignacio Mazzitelli et al.

Summary: The study found that neutrophils in severe COVID-19 patients expressed high levels of related proteins, spontaneously produced inflammatory cytokines, had a strong association with platelets, and showed a clear association with immune complexes. It was also discovered that sera from severe patients contained a large number of immune complexes, which could worsen the disease by activating neutrophils through a mechanism partially dependent on Fc gamma RII (CD32).

JOURNAL OF INFECTIOUS DISEASES (2021)

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Article Clinical Neurology

Blood neurofilament light concentration at admittance: a potential prognostic marker in COVID-19

Anne Hege Aamodt et al.

Summary: Elevated concentrations of NfL and GFAp in COVID-19 patients upon admission may indicate increased mortality risk, and these biomarker concentrations are associated with clinical outcomes.

JOURNAL OF NEUROLOGY (2021)

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Article Clinical Neurology

Neurological update: COVID-19

A. L. Ren et al.

Summary: COVID-19 is primarily a respiratory disease, but can also lead to neurological complications. The main processes causing neurological damage include cerebrovascular disease, immunologically mediated neurological disorders, and the harmful effects of critical illness on the nervous system. While it is still uncertain if the virus directly invades the nervous system, the large number of infections at present suggests that nervous system infection may not be a significant issue.

JOURNAL OF NEUROLOGY (2021)

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Article Clinical Neurology

Blood neurofilament light chain and total tau levels at admission predict death in COVID-19 patients

Rebecca De Lorenzo et al.

Summary: The study investigated the clinical prognostic value of markers of neural tissue damage in predicting survival or transfer to ICU in patients infected with COVID-19. Results showed that certain markers were significantly increased in patients with fatal outcomes or needing ICU transfer, with total tau levels accurately predicting mortality. Blood neural markers may offer additional prognostic value for predicting COVID-19 outcomes.

JOURNAL OF NEUROLOGY (2021)

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Article Hematology

Progressive endothelial cell damage in correlation with sepsis severity. Defibrotide as a contender

Sara Fernandez et al.

Summary: The study demonstrated that the activation of endothelial cells varied with the severity of sepsis, and DF showed promising potential in preventing these changes. Therefore, targeting the endothelium could be crucial in preventing complications of sepsis, and DF may serve as a pharmacological tool to mitigate its consequences, including multiorgan failure.

JOURNAL OF THROMBOSIS AND HAEMOSTASIS (2021)

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Review Rheumatology

Systemic and organ-specific immune-related manifestations of COVID-19

Manuel Ramos-Casals et al.

Summary: Immune-related disorders in patients with COVID-19 present with diverse manifestations mimicking various inflammatory and autoimmune diseases, with clinical phenotype influenced by factors like age, sex, and ethnicity. The severity of symptoms varies greatly, from benign to life-threatening, and the pathogenesis and optimal therapy for these manifestations require further research.

NATURE REVIEWS RHEUMATOLOGY (2021)

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Letter Clinical Neurology

Neurofilament Light Chain in Patients with COVID-19 and Bacterial Pneumonia

Ha-Yeun Chung et al.

ANNALS OF NEUROLOGY (2021)

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Article Immunology

Establishing the prevalence of common tissue-specific autoantibodies following severe acute respiratory syndrome coronavirus 2 infection

Alex G. Richter et al.

Summary: The study revealed a higher frequency of autoantibodies associated with SARS-CoV-2 infection in COVID-19 patients, even detectable months post-infection. COVID-19 patients displayed a more restricted pattern of autoantibodies, including skin, skeletal muscle, and cardiac antibodies.

CLINICAL AND EXPERIMENTAL IMMUNOLOGY (2021)

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Article Immunology

Neurological symptoms and axonal damage in COVID-19 survivors: are there sequelae?

Silvia Bozzetti et al.

Summary: The persistence of neurological symptoms and late axonal damage after SARS-CoV-2 infection is still unknown. The study found that a significant number of COVID-19 patients still experienced neurological symptoms during follow-up, with hyposmia, fatigue, myalgia, and impaired memory being the most common. Serum neurofilament light chain levels were not able to differentiate patients with or without persistent neurological symptoms, but there was a significant decrease in levels during follow-up. The study suggests that COVID-19 survivors do not show active axonal damage, which is a unique feature of acute SARS-CoV-2 infection.

IMMUNOLOGIC RESEARCH (2021)

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Article Immunology

Complex Autoantibody Responses Occur following Moderate to Severe Traumatic Brain Injury

Edward J. Needham et al.

Summary: The study found that individuals exhibit different autoimmune responses following severe TBI, with these responses potentially impacting patient outcomes and persisting for several years. Patients with stronger IgM responses in the acute phase may experience worse outcomes.

JOURNAL OF IMMUNOLOGY (2021)

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Review Biochemistry & Molecular Biology

Neurochemical biomarkers to study CNS effects of COVID-19: A narrative review and synthesis

Arvid Eden et al.

Summary: Neurological symptoms are commonly observed in COVID-19 patients, with anosmia and diffuse encephalopathy being frequent CNS-related manifestations. These symptoms are believed to be caused by systemic inflammatory responses and microvascular injuries in the CNS. However, typical signs of neurotropic viral infections in CSF studies are usually mild or absent in SARS-CoV-2 infection.

JOURNAL OF NEUROCHEMISTRY (2021)

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Review Rheumatology

Autoinflammation and autoimmunity across rheumatic and musculoskeletal diseases

Zoltan Szekanecz et al.

Summary: Most rheumatic and musculoskeletal diseases (RMDs) fall along a spectrum of disorders from autoinflammatory diseases to autoimmune diseases, with 'mixed-pattern' RMDs having features of both autoinflammation and autoimmunity. Understanding the pathogenic pathways of autoinflammation and autoimmunity in RMDs could enhance targeted treatment strategies.

NATURE REVIEWS RHEUMATOLOGY (2021)

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Article Multidisciplinary Sciences

Development of ACE2 autoantibodies after SARS-CoV-2 infection

John M. Arthur et al.

Summary: Many patients with a history of SARS-CoV-2 infection have developed specific antibodies against ACE2, which may decrease the activity of soluble ACE2 in plasma and increase levels of Ang II, potentially triggering symptoms of PASC.

PLOS ONE (2021)

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Article Cell Biology

Type I interferon autoantibodies are associated with systemic immune alterations in patients with COVID-19

Monique G. P. van der Wijst et al.

Summary: Autoantibodies against type I interferons have been identified in some patients with critical COVID-19, with higher prevalence in severe cases. The longitudinal dynamics and functional effects of these antibodies on circulating leukocytes remain unclear.

SCIENCE TRANSLATIONAL MEDICINE (2021)

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Article Cell Biology

Serum neurofilament light protein correlates with unfavorable clinical outcomes in hospitalized patients with COVID-19

Mercedes Prudencio et al.

Summary: Brain imaging studies of COVID-19 patients have shown evidence of neuroaxonal injury, and serum levels of neurofilament light chain (NFL) may predict the extent of neuronal damage and are associated with clinical outcomes. Lower NFL serum concentrations were observed in COVID-19 patients treated with remdesivir, suggesting that neuroaxonal injury should be considered as an outcome in acute pharmacotherapeutic trials for COVID-19.

SCIENCE TRANSLATIONAL MEDICINE (2021)

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Article Multidisciplinary Sciences

New-onset IgG autoantibodies in hospitalized patients with COVID-19

Sarah Esther Chang et al.

Summary: In hospitalized COVID-19 patients, approximately 50% have detectable autoantibodies primarily targeting autoantigens associated with rare disorders. Additionally, a subset of autoantibodies develop de novo following SARS-CoV-2 infection.

NATURE COMMUNICATIONS (2021)

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Article Clinical Neurology

Network medicine links SARS-CoV-2/COVID-19 infection to brain microvascular injury and neuroinflammation in dementia-like cognitive impairment

Yadi Zhou et al.

Summary: The study identified significant mechanistic overlap between COVID-19 and AD, focusing on neuroinflammation and microvascular injury pathways, which provide insights into the potential connection between COVID-19-associated neurological manifestations and Alzheimer's disease.

ALZHEIMERS RESEARCH & THERAPY (2021)

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Article Medicine, General & Internal

Neurochemical signs of astrocytic and neuronal injury in acute COVID-19 normalizes during long-term follow-up

Nelly Kanberg et al.

Summary: Plasma biomarkers of CNS injury were significantly elevated in severe COVID-19 cases during the acute phase but normalized after six months, indicating that neurological sequelae post COVID-19 are not associated with ongoing CNS injury. Despite this normalization, a considerable number of patients reported persistent neurological symptoms, suggesting that additional factors beyond CNS injury biomarkers may contribute to long-term neurological effects of COVID-19.

EBIOMEDICINE (2021)

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Article Immunology

Autoantibodies neutralizing type I IFNs are present in ∼4% of uninfected individuals over 70 years old and account for ∼20% of COVID-19 deaths

Paul Bastard et al.

Summary: Autoantibodies neutralizing interferons are present in a significant percentage of critical COVID-19 patients, especially in older individuals, and their prevalence increases with age.

SCIENCE IMMUNOLOGY (2021)

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Article Microbiology

Post-COVID-19 Syndrome: Nine Months after SARS-CoV-2 Infection in a Cohort of 354 Patients: Data from the First Wave of COVID-19 in Nord Franche-Comte Hospital, France

Souheil Zayet et al.

Summary: More than a third of COVID-19 patients experienced persistent symptoms after SARS-CoV-2 infection, with a particular focus on loss of smell, loss of taste, fatigue, and dyspnea. Among COVID-19 outpatients, healthcare workers had a higher prevalence of post-COVID-19 syndrome.

MICROORGANISMS (2021)

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Article Clinical Neurology

Serum and cerebrospinal fluid biomarker profiles in acute SARS-CoV-2-associated neurological syndromes

Ross W. Paterson et al.

Summary: Preliminary data on pathological and biomarkers indicate that SARS-CoV-2 infection may damage the nervous system, particularly causing CNS inflammation. Elevated levels of serum neurofilament light were found in COVID-19 patients, but not in community cases, suggesting potential peripheral nerve damage in response to severe illness rather than significant neurological damage. Astrocytic activation does not appear to be a major mediator of neuronal damage in COVID-19.

BRAIN COMMUNICATIONS (2021)

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Article Immunology

Antibodies against type I interferon: detection and association with severe clinical outcome in COVID-19 patients

David Goncalves et al.

Summary: The study found that some critically ill COVID-19 patients have autoantibodies against IFN-I, which may impair the immune response. However, patients with neutralizing anti-IFN-alpha(2) autoantibodies showed no significant differences in clinical characteristics or outcomes.

CLINICAL & TRANSLATIONAL IMMUNOLOGY (2021)

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Letter Medicine, General & Internal