Would Repurposing Minocycline Alleviate Neurologic Manifestations of COVID-19?
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ABSTRACT:
SUBMITTER: Oliveira AC
PROVIDER: S-EPMC7561411 | biostudies-literature | 2020
REPOSITORIES: biostudies-literature
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Would Repurposing Minocycline Alleviate Neurologic Manifestations of COVID-19?
Oliveira Aline C AC Richards Elaine M EM Karas Marianthi M MM Pepine Carl J CJ Raizada Mohan K MK
Frontiers in neuroscience 20200930
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Project description: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.
| S-EPMC9302225 | biostudies-literature
Project description:ObjectivesTo provide an overview of the spectrum, characteristics and outcomes of neurologic manifestations associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.MethodsWe conducted a single-centre retrospective study during the French coronavirus disease 2019 (COVID-19) epidemic in March-April 2020. All COVID-19 patients with de novo neurologic manifestations were eligible.ResultsWe included 222 COVID-19 patients with neurologic manifestations from 46 centres in France. Median (interquartile range, IQR) age was 65 (53-72) years and 136 patients (61.3%) were male. COVID-19 was severe or critical in 102 patients (45.2%). The most common neurologic diseases were COVID-19-associated encephalopathy (67/222, 30.2%), acute ischaemic cerebrovascular syndrome (57/222, 25.7%), encephalitis (21/222, 9.5%) and Guillain-Barré syndrome (15/222, 6.8%). Neurologic manifestations appeared after the first COVID-19 symptoms with a median (IQR) delay of 6 (3-8) days in COVID-19-associated encephalopathy, 7 (5-10) days in encephalitis, 12 (7-18) days in acute ischaemic cerebrovascular syndrome and 18 (15-28) days in Guillain-Barré syndrome. Brain imaging was performed in 192 patients (86.5%), including 157 magnetic resonance imaging (70.7%). Among patients with acute ischaemic cerebrovascular syndrome, 13 (22.8%) of 57 had multiterritory ischaemic strokes, with large vessel thrombosis in 16 (28.1%) of 57. Brain magnetic resonance imaging of encephalitis patients showed heterogeneous acute nonvascular lesions in 14 (66.7%) of 21. Cerebrospinal fluid of 97 patients (43.7%) was analysed, with pleocytosis found in 18 patients (18.6%) and a positive SARS-CoV-2 PCR result in two patients with encephalitis. The median (IQR) follow-up was 24 (17-34) days with a high short-term mortality rate (28/222, 12.6%).ConclusionsClinical spectrum and outcomes of neurologic manifestations associated with SARS-CoV-2 infection were broad and heterogeneous, suggesting different underlying pathogenic processes.
| S-EPMC7661948 | biostudies-literature
Project description:The novel coronavirus SARS-CoV-2 is known to cause hypoxemia and acute respiratory distress syndrome (ARDS) in a significant portion of those with severe disease. Survivors of critical illness and ARDS often experience neurocognitive impairment but, to date, there is scant literature correlating radiographic hypoxic brain injury to hypoxemia related to ARDS. In this case series, we describe three cases of hypoxic brain injury seen on magnetic resonance imaging (MRI) in patients with hypoxemia secondary to COVID-19-related ARDS. The lack of severe observed hypoxemia in two of the cases suggests that unrecognized or asymptomatic hypoxemia may play a role in hypoxic brain injury related to COVID-19.
| S-EPMC7474836 | biostudies-literature
Project description: Not available
| S-EPMC8240497 | biostudies-literature
Project description:BackgroundThe coronavirus disease 2019 (COVID-19) is a systemic entity that frequently implies neurologic features at presentation and complications during the disease course. We aimed to describe the characteristics and predictors for developing in-hospital neurologic manifestations in a large cohort of hospitalized patients with COVID-19 in Mexico City.MethodsWe analyzed records from consecutive adult patients hospitalized from March 15 to June 30, 2020, with moderate to severe COVID-19 confirmed by reverse transcription real-time polymerase chain reaction (rtRT-PCR) for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Neurologic syndromes were actively searched by a standardized structured questionnaire and physical examination, confirmed by neuroimaging, neurophysiology of laboratory analyses, as applicable.ResultsWe studied 1,072 cases (65% men, mean age 53.2±13 years), 71 patients had pre-existing neurologic diseases (diabetic neuropathy: 17, epilepsy: 15, history of ischemic stroke: eight, migraine: six, multiple sclerosis: one, Parkinson disease: one), and 163 (15.2%) developed a new neurologic complication. Headache (41.7%), myalgia (38.5%), dysgeusia (8%), and anosmia (7%) were the most common neurologic symptoms at hospital presentation. Delirium (13.1%), objective limb weakness (5.1%), and delayed recovery of mental status after sedation withdrawal (2.5%), were the most common new neurologic syndromes. Age, headache at presentation, preexisting neurologic disease, invasive mechanical ventilation, and neutrophil/lymphocyte ratio ≥9 were independent predictors of new in-hospital neurologic complications.ConclusionsEven after excluding initial clinical features and pre-existing comorbidities, new neurologic complications in hospitalized patients with COVID-19 are frequent and can be predicted from clinical information at hospital admission.
| S-EPMC8031187 | biostudies-literature
Project description:BackgroundNeurological manifestations are present in about one-third of COVID-19 cases, ranging from mild symptoms, such as anosmia, to more severe forms like demyelinating syndromes. Although direct invasion of the CNS has been demonstrated, the immune- mediated pathway is also described and more accepted. Even in cases where viral detection in CSF is absent, it should not rule out neuroinvasion. There are few prospective studies about neurological manifestations of COVID-19, especially with viral tests in CSF; as well there are still many questions about COVID-19 associated with neurological disease. Thus, we describe clinical and CSF findings of a prospective cohort of patients with nasal positive tests for SARS-CoV-2 and neurological involvement. We also discuss the pathogenic mechanisms related to these manifestations.Methods and findingsThis is a prospective cohort study; 27 patients were evaluated according to clinical presentation, the time interval between COVID-19 diagnosis and onset of neurological alterations, syndromic diagnosis, imaging and CSF findings. Real time polymerase chain reaction for SARS-CoV-2 genome was performed in all CSF samples. 2 RT-PCR in spinal cord fluid resulted positive in 9 (33.3%) cases, five of them had a positive swab nasal test concomitant to neurologic disease. Respiratory signs were described in 12 out 27 patients, five of them with viral detection in CSF. White cell counts in CSF were normal range in the majority of cases, except for 3 occurrences: two patients had elevated CSF WBC counts and viral detection in CSF (10 and 36 cells/mm3) and one also had elevated CSF WBC count but viral detection in CSF was negative (21cells/mm3). The observed neurological signs encompassed a diverse neurologic spectrum, including seizures, paresis, gait abnormalities, headaches, alteration in consciousness and memory or cognitive impairment. Both imaging and CSF alterations exhibited non-specific characteristics. Syndromic diagnoses included stroke, dementia or cognitive impairments, Guillain-Barré Syndrome, encephalitis, encephalomyelitis, acute flaccid palsy and optical neuritis.ConclusionsThe patients in the present study had COVID-19 and neurologic involvement including a wide range of clinical manifestations. SARS-CoV-2 was detected in one-third of CSF samples, regardless of time interval between COVID-19 diagnosis and the onset of neurological signs. These conditions encompass various pathogenic pathways and the neuroinvasion potential of SARS-CoV-2 should be more studied.
| S-EPMC11922214 | biostudies-literature
Project description:ObjectiveCovid-19 can involve multiple organs including the nervous system. We sought to characterize the neurologic manifestations, their risk factors, and associated outcomes in hospitalized patients with Covid-19.MethodsWe examined neurologic manifestations in 509 consecutive patients admitted with confirmed Covid-19 within a hospital network in Chicago, Illinois. We compared the severity of Covid-19 and outcomes in patients with and without neurologic manifestations. We also identified independent predictors of any neurologic manifestations, encephalopathy, and functional outcome using binary logistic regression.ResultsNeurologic manifestations were present at Covid-19 onset in 215 (42.2%), at hospitalization in 319 (62.7%), and at any time during the disease course in 419 patients (82.3%). The most frequent neurologic manifestations were myalgias (44.8%), headaches (37.7%), encephalopathy (31.8%), dizziness (29.7%), dysgeusia (15.9%), and anosmia (11.4%). Strokes, movement disorders, motor and sensory deficits, ataxia, and seizures were uncommon (0.2 to 1.4% of patients each). Severe respiratory disease requiring mechanical ventilation occurred in 134 patients (26.3%). Independent risk factors for developing any neurologic manifestation were severe Covid-19 (OR 4.02; 95% CI 2.04-8.89; P < 0.001) and younger age (OR 0.982; 95% CI 0.968-0.996; P = 0.014). Of all patients, 362 (71.1%) had a favorable functional outcome at discharge (modified Rankin Scale 0-2). However, encephalopathy was independently associated with worse functional outcome (OR 0.22; 95% CI 0.11-0.42; P < 0.001) and higher mortality within 30 days of hospitalization (35 [21.7%] vs. 11 [3.2%] patients; P < 0.001).InterpretationNeurologic manifestations occur in most hospitalized Covid-19 patients. Encephalopathy was associated with increased morbidity and mortality, independent of respiratory disease severity.
| S-EPMC7664279 | biostudies-literature
Project description:Since the first reports of SARS-CoV-2 infection from China, multiple studies have been published regarding the epidemiologic aspects of COVID-19 including clinical manifestations and outcomes. The majority of these studies have focused on respiratory complications. However, recent findings have highlighted the systemic effects of the virus, including its potential impact on the nervous system. Similar to SARS-CoV-1, cellular entry of SARS-CoV-2 depends on the expression of ACE2, a receptor that is abundantly expressed in the nervous system. Neurologic manifestations in adults include cerebrovascular insults, encephalitis or encephalopathy, and neuromuscular disorders. However, the presence of these neurologic findings in the pediatric population is unclear. In this review, the potential neurotropism of SARS-CoV-2, known neurologic manifestations of COVID-19 in children, and management of preexisting pediatric neurologic conditions during the COVID-19 pandemic are discussed.
| S-EPMC7859660 | biostudies-literature
Project description:Patients suffering from Coronavirus disease 2019 (COVID-19) can develop neurological sequelae, such as headache, neuroinflammatory or cerebrovascular disease. These conditions - here termed Neuro-COVID - are more frequent in patients with severe COVID-19. To understand the etiology of these neurological sequelae, we utilized single-cell sequencing and examined the immune cell profiles from the cerebrospinal fluid (CSF) of Neuro-COVID patients compared to patients with non-inflammatory and autoimmune neurological diseases or with viral encephalitis. The CSF of Neuro-COVID patients exhibited an expansion of dedifferentiated monocytes and of exhausted CD4+ T cells. Neuro-COVID CSF leukocytes featured an enriched interferon signature; however, this was less pronounced than in viral encephalitis. Repertoire analysis revealed broad clonal T cell expansion and curtailed interferon response in severe compared to mild Neuro-COVID patients. Collectively, our findings document the CSF immune compartment in Neuro-COVID patients and suggest compromised antiviral responses in this setting.
2020-12-11 | GSE163005 | GEO
Project description:BackgroundNeurologic manifestations are increasingly reported in patients with coronavirus disease 2019 (COVID-19). Yet, data on prevalence, predictors and relevance for outcome of neurological manifestations in patients requiring intensive care are scarce. We aimed to characterize prevalence, risk factors and impact on outcome of neurologic manifestations in critically ill COVID-19 patients.MethodsIn the prospective, multicenter, observational registry study PANDEMIC (Pooled Analysis of Neurologic DisordErs Manifesting in Intensive care of COVID-19), we enrolled COVID-19 patients with neurologic manifestations admitted to 19 German intensive care units (ICU) between April 2020 and September 2021. We performed descriptive and explorative statistical analyses. Multivariable models were used to investigate factors associated with disorder categories and their underlying diagnoses as well as to identify predictors of outcome.ResultsOf the 392 patients included in the analysis, 70.7% (277/392) were male and the mean age was 65.3 (SD ± 3.1) years. During the study period, a total of 2681 patients with COVID-19 were treated at the ICUs of 15 participating centers. New neurologic disorders were identified in 350 patients, reported by these centers, suggesting a prevalence of COVID-19-associated neurologic disorders of 12.7% among COVID-19 ICU patients. Encephalopathy (46.2%; 181/392), cerebrovascular (41.0%; 161/392) and neuromuscular disorders (20.4%; 80/392) were the most frequent categories identified. Out of 35 cerebrospinal fluid analyses with reverse transcriptase PCR for SARS-COV-2, only 3 were positive. In-hospital mortality was 36.0% (140/389), and functional outcome (mRS 3 to 5) of surviving patients was poor at hospital discharge in 70.9% (161/227). Intracerebral hemorrhage (OR 6.2, 95% CI 2.5-14.9, p < 0.001) and acute ischemic stroke (OR 3.9, 95% CI 1.9-8.2, p < 0.001) were the strongest predictors of poor outcome among the included patients.ConclusionsBased on this well-characterized COVID-19 ICU cohort, that comprised 12.7% of all severe ill COVID-19 patients, neurologic manifestations increase mortality and morbidity. Since no reliable evidence of direct viral affection of the nervous system by COVID-19 could be found, these neurologic manifestations may for a great part be indirect para- or postinfectious sequelae of the infection or severe critical illness. Neurologic ICU complications should be actively searched for and treated.
| S-EPMC9287707 | biostudies-literature