Tag: long covid neurology

Deep Phenotyping of Neurologic Postacute Sequelae of SARS-CoV-2 Infection

Abstract:

Background and Objectives SARS-CoV-2 infection has been associated with a syndrome of long-term neurologic sequelae that is poorly characterized. We aimed to describe and characterize in-depth features of neurologic postacute sequelae of SARS-CoV-2 infection (neuro-PASC).

Methods Between October 2020 and April 2021, 12 participants were seen at the NIH Clinical Center under an observational study to characterize ongoing neurologic abnormalities after SARS-CoV-2 infection. Autonomic function and CSF immunophenotypic analysis were compared with healthy volunteers (HVs) without prior SARS-CoV-2 infection tested using the same methodology.

Results Participants were mostly female (83%), with a mean age of 45 ± 11 years. The median time of evaluation was 9 months after COVID-19 (range 3–12 months), and most (11/12, 92%) had a history of only a mild infection. The most common neuro-PASC symptoms were cognitive difficulties and fatigue, and there was evidence for mild cognitive impairment in half of the patients (MoCA score <26). The majority (83%) had a very disabling disease, with Karnofsky Performance Status ≤80. Smell testing demonstrated different degrees of microsmia in 8 participants (66%). Brain MRI scans were normal, except 1 patient with bilateral olfactory bulb hypoplasia that was likely congenital. CSF analysis showed evidence of unique intrathecal oligoclonal bands in 3 cases (25%). Immunophenotyping of CSF compared with HVs showed that patients with neuro-PASC had lower frequencies of effector memory phenotype both for CD4+ T cells (p < 0.0001) and for CD8+ T cells (p = 0.002), an increased frequency of antibody-secreting B cells (p = 0.009), and increased frequency of cells expressing immune checkpoint molecules. On autonomic testing, there was evidence for decreased baroreflex-cardiovagal gain (p = 0.009) and an increased peripheral resistance during tilt-table testing (p < 0.0001) compared with HVs, without excessive plasma catecholamine responses.

Discussion CSF immune dysregulation and neurocirculatory abnormalities after SARS-CoV-2 infection in the setting of disabling neuro-PASC call for further evaluation to confirm these changes and explore immunomodulatory treatments in the context of clinical trials.

Source: Yair Mina, Yoshimi Enose-Akahata, Dima A. Hammoud, Anthony J. Videckis, Sandeep R. Narpala, Sarah E. O’Connell, Robin Carroll, Bob C. Lin, Cynthia Chen McMahan, Govind Nair, Lauren B. Reoma, Adrian B. McDermott, Brian Walitt, Steven Jacobson, David S. Goldstein, Bryan R. Smith, Avindra Nath. Deep Phenotyping of Neurologic Postacute Sequelae of SARS-CoV-2 Infection. Neurol Neuroimmunol Neuroinflamm Jul 2023, 10 (4) e200097; DOI: 10.1212/NXI.0000000000200097 

Changes in the State of Vital Systems with Long COVID-19

Abstract:

Long COVID-19 is a chronic disease that continues to be studied. Data on epidemiology and the main symptoms typical for long COVID-19 are presented. Issues related to the pathogenesis of the disease are discussed. At the same time, special attention is paid to the inflammation process (including of the vascular wall endothelium), the state of the immune system (cytokine storm), the hemostasis system (the mechanism for the development of microangiopathy and thrombosis), and oxidative stress. During the analysis, a special place is given to central nervous system disorders (including organic brain damage) and disorders of cognitive functions. In addition, currently known complications from the cardiovascular system and respiratory organs are described. The treatment and rehabilitation of patients with long COVID-19 is not only a medical, but also a significant social problem.

Source: Kuznik, B.I., Shapovalov, K.G. & Chalisova, N.I. Changes in the State of Vital Systems with Long COVID-19. Biol Bull Rev 13, 112–123 (2023). https://doi.org/10.1134/S2079086423020044 (Full text)

A Review of Neurological Symptoms in Long COVID and Clinical Management

Abstract:

Long COVID is a clinical diagnosis generally referring to the persistence or development of new symptoms, affecting multiple organ systems after SARS-CoV-2 COVID-19 infection. Long COVID is thought to affect ∼20% of people after infection, including all age ranges and severity of infection. Fatigue, postexertional malaise, and respiratory and cardiac symptoms are commonly described. Neurological symptoms such as cognitive changes, sensory disturbances, headaches, and dysautonomia are common as well. The underlying pathophysiology remains unclear but immune dysregulation, autoimmunity, persistent viral reservoirs, and microvascular dysfunction have been implicated. As there are no tests at this time to diagnose long COVID, work-up should be focused on assessing reversible or treatable causes of symptoms. Furthermore, no treatments for long COVID currently exist, and management remains focused on a multimodal approach and symptom management, with many people showing improvement in symptoms over time.

Source: Navis A. A Review of Neurological Symptoms in Long COVID and Clinical Management. Semin Neurol. 2023 Apr 17. doi: 10.1055/s-0043-1767781. Epub ahead of print. PMID: 37068519. https://pubmed.ncbi.nlm.nih.gov/37068519/

Low vitamin D levels are associated with Long COVID syndrome in COVID-19 survivors

Abstract:

Purpose: Long-COVID is an emerging syndrome affecting 50-70% of COVID-19 survivors which still lacks predicting factors. Due to the extra-skeletal effects of vitamin D, we retrospectively assessed in COVID-19 survivors 6-months after hospitalization the association between 25(OH)vitamin D levels and Long-COVID.

Methods: Long-COVID was defined according to NICE-guidelines. Fifty Long-COVID and 50 non-Long-COVID subjects matched on a 1:1-basis were enrolled from an outpatient-post-COVID clinic-cohort seen from August to November 2020. Therapies/comorbidities affecting calcium/vitamin-D/bone metabolism, and/or admission in ICU during hospitalization were exclusion criteria. 25(OH)vitamin D was measured at hospital-admission and 6-months after discharge.

Results: We observed lower 25(OH)vitamin D levels, evaluated at follow-up, in subjects with Long-COVID than those without (20.1vs23.2 ng/mL-p = 0.03). Regarding the affected health-areas evaluated in the entire cohort, we observed lower 25(OH)vitamin D levels in those with neurocognitive symptoms at follow-up (n.7) as compared to those without (n.93) (14.6vs20.6 ng/mL-p = 0.042). In patients presenting vitamin D deficiency (<20 ng/mL) both at admission and at follow-up (n.42), those affected by Long-COVID (n.22) presented lower 25(OH)vitamin D levels, at follow-up, compared to those not affected (n.20) (12.7vs15.2 ng/mL-p = 0.041). In multiple-regression analyses, lower 25(OH)vitamin D levels, at follow-up, resulted as the only variable significantly associated with Long-COVID in our cohort (p = 0.008, OR 1.09-CI 1.01-1.16).

Conclusions: COVID-19 survivors with Long-COVID have lower 25(OH)vitamin D levels as compared to matched-patients without Long-COVID. Our data suggest that vitamin D levels should be evaluated in COVID-19 patients after hospital-discharge. Role of vitamin D supplementation as preventive strategy of COVID-19 sequelae should be tested in randomized-controlled trials.

Source: di Filippo L, Frara S, Nannipieri F, Cotellessa A, Locatelli M, Rovere Querini P, Giustina A. Low vitamin D levels are associated with Long COVID syndrome in COVID-19 survivors. J Clin Endocrinol Metab. 2023 Apr 13:dgad207. doi: 10.1210/clinem/dgad207. Epub ahead of print. PMID: 37051747. https://academic.oup.com/jcem/advance-article/doi/10.1210/clinem/dgad207/7116659 (Full text available as PDF file)

Mouse Adapted SARS-CoV-2 Model Induces “Long-COVID” Neuropathology in BALB/c Mice

Abstract:

The novel coronavirus SARS-CoV-2 has caused significant global morbidity and mortality and continues to burden patients with persisting neurological dysfunction. COVID-19 survivors develop debilitating symptoms to include neuro-psychological dysfunction, termed “Long COVID”, which can cause significant reduction of quality of life. Despite vigorous model development, the possible cause of these symptoms and the underlying pathophysiology of this devastating disease remains elusive.

Mouse adapted (MA10) SARS-CoV-2 is a novel mouse-based model of COVID-19 which simulates the clinical symptoms of respiratory distress associated with SARS-CoV-2 infection in mice. In this study, we evaluated the long-term effects of MA10 infection on brain pathology and neuroinflammation. 10-week and 1-year old female BALB/cAnNHsd mice were infected intranasally with 10 4 plaque-forming units (PFU) and 10 3 PFU of SARS-CoV-2 MA10, respectively, and the brain was examined 60 days post-infection (dpi).

Immunohistochemical analysis showed a decrease in the neuronal nuclear protein NeuN and an increase in Iba-1 positive amoeboid microglia in the hippocampus after MA10 infection, indicating long-term neurological changes in a brain area which is critical for long-term memory consolidation and processing. Importantly, these changes were seen in 40-50% of infected mice, which correlates to prevalence of LC seen clinically.

Our data shows for the first time that MA10 infection induces neuropathological outcomes several weeks after infection at similar rates of observed clinical prevalence of “Long COVID”. These observations strengthen the MA10 model as a viable model for study of the long-term effects of SARS-CoV-2 in humans. Establishing the viability of this model is a key step towards the rapid development of novel therapeutic strategies to ameliorate neuroinflammation and restore brain function in those suffering from the persistent cognitive dysfunction of “Long-COVID”.

Source: Gressett TE, Leist SR, Ismael S, Talkington G, Dinnon KH, Baric RS, Bix G. Mouse Adapted SARS-CoV-2 Model Induces “Long-COVID” Neuropathology in BALB/c Mice. bioRxiv [Preprint]. 2023 Mar 20:2023.03.18.533204. doi: 10.1101/2023.03.18.533204. PMID: 36993423; PMCID: PMC10055301. https://www.biorxiv.org/content/10.1101/2023.03.18.533204v1.full (Full text)

Risk factors for psychiatric symptoms in patients with long COVID: A systematic review

Abstract:

Prolonged symptoms of COVID-19 have been found in many patients, often known as Long COVID. Psychiatric symptoms are commonly seen in Long COVID patients and could last for weeks, even months, after recovery. However, the symptoms and risk factors associated with it remain unclear.

In the current systematic review, we provide an overview of psychiatric symptoms in Long COVID patients and risk factors associated with the development of those symptoms. Articles were systematically searched on SCOPUS, PubMed, and EMBASE up to October 2021. Studies involving adults and geriatric participants with a confirmed previous COVID-19 diagnosis and reported psychiatric symptoms that persist for more than four weeks after the initial infection were included. The risk of bias was assessed using the Newcastle-Ottawa Scale (NOS) for observational studies. Prevalence rates and risk factors associated with psychiatric symptoms were collected. This present study was registered at PROSPERO (CRD42021240776). In total, 23 studies were included.

Several limitations in this review were the heterogeneity of studies’ outcomes and designs, studies limited to articles published in English, and the psychiatric symptoms mainly were assessed using self-report questionnaires. The most prevalent  reported psychiatric symptoms, from the most to the least reported, were anxiety, depression, post-traumatic stress disorder (PTSD), poor sleep qualities, somatic symptoms, and cognitive deficits. Being female and having previous psychiatric diagnoses were risk factors for the development of the reported symptoms.

Source: Zakia H, Pradana K, Iskandar S. Risk factors for psychiatric symptoms in patients with long COVID: A systematic review. PLoS One. 2023 Apr 7;18(4):e0284075. doi: 10.1371/journal.pone.0284075. PMID: 37027455; PMCID: PMC10081737. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10081737/ (Full text)

Five cluster classifications of long COVID and their background factors: A cross-sectional study in Japan

Abstract:

Purpose: The long-term symptoms of coronavirus disease 2019 (COVID-19), i.e., long COVID, have drawn research attention. Evaluating its subjective symptoms is difficult, and no established pathophysiology or treatment exists. Although there are several reports of long COVID classifications, there are no reports comparing classifications that include patient characteristics, such as autonomic dysfunction and work status. We aimed to classify patients into clusters based on their subjective symptoms during their first outpatient visit and evaluate their background for these clusters.

Methods: Included patients visited our outpatient clinic between January 18, 2021, and May 30, 2022. They were aged ≥ 15 years and confirmed to have SARS-CoV-2 infection and residual symptoms lasting at least 2 months post-infection. Patients were evaluated using a 3-point scale for 23 symptoms and classified into five clusters (1. fatigue only; 2. fatigue, dyspnea, chest pain, palpitations, and forgetfulness; 3. fatigue, headache, insomnia, anxiety, motivation loss, low mood, and forgetfulness; 4. hair loss; and 5. taste and smell disorders) using CLUSTER. For continuous variables, each cluster was compared using the Kruskal–Wallis test. Multiple comparison tests were performed using the Dunn’s test for significant results. For nominal variables, a Chi-square test was performed; for significant results, a residual analysis was conducted with the adjusted residuals.

Results: Compared to patients in other cluster categories, those in cluster categories 2 and 3 had higher proportions of autonomic nervous system disorders and leaves of absence, respectively.

Conclusions: Long COVID cluster classification provided an overall assessment of COVID-19. Different treatment strategies must be used based on physical and psychiatric symptoms and employment factors.

Source: Tsuchida, T., Yoshimura, N., Ishizuka, K. et al. Five cluster classifications of long COVID and their background factors: A cross-sectional study in Japan. Clin Exp Med (2023). https://doi.org/10.1007/s10238-023-01057-6 (Full text)

Post-COVID-19 condition and persisting symptoms in English schoolchildren: repeated surveys to March 2022

Abstract:

Background: Both post-COVID-19 condition (long COVID) and the presence of persisting symptoms that do not meet formal definitions of post-COVID-19-condition may adversely affect quality of life and function. However, their prevalence among children and young people in England is unclear.

Methods: We used data from repeated surveys in a large cohort of English schoolchildren from the COVID-19 Schools Infection Survey (SIS) for the school year 2021/22 to describe the weighted prevalence of post-COVID-19-condition and compare persisting symptoms between individuals with a positive SARS-CoV-2 test and those with neither a positive test history nor suspected infection.

Results: Among 7797 children from 173 schools, 1.8% of primary school pupils (aged 4 to 11 years), 4.5% of secondary school pupils in years 7-11 (aged 11 to 16 years) and 6.9% of those in years 12-13 (aged 16 to 18 years) met a definition of post-COVID-19 condition in March 2022. Specific persisting symptoms such as anxiety or difficulty concentrating were frequently reported regardless of prior infection status and increased with age: 48.0% of primary school pupils, 52.9% of secondary school pupils in years 7-11 and 79.5% in years 12-13 reporting at least one symptom lasting more than 12 weeks. Persisting loss of smell and taste, cardiovascular and some systemic symptoms were more frequently reported by those with a previous positive test.

Conclusions: We showed that ongoing symptoms were frequently reported by English schoolchildren regardless of SARS-CoV-2 test results and some specific symptoms such as loss of smell and taste were more prevalent in those with a positive test history. Our study emphasises the wide-ranging impacts of the COVID-19 pandemic on the health and wellbeing of children and young people.

Source: Warren-Gash C, Lacey A, Cook S, Stocker D, Toon S, Lelii F, Ford B, Ireland G, Ladhani SN, Stephenson T, Nguipdop-Djomo P, Mangtani P; COVID-19 Schools Infection Survey 2 Study Group. Post-COVID-19 condition and persisting symptoms in English schoolchildren: repeated surveys to March 2022. BMC Infect Dis. 2023 Apr 5;23(1):201. doi: 10.1186/s12879-023-08203-1. PMID: 37020190; PMCID: PMC10075149. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10075149/ (Full text)

Long COVID: Cognitive and FDG PET evolutions in six patients

Abstract:

Long COVID is often characterized by cognitive complaints and deficits occurring immediately or several weeks after the infectious disease. Neuropsychological tests can revealed attention and executive function anomalies and FDG PET can display hypometabolic areas affecting various regions including frontal and cingulate cortices as well as precuneus and brainstem. We report here the cognitive and FDG PET evolutions over one year in 6 patients suffering from long COVID. Our study shows cognitive and FDG PET improvements in most of the cases and highlight the importance of a careful neurological follow-up in these patients.

Source: Jacques Hugon, Karim Farid, Mathieu Queneau et al. Long COVID: Cognitive and FDG PET evolutions in six patients, 03 April 2023, PREPRINT (Version 1) available at Research Square. https://doi.org/10.21203/rs.3.rs-2703691/v1 https://www.researchsquare.com/article/rs-2703691/v1 (Full text)

Miscellaneous neuromuscular symptoms and signs in long Covid

Abstract:

We have completed the 3rd year of the Covid-19 pandemic. In the early stages of the disease, we were faced with a wide variety of symptoms and signs, including the neuromuscular system, as well as life-threatening cardiopulmonary, neurovascular and immune complications.

In our study, we questioned fatigue, myalgia, arthralgia, dyspnea, headache, dizziness, neck pain, back pain, low back pain, knee-hip-foot joint pain, vascular claudication (lower extremity pain/cramp), neuropathic pain, morning stiffness, joint swelling, pernio, imbalance in walking in patients (N=111; 65 female, 29 male) aged 20-59 years, who applied to our outpatient clinic in the last 1 year and had Covid-19.

The mean time after Covid-19 was 5.8 ±2.1 months. The duration of Covid-19 treatment was a minimum of 5 days and a maximum of 12 days (median=5 days). Weight loss in 14.4% (median=3.5 kg), anorexia 17.1%, myalgia 41.4% (visual analog scale, VAS=5.1±1.9 cm), arthralgia 24.3% (VAS=5.1±2 cm), fatigue 63.1%, joint swelling 1.8%, pernio sign 0.9%, morning stiffness 7.2% (median=15 min, min 5-maximum 60 min), headache 39.6%, neuropathic pain 15.3%, effort dyspnea 38.7%, 30 second chair stand test= 14.9 ±3.6, vascular claudication symptom 11.7%, neck pain 27.0%, low back pain 30.6%, back pain 36%, hip-knee-foot pain 18.0%, gait imbalance 1.8%, dizziness 18.9% were observed. While fatigue (p=0.05), headache (p=0.04), and dyspnea (p=0.021) complaints were higher in males; VAS (arthralgia) was found higher in females (p=0.026).

In the post-Covid-19 period, we see many neuromuscular symptoms and signs, especially fatigue, myalgia, headache and back pain. In addition, lower extremity vascular claudication and neuropathic pain related with chronic pain should not be overlooked in these patients.

Source: Koca TT, Erzurumluoglu O, Kocyigit BF. Miscellaneous neuromuscular symptoms and signs in long Covid. Med Science. 2023;12(1):238-43. https://www.medicinescience.org/article/3381 (Full text)