Tag: long covid neurology

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)

Direct and indirect impact of SARS-CoV-2 on the brain

Abstract:

Although COVID-19 is mostly a pulmonary disease, it is now well accepted that it can cause a much broader spectrum of signs and symptoms and affect many other organs and tissue. From mild anosmia to severe ischemic stroke, the impact of SARS-CoV-2 on the central nervous system is still a great challenge to scientists and health care practitioners.

Besides the acute and severe neurological problems described, as encephalopathies, leptomeningitis, and stroke, after 2 years of pandemic, the chronic impact observed during long-COVID or the post-acute sequelae of COVID-19 (PASC) greatly intrigues scientists worldwide. Strikingly, even asymptomatic, and mild diseased patients may evolve with important neurological and psychiatric symptoms, as confusion, memory loss, cognitive decline, chronic fatigue, associated or not with anxiety and depression. Thus, the knowledge on the correlation between COVID-19 and the central nervous system is of great relevance.

In this sense, here we discuss some important mechanisms obtained from in vitro and in vivo investigation regarding how SARS-CoV-2 impacts the brain and its cells and function.

Source: Peron JPS. Direct and indirect impact of SARS-CoV-2 on the brain. Hum Genet. 2023 Apr 1:1–10. doi: 10.1007/s00439-023-02549-x. Epub ahead of print. PMID: 37004544; PMCID: PMC10066989. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10066989/ (Full text)

Brain disorders: Impact of mild SARS-CoV-2 may shrink several parts of the brain

Abstract:

Coronavirus (COVID-19) is a highly infectious respiratory infection discovered in Wuhan, China, in December 2019. As a result of the pandemic, several individuals have experienced life-threatening diseases, the loss of loved ones, lockdowns, isolation, an increase in unemployment, and household conflict. Moreover, COVID-19 may cause direct brain injury via encephalopathy. The long-term impacts of this virus on mental health and brain function need to be analysed by researchers in the coming years.

This article aims to describe the prolonged neurological clinical consequences related to brain changes in people with mild COVID-19 infection. When compared to a control group, people those who tested positive for COVID-19 had more brain shrinkage, grey matter shrinkage, and tissue damage. The damage occurs predominantly in areas of the brain that are associated with odour, ambiguity, strokes, reduced attention, headaches, sensory abnormalities, depression, and mental abilities for few months after the first infection. Therefore, in patients after a severe clinical condition of COVID-19, a deepening of persistent neurological signs is necessary.

Source: Kumar PR, Shilpa B, Jha RK. Brain Disorders: Impact of Mild SARS-CoV-2 May Shrink Several Parts of the Brain. Neurosci Biobehav Rev. 2023 Mar 31;149:105150. doi: 10.1016/j.neubiorev.2023.105150. Epub ahead of print. PMID: 37004892; PMCID: PMC10063523. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10063523/ (Full text)

Para-infectious brain injury in COVID-19 persists at follow-up despite attenuated cytokine and autoantibody responses

Abstract:

We measured brain injury markers, inflammatory mediators, and autoantibodies in 203 participants with COVID-19; 111 provided acute sera (1-11 days post admission) and 56 with COVID-19-associated neurological diagnoses provided subacute/convalescent sera (6-76 weeks post-admission).

Compared to 60 controls, brain injury biomarkers (Tau, GFAP, NfL, UCH-L1) were increased in acute sera, significantly more so for NfL and UCH-L1, in patients with altered consciousness. Tau and NfL remained elevated in convalescent sera, particularly following cerebrovascular and neuroinflammatory disorders. Acutely, inflammatory mediators (including IL-6, IL-12p40, HGF, M-CSF, CCL2, and IL-1RA) were higher in participants with altered consciousness, and correlated with brain injury biomarker levels. Inflammatory mediators were lower than acute levels in convalescent sera, but levels of CCL2, CCL7, IL-1RA, IL-2Rα, M-CSF, SCF, IL-16 and IL-18 in individual participants correlated with Tau levels even at this late time point.

When compared to acute COVID-19 patients with a normal GCS, network analysis showed significantly altered immune responses in patients with acute alteration of consciousness, and in convalescent patients who had suffered an acute neurological complication. The frequency and range of autoantibodies did not associate with neurological disorders. However, autoantibodies against specific antigens were more frequent in patients with altered consciousness in the acute phase (including MYL7, UCH-L1, GRIN3B, and DDR2), and in patients with neurological complications in the convalescent phase (including MYL7, GNRHR, and HLA antigens).

In a novel low-inoculum mouse model of SARS-CoV-2, while viral replication was only consistently seen in mouse lungs, inflammatory responses were seen in both brain and lungs, with significant increases in CCL4, IFNγ, IL-17A, and microglial reactivity in the brain. Neurological injury is common in the acute phase and persists late after COVID-19, and may be driven by a para-infectious process involving a dysregulated host response.

Source: Benedict D. Michael, Cordelia Dunai, Edward J. Needham, Kukatharmini Tharmaratnam, Robyn Williams, Yun Huang, Sarah A. Boardman, Jordan Clark, Parul Sharma, Krishanthi Subramaniam, Greta K. Wood, Ceryce Collie, Richard Digby, Alexander Ren, Emma Norton, Maya Leibowitz, Soraya Ebrahimi, Andrew Fower, Hannah Fox, Esteban Tato, Mark Ellul, Geraint Sunderland, Marie Held, Claire Hetherington, Franklyn Nkongho, Alish Palmos, Alexander Grundmann, James P. Stewart, Michael Griffiths, Tom Solomon, Gerome Breen, Alasdair Coles, Jonathan Cavanagh, Sarosh R. Irani, Angela Vincent, Leonie Taams, David K. Menon. Para-infectious brain injury in COVID-19 persists at follow-up despite attenuated cytokine and autoantibody responses. medRxiv 2023.04.03.23287902; doi: https://doi.org/10.1101/2023.04.03.23287902 (Full text available as PDF file)

Case Study: COVID-19 Brain Fog or Auditory Processing Disorder?

A wide array of symptoms have been directly associated with COVID-19 following recovery, but they can also occur several weeks or months after the diagnosis. These include, but are not limited to, damage to the respiratory tract as well as decreased cognition and other brain functions. The nonmedical term used to describe these post-COVID-19 problems is “brain fog.”

The symptoms of brain fog are similar to mild cognitive impairment or, of interest to audiologists, an auditory processing disorder (APD). 2 COVID-19 has neurological consequences and affects specific areas of the brain, such as the cingulate cortex (i.e. emotions, memory, depression, and decision of action). 3 Brain fog is also associated with several symptoms related to hearing and communication, which can affect the accomplishment of routine daily tasks. Many of those can be mistaken for or coexist with APD symptoms. These include “difficulty attending or staying focused, difficulty concentrating, difficulty understanding or remembering instructions, language problems, short-term memory problems,” to mention a few. 2 However, what might appear as a brain fog case could be an undiagnosed or even a pre-existing APD issue. 2 Symptoms could include struggling to keep track of conversations, forgetfulness and memory issues, problems following directions, and several cognitive difficulties. 2

This report presents the case of a 31-year-old medical doctor who was diagnosed with COVID-19 in December 2020, and later identified with APD symptoms that are now commonly seen in post-COVID-19 brain fog patients. Auditory training following the Buffalo Model 4 resolved the patient’s chief complaints following 12 treatment sessions. This issue is one of many that could shed light on the great potential auditory training has in resolving brain fog complaints that overlap with what is commonly seen in APD patients, highlighting the concerns regarding COVID-19’s direct effects on auditory processing.

Source: Alexander, Angela Loucks AuD, MNZAS, CCC-A; DiSogra, Robert M. AuD; Abbas, Fatima BS; Braund, Stacey AuD, CCC-A; Spokes, Chelsea BSpHLSc, MClinAud. Case Study: COVID-19 Brain Fog or Auditory Processing Disorder?. The Hearing Journal 76(04):p 18,19,20,22,23,24, April 2023. | DOI: 10.1097/01.HJ.0000927332.17564.4e https://journals.lww.com/thehearingjournal/Fulltext/2023/04000/Case_Study__COVID_19_Brain_Fog_or_Auditory.2.aspx (Full text)