Long-term cognitive dysfunction after the COVID-19 pandemic: a narrative review

Introduction: SARS-CoV-2, the virus responsible for the COVID-19 pandemic, has brought a conglomerate of novel chronic disabling conditions described as ‘Long COVID/Post-COVID-19 Syndrome’. Recent evidence suggests that the multifaceted nature of this syndrome results in both pulmonary and extrapulmonary sequelae,chronic dyspnoea, persistent fatigue, and cognitive dysfunction being the most common, debilitating symptoms. Several mechanisms engender or exacerbate cognitive impairment, including central nervous system and extra-central nervous system causes, although the exact mechanism remains unclear. Both hospitalized and non-hospitalized patients may suffer varying degrees of cognitive impairment, ranging from fatigue and brain fog to prolonged deficits in memory and attention, detrimental to the quality-of-life years post-recovery. The aim of this review is to understand the underlying mechanisms, associations, and attempts for prevention with early intervention of long-term cognitive impairment post-COVID-19. Methodology: A systematic search was conducted through multiple databases such as Medline, National Library of Medicine, Ovid, Scopus database to retrieve all the articles on the long-term sequalae of cognitive dysfunction after SARS-CoV-2 infection. The inclusion criteria included all articles pertinent to this specific topic and exclusion criteria subtracted studies pertaining to other aetiologies of cognitive dysfunction. This search was carefully screened for duplicates and the relevant information was extracted and analysed. Results/discussion: To date, the exact pathogenesis, and underlying mechanisms behind cognitive dysfunction in COVID-19, remain unclear, hindering the development of adequate management strategies. However, the proposed mechanisms suggested by various studies include direct damage to the blood-brain barrier, systemic inflammation, prolonged hypoxia, and extended intensive care admissions. However, no clear-cut guidelines for management are apparent. Conclusion: This review of the COVID-19 pandemic has elucidated a new global challenge which is affecting individuals’ quality of life by inducing long-term impaired cognitive function. The authors have found that comprehensive evaluations and interventions are crucial to address the cognitive sequelae in all COVID-19 patients, especially in patients with pre-existing cognitive impairment. Nevertheless, the authors recommend further research for the development of relevant, timely neurocognitive assessments and treatment plans

Genetics and Genomics of Chronic Pancreatitis with a Focus on Disease Biology and Molecular Pathogenesis

Chronic pancreatitis is a long-term fibroinflammatory condition of the pancreas with varying incidences across countries. The recent increase in its occurrence implies the involvement of genetic, hereditary, and unconventional risk factors. However, there is a lack of updated literature on recent advances in genetic polymorphisms of chronic pancreatitis. Therefore, this review aims to present recent findings on the genetic implications of chronic pancreatitis based on individual gene mechanisms and to discuss epigenetics and epistasis involved in the disease. Four mechanisms have been implicated in the pathogenesis of chronic pancreatitis, including premature activation of proteases, endoplasmic reticulum stress, ductal pathway dysfunction, and inflammatory pathway dysfunction. These mechanisms involve genes such as PRSS1, PRSS2, SPINK, CEL, PNLIP, PNLIPRP2, CFTR, CaSR, CLDN2, Alpha 1 antitrypsin, and GGT1. Studying genetic polymorphisms on the basis of altered genes and their products may aid clinicians in identifying predispositions in patients with and without common risk factors. Further research may also identify associations between genetic predispositions and disease staging or prognosis, leading to personalized treatment protocols and precision medicine

Epidemiology and etiology of brain cancer in Africa: A systematic review

BACKGROUND: Cancer is a significant threat to public health and a leading cause of morbidity across the globe. Of all cancers, brain cancer can be particularly catastrophic as treatment often fails to achieve the desired degree of effectiveness and diagnosis remains associated with a high mortality rate. Africa, as a continent with resource-limited countries, needs to allocate the necessary proper healthcare infrastructure to significantly reduce cancer rates and improve patient survival. In addition, the relative paucity of data within this field in Africa makes effective management a challenge. OBJECTIVE: This review is aimed at elucidating the currently available evidence base with regard to the epidemiology and etiology of brain cancer within resource-limited African countries. This review hopes to bring to the attention of the wider clinical community the growing burden of brain cancer within Africa and to encourage future research into this field of research. METHODS: The available literature for this Systematic Review was searched on two bibliographic databases, PubMed and Scopus, using an individually verified, prespecified approach. In addition, the Global Cancer Observatory and Global Burden of Disease databases were also utilized. Studies reporting on the epidemiology, etiology, and impact of brain cancer in Africa were suitable for inclusion. The level of evidence of the included studies was considered as per the Centre for Evidence-Based Medicine recommendations. RESULTS: Out of the four databases searched, 3848 articles were initially screened rigorously, filtered into 54 articles, and finally assessed qualitatively and quantitatively. We have demonstrated a poor survival rate and lack of proper funds/resources necessary to report, identify, and treat cases, as well as the dearth of comprehensive research on the subject of brain cancer that has become a challenging healthcare concern in many African developing nations. Also, because of the gradual improvement in healthcare facilities and the increasing population within many countries in Africa, the number of patients with central nervous system and intracranial tumors is rising specifically in the elder population. In addition, the population in West Africa is at a higher risk of HIV-related malignancies due to the high prevalence of HIV in West Africa. The burden of brain cancer in Africa is increasing in comparison with the developed parts of the world in which it is decreasing. Moreover, the mismanagement of cancers in Africa leads to higher morbidity and mortality and decreased quality of life. CONCLUSION: This study addresses the burden of brain cancer as a major public health crisis in Africa. Improved treatment modalities and access to screening are required to better address the burden of this disease. Therefore, there is a clear need for more substantial and comprehensive research on etiology, epidemiology, and treatment of brain cancer within Africa to understand its epidemiological distribution and provide a means for managing and reducing the associated morbidity and mortality

Developing Novel Experimental Models of m-TORopathic Epilepsy and Related Neuropathologies: Translational Insights from Zebrafish

The mammalian target of rapamycin (mTOR) is an important molecular regulator of cell growth and proliferation. Brain mTOR activity plays a crucial role in synaptic plasticity, cell development, migration and proliferation, as well as memory storage, protein synthesis, autophagy, ion channel expression and axonal regeneration. Aberrant mTOR signaling causes a diverse group of neurological disorders, termed ‘mTORopathies’. Typically arising from mutations within the mTOR signaling pathway, these disorders are characterized by cortical malformations and other neuromorphological abnormalities that usually co-occur with severe, often treatment-resistant, epilepsy. Here, we discuss recent advances and current challenges in developing experimental models of mTOR-dependent epilepsy and other related mTORopathies, including using zebrafish models for studying these disorders, as well as outline future directions of research in this field

Kinetics of Anti-Nucleocapsid IgG Response in COVID-19 Immunocompetent Convalescent Patients

International audienceAbstract The comprehension of a long-term humoral immune response against SARS-CoV-2 can shed light on the treatment and vaccination strategies of COVID-19 disease, improving the knowledge about this virus infection and/or re-infection. We assessed the IgG antibodies against SARS-CoV-2 nucleocapsid (N) protein (anti-SARS-CoV-2 (N) IgG) in 1441 COVID-19 convalescent patients within 15~months longitudinal study from middle-developed country. The main inclusion criteria was positive RT\textendash PCR result on nasopharyngeal swab samples at least one month before antibody testing and absence of any induced or inherited immunodeficiency. 92.7% of convalescent patients' serum contained anti-SARS-CoV-2 (N) IgG and only 1.3% of patients had a delayed antibody response. In the majority of convalescent patients' the durability of antibodies lasted more than one year. The kinetics of anti-SARS-CoV-2 (N) IgG took a bell-shaped character\textemdash increased first 25\textendash 30~weeks, then started to decrease, but were still detectable for more than 15~months. We found that on the one hand anti-SARS-CoV-2 humoral response level correlates with disease severity, on the other, in particular, the level of peak antibodies correlates with age\textemdash older patients develop more robust humoral response regardless of sex, disease severity and BMI