Pub Date : 2023-06-01DOI: 10.1016/j.lpm.2023.104182
Benjamin Rohaut
{"title":"Disorders of Consciousness: navigating between nihilism and unrealistic hopes","authors":"Benjamin Rohaut","doi":"10.1016/j.lpm.2023.104182","DOIUrl":"10.1016/j.lpm.2023.104182","url":null,"abstract":"","PeriodicalId":20530,"journal":{"name":"Presse Medicale","volume":"52 2","pages":"Article 104182"},"PeriodicalIF":2.7,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41210479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-06-01DOI: 10.1016/j.lpm.2023.104183
Armance Neveu , Vincent Degos , Anouk Barberousse
Recent work in the field of consciousness science has predominantly focused on the search for neural correlates of consciousness (NCC). However, despite significant technological advances in recent decades, defining NCC remains an ambitious goal in consciousness research. The main difficulty stems from an epistemological challenge known as the “Problem of coordination”, which hinders or at least slows down the experimental process inherent to the study of consciousness. Fundamental research has mainly focused on a content-based conception of consciousness, often referred to as a “local” conception of consciousness. This approach suffers from the Problem of coordination and its consequences. However, an alternative, more reliable approach could be considered, namely, the global or “state-based” approach, which is grounded in clinical research on consciousness disorders.
{"title":"Epistemological challenges for neural correlates of consciousness: A defense of medical research on consciousness","authors":"Armance Neveu , Vincent Degos , Anouk Barberousse","doi":"10.1016/j.lpm.2023.104183","DOIUrl":"10.1016/j.lpm.2023.104183","url":null,"abstract":"<div><p>Recent work in the field of consciousness science has predominantly focused on the search for neural correlates of consciousness (NCC). However, despite significant technological advances in recent decades, defining NCC remains an ambitious goal in consciousness research. The main difficulty stems from an epistemological challenge known as the “Problem of coordination”, which hinders or at least slows down the experimental process inherent to the study of consciousness. Fundamental research has mainly focused on a content-based conception of consciousness, often referred to as a “local” conception of consciousness. This approach suffers from the Problem of coordination and its consequences. However, an alternative, more reliable approach could be considered, namely, the global or “state-based” approach, which is grounded in clinical research<span> on consciousness disorders.</span></p></div>","PeriodicalId":20530,"journal":{"name":"Presse Medicale","volume":"52 2","pages":"Article 104183"},"PeriodicalIF":2.7,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41237925","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-06-01DOI: 10.1016/j.lpm.2023.104181
Camille Lakhlifi , Benjamin Rohaut
Neuropronostication for consciousness disorders can be very complex and prone to high uncertainty. Despite notable advancements in the development of dedicated scales and physiological markers using innovative paradigms, these technical progressions are often overshadowed by factors intrinsic to the medical environment. Beyond the scarcity of objective data guiding medical decisions, factors like time pressure, fatigue, multitasking, and emotional load can drive clinicians to rely more on heuristic-based clinical reasoning. Such an approach, albeit beneficial under certain circumstances, may lead to systematic error judgments and impair medical decisions, especially in complex and uncertain environments. After a brief review of the main theoretical frameworks, this paper explores the influence of clinicians' cognitive biases on clinical reasoning and decision-making in the challenging context of neuroprognostication for consciousness disorders. The discussion further revolves around developing and implementing various strategies designed to mitigate these biases and their impact, aiming to enhance the quality of care and the patient safety.
{"title":"Heuristics and biases in medical decision-making under uncertainty: The case of neuropronostication for consciousness disorders","authors":"Camille Lakhlifi , Benjamin Rohaut","doi":"10.1016/j.lpm.2023.104181","DOIUrl":"10.1016/j.lpm.2023.104181","url":null,"abstract":"<div><p>Neuropronostication for consciousness disorders<span> can be very complex and prone to high uncertainty. Despite notable advancements in the development of dedicated scales and physiological markers using innovative paradigms, these technical progressions are often overshadowed by factors intrinsic to the medical environment. Beyond the scarcity of objective data guiding medical decisions, factors like time pressure, fatigue, multitasking, and emotional load can drive clinicians to rely more on heuristic-based clinical reasoning. Such an approach, albeit beneficial under certain circumstances, may lead to systematic error judgments and impair medical decisions, especially in complex and uncertain environments. After a brief review of the main theoretical frameworks, this paper explores the influence of clinicians' cognitive biases on clinical reasoning and decision-making in the challenging context of neuroprognostication for consciousness disorders. The discussion further revolves around developing and implementing various strategies designed to mitigate these biases and their impact, aiming to enhance the quality of care and the patient safety.</span></p></div>","PeriodicalId":20530,"journal":{"name":"Presse Medicale","volume":"52 2","pages":"Article 104181"},"PeriodicalIF":2.7,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41210480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-06-01DOI: 10.1016/j.lpm.2022.104161
Nicholas D. Schiff
The ‘mesocircuit hypothesis’ proposes mechanisms underlying the recovery of consciousness following severe brain injuries. The model builds up from a single premise that multifocal brain injuries resulting in coma and subsequent disorders of consciousness produce widespread neuronal death and dysfunction. Considering the general properties of cortical, thalamic, and striatal neurons, a lawful and specific circuit-level mechanism is constructed based on these known anatomical and physiological specializations of neuronal subtypes. The mesocircuit model generates many testable predictions at the mesocircuit, local circuit, and cellular level across multiple cerebral structures to correlate diagnostic measurements and interpret therapeutic interventions. The anterior forebrain mesocircuit is integrally related to the frontal-parietal network, another network demonstrated to show strong correlation with levels of recovery in disorders of consciousness. A further extension known as the “ABCD” model has been used to examine interaction of these models in recovery of consciousness using electrophysiological data types. Many studies have examined predictions of the mesocircuit model; here we first present the model and review the accumulated evidence for several predictions of model across multiple stages of recovery function in human subjects. Recent studies linking the mesocircuit model, the ABCD model, and interactions with the frontoparietal network are reviewed. Finally, theoretical implications of the mesocircuit model at the neuronal level are considered to interpret recent studies of deep brain stimulation in the central lateral thalamus in patients recovering from coma and in new experimental models in the context of emerging understanding of neuronal and local circuit mechanisms underlying conscious brain states.
{"title":"Mesocircuit mechanisms in the diagnosis and treatment of disorders of consciousness","authors":"Nicholas D. Schiff","doi":"10.1016/j.lpm.2022.104161","DOIUrl":"10.1016/j.lpm.2022.104161","url":null,"abstract":"<div><p><span>The ‘mesocircuit hypothesis’ proposes mechanisms underlying the recovery of consciousness following severe brain injuries. The model builds up from a single premise that multifocal brain injuries<span> resulting in coma and subsequent disorders of consciousness<span><span> produce widespread neuronal death and dysfunction. Considering the general properties of cortical, thalamic, and striatal neurons, a lawful and specific circuit-level mechanism is constructed based on these known anatomical and physiological specializations of neuronal subtypes. The mesocircuit model generates many testable predictions at the mesocircuit, local circuit, and cellular level across multiple cerebral structures to correlate diagnostic measurements and interpret therapeutic interventions. The anterior forebrain mesocircuit is integrally related to the frontal-parietal network, another network demonstrated to show strong correlation with levels of recovery in disorders of consciousness. A further extension known as the “ABCD” model has been used to examine interaction of these models in recovery of consciousness using electrophysiological data types. Many studies have examined predictions of the mesocircuit model; here we first present the model and review the accumulated evidence for several predictions of model across multiple stages of recovery function in human subjects. Recent studies linking the mesocircuit model, the ABCD model, and interactions with the frontoparietal network are reviewed. Finally, theoretical implications of the mesocircuit model at the neuronal level are considered to interpret recent studies of </span>deep brain stimulation<span> in the central lateral thalamus </span></span></span></span>in patients recovering from coma and in new experimental models in the context of emerging understanding of neuronal and local circuit mechanisms underlying conscious brain states.</p></div>","PeriodicalId":20530,"journal":{"name":"Presse Medicale","volume":"52 2","pages":"Article 104161"},"PeriodicalIF":2.7,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10724398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-06-01DOI: 10.1016/j.lpm.2023.104180
Aditya Kumar, Mohamed Ridha, Jan Claassen
Assessments of consciousness are a critical part of prognostic algorithms for critically ill patients suffering from severe brain injuries. There have been significant advances in the field of coma science over the past two decades, providing clinicians with more advanced and precise tools for diagnosing and prognosticating disorders of consciousness (DoC). Advanced neuroimaging and electrophysiological techniques have vastly expanded our understanding of the biological mechanisms underlying consciousness, and have helped identify new states of consciousness. One of these, termed cognitive motor dissociation, can predict functional recovery at 1 year post brain injury, and is present in up to 15–20% of patients with DoC. In this chapter, we review several tools that are used to predict DoC, describing their strengths and limitations, from the neurological examination to advanced imaging and electrophysiologic techniques. We also describe multimodal assessment paradigms that can be used to identify covert consciousness and thus help recognize patients with the potential for future recovery and improve our prognostication practices.
{"title":"Prognosis of consciousness disorders in the intensive care unit","authors":"Aditya Kumar, Mohamed Ridha, Jan Claassen","doi":"10.1016/j.lpm.2023.104180","DOIUrl":"10.1016/j.lpm.2023.104180","url":null,"abstract":"<div><p>Assessments of consciousness are a critical part of prognostic algorithms for critically ill patients suffering from severe brain injuries. There have been significant advances in the field of coma science over the past two decades, providing clinicians with more advanced and precise tools for diagnosing and prognosticating disorders of consciousness (DoC). Advanced neuroimaging and electrophysiological techniques have vastly expanded our understanding of the biological mechanisms underlying consciousness, and have helped identify new states of consciousness. One of these, termed cognitive motor dissociation, can predict functional recovery at 1 year post brain injury, and is present in up to 15–20% of patients with DoC. In this chapter, we review several tools that are used to predict DoC, describing their strengths and limitations, from the neurological examination to advanced imaging and electrophysiologic techniques. We also describe multimodal assessment paradigms that can be used to identify covert consciousness and thus help recognize patients with the potential for future recovery and improve our prognostication practices.</p></div>","PeriodicalId":20530,"journal":{"name":"Presse Medicale","volume":"52 2","pages":"Article 104180"},"PeriodicalIF":2.7,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41148275","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-06-01DOI: 10.1016/j.lpm.2023.104165
Jacques Luauté , Maude Beaudoin-Gobert
Background
Several methods have been proposed to foster recovery of consciousness in patients with disorders of consciousness (DoC).
Objective
Critically assess pharmacological and non-pharmacological treatments for patients with chronic DoC.
Methods
A narrative mini-review, and critical analysis of the scientific literature on the various proposed therapeutic approaches, with particular attention to level of evidence, risk-benefit ratio, and feasibility.
Results and discussion
Personalised sensory stimulation, median nerve stimulation, transcranial direct current stimulation (tDCS), amantadine and zolpidem all have favourable risk-benefit ratios and are easy to implement in clinical practice. These treatments should be proposed to every patient with chronic DoC. Comprehensive patient management should also include regular lifting, pain assessment and treatment, attempts to restore sleep and circadian rhythms, implementation of rest periods, comfort and nursing care, and a rehabilitation program with a multi-disciplinary team with expertise in this field. More invasive treatments may cause adverse effects and require further investigation to confirm preliminary, encouraging results and to better define responders’ intervention parameters. Scientific studies are essential and given the severity of the disability and handicap that results from DoC, research in this area should aim to develop new therapeutic approaches.
{"title":"Optimising recovery of consciousness after coma. From bench to bedside and vice versa","authors":"Jacques Luauté , Maude Beaudoin-Gobert","doi":"10.1016/j.lpm.2023.104165","DOIUrl":"10.1016/j.lpm.2023.104165","url":null,"abstract":"<div><h3>Background</h3><p>Several methods have been proposed to foster recovery of consciousness in patients<span> with disorders of consciousness (DoC).</span></p></div><div><h3>Objective</h3><p>Critically assess pharmacological and non-pharmacological treatments for patients with chronic DoC.</p></div><div><h3>Methods</h3><p>A narrative mini-review, and critical analysis of the scientific literature on the various proposed therapeutic approaches, with particular attention to level of evidence, risk-benefit ratio, and feasibility.</p></div><div><h3>Results and discussion</h3><p>Personalised sensory stimulation<span>, median nerve<span><span> stimulation, transcranial direct current stimulation (tDCS), amantadine and </span>zolpidem all have favourable risk-benefit ratios and are easy to implement in clinical practice. These treatments should be proposed to every patient with chronic DoC. Comprehensive patient management should also include regular lifting, pain assessment and treatment, attempts to restore sleep and circadian rhythms, implementation of rest periods, comfort and nursing care, and a rehabilitation program with a multi-disciplinary team with expertise in this field. More invasive treatments may cause adverse effects and require further investigation to confirm preliminary, encouraging results and to better define responders’ intervention parameters. Scientific studies are essential and given the severity of the disability and handicap that results from DoC, research in this area should aim to develop new therapeutic approaches.</span></span></p></div>","PeriodicalId":20530,"journal":{"name":"Presse Medicale","volume":"52 2","pages":"Article 104165"},"PeriodicalIF":2.7,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9611025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-03-01DOI: 10.1016/j.lpm.2022.104160
Nelson Wang , Sophia Zoungas , John Chalmers
Adequate blood glucose and blood pressure control is paramount for the prevention of microvascular and macrovascular complications in patients with type 2 diabetes (T2D). This review article summarises the important advances in blood glucose and blood pressure lowering from the last three decades, with a focus on the evidence from large scale randomized clinical trials and meta-analyses. This paper focuses on evidence supporting specific blood glucose and blood pressure targets, and the importance of long-term sustained risk factor control. Novel therapies including the glucagon-like peptide-1 receptor agonists (GLP1-RA) and the sodium glucose co-transporter 2 inhibitors (SGLT2i) have revolutionized the treatment of type 2 diabetes and highlighted the importance of approaches that deliver benefits beyond glucose or blood pressure lowering. This article provides an overview of contemporary management of T2D with an emphasis on tailoring treatment plans to the individual.
{"title":"Benefits of intensified reductions in blood glucose and in blood pressure for patients with type 2 diabetes","authors":"Nelson Wang , Sophia Zoungas , John Chalmers","doi":"10.1016/j.lpm.2022.104160","DOIUrl":"10.1016/j.lpm.2022.104160","url":null,"abstract":"<div><p><span>Adequate blood glucose and blood pressure control is paramount for the prevention of microvascular and macrovascular complications in patients with type 2 diabetes (T2D). This review article summarises the important advances in blood glucose and blood pressure lowering from the last three decades, with a focus on the evidence from large scale </span>randomized clinical trials<span> and meta-analyses. This paper focuses on evidence supporting specific blood glucose and blood pressure targets, and the importance of long-term sustained risk factor control. Novel therapies including the glucagon-like peptide-1 receptor agonists (GLP1-RA) and the sodium glucose co-transporter 2 inhibitors (SGLT2i) have revolutionized the treatment of type 2 diabetes and highlighted the importance of approaches that deliver benefits beyond glucose or blood pressure lowering. This article provides an overview of contemporary management of T2D with an emphasis on tailoring treatment plans to the individual.</span></p></div>","PeriodicalId":20530,"journal":{"name":"Presse Medicale","volume":"52 1","pages":"Article 104160"},"PeriodicalIF":2.7,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10738641","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-03-01DOI: 10.1016/j.lpm.2022.104159
Luigi Gnudi
{"title":"Renal disease in patients with type 2 diabetes: Magnitude of the problem, risk factors and preventive strategies","authors":"Luigi Gnudi","doi":"10.1016/j.lpm.2022.104159","DOIUrl":"10.1016/j.lpm.2022.104159","url":null,"abstract":"","PeriodicalId":20530,"journal":{"name":"Presse Medicale","volume":"52 1","pages":"Article 104159"},"PeriodicalIF":2.7,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10738642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-03-01DOI: 10.1016/j.lpm.2023.104164
Ninon Foussard , Loubna Dari , Eric Ducasse , Vincent Rigalleau , Kamel Mohammedi , Caroline Caradu
Lower-limb peripheral arterial disease (PAD), is a common manifestation of systemic atherosclerosis, resulting from a partial or complete obstruction of at least one lower-limb arteries. PAD is a major endemic disease with an excess risk of major cardiovascular events and death. It also leads to disability, high rates of lower-limb adverse events and non-traumatic amputation. In patients with diabetes, PAD is particularly frequent and has a worse prognosis than in patients without diabetes. The risk factors of PAD are comparable to those for cardiovascular disease. The ankle-brachial index is usually recommended to screen PAD despite its limited performance in patients with diabetes, affected by the presence of peripheral neuropathy, medial arterial calcification, incompressible arteries and infection. Toe brachial index and toe pressure emerge as alternative screening tools. The management of PAD requires strict control of cardiovascular risk factors including diabetes, hypertension and dyslipidaemia, the use of antiplatelet agents and lifestyle management, to reduce cardiovascular adverse events, but few randomized controlled trials have evaluated the benefits of these treatments in PAD. Several advances have been achieved in endovascular and surgical revascularization procedures, with obvious improvement in PAD prognosis. Further studies are required to increase our understanding of the pathophysiology of PAD and to evaluate the interest of different therapeutic strategies in the occurrence and progression of PAD in patients with diabetes. Here, we present a narrative and contemporary review to synthesize the key epidemiology findings, screening and diagnosis methods, and major therapeutic advances regarding PAD in patients with diabetes.
{"title":"Lower-limb peripheral arterial disease and amputations in people with diabetes: Risk factors, prognostic value and management","authors":"Ninon Foussard , Loubna Dari , Eric Ducasse , Vincent Rigalleau , Kamel Mohammedi , Caroline Caradu","doi":"10.1016/j.lpm.2023.104164","DOIUrl":"10.1016/j.lpm.2023.104164","url":null,"abstract":"<div><p><span><span><span><span>Lower-limb peripheral arterial disease (PAD), is a common manifestation of systemic </span>atherosclerosis<span>, resulting from a partial or complete obstruction of at least one lower-limb arteries. PAD is a major endemic disease with an excess risk of major cardiovascular events and death. It also leads to disability, high rates of lower-limb adverse events and non-traumatic amputation. </span></span>In patients<span><span> with diabetes, PAD is particularly frequent and has a worse prognosis than in patients without diabetes. The risk factors of PAD are comparable to those for cardiovascular disease. The ankle-brachial index is usually recommended to screen PAD despite its limited performance in patients with diabetes, affected by the presence of peripheral neuropathy, medial arterial calcification<span>, incompressible arteries and infection. Toe brachial index and toe pressure emerge as alternative screening tools. The management of PAD requires strict control of cardiovascular risk factors including diabetes, hypertension and </span></span>dyslipidaemia<span>, the use of antiplatelet agents and lifestyle management, to reduce cardiovascular adverse events, but few </span></span></span>randomized controlled trials<span> have evaluated the benefits of these treatments in PAD. Several advances have been achieved in endovascular and surgical </span></span>revascularization<span><span> procedures, with obvious improvement in PAD prognosis. Further studies are required to increase our understanding of the pathophysiology of PAD and to evaluate the interest of different therapeutic strategies in the occurrence and progression of PAD in patients with diabetes. Here, we present a narrative and contemporary review to synthesize the key </span>epidemiology findings, screening and diagnosis methods, and major therapeutic advances regarding PAD in patients with diabetes.</span></p></div>","PeriodicalId":20530,"journal":{"name":"Presse Medicale","volume":"52 1","pages":"Article 104164"},"PeriodicalIF":2.7,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9256286","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-03-01DOI: 10.1016/j.lpm.2023.104167
Patrick Berche
In nature, wild viruses adapted for transmission circulate in many animal species (bats, birds, primates…). Contamination of other animals, including humans, may occur by crossing of the species barrier. Genetic manipulations have been carried out on wild viruses to favor the species jumping and to increase of viral virulence. The aim was to identify the critical genes for pathogenicity. This has been mainly performed on potentially epidemic pathogens, as Myxovirus influenzae of avian flu and coronaviruses of SARS and MERS epidemics. These dangerous experiments were subject to a moratorium in the United States (2014–2017). Three years after the emergence of Covid-19, the origin of du SARS-CoV2 remains a mystery. Covid19 appeared in Wuhan, officially in December 2019, but probably during the autumn 2019. The virus was identified in January 2020. It belongs to the genus Betacoronavirus (subgenus Sarbecovirus). It was at once highly contagious. In addition, the primary isolates were genetically very homogeneous, differing only by two nucleotides without evidence for adaptive mutations. In addition, the Spike protein, a major virulence factor, has a furin site, not found in any other known sarbecovirus. Unlike the SARS and MERS epidemics, no intermediate host has been detected so far. Finally, no other outbreaks were reported at the beginning of the pandemic outside of Wuhan, contrary to what happened with the emergence of SARS (2002) and H7N9 avian influenza (2013). Today, there are two scenarios to explain the emergence of SARS-CoV2. Proponents of the natural origin argue that the bat virus might have directly infected humans, spreading silently at a low level in humans for years, without eliminating the existence of undetected intermediate hosts. This does not explain the origin in Wuhan, far away from the natural virus reservoirs. The furin site would have arisen spontaneously from other coronaviruses. The alternative scenario is that of a laboratory accident after gain-of-function manipulations from a SARS-like virus, or even the occurrence of a human contamination by a natural CoV virus grown on cells in Wuhan.
This article is an update to the Quarterly Medical Review (QMR) devoted to the history of modern pandemics. To access this QMR contents, please go here: https://www.sciencedirect.com/journal/la-presse-medicale/vol/51/issue/3
{"title":"Gain-of-function and origin of Covid19","authors":"Patrick Berche","doi":"10.1016/j.lpm.2023.104167","DOIUrl":"10.1016/j.lpm.2023.104167","url":null,"abstract":"<div><p><span><span>In nature, wild viruses adapted for transmission circulate in many animal species (bats, birds, primates…). Contamination of other animals, including humans, may occur by crossing of the species barrier. Genetic manipulations have been carried out on wild viruses to favor the species jumping and to increase of </span>viral virulence<span>. The aim was to identify the critical genes for pathogenicity. This has been mainly performed on potentially epidemic pathogens, as </span></span><em>Myxovirus influenzae</em><span><span> of avian flu and coronaviruses of SARS and </span>MERS epidemics. These dangerous experiments were subject to a moratorium in the United States (2014–2017). Three years after the emergence of Covid-19, the origin of du SARS-CoV2 remains a mystery. Covid19 appeared in Wuhan, officially in December 2019, but probably during the autumn 2019. The virus was identified in January 2020. It belongs to the genus </span><span><em>Betacoronavirus</em></span> (subgenus <em>Sarbecovirus</em><span><span><span>). It was at once highly contagious. In addition, the primary isolates were genetically very homogeneous, differing only by two nucleotides without evidence for adaptive mutations. In addition, the Spike protein, a major virulence factor, has a </span>furin site, not found in any other known sarbecovirus. Unlike the SARS and MERS epidemics, no intermediate host has been detected so far. Finally, no other outbreaks were reported at the beginning of the pandemic outside of Wuhan, contrary to what happened with the emergence of SARS (2002) and </span>H7N9<span> avian influenza (2013). Today, there are two scenarios to explain the emergence of SARS-CoV2. Proponents of the natural origin argue that the bat virus might have directly infected humans, spreading silently at a low level in humans for years, without eliminating the existence of undetected intermediate hosts. This does not explain the origin in Wuhan, far away from the natural virus reservoirs. The furin site would have arisen spontaneously from other coronaviruses. The alternative scenario is that of a laboratory accident after gain-of-function manipulations from a SARS-like virus, or even the occurrence of a human contamination by a natural CoV virus grown on cells in Wuhan.</span></span></p><p>This article is an update to the Quarterly Medical Review (QMR) devoted to the history of modern pandemics. To access this QMR contents, please go here: <span>https://www.sciencedirect.com/journal/la-presse-medicale/vol/51/issue/3</span><svg><path></path></svg></p></div>","PeriodicalId":20530,"journal":{"name":"Presse Medicale","volume":"52 1","pages":"Article 104167"},"PeriodicalIF":2.7,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10234839/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9641414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}