Long COVID is an often debilitating illness that occurs in at least 10% of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. More than 200 symptoms have been identified with impacts on multiple organ systems. At least 65 million individuals worldwide are estimated to have long COVID, with cases increasing daily. Biomedical research has made substantial progress in identifying various pathophysiological changes and risk factors and in characterizing the illness; further, similarities with other viral-onset illnesses such as myalgic encephalomyelitis/chronic fatigue syndrome and postural orthostatic tachycardia syndrome have laid the groundwork for research in the field. In this Review, we explore the current literature and highlight key findings, the overlap with other conditions, the variable onset of symptoms, long COVID in children and the impact of vaccinations. Although these key findings are critical to understanding long COVID, current diagnostic and treatment options are insufficient, and clinical trials must be prioritized that address leading hypotheses. Additionally, to strengthen long COVID research, future studies must account for biases and SARS-CoV-2 testing issues, build on viral-onset research, be inclusive of marginalized populations and meaningfully engage patients throughout the research process. Long COVID is an often debilitating illness of severe symptoms that can develop during or following COVID-19. In this Review, Davis, McCorkell, Vogel and Topol explore our knowledge of long COVID and highlight key findings, including potential mechanisms, the overlap with other conditions and potential treatments. They also discuss challenges and recommendations for long COVID research and care. 

https://www.nature.com/articles/s41579-022-00846-2.pdf

Long COVID: major findings, mechanisms and recommendations

https://doi.org/10.1016/j.jacc.2022.02.003

2022 ACC Expert Consensus Decision Pathway on Cardiovascular Sequelae of COVID-19 in Adults: Myocarditis and Other Myocardial Involvement, Post-Acute Sequelae of SARS-CoV-2 Infection, and Return to Play

Fatigue, exertion intolerance and post-exertional malaise are among the most frequent symptoms of Post-COVID Syndrome (PCS), with a subset of patients fulfilling criteria for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). As SARS-CoV-2 infects endothelial cells, causing endotheliitis and damaging the endothelium, we investigated endothelial dysfunction (ED) and endothelial biomarkers in patients with PCS.We studied the endothelial function in 30 PCS patients with persistent fatigue and exertion intolerance as well as in 15 age- and sex matched seronegative healthy controls (HCs). 14 patients fulfilled the diagnostic criteria for ME/CFS. The other patients were considered to have PCS. Peripheral endothelial function was assessed by the reactive hyperaemia index (RHI) using peripheral arterial tonometry (PAT) in patients and HCs. In a larger cohort of patients and HCs, including post-COVID reconvalescents (PCHCs), Endothelin-1 (ET-1), Angiopoietin-2 (Ang-2), Endocan (ESM-1), IL-8, Angiotensin-Converting Enzyme (ACE) and ACE2 were analysed as endothelial biomarkers.Five of the 14 post-COVID ME/CFS patients and five of the 16 PCS patients showed ED defined by a diminished RHI (< 1.67), but none of HCs exhibited this finding. A paradoxical positive correlation of RHI with age, blood pressure and BMI was found in PCS but not ME/CFS patients. The ET-1 concentration was significantly elevated in both ME/CFS and PCS patients compared to HCs and PCHCs. The serum Ang-2 concentration was lower in both PCS patients and PCHCs compared to HCs.A subset of PCS patients display evidence for ED shown by a diminished RHI and altered endothelial biomarkers. Different associations of the RHI with clinical parameters as well as varying biomarker profiles may suggest distinct pathomechanisms among patient subgroups. 

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Endothelial dysfunction and altered endothelial biomarkers in patients with post-COVID-19 syndrome and chronic fatigue syndrome (ME/CFS)

/pdf/endothelial-dysfunction-and-altered-endothelial-biomarkers-63gsqlqg.pdf

Many discharged COVID-19 patients affected by sequelae experience reduced quality of life leading to an increased burden on the healthcare system, their families and society at large. Possible pathophysiological mechanisms of long COVID include: persistent viral replication, chronic hypoxia and inflammation. Ongoing vascular endothelial damage promotes platelet adhesion and coagulation, resulting in the impairment of various organ functions. Meanwhile, thrombosis will further aggravate vasculitis contributing to further deterioration. Thus, long COVID is essentially a thrombotic sequela. Unfortunately, there is currently no effective treatment for long COVID. This article summarizes the evidence for coagulation abnormalities in long COVID, with a focus on the pathophysiological mechanisms of thrombosis. Extracellular vesicles (EVs) released by various types of cells can carry SARS-CoV-2 through the circulation and attack distant tissues and organs. Furthermore, EVs express tissue factor and phosphatidylserine (PS) which aggravate thrombosis. Given the persistence of the virus, chronic inflammation and endothelial damage are inevitable. Pulmonary structural changes such as hypertension, embolism and fibrosis are common in long COVID. The resulting impaired lung function and chronic hypoxia again aggravates vascular inflammation and coagulation abnormalities. In this article, we also summarize recent research on antithrombotic therapy in COVID-19. There is increasing evidence that early anticoagulation can be effective in improving outcomes. In fact, persistent systemic vascular inflammation and dysfunction caused by thrombosis are key factors driving various complications of long COVID. Early prophylactic anticoagulation can prevent the release of or remove procoagulant substances, thereby protecting the vascular endothelium from damage, reducing thrombotic sequelae, and improving quality of life for long-COVID patients.

/pdf/long-covid-the-nature-of-thrombotic-sequelae-determines-the-3cw2b99w.pdf

Long COVID: The Nature of Thrombotic Sequelae Determines the Necessity of Early Anticoagulation

The COVID-19 disease is a multisystem disease due to in part to the vascular endothelium injury. Lasting effects and long -term sequalae could persist after the infection and may be due to persistent endothelial dysfunction. Our study focused on the evaluation of endothelial quality index (EQI) by finger thermal monitoring with E4 diagnosis Polymath in a large cohort of long COVID-19 patients to determine whether long-covid 19 symptoms are associated to endothelial dysfunction. This is a cross sectional multicenter observational study with a prospective recruitment of patients. A total of 798 patients were included in this study. A total of 618 patients (77.4%) had long COVID-19 symptoms. The mean EQI was 2.02 ± 0.99 IC95% [1.95 – 2.08]. A total of 397 (49.7%) patients had impaired EQI. Fatigue, chest pain and neuro-cognitive difficulties were significantly associated to endothelium dysfunction with an EQI <2 after adjustment with age, sex, diabetes, hypertension, dyslipidemia, coronary heart disease and the severity of acute COVID-19 infection. In multivariate analysis, endothelial dysfunction (EQI < 2), female gender and severe clinical status at acute COVID-19 infection with a need to oxygen supplementation were independent risk factors of long COVID-19 syndrome. Long COVID-19 symptoms specifically non-respiratory symptoms are due to persistent endothelial dysfunction. These findings allow a better care of patients with long COVID-19 symptoms.

Long COVID 19 Syndrome: Is It Related to Microcirculation and Endothelial Dysfunction? Insights From TUN-EndCOV Study

Isolated sternal tuberculosis is a rarely described entity even in countries where tuberculosis is endemic. We report the case of 25 old years patient who presented with a chest wall mass. Imaging concluded to a (ring-enhancing hypodense soft tissue mass surrounding the sternum with sternal fracture). Malignancy was eliminated by a core needle biopsy. We noted clinical and radiological recovery with medical tuberculosis treatment. Neoplastic origin was removed by biopsy and anatomopathological study of the lesion.

Isolated sternal tuberculosis in immunocompétent adult

Introduction Le cancer du poumon (CP) est l’une des principales causes de deces par cancer dans le monde entier. La survie ne s’est que peu amelioree en depit des nouvelles therapies. Compte tenu de l’importance des symptomes et d’une morbidite toujours tres severe, l’evaluation de la qualite de vie devient un enjeu important chez ces patients. Methodes Etude prospective menee entre juillet 2016 et juin 2017, au service de pneumologie de Sfax ayant inclus 80 patients porteurs d’un CP confirme histologiquement stade III B et IV. La qualite de vie etait evaluee par le questionnaire (EORTC QLQ-C30), la depression par le score HAD, la douleur par l’echelle visuelle analogique et le Performance Status (PS) par l’indice de karnofsky. Resultats L’âge moyen de nos patients etait de 61,20 ans avec un sex-ratio de (19). Soixante-seize patients etaient tabagiques actifs avec une consommation moyenne de 62,53 PA. Le PS etait a 1 (8 %) PS a 2 (12 %) PS a 3 (45 %) et PS a 4 (35 %). Le CP etait classe stade III B dans 35 % des cas et IV dans 65 %. Parmi les patients, 95 % recevaient une chimiotherapie palliative. Quatre-vingt-dix pour cent des patients etaient sous antalgique palier 1 et 25 % sous paliers 2 et 40 % sous derives morphiniques avec une dose moyenne de 46 mg. La douleur etait rapportee par 85 % des patients malgre la prise d’antalgiques. Une alteration de la qualite de vie en se basant sur le questionnaire (EORTC QLQ-C30) etait constatee chez 42 % des patients [1] . Une humeur depressive etait presente chez 48 patients soit 60 %. Les patients ayant une alteration de leur qualite de vie avaient un PS a 4 dans 58 % des et un PS a 3 dans 41 % des cas. Il y avait une correlation statistiquement significative entre l’alteration de la qualite de vie et la presence de troubles depressifs (p = 0,01) [2] , l’absence de controle de la douleur et le stade avance de PS (p = 0,005). Conclusion L’analyse de la qualite de vie est consideree comme une composante essentielle de la gestion therapeutique du CP et doit etre effectuee regulierement. Mais l’outil de son evaluation ideal n’existe pas, et les problemes de subjectivite et de perte de donnees representent encore des facteurs limitant a son utilisation en routine.

Évaluation de la qualité de vie en oncologie thoracique

Introduction Il est actuellement etabli que la denutrition est associee a une aggravation du pronostic du BPCO independamment des parametres ventilatoires. Objectifs determiner la prevalence de la denutrition chez les patients BPCO et evaluer l’impact de la perte de la masse musculaire sur la morbidite, le recours aux soins et la qualite de vie. Methodes Etude prospective menee entre janvier et decembre 2016, incluant les patients atteints d’une BPCO moderee a severe a l’etat stable, suivis a notre service. Ont ete exclus les patients ayant une autre pathologie respiratoire et ceux ayant une pathologie pouvant interferer sur l’etat nutritionnel (cancer, troubles gastro-intestinaux ou metaboliques ou endocriniens, une intervention chirurgicale recente). L’evaluation de l’etat nutritionnel comportait la mesure du poids corporel et le calcul de l’index de masse corporelle (IMC). La composition corporelle etait determinee par impedancemetrie bioelectrique. L’indice de masse maigre etait considere abaisse s’il est inferieur a 16. La qualite de vie etait determinee en utilisant le questionnaire de Saint-Georges. Le recours aux soins notamment le nombre d’exacerbations au cours de l’annee etait note. Resultats Il s’agissait de 43 patients (42 hommes et 1 femme). L’âge moyen etait de 66 ans avec des extremes allant de 47 a 85 ans. Un IMC  [1] etait constatee dans 9 % des cas. L’indice de masse maigre etait inferieur a 16 chez 26 % de nos patients. La perte de masse maigre etait correlee aux nombre d’exacerbations necessitant le recours aux soins ainsi qu’une alteration de la qualite de vie (avec p  Conclusion La perte de masse maigre est un facteur predictif de mortalite. De ce fait, une evaluation nutritionnelle comportant une mesure de la composition corporelle devrait etre systematique chez le patient BPCO [2] .

N. Moussa

Papers

Long COVID 19 Syndrome: Is It Related to Microcirculation and Endothelial Dysfunction? Insights From TUN-EndCOV Study

Isolated sternal tuberculosis in immunocompétent adult

Évaluation de la qualité de vie en oncologie thoracique

Évaluation de l’état nutritionnel chez le BPCO

Profil clinique, paraclinique et évolutif des pneumopathies interstitielles non spécifiques (PINS)