BACKGROUND While stroke and lower extremity venous thromboemboli have been commonly reported following acute infection with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),spinal cord infarction or ischemi...BACKGROUND While stroke and lower extremity venous thromboemboli have been commonly reported following acute infection with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),spinal cord infarction or ischemia has been extremely rare.Findings of long coronavirus disease(COVID)in this select population have not been studied.CASE SUMMARY We present the case of a 70-year-old female with sudden onset of trunk and lower extremity sensorimotor loss due to spinal cord infarction,attributed to acute infection with SARS-CoV-2.Diagnostic work up confirmed a T3 complete(ASIA impairment Scale A)paraplegia resulting from a thrombotic infarct.Her reported myalgias,neuropathic pain,spasticity,bladder spasms,and urinary tract infections exceeded the frequency and severity of many spinal cord injury(SCI)individuals of similar age and degree of neurologic impairment.In her first year after contracting COVID-19,she underwent 2 separate inpatient rehabilitation courses,but also required acute hospitalization 6 additional times for subsequent infections or uncontrolled pain.Yet other complications of complete non-traumatic SCI(NTSCI),including neurogenic bowel and temperature hypersens-itivity,were mild,and pressure injuries were absent.She has now transitioned from the acute to chronic phase of spinal cord injury care,with subsequent development of post-acute sequelae of SARS-CoV-2 infection(PASC).CONCLUSION This individual experienced significant challenges with the combined effects of acute T3 NTSCI and acute COVID-19,with subsequent progression to PASC.Core Tip:Although stroke and venous thromboembolism have been frequently observed with acute coronavirus disease 2019(COVID-19),spinal cord infarction leading to paraplegia has rarely been seen.We report a case of spinal cord infarction shortly following infection with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).Consequently,this individual has experienced severe neurologic disability,with subsequent development of long COVID.Symptoms such as myalgias,neuropathic pain,muscle spasms,and frequent bacterial infections are present in post-acute sequelae of SARS-CoV-2 infection(PASC),independent of spinal cord injury(SCI).Over the past 3 years,the dual presence of PASC and recent SCI may have led to increased severity of symptoms shared by both conditions.INTRODUCTION Among vascular events,spinal cord infarction is relatively rare,accounting for only 0.3%-1%of all strokes[1]and 5%-8%of acute myelopathies[2].One cause of spinal cord infarction arises from a thrombotic event in vulnerable areas of the thoracic cord,particularly between T8-12,which is supplied by the artery of Adamkiewicz.While deep vein thrombosis,pulmonary embolism,and stroke are commonly observed complications of coronavirus disease 2019(COVID-19),spinal cord infarction is comparatively infrequent[3-6].The cytokine release following acute infection,which peaks 7 d after contracting the virus,may be responsible for the increase in thrombotic events associated with acute infection with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)[7,8].This case discussed in this report differs from other published accounts describing spinal cord infarcts attributed to acute SARS-CoV-2,because we have followed this individual for nearly 3 years after contracting COVID-19,covering her difficulties with“long COVID,”which has now officially named post-acute sequelae of SARS-CoV-2 infection(PASC)by the World Health Organization[9].The term PASC may be assigned to“individuals with a history of probable or confirmed SARS-CoV-2 infection,usually 3 mo from the onset of COVID-19 with symptoms that last for at least 2 mo and cannot be explained by an alternative diagnosis”.The definition further states that PASC generally impacts everyday functioning and that symptoms may be of new onset,follow initial recovery from an acute COVID-19 episode,or persist from the initial illness.Moreover,symptoms may also fluctuate or relapse over time[9].Common complaints of PASC include fatigue,cough shortness of breath,cognitive deficits or“brain fog”.Reported features of PASC may also involve headache,heart palpitations,exercise intolerance,joint pain or swelling,myalgias,vertigo,peripheral neuropathy,altered taste or smell,disordered sleep,anxiety,depression,and thromboembolic events[10-13].While a number of the above symptoms may occur subsequent to SCI,many would be unusual,such as persistent cough,fatigue months after SCI,changes in taste or smell,continued exercise intolerance,new onset cognitive deficits or“brain fog”,unrelated to any sedating medications or concomitant brain injury.Our patient became symptomatic prior to COVID-19 vaccine availability and has given written consent to share her story for educational publication.This project was approved by the Institutional Review Board of the MetroHealth System.展开更多
The principal goal of psychiatric rehabilitation is to improve the global functioning of a person who suffer from a mental disorder. New emerging groups of patients meet difficult to attend to a rehabilitation program...The principal goal of psychiatric rehabilitation is to improve the global functioning of a person who suffer from a mental disorder. New emerging groups of patients meet difficult to attend to a rehabilitation program. Sport represents a new flexible model that can be used in psychiatric rehabilitation. Sport improves physical health and well being, increases sociality, increases self-efficacy and self-esteem. It is well accepted and well tolerated by the patients, too. Its use goes over the chronic phase of illness (typical target of rehabilitation) and it extends to the post-acute and pre acute phase, too.展开更多
SARS COV-2 infection causes acute and frequently severe respiratory disease with associated multi-organ damage and systemic disturbances in many biochemical pathways.Metabolic phenotyping provides deep insights into t...SARS COV-2 infection causes acute and frequently severe respiratory disease with associated multi-organ damage and systemic disturbances in many biochemical pathways.Metabolic phenotyping provides deep insights into the complex immunopathological problems that drive the resulting COVID-19 disease and is also a source of novel metrics for assess-ing patient recovery.A multiplatform metabolic phenotyping approach to studying the pathology and systemic metabolic sequelae of COVID-19 is considered here,together with a framework for assessing post-acute COVID-19 Syndrome(PACS)that is a major long-term health consequence for many patients.The sudden emergence of the disease presents a biological discovery challenge as we try to understand the pathological mechanisms of the disease and develop effective mitigation strategies.This requires technologies to measure objectively the extent and sub-phenotypes of the disease at the molecular level.Spectroscopic methods can reveal metabolic sub-phenotypes and new biomarkers that can be monitored during the acute disease phase and beyond.This approach is scalable and translatable to other pathologies and provides as an exem-plar strategy for the investigation of other emergent zoonotic diseases with complex immunological drivers,multi-system involvements and diverse persistent symptoms.展开更多
Objective Coronavirus disease 2019(COVID-19)can result in fatigue and post-exertional malaise;however,whether severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection exacerbates lower urinary tract sympto...Objective Coronavirus disease 2019(COVID-19)can result in fatigue and post-exertional malaise;however,whether severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection exacerbates lower urinary tract symptoms(LUTS)is unclear.This study investigated the association between prenatal SARS-CoV-2 infection and postpartum LUTS.Methods A multicenter,retrospective cohort study was conducted at two tertiary hospitals in China from November 1,2022,to November 1,2023.Participants were classified into infected and uninfected groups based on SARS-CoV-2 antigen results.LUTS prevalence and severity were assessed using self-reported symptoms and the Incontinence Impact Questionnaire-Short Form(IIQ-7).Pelvic floor muscle activity was measured using electromyography following the Glazer protocol.Group comparisons were performed to evaluate the association of SARS-CoV-2 infection with LUTS and electromyography parameters,with stratified analyses conducted using SPSS version 26.0.Results Among 3,652 participants(681 infected,2,971 uninfected),no significant differences in LUTS prevalence or IIQ-7 scores were observed.However,SARS-CoV-2 infection was an independent factor influencing the electromyographic activity of the pelvic floor muscles(mean tonic contraction amplitudes),regardless of delivery mode(P=0.001).Conclusion Prenatal SARS-CoV-2 infection was not significantly associated with an increased risk of postpartum LUTS but independently altered pelvic floor muscle electromyographic activity,suggesting potential neuromuscular effects.展开更多
Since the beginning of the coronavirus disease(COVID)2019 pandemic,thou-sands of articles on the topic have been published,and although there is a growing trend of research on another associated condition,long coronav...Since the beginning of the coronavirus disease(COVID)2019 pandemic,thou-sands of articles on the topic have been published,and although there is a growing trend of research on another associated condition,long coronavirus disease,important points still remain to be clarified in this respect.Robust evidence has suggested a relevant link between new clinical discoveries and molecular mechanisms that could be associated with the manifestations of different signs and symptoms involving cases of long COVID.However,one of the existing gaps that requires further investigation concerns a possible rela-tionship between gut candidiasis and long COVID.While recent studies also suggest an interplay between the occurrence of these two conditions,it is not yet fully clear how this may happen,as well as the specifics regarding the possible pathophysiological mechanisms involved.In this connection and with the advent of a potential strengthening of the body of evidence supporting the hypothesis of a link between gut candidiasis and long COVID,a better understanding of the clinical presentation,pathophysiology and clinical management of such a relationship should be essential and useful for both,additional advances towards more targeted research and appropriate case management.Knowing more about the signs,symptoms,and complications associated with cases of long COVID is essential in order to more effectively mitigate the related burden and provide a higher quality of care and life for the affected population.In light of this and the need for better outcomes,here we review and discuss the content on different aspects of long COVID,including its pathophysiology and the existing evidence of a potential relationship between such a condition and gut candidiasis,as well as suggest propositions for future related research.INTRODUCTION Long coronavirus disease(COVID)is a condition characterized by the emergence of new symptoms or the persistence of existing symptoms for at least two months,three months after the initial infection[1].Although such a condition has initially been extensively studied,there are still many contradictions between the findings and methodologies of different related research articles[2,3].Within this context and since the middle of the COVID-19 pandemic,important studies have been published in the literature reporting the occurrence of fungal infections among COVID-19 patients[4,5],including mucormycosis,and oral candidiasis[6].On the other hand,evidence on a possible relationship between gut candidiasis and long COVID is still recent[7].Indeed,a marked gastrointestinal(GI)fungal dysbiosis together with perturbation of the lung-gut axis has been observed in severe COVID-19 patients.This combined with neutrophilia and an exacerbated worsening of the inflammatory response,which can be implicated in the acute and chronic immunopathology of such a viral disease[7,8].Furthermore,persistent changes in the immune system may also occur,resulting in a possible relationship with the occurrence of long COVID[7].However,more targeted evidence is still scarce and the specific topic related to gut candidiasis has been the subject of little discussion.In response to this,in this article we discuss general aspects of long COVID,the inherent pathophysiology and current evidence of a potential relationship between this condition and gut candidiasis,in addition to providing recommendations for future research.ACKNOWLEDGEMENTS Tovani-Palone MR thanks the Saveetha Institute of Medical and Technical Sciences for supporting this study.展开更多
Purpose: The involvement of the ocular anterior segment by SARS-CoV-2 has been the subject of many studies, however, the repercussions on the posterior segment, particularly on the different layers of the retina and o...Purpose: The involvement of the ocular anterior segment by SARS-CoV-2 has been the subject of many studies, however, the repercussions on the posterior segment, particularly on the different layers of the retina and optic nerve, are still little known. The purpose of this study was to evaluate the impact of severe COVID-19 on the retinal ganglion cell layer (RGCL) thickness. Methods: This observational, prospective and analytical study was performed in the Ophthalmology Department of the FACISA University Center, Campina Grande. Three groups were included: group I (control), 29 healthy individuals who had not severe COVID-19;group II (infirmary), 24 individuals who had COVID-19 and were hospitalized in the infirmary;and group III, 25 individuals who had severe COVID-19 and required Intense Care Unit (ICU). All individuals had ophthalmologic examination and assessment of RGCL thickness using Optical Coherence Tomography (OCT). Statistical tests required p ≤ 0.05 to reject the null hypothesis. Results: The mean of RGCL thickness was significantly reduced in individuals from GIII (77.9 ± 8.9 µm), as compared with GII (83.9 ± 10.9 µm) and GI (82.8 ± 6.5 µm) (p = 0.0027). The mean measurements from the retinal neve fiber layer (RNFL) of the optic nerve head were similar. However, when evaluated sectoral, the mean of RNFL at the temporal sector of the optic disc was significantly lower in group GIII (p Conclusion: The RGCL thickness from patients with severe COVID-19 was significantly reduced. This finding supports that the SARS-CoV-2 has systemic action and affinity for nerve cells, including those from the retina and are related to the severity of the infection.展开更多
BACKGROUND Prolonged symptoms after corona virus disease 2019(Long-COVID) in dialysisdependent patients and kidney transplant(KT) recipients are important as a possible risk factor for organ dysfunctions,especially ga...BACKGROUND Prolonged symptoms after corona virus disease 2019(Long-COVID) in dialysisdependent patients and kidney transplant(KT) recipients are important as a possible risk factor for organ dysfunctions,especially gastrointestinal(GI)problems,during immunosuppressive therapy.AIM To identify the characteristics of GI manifestations of Long-COVID in patients with dialysis-dependent or KT status.METHODS This observational,prospective study included patients with COVID-19 infection,confirmed by reverse transcription polymerase chain reaction,with the onset of symptoms between 1 January 2022 and 31 July 2022 which was explored at 3 mo after the onset,either through the out-patient follow-up or by telephone interviews.RESULTS The 645 eligible participants consisted of 588 cases with hemodialysis(HD),38 patients with peritoneal dialysis(PD),and 19 KT recipients who were hospitalized with COVID-19 infection during the observation. Of these,577(89.5%) cases agreed to the interviews,while 64(10.9%)patients with HD and 4(10.5%) cases of PD were excluded. The mean age was 52 ± 11 years with 52% women. The median dialysis duration was 7 ± 3 and 5 ± 1 years for HD and PD groups,respectively,and the median time post-transplantation was 6 ± 2 years. Long-COVID was identified in 293/524(56%) and 21/34(62%) in HD and PD,respectively,and 7/19(37%) KT recipients. Fatigue was the most prevalent(96%) of the non-GI tract symptoms,whereas anorexia(90.9%),loss of taste(64.4%),and abdominal pain(62.5%) were the first three common GI manifestations of Long-COVID. Notably,there were 6 cases of mesenteric panniculitis from 19patients with GI symptoms in the KT group.CONCLUSION Different from patients with non-chronic kidney disease,there was a high prevalence of GI manifestations of Long-COVID in dialysis-dependent patients and KT recipients. An appropriate long-term follow-up in these vulnerable populations after COVID-19 infection is possibly necessary.展开更多
The coronavirus disease 2019(COVID-19)hit the entire world as a global pandemic and soon became the most important concern for all patients with chronic diseases.An early trend in higher mortality in patients with acu...The coronavirus disease 2019(COVID-19)hit the entire world as a global pandemic and soon became the most important concern for all patients with chronic diseases.An early trend in higher mortality in patients with acute respiratory distress attracted all researchers to closely monitor patients for the involvement of other systems.It soon became apparent that patients with chronic liver diseases are at increased risk of mortality given their cirrhosis-associated immune dysfunction.Additionally,liver function abnormalities were noted in patients with severe COVID-19.Profound cytokine storm,direct viral infection,drugs and reactivation of viral infections were causes of deranged liver functions.Here,we discuss the relation between COVID-19 and chronic liver disease,specifically cirrhosis,hepatitis B,hepatitis C,and non-alcoholic fatty liver disease(NAFLD),as well as the liver manifestations of COVID-19.The metabolic syndrome,obesity,diabetes mellitus and NAFLD were found to worsen outcome in different studies reported worldwide.Decompensated cirrhosis should be considered a risk factor for death and severe COVID-19.Recently,COVID-19 related cholangiopathy has also been reported with changes of secondary sclerosing cholangitis.The long-term persistence of viral antigens in gut epithelia raises concern regarding the future risk of autoimmune liver diseases.展开更多
BACKGROUND Acute pancreatitis(AP)is a disease spectrum ranging from mild to severe disease.During the coronavirus disease 2019(COVID-19)pandemic,numerous reports of AP have been published,with most authors concluding ...BACKGROUND Acute pancreatitis(AP)is a disease spectrum ranging from mild to severe disease.During the coronavirus disease 2019(COVID-19)pandemic,numerous reports of AP have been published,with most authors concluding a causal relationship between COVID-19 and AP.Retrospective case reports or small case series are unable to accurately determine the cause-effect relationship between COVID-19 and AP.AIM To establish whether COVID-19 is a cause of AP using the modified Naranjo scoring system.METHODS A systematic review was conducted on PubMed,World of Science and Embase for articles reporting COVID-19 and AP from inception to August 2021.Exclusion criteria were cases of AP which were not reported to be due to COVID-19 infection,age<18 years old,review articles and retrospective cohort studies.The original 10-item Naranjo scoring system(total score 13)was devised to approximate the likelihood of a clinical presentation to be secondary to an adverse drug reaction.We modified the original scoring system into a 8-item modified Naranjo scoring system(total score 9)to determine the cause-effect relationship between COVID-19 and AP.A cumulative score was decided for each case presented in the included articles.Interpretation of the modified Naranjo scoring system is as follows:≤3:Doubtful,4-6:Possible,≥7:Probable cause.RESULTS The initial search resulted in 909 articles,with 740 articles after removal of duplicates.A total of 67 articles were included in the final analysis,with 76 patients which had AP reported to be due to COVID-19.The mean age was 47.8(range 18-94)years.Majority of patients(73.3%)had≤7 d between onset of COVID-19 infection and diagnosis of AP.There were only 45(59.2%)patients who had adequate investigations to rule out common aetiologies(gallstones,choledocholithiasis,alcohol,hypertriglyceridemia,hypercalcemia and trauma)of AP.Immunoglobulin G4 testing was conducted in 9(13.5%)patients to rule out autoimmune AP.Only 5(6.6%)patients underwent endoscopic ultrasound and/or magnetic resonance cholangiopancreatogram to rule out occult microlithiasis,pancreatic malignancy and pancreas divisum.None of the patients had other recently diagnosed viral infections apart from COVID-19 infection,or underwent genetic testing to rule out hereditary AP.There were 32(42.1%),39(51.3%)and 5(6.6%)patients with doubtful,possible,and probable cause-effect relationship respectively between COVID-19 and AP.CONCLUSION Current evidence is weak to establish a strong link between COVID-19 and AP.Investigations should be performed to rule out other causes of AP before establishing COVID-19 as an aetiology.展开更多
Despite gaps in knowledge,long-term sequelae of coronavirus disease 2019(COVID-19)infections are globally acknowledged and thus require special attention by public health organizations and services.Therefore,it is nec...Despite gaps in knowledge,long-term sequelae of coronavirus disease 2019(COVID-19)infections are globally acknowledged and thus require special attention by public health organizations and services.Therefore,it is necessary to support and promote public health initiatives that address long-term disability due to COVID-19.展开更多
Infection with the severe acute respiratory syndrome novel type-2 novel coronavirus (SARS-CoV-2) responsible for the 2019 coronavirus disease (CO<span style="font-family:;" "="">VID-19) ...Infection with the severe acute respiratory syndrome novel type-2 novel coronavirus (SARS-CoV-2) responsible for the 2019 coronavirus disease (CO<span style="font-family:;" "="">VID-19) shows a highly heterogeneous clinical presentation and age affliction in children and adults, ranging from asymptomatic or mild disease to severe inv<span>olvement, with potentially fatal respiratory failure and multiple organ dysfunction. As susceptibility to severe COVID-19 depends upon comorbid factors including immune competence, optimizing the latter through low-dose supplementation or high dose treatment with immune globulin therapy in those with primary immune deficiency and post-infectiou</span>s immune sequelae of SARS-CoV-2 and existing autoimmune disorders is essential. There are no existing guidelines hence;this paper provides a framework for considering preliminary guidelines for the use of immune globulin therapy during COVID-19.</span>展开更多
BACKGROUND The respiratory infection caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has evolved into a multi-organ disorder,with longterm effects known as post-acute sequelae of SARS-CoV-2 infect...BACKGROUND The respiratory infection caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has evolved into a multi-organ disorder,with longterm effects known as post-acute sequelae of SARS-CoV-2 infection or long coronavirus disease(COVID).AIM To examine the current knowledge and outcomes of long-term neurological and gastrointestinal(GI)symptoms in adult cohorts,including United States minority populations.METHODS PubMed and Google Scholar were searched using relevant terms,and data from five studies were analyzed,comprising 27383 patients with persistent neurological and GI sequelae.RESULTS The main symptoms included anxiety,depression,dysphagia,headache,vomiting,nausea,gastroesophageal reflux,fatigue,and abdominal pain.Patients with comorbidities and metabolic syndromes were at higher risk for long COVID.While most patients were European Americans,there was a need for further study on African Americans.CONCLUSION The underlying causes of these symptoms remain unclear,warranting more investigation into the long-term impact of the SARS-CoV-2 on different populations.展开更多
Respiratory post-acute sequelae of COVID-19(PASC)persists in many SARS-CoV-2 survivors,yet no therapies specifically address its long-term pulmonary damage.We demonstrate that a single-dose clustered regularly intersp...Respiratory post-acute sequelae of COVID-19(PASC)persists in many SARS-CoV-2 survivors,yet no therapies specifically address its long-term pulmonary damage.We demonstrate that a single-dose clustered regularly interspaced short palindromic repeats(CRISPR)–CasRx nanotherapy targeting the host enzyme cathepsin L(SCNC)effectively reduces acute SARS-CoV-2 infection in Syrian hamsters,with antiviral efficacy comparable to Paxlovid.Importantly,SCNC outperforms Paxlovid in alleviating alveolar epithelial hyperplasia and lung inflammation at 31 days post-infection,a recognized PASC time point.Single-cell RNA sequencing reveals that SCNC enhances alveolar repair by promoting the differentiation of alveolar type 2 cells into alveolar type 1 cells and by reducing inflammatory infiltration through multiple signaling pathways.Thus,SCNC exerts a dual mechanism:host-directed viral inhibition and promotion of epithelial repair with reduced inflammation.This distinguishes it from therapies focused solely on viral suppression or symptom relief.These findings support SCNC as a promising therapeutic candidate for acute infection and,particularly,for PASC-related lung injury,where options remain limited.展开更多
Background The long-term sequelae of COVID-19 in children and adolescents remain poorly understood and characterized.This systematic review and meta-analysis sought to summarize the risk factors for long COVID in the ...Background The long-term sequelae of COVID-19 in children and adolescents remain poorly understood and characterized.This systematic review and meta-analysis sought to summarize the risk factors for long COVID in the pediatric population.Methods We searched six databases from January 2020 to May 2023 for observational studies reporting on risk factors for long COVID or persistent symptoms those were present 12 or more weeks post-infection using multivariable regression analyses.Trial registries,reference lists of included studies,and preprint servers were hand-searched for relevant studies.Random-effects meta-analyses were conducted to pool odds ratios for each risk factor.Individual study risk of bias was rated using QUIPS,and the GRADE framework was used to assess the certainty of evidence for each unique factor.Results Sixteen observational studies(N=46,262)were included,and 19 risk factors were amenable to meta-analysis.With moderate certainty in the evidence,age(per 2-year increase),allergic rhinitis,obesity,previous respiratory diseases,hospitalization,severe acute COVID-19,and symptomatic acute COVID-19 are probably associated with an increased risk of long COVID.Female sex,asthma,comorbidity,and heart diseases may be associated with an increased risk of long COVID,and Asian and Black races may be associated with a decreased risk of long COVID.We did not observe any credible subgroup effects for any risk factor.Conclusions The current body of literature presents several compelling risk factors for the development of long COVID in the pediatric population.Further research is necessary to elucidate the pathophysiology of long COVID.展开更多
Recent scientific breakthroughs have blurred traditional boundaries between innate and adaptive immunity,revealing a sophisticated network of tissue-resident cells that deliver immediate,localized immune responses.The...Recent scientific breakthroughs have blurred traditional boundaries between innate and adaptive immunity,revealing a sophisticated network of tissue-resident cells that deliver immediate,localized immune responses.These lymphocytes not only provide rapid frontline defense but also present a paradoxical role in the pathogenesis of respiratory diseases such as asthma,chronic obstructive pulmonary disease,pulmonary fibrosis,and the long-term tissue consequences of viral infections including severe acute respiratory syndrome coronavirus-2(SARS-CoV-2).This review traverses the intricate landscape of lung-resident lymphocytes,delving into their origins,diverse functions,and their dualistic impact on pulmonary health.We dissect their interactions with the microenvironment and the regulatory mechanisms guiding their activity,with an emphasis on their contribution to both immune protection and immunopathology.This review aims to elucidate the complex narrative of these cells,enhancing our understanding of the development of precise therapeutic strategies to combat acute and chronic pulmonary diseases.Through this exploration,the review aspires to shed light on the potential of harnessing lung-resident lymphocytes for the treatment of respiratory conditions.展开更多
The coronavirus disease 2019(COVID-19)pandemic has been ongoing for more than 3 years,with an enormous impact on global health and economies.In some patients,symptoms and signs may remain after recovery from severe ac...The coronavirus disease 2019(COVID-19)pandemic has been ongoing for more than 3 years,with an enormous impact on global health and economies.In some patients,symptoms and signs may remain after recovery from severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection,which cannot be explained by an alter-nate diagnosis;this condition has been defined as long COVID.Long COVID may exist in patients with both mild and severe disease and is prevalent after infection with different SARS-CoV-2 variants.The most common symp-toms include fatigue,dyspnea,and other symptoms involving multiple organs.Vaccination results in lower rates of long COVID.To date,the mechanisms of long COVID remain unclear.In this narrative review,we summarized the clinical presentations and current evidence regarding the pathogenesis of long COVID.展开更多
文摘BACKGROUND While stroke and lower extremity venous thromboemboli have been commonly reported following acute infection with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),spinal cord infarction or ischemia has been extremely rare.Findings of long coronavirus disease(COVID)in this select population have not been studied.CASE SUMMARY We present the case of a 70-year-old female with sudden onset of trunk and lower extremity sensorimotor loss due to spinal cord infarction,attributed to acute infection with SARS-CoV-2.Diagnostic work up confirmed a T3 complete(ASIA impairment Scale A)paraplegia resulting from a thrombotic infarct.Her reported myalgias,neuropathic pain,spasticity,bladder spasms,and urinary tract infections exceeded the frequency and severity of many spinal cord injury(SCI)individuals of similar age and degree of neurologic impairment.In her first year after contracting COVID-19,she underwent 2 separate inpatient rehabilitation courses,but also required acute hospitalization 6 additional times for subsequent infections or uncontrolled pain.Yet other complications of complete non-traumatic SCI(NTSCI),including neurogenic bowel and temperature hypersens-itivity,were mild,and pressure injuries were absent.She has now transitioned from the acute to chronic phase of spinal cord injury care,with subsequent development of post-acute sequelae of SARS-CoV-2 infection(PASC).CONCLUSION This individual experienced significant challenges with the combined effects of acute T3 NTSCI and acute COVID-19,with subsequent progression to PASC.Core Tip:Although stroke and venous thromboembolism have been frequently observed with acute coronavirus disease 2019(COVID-19),spinal cord infarction leading to paraplegia has rarely been seen.We report a case of spinal cord infarction shortly following infection with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).Consequently,this individual has experienced severe neurologic disability,with subsequent development of long COVID.Symptoms such as myalgias,neuropathic pain,muscle spasms,and frequent bacterial infections are present in post-acute sequelae of SARS-CoV-2 infection(PASC),independent of spinal cord injury(SCI).Over the past 3 years,the dual presence of PASC and recent SCI may have led to increased severity of symptoms shared by both conditions.INTRODUCTION Among vascular events,spinal cord infarction is relatively rare,accounting for only 0.3%-1%of all strokes[1]and 5%-8%of acute myelopathies[2].One cause of spinal cord infarction arises from a thrombotic event in vulnerable areas of the thoracic cord,particularly between T8-12,which is supplied by the artery of Adamkiewicz.While deep vein thrombosis,pulmonary embolism,and stroke are commonly observed complications of coronavirus disease 2019(COVID-19),spinal cord infarction is comparatively infrequent[3-6].The cytokine release following acute infection,which peaks 7 d after contracting the virus,may be responsible for the increase in thrombotic events associated with acute infection with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)[7,8].This case discussed in this report differs from other published accounts describing spinal cord infarcts attributed to acute SARS-CoV-2,because we have followed this individual for nearly 3 years after contracting COVID-19,covering her difficulties with“long COVID,”which has now officially named post-acute sequelae of SARS-CoV-2 infection(PASC)by the World Health Organization[9].The term PASC may be assigned to“individuals with a history of probable or confirmed SARS-CoV-2 infection,usually 3 mo from the onset of COVID-19 with symptoms that last for at least 2 mo and cannot be explained by an alternative diagnosis”.The definition further states that PASC generally impacts everyday functioning and that symptoms may be of new onset,follow initial recovery from an acute COVID-19 episode,or persist from the initial illness.Moreover,symptoms may also fluctuate or relapse over time[9].Common complaints of PASC include fatigue,cough shortness of breath,cognitive deficits or“brain fog”.Reported features of PASC may also involve headache,heart palpitations,exercise intolerance,joint pain or swelling,myalgias,vertigo,peripheral neuropathy,altered taste or smell,disordered sleep,anxiety,depression,and thromboembolic events[10-13].While a number of the above symptoms may occur subsequent to SCI,many would be unusual,such as persistent cough,fatigue months after SCI,changes in taste or smell,continued exercise intolerance,new onset cognitive deficits or“brain fog”,unrelated to any sedating medications or concomitant brain injury.Our patient became symptomatic prior to COVID-19 vaccine availability and has given written consent to share her story for educational publication.This project was approved by the Institutional Review Board of the MetroHealth System.
文摘The principal goal of psychiatric rehabilitation is to improve the global functioning of a person who suffer from a mental disorder. New emerging groups of patients meet difficult to attend to a rehabilitation program. Sport represents a new flexible model that can be used in psychiatric rehabilitation. Sport improves physical health and well being, increases sociality, increases self-efficacy and self-esteem. It is well accepted and well tolerated by the patients, too. Its use goes over the chronic phase of illness (typical target of rehabilitation) and it extends to the post-acute and pre acute phase, too.
文摘SARS COV-2 infection causes acute and frequently severe respiratory disease with associated multi-organ damage and systemic disturbances in many biochemical pathways.Metabolic phenotyping provides deep insights into the complex immunopathological problems that drive the resulting COVID-19 disease and is also a source of novel metrics for assess-ing patient recovery.A multiplatform metabolic phenotyping approach to studying the pathology and systemic metabolic sequelae of COVID-19 is considered here,together with a framework for assessing post-acute COVID-19 Syndrome(PACS)that is a major long-term health consequence for many patients.The sudden emergence of the disease presents a biological discovery challenge as we try to understand the pathological mechanisms of the disease and develop effective mitigation strategies.This requires technologies to measure objectively the extent and sub-phenotypes of the disease at the molecular level.Spectroscopic methods can reveal metabolic sub-phenotypes and new biomarkers that can be monitored during the acute disease phase and beyond.This approach is scalable and translatable to other pathologies and provides as an exem-plar strategy for the investigation of other emergent zoonotic diseases with complex immunological drivers,multi-system involvements and diverse persistent symptoms.
基金supported by National High Level Hospital Clinical Research Funding[BJ-2023-112,BJ-2018-204]Central Government Guidance Fund for Local Science and Technology Development[202407AB110013].
文摘Objective Coronavirus disease 2019(COVID-19)can result in fatigue and post-exertional malaise;however,whether severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection exacerbates lower urinary tract symptoms(LUTS)is unclear.This study investigated the association between prenatal SARS-CoV-2 infection and postpartum LUTS.Methods A multicenter,retrospective cohort study was conducted at two tertiary hospitals in China from November 1,2022,to November 1,2023.Participants were classified into infected and uninfected groups based on SARS-CoV-2 antigen results.LUTS prevalence and severity were assessed using self-reported symptoms and the Incontinence Impact Questionnaire-Short Form(IIQ-7).Pelvic floor muscle activity was measured using electromyography following the Glazer protocol.Group comparisons were performed to evaluate the association of SARS-CoV-2 infection with LUTS and electromyography parameters,with stratified analyses conducted using SPSS version 26.0.Results Among 3,652 participants(681 infected,2,971 uninfected),no significant differences in LUTS prevalence or IIQ-7 scores were observed.However,SARS-CoV-2 infection was an independent factor influencing the electromyographic activity of the pelvic floor muscles(mean tonic contraction amplitudes),regardless of delivery mode(P=0.001).Conclusion Prenatal SARS-CoV-2 infection was not significantly associated with an increased risk of postpartum LUTS but independently altered pelvic floor muscle electromyographic activity,suggesting potential neuromuscular effects.
文摘Since the beginning of the coronavirus disease(COVID)2019 pandemic,thou-sands of articles on the topic have been published,and although there is a growing trend of research on another associated condition,long coronavirus disease,important points still remain to be clarified in this respect.Robust evidence has suggested a relevant link between new clinical discoveries and molecular mechanisms that could be associated with the manifestations of different signs and symptoms involving cases of long COVID.However,one of the existing gaps that requires further investigation concerns a possible rela-tionship between gut candidiasis and long COVID.While recent studies also suggest an interplay between the occurrence of these two conditions,it is not yet fully clear how this may happen,as well as the specifics regarding the possible pathophysiological mechanisms involved.In this connection and with the advent of a potential strengthening of the body of evidence supporting the hypothesis of a link between gut candidiasis and long COVID,a better understanding of the clinical presentation,pathophysiology and clinical management of such a relationship should be essential and useful for both,additional advances towards more targeted research and appropriate case management.Knowing more about the signs,symptoms,and complications associated with cases of long COVID is essential in order to more effectively mitigate the related burden and provide a higher quality of care and life for the affected population.In light of this and the need for better outcomes,here we review and discuss the content on different aspects of long COVID,including its pathophysiology and the existing evidence of a potential relationship between such a condition and gut candidiasis,as well as suggest propositions for future related research.INTRODUCTION Long coronavirus disease(COVID)is a condition characterized by the emergence of new symptoms or the persistence of existing symptoms for at least two months,three months after the initial infection[1].Although such a condition has initially been extensively studied,there are still many contradictions between the findings and methodologies of different related research articles[2,3].Within this context and since the middle of the COVID-19 pandemic,important studies have been published in the literature reporting the occurrence of fungal infections among COVID-19 patients[4,5],including mucormycosis,and oral candidiasis[6].On the other hand,evidence on a possible relationship between gut candidiasis and long COVID is still recent[7].Indeed,a marked gastrointestinal(GI)fungal dysbiosis together with perturbation of the lung-gut axis has been observed in severe COVID-19 patients.This combined with neutrophilia and an exacerbated worsening of the inflammatory response,which can be implicated in the acute and chronic immunopathology of such a viral disease[7,8].Furthermore,persistent changes in the immune system may also occur,resulting in a possible relationship with the occurrence of long COVID[7].However,more targeted evidence is still scarce and the specific topic related to gut candidiasis has been the subject of little discussion.In response to this,in this article we discuss general aspects of long COVID,the inherent pathophysiology and current evidence of a potential relationship between this condition and gut candidiasis,in addition to providing recommendations for future research.ACKNOWLEDGEMENTS Tovani-Palone MR thanks the Saveetha Institute of Medical and Technical Sciences for supporting this study.
文摘Purpose: The involvement of the ocular anterior segment by SARS-CoV-2 has been the subject of many studies, however, the repercussions on the posterior segment, particularly on the different layers of the retina and optic nerve, are still little known. The purpose of this study was to evaluate the impact of severe COVID-19 on the retinal ganglion cell layer (RGCL) thickness. Methods: This observational, prospective and analytical study was performed in the Ophthalmology Department of the FACISA University Center, Campina Grande. Three groups were included: group I (control), 29 healthy individuals who had not severe COVID-19;group II (infirmary), 24 individuals who had COVID-19 and were hospitalized in the infirmary;and group III, 25 individuals who had severe COVID-19 and required Intense Care Unit (ICU). All individuals had ophthalmologic examination and assessment of RGCL thickness using Optical Coherence Tomography (OCT). Statistical tests required p ≤ 0.05 to reject the null hypothesis. Results: The mean of RGCL thickness was significantly reduced in individuals from GIII (77.9 ± 8.9 µm), as compared with GII (83.9 ± 10.9 µm) and GI (82.8 ± 6.5 µm) (p = 0.0027). The mean measurements from the retinal neve fiber layer (RNFL) of the optic nerve head were similar. However, when evaluated sectoral, the mean of RNFL at the temporal sector of the optic disc was significantly lower in group GIII (p Conclusion: The RGCL thickness from patients with severe COVID-19 was significantly reduced. This finding supports that the SARS-CoV-2 has systemic action and affinity for nerve cells, including those from the retina and are related to the severity of the infection.
文摘BACKGROUND Prolonged symptoms after corona virus disease 2019(Long-COVID) in dialysisdependent patients and kidney transplant(KT) recipients are important as a possible risk factor for organ dysfunctions,especially gastrointestinal(GI)problems,during immunosuppressive therapy.AIM To identify the characteristics of GI manifestations of Long-COVID in patients with dialysis-dependent or KT status.METHODS This observational,prospective study included patients with COVID-19 infection,confirmed by reverse transcription polymerase chain reaction,with the onset of symptoms between 1 January 2022 and 31 July 2022 which was explored at 3 mo after the onset,either through the out-patient follow-up or by telephone interviews.RESULTS The 645 eligible participants consisted of 588 cases with hemodialysis(HD),38 patients with peritoneal dialysis(PD),and 19 KT recipients who were hospitalized with COVID-19 infection during the observation. Of these,577(89.5%) cases agreed to the interviews,while 64(10.9%)patients with HD and 4(10.5%) cases of PD were excluded. The mean age was 52 ± 11 years with 52% women. The median dialysis duration was 7 ± 3 and 5 ± 1 years for HD and PD groups,respectively,and the median time post-transplantation was 6 ± 2 years. Long-COVID was identified in 293/524(56%) and 21/34(62%) in HD and PD,respectively,and 7/19(37%) KT recipients. Fatigue was the most prevalent(96%) of the non-GI tract symptoms,whereas anorexia(90.9%),loss of taste(64.4%),and abdominal pain(62.5%) were the first three common GI manifestations of Long-COVID. Notably,there were 6 cases of mesenteric panniculitis from 19patients with GI symptoms in the KT group.CONCLUSION Different from patients with non-chronic kidney disease,there was a high prevalence of GI manifestations of Long-COVID in dialysis-dependent patients and KT recipients. An appropriate long-term follow-up in these vulnerable populations after COVID-19 infection is possibly necessary.
文摘The coronavirus disease 2019(COVID-19)hit the entire world as a global pandemic and soon became the most important concern for all patients with chronic diseases.An early trend in higher mortality in patients with acute respiratory distress attracted all researchers to closely monitor patients for the involvement of other systems.It soon became apparent that patients with chronic liver diseases are at increased risk of mortality given their cirrhosis-associated immune dysfunction.Additionally,liver function abnormalities were noted in patients with severe COVID-19.Profound cytokine storm,direct viral infection,drugs and reactivation of viral infections were causes of deranged liver functions.Here,we discuss the relation between COVID-19 and chronic liver disease,specifically cirrhosis,hepatitis B,hepatitis C,and non-alcoholic fatty liver disease(NAFLD),as well as the liver manifestations of COVID-19.The metabolic syndrome,obesity,diabetes mellitus and NAFLD were found to worsen outcome in different studies reported worldwide.Decompensated cirrhosis should be considered a risk factor for death and severe COVID-19.Recently,COVID-19 related cholangiopathy has also been reported with changes of secondary sclerosing cholangitis.The long-term persistence of viral antigens in gut epithelia raises concern regarding the future risk of autoimmune liver diseases.
文摘BACKGROUND Acute pancreatitis(AP)is a disease spectrum ranging from mild to severe disease.During the coronavirus disease 2019(COVID-19)pandemic,numerous reports of AP have been published,with most authors concluding a causal relationship between COVID-19 and AP.Retrospective case reports or small case series are unable to accurately determine the cause-effect relationship between COVID-19 and AP.AIM To establish whether COVID-19 is a cause of AP using the modified Naranjo scoring system.METHODS A systematic review was conducted on PubMed,World of Science and Embase for articles reporting COVID-19 and AP from inception to August 2021.Exclusion criteria were cases of AP which were not reported to be due to COVID-19 infection,age<18 years old,review articles and retrospective cohort studies.The original 10-item Naranjo scoring system(total score 13)was devised to approximate the likelihood of a clinical presentation to be secondary to an adverse drug reaction.We modified the original scoring system into a 8-item modified Naranjo scoring system(total score 9)to determine the cause-effect relationship between COVID-19 and AP.A cumulative score was decided for each case presented in the included articles.Interpretation of the modified Naranjo scoring system is as follows:≤3:Doubtful,4-6:Possible,≥7:Probable cause.RESULTS The initial search resulted in 909 articles,with 740 articles after removal of duplicates.A total of 67 articles were included in the final analysis,with 76 patients which had AP reported to be due to COVID-19.The mean age was 47.8(range 18-94)years.Majority of patients(73.3%)had≤7 d between onset of COVID-19 infection and diagnosis of AP.There were only 45(59.2%)patients who had adequate investigations to rule out common aetiologies(gallstones,choledocholithiasis,alcohol,hypertriglyceridemia,hypercalcemia and trauma)of AP.Immunoglobulin G4 testing was conducted in 9(13.5%)patients to rule out autoimmune AP.Only 5(6.6%)patients underwent endoscopic ultrasound and/or magnetic resonance cholangiopancreatogram to rule out occult microlithiasis,pancreatic malignancy and pancreas divisum.None of the patients had other recently diagnosed viral infections apart from COVID-19 infection,or underwent genetic testing to rule out hereditary AP.There were 32(42.1%),39(51.3%)and 5(6.6%)patients with doubtful,possible,and probable cause-effect relationship respectively between COVID-19 and AP.CONCLUSION Current evidence is weak to establish a strong link between COVID-19 and AP.Investigations should be performed to rule out other causes of AP before establishing COVID-19 as an aetiology.
文摘Despite gaps in knowledge,long-term sequelae of coronavirus disease 2019(COVID-19)infections are globally acknowledged and thus require special attention by public health organizations and services.Therefore,it is necessary to support and promote public health initiatives that address long-term disability due to COVID-19.
文摘Infection with the severe acute respiratory syndrome novel type-2 novel coronavirus (SARS-CoV-2) responsible for the 2019 coronavirus disease (CO<span style="font-family:;" "="">VID-19) shows a highly heterogeneous clinical presentation and age affliction in children and adults, ranging from asymptomatic or mild disease to severe inv<span>olvement, with potentially fatal respiratory failure and multiple organ dysfunction. As susceptibility to severe COVID-19 depends upon comorbid factors including immune competence, optimizing the latter through low-dose supplementation or high dose treatment with immune globulin therapy in those with primary immune deficiency and post-infectiou</span>s immune sequelae of SARS-CoV-2 and existing autoimmune disorders is essential. There are no existing guidelines hence;this paper provides a framework for considering preliminary guidelines for the use of immune globulin therapy during COVID-19.</span>
文摘BACKGROUND The respiratory infection caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has evolved into a multi-organ disorder,with longterm effects known as post-acute sequelae of SARS-CoV-2 infection or long coronavirus disease(COVID).AIM To examine the current knowledge and outcomes of long-term neurological and gastrointestinal(GI)symptoms in adult cohorts,including United States minority populations.METHODS PubMed and Google Scholar were searched using relevant terms,and data from five studies were analyzed,comprising 27383 patients with persistent neurological and GI sequelae.RESULTS The main symptoms included anxiety,depression,dysphagia,headache,vomiting,nausea,gastroesophageal reflux,fatigue,and abdominal pain.Patients with comorbidities and metabolic syndromes were at higher risk for long COVID.While most patients were European Americans,there was a need for further study on African Americans.CONCLUSION The underlying causes of these symptoms remain unclear,warranting more investigation into the long-term impact of the SARS-CoV-2 on different populations.
文摘Respiratory post-acute sequelae of COVID-19(PASC)persists in many SARS-CoV-2 survivors,yet no therapies specifically address its long-term pulmonary damage.We demonstrate that a single-dose clustered regularly interspaced short palindromic repeats(CRISPR)–CasRx nanotherapy targeting the host enzyme cathepsin L(SCNC)effectively reduces acute SARS-CoV-2 infection in Syrian hamsters,with antiviral efficacy comparable to Paxlovid.Importantly,SCNC outperforms Paxlovid in alleviating alveolar epithelial hyperplasia and lung inflammation at 31 days post-infection,a recognized PASC time point.Single-cell RNA sequencing reveals that SCNC enhances alveolar repair by promoting the differentiation of alveolar type 2 cells into alveolar type 1 cells and by reducing inflammatory infiltration through multiple signaling pathways.Thus,SCNC exerts a dual mechanism:host-directed viral inhibition and promotion of epithelial repair with reduced inflammation.This distinguishes it from therapies focused solely on viral suppression or symptom relief.These findings support SCNC as a promising therapeutic candidate for acute infection and,particularly,for PASC-related lung injury,where options remain limited.
文摘Background The long-term sequelae of COVID-19 in children and adolescents remain poorly understood and characterized.This systematic review and meta-analysis sought to summarize the risk factors for long COVID in the pediatric population.Methods We searched six databases from January 2020 to May 2023 for observational studies reporting on risk factors for long COVID or persistent symptoms those were present 12 or more weeks post-infection using multivariable regression analyses.Trial registries,reference lists of included studies,and preprint servers were hand-searched for relevant studies.Random-effects meta-analyses were conducted to pool odds ratios for each risk factor.Individual study risk of bias was rated using QUIPS,and the GRADE framework was used to assess the certainty of evidence for each unique factor.Results Sixteen observational studies(N=46,262)were included,and 19 risk factors were amenable to meta-analysis.With moderate certainty in the evidence,age(per 2-year increase),allergic rhinitis,obesity,previous respiratory diseases,hospitalization,severe acute COVID-19,and symptomatic acute COVID-19 are probably associated with an increased risk of long COVID.Female sex,asthma,comorbidity,and heart diseases may be associated with an increased risk of long COVID,and Asian and Black races may be associated with a decreased risk of long COVID.We did not observe any credible subgroup effects for any risk factor.Conclusions The current body of literature presents several compelling risk factors for the development of long COVID in the pediatric population.Further research is necessary to elucidate the pathophysiology of long COVID.
基金supported by the US National Institutes of Health grants AI147394,AG069264,AI112844,HL170961,AI176171,and AI154598 to J.S.
文摘Recent scientific breakthroughs have blurred traditional boundaries between innate and adaptive immunity,revealing a sophisticated network of tissue-resident cells that deliver immediate,localized immune responses.These lymphocytes not only provide rapid frontline defense but also present a paradoxical role in the pathogenesis of respiratory diseases such as asthma,chronic obstructive pulmonary disease,pulmonary fibrosis,and the long-term tissue consequences of viral infections including severe acute respiratory syndrome coronavirus-2(SARS-CoV-2).This review traverses the intricate landscape of lung-resident lymphocytes,delving into their origins,diverse functions,and their dualistic impact on pulmonary health.We dissect their interactions with the microenvironment and the regulatory mechanisms guiding their activity,with an emphasis on their contribution to both immune protection and immunopathology.This review aims to elucidate the complex narrative of these cells,enhancing our understanding of the development of precise therapeutic strategies to combat acute and chronic pulmonary diseases.Through this exploration,the review aspires to shed light on the potential of harnessing lung-resident lymphocytes for the treatment of respiratory conditions.
基金This work was supported by the Fundamental Research Funds for the Central Universities(No.3332022078)Chinese Academy of Medical Sciences Institute of Respiratory Medicine Young Scientist Fund(No.2023-ZF-12)the Natural Science Foundation of Shandong Province(No.ZR2021MH266).
文摘The coronavirus disease 2019(COVID-19)pandemic has been ongoing for more than 3 years,with an enormous impact on global health and economies.In some patients,symptoms and signs may remain after recovery from severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection,which cannot be explained by an alter-nate diagnosis;this condition has been defined as long COVID.Long COVID may exist in patients with both mild and severe disease and is prevalent after infection with different SARS-CoV-2 variants.The most common symp-toms include fatigue,dyspnea,and other symptoms involving multiple organs.Vaccination results in lower rates of long COVID.To date,the mechanisms of long COVID remain unclear.In this narrative review,we summarized the clinical presentations and current evidence regarding the pathogenesis of long COVID.
