Tag: covid-19

High Prevalence of Alternative Diagnoses in Children and Adolescents with Suspected Long COVID-A Single Center Cohort Study

Abstract:

Background: Long COVID (LC) is a diagnosis that requires exclusion of alternative somatic and mental diseases. The aim of this study was to examine the prevalence of differential diagnoses in suspected pediatric LC patients and assess whether adult LC symptom clusters are applicable to pediatric patients.

Materials and methods: Pediatric presentations at the Pediatric Infectious Diseases Department of the University Hospital Essen (Germany) were assessed retrospectively. The correlation of initial symptoms and final diagnoses (LC versus other diseases or unclarified) was assessed. The sensitivity, specificity, negative and positive predictive values of adult LC symptom clusters were calculated.

Results: Of 110 patients, 32 (29%) suffered from LC, 52 (47%) were diagnosed with alternative somatic/mental diseases, and 26 (23%) remained unclarified. Combined neurological and respiratory clusters displayed a sensitivity of 0.97 (95% CI 0.91-1.00) and a negative predictive value of 0.97 (0.92-1.00) for LC.

Discussion/conclusions: The prevalence of alternative somatic and mental diseases in pediatric patients with suspected LC is high. The range of underlying diseases is wide, including chronic and potentially life-threatening conditions. Neurological and respiratory symptom clusters may help to identify patients that are unlikely to be suffering from LC.

Source: Goretzki SC, Brasseler M, Dogan B, Hühne T, Bernard D, Schönecker A, Steindor M, Gangfuß A, Della Marina A, Felderhoff-Müser U, Dohna-Schwake C, Bruns N. High Prevalence of Alternative Diagnoses in Children and Adolescents with Suspected Long COVID-A Single Center Cohort Study. Viruses. 2023 Feb 20;15(2):579. doi: 10.3390/v15020579. PMID: 36851793; PMCID: PMC9961131. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9961131/ (Full text)

Identification of the pathogenic relationship between Long COVID and Alzheimer’s disease by bioinformatics methods

Abstract:

Background: The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused an unprecedented global health crisis. Although many Corona Virus Disease 2019 (COVID-19) patients have recovered, the long-term consequences of SARS-CoV-2 infection are unclear. Several independent epidemiological surveys and clinical studies have found that SARS-CoV-2 infection and Long COVID are closely related to Alzheimer’s disease (AD). This could lead to long-term medical challenges and social burdens following this health crisis. However, the mechanism between Long COVID and AD is unknown.

Methods: Genes associated with Long COVID were collected from the database. Two sets of AD-related clinical sample datasets were collected in the Gene Expression Omnibus (GEO) database by limiting screening conditions. After identifying the differentially expressed genes (DEGs) of AD, the significant overlapping genes of AD and Long COVID were obtained by taking the intersection. Then, four kinds of analyses were performed, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis, protein-protein interaction (PPI) analysis, identification of hub genes, hub gene verification and transcription factors (TFs) prediction.

Results: A total of 197 common genes were selected for subsequent analysis. GO and KEGG enrichment analysis showed that these genes were mainly enriched in multiple neurodegenerative disease related pathways. In addition, 20 important hub genes were identified using cytoHubba. At the same time, these hub genes were verified in another data set, where 19 hub gene expressions were significantly different in the two diseases and 6 hub genes were significantly different in AD patients of different genders. Finally, we collected 9 TFs that may regulate the expression of these hub genes in the Transcriptional Regulatory Relationships Unraveled by Sentence-based Text mining (TRUSST) database and verified them in the current data set.

Conclusion: This work reveals the common pathways and hub genes of AD and Long COVID, providing new ideas for
the pathogenic relationship between these two diseases and further mechanism research.

Source:

Organ and cell-specific biomarkers of Long-COVID identified with targeted proteomics and machine learning

Abstract:

Background: Survivors of acute COVID-19 often suffer prolonged, diffuse symptoms post-infection, referred to as “Long-COVID”. A lack of Long-COVID biomarkers and pathophysiological mechanisms limits effective diagnosis, treatment and disease surveillance. We performed targeted proteomics and machine learning analyses to identify novel blood biomarkers of Long-COVID.

Methods: A case-control study comparing the expression of 2925 unique blood proteins in Long-COVID outpatients versus COVID-19 inpatients and healthy control subjects. Targeted proteomics was accomplished with proximity extension assays, and machine learning was used to identify the most important proteins for identifying Long-COVID patients. Organ system and cell type expression patterns were identified with Natural Language Processing (NLP) of the UniProt Knowledgebase.

Results: Machine learning analysis identified 119 relevant proteins for differentiating Long-COVID outpatients (Bonferonni corrected P < 0.01). Protein combinations were narrowed down to two optimal models, with nine and five proteins each, and with both having excellent sensitivity and specificity for Long-COVID status (AUC = 1.00, F1 = 1.00). NLP expression analysis highlighted the diffuse organ system involvement in Long-COVID, as well as the involved cell types, including leukocytes and platelets, as key components associated with Long-COVID.

Conclusions: Proteomic analysis of plasma from Long-COVID patients identified 119 highly relevant proteins and two optimal models with nine and five proteins, respectively. The identified proteins reflected widespread organ and cell type expression. Optimal protein models, as well as individual proteins, hold the potential for accurate diagnosis of Long-COVID and targeted therapeutics.

Source: Patel MA, Knauer MJ, Nicholson M, Daley M, Van Nynatten LR, Cepinskas G, Fraser DD. Organ and cell-specific biomarkers of Long-COVID identified with targeted proteomics and machine learning. Mol Med. 2023 Feb 21;29(1):26. doi: 10.1186/s10020-023-00610-z. PMID: 36809921; PMCID: PMC9942653. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9942653/ (Full text)

Cardiac abnormalities in Long COVID 1-year post-SARS-CoV-2 infection

Abstract:

Background: Long COVID is associated with multiple symptoms and impairment in multiple organs. Cross-sectional studies have reported cardiac impairment to varying degrees by varying methodologies. Using cardiac MR (CMR), we investigated a 12-month trajectory of abnormalities in Long COVID.

Objectives: To investigate cardiac abnormalities 1-year post-SARS-CoV-2 infection.

Methods: 534 individuals with Long COVID underwent CMR (T1/T2 mapping, cardiac mass, volumes, function and strain) and multiorgan MRI at 6 months (IQR 4.3-7.3) since first post-COVID-19 symptoms. 330 were rescanned at 12.6 (IQR 11.4-14.2) months if abnormal baseline findings were reported. Symptoms, questionnaires and blood samples were collected at both time points. CMR abnormalities were defined as ≥1 of low left or right ventricular ejection fraction (LVEF), high left or right ventricular end diastolic volume, low 3D left ventricular global longitudinal strain (GLS), or elevated native T1 in ≥3 cardiac segments. Significant change over time was reported by comparison with 92 healthy controls.

Results: Technical success of multiorgan and CMR assessment in non-acute settings was 99.1% and 99.6% at baseline, and 98.3% and 98.8% at follow-up. Of individuals with Long COVID, 102/534 (19%) had CMR abnormalities at baseline; 71/102 had complete paired data at 12 months. Of those, 58% presented with ongoing CMR abnormalities at 12 months. High sensitivity cardiac troponin I and B-type natriuretic peptide were not predictive of CMR findings, symptoms or clinical outcomes. At baseline, low LVEF was associated with persistent CMR abnormality, abnormal GLS associated with low quality of life and abnormal T1 in at least three segments was associated with better clinical outcomes at 12 months.

Conclusion: CMR abnormalities (left ventricular or right ventricular dysfunction/dilatation and/or abnormal T1mapping), occurred in one in five individuals with Long COVID at 6 months, persisting in over half of those at 12 months. Cardiac-related blood biomarkers could not identify CMR abnormalities in Long COVID.

Source: Fernandez AR, Wamil M, Telford A, Carapella V, Borlotti A, Monteiro D, Thomaides-Brears H, Kelly M, Dennis A, Banerjee R, Robson M, Brady M, Lip GYH, Bull S, Heightman M, Ntusi N, Banerjee A. Cardiac abnormalities in Long COVID 1-year post-SARS-CoV-2 infection. Open Heart. 2023 Feb;10(1):e002241. doi: 10.1136/openhrt-2022-002241. PMID: 36822818; PMCID: PMC9950586. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9950586/ (Full text)

Structural brain changes in patients with post-COVID fatigue: a prospective observational study

Summary:

Background: Post-COVID syndrome is a severe long-term complication of COVID-19. Although fatigue and cognitive complaints are the most prominent symptoms, it is unclear whether they have structural correlates in the brain. We therefore explored the clinical characteristics of post-COVID fatigue, describe associated structural imaging changes, and determine what influences fatigue severity.

Methods: We prospectively recruited 50 patients from neurological post-COVID outpatient clinics (age 18–69 years, 39f/8m) and matched non-COVID healthy controls between April 15 and December 31, 2021. Assessments included diffusion and volumetric MR imaging, neuropsychiatric, and cognitive testing. At 7.5 months (median, IQR 6.5–9.2) after the acute SARS-CoV-2 infection, moderate or severe fatigue was identified in 47/50 patients with post-COVID syndrome who were included in the analyses. As a clinical control group, we included 47 matched multiple sclerosis patients with fatigue.

Findings: Our diffusion imaging analyses revealed aberrant fractional anisotropy of the thalamus. Diffusion markers correlated with fatigue severity, such as physical fatigue, fatigue-related impairment in everyday life (Bell score) and daytime sleepiness. Moreover, we observed shape deformations and decreased volumes of the left thalamus, putamen, and pallidum. These overlapped with the more extensive subcortical changes in MS and were associated with impaired short-term memory. While fatigue severity was not related to COVID-19 disease courses (6/47 hospitalised, 2/47 with ICU treatment), post-acute sleep quality and depressiveness emerged as associated factors and were accompanied by increased levels of anxiety and daytime sleepiness.

Interpretation: Characteristic structural imaging changes of the thalamus and basal ganglia underlie the persistent fatigue experienced by patients with post-COVID syndrome. Evidence for pathological changes to these subcortical motor and cognitive hubs provides a key to the understanding of post-COVID fatigue and related neuropsychiatric complications.

Source: Josephine Heine, et al. Structural brain changes in patients with post-COVID fatigue: a prospective observational study. The Lancet, VOLUME 58, 101874, APRIL 2023.  Published: February 27, 2023 DOI: https://doi.org/10.1016/j.eclinm.2023.101874 (Full text)

Gastrointestinal and Hepatobiliary Symptoms and Disorders with Long (Chronic) COVID Infection

Abstract:

Long COVID is a novel syndrome characterizing new or persistent symptoms weeks after COVID-19 infection and involving multiple organ systems. This review summarizes the gastrointestinal and hepatobiliary sequelae of long COVID syndrome. It describes potential biomolecular mechanisms, prevalence, preventative measures, potential therapies, and health care and economic impact of long COVID syndrome, particularly of its gastrointestinal (GI) and hepatobiliary manifestations.

Source: Rizvi A, Ziv Y, Crawford JM, Trindade AJ. Gastrointestinal and Hepatobiliary Symptoms and Disorders with Long (Chronic) COVID Infection. Gastroenterol Clin North Am. 2023 Mar;52(1):139-156. doi: 10.1016/j.gtc.2022.09.002. PMID: 36813422; PMCID: PMC9940919. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9940919/ (Full text)

Brainstem volume changes in myalgic encephalomyelitis/chronic fatigue syndrome and long COVID patients

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long COVID patients have overlapping neurological, autonomic, pain, and post-exertional symptoms. We compared volumes of brainstem regions for 10 ME/CFS (CCC or ICC criteria), 8 long COVID (WHO Delphi consensus), and 10 healthy control (HC) subjects on 3D, T1-weighted MRI images acquired using sub-millimeter isotropic resolution using an ultra-high field strength of 7 Tesla.

Group comparisons with HC detected significantly larger volumes in ME/CFS for pons (p = 0.004) and whole brainstem (p = 0.01), and in long COVID for pons (p = 0.003), superior cerebellar peduncle (p = 0.009), and whole brainstem (p = 0.005). No significant differences were found between ME/CFS and long COVID volumes. In ME/CFS, we detected positive correlations between the pons and whole brainstem volumes with “pain” and negative correlations between the midbrain and whole brainstem volumes with “breathing difficulty.”

In long COVID patients a strong negative relationship was detected between midbrain volume and “breathing difficulty.” Our study demonstrated an abnormal brainstem volume in both ME/CFS and long COVID consistent with the overlapping symptoms.

Source: Thapaliya K, Marshall-Gradisnik S, Barth M, Eaton-Fitch N, Barnden L. Brainstem volume changes in myalgic encephalomyelitis/chronic fatigue syndrome and long COVID patients. Frontiers in Neuroscience, 2023 March 2; 17:1125208. https://www.frontiersin.org/articles/10.3389/fnins.2023.1125208/full (Full text)

Two-year follow-up of patients with post-COVID-19 condition in Sweden: a prospective cohort study

Summary:

Background: Few studies have reported the long-term health effects of COVID-19. The regional population-based Linköping COVID-19 study (LinCoS) included all patients hospitalised due to COVID-19 during the first pandemic wave. Four months post-discharge, over 40% (185/433) experienced persisting symptoms and activity/participation limitations, indicating post-COVID-19 condition (PCC). The present follow-up study aimed to determine the long-term recovery among these patients 24 months post-admission.

Methods: This prospective cohort study included all patients from LinCoS with PCC at four months post-discharge. We repeated the same structured interview at a 24-month follow-up to identify persisting symptoms and their impact on daily life. Intercurrent health issues were identified by reviewing medical records.

Findings: Of 185 patients with PCC at 4 months post-discharge, 181 were alive at the 24-month assessment and 165 agreed to participate. Of those, 21% (35/165) had been readmitted to hospital for various causes in the interim period. The majority of patients (139/165, 84%) reported persisting problems affecting everyday life at 24 months. Significant improvements were seen in the prevalence and magnitude of some symptoms/limitations compared with four months post-discharge. Cognitive, sensorimotor, and fatigue symptoms were the most common persisting symptoms at 24 months. No clear difference was evident between individuals treated in the intensive care unit (ICU) and non-ICU-treated individuals. Approximately half of those who were on sick leave related to PCC at four months after infection were on sick leave at 24 months.

Interpretation: This is one of the first studies to report 2-year outcomes in patients with PCC following COVID-19 hospitalisation. Despite some improvements over time, we found a high prevalence of persisting symptoms and a need for long-term follow-up and rehabilitation post COVID-19 infection.

Source: Carl Wahlgren et al. Two-year follow-up of patients with post-COVID-19 condition in Sweden: a prospective cohort study. The Lancet Regional Health – Europe. DOI:https://doi.org/10.1016/j.lanepe.2023.100595 https://www.thelancet.com/journals/lanepe/article/PIIS2666-7762(23)00013-3/fulltext (Full text)

The Very Long COVID: Persistence of Symptoms after 12–18 Months from the Onset of Infection and Hospitalization

Abstract:

According to the World Health Organization’s definition, long COVID is the persistence or development of new symptoms 3 months after the initial infection. Various conditions have been explored in studies with up to one-year follow-up but very few looked further. This prospective cohort study addresses the presence of a wide spectrum of symptoms in 121 patients hospitalized during the acute phase of COVID-19 infection, and the association between factors related to the acute phase of the disease and the presence of residual symptoms after one year or longer from hospitalization.
The main results are as follows: (i) post-COVID symptoms persist in up to 60% of the patient population at a mean follow-up of 17 months; (ii) the most frequent symptoms are fatigue and dyspnea, but neuropsychological disturbances persist in about 30% of the patients (iii) when corrected for the duration of follow-up with a freedom-from-event analysis; only complete (2 doses) vaccination at the time of hospital admission remained independently associated with persistence of the major physical symptoms, while vaccination and previous neuropsychological symptoms remained independently associated with persistence of major neuropsychological symptoms.
Source: Ranucci M, Baryshnikova E, Anguissola M, Pugliese S, Ranucci L, Falco M, Menicanti L. The Very Long COVID: Persistence of Symptoms after 12–18 Months from the Onset of Infection and Hospitalization. Journal of Clinical Medicine. 2023; 12(5):1915. https://doi.org/10.3390/jcm12051915 https://www.mdpi.com/2077-0383/12/5/1915 (Full text)

The role of serum brain injury biomarkers in individuals with a mild-to-moderate COVID infection and Long-COVID – results from the prospective population-based COVI-GAPP study

Abstract:

Background During and after mild (no hospitalization) or moderate (hospitalization without ICU) SARS-CoV-2 infections, a wide range of symptoms, including neurological disorders have been reported. It is, however, unknown if these neurological symptoms are associated with brain injury and whether brain injury and related symptoms also emerge in patients suffering from Long-COVID. Neuronal biomarkers such as serum neurofilament light chain and glial fibrillary acidic protein can be used to elucidate neuro-axonal and astroglial injuries. We therefore investigated whether these biomarkers are associated with the COVID-19 infection status (mild-to-moderate), the associated symptoms and Long-COVID.

Methods From 146 individuals of the general population with a post-acute, mild-to-moderate SARS-CoV-2 infection, serum neurofilament light chain (sNfL; marker of intra-axonal neuronal injury) and serum glial fibrillary acidic protein (sGFAP; marker of astrocytic activation/injury) were measured. Samples were taken before, during and after (five and ten months) a SARS-CoV-2 infection. Individual symptoms and Long-COVID status were assessed using questionnaires.

Results Neurological symptoms were described for individuals after a mild and moderate COVID-19 infection, however, serum markers of brain injury (sNfL/sGFAP) did not change after an infection (sNfL: P = 0.74; sGFAP: P = 0.24) and were not associated with headache (P = 0.51), fatigue (P = 0.93), anosmia (P = 0.77) and ageusia (P = 0.47). In participants with Long-COVID, sGFAP (P = 0.038), but not sNfL (P = 0.58) significantly increased but was not associated with neurological symptoms.

Conclusion Neurological symptoms in individuals after a mild-to-moderate SARS-CoV-2 infection with and without Long-COVID were not associated with brain injury, although there was some astroglial injury observed in Long-COVID patients.

Source: Julia Telser, Kirsten Grossmann, Ornella C Weideli, Dorothea Hillmann, Stefanie Aeschbacher, Niklas Wohlwend, Laura Velez, Jens Kuhle, Aleksandra Maleska, Pascal Benkert, Corina Risch, David Conen, Martin Risch, Lorenz Risch. The role of serum brain injury biomarkers in individuals with a mild-to-moderate COVID infection and Long-COVID – results from the prospective population-based COVI-GAPP study. medRxiv 2023.02.15.23285972; doi: https://doi.org/10.1101/2023.02.15.23285972 https://www.medrxiv.org/content/10.1101/2023.02.15.23285972v1.full-text (Full text)