Category: Overlapping Illnesses

Long COVID: An unpredicted multisystem syndrome of COVID-19 disease

Abstract:

Long COVID is multisystem syndrome with nonspecific symptoms and organic signs of unidentified pathology occurs after COVID-19 disease. Long COVID symptoms has been documented in some cases irrespective of disease severity or hospitalization.
Long COVID symptoms has significant impact on quality of life in those cases suffered from disease in recent past and lingering to almost two years since infection. Importantly, not all cases of COVID-19 were shown long COVID symptoms. Pathophysiology resulting into long COVID manifestations is still not completely validated.
Researchers have reported ‘immune dysregulation’ and ‘coagulation abnormalities’ are probable pathophysiological mechanism for long COVID. Some of the long COVID effects shown complete reversibility including post COVID lung fibrosis. Reboot system to restore immune dysregulation and recovery in long COVID is real concern. Vaccination has not shown significant effect modifying long COVID manifestation. [Editor’s note: See conclusion in full text for a contradictory statement.]
Source: Hital Vishnu Patil, Neel Tandel and Gajanan Godhali. Long COVID: An unpredicted multisystem syndrome of COVID-19 disease. World Journal of Advanced Pharmaceutical and Life Sciences, 2023, 04(01), 005–012. https://www.researchgate.net/publication/368757849_Long_COVID_An_unpredicted_multisystem_syndrome_of_COVID-19_disease (Full text)

Social Stigma, Mental Health, Stress, and Health-Related Quality of Life in People with Long COVID

Abstract:

A considerable amount of people who have been infected with SARS-CoV-2 experience ongoing symptoms, a condition termed long COVID. This study examined nuanced experiences of social stigma in people with long COVID and their associations with perceived stress, depressive symptoms, anxiety, and mental and physical health-related quality of life (hrqol).
A total of N = 253 participants with long COVID symptoms (mean age = 45.49, SD = 12.03; n = 224, 88.5% women) completed a cross-sectional online survey on overall social stigma and the subfacets enacted and perceived external stigma, disclosure concerns, and internalized stigma. Data were analysed using multiple regression and controlling for overall burden of consequences of long COVID, overall burden of symptoms of long COVID, and outcome-specific confounders.
In line with our preregistered hypotheses, total social stigma was related to more perceived stress, more depressive symptoms, higher anxiety, and lower mental hrqol, but—in contrast to our hypothesis—it was unrelated to physical hrqol after controlling for confounders. The three subscales of social stigma resulted in differential associations with the outcomes.
Social stigma experiences go hand in hand with worse mental health in people with long COVID. Future studies should examine potential protective factors to buffer the effects of social stigma on people’s well-being.
Source: Scholz U, Bierbauer W, Lüscher J. Social Stigma, Mental Health, Stress, and Health-Related Quality of Life in People with Long COVID. International Journal of Environmental Research and Public Health. 2023; 20(5):3927. https://doi.org/10.3390/ijerph20053927. https://www.mdpi.com/1660-4601/20/5/3927 (Full text)

Pain and Clinical Presentation: A Cross-Sectional Study of Patients with New-Onset Chronic Pain in Long-COVID-19 Syndrome

Abstract:

The aim of this study was to evaluate the characteristics of pain (i.e., pain intensity, pain interference, clinical presentation) in Long-COVID-19 patients and compare the location of pain between successfully recovered COVID-19 patients and healthy matched controls.
A cross-sectional case-control study was carried out. Long-COVID-19 patients, age- and sex-matched patients with a history of COVID-19 who had successfully recovered, and healthy controls were included. Outcomes included were pain characteristics (Brief Pain Inventory and Short-Form McGill Pain Questionnaire) and clinical presentation (Widespread Pain Index and Euroqol-5 Dimensions 5 Levels Visual Analogue Scale). Sixty-nine patients with Long-COVID-19 syndrome, sixty-six successfully recovered COVID-19 patients, and sixty-seven healthy controls were evaluated.
Patients with Long-COVID-19 syndrome showed greater pain intensity and interference. In addition, they showed worse quality of life and greater widespread pain, with the most frequent locations of pain being the neck, legs, and head.
In conclusion, patients with Long-COVID-19 syndrome show a high prevalence of pain, characterized by widespread pain of moderate intensity and interference, with the most frequent locations being the neck, legs, and head, significantly affecting the quality of life of these patients.
Source: Calvache-Mateo A, López-López L, Martín-Núñez J, Heredia-Ciuró A, Granados-Santiago M, Ortiz-Rubio A, Valenza MC. Pain and Clinical Presentation: A Cross-Sectional Study of Patients with New-Onset Chronic Pain in Long-COVID-19 Syndrome. International Journal of Environmental Research and Public Health. 2023; 20(5):4049. https://doi.org/10.3390/ijerph20054049 https://www.mdpi.com/1660-4601/20/5/4049 (Full text)

Potential of Black Seeds (Nigella Sativa) in the Management of Long COVID or Post-acute Sequelae of COVID-19 (PASC) and Persistent COVID-19 Symptoms – An Insight

Abstract:

Background: Some individuals may experience symptoms persisting for many months after the recovery from COVID-19 and patients with Long COVID are managed mainly with symptomatic treatment and supportive care.

Objective: This review article focuses on the beneficial effects of black seeds (Nigella Sativa) in the management of long COVID and persistent COVID symptoms.

Methods: The literature was searched in databases such as LitCOVID, Web of Science, Google Scholar, bioRxiv, medRxiv, Science Direct, EBSCO, Scopus, Embase, and reference lists to identify studies, which evaluated various effects of black seeds (N. sativa) related to signs and symptoms of Long COVID.

Results: Black seeds (N. sativa) have shown potential anti-COVID, antiviral, anti-inflammatory, antioxidant, immunomodulatory, antihypertensive, anti-obesity, antidiabetic, antihyperlipidemic, and antiasthmatic properties in various clinical, animal, in-vitro, in-vivo, and in-silico studies, which would help the patients recovered from COVID to mitigate Long COVID complications.

Conclusion: Patients experiencing Long COVID may use black seeds (N. sativa) as adjunctive therapy in combination with symptomatic treatment and supportive care to prevent further deterioration and hospitalization. The safety and efficacy of N. sativa in patients with Long-COVID would further be established by future randomized controlled clinical trials.

Source: Pakkir Maideen NM, Hassan Jumale A, Ramadan Barakat I, Khalifa Albasti A. Potential of Black Seeds (Nigella Sativa) in the Management of Long COVID or Post-acute Sequelae of COVID-19 (PASC) and Persistent COVID-19 Symptoms – An Insight. Infect Disord Drug Targets. 2023 Feb 23. doi: 10.2174/1871526523666230223112045. Epub ahead of print. PMID: 36825730.

Cystatin-c May Indicate Subclinical Renal Involvement, While Orosomucoid Is Associated with Fatigue in Patients with Long-COVID Syndrome

Abstract:

Long-COVID syndrome is associated with high healthcare costs, but its pathophysiology is not yet fully understood. Inflammation, renal impairment or disturbance of the NO system emerge as potential pathogenetic factors. We aimed to investigate the relationship between symptoms of long-COVID syndrome and serum levels of cystatin-c (CYSC), orosomucoid (ORM), l-arginine, symmetric dimethylarginine (SDMA) and asymmetric dimethylarginine (ADMA). A total of 114 patients suffering from long-COVID syndrome were included in this observational cohort study.

We found that serum CYSC was independently associated with the anti-spike immunoglobulin (S-Ig) serum level (OR: 5.377, 95% CI: 1.822-12.361; p = 0.02), while serum ORM (OR: 9.670 (95% CI: 1.34-9.93; p = 0.025) independently predicted fatigue in patients with long-COVID syndrome, both measured at baseline visit. Additionally, the serum CYSC concentrations measured at the baseline visit showed a positive correlation with the serum SDMA levels. The severity of abdominal and muscle pain indicated by patients at the baseline visit showed a negative correlation with the serum level of L-arginine.

In summary, serum CYSC may indicate subclinical renal impairment, while serum ORM is associated with fatigue in long-COVID syndrome. The potential role of l-arginine in alleviating pain requires further studies.

Source: Zavori L, Molnar T, Varnai R, Kanizsai A, Nagy L, Vadkerti B, Szirmay B, Schwarcz A, Csecsei P. Cystatin-c May Indicate Subclinical Renal Involvement, While Orosomucoid Is Associated with Fatigue in Patients with Long-COVID Syndrome. J Pers Med. 2023 Feb 19;13(2):371. doi: 10.3390/jpm13020371. PMID: 36836605; PMCID: PMC9958557. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9958557/ (Full text)

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)