Tag: long covid symptoms

Long-term gastrointestinal outcomes of COVID-19

Abstract:

A comprehensive evaluation of the risks and 1-year burdens of gastrointestinal disorders in the post-acute phase of COVID-19 is needed but is not yet available. Here we use the US Department of Veterans Affairs national health care databases to build a cohort of 154,068 people with COVID-19, 5,638,795 contemporary controls, and 5,859,621 historical controls to estimate the risks and 1-year burdens of a set of pre-specified incident gastrointestinal outcomes.

We show that beyond the first 30 days of infection, people with COVID-19 exhibited increased risks and 1-year burdens of incident gastrointestinal disorders spanning several disease categories including motility disorders, acid related disorders (dyspepsia, gastroesophageal reflux disease, peptic ulcer disease), functional intestinal disorders, acute pancreatitis, hepatic and biliary disease.

The risks were evident in people who were not hospitalized during the acute phase of COVID-19 and increased in a graded fashion across the severity spectrum of the acute phase of COVID-19 (non-hospitalized, hospitalized, and admitted to intensive care). The risks were consistent in comparisons including the COVID-19 vs the contemporary control group and COVID-19 vs the historical control group as the referent category.

Altogether, our results show that people with SARS-CoV-2 infection are at increased risk of gastrointestinal disorders in the post-acute phase of COVID-19. Post-covid care should involve attention to gastrointestinal health and disease.

Source: Xu, E., Xie, Y. & Al-Aly, Z. Long-term gastrointestinal outcomes of COVID-19. Nat Commun 14, 983 (2023). https://doi.org/10.1038/s41467-023-36223-7 https://www.nature.com/articles/s41467-023-36223-7 (Full text)

Investigating brain cortical activity in patients with post-COVID-19 brain fog

Abstract:

Brain fog is a kind of mental problem, similar to chronic fatigue syndrome, and appears about 3 months after the infection with COVID-19 and lasts up to 9 months. The maximum magnitude of the third wave of COVID-19 in Poland was in April 2021.

The research referred here aimed at carrying out the investigation comprising the electrophysiological analysis of the patients who suffered from COVID-19 and had symptoms of brain fog (sub-cohort A), suffered from COVID-19 and did not have symptoms of brain fog (sub-cohort B), and the control group that had no COVID-19 and no symptoms (sub-cohort C). The aim of this article was to examine whether there are differences in the brain cortical activity of these three sub-cohorts and, if possible differentiate and classify them using the machine-learning tools. The dense array electroencephalographic amplifier with 256 electrodes was used for recordings.

The event-related potentials were chosen as we expected to find the differences in the patients’ responses to three different mental tasks arranged in the experiments commonly known in experimental psychology: face recognition, digit span, and task switching. These potentials were plotted for all three patients’ sub-cohorts and all three experiments. The cross-correlation method was used to find differences, and, in fact, such differences manifested themselves in the shape of event-related potentials on the cognitive electrodes.

The discussion of such differences will be presented; however, an explanation of such differences would require the recruitment of a much larger cohort. In the classification problem, the avalanche analysis for feature extractions from the resting state signal and linear discriminant analysis for classification were used. The differences between sub-cohorts in such signals were expected to be found. Machine-learning tools were used, as finding the differences with eyes seemed impossible. Indeed, the A&B vs. C, B&C vs. A, A vs. B, A vs. C, and B vs. C classification tasks were performed, and the efficiency of around 60-70% was achieved.

In future, probably there will be pandemics again due to the imbalance in the natural environment, resulting in the decreasing number of species, temperature increase, and climate change-generated migrations. The research can help to predict brain fog after the COVID-19 recovery and prepare the patients for better convalescence. Shortening the time of brain fog recovery will be beneficial not only for the patients but also for social conditions.

Source: Wojcik GM, Shriki O, Kwasniewicz L, Kawiak A, Ben-Horin Y, Furman S, Wróbel K, Bartosik B, Panas E. Investigating brain cortical activity in patients with post-COVID-19 brain fog. Front Neurosci. 2023 Feb 9;17:1019778. doi: 10.3389/fnins.2023.1019778. PMID: 36845422; PMCID: PMC9947499. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9947499/ (Full text)

Predictors of Long-COVID-19 and its Impact on Quality of Life: Longitudinal Analysis at 3, 6 and 9 Months after Discharge from a Portuguese Centre

Abstract:

Introduction: Long-COVID-19 impacts health-related quality of life (HR-QoL) but data is scarce. The aim of this study was to describe and prospectively assess the prevalence and risk factors for long-COVID-19 after hospital discharge, and to evaluate its impact on patient HR-QoL.

Material and methods: Single-centre longitudinal study including all COVID-19 patients discharged between December 2020 and February 2021. Patients were contacted remotely at three, six and nine months. Data were collected as follows: 1) Long-COVID-19 symptoms were self-reported; 2) HRQoL were assessed using the 3-level EuroQoL-5D (EQ-5D-3L) questionnaire. Pregnant women, demented, bedridden, and non-Portuguese-speaking patients were excluded.

Results: The three-, six- and nine-month assessments were completed by 152, 117 and 110 patients (median age: 61 years; male sex: 56.6%). Long-COVID-19 (≥ 1 symptom) was reported by 66.5%, 62.4% and 53.6% of patients and HR-QoL assessment showed impairment of at least some domain in 65.8%, 69.2% and 55.4% of patients at three, six and nine months, respectively. Fatigue was the most common long-COVID-19 symptom. Anxiety/depression domain was the most frequently affected in all three time-points, peaking at six months (39%), followed by pain/discomfort and mobility domains. Long-COVID-19 was associated with the impairment of all EQ-5D-3L domains except for self-care domain at each time-point. Neither intensive care unit admission nor disease severity were associated with long-COVID-19 nor with impairment of any EQ-5D-3L domain. After adjusting for sex, age, frailty status, and comorbid conditions, long-COVID-19 remained significantly associated with HR-QoL impairment at three (OR 4.27, 95% CI 1.92 – 9.52, p < 0.001), six (OR 3.46, 95% CI 1.40 – 8.57, p = 0.007) and nine months (OR 4.13, 95% CI 1.62 – 10.55, p = 0.003) after hospital discharge. In a longitudinal analysis, patients reporting long-COVID-19 at three months had an EQ-5D-3L index value decreased by 0.14 per visit (p < 0.001) compared to those without long-COVID-19 and both groups had a non-significant change in mean EQ-5D-3L index over the nine-month period (time-point assessment, Z = 0.91, p = 0.364).

Conclusion: Clinical sequelae associated with long-COVID-19 can persist for at least nine months after hospital discharge in most patients and can impair long-term HR-QoL in more than half of patients regardless of disease severity, and clinicodemographic characteristics.

Source: Gaspar P, Dias M, Parreira I, Gonçalves HD, Parlato F, Maione V, Atalaia Barbacena H, Carreiro C, Duarte L. Predictors of Long-COVID-19 and its Impact on Quality of Life: Longitudinal Analysis at 3, 6 and 9 Months after Discharge from a Portuguese Centre. Acta Med Port. 2023 Feb 24. doi: 10.20344/amp.19047. Epub ahead of print. PMID: 36827994. https://www.actamedicaportuguesa.com/revista/index.php/amp/article/view/19047 (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)

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)

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)