Tag: long covid symptoms

Effect of Repetitive Transcranial Magnetic Stimulation on Long Coronavirus Disease 2019 with Fatigue and Cognitive Dysfunction

Abstract:

Objectives: There is no established treatment for chronic fatigue and various cognitive dysfunctions (brain fog) caused by long coronavirus disease 2019 (COVID-19). We aimed to clarify the effectiveness of repetitive transcranial magnetic stimulation (rTMS) for treating these symptoms.

Methods: High-frequency rTMS was applied to occipital and frontal lobes in 12 patients with chronic fatigue and cognitive dysfunction 3 months after severe acute respiratory syndrome coronavirus 2 infection. Before and after ten sessions of rTMS, Brief Fatigue Inventory (BFI), Apathy Scale (AS), and Wechsler Adult Intelligence Scale-fourth edition (WAIS4) were determined and N-isopropyl-p-[123I]iodoamphetamine single photon emission computed tomography (SPECT) was performed.

Results: Twelve subjects completed ten sessions of rTMS without adverse events. The mean age of the subjects was 44.3 ± 10.7 years, and the mean duration of illness was 202.4 ± 114.5 days. BFI, which was 5.7 ± 2.3 before the intervention, decreased significantly to 1.9 ± 1.8 after the intervention. The AS was significantly decreased after the intervention from 19.2 ± 8.7 to 10.3 ± 7.2. All WAIS4 sub-items were significantly improved after rTMS intervention, and the full-scale intelligence quotient increased from 94.6 ± 10.9 to 104.4 ± 13.0. Hypoperfusion in the bilateral occipital and frontal lobes observed on SPECT improved in extent and severity after ten sessions of rTMS.

Conclusions: Although we are still in the early stages of exploring the effects of rTMS, the procedure has the potential for use as a new non-invasive treatment for the symptoms of long COVID.

Source: Sasaki N, Yamatoku M, Tsuchida T, Sato H, Yamaguchi K. Effect of Repetitive Transcranial Magnetic Stimulation on Long Coronavirus Disease 2019 with Fatigue and Cognitive Dysfunction. Prog Rehabil Med. 2023 Feb 28;8:20230004. doi: 10.2490/prm.20230004. PMID: 36861061; PMCID: PMC9968785. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9968785/ (Full text)

Could the fibromyalgia syndrome be triggered or enhanced by COVID-19?

Abstract:

Fibromyalgia (FM) is a complex disease with an uncertain aetiology and intricate pathophysiology. Although its genesis is not fully explained, potential environmental factors, such as viral infections might trigger FM or worsen patients’ clinical outcomes.

The SARS-CoV-2 virus may affect central and peripheral nervous systems, leading to musculoskeletal, neurological, and psychological disturbances. These symptoms might persist at least 12 months beyond the recovery, often referred to as post-COVID syndrome, which resembles FM syndrome. In this sense, we argued the potential consequences of COVID-19 exclusively on FM syndrome.

First, we have described post-COVID syndrome and its painful symptoms. Afterwards, we argued whether FM syndrome could be triggered or enhanced by COVID-19 infection or by numerous and persistent stressors imposed daily by the pandemic setting (isolation, uncertainty, depression, mental stress, generalized anxiety, and fear of the virus). In addition, we have demonstrated similarities between pathophysiological mechanisms and cardinal symptoms of FM and COVID-19, speculating that SARS-CoV-2 might represent a critical mediator of FM or an exacerbator of its symptoms once both syndromes share similar mechanisms and complaints.

Therefore, pharmacologic and non-pharmacological approaches commonly used to treat FM could serve as strategic therapies to attenuate painful and neurological manifestations of post-COVID syndrome. Although it is still theoretical, clinicians and researchers should be alert of patients who develop symptoms similar to FM or those who had their FM symptoms increased post-COVID to manage them better.

Source: Fialho MFP, Brum ES, Oliveira SM. Could the fibromyalgia syndrome be triggered or enhanced by COVID-19? Inflammopharmacology. 2023 Feb 27:1–19. doi: 10.1007/s10787-023-01160-w. Epub ahead of print. PMID: 36849853; PMCID: PMC9970139. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9970139/ (Full text)

Effect of covid-19 vaccination on long covid: systematic review

Abstract:

Objective To determine the effect of covid-19 vaccination, given before and after acute infection with the SARS-CoV-2 virus, or after a diagnosis of long covid, on the rates and symptoms of long covid.

Design Systematic review.

Data sources PubMed, Embase, and Cochrane covid-19 trials, and Europe PubMed Central (Europe PMC) for preprints, from 1 January 2020 to 3 August 2022.

Eligibility criteria for selecting studies Trials, cohort studies, and case-control studies reporting on patients with long covid and symptoms of long covid, with vaccination before and after infection with the SARS-CoV-2 virus, or after a diagnosis of long covid. Risk of bias was assessed with the ROBINS-I tool.

Results 1645 articles were screened but no randomised controlled trials were found. 16 observational studies from five countries (USA, UK, France, Italy, and the Netherlands) were identified that reported on 614 392 patients. The most common symptoms of long covid that were studied were fatigue, cough, loss of sense of smell, shortness of breath, loss of taste, headache, muscle ache, difficulty sleeping, difficulty concentrating, worry or anxiety, and memory loss or confusion. 12 studies reported data on vaccination before infection with the SARS-CoV-2 virus, and 10 showed a significant reduction in the incidence of long covid: the odds ratio of developing long covid with one dose of vaccine ranged from 0.22 to 1.03; with two doses, odds ratios were 0.25-1; with three doses, 0.16; and with any dose, 0.48-1.01. Five studies reported on vaccination after infection, with odds ratios of 0.38-0.91. The high heterogeneity between studies precluded any meaningful meta-analysis. The studies failed to adjust for potential confounders, such as other protective behaviours and missing data, thus increasing the risk of bias and decreasing the certainty of evidence to low.

Conclusions Current studies suggest that covid-19 vaccines might have protective and therapeutic effects on long covid. More robust comparative observational studies and trials are needed, however, to clearly determine the effectiveness of vaccines in preventing and treating long covid.

Source: Byambasuren O, Stehlik P, Clark J, et al. Effect of covid-19 vaccination on long covid: systematic review BMJ Medicine 2023;2:e000385. doi: 10.1136/bmjmed-2022-000385. https://bmjmedicine.bmj.com/content/2/1/e000385?s=08 (Full text)

Efficacy of first dose of covid-19 vaccine versus no vaccination on symptoms of patients with long covid: target trial emulation based on ComPaRe e-cohort

Abstract:

Objective To evaluate the effect of covid-19 vaccination on the severity of symptoms in patients with long covid.

Design Target trial emulation based on ComPaRe e-cohort.

Data source ComPaRe long covid cohort, a nationwide e-cohort (ie, a cohort where recruitment and follow-up are performed online) of patients with long covid, in France.

Methods Adult patients (aged ≥18 years) enrolled in the ComPaRe cohort before 1 May 2021 were included in the study if they reported a confirmed or suspected SARS-CoV-2 infection, symptoms persistent for >3 weeks after onset, and at least one symptom attributable to long covid at baseline. Patients who received a first covid-19 vaccine injection were matched with an unvaccinated control group in a 1:1 ratio according to their propensity scores. Number of long covid symptoms, rate of complete remission of long covid, and proportion of patients reporting an unacceptable symptom state at 120 days were recorded.

Results 910 patients were included in the analyses (455 in the vaccinated group and 455 in the control group). By 120 days, vaccination had reduced the number of long covid symptoms (mean 13.0 (standard deviation 9.4) in the vaccinated group v 14.8 (9.8) in the control group; mean difference −1.8, 95% confidence interval −3.0 to −0.5) and doubled the rate of patients in remission (16.6% v 7.5%, hazard ratio 1.93, 95% confidence interval 1.18 to 3.14). Vaccination reduced the effect of long covid on patients’ lives (mean score on the impact tool 24.3 (standard deviation 16.7) v 27.6 (16.7); mean difference −3.3, 95% confidence interval −5.7 to −1.0) and the proportion of patients with an unacceptable symptom state (38.9% v 46.4%, risk difference −7.4%, 95% confidence interval −14.5% to −0.3%). In the vaccinated group, two (0.4%) patients reported serious adverse events requiring admission to hospital.

Conclusion In this study, covid-19 vaccination reduced the severity of symptoms and the effect of long covid on patients’ social, professional, and family lives at 120 days in those with persistent symptoms of infection.

Source: Tran V, Perrodeau E, Saldanha J, et al. Efficacy of first dose of covid-19 vaccine versus no vaccination on symptoms of patients with long covid: target trial emulation based on ComPaRe e-cohort. BMJ Medicine 2023;2:e000229. doi: 10.1136/bmjmed-2022-000229 https://bmjmedicine.bmj.com/content/2/1/e000229 (Full text)

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)