Tag: long covid symptoms

Myopathy as a cause of Long COVID fatigue: Evidence from quantitative and single fiber EMG and muscle histopathology

Highlights:

• Myopathic changes in qEMG and/or increased jitter in sfEMG were seen in 63% of 84 patients with Long COVID neuromuscular symptoms.

• Low quality of life score correlated with higher mean jitter values in sfEMG but not with qEMG measures.

• Electron microscopy showed damage of terminal nerves and motor endplate.Abstract:

Objective: To describe neurophysiological abnormalities in Long COVID and correlate quantitative electromyography (qEMG) and single fiber EMG (sfEMG) results to clinical scores and histopathology.

Methods: 84 patients with non-improving musculoskeletal Long COVID symptoms were examined with qEMG and sfEMG. Muscle biopsies were taken in a subgroup.

Results: Mean motor unit potential (MUP) duration was decreased in ≥1 muscles in 52% of the patients. Mean jitter was increased in 17% of the patients in tibialis anterior and 25% in extensor digitorum communis. Increased jitter was seen with or without myopathic qEMG. Low quality of life score correlated with higher jitter values but not with qEMG measures. In addition to our previously published mitochondrial changes, inflammation, and capillary injury, we show now in muscle biopsies damage of terminal nerves and motor endplate with abundant basal lamina material. At the endplate, axons were present but no vesicle containing terminals. The post-synaptic cleft in areas appeared atrophic with short clefts and coarse crests.

Conclusions: Myopathic changes are common in Long COVID. sfEMG abnormality is less common but may correlate with clinical scores. sfEMG changes may be due to motor endplate pathology.

Significance: These findings may indicate a muscle pathophysiology behind fatigue in Long COVID.

Source: Jane Agergaard, Benjamin Yamin Ali Khan, Thomas Engell-Sørensen, Berit Schiøttz-Christensen, Lars Østergaard, Eva K. Hejbøl, Henrik D. Schrøder, Henning Andersen, Jakob Blicher, Thomas Holm Pedersen, Thomas Harbo, Hatice Tankisi,
Myopathy as a cause of Long COVID fatigue: Evidence from quantitative and single fiber EMG and muscle histopathology,
Clinical Neurophysiology, 2023, ISSN 1388-2457, https://doi.org/10.1016/j.clinph.2023.01.010.
https://www.sciencedirect.com/science/article/pii/S1388245723000196 (Full text)

Post-acute sequelae of SARS-CoV-2 (PASC) syndrome presenting as postural orthostatic tachycardia syndrome (POTS)

Abstract:

The novel SARS-CoV-2 emerged in 2019, and the global COVID-19 pandemic continues into 2022. It has been known that a subset of patients develops chronic, debilitating symptoms after otherwise complete recovery from acute infection of COVID-19.

Multiple terms have been used to describe this constellation of symptoms, including long COVID, long-haul COVID, and post-acute sequelae of SARS-CoV-2 syndrome (PASC). PASC is broadly defined as a wide range of new, returning, or ongoing symptoms at least four weeks after infection. Those patients are often seen in emergency departments after acute COVID- 19 infection, but their symptoms are not adequately managed because the underlying pathophysiology of PASC is not well understood.

Among patients with PASC, postural orthostatic tachycardic syndrome (POTS) has been increasingly recognized. POTS is one of the most common forms of autonomic dysfunction and defined by a sustained orthostatic tachycardia during active standing or head-up tilt test in the absence of orthostatic hypotension or other cardiopulmonary diseases. Because POTS is a treatable condition, it is important to recognize POTS among PASC patients. Herein, we reviewed the current literature on POTS and dysautonomia in PASC in order to better understand the overlap and distinction between these pathologies.

Source: Diekman S, Chung T. Post-acute sequelae of SARS-CoV-2 (PASC) syndrome presenting as postural orthostatic tachycardia syndrome (POTS). Clin Exp Emerg Med. 2023 Jan 30. doi: 10.15441/ceem.22.409. Epub ahead of print. PMID: 36718484. https://pubmed.ncbi.nlm.nih.gov/36718484/ (Full text available as PDF file)

No Causal Effects Detected in COVID-19 and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Two Sample Mendelian Randomization Study

Abstract

New clinical observational studies suggest that Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a sequela of COVID-19 infection, but whether there is an exact causal relationship between COVID-19 and ME/CFS remains to be verified. To investigate whether infection with COVID-19 actually causes ME/CFS, this paper obtained pooled data from the Genome Wide Association Study (GWAS) and analyzed the relationship between COVID susceptibility, hospitalization and severity of COVID and ME/CFS, respectively, using two-sample Mendelian randomization (TSMR).
TSMR analysis was performed by inverse variance weighting (IVW), weighted median method, MR-Egger regression and weighted mode and simple mode methods, respectively, and then the causal relationship between COVID-19 and ME/CFS was further evaluated by odds ratio (OR). Eventually, we found that COVID-19 severity, hospitalization and susceptibility were all not significantly correlated with ME/CFS (OR:1.000,1.000,1.000; 95% CI:0.999–1.000, 0.999–1.001, 0.998–1.002; p = 0.333, 0.862, 0.998, respectively). We found the results to be reliable after sensitivity analysis.
These results suggested that SARS-CoV-2 infection may not significantly contribute to the elevated risk of developing CFS, and therefore ME/CFS may not be a sequela of COVID-19, but may simply present with symptoms similar to those of CFS after COVID-19 infection, and thus should be judged and differentiated by physicians when diagnosing and treating the disease in clinical practice.
Source: Xu W, Cao Y, Wu L. No Causal Effects Detected in COVID-19 and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Two Sample Mendelian Randomization Study. International Journal of Environmental Research and Public Health. 2023; 20(3):2437. https://doi.org/10.3390/ijerph20032437 https://www.mdpi.com/1660-4601/20/3/2437 (Full text)

Long COVID Syndrome and Cardiovascular Manifestations: A Systematic Review and Meta-Analysis

Abstract:

Background: Long COVID syndrome is a significant cause of morbidity in COVID-19 patients who remain symptomatic with varied clinical presentations beyond three weeks. Furthermore, the relevance of considering cardiovascular outcomes in post-COVID-19 syndrome is important in the current COVID-19 pandemic.
Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed for this systematic review and meta-analysis. Systematic searches were conducted from multiple databases without language restrictions until October 8, 2022, to find studies evaluating cardiovascular outcomes such as arrhythmias, myocardium and pericardium diseases, coronary vessel disease, and thromboembolic disorders in post-COVID cases. The pooled odds ratio (OR), and standard mean difference (SMD) with their corresponding 95% confidence intervals (CI) were computed to find the association.
Results: Altogether, seven studies with a total of 8,126,462 (cases: 1,321,305; controls: 6,805,157) participants were included in the meta-analysis. Pooled odds ratios of cardiovascular outcomes were significantly higher in post-COVID cases (OR > 1, p < 0.05) than in controls. However, the mortality (OR: 4.76, p = 0.13), and heart rate variability (SMD: −0.06, p = 0.91) between cases and controls were not statistically significant.
Conclusions: Significant cardiovascular sequelae in long COVID syndrome highlight the importance of careful cardiac monitoring of COVID-19 patients in the post-COVID phase to address cardiovascular complications as soon as possible; larger-scale prospective studies are required for accurate estimation.
Source: Shrestha AB, Mehta A, Pokharel P, Mishra A, Adhikari L, Shrestha S, Yadav RS, Khanal S, Sah R, Nowrouzi-Kia B, Padhi BK, Chattu VK. Long COVID Syndrome and Cardiovascular Manifestations: A Systematic Review and Meta-Analysis. Diagnostics. 2023; 13(3):491. https://doi.org/10.3390/diagnostics13030491 https://www.mdpi.com/2075-4418/13/3/491 (Full text)

Marital status and post-COVID-19 conditions

Abstract:

Although studies have investigated the factors associated with psychological post-COVID-19 symptoms, the impact of marital status on symptom development has not been fully determined. This study conducts a questionnaire survey to investigate the association between marital status and the proportion of patients with post-COVID-19 symptoms in 749 cases as valid responses.

Depressive state and memory impairment were more frequently seen in the no-spouse group when each symptom was compared according to marital status. Particularly in individuals in the 40s who had minor COVID-19 illness, this trend was noted. Single patients with mild COVID-19 illness may need proactive psychological support.

Source: Kudoh R, Komiya K, Shinohara A, Kageyama T, Hiramatsu K, Kadota JI. Marital status and post-COVID-19 conditions. Respir Investig. 2023 Jan 23;61(2):181-185. doi: 10.1016/j.resinv.2023.01.001. Epub ahead of print. PMID: 36720183; PMCID: PMC9868354. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9868354/ (Full text)

Functional Neurological Disorder in people with Long-Covid: A Systematic Review

Abstract:

Background: Acute health events, including infections, can trigger the onset of functional neurological disorder (FND). We hypothesised that a proportion of people with long-COVID might be experiencing functional symptoms.

Methods: We performed a systematic review of studies containing original data on long-COVID. We reviewed the frequency and characteristics of neurological symptoms, looking for positive evidence suggesting an underlying functional disorder, and the hypothesised causes of long-COVID.

Results: We included 102 studies in our narrative synthesis. The most consistently reported neurological symptoms were cognitive difficulties, headaches, pain, dizziness, fatigue, sleep-related symptoms, and ageusia/anosmia. Overall, we found no evidence that any authors had systematically looked for positive features of FND. An exception were three studies describing temporal inconsistency. In general, the neurological symptoms were insufficiently characterised in order to support or refute a diagnosis of FND. Moreover, only 13 studies specifically focussed on long-COVID after mild infection, where the impact of confounders from the general effects of severe illness would be mitigated. Only one study hypothesised that some people with long-COVID might have a functional disorder, and another 8 studies a chronic fatigue syndrome-like response.

Discussion: Neurological symptoms are prevalent in long-COVID, but poorly characterised. We are struck by the similarities between some manifestations of long-COVID and functional disorders triggered by acute illnesses. Unfortunately, the current literature is plagued by confounders, including the mixing of patients with initial mild infection with those with severe acute medical complications. The hypothesis that long-COVID might in part correspond to a functional disorder remains untested.

Source: Teodoro T, Chen J, Gelauff J, Edwards MJ. Functional Neurological Disorder in people with Long-Covid: A Systematic Review. Eur J Neurol. 2023 Jan 31. doi: 10.1111/ene.15721. Epub ahead of print. PMID: 36719069. https://onlinelibrary.wiley.com/doi/10.1111/ene.15721 (Full text available as PDF file)

Awareness and perceptions of Long COVID among people in the REACT programme: Early insights from a pilot interview study

Abstract:

Background: Long COVID is a patient-made term describing new or persistent symptoms experienced following SARS-CoV-2 infection. The Real-time Assessment of Community Transmission-Long COVID (REACT-LC) study aims to understand variation in experiences following infection, and to identify biological, social, and environmental factors associated with Long COVID. We undertook a pilot interview study to inform the design, recruitment approach, and topic guide for the REACT-LC qualitative study. We sought to gain initial insights into the experience and attribution of new or persistent symptoms and the awareness or perceived applicability of the term Long COVID.

Methods: People were invited to REACT-LC assessment centres if they had taken part in REACT, a random community-based prevalence study, and had a documented history of SARS-CoV-2 infection. We invited people from REACT-LC assessment centres who had reported experiencing persistent symptoms for more than 12 weeks to take part in an interview. We conducted face to face and online semi-structured interviews which were transcribed and analysed using Thematic Analysis.

Results: We interviewed 13 participants (6 female, 7 male, median age 31). Participants reported a wide variation in both new and persistent symptoms which were often fluctuating or unpredictable in nature. Some participants were confident about the link between their persistent symptoms and COVID-19; however, others were unclear about the underlying cause of symptoms or felt that the impact of public health measures (such as lockdowns) played a role. We found differences in awareness and perceived applicability of the term Long COVID.

Conclusion: This pilot has informed the design, recruitment approach and topic guide for our qualitative study. It offers preliminary insights into the varied experiences of people living with persistent symptoms including differences in symptom attribution and perceived applicability of the term Long COVID. This variation shows the value of recruiting from a nationally representative sample of participants who are experiencing persistent symptoms.

Severe Fatigue and Persistent Symptoms at Three Months Following SARS-CoV-2 Infections During the Pre-Delta, Delta, and Omicron Time Periods: A Multicenter Prospective Cohort Study

Abstract:

Background: Most research on SARS-CoV-2 variants focuses on initial symptomatology with limited data on longer-term sequelae. We sought to characterize the prevalence and differences in prolonged symptoms at three months post SARS-CoV-2-infection across the three major variant time-periods (pre-Delta, Delta, and Omicron).

Methods: This multicenter prospective cohort study of adults with acute illness tested for SARS-CoV-2 compared fatigue severity, fatigue symptoms, individual and organ system-based symptoms, and presence of ≥3 total symptoms across variants among COVID-positive and COVID-negative participants 3 months after their initial SARS-CoV-2 diagnosis. Variant periods were defined by dates with ≥50% dominant strain. We performed a sensitivity analysis using ≥90% dominance threshold and multivariable logistic regression modeling to estimate the independent effects of each variant adjusting for socio-demographic characteristics, baseline health, and vaccine status.

Results: The study included 3,223 participants (2,402 COVID-positive and 821 COVID-negative). Among the COVID-positive cohort, 463 (19.3%) were pre-Delta, 1,198 (49.9%) during Delta, and 741 (30.8%) during Omicron. Prolonged severe fatigue was highest in the pre-Delta COVID-positive cohort compared with Delta and Omicron cohorts (16.7% vs 11.5% vs 12.3%, respectively; p = 0.017), as was presence of ≥3 prolonged symptoms (28.4% vs 21.7% vs 16.0%; p < 0.001). No difference was seen in the COVID-negative cohort between variant time-periods. In multivariable models, there was no difference in severe fatigue between variants. There was decreased odds of having ≥3 symptoms in Omicron compared with other variants; this was not significant after adjusting for vaccination status.

Conclusions: Prolonged symptoms following SARS-CoV-2 infection were more common among participants infected during the pre-Delta period compared with Delta and Omicron periods; however, these differences were no longer significant after adjusting for vaccination status. This suggests a potential beneficial effect of vaccination on the risk of developing long-term symptoms.

Source: Gottlieb M, Wang R, Yu H, Spatz ES, Montoy JC, Rodriguez R, Chang AM, Elmore JG, Hannikainen PA, Hill M, Huebinger RM, Idris AH, Lin Z, Koo K, McDonald S, O’Laughlin KN, Plumb ID, Santangelo M, Saydah S, Willis M, Wisk LE, Venkatesh A, Stephens KA, Weinstein RA; INSPIRE Group. Severe Fatigue and Persistent Symptoms at Three Months Following SARS-CoV-2 Infections During the Pre-Delta, Delta, and Omicron Time Periods: A Multicenter Prospective Cohort Study. Clin Infect Dis. 2023 Jan 27:ciad045. doi: 10.1093/cid/ciad045. Epub ahead of print. PMID: 36705268.  https://pubmed.ncbi.nlm.nih.gov/36705268/ (Full study available as PDF file)

Long-term high-dose immunoglobulin successfully treats Long COVID patients with pulmonary, neurologic, and cardiologic symptoms

Abstract:

Introduction: Long COVID is the overarching name for a wide variety of disorders that may follow the diagnosis of acute SARS-COVID-19 infection and persist for weeks to many months. Nearly every organ system may be affected.

Methods: We report nine patients suffering with Long COVID for 101 to 547 days. All exhibited significant perturbations of their immune systems, but only one was known to be immunodeficient prior to the studies directed at evaluating them for possible treatment. Neurological and cardiac symptoms were most common. Based on this data and other evidence suggesting autoimmune reactivity, we planned to treat them for 3 months with long-term high-dose immunoglobulin therapy. If there was evidence of benefit at 3 months, the regimen was continued.

Results: The patients’ ages ranged from 34 to 79 years—with five male and four female patients, respectively. All nine patients exhibited significant immune perturbations prior to treatment. One patient declined this treatment, and insurance support was not approved for two others. The other six have been treated, and all have had a significant to remarkable clinical benefit.

Conclusion: Long-term high-dose immunoglobulin therapy is an effective therapeutic option for treating patients with Long COVID.

Source: Thompson JS, Thornton AC, Ainger T and Garvy BA (2023) Long-term high-dose immunoglobulin successfully treats Long COVID patients with pulmonary, neurologic, and cardiologic symptoms. Front. Immunol. 13:1033651. doi: 10.3389/fimmu.2022.1033651 https://www.frontiersin.org/articles/10.3389/fimmu.2022.1033651/full (Full text)

Mechanisms, Effects, and Management of Neurological Complications of Post-Acute Sequelae of COVID-19 (NC-PASC)

Abstract:

With a growing number of patients entering the recovery phase following infection with SARS-CoV-2, understanding the long-term neurological consequences of the disease is important to their care. The neurological complications of post-acute sequelae of SARS-CoV-2 infection (NC-PASC) represent a myriad of symptoms including headaches, brain fog, numbness/tingling, and other neurological symptoms that many people report long after their acute infection has resolved.
Emerging reports are being published concerning COVID-19 and its chronic effects, yet limited knowledge of disease mechanisms has challenged therapeutic efforts. To address these issues, we review broadly the literature spanning 2020–2022 concerning the proposed mechanisms underlying NC-PASC, outline the long-term neurological sequelae associated with COVID-19, and discuss potential clinical interventions.
Source: Ong IZ, Kolson DL, Schindler MK. Mechanisms, Effects, and Management of Neurological Complications of Post-Acute Sequelae of COVID-19 (NC-PASC). Biomedicines. 2023; 11(2):377. https://doi.org/10.3390/biomedicines11020377 https://www.mdpi.com/2227-9059/11/2/377