Tag: long covid fatigue

Assessment of short- and long-term functionality and quality of life in patients with post-acute COVID-19 syndrome

Abstract:

Background: Although the number of new cases of coronavirus 2019 (COVID-19) has been drastically reduced worldwide, patients who demonstrate long-term symptoms need more attention from health systems, as these symptoms can negatively affect functionality and quality of life.

Objective: To evaluate muscle function and quality of life at 3, 6, 9 and 12 months in patients with post-acute COVID-19 syndrome and to assess their associations with general fatigue and lung function.

Methods: This observational and longitudinal study evaluated patients with post-acute COVID-19 syndrome. Participants were subjected to the following evaluations: Short Form-36; handgrip strength; Functional Assessment of Chronic Illness Therapy-Fatigue scale; and spirometry.

Results: Among the 350 participants who were evaluated in the third month, 74.6%, 61.4% and 45.4% reported general fatigue, dyspnoea and cough, respectively. In the comparisons between the third month and the sixth month, there were significant increases in Functional Assessment of Chronic Illness Therapy-Fatigue scale, pulmonary function and several Short Form-36 domains. In the comparisons between the sixth month and the ninth month, there was a significant increase only in the social functioning domain of the Short Form-36. In the comparisons between the ninth month and the twelfth month, there was an increase only in some Short Form-36 domains. Significant correlations were observed between the Short Form-36 domains with Functional Assessment of Chronic Illness Therapy-Fatigue scale, handgrip strength and pulmonary function.

Conclusion: In patients with post-acute COVID-19 syndrome, there was a progressive improvement in quality of life, general fatigue and pulmonary function during the 12 months of follow-up, with this improvement being more pronounced in the first 6 months. There was a relationship between functionality and quality of life in these patients.

Source: de Azevedo Vieira JE, Mafort TT, Monnerat LB, da Cal MS, Ghetti ATA, Lopes AJ. Assessment of short- and long-term functionality and quality of life in patients with post-acute COVID-19 syndrome. J Back Musculoskelet Rehabil. 2023 Feb 2. doi: 10.3233/BMR-220308. Epub ahead of print. PMID: 36776041. https://content.iospress.com/articles/journal-of-back-and-musculoskeletal-rehabilitation/bmr220308 (Full text)

Role of the MicroRNAs in the Pathogenic Mechanism of Painful Symptoms in Long COVID: Systematic Review

Abstract:

The ongoing pandemic of COVID-19 has caused more than 6.7 million tragic deaths, plus, a large percentage of people who survived it present a myriad of chronic symptoms that last for at least 6 months; this has been named as long COVID. Some of the most prevalent are painful symptoms like headache, joint pain, migraine, neuropathic-like pain, fatigue and myalgia. MicroRNAs are small non-coding RNAs that regulate genes, and their involvement in several pathologies has been extensively shown. A deregulation of miRNAs has been observed in patients with COVID-19.
The objective of the present systematic review was to show the prevalence of chronic pain-like symptoms of patients with long COVID and based on the expression of miRNAs in patients with COVID-19, and to present a proposal on how they may be involved in the pathogenic mechanisms of chronic pain-like symptoms.
A systematic review was carried out in online databases for original articles published between March 2020 to April 2022; the systematic review followed the PRISMA guidelines, and it was registered in PROSPERO with registration number CRD42022318992. A total of 22 articles were included for the evaluation of miRNAs and 20 regarding long COVID; the overall prevalence of pain-like symptoms was around 10 to 87%, plus, the miRNAs that were commonly up and downregulated were miR-21-5p, miR-29a,b,c-3p miR-92a,b-3p, miR-92b-5p, miR-126-3p, miR-150-5p, miR-155-5p, miR-200a, c-3p, miR-320a,b,c,d,e-3p, and miR-451a.
The molecular pathways that we hypothesized to be modulated by these miRNAs are the IL-6/STAT3 proinflammatory axis and the compromise of the blood–nerve barrier; these two mechanisms could be associated with the prevalence of fatigue and chronic pain in the long COVID population, plus they could be novel pharmacological targets in order to reduce and prevent these symptoms.
Source: Reyes-Long S, Cortés-Altamirano JL, Bandala C, Avendaño-Ortiz K, Bonilla-Jaime H, Bueno-Nava A, Ávila-Luna A, Sánchez-Aparicio P, Clavijo-Cornejo D, Dotor-LLerena AL, Cabrera-Ruiz E, Alfaro-Rodríguez A. Role of the MicroRNAs in the Pathogenic Mechanism of Painful Symptoms in Long COVID: Systematic Review. International Journal of Molecular Sciences. 2023; 24(4):3574. https://doi.org/10.3390/ijms24043574 https://www.mdpi.com/1422-0067/24/4/3574 (Full text)

Long COVID could become a widespread post-pandemic disease? A debate on the organs most affected

Abstract:

Long COVID is an emerging problem in the current health care scenario. It is a syndrome with common symptoms of shortness of breath, fatigue, cognitive dysfunction, and other conditions that have a high impact on daily life. They are fluctuating or relapsing states that occur in patients with a history of SARS-CoV-2 infection for at least 2 months. They are usually conditions that at 3 months after onset cannot be explained by an alternative diagnosis. Currently very little is known about this syndrome.

A thorough review of the literature highlights that the cause is attributable to deposits of tau protein. Massive phosphorylation of tau protein in response to SARS-CoV-2 infection occurred in brain samples from autopsies of people previously affected with COVID-19. The neurological disorders resulting from this clinical condition are termed tauopathies and can give different pathological symptoms depending on the involved anatomical region of the brain.

Peripheral small-fiber neuropathies are also evident among patients with Long COVID leading to fatigue, which is the main symptom of this syndrome. Certainly more research studies could confirm the association between tau protein and Long COVID by defining the main role of tau protein as a biomarker for the diagnosis of this syndrome that is widespread in the post-pandemic period.

Source: Ferrara, F., Zovi, A., Masi, M. et al. Long COVID could become a widespread post-pandemic disease? A debate on the organs most affected. Naunyn-Schmiedeberg’s Arch Pharmacol (2023). https://doi.org/10.1007/s00210-023-02417-5 https://link.springer.com/article/10.1007/s00210-023-02417-5 (Full text)

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)

Post-Viral Fatigue Following SARS-CoV-2 Infection during Pregnancy: A Longitudinal Comparative Study

Abstract:

Studies reported post-COVID-19 fatigue in the general population, but not among pregnant women. Our objectives were to determine prevalence, duration, and risk factors of post-viral fatigue among pregnant women with SARS-CoV-2.

This study involved 588 pregnant women with SARS-CoV-2 during pregnancy or delivery in Brazil. Three groups were investigated: G1 (n = 259, symptomatic infection during pregnancy); G2 (n = 131, positive serology at delivery); G3 (n = 198, negative serology at delivery). We applied questionnaires investigating fatigue at determined timepoints after infection for G1, and after delivery for all groups; fatigue prevalence was then determined.

Cox regression was used to estimate hazard ratio (HR) and 95% CI of the risk of remaining with fatigue in G1. Overall fatigue prevalence in G1 at six weeks, three months and six months were 40.6%, 33.6%, and 27.8%, respectively. Cumulative risk of remaining with fatigue increased over time, with HR of 1.69 (95% CI: 0.89-3.20) and 2.43 (95% CI: 1.49-3.95) for women with moderate and severe symptoms, respectively.

Multivariate analysis showed cough and myalgia as independent risk factors in G1. Fatigue prevalence was significantly higher in G1 compared to G2 and G3. Post-viral fatigue prevalence is higher in women infected during pregnancy; fatigue’s risk and duration increased with the severity of infection.

Source: Oliveira AMDSS, Carvalho MA, Nacul L, Cabar FR, Fabri AW, Peres SV, Zaccara TA, O’Boyle S, Alexander N, Takiuti NH, Mayaud P, Brizot ML, Francisco RPV. Post-Viral Fatigue Following SARS-CoV-2 Infection during Pregnancy: A Longitudinal Comparative Study. Int J Environ Res Public Health. 2022 Nov 26;19(23):15735. doi: 10.3390/ijerph192315735. PMID: 36497810; PMCID: PMC9737157. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9737157/ (Full text)

The Prevalence, Severity, and Impact of Post-COVID Persistent Fatigue, Post-Exertional Malaise, and Chronic Fatigue Syndrome

Background: Fatigue is common after viral infections, including SARS-CoV-2.1 Our purpose was to report the prevalence and impact of persistent fatigue 6 months after SARS-CoV-2 infection, considering post-exertional malaise2 and criteria for chronic fatigue syndrome.3

Methods: Since March 2020, individuals tested for SARS-CoV-2 at the Geneva University Hospitals outpatient testing center benefit from remote ambulatory follow-up (COVICARE). This study included all individuals tested between March 2020 and December 2020 and whose follow-up was at 6 months or more after their test date.

Follow-up included questions about the prevalence of symptoms (yes/no) and their severity using a Likert scale (mild, moderate, or severe). Fatigue was assessed using the Eastern Cooperative Oncology Group (ECOG) scale and the Chalder fatigue scale. The Chalder fatigue scale was scored using the 4-item Likert and the bimodal scoring schemes. A score of ≥ 4 on bimodal scoring indicated severe fatigue.

The DePaul brief questionnaire was used to identify post-exertional malaise and criteria for chronic fatigue syndrome.

The Sheehan Disability Scale was used to assess functional impairment. Reduced work capacity was defined as missing days off work or having a reduced productivity on the Sheehan disability scale.

Comorbidities were considered present if pre-existing prior to SARS-CoV-2 infection. Statistical analysis included descriptive comparisons of percentages using chi-square tests and Student’s t test.

Results: Overall, 5515 individuals participated in this study (response rate 70.7%), with 5406 participants at 6 months or more after their test date. A total of 1497 (27.7%) participants had a documented positive SARS-CoV-2 test and were ultimately included in the study. The median time for follow-up was 225 days (interquartile range 207–398). Respectively, fatigue was reported by 17.2%, post-exertional malaise by 8.2%, and the presence of criteria for chronic fatigue syndrome by 1.1% of SARS-CoV-2-positive individuals, compared to 8.9%, 3.5%, and 0.5% of SARS-CoV-2-negative individuals. Characteristics are presented in Table 1.

Out of SARS-CoV-2-positive participants with fatigue (n = 258), 35.3% had moderate to severe limitations on the ECOG scale, and 83.0% had a score ≥ 4 on the Chalder fatigue scale. The Chalder fatigue scale revealed a mean score of 19 out of 33, SD 5.4, and a mean score of 6.7 out of 11, SD 3.3 using bimodal scoring. After adjusting for age and sex, 47.7% of SARS-CoV-2-positive individuals with fatigue at 6 months or more had the frequency and severity criteria for post-exertional malaise, and 6.2% had criteria for chronic fatigue syndrome.

Individuals had a higher prevalence of insomnia, cognitive impairment, headaches, generalized pain, functional impairment, reduced work capacity, and decreased physical activity, after SARS-CoV-2 infection. The prevalence of these sequelae was adjusted for age and sex and was increasingly higher with severe fatigue, with post-exertional malaise, or when criteria for chronic fatigue syndrome were present (Fig. 1).

Discussion: Fatigue is the most common and persistent post-COVID symptom. The spectrum of fatigue severity in post-COVID individuals ranges from feeling tired to having severe fatigue, post-exertional malaise, or criteria for chronic fatigue syndrome with an increasing impact on health, functional capacity, and physical activity.

Almost half of individuals experiencing fatigue at 6 months after the infection had post-exertional malaise, and 6.2% had criteria for chronic fatigue syndrome, prompting physicians to consider pacing as a management option, in the absence of other treatment options at this stage. SARS-CoV-2 infection was positively associated with fatigue and post-exertional malaise.

Results showed that individuals with fatigue were more likely to be vaccinated. This was partially explained by the baseline distribution as older individuals and those with more comorbidities were more likely to get vaccinated.

Results compare to recent reviews showing an overlap between post-COVID condition and chronic fatigue syndrome. Our study graded post-COVID fatigue by severity in correlation with functional capacity, and showed the high prevalence of post-exertional malaise.

Limitations include the self-reported nature of this follow-up with individuals infected in 2020 and follow-up in 2021, lacking comparisons to individuals infected with other variants. Additionally, this study considered having received at least 2 doses as full vaccination, a concept that continues to evolve with time.

Physicians, employers, and insurance companies should address fatigue on a spectrum, accounting for the correlated functional impairment, decreased activity levels, and potentially poorer quality of life.

Source: Nehme M, Chappuis F, Kaiser L, Assal F, Guessous I. The Prevalence, Severity, and Impact of Post-COVID Persistent Fatigue, Post-Exertional Malaise, and Chronic Fatigue Syndrome. J Gen Intern Med. 2022 Nov 10:1–5. doi: 10.1007/s11606-022-07882-x. Epub ahead of print. PMID: 36357723; PMCID: PMC9648889. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9648889/ (Full text)

 

Long-COVID in patients with a history of mild or asymptomatic SARS-CoV-2 infection: a Nationwide Cohort Study

Abstract:

Objective: Evaluating the prevalence of long-COVID symptoms in patients with a history of mild or asymptomatic infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and the factors associated with developing long-COVID.

Design: A nationwide cohort study. Using a centralized database, we have identified patients with and without a history of SARS-CoV-2 infection 1-6 months before data collection. Patients were asked to fill out an online questionnaire through text messages.

Setting: Israeli general practice.

Subjects: 2755 persons participated in the study in September 2021 (a response rate of 7.5%): 819 with and ,936 without a history of SARS-CoV-2 infection.

Main outcome measures: We asked patients to provide details about their demographic status, medical history, COVID-related variables and the presence of long-COVID symptoms.

Results: Most prevalent long-COVID symptoms were decreased smell sensation (35.1% vs. 4.3%, p < 0.001), decreased taste sensation (25.2% vs. 3.2%, p < 0.001), memory disturbances (36.9% vs. 14.4%, p < 0.001), dyspnea (24.2% vs. 10.7%, p < 0.001) and arthralgia (33% vs. 16.3%, p < 0.001). Risk factors associated with long-COVID included female gender, symptomatic COVID-19, overweight or obesity and the presence of dyslipidemia. About 34.6% of participants reported not returning to their baseline health condition after the acute illness.

Conclusion: Long-COVID is frequently seen following a mild symptomatic COVID-19 infection and, to a lesser extent, following an asymptomatic SARS-CoV-2 infection. Primary care physicians should be aware of these symptoms and consider this option in their differential diagnosis. Health policymakers should expect a significant impact of this syndrome on public health.

Key Points

Long-COVID has emerged as a significant health problem with a serious impact on normal daily function• Long-COVID symptoms were evident in patients with mild symptomatic disease and in asymptomatic patients to a lesser extent.• Risk factors for having Long-COVID symptoms include female gender, symptomatic disease, increased BMI, and the presence of dyslipidemia.• Fatigue, dyspnea, weakness, decreased libido, weight changes, memory, and sleep disturbances were associated with not returning to the baseline health state.

Source: Adler L, Gazit S, Pinto Y, Perez G, Mizrahi Reuveni M, Yehoshua I, Hoffman R, Azuri J, Patalon T. Long-COVID in patients with a history of mild or asymptomatic SARS-CoV-2 infection: a Nationwide Cohort Study. Scand J Prim Health Care. 2022 Oct 31:1-8. doi: 10.1080/02813432.2022.2139480. Epub ahead of print. PMID: 36314555. https://www.tandfonline.com/doi/full/10.1080/02813432.2022.2139480 (Full text)

Cross-sectional analysis of clinical aspects in patients with long-COVID and post-COVID syndrome

Abstract:

Objective: Regarding pathogenesis, clinical manifestations, at-risk individuals, and diagnostic methods for stratifying patients for therapeutic approaches, our understanding of post-COVID syndrome is limited. Here, we set out to assess sociodemographic and clinical aspects in patients with the long-COVID and post-COVID syndrome.

Methods: We performed a cross-sectional analysis of patients presenting at our specialized university hospital outpatient clinic. We assessed patients’ clinical presentation, fatigue, symptoms of depression and anxiety, and impairment of smell.

Results: A total of 101 patients were included (73.3% female), of whom 78.2% had a mild course of COVID-19. At presentation, 93.1% suffered from fatigue, 82.2% from impaired concentration, and 79.2% from impaired memory, 53.5% had impaired sleep. The most common secondary diagnosis found in our cohort was thyroid disease. Fatigue analysis showed that 81.3% of female and 58.8% of male patients had severe combined fatigue. Female gender was an independent risk factor for severe fatigue (severe cognitive fatigue OR = 8.045, p = 0.010; severe motor fatigue OR = 7.698, p = 0.013). Males suffered from more depressive symptoms, which correlated positively with the duration of symptom onset. 70.3% of patients with anamnestic smell impairment had hyposmia, and 18.9% were anosmic.

Interpretation: Most long-COVID patients suffered from severe fatigue, with the female sex as an independent risk factor. Fatigue was not associated with symptoms of depression or anxiety. Patients with long-COVID symptoms should receive an interdisciplinary diagnostic and therapeutic approach depending on the clinical presentation.

Source: Schulze H, Charles James J, Trampe N, Richter D, Pakeerathan T, Siems N, Ayzenberg I, Gold R, Faissner S. Cross-sectional analysis of clinical aspects in patients with long-COVID and post-COVID syndrome. Front Neurol. 2022 Oct 14;13:979152. doi: 10.3389/fneur.2022.979152. PMID: 36313487; PMCID: PMC9614029. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9614029/ (Full text)

Post-Viral Fatigue in COVID-19: A Review of Symptom Assessment Methods, Mental, Cognitive, and Physical Impairment

Abstract:

Coronavirus 2 is responsible for Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2), and the main sequela is persistent fatigue. Post-viral fatigue is common and affects patients with mild, asymptomatic coronavirus disease-2019 (COVID-19). However, the exact mechanisms involved in developing post-COVID-19 fatigue remain unclear. Furthermore, physical and cognitive impairments in these individuals have been widely described. Therefore, this review aims to summarize and propose tools from a multifaceted perspective to assess COVID-19 infection.

Herein, we point out the instruments that can be used to assess fatigue in long-term COVID-19: fatigue in a subjective manner or fatigability in an objective manner. For physical and mental fatigue, structured questionnaires were used to assess perceived symptoms, and physical and cognitive performance assessment tests were used to measure fatigability using reduced performance.

Source: Campos MC, Nery T, Starke AC, de Bem Alves AC, Speck AE, Junior ASA. Post-Viral Fatigue in COVID-19: A Review of Symptom Assessment Methods, Mental, Cognitive, and Physical Impairment. Neurosci Biobehav Rev. 2022 Oct 3:104902. doi: 10.1016/j.neubiorev.2022.104902. Epub ahead of print. PMID: 36202253; PMCID: PMC9528075. https://www.sciencedirect.com/science/article/pii/S0149763422003918 (Full text)

Myopathy as a cause of fatigue in long-term post-COVID-19 symptoms: Evidence of skeletal muscle histopathology

Abstract:

Background: Among post-COVID-19 symptoms, fatigue is reported as one of the most common, even after mild acute infection, and as the cause of fatigue, myopathy diagnosed by electromyography has been proposed in previous reports. This study aimed to explore the histopathological changes in patients with post-COVID-19 fatigue.

Methods: Sixteen patients (mean age:46 years) with post-COVID-19 complaints of fatigue, myalgia or weakness persisting for up to 14 months were included. In all patients, quantitative electromyography and muscle biopsies analysed with light and electron microscopy were taken.

Results: Muscle weakness was present in 50%, myopathic electromyography in 75% while in all patients, there were histological changes. Muscle fiber atrophy was found in 38%, and 56% showed indications of fiber regeneration. Mitochondrial changes, comprising loss of COX activity, subsarcollemmal accumulation and/or abnormal cristae, were present in 62%. Inflammation was found in 62%, seen as T-lymphocytes and/or muscle fiber HLA-ABC expression. In 75%, capillaries were affected involving basal lamina and cells. In two patients, uncommon amounts of basal lamina were found, not only surrounding muscle fibers but also around nerves and capillaries.

Conclusions: The wide variety of histological changes in this study suggest that skeletal muscles may be a major target of SARS-CoV-2 causing muscular post-COVID-19 symptoms. The mitochondrial changes, inflammation and capillary injury in muscle biopsies can cause fatigue in part due to reduced energy supply. Since most patients had mild-moderate acute affection, the new variants that might cause less severe acute disease could still have the ability to cause long-term myopathy.

Source: Hejbøl EK, Harbo T, Agergaard J, Madsen LB, Pedersen TH, Østergaard LJ, Andersen H, Schrøder HD, Tankisi H. Myopathy as a cause of fatigue in long-term post-COVID-19 symptoms: Evidence of skeletal muscle histopathology. Eur J Neurol. 2022 Jun 6. doi: 10.1111/ene.15435. Epub ahead of print. PMID: 35661354.  https://pubmed.ncbi.nlm.nih.gov/35661354/ https://pubmed.ncbi.nlm.nih.gov/35661354/ (Full text available as PDF file)