Tag: long covid symptoms

Role of Tau protein in long COVID and potential therapeutic targets

Abstract:

Introduction: Long COVID is an emerging public health burden and has been defined as a syndrome with common symptoms of fatigue, shortness of breath, cognitive dysfunction, and others impacting day-to-day life, fluctuating or relapsing over, occurring for at least two months in patients with a history of probable or confirmed SARS CoV-2 infection; usually three months from the onset of illness and cannot be explained by an alternate diagnosis. The actual prevalence of long-term COVID-19 is unknown, but it is believed that more than 17 million patients in Europe may have suffered from it during pandemic.

Pathophysiology: Currently, there is limited understanding of the pathophysiology of this syndrome, and multiple hypotheses have been proposed. Our literature review has shown studies reporting tau deposits in tissue samples of the brain from autopsies of COVID-19 patients compared to the control group, and the in-vitro human brain organoid model has shown aberrant phosphorylation of tau protein in response to SARS-CoV-2 infection. Tauopathies, a group of neurodegenerative disorders with the salient features of tau deposits, can manifest different symptoms based on the anatomical region of brain involvement and have been shown to affect the peripheral nervous system as well and explained even in rat model studies.

Long COVID has more than 203 symptoms, with predominant symptoms of fatigue, dyspnea, and cognitive dysfunction, which tauopathy-induced CNS and peripheral nervous system dysfunction can explain. There have been no studies up till now to reveal the pathophysiology of long COVID. Based on our literature review, aberrant tau phosphorylation is a promising hypothesis that can be explored in future studies.

Therapeutic approaches for tauopathies have multidimensional aspects, including targeting post-translational modifications, tau aggregation, and tau clearance through the autophagy process with the help of lysosomes, which can be potential targets for developing therapeutic interventions for the long COVID. In addition, future studies can attempt to find the tau proteins in CSF and use those as biomarkers for the long COVID.

Source: Marwaha B. Role of Tau protein in long COVID and potential therapeutic targets. Front Cell Infect Microbiol. 2023 Oct 25;13:1280600. doi: 10.3389/fcimb.2023.1280600. PMID: 37953801; PMCID: PMC10634420. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10634420/ (Full text)

Post-COVID-19 and Irritable Bowel Syndrome: A Literature Review

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The emergence of post-COVID-19 syndrome (PCS), a complex and multifactorial condition that follows the acute COVID-19 infection, has raised serious concerns within the global medical community. Concurrently, Irritable Bowel Syndrome (IBS), a widespread chronic gastrointestinal (GI) dysfunction, is considered to be one of the most common disorders of gut–brain interaction (DGBI) that significantly affects the quality of life and social functioning of patients. PCS presents a wide range of symptoms and GI manifestations, including IBS.
This review aims to analyze the GI involvement and the prolonged symptoms of COVID-19 infection as part of PCS, in order to explore the potential development of post-infection IBS (PI-IBS) in COVID-19 patients. Irritating factors such as enteric infection, psychosocial conditions, food antigens, and antibiotics may lead to abnormalities in the physiological function of the GI system and could be involved in the development of PI-IBS. Through the presentation of the pathophysiological mechanisms and epidemiological studies that assessed the prevalence of IBS as part of PCS, we attempted to provide a better understanding of the long-term consequences of COVID-19 and the pathogenesis of PI-IBS.
Even though PI-IBS is becoming a global challenge, there are only a few studies about it and therefore limited knowledge. Currently, the majority of the existing treatment options are referred to non-COVID-19-associated DGBIs. Forthcoming studies may shed light on the mechanisms of PI-IBS that could be targeted for treatment development. Paramythiotis D, Karlafti E, Didagelos M, Fafouti M, Veroplidou K, Protopapas AA, Kaiafa G, Netta S, Michalopoulos A, Savopoulos C. Post-COVID-19 and Irritable Bowel Syndrome: A Literature Review. Medicina. 2023; 59(11):1961. https://doi.org/10.3390/medicina59111961 https://www.mdpi.com/1648-9144/59/11/1961 (Full text)
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Analysis of the correlation between heart rate variability and palpitation symptoms in female patients with long COVID

Abstract:

Objectives: To analyze the correlation between heart rate variability (HRV) and palpitation symptoms in female patients with long COVID.

Methods: A total of 272 female healthcare workers who were infected with SARS-CoV-2 for the first time in December 2022 at Fuzhou First Hospital affiliated with Fujian Medical University, were selected as study subjects. These subjects were divided into three groups based on their symptoms: a group with palpitations (70 cases), a group without palpitations but with other symptoms (124 cases), and a group consisting of asymptomatic cases (78 cases). The study compared the general information, COMPASS-31 scores, quality of life scores, and HRV parameters among the three groups. Furthermore, it analyzed the factors influencing palpitation symptoms in female patients with long COVID.

Results: Compared to the other two groups, the HRV parameters SDNN, HRVIndex, LF, and TP were significantly reduced in the group with palpitations (p < 0.05). Multivariate analysis revealed that HRVIndex (p = 0.016; OR: 0.966, 95% CI: 0.940∼0.994) had a significant impact on palpitation symptoms in female patients with long COVID.

Conclusions: The symptoms of palpitations in female patients with long COVID were found to be related to HRV parameters. Autonomic dysfunction may be connected to the occurrence of palpitation symptoms in long COVID.

Source: Jiang Yu, Cheng Yan, Xiao Jingwen, Wang Yicheng, Chen Geng, Zhang Yan. Analysis of the correlation between heart rate variability and palpitation symptoms in female patients with long COVID. Frontiers in Cardiovascular Medicine, 10, 2023 DOI=10.3389/fcvm.2023.1273156 ISSN=2297-055X  https://www.frontiersin.org/articles/10.3389/fcvm.2023.1273156 (Full text)

Long COVID with Persistent High Fever as the Main Manifestation: A Case Report

Abstract:

Background COVID-19, caused by SARS-CoV-2, has had a profound global impact, affecting millions of people. Long COVID, also known as Post-Acute Sequelae of SARS-CoV-2 infection (PASC), is characterized by persistent symptoms following acute COVID-19, affecting more than 65 million individuals worldwide. In this case report, we highlight a rare occurrence of Long COVID with high fever, underlining its clinical significance.

Case presentation A 34-year-old female with a 24-day history of recurrent fever, initially reaching 37.5°C, accompanied by headache, fatigue, and joint pain, was admitted with a diagnosis of “fever of unknown origin.” Extensive testing, including negative nucleic acid tests for the novel coronavirus, negative blood cultures, and normal imaging, prompted the use of blood Next-Generation Sequencing (NGS) to detect COVID-19. Despite repeated negative nucleic acid tests, elevated COVID-19 antibody levels indicated the presence of long COVID. Methylprednisolone was administered, resulting in the resolution of symptoms. The patient remained asymptomatic during the follow-up.

Source: Chuangsen Fang, Liangliang Zheng, Ao Li et al. Long COVID with Persistent High Fever as the Main Manifestation: A Case Report, 06 November 2023, PREPRINT (Version 1) available at Research Square [https://doi.org/10.21203/rs.3.rs-3506143/v1] https://www.researchsquare.com/article/rs-3506143/v1 (Full text)

Beyond the acute illness: Exploring long COVID and its impact on multiple organ systems

Abstract:

Unprecedented worldwide health catastrophe due to the COVID-19 pandemic has ended up resulting in high morbidity and mortality rates. Even though many people recover from acute infection, there is rising concern regarding post-COVID-19 conditions (PCCs), often referred to as post-acute sequelae of SARS-CoV-2 infection (PASC) or “long COVID.”

The respiratory, cardiovascular, neurological, and endocrine systems are just a few of the many organ systems that can be impacted by this multifarious, complicated illness. The clinical manifestations of long COVID can vary among individuals and may include fatigue, dyspnea, chest pain, cognitive impairment, and new-onset diabetes, among others.

Although the underlying processes of long COVID are not fully understood, they probably involve unregulated immune response, persistent generation of pro-inflammatory cytokines (chronic inflammation), autoimmune-like reactions, persistent viral replication, and micro-clot formation.

To create successful treatments and care plans, it is essential to comprehend the immunological mechanisms causing these difficulties. The pathogenesis of long COVID should be clarified and potential biomarkers to help with diagnosis and treatment should be sought after. To reduce the burden of long COVID on people and healthcare systems around the world, the need for long-term monitoring and management of long COVID problems should be emphasized. It also underscores the significance of a multidisciplinary approach to patient care. The goal of this review is to carefully evaluate the clinical signs and symptoms of long COVID, their underlying causes, and any potential immunological implications.

Source: Bhattacharjee N, Sarkar P, Sarkar T. Beyond the acute illness: Exploring long COVID and its impact on multiple organ systems. Physiol Int. 2023 Nov 9. doi: 10.1556/2060.2023.00256. Epub ahead of print. PMID: 37943302. https://akjournals.com/view/journals/2060/aop/article-10.1556-2060.2023.00256/article-10.1556-2060.2023.00256.xml (Full text)

Association between SARS-CoV-2 variants and post COVID-19 condition: findings from a longitudinal cohort study in the Belgian adult population

Abstract:

Background: While many studies on the determinants of post-COVID-19 conditions (PCC) have been conducted, little is known about the relationship between SARS-CoV-2 variants and PCC. This study aimed to assess the association between different SARS-CoV-2 variants and the probability of having PCC three months after the infection.

Methods: This study was a longitudinal cohort study conducted between April 2021 and September 2022 in Belgium. In total, 8,238 adults with a confirmed SARS-CoV-2 infection were followed up between the time of their infection and three months later. The primary outcomes were the PCC status three months post infection and seven PCC symptoms categories (neurocognitive, autonomic, gastrointestinal, respiratory, musculoskeletal, anosmia and/or dysgeusia, and other manifestations). The main exposure variable was the type of SARS-CoV-2 variants (i.e. Alpha, Delta, and Omicron), extracted from national surveillance data. The association between the different SARS-CoV-2 variants and PCC as well as PCC symptoms categories was assessed using multivariable logistic regression.

Results: The proportion of PCC among participants infected during the Alpha, Delta, and Omicron-dominant periods was significantly different and respectively 50%, 50%, and 37%. Participants infected during the Alpha- and Delta-dominant periods had a significantly higher odds of having PCC than those infected during the Omicron-dominant period (OR = 1.61, 95% confidence interval [CI] = 1.33-1.96 and OR = 1.73, 95%CI = 1.54-1.93, respectively). Participants infected during the Alpha and Delta-dominant periods were more likely to report neurocognitive, respiratory, and anosmia/dysgeusia symptoms of PCC.

Conclusions: People infected during the Alpha- and Delta-dominant periods had a higher probability of having PCC three months after infection than those infected during the Omicron-dominant period. The lower probability of PCC with the Omicron variant must also be interpreted in absolute figures. Indeed, the number of infections with the Omicron variant being higher than with the Alpha and Delta variants, it is possible that the overall prevalence of PCC in the population increases, even if the probability of having a PCC decreases.

Source: Thi Khanh HN, Cornelissen L, Castanares-Zapatero D, De Pauw R, Van Cauteren D, Demarest S, Drieskens S, Devleesschauwer B, De Ridder K, Charafeddine R, Smith P. Association between SARS-CoV-2 variants and post COVID-19 condition: findings from a longitudinal cohort study in the Belgian adult population. BMC Infect Dis. 2023 Nov 8;23(1):774. doi: 10.1186/s12879-023-08787-8. PMID: 37940843; PMCID: PMC10634063. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10634063/ (Full text)

Decreased Pulmonary Blood Flow and Airway Volumes in Patients With Long COVID Syndrome Assessed by Functional Respiratory Imaging

Abstract:

Introduction: In contrast to normal chest X-ray, lung computed tomography (CT), and physiological lung and cardiac functions, many patients with long COVID syndrome suffer from shortness of breath.

Hypothesis: The aim of this study was to quantify the pulmonary blood and airway volumes of long COVID patients compared with that of healthy controls.

Methods: Patients with long COVID syndromes were included if they had PCR-verified previous (≥3 months) SARS-CoV-2 infection, had normal laboratory (e.g. inflammation, coagulation, cardiac or other organ) parameter, normal pulmonary morphology (chest X-ray and CT) and function (spirometry and body plethysmography). The lung CT images were postprocessed by Functional Respiratory imaging analysis by using 3D reconstruction with automated lung vessel segmentation algorithm. Data of the quantitative images were compared with age, gender, and BMI-matched healthy controls.

Results: Thirty patients (45±13 years, 37% male, 25.9±4.3 kg/m^2) at a median time of 256 (118-574) days after a confirmed COVID infection and 30 healthy controls (55±7y, 37% male, 26.3±2.7 kg/m^2) were included. All long COVID patients complained of dyspnoea and 14 (48.3%) patients reported thoracic pain. The total pulmonary blood volume was significantly lower in the long COVID patients compared to controls (190±24.3 mL/m^2 vs230.6±26.2 ml/m^2, p<0.001). Similarly, the capillary-small vessel blood flow (vessel cross sectional area <5 mm^2) was reduced in the long COVID population (118±19 mL vs 132±23 mL, p=0.011). (Figure). The specific image-based airway volume of the distal lung regions was lower than that of the healthy population (11.1±6.74 mL vs 17.33±7.7 mL, p<0.05).

Conclusions: Both the reduced global and capillary pulmonary blood flow, and distal airway volumes indicate impaired gas exchange and might explain the pulmonary complaints of patient with long COVID syndromes even severe months after Coronavirus infection.

Source: Mariann Gyongyosi, Emilie Han, Dominika Lukovic, Eslam Samaha, Jutta K Bergler-Klein and Ena Hasimbegovic. Decreased Pulmonary Blood Flow and Airway Volumes in Patients With Long COVID Syndrome Assessed by Functional Respiratory Imaging. Originally published6 Nov 2023Circulation. 2023;148:A16513 https://www.ahajournals.org/doi/abs/10.1161/circ.148.suppl_1.16513

Correlations of Long COVID Symptoms and Inflammatory Markers of Complete Blood Count (CBC): A cross-sectional study

Abstract:

Background: Long-COVID refers to lasting unspecific symptoms like fatigue, decreased concentration and sleep issues after infection which persist for at least three months and cannot be attributed to other causes. Previous studies surveyed the association between inflammatory markers like C – reactive protein (CRP) at hospital admission and long-COVID symptoms in the preceding months. Post-COVID syndrome can affect one-third of patients. Thus early diagnosis can assist in reducing burdens on public health. We attempted to see any correlations between complete blood count (CBC) markers (like red blood cell (RBC), white blood cell (WBC), Neutrophil to lymphocyte ratio (NLR), etc.) at hospital admission and long COVID symptoms at a 6-month follow-up.

Methods: 167 patients (44.9% females, mean age 49 years old) answered semi-structural interviews through telemedicine which focused on the three prominent symptoms: fatigue, loss of concentration and decreased libido.

Results: Two third of patients have symptoms of long COVID and others do not have. NLR in the symptomatic group was statically higher. Patients who underwent decreased libido at a 6-month follow-up had significantly more severe lymphopenia (p ¼ 0.028) and higher NLR values (p-value ¼ 0.007). Poor mental concentration is associated with high WBC in numbers and polymorphonuclear (PMN) count. Other symptoms do not correlate with blood markers.

Conclusion: Utilizing available data like CBC can help predict the upcoming symptoms of previously hospitalized patients and further measures like rehabilitation. Additional investigations should be done on the

Source: Radkhah, Hanieh; Omidali, Mehrnia; Hejrati, Alireza; Bahri, Razman Arabzadeh; Arefi, Sara; Behzadi, Amirhossein; Eslami, Mohamad; Khadembashiri, Mohammadmehdi; Khadembashiri, Mohammadamin; Najafirashed, Maryam; and Amiri, Bahareh Shateri (2023) “Correlations of Long COVID Symptoms and Inflammatory Markers of Complete Blood Count (CBC): A cross-sectional study.,” Journal of Community Hospital Internal Medicine Perspectives: Vol. 13: Iss. 6, Article 25. DOI: 10.55729/2000-9666.1259 https://scholarlycommons.gbmc.org/cgi/viewcontent.cgi?article=1259&context=jchimp (Full text)

Examining the relationship between inflammatory biomarkers during COVID-19 hospitalization and subsequent long-COVID symptoms: A longitudinal and retrospective study

Abstract:

Introduction: Long-COVID is a heterogeneous condition with a litany of physical and neuropsychiatric presentations and its pathophysiology remains unclear. Little is known about the association between inflammatory biomarkers, such as interleukin-6 (IL-6) and C-reactive protein (CRP) in the acute phase, and persistent symptoms after hospitalization in COVID-19 patients.

Methods: IL-6, CRP, troponin-T, and ferritin were analyzed at admission for all patients with COVID-19 between September 1, 2020 to January 10, 2021. Survivors were followed up 3-months following hospital discharge and were asked to report persistent symptoms they experienced. Admission data were retrospectively collected. Independent t-tests and Mann-Whitney U tests were performed.

Results: In a sample of 144 patients (62.5% male, mean Age 62 years [SD = 13.6]) followed up 3 months after hospital discharge, the commonest symptoms reported were fatigue (54.2%), breathlessness (52.8%), and sleep disturbance (37.5%). In this sample, admission levels of IL-6, CRP and ferritin were elevated. However, those reporting myalgia, low mood, and anxiety at follow-up had lower admission levels of IL-6 (34.9 vs. 52.0 pg/mL, p = .043), CRP (83 vs. 105 mg/L, p = .048), and ferritin (357 vs. 568 ug/L, p = .01) respectively, compared with those who did not report these symptoms. Multivariate regression analysis showed that these associations were confounded by gender, as female patients had significantly lower levels of IL-6 and ferritin on admission (29.5 vs. 56.1, p = .03 and 421.5 vs. 589, p = .001, respectively) and were more likely to report myalgia, low mood and anxiety, when compared to males.

Conclusions: Our data demonstrate that female patients present more often with lower levels of inflammatory biomarkers on admission which are subsequently associated with long-term post-COVID symptoms, such as myalgia and anxiety, in those discharged from hospital with severe COVID-19. Further research is needed into the role of serum biomarkers in post-COVID prognostication.

Source: Sykes DL, Van der Feltz-Cornelis CM, Holdsworth L, Hart SP, O’Halloran J, Holding S, Crooks MG. Examining the relationship between inflammatory biomarkers during COVID-19 hospitalization and subsequent long-COVID symptoms: A longitudinal and retrospective study. Immun Inflamm Dis. 2023 Oct;11(10):e1052. doi: 10.1002/iid3.1052. PMID: 37904690; PMCID: PMC10614127. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10614127/ (Full text)

Core outcome measurement instruments for use in clinical and research settings for adults with post-COVID-19 condition: an international Delphi consensus study

Abstract:

Post-COVID-19 condition (also known as long COVID) is a new, complex, and poorly understood disorder. A core outcome set (COS) for post-COVID-19 condition in adults has been developed and agreement is now required on the most appropriate measurement instruments for these core outcomes.

We conducted an international consensus study involving multidisciplinary experts and people with lived experience of long COVID. The study comprised a literature review to identify measurement instruments for the core outcomes, a three-round online modified Delphi process, and an online consensus meeting to generate a core outcome measurement set (COMS). 594 individuals from 58 countries participated.

The number of potential instruments for the 12 core outcomes was reduced from 319 to 19. Consensus was reached for inclusion of the modified Medical Research Council Dyspnoea Scale for respiratory outcomes. Measures for two relevant outcomes from a previously published COS for acute COVID-19 were also included: time until death, for survival, and the Recovery Scale for COVID-19, for recovery. Instruments were suggested for consideration for the remaining nine core outcomes: fatigue or exhaustion, pain, post-exertion symptoms, work or occupational and study changes, and cardiovascular, nervous system, cognitive, mental health, and physical outcomes; however, consensus was not achieved for instruments for these outcomes.

The recommended COMS and instruments for consideration provide a foundation for the evaluation of post-COVID-19 condition in adults, which should help to optimise clinical care and accelerate research worldwide. Further assessment of this COMS is warranted as new data emerge on existing and novel measurement instruments.

Source: Gorst SL, Seylanova N, Dodd SR, Harman NL, O’Hara M, Terwee CB, Williamson PR, Needham DM, Munblit D, Nicholson TR; PC-COS study group. Core outcome measurement instruments for use in clinical and research settings for adults with post-COVID-19 condition: an international Delphi consensus study. Lancet Respir Med. 2023 Nov 2:S2213-2600(23)00370-3. doi: 10.1016/S2213-2600(23)00370-3. Epub ahead of print. PMID: 37926103. https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(23)00370-3/fulltext (Full text)