Tag: long covid symptoms

Incidence of long-term post-acute sequelae of SARS-CoV-2 infection related to pain and other symptoms: A systematic review and meta-analysis

Abstract:

Background: Persistent symptoms are reported in patients who survive the initial stage of COVID-19, often referred to as “long COVID” or “post-acute sequelae of SARS-CoV-2 infection” (PASC); however, evidence on their incidence is still lacking, and symptoms relevant to pain are yet to be assessed.

Methods: A literature search was performed using the electronic databases PubMed, EMBASE, Scopus, and CHINAL and preprint servers MedRχiv and BioRχiv through January 15, 2021. The primary outcome was pain-related symptoms such as headache or myalgia. Secondary outcomes were symptoms relevant to pain (depression or muscle weakness) and symptoms frequently reported (anosmia and dyspnea). Incidence rates of symptoms were pooled using inverse variance methods with a DerSimonian-Laird random-effects model. The source of heterogeneity was explored using meta-regression, with follow-up period, age and sex as covariates.

Results: In total, 38 studies including 19,460 patients were eligible. Eight pain-related symptoms and 26 other symptoms were identified. The highest pooled incidence among pain-related symptoms was chest pain (17%, 95% confidence interval [CI], 11%-24%), followed by headache (16%, 95% CI, 9%-27%), arthralgia (13%, 95% CI, 7%-24%), neuralgia (12%, 95% CI, 3%-38%) and abdominal pain (11%, 95% CI, 7%-16%). The highest pooled incidence among other symptoms was fatigue (44%, 95% CI, 32%-57%), followed by insomnia (27%, 95% CI, 10%-55%), dyspnea (26%, 95% CI, 17%-38%), weakness (25%, 95% CI, 8%-56%) and anosmia (19%, 95% CI, 13%-27%). Substantial heterogeneity was identified (I2, 50-100%). Meta-regression analyses partially accounted for the source of heterogeneity, and yet, 53% of the symptoms remained unexplained.

Conclusions: The current meta-analysis may provide a complete picture of incidence in PASC. It remains unclear, however, whether post-COVID symptoms progress or regress over time or to what extent PASC are associated with age or sex.

Source: Hoshijima H, Mihara T, Seki H, Hyuga S, Kuratani N, Shiga T. Incidence of long-term post-acute sequelae of SARS-CoV-2 infection related to pain and other symptoms: A systematic review and meta-analysis. PLoS One. 2023 Nov 29;18(11):e0250909. doi: 10.1371/journal.pone.0250909. PMID: 38019841; PMCID: PMC10686440. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10686440/ (Full text)

Molecular Mechanisms Involved in the Occurrence and Progression of Long COVID and Associated Analysis Techniques

Abstract:

Long COVID, also known as post-acute sequelae of SARS-CoV-2 infection (PASC), has emerged as a significant health concern following the COVID-19 pandemic. Molecular mechanisms underlying the occurrence and progression of long COVID include viral persistence, immune dysregulation, endothelial dysfunction, and neurological involvement, and highlight the need for further research to develop targeted therapies for this condition.
While a clearer picture of the clinical symptomatology is shaping, many molecular mechanisms are yet to be unraveled, given their complexity and high level of interaction with other metabolic pathways. This review summarizes some of the most important symptoms and associated molecular mechanisms that occur in long COVID, as well as the most relevant molecular techniques that can be used in understanding the viral pathogen, its affinity towards the host and the possible outcomes of host-pathogen interaction.
Source: Constantinescu-Bercu, A.; Lobiuc, A.; Caliman Sturdza, O.A.; Oita, R.; Iavorschi, M.; Paval, N.; Soldanescu, I.; Dimian, M.; Covasa, M. Molecular Mechanisms Involved in the Occurrence and Progression of Long COVID and Associated Analysis Techniques. Preprints 2023, 2023111865. https://doi.org/10.20944/preprints202311.1865.v1 https://www.preprints.org/manuscript/202311.1865/v1 (Full text available as PDF file)

Exploring the Influence of VDR Genetic Variants TaqI, ApaI, and FokI on COVID-19 Severity and Long-COVID-19 Symptoms

Abstract:

There is increasing evidence regarding the importance of vitamin D in the prognosis of coronavirus disease 2019 (COVID-19). Genetic variants in the vitamin D receptor (VDR) gene affect the response to vitamin D and have been linked to various diseases. This study investigated the associations of the major VDR genetic variants ApaI, FokI, and TaqI with the severity and long post-infection symptoms of COVID-19. In total, 100 Jordanian patients with confirmed COVID-19 were genotyped for the VDR ApaI, FokI, and TaqI variants using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method.
COVID-19 severity, the most commonly reported long-COVID-19 symptoms that lasted for >4 weeks from the onset of infection, and other variables were analyzed according to VDR genetic variants. In this study, ApaI and FokI polymorphisms showed no significant associations with COVID-19 severity (p > 0.05). However, a significant association was detected between the TaqI polymorphism and the severity of symptoms after infection with the SARS-CoV-2 virus (p = 0.04). The wild-type TaqI genotype was typically present in patients with mild illness, whereas the heterozygous TaqI genotype was present in asymptomatic patients.
With regard to long-COVID-19 symptoms, the VDR heterozygous ApaI and wild-type TaqI genotypes were significantly associated with persistent fatigue and muscle pain after COVID-19 (p ˂ 0.05). Most carriers of the heterozygous ApaI genotype and carriers of the wild-type TaqI genotype reported experiencing fatigue and muscle pain that lasted for more than 1 month after the onset of COVID-19. Furthermore, the TaqI genotype was associated with persistent shortness of breath after COVID-19 (p = 0.003). Shortness of breath was more common among individuals with homozygous TaqI genotype than among individuals with the wild-type or heterozygous TaqI genotype.
VDR TaqI is a possible genetic variant related to both COVID-19 severity and long-COVID-19 symptoms among Jordanian individuals. The associations between VDR TaqI polymorphisms and long-COVID-19 symptoms should be investigated in larger and more diverse ethnic populations.
Source: Alhammadin G, Jarrar Y, Madani A, Lee S-J. Exploring the Influence of VDR Genetic Variants TaqI, ApaI, and FokI on COVID-19 Severity and Long-COVID-19 Symptoms. Journal of Personalized Medicine. 2023; 13(12):1663. https://doi.org/10.3390/jpm13121663 https://www.mdpi.com/2075-4426/13/12/1663 (Full text)

Long Covid Clinical Severity Types Based on Symptoms and Functional Disability: A Longitudinal Evaluation

Abstract:

Background: Long Covid (LC) is a multisystem clinical syndrome with Functional Disability (FD) and compromised Overall Health (OH). There is a lack of distinct clinical symptom clusters (phenotypes) identified in LC so far but there is emerging information on LC clinical severity types. This study explores the consistency of these clinical severity types over time and the relationship between Symptom Severity (SS), FD, and OH in the context of the clinical severity types in a prospective sample.

Methods: A purposive sample of LC patients recruited to the LOng COvid Multidisciplinary consortium Optimising Treatments and servIces acrOss the NHS (LOCOMOTION) study were assessed using the modified COVID-19 Yorkshire Rehabilitation Scale (C19-YRSm) at two assessment time points. A cluster analysis for clinical severity types was undertaken at both time points using k-means partition using two, three, and four initial clusters and different starting values. Cluster analysis was also carried out to assess the presence of symptom phenotypes (symptom clusters).

Findings: Cross-sectional data was available for 759 patients with 356 patients completing C19-YRSm at the two assessment points. Mean age was 46·8 years (SD = 12·7), 69·4% were females, and median duration of LC symptoms at first assessment was 360 days (IQR 217 to 703 days). Cluster analysis revealed three distinct SS and FD clinical severity types – mild (N=96), moderate (N=422), and severe (N=241) – with no distinct symptom phenotypes. The three-level clinical severity pattern remained consistent over time between the two assessments, with 51% of patients switching the clinical severity type between the assessments. The fluctuation was independent of the LC severity and time between the assessments.

Interpretation: This is the first study in the literature to show the consistency of the three clinical severity types over time with patients also switching between severity types indicating the fluctuating nature of LC.

Source: Sivan, Manoj and Smith, Adam B. and Osborne, Thomas and Goodwin, Madeline and Lawrence, Román Rocha and Baley, Sareeta and Williams, Paul and Lee, Cassie and Davies, Helen and Balasundaram, Kumaran and Greenwood, Darren C., Long Covid Clinical Severity Types Based on Symptoms and Functional Disability: A Longitudinal Evaluation. Available at SSRN: https://ssrn.com/abstract=4642650 or http://dx.doi.org/10.2139/ssrn.4642650 https://papers.ssrn.com/sol3/papers.cfm?abstract_id=4642650 (Full text available as PDF file)

The association of insomnia with long COVID: An international collaborative study (ICOSS-II)

Abstract:

Objective: There is evidence of a strong association between insomnia and COVID-19, yet few studies have examined the relationship between insomnia and long COVID. This study aimed to investigate whether COVID-19 patients with pre-pandemic insomnia have a greater risk of developing long COVID and whether long COVID is in turn associated with higher incident rates of insomnia symptoms after infection.

Methods: Data were collected cross-sectionally (May-Dec 2021) as part of an international collaborative study involving participants from 16 countries. A total of 2311 participants (18-99 years old) with COVID-19 provided valid responses to a web-based survey about sleep, insomnia, and health-related variables. Log-binomial regression was used to assess bidirectional associations between insomnia and long COVID. Analyses were adjusted for age, sex, and health conditions, including sleep apnea, attention and memory problems, chronic fatigue, depression, and anxiety.

Results: COVID-19 patients with pre-pandemic insomnia showed a higher risk of developing long COVID than those without pre-pandemic insomnia (70.8% vs 51.4%; adjusted relative risk [RR]: 1.33, 95% confidence interval [CI]: 1.07-1.65). Among COVID-19 cases without pre-pandemic insomnia, the rates of incident insomnia symptoms after infection were 24.1% for short COVID cases and 60.6% for long COVID cases (p < .001). Compared with short COVID cases, long COVID cases were associated with an increased risk of developing insomnia symptoms (adjusted RR: 2.00; 95% CI: 1.50-2.66).

Conclusions: The findings support a bidirectional relationship between insomnia and long COVID. These findings highlight the importance of addressing sleep and insomnia in the prevention and management of long COVID.

Source: Chen SJ, Morin CM, Ivers H, Wing YK, Partinen M, Merikanto I, Holzinger B, Espie CA, De Gennaro L, Dauvilliers Y, Chung F, Yordanova J, Vidović D, Reis C, Plazzi G, Penzel T, Nadorff MR, Matsui K, Mota-Rolim S, Leger D, Landtblom AM, Korman M, Inoue Y, Hrubos-Strøm H, Chan NY, Bjelajac AK, Benedict C, Bjorvatn B. The association of insomnia with long COVID: An international collaborative study (ICOSS-II). Sleep Med. 2023 Dec;112:216-222. doi: 10.1016/j.sleep.2023.09.034. Epub 2023 Oct 24. PMID: 37922783. https://www.sciencedirect.com/science/article/abs/pii/S1389945723003672

Determinants of the onset and prognosis of the post-COVID-19 condition: a 2-year prospective observational cohort study

Abstract:

Background: At least 5-10% of subjects surviving COVID-19 develop the post-COVID-19 condition (PCC) or “Long COVID”. The clinical presentation of PCC is heterogeneous, its pathogenesis is being deciphered, and objective, validated biomarkers are lacking. It is unknown if PCC is a single entity or a heterogeneous syndrome with overlapping pathophysiological basis. The large US RECOVER study identified four clusters of subjects with PCC according to their presenting symptoms. However, the long-term clinical implications of PCC remain unknown.

Methods: We conducted a 2-year prospective cohort study of subjects surviving COVID-19, including individuals fulfilling the WHO PCC definition and subjects with full clinical recovery. We systematically collected post-COVID-19 symptoms using prespecified questionnaires and performed additional diagnostic imaging tests when needed. Factors associated with PCC were identified and modelled using logistic regression. Unsupervised clustering analysis was used to group subjects with PCC according to their presenting symptoms. Factors associated with PCC recovery were modelled using a direct acyclic graph approach.

Findings: The study included 548 individuals, 341 with PCC, followed for a median of 23 months (IQR 16.5-23.5), and 207 subjects fully recovered. In the model with the best fit, subjects who were male and had tertiary studies were less likely to develop PCC, whereas a history of headache, or presence of tachycardia, fatigue, neurocognitive and neurosensitive complaints and dyspnea at COVID-19 diagnosis predicted the development of PCC. The cluster analysis revealed the presence of three symptom clusters with an additive number of symptoms. Only 26 subjects (7.6%) recovered from PCC during follow-up; almost all of them (n = 24) belonged to the less symptomatic cluster A, dominated mainly by fatigue. Recovery from PCC was more likely in subjects who were male, required ICU admission, or had cardiovascular comorbidities, hyporexia and/or smell/taste alterations during acute COVID-19. Subjects presenting with muscle pain, impaired attention, dyspnea, or tachycardia, conversely, were less likely to recover from PCC.

Interpretation: Preexisting medical and socioeconomic factors, as well as acute COVID-19 symptoms, are associated with the development of and recovery from the PCC. Recovery is extremely rare during the first 2 years, posing a major challenge to healthcare systems.

Source: Mateu L, Tebe C, Loste C, Santos JR, Lladós G, López C, España-Cueto S, Toledo R, Font M, Chamorro A, Muñoz-López F, Nevot M, Vallejo N, Teis A, Puig J, Fumaz CR, Muñoz-Moreno JA, Prats A, Estany-Quera C, Coll-Fernández R, Herrero C, Casares P, Garcia A, Clotet B, Paredes R, Massanella M. Determinants of the onset and prognosis of the post-COVID-19 condition: a 2-year prospective observational cohort study. Lancet Reg Health Eur. 2023 Sep 5;33:100724. doi: 10.1016/j.lanepe.2023.100724. PMID: 37954002; PMCID: PMC10636281. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10636281/ (Full text)

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

Abstract:

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)