Tag: 2023

Persistence of post-COVID symptoms in the general population two years after SARS-CoV-2 infection: A systematic review and meta-analysis

Abstract:

Objective: This meta-analysis investigated the prevalence of post-COVID symptoms two-years after SARS-CoV-2 infection.

Methods: Electronic literature searches on PubMed, MEDLINE, CINAHL, EMBASE, Web of Science databases, and on medRxiv/bioRxiv preprint servers were conducted up to October 1, 2023. Studies reporting data on post-COVID symptoms at two-years after infection were included. Methodological quality was assessed using the Newcastle-Ottawa Scale. Random-effects models were used for meta-analytical pooled prevalence of each symptom.

Results: From 742 studies identified, twelve met inclusion criteria. The sample included 7912 COVID-19 survivors (50.7% female; age: 59.5, SD: 16.3). Post-COVID symptoms were assessed at a follow-up of 722.9 (SD: 51.5) days after. The overall methodological quality of studies was moderate (mean: 6/10, SD: 1.2 points). The most prevalent post-COVID symptoms two-years after SARS-CoV-2 infection were fatigue (28.0%, 95%CI 12.0-47.0), cognitive impairments (27.6%, 95%CI 12.6-45.8), and pain (8.4%, 95%CI 4.9-12.8). Psychological disturbances such as anxiety (13.4%, 95%CI 6.3-22.5) and depressive (18.0%, 95%CI 4.8-36.7) levels as well as sleep problems (20.9%, 95%CI 5.25-43.25) were also prevalent. Pooled data showed high heterogeneity (I2 ≥ 75%).

Conclusion: This meta-analysis shows the presence of post-COVID symptoms in 30% of patients two-years after COVID-19. Fatigue, cognitive disorders, and pain were the most prevalent post-COVID symptoms. Psychological disturbances as well as sleep problems were still present two-years after COVID-19.

Source: Fernandez-de-Las-Peñas C, Notarte KI, Macasaet R, Velasco JV, Catahay JA, Ver AT, Chung W, Valera-Calero JA, Navarro-Santana M. Persistence of post-COVID symptoms in the general population two years after SARS-CoV-2 infection: A systematic review and meta-analysis. J Infect. 2023 Dec 13:S0163-4453(23)00590-X. doi: 10.1016/j.jinf.2023.12.004. Epub ahead of print. PMID: 38101521. https://www.journalofinfection.com/article/S0163-4453(23)00590-X/fulltext (Full text)

Intravenous immunoglobulin as a potential treatment for long COVID

Abstract:

Introduction: On 31 July 2023, the United States Department of Health and Human Services announced the formation of the Office of Long COVID Research and Practice and the United States National Institutes of Health (NIH) opened enrollment for the therapeutic arm of the RECOVER initiative, a prospective, randomized study to evaluate new treatment options for long coronavirus disease 2019 (long COVID).

Areas covered: One of the first drugs to be studied in this nationwide initiative is intravenous immunoglobulin (IVIG), which will be a treatment option for subjects enrolled in RECOVER-AUTO, a randomized trial to investigate therapeutic strategies for autonomic dysfunction related to long COVID.

Expert opinion: IVIG is a mixture of human antibodies (human immunoglobulin) that has been widely used to treat a variety of diseases, including immune thrombocytopenia purpura, Kawasaki disease, chronic inflammatory demyelinating polyneuropathy, and certain infections such as influenza, human immunodeficiency virus, and measles. However, the role of IVIG in the treatment of post-COVID-19 conditions is uncertain. This manuscript examines what is known about IVIG in the treatment of long COVID and explores how this therapeutic agent may be used in the future to address this condition.

Source: McCarthy MW. Intravenous immunoglobulin as a potential treatment for long COVID. Expert Opin Biol Ther. 2023 Jul-Dec;23(12):1211-1217. doi: 10.1080/14712598.2023.2296569. Epub 2023 Dec 28. PMID: 38100573. https://www.tandfonline.com/doi/full/10.1080/14712598.2023.2296569

Extensive acute and sustained changes to neutrophil proteomes post-SARS-CoV-2 infection

Abstract:

Background Neutrophils are important in the pathophysiology of COVID-19 but the molecular changes contributing to altered neutrophil phenotypes following SARS-CoV-2 infection are not fully understood. We used quantitative mass spectrometry-based proteomics to explore neutrophil phenotypes immediately following acute SARS-CoV-2 infection and during recovery.

Methods Prospective observational study of hospitalised patients with PCR-confirmed SARS-CoV-2 infection (May-December 2020). Patients were enrolled within 96 h of admission, with longitudinal sampling up to 29 days. Control groups comprised non-COVID-19 acute lower respiratory tract infection (LRTI) and age-matched non-infected controls. Neutrophils were isolated from peripheral blood and analysed by mass spectrometry. COVID-19 severity and recovery were defined using the WHO ordinal scale.

Results Neutrophil proteomes from 84 COVID-19 patients were compared to those from 91 LRTI and 42 control participants. 5800 neutrophil proteins were identified, with >1700 proteins significantly changed in neutrophils from COVID-19 patients compared to non-infected controls. Neutrophils from COVID-19 patients initially all demonstrated a strong interferon (IFN) signature but this signature rapidly declined in patients with severe disease. Severe disease was associated with increased abundance of proteins involved in metabolism, immunosuppression and pattern recognition, while delayed recovery from COVID-19 was associated with decreased granule components and reduced abundance of metabolic proteins, chemokine and leukotriene receptors, integrins and inhibitory receptors.

Conclusions SARS-CoV-2 infection results in the sustained presence of circulating neutrophils with distinct proteomes suggesting altered metabolic and immunosuppressive profiles and altered capacities to respond to migratory signals and cues from other immune cells, pathogens or cytokines.

Footnotes

This manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.

Source: Merete B Long, Andrew JM Howden, Holly R Keir, Christina M Rollings, Yan Hui Giam, Thomas Pembridge, Lilia Delgado, Hani Abo-Leyah, Amy F Lloyd, Gabriel Sollberger, Rebecca Hull, Amy Gilmour, Chloe Hughes, Benjamin JM New, Diane Cassidy, Amelia Shoemark, Hollian Richardson, Angus I Lamond, Doreen A Cantrell, James D Chalmers, Alejandro J Brenes. Extensive acute and sustained changes to neutrophil proteomes post-SARS-CoV-2 infection. European Respiratory Journal Jan 2023, 2300787; DOI: 10.1183/13993003.00787-2023 https://erj.ersjournals.com/content/early/2023/11/23/13993003.00787-2023 (Full text available as PDF file)

Long-COVID-19: the persisting imprint of SARS-CoV-2 infections on the innate immune system

In a recent Cell publication, Cheong et al. uncover how COVID-19 causes IL-6 induced epigenetic reprogramming of human immune stem cells, which causes lasting alterations in the composition and response characteristics of circulating immune cells.1 The study provides important insights into the mechanisms by which SARS-CoV-2 infections impact the human immune system and is an important hook into unraveling the mechanisms of post-acute sequelae of COVID-19 (PASC) commonly referred to as long-COVID.

While vaccination and drugs are reducing the societal impact of acute SARS-CoV-2 infections, between 10 and 40% of patients continue to suffer long after the acute infection has been cleared. The diverse PASC symptoms range from short breath and headaches to cognitive impairment (‘brain fog’) and debilitating fatigue. Not only are no treatments for PASC available but also the underlying molecular mechanisms remain opaque.2

Cheong et al. investigated in patients’ circulating immune cells if detectable changes persisted after clearance of the acute SARS-CoV-2 infection 3 weeks after the first symptoms. They assembled a cohort of COVID-19 convalescent patients, which was sampled between 1–3 and 4–12 months after SARS-CoV-2 infections requiring intensive care unit (ICU) admission and compared these patients to non-infected controls and to patients that had been on the ICU for different reasons. Focusing on peripheral blood mononuclear cells (PBMC) they investigated transcriptional or epigenetic changes using an integrated pipeline of single-nuclei transcriptome analysis and ATAC-seq sequencing, which identifies accessible chromatin regions. Among PBMCs CD14+ monocytes exhibited the most drastic changes. CD14+ monocytes are a group of heterogenous, short-lived antigen presenting cells that help orchestrating immune responses. Among these the authors could distinguish one cluster, M.SC3, which was more abundant even 12 months after the infection. Cells in this cluster resembled intermediate-type monocytes with functions that altogether resemble dendritic cells, the most effective amongst professional antigen presenting cells. In response to stimuli indicating viral infections, post-COVID monocytes showed up to 100-fold increased secretion of proinflammatory cytokines and enhanced transcriptional responses relating to cytokine signaling and monocyte activation. ATAC-seq also revealed a persistent pattern of differentially accessible chromatin which increased in abundance in early convalescent patients and did not return to the low levels observed in healthy individuals even 12 months after the acute infection. Thus, following severe SARS-CoV-2 infections, patients’ CD14+ monocytes carry specific and persistent epigenetic changes that puts them into an alerted state with heightened response characteristics.

Given that monocytes have a lifespan of a single day, the discovery of persistent epigenetic changes is notable and may reflect altered hematopoiesis and inheritance of epigenetic states from hematopoietic stem and progenitor cells (HSPC). To overcome the challenges associated with obtaining bone marrow resident HSPC, Cheong et al. developed a platform to enrich rare circulating HSPCs from PBMC and demonstrated that these faithfully represent the diversity and functional characteristics of their bone marrow-derived counterparts. With this platform, they discovered lasting epigenetic changes in HSPC of post-COVID patients that resembled those observed in mature monocytes. Especially late post-COVID HSPC exhibited skewed hematopoiesis with a significant increase of granulocyte monocyte precursor (GMP) cells. Intriguingly, the stem cells and the mature monocytes shared epigenetic signatures indicating that epigenetic and transcriptional programs are inherited by the mature progeny. The previously identified M.SC3 module activity was similarly increased in stem cells of the same patients.

Read the rest of this article HERE. 

Source: Boes, M., Falter-Braun, P. Long-COVID-19: the persisting imprint of SARS-CoV-2 infections on the innate immune system. Sig Transduct Target Ther 8, 460 (2023). https://doi.org/10.1038/s41392-023-01717-9 https://www.nature.com/articles/s41392-023-01717-9 (Full text)

Creatine supplementation combined with breathing exercises reduces respiratory discomfort and improves creatine status in patients with long-COVID

Abstract:

Eight long-COVID patients with moderate fatigue that had lasted for ≥3 months were recruited. All patients were allocated in a double-blind parallel-group design to receive either 4 g of creatine per day plus breathing exercises (study group) or breathing exercises only (control group) for 3 months.

Creatine induced a significant increase in tissue total creatine levels for all 14 locations evaluated in the present study (P < 0.05), while its levels significantly dropped in the right frontal gray matter and left parietal mesial gray matter at follow-up in the control group (P < 0.05).

No change in time to exhaustion was demonstrated in the control group (P > 0.05), while the mean time to exhaustion was significantly improved for 54 s in the study group post-administration (P = 0.05).

These preliminary findings suggest that creatine is as an effective adjuvant therapeutic to breathing exercises for tackling the clinical features in long-COVID.

Source: Slankamenac, J; Ranisavljev, M; Todorovic, N; Ostojic, J; Stajer, V; Ostojic, SM. Creatine supplementation combined with breathing exercises reduces respiratory discomfort and improves creatine status in patients with long-COVID. Journal of Postgraduate Medicine ():, December 07, 2023. | DOI: 10.4103/jpgm.jpgm_650_23  https://journals.lww.com/jopm/abstract/9000/creatine_supplementation_combined_with_breathing.99983.aspx (Full text available as PDF file)

Low handgrip strength is associated with worse functional outcomes in long-Covid

Abstract:

The diagnosis of long-Covid is troublesome, even when functional limitations are present. Dynapenia is a decrease in muscle strength and power production and may explain in part these limitations. This study aimed to identify the distribution and possible association of dynapenia with functional assessment in patients with long-Covid.

A total of 113 inpatients with COVID-19 were evaluated by functional assessment 120 days post-acute severe disease. Body composition, respiratory muscle strength, spirometry, six-minute walk test (6MWT) and hand-grip strength (HGS) were assessed.

Dynapenia was defined as HGS < 30kg/f (men), and < 20kg/f (women). Twenty-five (22%) participants were dynapenic, presenting lower muscle mass (p < 0.001), worse forced expiratory volume in the first second (FEV1) (p = 0.0001), lower forced vital capacity (p < 0.001), and inspiratory (p = 0.007) and expiratory (p = 0.002) peek pressures, as well as worse 6MWT performance (p < 0.001). Dynapenia was associated with worse FEV1, MEP, and 6MWT, independent of age (p < 0.001).

Patients with dynapenia had higher ICU admission rates (p = 0.01) and need for invasive mechanical ventilation (p = 0.007) during hospitalization. The HGS is a simple, reliable, and low-cost measurement that can be performed in outpatient clinics in low- and middle-income countries. Thus, HGS may be used as a proxy indicator of functional impairment in this population.

Source: Camila Miriam Suemi Sato Barros do Amaral AMARAL, Cássia da Luz Goulart GOULART, Bernardo Maia da Silva SILVA et al. Low handgrip strength is associated with worse functional outcomes in long-Covid, 11 December 2023, PREPRINT (Version 1) available at Research Square [https://doi.org/10.21203/rs.3.rs-3695556/v1] https://www.researchsquare.com/article/rs-3695556/v1 (Full text)

Prevalence of covid-19 and long covid in collegiate student athletes from spring 2020 to fall 2021: a retrospective survey

Abstract:

Background: Symptomatic COVID-19 and Long COVID, also referred to as post-acute sequelae of SARS-CoV-2 (PASC) or post-COVID conditions, have been widely reported in young, healthy people, but their prevalence has not yet been determined in student athletes. We sought to estimate the prevalence of reported COVID-19, symptomatic COVID-19, and Long COVID in college athletes in the United States attending 18 schools from spring 2020 to fall 2021.

Methods: We developed an online survey to measure the prevalence of student athletes who tested positive for COVID-19, developed Long COVID, and did not return to their sport during the relevant time period. We surveyed a convenience sample of 18 collegiate school administrators, representing about 7,000 student athletes. Of those schools surveyed, 16 responded regarding the spring 2020 semester, and 18 responded regarding the full academic year of fall 2020 to spring 2021 (both semesters).

Results: According to the survey responses, there were 9.8% of student athletes who tested positive for COVID-19 in spring 2020 and 25.4% who tested positive in the academic year of fall 2020 to spring 2021. About 4% of student athletes who tested positive from spring 2020 to spring 2021 developed Long COVID, defined as new, recurring, or ongoing physical or mental health consequences occurring 4 or more weeks after SARS-CoV-2 infection.

Conclusions: This study highlights that Long COVID occurs among young, healthy athletes and is a real consequence of COVID-19. Understanding the prevalence of Long COVID in this population requires longer follow-up and further study.

Source: Massey D, Saydah S, Adamson B, Lincoln A, Aukerman DF, Berke EM, Sikka R, Krumholz HM. Prevalence of covid-19 and long covid in collegiate student athletes from spring 2020 to fall 2021: a retrospective survey. BMC Infect Dis. 2023 Dec 13;23(1):876. doi: 10.1186/s12879-023-08801-z. PMID: 38093182; PMCID: PMC10717379. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10717379/ (Full text)

“None of us are lying”: an interpretive description of the search for legitimacy and the journey to access quality health services by individuals living with Long COVI

Abstract:

Background: Understanding of Long COVID has advanced through patient-led initiatives. However, research about barriers to accessing Long COVID services is limited. This study aimed to better understand the need for, access to, and quality of, Long COVID services. We explored health needs and experiences of services, including ability of services to address needs.

Methods: Our study was informed by the Levesque et al.’s (2013) “conceptual framework of access to health care.” We used Interpretive Description, a qualitative approach partly aimed at informing clinical decisions. We recruited participants across five settings. Participants engaged in one-time, semi-structured, virtual interviews. Interviews were transcribed verbatim. We used reflexive thematic analysis. Best practice to ensure methodological rigour was employed.

Results: Three key themes were generated from 56 interviews. The first theme illustrated the rollercoaster-like nature of participants’ Long COVID symptoms and the resulting impact on function and health. The second theme highlighted participants’ attempts to access Long COVID services. Guidance received from healthcare professionals and self-advocacy impacted initial access. When navigating Long COVID services within the broader system, participants encountered barriers to access around stigma; appointment logistics; testing and ‘normal’ results; and financial precarity and affordability of services. The third theme illuminated common factors participants liked and disliked about Long COVID services. We framed each sub-theme as the key lesson (stemming from all likes and dislikes) that, if acted upon, the health system can use to improve the quality of Long COVID services. This provides tangible ways to improve the system based directly on what we heard from participants.

Conclusion: With Long COVID services continuously evolving, our findings can inform decision makers within the health system to better understand the lived experiences of Long COVID and tailor services and policies appropriately.

Source: Brehon K, Miciak M, Hung P, Chen SP, Perreault K, Hudon A, Wieler M, Hunter S, Hoddinott L, Hall M, Churchill K, Brown DA, Brown CA, Bostick G, Skolnik K, Lam G, Weatherald J, Gross DP. “None of us are lying”: an interpretive description of the search for legitimacy and the journey to access quality health services by individuals living with Long COVID. BMC Health Serv Res. 2023 Dec 12;23(1):1396. doi: 10.1186/s12913-023-10288-y. PMID: 38087299; PMCID: PMC10714615. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10714615/ (Full text)

Characterization of subgroups of myalgic encephalomyelitis/chronic fatigue syndrome based on disease onset, symptoms and biomarkers

Abstract:

Myalgic encephalomyelitis, also called chronic fatigue syndrome (ME/CFS), is an acquired multisystem disease. The core symptoms include fatigue, exercise intolerance and pain as well as cognitive, autonomic and immunological manifestations. The diagnosis of ME/CFS is based on clinical criteria. Specific biomarkers do not currently exist, but studies suggest a role for soluble cluster of differentiation 26 (sCD26) and autoantibodies (AAK) against G protein-coupled receptors (GPCR). In many cases, the disease begins as a result of infections. 

The aim of this work was to determine the pathophysiological significance of potential biomarkers, assuming different development mechanisms in patients with infection-associated disease onset compared to those with other triggers. In a first study, sCD26, also called dipeptidyl peptidase-4 (DPP-4) due to its enzymatic activity, was analyzed and compared in the serum of 205 ME/CFS patients and 98 controls. This was followed by a comprehensive correlation analysis between sCD26 and clinical and laboratory parameters for ME/CFS patients, separated by type of disease onset. In addition, CD26 expression on lymphocyte subpopulations was determined for 12 patients and 12 controls. 

In another study, a correlation analysis was carried out between AAK against vasoregulatory GPCR and symptoms in 116 ME/CFS patients, separated by type of disease onset. It was shown that in ME/CFS patients with infection-associated disease onset, sCD26 correlated with numerous immunological and metabolic parameters, the changes of which have also been described in connection with DPP-4 inhibitors. In addition, there were inverse correlations with AAK against alpha1-adrenergic and M3-acetylcholine receptors. 

In this subgroup, the second study found correlations between numerous GPCR-AAK and the severity of fatigue, muscle pain and cognitive symptoms as well as greater functional impairment relevant to everyday life. None of these correlations were found in patients without infection-associated disease onset. 

Here, sCD26 correlated inversely with orthostatically induced heart rate increases and AAK against alpha- and beta-adrenergic receptors with the severity of orthostatic symptoms. Different correlation patterns between AAK against GPCR and symptoms allow us to assume that in patients with ME/CFS, an altered function of the AAK or its receptors or signaling pathways has occurred as a result of an infection. The association of sCD26 and GPCR-AAK also indicates the dysregulation of other parts of the immune system with potentially pathological consequences. The differences presented compared to patients with non-infectious genesis suggest two definable subgroups.

Source: Szklarski, Marvin. Characterization of subgroups of myalgic encephalomyelitis/chronic fatigue syndrome based on disease onset, symptoms and biomarkers. Charité – University Medicine Berlin, dissertation. https://refubium.fu-berlin.de/handle/fub188/40276