Tag: covid-19

Predictive Factors and ACE-2 Gene Polymorphisms in Susceptibility to Long COVID-19 Syndrome

Abstract:

Long COVID-19 syndrome is present in 5–10% of patients infected with SARS-CoV-2, and there is still little information on the predisposing factors that lead to its development. The purpose of the study was to evaluate the predictive factors in early symptoms, clinical features and the role of Angiotensin-Converting Enzyme-2 (ACE-2) c.513-1451G>A (rs2106806) and c.15643279T>C (rs6629110) polymorphisms in the susceptibility to developing Long COVID-19 syndrome subsequent to COVID-19 infection.
A total of 29 patients who suffered COVID-19 were recruited in a descriptive longitudinal study of two groups: Long COVID-19 (n = 16) and non-Long COVID-19 (n = 13). Early symptoms and clinical features during COVID-19 were classified by a medical service. ACE-2 polymorphisms were genotyped by using a Single Nucleotide Primer Extension (SNPE). Of the early symptoms, fatigue, myalgia and headache showed a high risk of increasing Long COVID-19 susceptibility. Clinical features such as emergency care, SARS-CoV-2 reinfection, previous diseases, respiratory disease and brain fog also had a high risk of increasing Long COVID-19 susceptibility.
The A allele in the rs2106806 variant was associated with an odds ratio (OR) of 4.214 (95% CI 2.521–8.853; p < 0.001), and the T allele in the rs6629110 variant was associated with an OR of 3.754 (95% CI 1.785–6.105; p = 0.002) of increasing Long COVID-19 susceptibility. This study shows the risk of ACE-2 polymorphisms, different early symptoms and clinical features during SARS-CoV-2 infection in susceptibility to Long COVID-19.
Source: Varillas-Delgado D, Jimenez-Antona C, Lizcano-Alvarez A, Cano-de-la-Cuerda R, Molero-Sanchez A, Laguarta-Val S. Predictive Factors and ACE-2 Gene Polymorphisms in Susceptibility to Long COVID-19 Syndrome. International Journal of Molecular Sciences. 2023; 24(23):16717. https://doi.org/10.3390/ijms242316717 https://www.mdpi.com/1422-0067/24/23/16717 (Full text)

Assessing symptoms of long/post COVID and chronic fatigue syndrome using the DePaul symptom questionnaire-2: a validation in a German-speaking population

Abstract:

Objective: A subset of Covid-19 survivors will develop persisting health sequelae (i.e. Long Covid/LC or Post Covid/PC) similar to Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). In the absence of a reliable biomarker to diagnose LC/PC and ME/CFS, their classification based on symptoms becomes indispensable. Hence, we translated and validated the DePaul Symptom Questionnaire−2 (DSQ-2), to offer a screening tool for the German-speaking population.

Methods: A sample of healthy adults, and adults with ME/CFS and LC/PC (N = 502) completed a reduced-item version of the DSQ-2 and SF-36 questionnaire online. We performed an exploratory factor analysis, assessed construct validity, diagnostic accuracy and compared the symptom profiles of individuals with ME/CFS versus LC/PC versus healthy adults.

Results: Exploratory factor analysis revealed a 10-factor solution with excellent internal consistencies. The sensitivity of the DSQ-2 was excellent. The specificity was moderate with moderate inter-rater reliability. Construct validity of the DSQ-2 was supported by strong negative correlations with physical health subscales of the SF-36. A visual comparison of the symptom profiles of individuals with ME/CFS versus LC/PC revealed a comparable pattern.

Conclusion: Despite lower symptom severity, individuals with LC/PC reported significantly stronger limitations in general health and physical functioning and were more likely to meet ME/CFS diagnostic criteria with ongoing sickness duration, suggesting that ME/CFS can be considered a long-term sequela of LC/PC. This study offers a translated and validated version of the reduced-item DSQ-2 that can guide medical evaluation and aid physicians in identifying a ME/CFS-like subtype of LC/PC.

Source: Nina Buntić, Leonard A. Jason, Jochen Schneider, Marc Schlesser & André Schulz (2023) Assessing symptoms of long/post COVID and chronic fatigue syndrome using the DePaul symptom questionnaire-2: a validation in a German-speaking population, Fatigue: Biomedicine, Health & Behavior, DOI: 10.1080/21641846.2023.2295419 https://www.tandfonline.com/doi/full/10.1080/21641846.2023.2295419 (Full text)

Urine Metabolite Analysis to Identify Pathomechanisms of Long COVID: A Pilot Study

Abstract:

Background: Around 10% of people who had COVID-9 infection suffer from persistent symptoms such as fatigue, dyspnoea, chest pain, arthralgia/myalgia, sleep disturbances, cognitive dysfunction and impairment of mental health. Different underlying pathomechanisms appear to be involved, in particular inflammation, alterations in amino acid metabolism, autonomic dysfunction and gut dysbiosis.

Aim: As routine tests are often inconspicuous in patients with Long COVID (LC), similarly to patients suffering from myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), accessible biomarkers indicating dysregulation of specific pathways are urgently needed to identify underlying pathomechanisms and enable personalized medicine treatment. Within this pilot study we aimed to proof traceability of altered metabolism by urine analysis.

Patients and methods: Urine metabolome analyses were performed to investigate the metabolic signature of patients with LC (n = 25; 20 women, 5 men) in comparison to healthy controls (Ctrl, n = 8; 7 women, 1 man) and individuals with ME/CFS (n = 8; 2 women, 6 men). Concentrations of neurotransmitter precursors tryptophan, phenylalanine and their downstream metabolites, as well as their association with symptoms (fatigue, anxiety and depression) in the patients were examined.

Results and conclusion: Phenylalanine levels were significantly lower in both the LC and ME/CFS patient groups when compared to the Ctrl group. In many LC patients, the concentrations of downstream metabolites of tryptophan and tyrosine, such as serotonin, dopamine and catecholamines, deviated from the reference ranges. Several symptoms (sleep disturbance, pain or autonomic dysfunction) were associated with certain metabolites. Patients experiencing fatigue had lower levels of kynurenine, phenylalanine and a reduced kynurenine to tryptophan ratio (Kyn/Trp). Lower concentrations of gamma-aminobutyric acid (GABA) and higher activity of kynurenine 3-monooxygenase (KMO) were observed in patients with anxiety.

Conclusively, our results suggest that amino acid metabolism and neurotransmitter synthesis is disturbed in patients with LC and ME/CFS. The identified metabolites and their associated dysregulations could serve as potential biomarkers for elucidating underlying pathomechanisms thus enabling personalized treatment strategies for these patient populations.

Source: Taenzer M, Löffler-Ragg J, Schroll A, Monfort-Lanzas P, Engl S, Weiss G, Brigo N, Kurz K. Urine Metabolite Analysis to Identify Pathomechanisms of Long COVID: A Pilot Study. Int J Tryptophan Res. 2023 Dec 22;16:11786469231220781. doi: 10.1177/11786469231220781. PMID: 38144169; PMCID: PMC10748708. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10748708/ (Full text)

Clinical features of Japanese patients with gastrointestinal long-COVID symptoms

Introduction:

Although the development of new therapeutic approaches and vaccines has decreased coronavirus disease 2019 (COVID-19)-associated mortality, prolonged systemic symptoms after COVID-19, termed long-COVID, have been a major concern, considering their potential impact on health-related quality of life (QOL). Gastrointestinal (GI) symptoms, including diarrhea and abdominal pain, have been reported in patients with long-COVID even months after the initial COVID-19 symptoms have resolved.

Although emerging evidence suggests that GI symptoms in long-COVID are affected by the dysregulation of the immune system or ongoing inflammation and damage to the GI tract caused by the initial COVID-19 infection, the clinical features of patients with GI long-COVID symptoms remain elusive. Our study aimed to clarify these features.

Source: Kazuma Yagi, Takanori Asakura, Hideki Terai, Keiko Ohgino, Katsunori Masaki, Ho Namkoong, Shotaro Chubachi, Jun Miyata, Ichiro Kawada, Nobuhiro Kodama, Satoshi Sakamoto, Akira Umeda, Takashi Ishiguro, Makoto Ishii, Koichi Fukunaga. JGH Open. First published: 06 December 2023 https://doi.org/10.1002/jgh3.13006 https://onlinelibrary.wiley.com/doi/full/10.1002/jgh3.13006 (Full text)

Mechanisms of long COVID: An updated review

Abstract:

The coronavirus disease 2019 (COVID-19) pandemic has been ongoing for more than 3 years, with an enormous impact on global health and economies. In some patients, symptoms and signs may remain after recovery from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which cannot be explained by an alternate diagnosis; this condition has been defined as long COVID.

Long COVID may exist in patients with both mild and severe disease and is prevalent after infection with different SARS-CoV-2 variants. The most common symptoms include fatigue, dyspnea, and other symptoms involving multiple organs. Vaccination results in lower rates of long COVID. To date, the mechanisms of long COVID remain unclear. In this narrative review, we summarized the clinical presentations and current evidence regarding the pathogenesis of long COVID.

Source: Yan Liu, Xiaoying Gu, Haibo Li, Hui Zhang, Jiuyang Xu. Mechanisms of long COVID: An updated review. Chinese Medical Journal Pulmonary and Critical Care Medicine, Volume 1, Issue 4, December 2023, Pages 231-240. https://www.sciencedirect.com/science/article/pii/S2772558823000580 (Full text)

Investigating the Human Intestinal DNA Virome and Predicting Disease-Associated Virus-Host Interactions in Severe Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)

Abstract:

Understanding how the human virome, and which of its constituents, contributes to health or disease states is reliant on obtaining comprehensive virome profiles. By combining DNA viromes from isolated virus-like particles (VLPs) and whole metagenomes from the same faecal sample of a small cohort of healthy individuals and patients with severe myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), we have obtained a more inclusive profile of the human intestinal DNA virome.

Key features are the identification of a core virome comprising tailed phages of the class Caudoviricetes, and a greater diversity of DNA viruses including extracellular phages and integrated prophages. Using an in silico approach, we predicted interactions between members of the Anaerotruncus genus and unique viruses present in ME/CFS microbiomes. This study therefore provides a framework and rationale for studies of larger cohorts of patients to further investigate disease-associated interactions between the intestinal virome and the bacteriome.

Source: Hsieh SY, Savva GM, Telatin A, Tiwari SK, Tariq MA, Newberry F, Seton KA, Booth C, Bansal AS, Wileman T, Adriaenssens EM, Carding SR. Investigating the Human Intestinal DNA Virome and Predicting Disease-Associated Virus-Host Interactions in Severe Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Int J Mol Sci. 2023 Dec 8;24(24):17267. doi: 10.3390/ijms242417267. PMID: 38139096. https://www.mdpi.com/1422-0067/24/24/17267 (Full text)

Large scale phenotyping of long COVID inflammation reveals mechanistic subtypes of disease after COVID-19 hospitalisation

Abstract:

One in ten SARS-CoV-2 infections result in prolonged symptoms termed long COVID, yet disease phenotypes and mechanisms are poorly understood. We studied the blood proteome of 719 previously hospitalised adults with long COVID grouped by symptoms. Elevated markers of myeloid inflammation and complement activation were associated with long COVID; elevated IL1R2, MATN2 and COLEC12 were associated with cardiorespiratory symptoms, fatigue, and anxiety/depression, while MATN2 and DPP10 were elevated in gastrointestinal (GI) symptoms, and C1QA in cognitive impairment.
Proteins suggestive of neurodegeneration were elevated in cognitive impairment, whilst SCG3 (indicative of brain-gut axis disturbance) was specific to GI symptoms. Nasal inflammation was apparent after COVID-19 but did not associate with symptoms. Although SARS-CoV-2 specific IgG was elevated with some long COVID symptoms, virus was not detected from sputum. Thus, systemic inflammation is evident in long COVID and could be targeted in therapeutic trials tailored to pathophysiological differences between symptom groups.

Source: Peter Openshaw, Felicity Liew, Claudia Efstathiou et al. Large scale phenotyping of long COVID inflammation reveals mechanistic subtypes of disease after COVID-19 hospitalisation, 04 December 2023, PREPRINT (Version 1) available at Research Square [https://doi.org/10.21203/rs.3.rs-3427282/v1] https://www.researchsquare.com/article/rs-3427282/v1 (Full text)

COVID-19 mRNA Vaccination Reduces the Occurrence of Post-COVID Conditions in U.S. Children Aged 5-17 Years Following Omicron SARS-CoV-2 Infection, July 2021-September 2022

Abstract:

Background An estimated 1-3% of children with SARS-CoV-2 infection will develop Post-COVID Conditions (PCC). This study evaluates mRNA COVID-19 vaccine impact on likelihood of PCC in children.
Methods A multi-site cohort of children enrolled 7/21/2021-9/1/2022 underwent weekly SARS-CoV-2 screening tests and were surveyed via self- or parental report 12/1/2022-5/31/2023 regarding PCC (defined as ≥1 new or on-going symptoms lasting ≥ 1 month after infection). Multivariable logistic regression was performed to estimate the occurrence of PCC by vaccination status among children aged 5–17 years whose first PCR-confirmed SARS-CoV-2 infection occurred in-study with Omicron variant, who completed the survey >60 days from infection, and who were vaccine age-eligible at time of infection per ACIP recommendations. Vaccination status was categorized as vaccinated (at least primary series completed >14 days before infection) and unvaccinated (no vaccine doses before infection). Vaccination status was verified through vaccine registry and/or medical records.
Results Of 622 participants surveyed, 5% (n=28) had PCC (Table 1) and 67% (n=474) were vaccinated (Table 2). Surveys were completed a median (IQR) of 203.7 days (119.0–293.0) after infection. Children with non-Hispanic Black race/ethnicity and good/fair/poor self-rated baseline health were more likely to report PCC. Children aged 12-18 years, Non-Hispanic Asian and White children, those reporting symptomatic SARS-CoV-2 infection, and those with excellent/very good self-rated baseline health were more likely to report vaccination When comparing children with and without PCC symptoms, COVID-19 mRNA vaccination was associated with a decreased likelihood of >1 PCC symptom (aOR 0.66, 95% CI 0.43-0.99), >2 PCC symptoms (aOR 0.52, 95% 0.32-0.83), and respiratory PCC symptoms (aOR 0.53, 95% CI 0.33-0.87) (Table 3).
Conclusion In this study, mRNA COVID-19 vaccination appeared to be protective against PCC in children following Omicron SARS-CoV-2 infection. The adjusted ORs correspond to an estimated 34%, 48%, and 47% reduced likelihood of >1, >2, and respiratory PCC symptoms among vaccinated children, respectively. These findings support COVID-19 vaccination for children and may encourage increased pediatric vaccine uptake.
Source: Anna R Yousaf, Josephine Mak, Lisa Gwynn, Robin Bloodworth, Ramona Rai, Zuha Jeddy, Lindsay B LeClair, Laura Edwards, Lauren E W Olsho, Gabriella Newes-Adeyi, Alexandra F Dalton, Manjusha Gaglani, Sarang K Yoon, Kurt Hegmann, Katherine Ellingson, Leora R Feldstein, Angela P Campbell, Amadea Britton, Sharon Saydah, 1935. COVID-19 mRNA Vaccination Reduces the Occurrence of Post-COVID Conditions in U.S. Children Aged 5-17 Years Following Omicron SARS-CoV-2 Infection, July 2021-September 2022, Open Forum Infectious Diseases, Volume 10, Issue Supplement_2, December 2023, ofad500.2466, https://doi.org/10.1093/ofid/ofad500.2466 https://academic.oup.com/ofid/article/10/Supplement_2/ofad500.2466/7448254 (Full text available as PDF file)

Differential Cardiopulmonary Hemodynamic Phenotypes in PASC Related Exercise Intolerance

Abstract:

Background Post-acute sequelae of COVID-19 (PASC) affects a significant portion of patients who have previously contracted SARS-CoV-2, with exertional intolerance being a prominent symptom.

Study Objective This study aimed to characterize the invasive hemodynamic abnormalities of PASC-related exertional intolerance using a larger data set from invasive cardiopulmonary exercise testing (iCPET).

Study Design & Intervention Fifty-five patients were recruited from the Yale Post-COVID-19-Recovery-Program, with most experiencing mild acute illness. Supine right heart catheterization (RHC) and iCPET were performed on all participants.

Main results The majority (75%) of PASC patients exhibited impaired peak systemic oxygen extraction (pEO2) during iCPET in conjunction with supranormal cardiac output (CO) (i.e., PASC alone group), On average, the PASC alone group exhibited a “normal” peak exercise capacity, VO2 (89±18% predicted). Approximately 25% of patients had evidence of central cardiopulmonary pathology (i.e., 12 with resting and exercise HFpEF and 2 with exercise PH). PASC patient with HFpEF (i.e., PASC HFpEF group) exhibited similarly impaired pEO2 with well compensated PH (i.e., peak VO2 and cardiac output >80% respectively) despite aberrant central cardiopulmonary exercise hemodynamics. PASC patients with HFpEF also exhibited increased body mass index of 39±7 kg·m−2. To examine the relative contribution of obesity to exertional impairment in PASC HFpEF, a control group compromising of obese non-PASC group (n=61) derived from historical iCPET cohort was used. The non-PASC obese patients with preserved peak VO2 (>80% predicted) exhibited a normal peak pulmonary artery wedge pressure (17±14 versus 25±6 mmHg; p=0.03) with similar maximal voluntary ventilation (90±12 versus 86±10%predicted; p=0.53) compared to PASC HFpEF patients. Impaired pEO2 was not significantly different between PASC patients who underwent supervised rehabilitation and those who did not (p=0.19).

Conclusions This study highlights the importance of considering impaired pEO2 in PASC patients with persistent exertional intolerance unexplained by conventional investigative testing. Results of current study also highlights the prevalence of a distinct high output failure HFpEF phenotype in PASC with a primary peripheral limitation to exercise.

Source: Peter A. Kahn, Phillip Joseph, Paul M. Heerdt, Inderjit Singh. Differential Cardiopulmonary Hemodynamic Phenotypes in PASC Related Exercise Intolerance. ERJ Open Research Jan 2023, 00714-2023; DOI: 10.1183/23120541.00714-2023 https://openres.ersjournals.com/content/early/2023/12/07/23120541.00714-2023 (Full text available as PDF file)

Microvascular Capillary and Precapillary Cardiovascular Disturbances Strongly Interact to Severely Affect Tissue Perfusion and Mitochondrial Function in ME/CFS Evolving from the Post COVID-19 Syndrome

Abstract:

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a frequent, debilitating and still enigmatic disease. There is a broad overlap in the symptomatology of ME/CFS and the Post-COVID Syndrome (PCS). A fraction of the PCS patients develops the full clinical picture of ME/CFS.
New observations in microvessels and blood from patients suffering from PCS have appeared and include microclots and malformed pathological blood cells. Capillary blood flow is impaired not only by pathological blood components but also by prothrombotic changes in the vascular wall, endothelial dysfunction, and expression of adhesion molecules in the capillaries. These disturbances can finally cause a low capillary flow and even capillary stasis. A low cardiac stroke volume due to hypovolemia and the inability of the capacitance vessels to adequately constrict to deliver the necessary cardiac preload generate an unfavorable low precapillary perfusion pressure.
Furthermore, a predominance of vasoconstrictor over vasodilator influences exists, in which sympathetic hyperactivity and endothelial dysfunction play a strong role, causing constriction of resistance vessels and of precapillary sphincters which leads to a fall in capillary pressure behind the sphincters. The interaction of these two precapillary cardiovascular mechanisms causing a low capillary perfusion pressure is hemodynamically highly unfavorable in the presence of a primary capillary stasis already caused by the pathological blood components and their interaction with the capillary wall, to severely impair organ perfusion.
The detrimental coincidence of the microcirculatory with the precapillary cardiovascular disturbances may constitute the key disturbance of the Post-COVID-19 syndrome and finally lead to ME/CFS in pre-disposed patients because the interaction causes a particular kind of perfusion disturbance – capillary ischemia-reperfusion – which has a high potential of causing mitochondrial dysfunction by inducing sodium- and calcium-overload in skeletal muscles. The latter in turns worsens the vascular situation by the generation of reactive oxygen species to close a vicious cycle from which the patient can hardly escape.
Source: Wirth, K.J.; Löhn, M. Microvascular Capillary and Precapillary Cardiovascular Disturbances Strongly Interact to Severely Affect Tissue Perfusion and Mitochondrial Function in ME/CFS Evolving from the Post COVID-19 Syndrome. Preprints 2023, 2023120791. https://doi.org/10.20944/preprints202312.0791.v1  https://www.preprints.org/manuscript/202312.0791/v1 (Full text available as PDF file)