Core mitochondrial genes are down-regulated during SARS-CoV-2 infection of rodent and human hosts

Editor’s summary:

SARS-CoV-2 needs host cells to generate molecules for viral replication and propagation. Guarnieri et al. now show that the virus is able to block expression of both nuclear-encoded and mitochondrial-encoded mitochondrial genes, resulting in impaired host mitochondrial function. They analyzed human nasopharyngeal samples and autopsy tissues from patients with COVID-19 and tissues from hamsters and mice infected with SARS-CoV-2. Host cells attempt to compensate by activating innate immune defenses and mitochondrial gene expression, but chronically impaired mitochondrial function ultimately may result in serious COVID-19 sequelae such as organ failure. —Orla Smith
Abstract:
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral proteins bind to host mitochondrial proteins, likely inhibiting oxidative phosphorylation (OXPHOS) and stimulating glycolysis. We analyzed mitochondrial gene expression in nasopharyngeal and autopsy tissues from patients with coronavirus disease 2019 (COVID-19).
In nasopharyngeal samples with declining viral titers, the virus blocked the transcription of a subset of nuclear DNA (nDNA)–encoded mitochondrial OXPHOS genes, induced the expression of microRNA 2392, activated HIF-1α to induce glycolysis, and activated host immune defenses including the integrated stress response.
In autopsy tissues from patients with COVID-19, SARS-CoV-2 was no longer present, and mitochondrial gene transcription had recovered in the lungs. However, nDNA mitochondrial gene expression remained suppressed in autopsy tissue from the heart and, to a lesser extent, kidney, and liver, whereas mitochondrial DNA transcription was induced and host-immune defense pathways were activated.
During early SARS-CoV-2 infection of hamsters with peak lung viral load, mitochondrial gene expression in the lung was minimally perturbed but was down-regulated in the cerebellum and up-regulated in the striatum even though no SARS-CoV-2 was detected in the brain. During the mid-phase SARS-CoV-2 infection of mice, mitochondrial gene expression was starting to recover in mouse lungs.
These data suggest that when the viral titer first peaks, there is a systemic host response followed by viral suppression of mitochondrial gene transcription and induction of glycolysis leading to the deployment of antiviral immune defenses. Even when the virus was cleared and lung mitochondrial function had recovered, mitochondrial function in the heart, kidney, liver, and lymph nodes remained impaired, potentially leading to severe COVID-19 pathology.
Source: Guarnieri JW, Dybas JM, Fazelinia H, Kim MS, Frere J, Zhang Y, Soto Albrecht Y, Murdock DG, Angelin A, Singh LN, Weiss SL, Best SM, Lott MT, Zhang S, Cope H, Zaksas V, Saravia-Butler A, Meydan C, Foox J, Mozsary C, Bram Y, Kidane Y, Priebe W, Emmett MR, Meller R, Demharter S, Stentoft-Hansen V, Salvatore M, Galeano D, Enguita FJ, Grabham P, Trovao NS, Singh U, Haltom J, Heise MT, Moorman NJ, Baxter VK, Madden EA, Taft-Benz SA, Anderson EJ, Sanders WA, Dickmander RJ, Baylin SB, Wurtele ES, Moraes-Vieira PM, Taylor D, Mason CE, Schisler JC, Schwartz RE, Beheshti A, Wallace DC. Core mitochondrial genes are down-regulated during SARS-CoV-2 infection of rodent and human hosts. Sci Transl Med. 2023 Aug 9;15(708):eabq1533. doi: 10.1126/scitranslmed.abq1533. Epub 2023 Aug 9. PMID: 37556555. https://pubmed.ncbi.nlm.nih.gov/37556555/

A technology-enabled multi-disciplinary team-based care model for the management of Long COVID and other fatiguing illnesses within a federally qualified health center: protocol for a two-arm, single-blind, pragmatic, quality improvement professional cluster randomized controlled trial

Abstract:

Background: The clinical burden of Long COVID, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and other post-infectious fatiguing illnesses (PIFI) is increasing. There is a critical need to advance understanding of the effectiveness and sustainability of innovative approaches to clinical care of patients having these conditions.

Methods: We aim to assess the effectiveness of a Long COVID and Fatiguing Illness Recovery Program (LC&FIRP) in a two-arm, single-blind, pragmatic, quality improvement, professional cluster, randomized controlled trial in which 20 consenting clinicians across primary care clinics in a Federally Qualified Health Center system in San Diego, CA, will be randomized at a ratio of 1:1 to either participate in (1) weekly multi-disciplinary team-based case consultation and peer-to-peer sharing of emerging best practices (i.e., teleECHO (Extension for Community Healthcare Outcomes)) with monthly interactive webinars and quarterly short courses or (2) monthly interactive webinars and quarterly short courses alone (a control group); 856 patients will be assigned to participating clinicians (42 patients per clinician). Patient outcomes will be evaluated according to the study arm of their respective clinicians. Quantitative and qualitative outcomes will be measured at 3- and 6-months post-baseline for clinicians and every 3-months post assignment to a participating clinician for patients. The primary patient outcome is change in physical function measured using the Patient-Reported Outcomes Measurement Information System (PROMIS)-29. Analyses of differences in outcomes at both the patient and clinician levels will include a linear mixed model to compare change in outcomes from baseline to each post-baseline assessment between the randomized study arms. A concurrent prospective cohort study will compare the LC&FIRP patient population to the population enrolled in a university health system. Longitudinal data analysis approaches will allow us to examine differences in outcomes between cohorts.

Discussion: We hypothesize that weekly teleECHO sessions with monthly interactive webinars and quarterly short courses will significantly improve clinician- and patient-level outcomes compared to the control group. This study will provide much needed evidence on the effectiveness of a technology-enabled multi-disciplinary team-based care model for the management of Long COVID, ME/CFS, and other PIFI within a federally qualified health center.

Trial registration: ClinicalTrials.gov, NCT05167227 . Registered on December 22, 2021.

Source: Godino JG, Samaniego JC, Sharp SP, Taren D, Zuber A, Armistad AJ, Dezan AM, Leyba AJ, Friedly JL, Bunnell AE, Matthews E, Miller MJ, Unger ER, Bertolli J, Hinckley A, Lin JS, Scott JD, Struminger BB, Ramers C. A technology-enabled multi-disciplinary team-based care model for the management of Long COVID and other fatiguing illnesses within a federally qualified health center: protocol for a two-arm, single-blind, pragmatic, quality improvement professional cluster randomized controlled trial. Trials. 2023 Aug 12;24(1):524. doi: 10.1186/s13063-023-07550-3. PMID: 37573421. https://trialsjournal.biomedcentral.com/articles/10.1186/s13063-023-07550-3 (Full text)

Long COVID in a highly vaccinated population infected during a SARS-CoV-2 Omicron wave – Australia, 2022

Abstract:

Objective To characterise Long COVID in a highly vaccinated population infected by Omicron.

Design Follow-up survey of persons testing positive for SARS-CoV-2 in Western Australia, 16 July-3 August 2022.

Setting Community

Participants 22,744 persons with COVID-19 who had agreed to participate in research at the time of diagnosis were texted a survey link 90 days later; non-responders were telephoned. Post stratification weights were applied to responses from 11,697 (51.4%) participants, 94.0% of whom had received >= 3 vaccine doses.

Main outcome measures Prevalence of ‘Long COVID’ – defined as reporting new or ongoing COVID-19 illness-related symptoms or health issues 90 days post diagnosis; associated health care utilisation, reductions in work/study and risk factors were assessed using log-binomial regression.

Results 18.2% (n=2,130) of respondents met case definition for Long COVID. Female sex, being 50-69 years of age, pre-existing health issues, residing in a rural or remote area, and receiving fewer vaccine doses were significant independent predictors of Long COVID (p < 0.05). Persons with Long COVID reported a median of 6 symptoms, most commonly fatigue (70.6%) and difficulty concentrating (59.6%); 38.2% consulted a GP and 1.6% reported hospitalisation in the month prior to the survey due to ongoing symptoms. Of 1,778 respondents with Long COVID who were working/studying before their COVID-19 diagnosis, 17.9% reported reducing/discontinuing work/study.

Conclusion 90 days post Omicron infection, almost 1 in 5 respondents reported Long COVID symptoms; 1 in 15 of all persons with COVID-19 sought healthcare for associated health concerns >=2 months after the acute illness.

The known The prevalence of Long COVID varies widely across studies conducted in diverse settings globally (range: 9%-81%).

The new In a highly vaccinated population (94% with >=3 vaccine doses), almost 20% of persons infected with the SARS-CoV-2 Omicron variant reported symptoms consistent with Long COVID 90 days post diagnosis. Long COVID was associated with sustained negative impacts on work/study and a substantial utilisation of GP services 2-3 months after the acute illness; however, ED presentations and hospitalisations for Long COVID were rare.

The implications GP clinics play a significant role in managing the burden of Long COVID in Australia.

Source: Mulu Woldegiorgis, Gemma Cadby, Sera Ngeh, Rosemary Korda, Paul Armstrong, Jelena Maticevic, Paul Knight, Andrew Jardine, Lauren Bloomfield, Paul Effler. Long COVID in a highly vaccinated population infected during a SARS-CoV-2 Omicron wave – Australia, 2022. medRxiv 2023.08.06.23293706; doi: https://doi.org/10.1101/2023.08.06.23293706 https://www.medrxiv.org/content/10.1101/2023.08.06.23293706v1.full-text (Full text)

SARS-CoV-2 Spike Protein Accumulation in the Skull-Meninges-Brain Axis: Potential Implications for Long-Term Neurological Complications in post-COVID-19

Abstract:

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), has been associated mainly with a range of neurological symptoms, including brain fog and brain tissue loss, raising concerns about the virus’s acute and potential chronic impact on the central nervous system. In this study, we utilized mouse models and human post-mortem tissues to investigate the presence and distribution of the SARS-CoV-2 spike protein in the skull-meninges-brain axis.

Our results revealed the accumulation of the spike protein in the skull marrow, brain meninges, and brain parenchyma. The injection of the spike protein alone caused cell death in the brain, highlighting a direct effect on brain tissue. Furthermore, we observed the presence of spike protein in the skull of deceased long after their COVID-19 infection, suggesting that the spike’s persistence may contribute to long-term neurological symptoms. The spike protein was associated with neutrophil-related pathways and dysregulation of the proteins involved in the PI3K-AKT as well as complement and coagulation pathway.

Overall, our findings suggest that SARS-CoV-2 spike protein trafficking from CNS borders into the brain parenchyma and identified differentially regulated pathways may present insights into mechanisms underlying immediate and long-term consequences of SARS-CoV-2 and present diagnostic and therapeutic opportunities.

Source: Zhouyi Rong, Hongcheng Mai, Saketh Kapoor, Victor G. Puelles, Jan Czogalla, Julia Schädler, Jessica Vering, Claire Delbridge, Hanno Steinke, Hannah Frenzel, Katja Schmidt, Özüm Sehnaz Caliskan, Jochen Martin Wettengel, Fatma Cherif, Mayar Ali, Zeynep Ilgin Kolabas, Selin Ulukaya, Izabela Horvath, Shan Zhao, Natalie Krahmer, Sabina Tahirovic, Ali Önder Yildirim, Tobias B. Huber, Benjamin Ondruschka, Ingo Bechmann, Gregor Ebert, Ulrike Protzer, Harsharan Singh Bhatia, Farida Hellal, Ali Ertürk. SARS-CoV-2 Spike Protein Accumulation in the Skull-Meninges-Brain Axis: Potential Implications for Long-Term Neurological Complications in post-COVID-19. bioRxiv 2023.04.04.535604; doi: https://doi.org/10.1101/2023.04.04.535604 https://www.biorxiv.org/content/10.1101/2023.04.04.535604v1.full (Full text)

Assessing health state utilities for people with myalgic encephalomyelitis/chronic fatigue syndrome in Australia using the EQ-5D-5L, AQoL-8D and EQ-5D-5L-psychosocial instruments

Abstract:

Purpose: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic condition with a constellation of symptoms presenting as severe and profound fatigue of ≥ 6 months not relieved by rest. ME/CFS affects health-related quality of life (HRQoL), which can be measured using multi-attribute health state utility (HSU) instruments. The aims of this study were to quantify HSUs for people living with ME/CFS, and to identify an instrument that is preferentially sensitive for ME/CFS.

Methods: Cross-sectional national survey of people with ME/CFS using the AQoL-8D and EQ-5D-5L. Additional questions from the AQoL-8D were used as ‘bolt-ons’ to the EQ-5D-5L (i.e., EQ-5D-5L-Psychosocial). Disability and fatigue severity were assessed using the De Paul Symptom Questionnaire-Short Form (DSQ-SF). HSUs were generated using Australian tariffs. Mean HSUs were stratified for sociodemographic and clinical factors. Bland-Altman plots were used to compare the three HSU instruments.

Results: For the 198 participants, mean HSUs (95% confidence intervals) were EQ-5D-5L: 0.46 (0.42-0.50); AQoL-8D: 0.43 (0.41-0.45); EQ-5D-5L-Psychosocial: 0.44 (0.42-0.46). HSUs were substantially lower than population norms: EQ-5D-5L: 0.89; AQoL-8D: 0.77. As disability and fatigue severity increased, HSUs decreased in all three instruments. Bland-Altman plots revealed interchangeability between the AQoL-8D and EQ-5D-5LPsychosocial. Floor and ceiling effects of 13.5% and 2.5% respectively were observed for the EQ-5D-5L instrument only.

Conclusions: ME/CFS has a profound impact on HRQoL. The AQoL-8D and EQ-5D-5L-Psychosocial can be used interchangeably: the latter represents a reduced participant burden.

Source: Orji NC, Cox IA, Jason LA, Chen G, Zhao T, Rogerson MJ, Kelly RM, Wills K, Hensher M, Palmer AJ, de Graaff B, Campbell JA. Assessing health state utilities for people with myalgic encephalomyelitis/chronic fatigue syndrome in Australia using the EQ-5D-5L, AQoL-8D and EQ-5D-5L-psychosocial instruments. Qual Life Res. 2023 Aug 10. doi: 10.1007/s11136-023-03498-8. Epub ahead of print. PMID: 37561337. https://link.springer.com/article/10.1007/s11136-023-03498-8 (Full text)

Coaching to strengthen critical success factors in integrative care for chronic fatigue patients: the Patient Needs-Resources Model

Abstract:

Theoretical and empirical studies discover that an integrative approach is particularly important in chronic disorders and multiple long-term conditions, such as chronic fatigue. Chronic fatigue syndrome (CFS) is a classic example of a potentially severe, multisystemic illness with a wide diversity of symptoms and the corresponding diagnostic complexity.

The prevalence of CFS-like syndromes expanded in the context of the COVID-19 pandemic, increasing the disorder and treatment burden. Thus, this article aimed to draw attention to the possibilities to strengthen the integrative approach to diagnosing and treating chronic disorders and multiple long-term conditions.

The main critical success factors identified for integrative approaches were: a holistic approach, that provides a more comprehensive diagnostic and personalized treatment strategy, a multidisciplinary team, and patient engagement. The strengths and weaknesses of these factors were explored and coaching was identified as a potential unifying and reinforcing element.

Coaching has a wide spectrum of manifestations clearly representing a holistic approach, that has been successfully used in multidisciplinary team building. Moreover, coaching exposes support addressing the patient engagement issues identified by the Patient Needs-Resources Model (PN-R Model) such as low levels of self-efficacy, optimism, and subjective well-being.

Coaching may assist patients to identify and prioritize their goals, becoming aware of their personal resources, developing strategies for managing symptoms, and building skills to increase their self-efficacy and active engagement in the treatment process. Therefore, the authors emphasize coaching as a perspective element of optimization of patient care, that requires additional theoretical and long-term empirical research.

Source: Araja D, Krumina A, Nora-Krukle Z, Schneider ME, Berkis U, Murovska M. Coaching to strengthen critical success factors in integrative care for chronic fatigue patients: the Patient Needs-Resources Model. Front Neurosci. 2023 Jul 21;17:1202930. doi: 10.3389/fnins.2023.1202930. PMID: 37547141; PMCID: PMC10400772. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10400772/ (Full text)

Ivabradine effects on COVID-19-associated postural orthostatic tachycardia syndrome: a single center prospective study

Abstract:

Background: A wide range of cardiac arrhythmias were reported in the setting of active infection or as a complication of COVID-19. The main pathophysiology can be attributed to dysautonomia or autonomic nervous system dysfunction. Postural orthostatic tachycardia syndrome (POTS) is a complex, multisystemic disorder affecting usually younger age with tachycardia at rest or with minimal effort being the main symptom. Data regarding the safety and efficacy of ivabradine in POTS treatment is limited to small studies and case reports.

Methods: This prospective observational study included a total of 55 COVID-19-associated POTS patients after the exclusion of other causes of tachycardia. Ivabradine 5 mg twice daily was initiated. Re-assessment of patients’ symptoms, heart rate, and heart rate variability (HRV) parameters’ changes after 3 days of ivabradine therapy was done.

Results: The mean age of the included patients was 30.5±6.9 years with 32 patients being males (58.2%). 43 of 55 (78%) of the included patients reported significant improvement of the symptoms within 7 days of ivabradine therapy. 24-hour heart rate (minimum, average, and maximum) was significantly lower (p-value < 0.0001*, = 0.001*, < 0.0001* consecutively) with a significant difference in HRV time-domain parameters (SDNN, rMSSD) (p-value < 0.0001*) after ivabradine therapy.

Conclusion: In a prospective study that evaluated the effects of ivabradine in post-COVID-19 POTS, patients treated with ivabradine reported improvement of their symptoms within 7 days of ivabradine treatment with a significant reduction of 24-hour average, minimum, and maximum heart rate, and improvement of HRV time domains parameters. Ivabradine might be a useful option to relieve symptoms of tachycardia in COVID-19 POTS. Further research is required to confirm the safety and efficacy of ivabradine in POTS treatment.

Source: Abdelnabi M, Saleh Y, Ahmed A, Benjanuwattra J, Leelaviwat N, Almaghraby A. Ivabradine effects on COVID-19-associated postural orthostatic tachycardia syndrome: a single center prospective study. Am J Cardiovasc Dis. 2023 Jun 25;13(3):162-167. PMID: 37469536; PMCID: PMC10352820. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10352820/ (Full text)

Prolonged indoleamine 2,3-dioxygenase-2 activity and associated cellular stress in post-acute sequelae of SARS-CoV-2 infection

Abstract:

Background: Post-acute sequela of SARS-CoV-2 infection (PASC) encompass fatigue, post-exertional malaise and cognitive problems. The abundant expression of the tryptophan-catabolizing enzyme indoleamine 2,3-dioxygenase-2 (IDO2) in fatal/severe COVID-19, led us to determine, in an exploratory observational study, whether IDO2 is expressed and active in PASC, and may correlate with pathophysiology.

Methods: Plasma or serum, and peripheral blood mononuclear cells (PBMC) were obtained from well-characterized PASC patients and SARS-CoV-2-infected individuals without PASC. We assessed tryptophan and its degradation products by UPLC-MS/MS. IDO2 activity, its potential consequences, and the involvement of the aryl hydrocarbon receptor (AHR) in IDO2 expression were determined in PBMC from another PASC cohort by immunohistochemistry (IHC) for IDO2, IDO1, AHR, kynurenine metabolites, autophagy, and apoptosis. These PBMC were also analyzed by metabolomics and for mitochondrial functioning by respirometry. IHC was also performed on autopsy brain material from two PASC patients.

Findings: IDO2 is expressed and active in PBMC from PASC patients, as well as in brain tissue, long after SARS-CoV-2 infection. This is paralleled by autophagy, and in blood cells by reduced mitochondrial functioning, reduced intracellular levels of amino acids and Krebs cycle-related compounds. IDO2 expression and activity is triggered by SARS-CoV-2-infection, but the severity of SARS-CoV-2-induced pathology appears related to the generated specific kynurenine metabolites. Ex vivo, IDO2 expression and autophagy can be halted by an AHR antagonist.

Interpretation: SARS-CoV-2 infection triggers long-lasting IDO2 expression, which can be halted by an AHR antagonist. The specific kynurenine catabolites may relate to SARS-CoV-2-induced symptoms and pathology.

Source: Guo L, Appelman B, Mooij-Kalverda K, Houtkooper RH, van Weeghel M, Vaz FM, Dijkhuis A, Dekker T, Smids BS, Duitman JW, Bugiani M, Brinkman P, Sikkens JJ, Lavell HAA, Wüst RCI, van Vugt M, Lutter R; Amsterdam UMC COVID-19 Biobank study Group. Prolonged indoleamine 2,3-dioxygenase-2 activity and associated cellular stress in post-acute sequelae of SARS-CoV-2 infection. EBioMedicine. 2023 Jul 26;94:104729. doi: 10.1016/j.ebiom.2023.104729. Epub ahead of print. PMID: 37506544; PMCID: PMC10406961. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10406961/ (Full text)

Role of Janus Kinase inhibitors in the management of pulmonary involvement due to Long COVID-19 disease: A case control study

Abstract:

Objectives: Ongoing symptomatic coronavirus disease 2019 (OSC) is defined as persistent symptoms beyond 4 weeks of acute illness. OSC leads to prolonged hospitalization and oxygen dependence. We aimed to find the outcome of Janus kinase inhibitors (JAKi) as a steroid-sparing agent to treat OSC.

Methods: In this single-center case-controlled study comparing JAKi and corticosteroids in OSC cases, data of 41 cases out of 86 were included – 21 in the JAKi group and 20 in the corticosteroid group from 4 weeks of acute illness to the next 4 weeks. Clinical parameters and inflammatory markers were recorded. The primary outcome was to compare the proportion of patients who were able to maintain oxygen saturation ≥95% with any oxygen supplementation in the two groups.

Results: The baseline clinical and demographic characteristics were similar in the two groups. The age was 53.65 ± 9.8 years and 51.48 ± 14.0 years in the corticosteroid group and JAKi group, respectively. At the baseline, 85% of patients in the corticosteroid group and 85.8% in the JAKi group were on oxygen support. The most common symptom in both groups was breathlessness followed by cough. Twenty percent of patients in the JAKi group received baricitinib and the remaining were given tofacitinib. At the time of follow-up, the majority of cases had a significant reduction in C-reactive protein (CRP) and D-dimer; however, the change in CRP and D-dimer was similar in both groups. The number of patients off oxygen support at 4 weeks was higher in the JAKi group (85% in the corticosteroid group vs. 95.2% in the JAKi group, P = 0.269), and the median time to liberation from oxygen support was significantly lower in JAKi group (19 days in corticosteroid group vs. 9 days in JAKi group, P < 0.001). The frequency of any adverse event was also higher in the corticosteroid group (70% vs. 23.8%, P = 0.003).

Conclusion: JAKi can be used as immunomodulatory drugs in hypoxic OSC cases having evidence of ongoing inflammation.

Source: Singh PK, Sharma VK, Lalwani LK, Chaudhry D, Govindagoudar MB, Sriram CP, Ahuja A. Role of Janus Kinase inhibitors in the management of pulmonary involvement due to Long COVID-19 disease: A case control study. Turk J Emerg Med. 2023 Jun 26;23(3):149-155. doi: 10.4103/tjem.tjem_363_22. PMID: 37529783; PMCID: PMC10389097. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10389097/ (Full text)

Exercise Capacity and Vascular Function in Long-COVID Sufferers

Abstract:

Background: Exercise intolerance is a prominent aetiology of long-COVID syndrome, yet the mechanisms causing the debilitation remain unknown. Vascular dysfunction is thought to play a role, hence we sought to determine if there is a relationship between exercise capacity and vascular function in COVID survivors.

Methods: Forty-two COVID-19 survivors; 33 self-identified long-COVID sufferers and 9 recovered controls (40.7±11.8 vs 40.2±14.5 years, both 67% female) underwent extensive phenotyping >3 months post-infection. Blood pressure (BP) and heart rate were measured (automated BP device), before carotid, femoral, and radial tonometry (carotid–femoral pulse wave velocity; [cPWV], augmentation index; [AIx]) were performed to assess vascular stiffness. Endothelium-dependent and independent dilatation were assessed via brachial artery flow-mediated dilation ([FMD]; Doppler-ultrasound) in response to reactive hyperaemia and glyceryl trinitrate respectively. Cardiopulmonary exercise testing determined peak oxygen uptake (VO2).

Results: Long-COVID sufferers had reduced VO2 peak compared to controls (26.5±7.0 vs 32.8±11.3 ml/min/kg, p= 0.045). Haemodynamic and vascular function were similar between groups, though there was a medium effect size (ES) for between group differences in cPWV (6.6±1.2 vs 6.1±0.9 m/sec, p=0.20; ES 0.44) and AIx (14±15% vs 4±16%, p=0.11; ES 0.67). VO2 peak was inversely correlated with AIx (r = -0.60, p<0.001) and cPWV (r = -0.55, p<0.001). There was no significant association between endothelial function and exercise capacity parameters.

Conclusions: Lower VO2peak measures in long-COVID participants were strongly associated with increased AIx and cPWV. These findings indicate the need for further longitudinal investigations to determine if these manifestations persist and impact long-term cardiovascular health.

Source: I.Wallace, E. Howden, D. Green, G. Sesa-Ashton. Exercise Capacity and Vascular Function in Long-COVID Sufferers. Heart, Lung and Circulation. ABSTRACT| VOLUME 32, SUPPLEMENT 3, S114-S115, JULY 2023. https://www.heartlungcirc.org/article/S1443-9506(23)04000-3/fulltext