Tag: proinflammatory markers

Large-scale phenotyping of patients with long COVID post-hospitalization reveals mechanistic subtypes of disease

Abstract:

One in ten severe acute respiratory syndrome coronavirus 2 infections result in prolonged symptoms termed long coronavirus disease (COVID), yet disease phenotypes and mechanisms are poorly understood1. Here we profiled 368 plasma proteins in 657 participants ≥3 months following hospitalization. Of these, 426 had at least one long COVID symptom and 233 had fully recovered.

Elevated markers of myeloid inflammation and complement activation were associated with long COVID. IL-1R2, MATN2 and COLEC12 were associated with cardiorespiratory symptoms, fatigue and anxiety/depression; MATN2, CSF3 and C1QA were elevated in gastrointestinal symptoms and C1QA was elevated in cognitive impairment. Additional markers of alterations in nerve tissue repair (SPON-1 and NFASC) were elevated in those with cognitive impairment and SCG3, suggestive of brain-gut axis disturbance, was elevated in gastrointestinal symptoms.

Severe acute respiratory syndrome coronavirus 2-specific immunoglobulin G (IgG) was persistently elevated in some individuals with long COVID, but virus was not detected in sputum. Analysis of inflammatory markers in nasal fluids showed no association with symptoms.

Our study aimed to understand inflammatory processes that underlie long COVID and was not designed for biomarker discovery. Our findings suggest that specific inflammatory pathways related to tissue damage are implicated in subtypes of long COVID, which might be targeted in future therapeutic trials.

Source: Liew F, Efstathiou C, Fontanella S, Richardson M, Saunders R, Swieboda D, Sidhu JK, Ascough S, Moore SC, Mohamed N, Nunag J, King C, Leavy OC, Elneima O, McAuley HJC, Shikotra A, Singapuri A, Sereno M, Harris VC, Houchen-Wolloff L, Greening NJ, Lone NI, Thorpe M, Thompson AAR, Rowland-Jones SL, Docherty AB, Chalmers JD, Ho LP, Horsley A, Raman B, Poinasamy K, Marks M, Kon OM, Howard LS, Wootton DG, Quint JK, de Silva TI, Ho A, Chiu C, Harrison EM, Greenhalf W, Baillie JK, Semple MG, Turtle L, Evans RA, Wain LV, Brightling C, Thwaites RS, Openshaw PJM; PHOSP-COVID collaborative group; ISARIC investigators. Large-scale phenotyping of patients with long COVID post-hospitalization reveals mechanistic subtypes of disease. Nat Immunol. 2024 Apr;25(4):607-621. doi: 10.1038/s41590-024-01778-0. Epub 2024 Apr 8. PMID: 38589621; PMCID: PMC11003868. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11003868/ (Full text)

Blood–brain barrier disruption and sustained systemic inflammation in individuals with long COVID-associated cognitive impairment

Abstract:

Vascular disruption has been implicated in coronavirus disease 2019 (COVID-19) pathogenesis and may predispose to the neurological sequelae associated with long COVID, yet it is unclear how blood–brain barrier (BBB) function is affected in these conditions. Here we show that BBB disruption is evident during acute infection and in patients with long COVID with cognitive impairment, commonly referred to as brain fog.

Using dynamic contrast-enhanced magnetic resonance imaging, we show BBB disruption in patients with long COVID-associated brain fog. Transcriptomic analysis of peripheral blood mononuclear cells revealed dysregulation of the coagulation system and a dampened adaptive immune response in individuals with brain fog.

Accordingly, peripheral blood mononuclear cells showed increased adhesion to human brain endothelial cells in vitro, while exposure of brain endothelial cells to serum from patients with long COVID induced expression of inflammatory markers.

Together, our data suggest that sustained systemic inflammation and persistent localized BBB dysfunction is a key feature of long COVID-associated brain fog.

Source: Greene C, Connolly R, Brennan D, Laffan A, O’Keeffe E, Zaporojan L, O’Callaghan J, Thomson B, Connolly E, Argue R, Martin-Loeches I, Long A, Cheallaigh CN, Conlon N, Doherty CP, Campbell M. Blood-brain barrier disruption and sustained systemic inflammation in individuals with long COVID-associated cognitive impairment. Nat Neurosci. 2024 Mar;27(3):421-432. doi: 10.1038/s41593-024-01576-9. Epub 2024 Feb 22. PMID: 38388736; PMCID: PMC10917679. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10917679/ (Full text)

Neutrophil degranulation, endothelial and metabolic dysfunction in unvaccinated long COVID patients

Abstract:

Background: Long COVID symptoms are widely diffused and have a poorly understood pathophysiology, with possible involvement of inflammatory cytokines.

Materials and methods: A prospective follow-up study involved 385 unvaccinated patients, started 1 month after SARS-CoV-2 infection and continued for up to 12 months. We compared circulating biomarkers of neutrophil degranulation, endothelial and metabolic dysfunction in subjects with long COVID symptoms and in asymptomatic post-COVID controls.

Results: The highest occurrence of symptoms (71%) was after 3 months from the infection, decreasing to 62.3% and 29.4% at 6 and 12 months, respectively. Compared to controls, long COVID patients had increased levels of the neutrophilic degranulation indices MMP-8 and MPO, of endothelial dysfunction indices L-selectin and P-selectin. Among indices of metabolic dysfunction, leptin levels were higher in long COVID patients than in controls.

Conclusion: In unvaccinated patients, symptoms may persist up to 1 year after acute COVID infection, with increased indices of neutrophil degranulation, endothelial and metabolic dysfunction. The clinical implications of specific inflammatory biomarkers require further attention, especially in individuals with fatigue and long COVID-linked cognitive dysfunctions.

Source: Di Ciaula A, Liberale L, Portincasa P, Khalil M, Galerati I, Farella I, Noto A, JohnBritto S, Moriero M, Michelauz C, Frè F, Olivero C, Bertolotto M, Montecucco F, Carbone F, Bonfrate L. Neutrophil degranulation, endothelial and metabolic dysfunction in unvaccinated long COVID patients. Eur J Clin Invest. 2024 Jan 16:e14155. doi: 10.1111/eci.14155. Epub ahead of print. PMID: 38226472. https://pubmed.ncbi.nlm.nih.gov/38226472/

Metabolomic and immune alterations in long COVID patients with chronic fatigue syndrome

Introduction: A group of SARS-CoV-2 infected individuals present lingering symptoms, defined as long COVID (LC), that may last months or years post the onset of acute disease. A portion of LC patients have symptoms similar to myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS), which results in a substantial reduction in their quality of life. A better understanding of the pathophysiology of LC, in particular, ME/CFS is urgently needed.

Methods: We identified and studied metabolites and soluble biomarkers in plasma from LC individuals mainly exhibiting ME/CFS compared to age-sex-matched recovered individuals (R) without LC, acute COVID-19 patients (A), and to SARS-CoV-2 unexposed healthy individuals (HC).

Results: Through these analyses, we identified alterations in several metabolomic pathways in LC vs other groups. Plasma metabolomics analysis showed that LC differed from the R and HC groups. Of note, the R group also exhibited a different metabolomic profile than HC. Moreover, we observed a significant elevation in the plasma pro-inflammatory biomarkers (e.g. IL-1α, IL-6, TNF-α, Flt-1, and sCD14) but the reduction in ATP in LC patients. Our results demonstrate that LC patients exhibit persistent metabolomic abnormalities 12 months after the acute COVID-19 disease. Of note, such metabolomic alterations can be observed in the R group 12 months after the acute disease. Hence, the metabolomic recovery period for infected individuals with SARS-CoV-2 might be long-lasting. In particular, we found a significant reduction in sarcosine and serine concentrations in LC patients, which was inversely correlated with depression, anxiety, and cognitive dysfunction scores.

Conclusion: Our study findings provide a comprehensive metabolomic knowledge base and other soluble biomarkers for a better understanding of the pathophysiology of LC and suggests sarcosine and serine supplementations might have potential therapeutic implications in LC patients. Finally, our study reveals that LC disproportionally affects females more than males, as evidenced by nearly 70% of our LC patients being female.

Source: Saito Suguru, Shahbaz Shima, Luo Xian, Osman Mohammed, Redmond Desiree, Cohen Tervaert Jan Willem, Li Liang, Elahi Shokrollah. Metabolomic and immune alterations in long COVID patients with chronic fatigue syndrome. Frontiers in Immunology, Vol 15, 2024. DOI=10.3389/fimmu.2024.1341843  https://www.frontiersin.org/articles/10.3389/fimmu.2024.1341843/full (Full text)

Exploring the Joint Potential of Inflammation, Immunity, and Receptor-Based Biomarkers for Evaluating ME/CFS Progression

Abstract:

Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating chronic condition with no identified diagnostic biomarkers to date. Its prevalence is as high as 0.89% according to metastudies, with a quarter of patients bed-or home-bound, which presents a serious public health challenge. Investigations into the inflammation-immunity axis is encouraged by links to outbreaks and disease waves. Recently, research of our group revealed that antibodies to beta2adrenergic (anti-β2AdR) and muscarinic acetylcholine (anti-M4) receptors demonstrate sensitivity to the progression of ME/CFS.

The purpose of this study is to investigate the joint potential of inflammatome -characterized by interferon (IFN)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-2, IL-21, Il-23, IL-6, IL-17A, Activin-B, immunome (IgG1, IgG2, IgG3, IgG4, IgM, IgA) and receptor-based biomarkers (anti-M3, anti-M4, anti-β2AdR) determined for evaluating ME/CFS progression, and to identify an optimal selection for future validation in prospective clinical studies.

Methods: A dataset was used originating from 188 persons, including 54 healthy controls, 30 patients classified as “mild” by severity, 73 as “moderate,” and 31 as “severe,” clinically assessed by Fukuda/CDC 1994 and International consensus criteria. Markers characterizing inflammatome, immunome, and receptor-based biomarkers were determined in blood plasma via ELISA and multiplex methods.

Statistical analysis was done via correlation analysis, principal component, and linear discriminant analysis, and random forest classification; inter-group differences tested via nonparametric Kruskal-Wallis H test followed by the two-stage linear step-up procedure of Benjamini, Krieger, and Yekutieli, and via Mann-Whitney U test.

The association between inflammatome and immunome markers is broader and stronger (coupling) in severe group. Principal component factoring separate components affiliated with inflammatome, immunome, and receptor biomarkers. Random forest modeling demonstrates an out-of-box accuracy for splitting healthy/with condition groups of over 90%, and of 45% for healthy/severity groups. Classifiers with the highest potential are anti-β2AdR, anti-M4, IgG4, IL-2, and IL-6.

Discussion: Association between inflammatome and immunome markers is a candidate for controlled clinical study of ME/CFS progression markers that could be used for treatment individualization. Thus, coupling effects between inflammation and immunity have a potential for the identification of prognostic factors in the context of ME/CFS progression mechanism studies.

Source: Uldis Berkis, Simons Svirskis, Angelika Krumina, Sabine Gravelsina, Anda Vilmane, Diana Araja, Zaiga Nora-Krukle, Modra Murovska. Exploring the Joint Potential of Inflammation, Immunity, and Receptor-Based Biomarkers for Evaluating ME/CFS Progression. Frontiers in Immunology. Sec. Autoimmune and Autoinflammatory Disorders : Autoimmune Disorders. Volume 14- 2023.  https://www.frontiersin.org/articles/10.3389/fimmu.2023.1294758/abstract

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

Abstract:

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

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

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

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

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

Analyzing the Interplay between COVID-19 Viral Load, Inflammatory Markers, and Lymphocyte Subpopulations on the Development of Long COVID

Abstract:

The global impact of the SARS-CoV-2 infection has been substantial, affecting millions of people. Long COVID, characterized by persistent or recurrent symptoms after acute infection, has been reported in over 40% of patients. Risk factors include age and female gender, and various mechanisms, including chronic inflammation and viral persistence, have been implicated in long COVID’s pathogenesis. However, there are scarce studies in which multiple inflammatory markers and viral load are analyzed simultaneously in acute infection to determine how they predict for long COVID at long-term follow-up. This study explores the association between long COVID and inflammatory markers, viral load, and lymphocyte subpopulation during acute infection in hospitalized patients to better understand the risk factors of this disease.
This longitudinal retrospective study was conducted in patients hospitalized with COVID-19 in northern Mexico. Inflammatory parameters, viral load, and lymphocyte subpopulation during the acute infection phase were analyzed, and long COVID symptoms were followed up depending on severity and persistence (weekly or monthly) and assessed 1.5 years after the acute infection.
This study analyzed 79 patients, among them, 41.8% presented long COVID symptoms, with fatigue being the most common (45.5%). Patients with long COVID had higher lymphocyte levels during hospitalization, and NK cell subpopulation levels were also associated with long COVID. ICU admission during acute COVID-19 was also linked to the development of long COVID symptoms.
Source: Rivera-Cavazos A, Luviano-García JA, Garza-Silva A, Morales-Rodríguez DP, Kuri-Ayache M, Sanz-Sánchez MÁ, Santos-Macías JE, Romero-Ibarguengoitia ME, González-Cantú A. Analyzing the Interplay between COVID-19 Viral Load, Inflammatory Markers, and Lymphocyte Subpopulations on the Development of Long COVID. Microorganisms. 2023; 11(9):2241. https://doi.org/10.3390/microorganisms11092241 https://www.mdpi.com/2076-2607/11/9/2241 (Full text)

A Thesis on Immune Differences in Chronic Fatigue Syndrome, Fibromyalgia and Healthy Controls

Abstract:

Background: Chronic Fatigue Syndrome (CFS) and Fibromyalgia (FM) are debilitating disorders that significantly affect the daily lives of those suffering from them, as well as their loved ones. Both conditions have overlapping clinical features that resemble inflammatory disorders, and overlapping symptoms, such as depression, suggest central nervous system (CNS) involvement. The role of the immune system’s soluble messengers in the pathogenesis of CFS and FM has been under investigation, but so far the results are inconclusive. In addition, there is growing evidence that the kynurenine pathway is involved in the pathology of diseases related to the CNS, yet the role of each metabolite is not clear. The relationship between kynurenine metabolism and CFS and FM has not been extensively explored. Few studies have simultaneously examined the immunological status in both CFS and FM, making this thesis the first to comprehensively evaluate the potential distinct immunological differences between the two disorders.

Objective: The objective of this study was to compare the CFS and FM with healthy controls, regarding the levels of several soluble blood markers related to the immune system. The markers chosen were:

  • The inflammatory marker high-sensitive CRP (hsCRP)
  • The following cytokines and chemokines: Interferon (IFN)-γ, Interleukin (IL)-1β, IL1ra, IL-4, IL-6, IL-8, IL-10, IL-17, Interferon gamma-induced protein (IP)-10, Monocyte Chemoattractant Protein (MCP)-1, Transforming Growth Factor (TGF)-β1, TGF-β2, TGF-β3 and Tumour Necrosis Factor (TNF)-α
  • The metabolites and their ratios of the kynurenine pathway: Tryptophan (Try), kynurenine (Kyn), kynurenic acid (KA), 3-hydroxykykynurenine (HK), anthranilic acid (AA), xanthurenic acid (XA), 3-hydroxyanthranilic acid (HAA), quinolinic acid (QA) and picolinic acid (Pic).

Method: The population consisted of three groups: CFS patients (n = 49), FM patients (n = 58), and healthy controls (n = 54). All participants were females aged 18–60. Patients were recruited from a specialised university hospital clinic and controls were recruited by advertisement among the staff and students at the hospital and university.

Plasma levels of hsCRP were analysed at the hospital. The cytokines and chemokines IFN-γ, IL-1β, IL-1ra, xii IL-4, IL-6, IL-8, IL-10, IL-17, IP-10, MCP-1, TGF-β1, TGF-β2, TGF-β3, and TNF-α were analysed by multiplex. Kynurenine metabolites were analysed by LC-MS/MS.

Linear regression models of log-transformed data for hsCRP and the kynurenine metabolites were conducted for comparison of the three groups CFS, FM and controls. The Kruskal-Wallis test was used to analyse differences of cytokines between the three groups. Main findings were controlled for age, body mass index (BMI), and symptoms of anxiety and depression.

Results: hsCRP levels were significantly higher for both the CFS and FM groups compared to healthy controls when adjusting for age and BMI (p = .006). There was no difference between the two patient groups. Level of hsCRP was affected by BMI (p < .001) but not age.

MCP-1 was significantly increased in both patient groups compared to healthy controls (p < .001). IL-1β, Il-4, IL-6, TNF-α, TGF-β1, TGF-β2, TGF-β3 (all p < .001), IL-10 (p = .003) and IL17 (p = .002) all were significantly lower in the patient groups compared to healthy controls. IFN-γ was significantly lower in the FM group (p < .001). For IL-8, IP-10 and IL1ra there were no significant difference.

QA differed between CFS and FM patients (p = .036) and was related to higher levels of BMI (p = .002). The KA/QA ratio was lower for CFS patients compared to healthy controls (p = .016). The KA/HK ratio was lower for FM patients compared to healthy controls, and this lower ratio was associated with increased symptoms of pain (p = .002). The kynurenine aminotransferase II (KAT II) enzymatic activity given by XA/HK was lower for FM patients compared to healthy controls (p = .013). In addition, BMI was negatively associated with enhanced KAT II enzymatic activity (p = .039).

Symptoms of anxiety and depression were not associated with any of the immune markers studied.

Conclusion: In our material hsCRP and MCP-1 are increased in patients both with CFS and with FM, while several other cytokines are either similar or significantly lower in patients than controls. Our study also indicates associations between kynurenine metabolism and CFS and FM. Kynurenine also is associated with single symptoms such as fatigue and pain. Forthcoming studies indicating interactions and causative effects, or restoration of the inflammatory status, may place cytokines and kynurenine metabolites as a target for treatment as well as prevention of these conditions in the future.

Source: Groven, Nina. A Thesis on Immune Differences in Chronic Fatigue Syndrome, Fibromyalgia and Healthy Controls. PhD Thesis [Norwegian University of Science and Technology] https://ntnuopen.ntnu.no/ntnu-xmlui/handle/11250/3072207 (Full text available as PDF file)

Ultra-rare RTEL1 gene variants associate with acute severity of COVID-19 and evolution to pulmonary fibrosis as a specific long COVID disorder

Abstract:

Background: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a novel coronavirus that caused an ongoing pandemic of a pathology termed Coronavirus Disease 19 (COVID-19). Several studies reported that both COVID-19 and RTEL1 variants are associated with shorter telomere length, but a direct association between the two is not generally acknowledged. Here we demonstrate that up to 8.6% of severe COVID-19 patients bear RTEL1 ultra-rare variants, and show how this subgroup can be recognized.

Methods: A cohort of 2246 SARS-CoV-2-positive subjects, collected within the GEN-COVID Multicenter study, was used in this work. Whole exome sequencing analysis was performed using the NovaSeq6000 System, and machine learning methods were used for candidate gene selection of severity. A nested study, comparing severely affected patients bearing or not variants in the selected gene, was used for the characterisation of specific clinical features connected to variants in both acute and post-acute phases.

Results: Our GEN-COVID cohort revealed a total of 151 patients carrying at least one RTEL1 ultra-rare variant, which was selected as a specific acute severity feature. From a clinical point of view, these patients showed higher liver function indices, as well as increased CRP and inflammatory markers, such as IL-6. Moreover, compared to control subjects, they present autoimmune disorders more frequently. Finally, their decreased diffusion lung capacity for carbon monoxide after six months of COVID-19 suggests that RTEL1 variants can contribute to the development of SARS-CoV-2-elicited lung fibrosis.

Conclusion: RTEL1 ultra-rare variants can be considered as a predictive marker of COVID-19 severity, as well as a marker of pathological evolution in pulmonary fibrosis in the post-COVID phase. This notion can be used for a rapid screening in hospitalized infected people, for vaccine prioritization, and appropriate follow-up assessment for subjects at risk.

Trial Registration NCT04549831 (www.clinicaltrial.org)

Source: Bergantini, L., Baldassarri, M., d’Alessandro, M. et al. Ultra-rare RTEL1 gene variants associate with acute severity of COVID-19 and evolution to pulmonary fibrosis as a specific long COVID disorder. Respir Res 24, 158 (2023). https://doi.org/10.1186/s12931-023-02458-7 https://respiratory-research.biomedcentral.com/articles/10.1186/s12931-023-02458-7 (Full text)

Reduced exercise capacity, chronotropic incompetence, and early systemic inflammation in cardiopulmonary phenotype Long COVID

Abstract:

Background: Mechanisms underlying persistent cardiopulmonary symptoms following SARS-CoV-2 infection (post-acute sequelae of COVID-19 “PASC” or “Long COVID”) remain unclear. This study sought to elucidate mechanisms of cardiopulmonary symptoms and reduced exercise capacity.

Methods: We conducted cardiopulmonary exercise testing (CPET), cardiac magnetic resonance imaging (CMR) and ambulatory rhythm monitoring among adults > 1 year after confirmed SARS-CoV-2 infection in a post-COVID cohort, compared those with or without symptoms, and correlated findings with previously measured biomarkers.

Results: Sixty participants (median age 53, 42% female, 87% non-hospitalized) were studied at median 17.6 months following SARS-CoV-2 infection. On CPET, 18/37 (49%) with symptoms had reduced exercise capacity (<85% predicted) compared to 3/19 (16%) without symptoms (p = 0.02). Adjusted peak VO2 was 5.2 ml/kg/min lower (95%CI 2.1-8.3; p = 0.001) or 16.9% lower percent predicted (95%CI 4.3-29.6; p = 0.02) among those with symptoms. Chronotropic incompetence was common. Inflammatory markers and antibody levels early in PASC were negatively correlated with peak VO2 more than 1 year later. Late-gadolinium enhancement on CMR and arrhythmias were absent.

Conclusions: Cardiopulmonary symptoms >1 year following COVID-19 were associated with reduced exercise capacity, which was associated with elevated inflammatory markers early in PASC. Chronotropic incompetence may explain exercise intolerance among some with cardiopulmonary Long COVID.

Source: Durstenfeld MS, Peluso MJ, Kaveti P, Hill C, Li D, Sander E, Swaminathan S, Arechiga VM, Lu S, Goldberg SA, Hoh R, Chenna A, Yee BC, Winslow JW, Petropoulos CJ, Kelly JD, Glidden DV, Henrich TJ, Martin JN, Lee YJ, Aras MA, Long CS, Grandis DJ, Deeks SG, Hsue PY. Reduced exercise capacity, chronotropic incompetence, and early systemic inflammation in cardiopulmonary phenotype Long COVID. J Infect Dis. 2023 May 11:jiad131. doi: 10.1093/infdis/jiad131. Epub ahead of print. PMID: 37166076. https://academic.oup.com/jid/advance-article/doi/10.1093/infdis/jiad131/7159960 (Full text available as PDF file)