Tag: long covid pathomechanism

Long COVID: A proposed hypothesis-driven model of viral persistence for the pathophysiology of the syndrome

Abstract:

Background: Long COVID (coronavirus disease 2019) syndrome includes a group of patients who, after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), exhibit lingering mild-to-moderate symptoms and develop medical complications that can have lasting health problems. In this report, we propose a model for the pathophysiology of the long COVID presentation based on increased proinflammatory cytokine production that results from the persistence of the SARS-CoV-2 virus or one of its molecular components. Associated with this hyperproduction of inflammatory cytokines is a heightened activity of nuclear factor κ B (NF-κB) and p38 mitogen-activated protein kinase signaling pathways that regulate cytokine production.

Objective: The purpose of the present report was to review the causes of long COVID syndrome and suggest ways that can provide a basis for a better understanding of the clinical symptomatology for the of improved diagnostic and therapeutic procedures for the condition.

Methods: Extensive research was conducted in medical literature data bases by applying terms such as “long COVID” associated with “persistence of the SARS-CoV-2 virus” “spike protein’ “COVID-19” and “biologic therapies.”

Results and Conclusions: In this model of the long COVID syndrome, the persistence of SARS-CoV-2 is hypothesized to trigger a dysregulated immune system with subsequent heightened release of proinflammatory cytokines that lead to chronic low-grade inflammation and multiorgan symptomatology. The condition seems to have a genetic basis, which predisposes individuals to have a diminished immunologic capacity to completely clear the virus, with residual parts of the virus persisting. This persistence of virus and resultant hyperproduction of proinflammatory cytokines are proposed to form the basis of the syndrome.

Source: Buonsenso D, Piazza M, Boner AL, Bellanti JA. Long COVID: A proposed hypothesis-driven model of viral persistence for the pathophysiology of the syndrome. Allergy Asthma Proc. 2022 May 1;43(3):187-193. doi: 10.2500/aap.2022.43.220018. PMID: 35524358. https://pubmed.ncbi.nlm.nih.gov/35524358/ https://www.ingentaconnect.com/content/ocean/aap/2022/00000043/00000003/art00003;jsessionid=pp9ea7gev7kv.x-ic-live-01#  (Full text available as download)

Prevalence of vitamin D deficiency among patients attending Post COVID-19 follow-up clinic: a cross-sectional study

Abstract:

Objective: Post-COVID-19 syndrome appears to be a multi-organ illness with a broad spectrum of manifestations, occurring after even mild acute illness. Limited data currently available has suggested that vitamin D deficiency may play a role in COVID-19 cases. However, to our knowledge, no study has examined the frequency of vitamin D deficiency in post-COVID-19 cases and its effect on the symptom severity. The aim of this study is to both screen the frequency of vitamin D deficiency in post-COVID-19 syndrome patients and to study its relation to persistent symptoms.

Patients and methods: A cross-sectional, single-center study was conducted involving all cases attending post-COVID-19 follow-up clinic from November 2020 to May 2021. Complete history, clinical examination, and laboratory analysis [kidney functions, serum calcium, C-reactive protein, serum ferritin, Serum 25-(OH) vitamin D] was done as well as HRCT chest.

Results: The study included 219 post-COVID-19 cases, 84% had deficient vitamin D levels (< 20 ng/dL); 11.4% had insufficient level (20-30 ng/dL) and only 4.9 % reported normal level. There was no link between levels of vitamin D with either the acute or post-COVID-19 symptoms in the studied groups.

Conclusions: Despite the prevalence of vitamin D deficiency among the study population, no association was observed between the levels of vitamin D and post-COVID-19 symptoms. It appears that post-COVID-19 syndrome pathophysiology involves a more complex interaction with the immune system. Dedicated clinical trials are advised to better study vitamin D levels and the related disease severity in COVID-19 patients.

Source: Mohamed Hussein AAR, Galal I, Amin MT, Moshnib AA, Makhlouf NA, Makhlouf HA, Abd-Elaal HK, Kholief KMS, Abdel Tawab DA, Kamal Eldin KA, Attia AM, Othman AEA, Shah J, Aiash H. Prevalence of vitamin D deficiency among patients attending Post COVID-19 follow-up clinic: a cross-sectional study. Eur Rev Med Pharmacol Sci. 2022 Apr;26(8):3038-3045. doi: 10.26355/eurrev_202204_28635. PMID: 35503606. https://www.europeanreview.org/article/28635 (Full text)

Long-Term Cardiovascular Effects of COVID-19: Emerging Data Relevant to the Cardiovascular Clinician

Abstract:

Purpose of review: COVID-19 is now a global pandemic and the illness affects multiple organ systems, including the cardiovascular system. Long-term cardiovascular consequences of COVID-19 are not yet fully characterized. This review seeks to consolidate available data on long-term cardiovascular complications of COVID-19 infection.

Recent findings: Acute cardiovascular complications of COVID-19 infection include myocarditis, pericarditis, acute coronary syndrome, heart failure, pulmonary hypertension, right ventricular dysfunction, and arrhythmia. Long-term follow-up shows increased incidence of arrhythmia, heart failure, acute coronary syndrome, right ventricular dysfunction, myocardial fibrosis, hypertension, and diabetes mellitus. There is increased mortality in COVID-19 patients after hospital discharge, and initial myocardial injury is associated with increased mortality. Emerging data demonstrates increased incidence of cardiovascular illness and structural changes in recovered COVID-19 patients. Future research will be important in understanding the clinical significance of these structural abnormalities, and to determine the effect of vaccines on preventing long-term cardiovascular complications.

Source: Tobler DL, Pruzansky AJ, Naderi S, Ambrosy AP, Slade JJ. Long-Term Cardiovascular Effects of COVID-19: Emerging Data Relevant to the Cardiovascular Clinician. Curr Atheroscler Rep. 2022 May 4:1–8. doi: 10.1007/s11883-022-01032-8. Epub ahead of print. PMID: 35507278; PMCID: PMC9065238. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9065238/ (Full text)

Clinical, radiological, and transbronchial biopsy findings in patients with long COVID-19: a case series

Abstract:

in English, Portuguese

This brief communication demonstrates the correlation of persistent respiratory symptoms with functional, tomographic, and transbronchial pulmonary biopsy findings in patients with COVID-19 who had a long follow-up period. We report a series of six COVID-19 patients with pulmonary involvement who presented with persistent dyspnea within 4-15 months of discharge. We performed transbronchial biopsies, and the histopathological pattern consistently demonstrated peribronchial remodeling with interstitial pulmonary fibrosis. Therefore, lung biopsy may be useful in the approach of patients with long COVID-19, although the type of procedure, its precise indication, and the moment to perform it are yet to be clarified.

(Brazilian Registry of Clinical Trials-ReBEC; identifier: RBR-8j9kqy [http://www.ensaiosclinicos.gov.br]).

Source: Baldi BG, Fabro AT, Franco AC, Machado MHC, Prudente RA, Franco ET, Marrone SR, Vale SAD, Cezare TJ, Moraes MPT, Ferreira EVM, Albuquerque ALP, Sawamura MVY, Tanni SE. Clinical, radiological, and transbronchial biopsy findings in patients with long COVID-19: a case series. J Bras Pneumol. 2022 Apr 29;48(3):e20210438. doi: 10.36416/1806-3756/e20210438. PMID: 35508067; PMCID: PMC9064656. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9064656/  (Full text)

Evidence mapping and review of long-COVID and its underlying pathophysiological mechanism

Abstract:

Purpose: Apart from the global disease burden of acute COVID-19 disease, the health complications arising after recovery have been recognized as a long-COVID or post-COVID-19 syndrome. Evidences of long-COVID symptoms involving various organ systems are rapidly growing in literature. The objective was to perform a rapid review and evidence mapping of systemic complications and symptoms of long-COVID and underlying pathophysiological mechanisms.

Methods: Publications reporting clinical trials, observational cohort studies, case-control studies, case-series, meta-analysis, and systematic reviews, focusing on the squeal of the disease, consequences of COVID-19 treatment/hospitalization, long-COVID, chronic COVID syndrome, and post acute COVID-19 were reviewed in detail for the narrative synthesis of frequency, duration, risk factors, and pathophysiology.

Results: The review highlights that pulmonary, neuro-psychological, and cardiovascular complications are major findings in most epidemiological studies. However, dysfunctional gastrointestinal, endocrine, and metabolic health are recent findings for which underlying pathophysiological mechanisms are poorly understood. Analysis of the clinical trial landscape suggests that more than 50% of the industry-sponsored trials are focused on pulmonary symptoms. In contrast to the epidemiological trends and academic trials, cardiovascular complications are not a focus of industry-sponsored trials, suggestive of the gaps in the research efforts.

Conclusion: The gap in epidemiological trends and academic trials, particularly concerning cardiovascular complications not being a focus of industry-sponsored trials is suggestive of the gaps in research efforts and longer follow-up durations would help identify other long-COVID-related health issues such as reproductive health and fertility.

Source: Umesh A, Pranay K, Pandey RC, Gupta MK. Evidence mapping and review of long-COVID and its underlying pathophysiological mechanism. Infection. 2022 Apr 30:1–14. doi: 10.1007/s15010-022-01835-6. Epub ahead of print. PMID: 35489015; PMCID: PMC9055372. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9055372/ (Full text)

Dissecting the Molecular Mechanisms Surrounding Post-COVID-19 Syndrome and Neurological Features

Abstract:

Many of the survivors of the novel coronavirus disease (COVID-19) are suffering from persistent symptoms, causing significant morbidity and decreasing their quality of life, termed “post-COVID-19 syndrome” or “long COVID”. Understanding the mechanisms surrounding PCS is vital to developing the diagnosis, biomarkers, and possible treatments.

Here, we describe the prevalence and manifestations of PCS, and similarities with previous SARS epidemics. Furthermore, we look at the molecular mechanisms behind the neurological features of PCS, where we highlight important neural mechanisms that may potentially be involved and pharmacologically targeted, such as glutamate reuptake in astrocytes, the role of NMDA receptors and transporters (EAAT2), ROS signaling, astrogliosis triggered by NF-κB signaling, KNDy neurons, and hypothalamic networks involving Kiss1 (a ligand for the G-protein-coupled receptor 54 (GPR54)), among others. We highlight the possible role of reactive gliosis following SARS-CoV-2 CNS injury, as well as the potential role of the hypothalamus network in PCS manifestations.

Source: Mohamed MS, Johansson A, Jonsson J, Schiöth HB. Dissecting the Molecular Mechanisms Surrounding Post-COVID-19 Syndrome and Neurological Features. Int J Mol Sci. 2022 Apr 12;23(8):4275. doi: 10.3390/ijms23084275. PMID: 35457093. https://www.mdpi.com/1422-0067/23/8/4275/htm (Full text)

Risk factors and multidimensional assessment of long COVID fatigue: a nested case-control study

Abstract:

Background: Fatigue is the most prevalent and debilitating long COVID symptom, however risk factors and pathophysiology of this condition remain unknown. We assessed risk factors for long COVID fatigue and explored its possible pathophysiology.

Methods: Nested case-control study in a COVID recovery clinic. Individuals with (cases) and without (controls) significant fatigue were included. We performed a multidimensional assessment evaluating various parameters, including pulmonary function tests and cardiopulmonary exercise testing, and implemented multivariable logistic regression to assess risk factors for significant long COVID fatigue.

Results: Total of 141 individuals were included. Mean age was 47 (SD 13) years; 115 (82%) were recovering from mild COVID-19. Mean time for evaluation was 8 months following COVID-19. Sixty-six (47%) individuals were classified with significant long COVID fatigue. They had significantly higher number of children, lower proportion of hypothyroidism, higher proportion of sore throat during acute illness and long COVID symptoms, and of physical limitation in daily activities. Individuals with fatigue had poorer sleep quality and higher degree of depression. They had significantly lower heart rate [153.52 (22.64) vs 163.52 (18.53), p=0.038] and oxygen consumption per Kg [27.69 (7.52) vs 30.71 (7.52), p=0.036] at peak exercise. The two independent risk factors for fatigue identified in multivariable analysis were peak exercise heart rate (odds ratio [OR] 0.79 per 10 beats/minute, 95% confidence interval [CI] 0.65-0.96, p=0.019); and long COVID memory impairment (OR 3.76, 95% CI 1.57-9.01, p=0.003).

Conclusions: Long COVID fatigue may be related to autonomic dysfunction, impaired cognition and decreased mood. This may suggest a limbic-vagal pathophysiology. Clinical Trial registration: NCT04851561.

Source: Margalit I, Yelin D, Sagi M, Rahat MM, Sheena L, Mizrahi N, Gordin Y, Agmon H, Epstein NK, Atamna A, Tishler O, Daitch V, Babich T, Abecasis D, Yarom Y, Kazum S, Shitenberg D, Baltaxe E, Elkana O, Shapira-Lichter I, Leibovici L, Yahav D. Risk factors and multidimensional assessment of long COVID fatigue: a nested case-control study. Clin Infect Dis. 2022 Apr 11:ciac283. doi: 10.1093/cid/ciac283. Epub ahead of print. PMID: 35403679.  https://pubmed.ncbi.nlm.nih.gov/35403679/

Coronary microvascular health in patients with prior covid-19 infection: implications for long-covid syndrome

Background: SARS-CoV-2 infection has been shown to directly infect coronary vascular endothelium, causing inflammation and plaque instability. We aimed to assess the vascular health of patients with prior COVID-19 using Positron emission tomography (PET) derived coronary flow reserve (CFR).

Methods: A prospective cohort of consecutive patients with PCR confirmed prior COVID-19 infection undergoing clinically indicated PET myocardial perfusion imaging were included and compared to patients with no prior COVID19. CFR was determined by PET and microvascular dysfunction (CMD) was defined as CFR<2.

Results: The study population consisted of 2316 patients (4.4% prior COVID 19, 52% male, mean age 67±12 years, 55% hypertensive, 32% diabetic, 41% dyslipidemia). The mean duration between COVID19 diagnosis and PET was 191 (±131) days. CMD was more prevalent in those with prior COVID19 (58% vs 46%, p=0.012). After adjusting for baseline and clinical characteristics, patients with prior COVID19 had statistically significant higher odds of CMD (OR 1.8, p=0.008). Results were consistent in subgroups of patients with no clinical risk factors and normal stress tests.

Conclusion: Our analysis shows that patients with prior COVID19 have higher rates of CMD. This may in part explain the long-COVID symptoms. The prognostic implications of these findings need to be determined.

Source: Ahmed A, Saad J, Han Y, et al. CORONARY MICROVASCULAR HEALTH IN PATIENTS WITH PRIOR COVID-19 INFECTION: IMPLICATIONS FOR LONG-COVID SYNDROME. J Am Coll Cardiol. 2022 Mar, 79 (9_Supplement) 1822. https://doi.org/10.1016/S0735-1097(22)02813-3

Cardiovascular impairment in long covid one year post-sars-cov-2 infection

Background: Long Covid is associated with multi-organ inflammation, hypercoagulability, and several symptoms (fatigue, dyspnoea etc). Varying levels of cardiac involvement have been reported by cardiac magnetic resonance (CMR). We now describe longitudinal cardiovascular impairment in patients with Long Covid at 6 and 12 months post-SARS-CoV-2 infection.

Methods: 524 participants with Long Covid underwent a baseline scan at 6 months post infection (ClinicalTrials.gov: NCT04369807) and were rescanned 12 months post-infection if abnormal findings were reported at baseline. CMR (T1 and T2, cardiac mass, volumes, function, and strain), along with multi-organ MRI and blood samples were collected. Cardiovascular impairment was defined as one or more of: low left ventricular ejection fraction (LVEF), high left ventricular end diastolic volume (LVEDV), elevated native T1 in 3 or more cardiac segments. A significant longitudinal change was reported if greater than the repeatability coefficients derived from a population of 92 healthy controls.

Results: In 70 patients with cardiovascular impairment and Long Covid at baseline, 48 had complete paired data at 1 year, and of those 54% had not fully resolved. 19 (27%) patients with cardiovascular impairment had required hospitalization for acute COVID-19. Troponin or BNP were not predictive of CMR findings; however, hospitalization at the acute stage, male sex, kidney fibroinflammation and serum bicarbonate were. Individual symptoms were not specific to cardiovascular impairment or disease course.

Conclusion: CMR shows that cardiovascular impairment persists in Long Covid in some patients beyond 12 months post infection; however, this impairment may have pre-existing origin. Although there is an association with acute COVID-19 hospitalisation, male gender and high serum bicarbonate were predictive of cardiovascular impairment, subtypes of disease (based on symptoms, examination, and investigations) are yet to be established. Therefore, interventional trials with pre-specified subgroup analysis are required to inform therapeutic options.

Source: Roca-Fernandez A, Wamil M, Telford A, et al. CARDIOVASCULAR IMPAIRMENT IN LONG COVID ONE YEAR POST-SARS-COV-2 INFECTION. J Am Coll Cardiol. 2022 Mar, 79 (9_Supplement) 1312. https://doi.org/10.1016/S0735-1097(22)02303-8

Post-COVID-19 syndrome: persistent neuroimaging changes and symptoms 9 months after initial infection

Abstract:

A previously healthy and active middle-aged woman acquired COVID-19 as an occupational exposure with subsequent persistent post-COVID-19 symptoms including headache, dyspnoea on exertion, chest pressure, tachycardia, anosmia, parosmia, persistent myalgia, vertigo, cognitive decline and fatigue. She presented to a tertiary medical centre for further evaluation after 9 months of persistent symptoms and had a largely unremarkable workup with the exception of a persistently elevated monocyte chemoattractant protein 1, blunted cardiovagal response and non-specific scattered areas of low-level hypometabolism at the bilateral frontal, left precuneus, occipital and parietal regions on PET scan.

Source: Grach SL, Ganesh R, Messina SA, Hurt RT. Post-COVID-19 syndrome: persistent neuroimaging changes and symptoms 9 months after initial infection. BMJ Case Rep. 2022 Apr 8;15(4):e248448. doi: 10.1136/bcr-2021-248448. PMID: 35396239. https://casereports.bmj.com/content/15/4/e248448.long (Full text)