Tag: long covid pathomechanism

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)

Studying severe long COVID to understand post-infectious disorders beyond COVID-19

To the Editor — As the COVID Human Genetic Effort consortium (https://www.covidhge.com/), we have studied genetic and immunological determinants of life-threatening COVID-19 pneumonia1, multisystem inflammatory syndrome (MIS-C)2, resistance to SARS-CoV-2 infection3 and ‘COVID toes’4, and here we present our efforts to investigate post-acute COVID-19 syndrome, or ‘long COVID’.

Most people infected with SARS-CoV-2 experience a mild to moderate acute infection, while ~10% develop hypoxemic pneumonia and 3% develop critical illness, which are outcomes associated with older age and male sex. Inborn errors of type I interferon immunity involving the viral sensors TLR7 or TLR3 can explain critical disease in 1–5% of people less than 60 years of age, whereas neutralizing autoantibodies to the type I interferons IFN-α, IFN-β and IFN-ω are seen in 15–20% of people over 70 years of age1, which highlights the importance of type I interferon immunity for protective immunity against acute SARS-CoV-2 infection in the respiratory tract.

Although hypoxemic pneumonia typically occurs 2 weeks after infection, a small fraction of children and young adults develop MIS-C at about 4 weeks after infection. This disorder overlaps Kawasaki disease and superantigen-mediated toxic shock syndrome. Immunological analyses have revealed hyperinflammatory immune responses, distinct from those of acute COVID-19 and Kawasaki disease5, and activation of T cells, possibly by a SARS-CoV-2 superantigen6. There is massive expansion of T cells expressing the T cell receptor (TCR) β-chain variable region TRBV11-2 in combination with variable TCR α-chains and broadly reactive autoantibodies2. Intriguingly, the delayed presentation of MIS-C after infection is at odds with other superantigen-mediated disorders, which might be explained by viral persistence specifically in the intestine and repeated superantigen-mediated activation through a leaky gut. Viral persistence has been proposed to be associated with the degree of activation of the immune system during acute infection with SARS-CoV-27.

Signs and symptoms after SARS-CoV-2 infection have been reported to also persist even longer in some children and adults. The World Health Organization defines the ‘post COVID’ condition as one that “occurs in individuals with a history of probable or confirmed SARS CoV-2 infection, usually 3 months from the onset of COVID-19 with symptoms and that last for at least 2 months and cannot be explained by an alternative diagnosis” (https://www.who.int/publications/i/item/WHO-2019-nCoV-Post_COVID-19_condition-Clinical_case_definition-2021.1). Long COVID spans from very mild to severely debilitating disease with objective organ damage, but sometimes the distinction between recovery from post–intensive care unit syndrome and ongoing pathology is not clearly defined or reported in studies.

Interestingly, an acute multi-organ phenotype encompassing multiple neurological, neuropsychological–neurocognitive, cardiopulmonary, gastrointestinal and dermatological complaints during acute COVID-19 correlates with longer persistence of signs and symptoms8.

The World Health Organization’s definition of long COVID is vague, which leads to concerns that a variety of conditions, including psychosomatic complaints, become intermixed with more severe, post-infectious organ dysfunction. To maximize our chances of identifying the human genetic immunological determinants of disease, we will focus our efforts on the most severe cases of long COVID available through our international network of collaborators and clinics. We will include patients with over 3 months of persistent signs and symptoms after PCR-verified SARS-CoV-2 infection. We will also limit our studies to patients with severe organ damage or dysfunction that can be objectively verified by imaging and physiological or biochemical–molecular tests (Fig. 1a). Finally, to distinguish these patients with severe long COVID from patients with post–critical illness syndromes, we will include only patients whose persistent organ dysfunction cannot be explained by the severity of the preceding SARS-CoV-2 infection or by the treatments or medical interventions experienced.

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Source: Brodin P, Casari G, Townsend L, O’Farrelly C, Tancevski I, Löffler-Ragg J, Mogensen TH, Casanova JL; COVID Human Genetic Effort. Studying severe long COVID to understand post-infectious disorders beyond COVID-19. Nat Med. 2022 Apr 5. doi: 10.1038/s41591-022-01766-7. Epub ahead of print. PMID: 35383311. https://www.nature.com/articles/s41591-022-01766-7 (Full article)

Lowered oxygen saturation and increased body temperature in acute COVID-19 largely predict chronic fatigue syndrome and affective symptoms due to LONG COVID: a precision nomothetic approach

Abstract:

Background: Long coronavirus disease 2019 (LC) is a chronic sequel of acute COVID-19. The exact pathophysiology of the affective, chronic fatigue and physiosomatic symptoms labeled as physio-affective phenome of LC has remained elusive. Objective: The current study aims to delineate the effects of oxygen saturation (SpO2) and body temperature during the acute phase on the physio-affective phenome of LC.

Method: We recruited 120 LC patients and 36 controls. For all participants, we assessed the lowest SpO2 and peak body temperature during acute COVID-19, and the Hamilton Depression and Anxiety Rating Scale (HAMD/HAMA) and Fibro Fatigue (FF) scales 3 to 4 months later.

Results: Lowered SpO2 and increased body temperature during the acute phase and female sex predict 60.7% of the variance in the physio-affective phenome of LC. Using unsupervised learning techniques we were able to delineate a new endophenotype class, which comprises around 26.7% of the LC patients and is characterized by very low SpO2 and very high body temperature, and depression, anxiety, chronic fatigue, and autonomic and gastro-intestinal symptoms scores. Single latent vectors could be extracted from both biomarkers, depression, anxiety and FF symptoms or from both biomarkers, insomnia, chronic fatigue, gastro-intestinal and autonomic symptoms.

Conclusion: The newly constructed endophenotype class and pathway phenotypes indicate that the physio-affective phenome of LC is at least in part the consequence of the pathophysiology of acute COVID-19, namely the combined effects of lowered SpO2, increased body temperature and the associated immune-inflammatory processes and lung lesions.

Source: Dhurgham Shihab Al-Hadrawi, Haneen Tahseen Al-Rubaye, Abbas F. Almulla, Hussein Kadhem Al-Hakeim, Michael F. Maes. Lowered oxygen saturation and increased body temperature in acute COVID-19 largely predict chronic fatigue syndrome and affective symptoms due to LONG COVID: a precision nomothetic approach. medRxiv 2022.04.10.22273660; doi: https://doi.org/10.1101/2022.04.10.22273660 https://www.medrxiv.org/content/10.1101/2022.04.10.22273660v1 (Full text as PDF file)

Neurocognitive and psychiatric post-coronavirus disease 2019 conditions: pathogenic insights of brain dysfunction following severe acute respiratory syndrome coronavirus 2 infection

Abstract:

Purpose of review: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of coronavirus disease 2019 (COVID-19), can trigger a myriad of neuropsychiatric manifestations. As a 2-year-old disease (at the writing of this manuscript), its long-term cognitive and neuropsychiatric implications, known as post-COVID-19 conditions, are incompletely recognized and mechanistically obscure.

Recent findings: Fatigue, anxiety, depression, posttraumatic stress disorder, and cognitive dysfunction are reported more frequently in COVID-19 survivors than in matching, non-COVID-19 population. Risk factors are unclear, including comorbidities, age at COVID-19 onset, or disease severity; women, however, have been reported to be at increased risk than men. Although the frequency of these symptoms decreases over time, at least one in five will have persistent cognitive and neuropsychiatric manifestations one year after recovering from COVID-19.

Summary: Neurocognitive and psychiatric post-COVID-19 long-term conditions are frequent and complex multifactorial sequelae. Several acute and chronic factors such as hypoxemia, cerebral thrombotic and inflammatory endothelial damage, and disruption of the blood-brain barrier (leading to parenchymal translocation of pro-inflammatory molecules, cytokines, and cytotoxic T lymphocytes) are involved, leading to microglial activation and astrogliosis. As an evolving topic, evidence derived from prospective studies will expand our understanding of post-COVID-19 these long-term outcomes.

Source: García-Grimshaw M, Sankowski R, Valdés-Ferrer SI. Neurocognitive and psychiatric post-coronavirus disease 2019 conditions: pathogenic insights of brain dysfunction following severe acute respiratory syndrome coronavirus 2 infection. Curr Opin Neurol. 2022 Mar 11. doi: 10.1097/WCO.0000000000001046. Epub ahead of print. PMID: 35283463. https://pubmed.ncbi.nlm.nih.gov/35283463/

Early clues regarding the pathogenesis of long-COVID

Abstract:

Intense investigation into the predictors and determinants of post-acute sequelae of SARS-CoV-2 infection (PASC), including ‘long COVID’, is underway. Recent studies provide clues to the mechanisms that might drive this condition, with the goal of identifying host or virus factors that can be intervened upon to prevent or reverse PASC.

Source: Peluso MJ, Deeks SG. Early clues regarding the pathogenesis of long-COVID. Trends Immunol. 2022 Apr;43(4):268-270. doi: 10.1016/j.it.2022.02.008. Epub 2022 Mar 8. PMID: 35272932; PMCID: PMC8901423. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8901423/ (Full text)

The immunology and immunopathology of COVID-19

Abstract:

Considerable research effort has been made worldwide to decipher the immune response triggered upon severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, identify the drivers of severe and fatal COVID-19, and understand what leads to the prolongation of symptoms after disease resolution. We review the results of almost 2 years of COVID-19 immunology research and discuss definitive findings and remaining questions regarding our understanding of COVID-19 pathophysiology. We discuss emerging understanding of differences in immune responses seen in those with and without Long Covid syndrome, also known as post-acute sequelae of SARS-CoV-2. We hope that the knowledge gained from this COVID-19 research will be applied in studies of inflammatory processes involved in critical and chronic illnesses, which remain a major unmet need.
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Source: Merad M, Blish CA, Sallusto F, Iwasaki A. The immunology and immunopathology of COVID-19. Science. 2022 Mar 11;375(6585):1122-1127. doi: 10.1126/science.abm8108. Epub 2022 Mar 10. PMID: 35271343. https://www.science.org/doi/full/10.1126/science.abm8108 (Full text)

Post-acute COVID-19 syndrome presented as a cerebral and systemic vasculitis: a case report

To the Editor,

Post-acute Coronavirus Disease of 2019 (COVID-19) syndrome is defined as the appearance of symptoms or an organ dysfunction, which occurs at least 4 weeks after the first COVID-19 manifestations and cannot be explained by any alternative diagnosis []. Neurological complications are also well recognized, and include acute cerebrovascular events, encephalopathy, meningoencephalitis, Guillain–Barre syndrome, demyelination, dementia, parkinsonism, and others []. On the other hand, cerebral vasculitis is one of the causes which can lead to brain damage related to COVID-19 infection []. We present a 69-year-old male with systemic vasculitis and central nervous system (CNS) involvement as a manifestation of post-acute COVID-19 syndrome.

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Source: Ivanovic, Jovana et al. “Post-acute COVID-19 syndrome presented as a cerebral and systemic vasculitis: a case report.” Acta neurologica Belgica, 1–3. 13 Mar. 2022, doi:10.1007/s13760-022-01923-2 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8918071/ (Full text)