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1.
MEDICC Rev ; 24(3-4): 57-60, 2022 Oct 31.
Article in English | MEDLINE | ID: covidwho-2218182

ABSTRACT

INTRODUCTION: Polyserositis is described as inflammation with effusion of more than one serous membrane. There is very little published literature linking it to COVID-19 as a late complication. OBJECTIVE: Present and describe a case of post-COVID-19 polyserositis. METHODS: Data were collected from the medical record of a female patient admitted for fainting spells and marked weakness. The patient underwent a clinical evaluation, additional hematology, imaging and histopathology tests, and a surgical procedure. The new index, called the abdominal adipose deposit index, was obtained by multiplying the subcutaneous fat thickness by visceral fat thickness, both measured by ultrasound. A cutoff point was established that facilitated discernment of an unhealthy phenotype: normal weight but metabolically obese, a cardiometabolic risk factor. RESULTS: We present the case of a 57-year-old female patient admitted to hospital for fainting spells and marked weakness, four months after COVID-19 infection. She also had a history of obesity, asthma, type 2 diabetes mellitus and a cholecystectomy in December 1992 for gallstones. Clinical assessment revealed pericardial effusion and bilateral pleural effusion, in addition to a tumor-like lesion outside the pericardium, proximal to the right ventricular wall. A surgical procedure and findings from additional tests led to diagnoses of thymic remnants and polyserositis. CONCLUSIONS: This is a case of polyserositis in a post-COVID-19 patient. After other causes of polyserositis were ruled out, and since there is a likely physiological and pathogenic mechanism operating between the two diseases, the polyserositis was determined to be a late complication of COVID-19. To date, it is the second case reported in the world and the first reported in Cuba.


Subject(s)
COVID-19 , Diabetes Mellitus, Type 2 , Female , Humans , COVID-19/complications , Diabetes Mellitus, Type 2/complications , Cuba , Inflammation , Obesity/complications , Chronic Disease , Syncope
2.
Rev Inst Med Trop Sao Paulo ; 64: e73, 2022.
Article in English | MEDLINE | ID: covidwho-2214901

ABSTRACT

Leukocyte biomarkers, including the neutrophil-to-lymphocyte (NLR), monocyte-to-lymphocyte-(MLR), platelet-to-lymphocyte (PLR) ratios and systemic immune-inflammation index (SII) have been associated with severity and mortality of patients with COVID-19. The purpose of this study was to evaluate the association of baseline leukocyte biomarkers calculated in the emergency department (ED) with the disease severity and mortality. This was a retrospective cohort study that evaluated 1,535 (mean age 57+18 years) patients with SARS-CoV-2 infection in the ED of a single reference center. Outcomes were severity, defined as intensive care unit (ICU) admission requirement, and in-hospital mortality. All leukocyte biomarkers were calculated in the ED before the hospital admission. Their ability to predict the severity and mortality was measured using receiver operating characteristic (ROC) curves. Severity and mortality were observed in 30.9% and 12.6% of the patients, respectively, and were significantly correlated with NLR, MLR, PLR and SII, but only NLR was independently associated with both outcomes on multivariate analysis. Analysis of ROC curves revealed that NLR (0.78 for severity and 0.80 for mortality) and SII (0.77 for severity and 0.75 for mortality) had the best ability to predict mortality, when compared to other ratios. The highest AUC was observed for NLR, employing cut-off points of 5.4 for severity and 5.5 for mortality. Leukocyte biomarkers, particularly NLR, are capable of predicting the severity and mortality of patients with SARS-CoV-2 infection and could be important adjunct tools to identify patients in the ED that are more prone to develop adverse outcomes.


Subject(s)
COVID-19 , Humans , Adult , Middle Aged , Aged , Retrospective Studies , Prognosis , SARS-CoV-2 , Lymphocytes , Inflammation , Biomarkers
3.
preprints.org; 2023.
Preprint in English | PREPRINT-PREPRINTS.ORG | ID: ppzbmed-10.20944.preprints202302.0085.v1

ABSTRACT

Cardiac complications of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have been well-identified since the beginning of the current coronavirus disease 2019 (COVID-19) pandemic. Such conditions can occur of various etiologies, such as respiratory failure and hypoxemia, direct cardiac tissue damage due to viral replication, indirect myocarditis as systemic inflammation, and the interaction of different medications. Recently, with the start of the COVID-19 vaccination programs, COVID-19 vaccine-associated cardiac adverse events (AEs) have emerged and are increasingly being reported. Although these AEs are usually mild and self-limited, they can sometimes cause severe, catastrophic outcomes. This review compares the pathophysiology, diagnosis, and treatment of the de novo SARS-CoV-2 infection-related and COVID-19 vaccine-related myocarditis and pericarditis.


Subject(s)
Respiratory Insufficiency , Pericarditis , Coronavirus Infections , Myocarditis , COVID-19 , Hypoxia , Inflammation
4.
medrxiv; 2023.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2023.02.01.23285224

ABSTRACT

Olfactory and gustatory dysfunction persists in up to 4% of patients who have recovered from COVID19 beyond 6 months. Dysosmia (distorted smell) and dysgeusia (distorted taste) are frequently observed in the acute phase of many upper respiratory viral infections. However, persistent dysosmia in these patients is associated with persistent nasal inflammation. The purpose of this study was to determine the extent of patient self-assessed post-COVID-19 olfactory and gustatory dysfunction and to understand the quality and severity of the subjective symptoms over a year. A total of 426 registry participants were recruited to complete initial online questionnaires and follow up at three post-enrollment time points: 3 months, 6 months, 12 months. The Registry questionnaires assessed nasal inflammation (Sino Nasal Outcome Test - SNOT22), mental health (The Patient Health Questionnaire 2 PHQ2; Neuro QoL Positive Affect and Well-Being PAW 23), sleep quality (The Pittsburgh Sleep Quality Index PSQI), In a cohort of 74 patients, clinical measurements of smell (Smell Identification Test (UPSIT) and taste (Waterless Taste Test (B-WETT)) were performed to validate self-reported measures of sensory impairment. Our data indicate that persistent COVID19 olfactory and gustatory dysfunction is not associated with subjective measures of nasal inflammation. However, dryness of the nose/mouth, mood disturbance, and poor sleep quality are reported by the majority of participants. Participants struggle with detecting specific foul/dangerous odorants and tasting subtle flavors, which could have a negative effect on patient safety and well-being. Those infected during the earlier waves of the pandemic have more persistent and severe symptoms. Objective measure of both smell and taste are significantly reduced in the majority of participants with self-reported olfactory and gustatory dysfunction. Finally, standard anti-inflammatory topical and systemic therapy does not improve the subjective sense of smell while olfactory training is marginally more effective. This establishes persistent COVID19 olfactory and gustatory dysfunction as a chronic and difficult to treat syndrome resistant to standard anti-inflammatory therapy.


Subject(s)
Seizures , Respiratory Tract Infections , Dysgeusia , COVID-19 , Inflammation , Olfaction Disorders
5.
Curr Pharm Des ; 28(22): 1798-1814, 2022.
Article in English | MEDLINE | ID: covidwho-2197777

ABSTRACT

Defined by the World Health Organization as a global public health pandemic, coronavirus 2019 (COVID-19) has a global impact and has caused the death of thousands of people. The "severe acute respiratory syndrome coronavirus 2" virus (SARS-CoV-2) is the etiologic agent of this disease, which uses the angiotensinconverting enzyme receptor 2 (ACE2) to infect the body, so any organ that expresses the gene ACE2 is a possible target for the new coronavirus. In addition, in severe cases of COVID-19, a cytokine storm occurs, which triggers widespread systemic inflammation due to the uncontrolled release of proinflammatory cytokines. In this perspective, the modulation of purinergic receptors is highlighted in the literature as a possible therapy, considering its application in other viral infections and systemic inflammation. Therefore, this review aims to gather information on the modulation of the P2X7 receptor in the main organs directly affected by the virus and by the cytokine storm: the heart, brain, lung, liver and kidneys. Thus, demonstrating possible therapies for reducing inflammation and the level of morbidity and mortality of COVID-19. In severe cases of COVID-19, SARS-CoV-2 infection is capable of triggering an exacerbated release of cytokines, called a cytokine storm. With this inflammation, or less the direct infection of the virus, the whole organism can be affected. In this way, major and important organs such as the heart, lung, brain, and liver are affected, triggering different pathologies. In this perspective, purinergic signaling is highlighted in the literature for its anti-inflammatory role and has been listed in the pandemic scenario as a potential therapy. Therefore, knowing the expression of the purinergic receptor P2X7 in these tissues, the modulation of its inflammatory activity may be favorable in this severe and systemic condition.


Subject(s)
COVID-19 , Cytokine Release Syndrome , Angiotensin-Converting Enzyme 2 , Cytokines , Humans , Inflammation , Receptors, Purinergic P2X7 , SARS-CoV-2
6.
Cytokine ; 158: 156010, 2022 10.
Article in English | MEDLINE | ID: covidwho-2177981
7.
Immun Inflamm Dis ; 10(12): e750, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-2172973

ABSTRACT

Asthma and chronic obstructive pulmonary disease (COPD) are lung diseases characterized by airflow limitation and chronic inflammation. More and more studies have shown that the occurrence and development of asthma and COPD are related to abnormal immune responses caused by dysregulation of many genetic and environmental factors. The exact pathogenesis of the disease is still unclear. A large number of studies have shown that the NLRP3 inflammasome is involved in the process of chronic airway inflammation in asthma and COPD. Here, we summarize recent advances in the mechanism of NLRP3 inflammasome activation and regulation and its role in the pathogenesis of inflammatory lung diseases such as asthma and COPD. Meanwhile we propose possible therapeutic targets in asthma and COPD.


Subject(s)
Asthma , Pulmonary Disease, Chronic Obstructive , Humans , Inflammasomes , NLR Family, Pyrin Domain-Containing 3 Protein , Inflammation
8.
preprints.org; 2023.
Preprint in English | PREPRINT-PREPRINTS.ORG | ID: ppzbmed-10.20944.preprints202301.0586.v1

ABSTRACT

COVID-19 is a pandemic triggered by the coronavirus SARS-CoV-2 whose peak occurred in the years 2020 and 2021. The main target of the virus is the lung and infection is associated to an accentuated inflammatory process involving mainly the innate arm of the immune system. Here, we described the induction of a pulmonary inflammatory process triggered by the intranasal (IN) instillation of UV-inactivated SARS-CoV-2 in C57BL/6 mice and then the evaluation of vitamin D (VitD) ability to control this process. The assays used to estimate the severity of lung involvement included total and differential number of cells in the BALF, histopathological analysis, quantification of T cell subsets and inflammatory mediators by RT-PCR, cytokine quantification in lung homogenates and flow cytometric analysis of cells recovered from lung parenchyma. IN instillation of inactivated SARS-CoV-2 triggered a pulmonary inflammatory process, consisting of various cell types and mediators, resembling the typical inflammation found in COVID-19 patients. This inflammatory process was significantly decreased by IN delivery of vitD, but not by its IP administration, suggesting that this hormone has therapeutic potential in COVID-19 if locally applied.


Subject(s)
Inflammation , Severe Acute Respiratory Syndrome , COVID-19 , Vitamin D Deficiency
9.
Wiley Interdiscip Rev Nanomed Nanobiotechnol ; 14(2): e1763, 2022 03.
Article in English | MEDLINE | ID: covidwho-2173486

ABSTRACT

Pneumonia is a common but serious infectious disease, and is the sixth leading cause for death. The foreign pathogens such as viruses, fungi, and bacteria establish an inflammation response after interaction with lung, leading to the filling of bronchioles and alveoli with fluids. Although the pharmacotherapies have shown their great effectiveness to combat pathogens, advanced methods are under developing to treat complicated cases such as virus-infection and lung inflammation or acute lung injury (ALI). The inflammation modulation nanoparticles (NPs) can effectively suppress immune cells and inhibit inflammatory molecules in the lung site, and thereby alleviate pneumonia and ALI. In this review, the pathological inflammatory microenvironments in pneumonia, which are instructive for the design of biomaterials therapy, are summarized. The focus is then paid to the inflammation-modulating NPs that modulate the inflammatory cells, cytokines and chemokines, and microenvironments of pneumonia for better therapeutic effects. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Respiratory Disease.


Subject(s)
Acute Lung Injury , Nanoparticles , Pneumonia , Acute Lung Injury/drug therapy , Acute Lung Injury/pathology , Humans , Inflammation/drug therapy , Lung , Nanoparticles/therapeutic use , Pneumonia/drug therapy , Pneumonia/pathology
10.
arxiv; 2023.
Preprint in English | PREPRINT-ARXIV | ID: ppzbmed-2301.12340v1

ABSTRACT

Objectives: To investigate the value of radiomics features of epicardial adipose tissue (EAT) combined with lung for detecting the severity of Coronavirus Disease 2019 (COVID-19) infection. Methods: The retrospective study included data from 515 COVID-19 patients (Cohort1: 415, cohort2: 100) from the two centers between January 2020 and July 2020. A deep learning method was developed to extract the myocardium and visceral pericardium from chest CTs, and then a threshold was applied for automatic EAT extraction. Lung segmentation was achieved according to a published method. Radiomics features of both EAT and lung were extracted for the severity prediction. In a derivation cohort (290, cohort1), univariate analysis and Pearson correlation analysis were used to identify predictors of the severity of COVID-19. A generalized linear regression model for detecting the severity of COVID-19 was built in a derivation cohort and evaluated in internal (125, cohort1) and external (100, cohort2) validation cohorts. Results: For EAT extraction, the Dice similarity coefficients (DSC) of the two centers were 0.972 (0.011) and 0.968 (0.005), respectively. For severity detection, the AUC, net reclassification improvement (NRI), and integrated discrimination improvement (IDI) of the model with radiomics features of both lung and EAT increased by 0.09 (p<0.001), 22.4%, and 17.0%, respectively, compared with the model with lung radiomics features, in the internal validation cohort. The AUC, NRI, and IDI increased by 0.04 (p<0.001), 11.1%, and 8.0%, respectively, in the external validation cohort. Conclusion: Radiomics features of EAT combined with lung have incremental value in detecting the severity of COVID-19.


Subject(s)
Inflammation , COVID-19
11.
preprints.org; 2023.
Preprint in English | PREPRINT-PREPRINTS.ORG | ID: ppzbmed-10.20944.preprints202301.0460.v1

ABSTRACT

Each injection of any known vaccine results in a strong expression of pro-inflammatory cytokines. This is the result of the innate immune system activation, without which no adaptive response to the injection of vaccines is possible. COVID-19 mRNA vaccines would not escape this rule. Unfortunately, the degree of inflammation produced by these vaccines is variable, probably depending on the genetic background and previous immune experiences, which through epigenetic modifications, could have made the innate immune system of each individual tolerant or reactive to subsequent immune stimulations.We hypothesize that we can move from a limited pro-inflammatory condition to conditions of increasing expression of pro-inflammatory cytokines that can culminate in multisystem hyperinflammatory syndromes following COVID-19 mRNA vaccines (MIS-V). We have graphically represented this idea in a hypothetical inflammatory pyramid (IP) and we have correlated the time factor to the degree of inflammation produced after the injection of vaccines. Furthermore, we have placed the clinical manifestations within this hypothetical IP, correlating them to the degree of inflammation produced. Surprisingly, excluding the possible presence of an early MIS-V, the time factor and the complexity of clinical manifestations are correlated to the increasing degree of inflammation: symptoms, heart disease and syndromes (MIS-V).


Subject(s)
Heart Diseases , COVID-19 , Multiple System Atrophy , Inflammation
12.
researchsquare; 2023.
Preprint in English | PREPRINT-RESEARCHSQUARE | ID: ppzbmed-10.21203.rs.3.rs-2516078.v1

ABSTRACT

Introduction: In patients suffering from COVID-19, immunocompromised conditions or immunosuppressive medications such as corticosteroids may predispose them to early or delayed invasive fungal infections that invade cerebral components. This study, for the first time, describes a case of COVID-19 disease diagnosed with rhinocerebral mucormycosis through cerebrospinal fluid (CSF) analysis.Case presentation: A 32-year-old woman with a history of referral and hospitalization due to COVID-19 about a month ago was being treated with immunosuppressive drugs, manifested by lower extremity plegia. In the imaging assessment, intracranial hemorrhage (thalamus zone) and mass like lesion were revealed. In cytological assessment, acute inflammations associated with fungal infection in accordance with the diagnosis of mucormycosis were definitively confirmed. Despite antifungal medication, consciousness declined one week later, and the patient developed thromboembolism and died.Conclusion In patients with a COVID-19 background of immunosuppressive therapy or clinical situations related to immunosuppression such as uncontrolled diabetes, rhinocerebral mucormycosis will always be an ambush. Therefore, screening and prevention measures should be considered.


Subject(s)
Paralysis , Diabetes Mellitus , Thromboembolism , Mycoses , COVID-19 , Mucormycosis , Inflammation , Intracranial Hemorrhages
13.
preprints.org; 2023.
Preprint in English | PREPRINT-PREPRINTS.ORG | ID: ppzbmed-10.20944.preprints202301.0413.v1

ABSTRACT

Abstract. Marek's disease virus is an oncogenic avian herpesvirus and the problem of oncogenicity of this virus for humans remains unexplored. This pathology appeared in broiler chickens of 30 days and older, that is from now on the contact with poultry meat carries the risk of infecting people. This article analyzes the risks of the emergence of the epidemic potential of the Marek's disease virus in the Russian Federation taking into account the characteristics of modern pig and poultry farming. It was found that COVID 19 can serve as an additional factor in reducing the resistance of the population to herpesvirus infections. The COVID 19 epidemic is accompanied by folic acid deficiency which also increases the risk of contamination of diseases associated with DNA viruses, including an extended risk of animal viruse infection. Since, according to our estimates, Marek's disease occurred in at least 25% of broiler poultry farms in the Russian Federation, a possible expand in mortality from neoplasms of the reproductive system for the Russian Federation as a whole can contribute to the dynamics of oncological diseases of reproductive organs and breast cancer. Since 2011 a contagious form of intestinal pathology, vesicular enteritis, has widely spread at poultry farms in the Russian Federation. During periods of extending incidence of vesicular enteritis, we recorded cases of inflammation of the facial nerves and subfebrile temperature in contact persons, bursts of oncological diseases in veterinary personnel (ovarian cancer, breast cancer), abnormal and synchronous increases in the incidence of infectious larengotracheitis and Marek's disease in chickens under the age of 40 days which requires additional monitoring studies.


Subject(s)
Marek Disease , Ovarian Neoplasms , Communicable Diseases , Herpesviridae Infections , Breast Neoplasms , Inflammation , Neoplasms , Enteritis
14.
biorxiv; 2023.
Preprint in English | bioRxiv | ID: ppzbmed-10.1101.2023.01.20.524893

ABSTRACT

Pregnant people infected with the SARS-CoV-2 virus have shown a higher incidence of "preeclampsia-like syndrome". Preeclampsia is a systematic syndrome that affects 5% of people worldwide and is the leading cause of maternal mortality. It is characterised by placental dysfunction, leading to poor placental perfusion, maternal hypertension and neurological disturbances. Here, we used whole-transcriptome, spatial profiling of placental tissues to analyse the expression of genes between placentae from pregnant participants who contracted SARS-CoV-2 and those prior to the pandemic. Our analysis of the trophoblast and villous core stromal cell populations revealed tissue-specific pathways enriched in the SARS-CoV-2 placentae that align with a pre-eclampsia signature. Most notably, we found enrichment of pathways involved in vascular tension, blood pressure, inflammation, and oxidative stress. This study illustrates how spatially resolved transcriptomic analysis can aid in understanding the underlying pathogenic mechanisms of SARS-CoV-2 in pregnancy that are thought to induce "preeclampsia-like syndrome". Our study highlights the benefits of spatial profiling to map the crosstalk between trophoblast and villous core stromal cells linked to pathways involved in "preeclampsia-like syndrome."


Subject(s)
Inflammation , Pre-Eclampsia , Hypertension , Nervous System Diseases
15.
medrxiv; 2023.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2023.01.16.22283804

ABSTRACT

In COVID-19 neurological alterations are noticed during the systemic viral infection. Various pathophysiological mechanisms on the central nervous system (CNS) have been suggested in the past two years, including the viral neurotropism hypothesis. Nevertheless, neurological complications can also occur independent of neurotropism and at different stages of the disease and may be persistent. Previous autopsy studies of the CNS from patients with severe COVID-19 show infiltration of macrophages and T lymphocytes, especially in the perivascular regions as well as pronounced microglial activation, but without signs of viral encephalitis. However, there is an ongoing debate about long-term changes and cytotoxic effects in the CNS due to the systemic inflammation. Here, we show the brain-specific host response during and after COVID-19. We profile single-nucleus transcriptomes and proteomes of brainstem tissue from deceased COVID-19 patients who underwent rapid autopsy. We detect a disease phase-dependent inflammatory type-I interferon response in acute COVID-19 cases. Integrating single-nucleus RNA sequencing and spatial transcriptomics, we could localize two patterns of reaction to severe systemic inflammation. One neuronal with direct focus on cranial nerve nuclei and one diffusely affecting the whole brainstem, the latter reflecting a bystander effect that spreads throughout the vascular unit and alters the transcriptional state of oligodendrocytes, microglia and astrocytes. Our results indicate that even without persistence of SARS-CoV-2 in the CNS, the tissue activates highly protective mechanisms, which also cause functional disturbances that may explain the neurological symptoms of COVID-19, triggered by strong systemic type-I IFN signatures in the periphery.


Subject(s)
Encephalitis, Viral , Virus Diseases , COVID-19 , Inflammation
16.
biorxiv; 2023.
Preprint in English | bioRxiv | ID: ppzbmed-10.1101.2023.01.17.524329

ABSTRACT

Aging is the primary risk factor for most neurodegenerative diseases, and recently coronavirus disease 2019 (COVID-19) has been associated with severe neurological manifestations that can eventually impact neurodegenerative conditions in the long-term. The progressive accumulation of senescent cells in vivo strongly contributes to brain aging and neurodegenerative co-morbidities but the impact of virus-induced senescence in the aetiology of neuropathologies is unknown. Here, we show that senescent cells accumulate in physiologically aged brain organoids of human origin and that senolytic treatment reduces inflammation and cellular senescence; for which we found that combined treatment with the senolytic drugs dasatinib and quercetin rejuvenates transcriptomic human brain aging clocks. We further interrogated brain frontal cortex regions in postmortem patients who succumbed to severe COVID-19 and observed increased accumulation of senescent cells as compared to age-matched control brains from non-COVID-affected individuals. Moreover, we show that exposure of human brain organoids to SARS-CoV-2 evoked cellular senescence, and that spatial transcriptomic sequencing of virus-induced senescent cells identified a unique SARS-CoV-2 variant-specific inflammatory signature that is different from endogenous naturally-emerging senescent cells. Importantly, following SARS-CoV-2 infection of human brain organoids, treatment with senolytics blocked viral retention and prevented the emergence of senescent corticothalamic and GABAergic neurons. Furthermore, we demonstrate in human ACE2 overexpressing mice that senolytic treatment ameliorates COVID-19 brain pathology following infection with SARS-CoV-2. In vivo treatment with senolytics improved SARS-CoV-2 clinical phenotype and survival, alleviated brain senescence and reactive astrogliosis, promoted survival of dopaminergic neurons, and reduced viral and senescence-associated secretory phenotype gene expression in the brain. Collectively, our findings demonstrate SARS-CoV-2 can trigger cellular senescence in the brain, and that senolytic therapy mitigates senescence-driven brain aging and multiple neuropathological sequelae caused by neurotropic viruses, including SARS-CoV-2.


Subject(s)
Neurodegenerative Diseases , COVID-19 , Nervous System Diseases , Inflammation
17.
biorxiv; 2023.
Preprint in English | bioRxiv | ID: ppzbmed-10.1101.2023.01.13.523998

ABSTRACT

Deep metabolomic, proteomic and immunologic phenotyping of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) patients have matched a wide diversity of clinical symptoms with potential biomarkers for coronavirus disease 2019 (COVID-19). Within here, several studies described the role of metabolites, lipoproteins and inflammation markers during infection and in recovered patients. In fact, after SARS-CoV-2 viral infection almost 20-30% of patients experience persistent symptoms even after 12 weeks of recovery which has been defined as long-term COVID-19 syndrome (LTCS). Emerging evidence revealed that a dysregulated immune system and persisting inflammation could be one of the key drivers of LTCS. However, how these small biomolecules such as metabolites, lipoprotein, cytokines and chemokines altogether govern pathophysiology is largely underexplored. Thus, a clear understanding of how these parameters in an integrated fashion could predict the disease course may help to stratify LTCS patients from acute COVID-19 or recovered specimens and would help to elucidate a potential mechanistic role of these biomolecules during the disease course. Here, we report an integrated analysis of blood serum and plasma by in vitro diagnostics research NMR spectroscopy and flow cytometry-based cytokine quantification in a total of 125 individuals (healthy controls (HC; n=73), recovered (n=12), acute (n=7) and LTCS (n=33)). We identified that in LTCS patients lactate and pyruvate were significantly different from either healthy controls or acute COVID-19 patients. Further correlational analysis of cytokines and metabolites indicated that creatine, glutamine, and high-density lipoprotein (HDL) phospholipids were distributed differentially amongst patients or individuals. Of note, triglycerides and several lipoproteins (apolipoproteins Apo-A1 and A2) in LTCS patients demonstrate COVID-19-like alterations compared to HC. Interestingly, LTCS and acute COVID-19 samples were distinguished mostly by their creatinine, phenylalanine, succinate, 3-hydroxybutyrate (3-HB) and glucose concentrations, illustrating an imbalanced energy metabolism. Most of the cytokines and chemokines were present at low levels in LTCS patients compared with HC except IL-18 chemokine, which tended to be higher in LTCS patients and correlated positively with several amino acids (creatine, histidine, leucine, and valine), metabolites (lactate and 3-HB) and lipoproteins. The identification of these persisting plasma metabolites, lipoprotein and inflammation alterations will help to better stratify LTCS patients from other diseases and could help to predict the ongoing severity of LTCS patients.


Subject(s)
Severe Acute Respiratory Syndrome , Coronavirus Infections , Disruptive, Impulse Control, and Conduct Disorders , COVID-19 , Inflammation
18.
researchsquare; 2023.
Preprint in English | PREPRINT-RESEARCHSQUARE | ID: ppzbmed-10.21203.rs.3.rs-2483980.v1

ABSTRACT

Purpose: To present a case of a kidney transplant recipient with multiple, concurrent signs of retinal and choroidal microvascular dysfunction following mild coronavirus disease 2019 (COVID-19). Observations: An immunosuppressed, 51-year-old male with a history of kidney transplantation at an earlier stage, presented with bilateral conjunctivitis and blurry vision that coincided with a SARS-CoV-2-positive upper respiratory tract infection. On examination, we observed bilateral vitritis as well as choroidal congestion with signs of outer retinal and inner choroidal microvascular dysfunction. Moreover, cotton wool spots, consistent with inner retinal ischemia were noted while the rest of the clinical findings subsided. Conclusions and importance: COVID-19, a multi-systemic disease that primarily affects the respiratory system, has been associated with a number of seemingly diverse ocular phenotypes, where both inflammation and ischemia seem to play role. Moreover, the presence of underlying systemic comorbidities may have an impact on both infection outcomes and the ocular complications of the disease. Kidney transplant recipients that develop SARS-CoV-2 infection may be at higher risk for both choroidal and retinal microvasculopathy with prominent choroidal congestion, pigment epitheliopathy with or without subretinal fluid and hyper-reflective changes in optical coherence tomography suggesting ischemia in different retinal layers.


Subject(s)
Respiratory Tract Infections , Labyrinth Diseases , Ischemia , Severe Acute Respiratory Syndrome , Papilloma, Choroid Plexus , Eye Diseases , Deafness , Inflammation , Vision Disorders , Pigmentation Disorders , COVID-19 , Diabetic Nephropathies
19.
researchsquare; 2023.
Preprint in English | PREPRINT-RESEARCHSQUARE | ID: ppzbmed-10.21203.rs.3.rs-2448315.v1

ABSTRACT

Aims Long-COVID occurs after SARS-CoV-2 infection and results in diverse, prolonged symptoms. The present study aims to determine the underlying mechanisms, and to inform prognosis and treatment.Methods Plasma proteome from Long-COVID outpatients was analyzed in comparison to acutely ill COVID-19 (mild and severe) inpatients and healthy control subjects. The expression of approximately 3000 protein biomarkers was determined with proximity extension assays and then deconvoluted with multiple bioinformatics tools into both cell types and signaling mechanisms, as well as organ specificity.Results Compared to age- and sex-matched acutely ill COVID-19 inpatients and healthy control subjects, Long-COVID outpatients showed natural killer cells with a resting phenotype, as opposed to active, and neutrophils that formed extracellular traps. This resetting of cell phenotypes was reflected in vascular events mediated by both angiopoietin-1 (ANGPT1) and vascular-endothelial growth factor-A (VEGFA). Levels of ANGPT1 and VEGFA were validated by serological methods in different patient cohorts. Silent signaling of transforming growth factor-β1 with elevated EP300 favored not only vascular inflammation, but also tumor necrosis factor-α driven pathways. In addition, a vascular proliferative state associated with hypoxia inducible factor 1 pathway was predicted that progressed from COVID-19 to Long-COVID. The vasculo-proliferative process identified in Long-COVID was associated with significant changes in the organ-specific proteome reflective of neurological and cardiometabolic dysfunction.Conclusions Taken together, our study uncovered a vasculo-proliferative process in Long-COVID initiated by prior hypoxia, and identified potential organ-specific prognostic biomarkers and therapeutic targets.


Subject(s)
Necrosis , COVID-19 , Hypoxia , Nervous System Diseases , Inflammation , Neoplasms
20.
researchsquare; 2023.
Preprint in English | PREPRINT-RESEARCHSQUARE | ID: ppzbmed-10.21203.rs.3.rs-2444358.v1

ABSTRACT

Inflammation has a crucial role in COVID-19 pathogenesis, and previous studies have proposed an important function of IL-6 during inflammation. On the other hand, IL-6 levels and inflammation might be associated with hypoxia-inducible factor-1α (HIF-1α). Thus, due to the possible role of HIF-1α in inflammation and COVID-19 pathogenesis, we aimed to investigate the levels of HIF-1α and its correlation with inflammatory parameters (IL-6 and CRP) and D-dimer. In this case-control study, 84 patients (54 patients hospitalized in the ICU and 30 individuals as outpatient subjects) were included as the case group, and 50 healthy subjects were included as the control group. The levels of D-dimer, CRP, IL-6 (interleukin 6) and HIF-1α were assessed in all studied groups. The results of the present investigation showed that the levels of D-dimer, CRP and IL-6 were significantly increased in COVID-19 patients compared to healthy individuals. On the other hand, the level of HIF-1α significantly decreased in COVID-19 patients. In addition, there was a significant correlation between IL-6 and CRP and D-dimer, while HIF-1α was indirectly correlated with IL-6, CRP and D-dimer. Ultimately, our data indicated that the levels of CRP, D-dimer, IL-6 and HIF-1α were significantly different between ICU patients and the outpatient group with healthy individuals. Based on the study results, inflammation plays a crucial role in COVID-19 pathogenesis, and low HIF-1α is a consequence of inflammation due to COVID-19 infection and might have a protective role in COVID-19.


Subject(s)
COVID-19 , Hypoxia , Inflammation
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