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1.
Lancet Respir Med ; 9(5): 533-544, 2021 05.
Article in English | MEDLINE | ID: covidwho-1931217

ABSTRACT

Cough is one of the most common presenting symptoms of COVID-19, along with fever and loss of taste and smell. Cough can persist for weeks or months after SARS-CoV-2 infection, often accompanied by chronic fatigue, cognitive impairment, dyspnoea, or pain-a collection of long-term effects referred to as the post-COVID syndrome or long COVID. We hypothesise that the pathways of neurotropism, neuroinflammation, and neuroimmunomodulation through the vagal sensory nerves, which are implicated in SARS-CoV-2 infection, lead to a cough hypersensitivity state. The post-COVID syndrome might also result from neuroinflammatory events in the brain. We highlight gaps in understanding of the mechanisms of acute and chronic COVID-19-associated cough and post-COVID syndrome, consider potential ways to reduce the effect of COVID-19 by controlling cough, and suggest future directions for research and clinical practice. Although neuromodulators such as gabapentin or opioids might be considered for acute and chronic COVID-19 cough, we discuss the possible mechanisms of COVID-19-associated cough and the promise of new anti-inflammatories or neuromodulators that might successfully target both the cough of COVID-19 and the post-COVID syndrome.


Subject(s)
COVID-19/complications , COVID-19/physiopathology , Cough/etiology , Inflammation/etiology , Nervous System Diseases/etiology , Neuroimmunomodulation , Cough/physiopathology , Humans , Inflammation/physiopathology , Nervous System Diseases/physiopathology , SARS-CoV-2 , Syndrome
2.
Neurol Neuroimmunol Neuroinflamm ; 9(1)2022 01.
Article in English | MEDLINE | ID: covidwho-1928237

ABSTRACT

BACKGROUND AND OBJECTIVES: It is unclear how multiple sclerosis (MS) affects the severity of COVID-19. The aim of this study is to compare COVID-19-related outcomes collected in an Italian cohort of patients with MS with the outcomes expected in the age- and sex-matched Italian population. METHODS: Hospitalization, intensive care unit (ICU) admission, and death after COVID-19 diagnosis of 1,362 patients with MS were compared with the age- and sex-matched Italian population in a retrospective observational case-cohort study with population-based control. The observed vs the expected events were compared in the whole MS cohort and in different subgroups (higher risk: Expanded Disability Status Scale [EDSS] score > 3 or at least 1 comorbidity, lower risk: EDSS score ≤ 3 and no comorbidities) by the χ2 test, and the risk excess was quantified by risk ratios (RRs). RESULTS: The risk of severe events was about twice the risk in the age- and sex-matched Italian population: RR = 2.12 for hospitalization (p < 0.001), RR = 2.19 for ICU admission (p < 0.001), and RR = 2.43 for death (p < 0.001). The excess of risk was confined to the higher-risk group (n = 553). In lower-risk patients (n = 809), the rate of events was close to that of the Italian age- and sex-matched population (RR = 1.12 for hospitalization, RR = 1.52 for ICU admission, and RR = 1.19 for death). In the lower-risk group, an increased hospitalization risk was detected in patients on anti-CD20 (RR = 3.03, p = 0.005), whereas a decrease was detected in patients on interferon (0 observed vs 4 expected events, p = 0.04). DISCUSSION: Overall, the MS cohort had a risk of severe events that is twice the risk than the age- and sex-matched Italian population. This excess of risk is mainly explained by the EDSS score and comorbidities, whereas a residual increase of hospitalization risk was observed in patients on anti-CD20 therapies and a decrease in people on interferon.


Subject(s)
COVID-19/epidemiology , COVID-19/physiopathology , Multiple Sclerosis/epidemiology , Adult , COVID-19/immunology , COVID-19/therapy , Cohort Studies , Comorbidity , Female , Hospitalization/statistics & numerical data , Humans , Intensive Care Units/statistics & numerical data , Italy/epidemiology , Male , Middle Aged , Multiple Sclerosis/immunology , Multiple Sclerosis/physiopathology , Retrospective Studies , Risk Factors , Severity of Illness Index
3.
Chin J Integr Med ; 28(7): 627-635, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-1919991

ABSTRACT

OBJECTIVE: To investigate how the National Health Commission of China (NHCC)-recommended Chinese medicines (CMs) modulate the major maladjustments of coronavirus disease 2019 (COVID-19), particularly the clinically observed complications and comorbidities. METHODS: By focusing on the potent targets in common with the conventional medicines, we investigated the mechanisms of 11 NHCC-recommended CMs in the modulation of the major COVID-19 pathophysiology (hyperinflammations, viral replication), complications (pain, headache) and comorbidities (hypertension, obesity, diabetes). The constituent herbs of these CMs and their chemical ingredients were from the Traditional Chinese Medicine Information Database. The experimentally-determined targets and the activity values of the chemical ingredients of these CMs were from the Natural Product Activity and Species Source Database. The approved and clinical trial drugs against these targets were searched from the Therapeutic Target Database and DrugBank Database. Pathways of the targets was obtained from Kyoto Encyclopedia of Genes and Genomes and additional literature search. RESULTS: Overall, 9 CMs modulated 6 targets discovered by the COVID-19 target discovery studies, 8 and 11 CMs modulated 8 and 6 targets of the approved or clinical trial drugs for the treatment of the major COVID-19 complications and comorbidities, respectively. CONCLUSION: The coordinated actions of each NHCC-recommended CM against a few targets of the major COVID-19 pathophysiology, complications and comorbidities, partly have common mechanisms with the conventional medicines.


Subject(s)
COVID-19 , Medicine, Chinese Traditional , COVID-19/complications , COVID-19/drug therapy , COVID-19/epidemiology , COVID-19/physiopathology , Comorbidity , Drugs, Chinese Herbal/therapeutic use , Humans , Medicine , SARS-CoV-2
4.
Nature ; 606(7915): S5-S6, 2022 06.
Article in English | MEDLINE | ID: covidwho-1908120
5.
Front Immunol ; 13: 821721, 2022.
Article in English | MEDLINE | ID: covidwho-1902983

ABSTRACT

Many studies already reported on the association between patient characteristics on the severity of COVID-19 disease outcome, but the relation with SARS-CoV-2 antibody levels is less clear. To investigate this in more detail, we performed a retrospective observational study in which we used the IgG antibody response from 11,118 longitudinal antibody measurements of 2,082 unique COVID convalescent plasma donors. COVID-19 symptoms and donor characteristics were obtained by a questionnaire. Antibody responses were modelled using a linear mixed-effects model. Our study confirms that the SARS-CoV-2 antibody response is associated with patient characteristics like body mass index and age. Antibody decay was faster in male than in female donors (average half-life of 62 versus 72 days). Most interestingly, we also found that three symptoms (headache, anosmia, nasal cold) were associated with lower peak IgG, while six other symptoms (dry cough, fatigue, diarrhoea, fever, dyspnoea, muscle weakness) were associated with higher IgG concentrations.


Subject(s)
Age Factors , COVID-19/immunology , COVID-19/therapy , SARS-CoV-2/physiology , Adult , Antibodies, Viral/blood , Antibody Formation , Blood Donors , Body Mass Index , COVID-19/epidemiology , COVID-19/physiopathology , Convalescence , Female , Humans , Immunization, Passive/methods , Immunoglobulin G/blood , Male , Middle Aged , Netherlands/epidemiology , Retrospective Studies
6.
Saudi Med J ; 43(6): 579-586, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-1893429

ABSTRACT

OBJECTIVES: To investigate the relationship between physical activity level and disease severity, anxiety level, sleep quality, and fatigue in patients followed up with COVID-19 diagnosis. METHODS: This was a cross-sectional study of 111 volunteer patients who were receiving treatment with COVID-19 diagnosis at the Chest Diseases Polyclinic, Sanko University, Sani Konukoglu Practice and Research Hospital, Gaziantep, Turkey between May 2021 and July 2021 were included in the study and classified clinically and radiologically. They were evaluated on the basis of demographic characteristics, International Physical Activity Questionnaire, Beck Anxiety Inventory, Pittsburgh Sleep Quality Index, and Fatigue Severity Scale. RESULTS: Approximately 63% of the patients did not have a habit of exercise, while 52.3% of our patients were clinically mild cases, and 33.3% had normal lung tomography. While clinical disease severity was not associated with exercise habits, sleep quality was impaired in clinically severe patients. CONCLUSION: The results of our study suggested that physical inactivity is common. Anxiety is a frequent symptom in COVID-19 cases and also COVID-19 negatively affects sleep quality.


Subject(s)
COVID-19 , Exercise , Anxiety/epidemiology , COVID-19/diagnosis , COVID-19/physiopathology , COVID-19/therapy , Cross-Sectional Studies , Exercise/physiology , Fatigue/epidemiology , Follow-Up Studies , Humans , Severity of Illness Index
7.
Biosensors (Basel) ; 12(6)2022 Jun 05.
Article in English | MEDLINE | ID: covidwho-1884002

ABSTRACT

Biophysical insults that either reduce barrier function (COVID-19, smoke inhalation, aspiration, and inflammation) or increase mechanical stress (surfactant dysfunction) make the lung more susceptible to atelectrauma. We investigate the susceptibility and time-dependent disruption of barrier function associated with pulmonary atelectrauma of epithelial cells that occurs in acute respiratory distress syndrome (ARDS) and ventilator-induced lung injury (VILI). This in vitro study was performed using Electric Cell-substrate Impedance Sensing (ECIS) as a noninvasive evaluating technique for repetitive stress stimulus/response on monolayers of the human lung epithelial cell line NCI-H441. Atelectrauma was mimicked through recruitment/derecruitment (RD) of a semi-infinite air bubble to the fluid-occluded micro-channel. We show that a confluent monolayer with a high level of barrier function is nearly impervious to atelectrauma for hundreds of RD events. Nevertheless, barrier function is eventually diminished, and after a critical number of RD insults, the monolayer disintegrates exponentially. Confluent layers with lower initial barrier function are less resilient. These results indicate that the first line of defense from atelectrauma resides with intercellular binding. After disruption, the epithelial layer community protection is diminished and atelectrauma ensues. ECIS may provide a platform for identifying damaging stimuli, ventilation scenarios, or pharmaceuticals that can reduce susceptibility or enhance barrier-function recovery.


Subject(s)
COVID-19 , Pulmonary Atelectasis/etiology , Respiratory Distress Syndrome , Ventilator-Induced Lung Injury , COVID-19/complications , COVID-19/physiopathology , Electric Impedance , Humans , Lung/physiopathology , Pneumonia, Aspiration/complications , Pneumonia, Aspiration/physiopathology , Pulmonary Atelectasis/physiopathology , Smoke Inhalation Injury/etiology , Smoke Inhalation Injury/physiopathology , Ventilator-Induced Lung Injury/complications , Ventilator-Induced Lung Injury/prevention & control
8.
Odontoestomatol ; 24(39): 1-19, 2022.
Article in Spanish | WHO COVID, LILACS (Americas) | ID: covidwho-1863564

ABSTRACT

La enfermedad por coronavirus es una infección respiratoria causada por el virus SARS-CoV 2, el cual genera una cascada de eventos sistémicos, afectando diferentes órganos y tejidos. El entendimiento de la fisiopatología del COVID-19 es indispensable no solo al momento de brindar tratamiento a los pacientes, sino que también para comprender las causas de las complicaciones que presentan un número importante de pacientes recuperados. El objetivo de este trabajo es presentar una revisión actualizada de los efectos de la infección en diferentes órganos y sistemas principales que sea de utilidad como material de referencia para profesionales y estudiantes de la salud. Para ello se realizó una búsqueda bibliográfica en los portales PubMED, Scielo, Google Scholar, Cochrane y Springer Link, así como en las bases de repositorios científicos pre-publicación bioRxiv ("bioarchives") y medRxiv ("med-archives") y sobre un total de cerca de 200 mil artículos, se seleccionaron 100 artículos para esta revisión en base a su relevancia o sugerencias de parte de profesionales especializados.


Coronavirus disease is a respiratory infection caused by the SARS-CoV-2 virus, which causes a cascade of systemic events, affecting various organs and tissues. Understanding the pathophysiology of COVID-19 is essential to treat patients and understand the causes of the complications in a significant number of recovered patients. This article presents a review of the effects of infection on various organs and systems that will be useful as reference material for healthcare professionals and medical students. To this end, a literature search was conducted in PubMED, Scielo, Google Scholar, Cochrane, and Springer Link portals, as well as in the pre-publication scientific repositories bioRxiv ("bioarchives") and medRxiv ("med-archives") databases. From about 200,000 papers, 100 articles were selected for this review based on their relevance or suggestions from experts in the field.


A doença coronavírus é uma infecção respiratória causada pelo vírus SARS-CoV-2, que gera uma cascata de eventos sistêmicos, afetando diferentes órgãos e tecidos. Compreender a fisiopatologia da COVID-19 é essencial não apenas no tratamento de pacientes, mas também para compreender as causas das complicações que um número significativo de pacientes recuperados apresenta. O objetivo deste trabalho é apresentar uma revisão atualizada dos efeitos da infecção em diferentes órgãos e principais sistemas que seja útil como material de referência para profissionais de saúde e estudantes. Para isso, foi realizada uma pesquisa bibliográfica nos portais PubMED, Scielo, Google Scholar, Cochrane e Springer Link, bem como nos repositórios científicos de pré-publicação bioRxiv ("bioarquivos") e medRxiv ("arquivos med"). Num total de cerca de 200 mil artigos, 100 artigos foram selecionados para esta revisão por sua relevância ou sugestões de profissionais especializados.


Subject(s)
Humans , COVID-19/physiopathology , Pulmonary Alveoli/physiopathology , Cardiovascular Diseases/physiopathology , Central Nervous System Diseases/physiopathology , Digestive System Diseases/physiopathology , Endocrine System Diseases/physiopathology , SARS-CoV-2/metabolism , COVID-19/epidemiology , Mouth Diseases/physiopathology
9.
JAMA Netw Open ; 4(2): e210202, 2021 02 01.
Article in English | MEDLINE | ID: covidwho-1858185

ABSTRACT

Importance: Owing to concerns of coronavirus disease 2019 (COVID-19) outbreaks, many congregant settings are forced to close when cases are detected because there are few data on the risk of different markers of transmission within groups. Objective: To determine whether symptoms and laboratory results on the first day of COVID-19 diagnosis are associated with development of a case cluster in a congregant setting. Design, Setting, and Participants: This cohort study of trainees with COVID-19 from May 11 through August 24, 2020, was conducted at Joint Base San Antonio-Lackland, the primary site of entry for enlistment in the US Air Force. Symptoms and duration, known contacts, and cycle threshold for trainees diagnosed by reverse transcription-polymerase chain reaction were collected. A cycle threshold value represents the number of nucleic acid amplification cycles that occur before a specimen containing the target material generates a signal greater than the predetermined threshold that defines positivity. Cohorts with 5 or more individuals with COVID-19 infection were defined as clusters. Participants included 10 613 trainees divided into 263 parallel cohorts of 30 to 50 people arriving weekly for 7 weeks of training. Exposures: All trainees were quarantined for 14 days on arrival. Testing was performed on arrival, on day 14, and anytime during training when indicated. Protective measures included universal masking, physical distancing, and rapid isolation of trainees with COVID-19. Main Outcomes and Measures: Association between days of symptoms, specific symptoms, number of symptoms, or cycle threshold values of individuals diagnosed with COVID-19 via reverse transcription-polymerase chain reaction and subsequent transmission within cohorts. Results: In this cohort study of 10 613 US Air Force basic trainees in 263 cohorts, 403 trainees (3%) received a diagnosis of COVID-19 in 129 cohorts (49%). Among trainees with COVID-19 infection, 318 (79%) were men, and the median (interquartile range [IQR]) age was 20 (19-23) years; 204 (51%) were symptomatic, and 199 (49%) were asymptomatic. Median (IQR) cycle threshold values were lower in symptomatic trainees compared with asymptomatic trainees (21.2 [18.4-27.60] vs 34.8 [29.3-37.4]; P < .001). Cohorts with clusters of individuals with COVID-19 infection were predominantly men (204 cohorts [89%] vs 114 cohorts [64%]; P < .001), had more symptomatic trainees (146 cohorts [64%] vs 53 cohorts [30%]; P < .001), and had more median (IQR) symptoms per patient (3 [2-5] vs 1 [1-2]; P < .001) compared with cohorts without clusters. Within cohorts, subsequent development of clusters of 5 or more individuals with COVID-19 infection compared with those that did not develop clusters was associated with cohorts that had more symptomatic trainees (31 of 58 trainees [53%] vs 43 of 151 trainees [28%]; P = .001) and lower median (IQR) cycle threshold values (22.3 [18.4-27.3] vs 35.3 [26.5-37.8]; P < .001). Conclusions and Relevance: In this cohort study of US Air Force trainees living in a congregant setting during the COVID-19 pandemic, higher numbers of symptoms and lower cycle threshold values were associated with subsequent development of clusters of individuals with COVID-19 infection. These values may be useful if validated in future studies.


Subject(s)
COVID-19 Nucleic Acid Testing/methods , COVID-19/transmission , Military Personnel/statistics & numerical data , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19/physiopathology , Carrier State/diagnosis , Carrier State/epidemiology , Carrier State/transmission , Cohort Studies , Cough/physiopathology , Female , Headache/physiopathology , Humans , Male , Myalgia/physiopathology , Pharyngitis/physiopathology , Residence Characteristics , Risk Factors , SARS-CoV-2 , Severity of Illness Index , United States/epidemiology , Young Adult
10.
IUBMB Life ; 74(1): 62-73, 2022 01.
Article in English | MEDLINE | ID: covidwho-1850068

ABSTRACT

Airborne pollution has become a leading cause of global death in industrialized cities and the exposure to environmental pollutants has been demonstrated to have adverse effects on human health. Among the pollutants, particulate matter (PM) is one of the most toxic and although its exposure has been more commonly correlated with respiratory diseases, gastrointestinal (GI) complications have also been reported as a consequence to PM exposure. Due to its composition, PM is able to exert on intestinal mucosa both direct damaging effects, (by reaching it either via direct ingestion of contaminated food and water or indirect inhalation and consequent macrophagic mucociliary clearance) and indirect ones via generation of systemic inflammation. The relationship between respiratory and GI conditions is well described by the lung-gut axis and more recently, has become even clearer during coronavirus disease 2019 (COVID-19) pandemic, when respiratory symptoms were associated with gastrointestinal conditions. This review aims at pointing out the mechanisms and the models used to evaluate PM induced GI tract damage.


Subject(s)
COVID-19/etiology , Gastrointestinal Tract/injuries , Particulate Matter/toxicity , SARS-CoV-2 , Administration, Inhalation , Administration, Oral , COVID-19/physiopathology , COVID-19/prevention & control , Gastrointestinal Tract/physiopathology , Humans , Intestinal Mucosa/injuries , Intestinal Mucosa/physiopathology , Masks , Microplastics/toxicity , Models, Biological , Mucociliary Clearance/physiology , Nutrition Policy , Pandemics/prevention & control , Particulate Matter/administration & dosage , Respiratory System/injuries , Respiratory System/physiopathology
11.
J Med Virol ; 94(9): 4088-4096, 2022 Sep.
Article in English | MEDLINE | ID: covidwho-1838234

ABSTRACT

Innate and acquired immunity responses are crucial for viral infection elimination. However, genetic variations in coding genes may exacerbate the inflammation or initiate devastating cytokine storms which poses severe respiratory conditions in coronavirus disease-19 (COVID-19). Host genetic variations in particular those related to the immune responses determine the patients' susceptibility and COVID-19 severity and pathophysiology. Gene polymorphisms such as single nucleotide polymorphisms (SNPs) of interferons, TNF, IL1, IL4, IL6, IL7, IL10, and IL17 predispose patients to the severe form of COVID-19 or severe acute respiratory syndrome coronavirus-2 (SARS-COV-2). These variations mainly alter the gene expression and cause a severe response by B cells, T cells, monocytes, neutrophils, and natural killer cells participating in a cytokine storm. Moreover, cytokines and chemokines SNPs are associated with the severity of COVID-19 and clinical outcomes depending on the corresponding effect. Additionally, genetic variations in genes encoding toll-like receptors (TLRs) mainly TLR3, TLR7, and TLR9 have been related to the COVID-19 severe respiratory symptoms. The specific relation of these mutations with the novel variants of concern (VOCs) infection remains to be elucidated. Genetic variations mainly within genes encoding proinflammatory cytokines, cytokine receptors, and TLRs predispose patients to COVID-19 disease severity. Understanding host immune gene variations associated with the SARS-COV-2 infection opens insights to control the pathophysiology of emerging viral infections.


Subject(s)
COVID-19 , Cytokines , Receptors, Cytokine , Toll-Like Receptors , COVID-19/genetics , COVID-19/physiopathology , Cytokine Release Syndrome/genetics , Cytokines/genetics , Humans , Receptors, Cytokine/genetics , SARS-CoV-2 , Toll-Like Receptors/genetics
12.
Allergy Asthma Proc ; 43(3): 187-193, 2022 05 01.
Article in English | MEDLINE | ID: covidwho-1834259

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.


Subject(s)
COVID-19 , Cytokines , COVID-19/complications , COVID-19/physiopathology , Cytokines/metabolism , Humans , SARS-CoV-2
13.
PLoS One ; 16(4): e0250815, 2021.
Article in English | MEDLINE | ID: covidwho-1833533

ABSTRACT

BACKGROUND: COVID-19 is a respiratory infectious disease caused by SARS-CoV-2, and cardiovascular damage is commonly observed in affected patients. We sought to investigate the effect of SARS-CoV-2 infection on cardiac injury and hypertension during the current coronavirus pandemic. STUDY DESIGN AND METHODS: The clinical data of 366 hospitalized COVID-19-confirmed patients were analyzed. The clinical signs and laboratory findings were extracted from electronic medical records. Two independent, experienced clinicians reviewed and analyzed the data. RESULTS: Cardiac injury was found in 11.19% (30/268) of enrolled patients. 93.33% (28/30) of cardiac injury cases were in the severe group. The laboratory findings indicated that white blood cells, neutrophils, procalcitonin, C-reactive protein, lactate, and lactic dehydrogenase were positively associated with cardiac injury marker. Compared with healthy controls, the 190 patients without prior hypertension have higher AngⅡ level, of which 16 (8.42%) patients had a rise in blood pressure to the diagnostic criteria of hypertension during hospitalization, with a significantly increased level of the cTnI, procalcitonin, angiotensin-II (AngⅡ) than those normal blood pressure ones. Multivariate analysis indicated that elevated age, cTnI, the history of hypertension, and diabetes were independent predictors for illness severity. The predictive model, based on the four parameters and gender, has a good ability to identify the clinical severity of COVID-19 in hospitalized patients (area under the curve: 0.932, sensitivity: 98.67%, specificity: 75.68%). CONCLUSION: Hypertension, sometimes accompanied by elevated cTnI, may occur in COVID-19 patients and become a sequela. Enhancing Ang II signaling, driven by SARS-CoV-2 infection, might play an important role in the renin-angiotensin system, and consequently lead to the development of hypertension in COVID-19.


Subject(s)
COVID-19/complications , Heart Injuries/epidemiology , Hypertension/epidemiology , Adult , Aged , Aged, 80 and over , COVID-19/metabolism , COVID-19/physiopathology , Comorbidity , Disease Progression , Female , Heart Injuries/virology , Hospitalization , Humans , Hypertension/physiopathology , Hypertension/virology , Male , Medical Records , Middle Aged , Pandemics , Renin-Angiotensin System , SARS-CoV-2/pathogenicity
14.
Adv Biol (Weinh) ; 6(7): e2101327, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-1825809

ABSTRACT

Sars-Cov-2 may trigger molecular and functional alterations of cardiomyocytes (CMs) of the heart due to the presence of receptor angiotensin-converting enzyme 2 (ACE2) of the host cells. While the endocytic itinerary of the virus via cleavage of the spike protein of Sars-Cov-2 is well understood, the role of the remaining part of the spike protein subunit and ACE2 complex is still elusive. Herein, the possible effects of this complex are investigated by using synthetic spike proteins of Sars-Cov-2, human-induced pluripotent stem cells (hiPSC), and a culture device made of an arrayed monolayer of cross-linked nanofibers. hiPSCs are first differentiated into CMs that form cardiac tissue-like constructs with regular beating and expression of both ACE2 and gap junction protein Connexin 43. When incubated with the spike proteins, the hiPSC-CMs undergo a rhythmic fluctuation with overstretched sarcomere structures and dispersed gap junction proteins. When incubated with the spike proteins and supplementary angiotensin II, the damage of the spike protein on hiPSC-CMs is enhanced due to downregulated ACE2, chromatin margination, altered Connexin 43 expression, sarcomere disruption, and beating break. This discovery may imply latent effects of the spike proteins on the heart.


Subject(s)
Angiotensin-Converting Enzyme 2 , COVID-19 , Myocytes, Cardiac , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Angiotensin II/pharmacology , Angiotensin-Converting Enzyme 2/metabolism , COVID-19/metabolism , COVID-19/pathology , COVID-19/physiopathology , Connexin 43/metabolism , Culture Techniques , Humans , Induced Pluripotent Stem Cells , Myocytes, Cardiac/metabolism , Myocytes, Cardiac/pathology , Myocytes, Cardiac/virology , SARS-CoV-2/metabolism , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/metabolism
15.
Biomed Res Int ; 2022: 8078259, 2022.
Article in English | MEDLINE | ID: covidwho-1822112

ABSTRACT

Coronaviruses are a family of viruses that infect mammals and birds. Coronaviruses cause infections of the respiratory system in humans, which can be minor or fatal. A comparative transcriptomic analysis has been performed to establish essential profiles of the gene expression of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) linked to cystic fibrosis (CF). Transcriptomic studies have been carried out in relation to SARS-CoV-2 since a number of people have been diagnosed with CF. The recognition of differentially expressed genes demonstrated 8 concordant genes shared between the SARS-CoV-2 and CF. Extensive gene ontology analysis and the discovery of pathway enrichment demonstrated SARS-CoV-2 response to CF. The gene ontological terms and pathway enrichment mechanisms derived from this research may affect the production of successful drugs, especially for the people with the following disorder. Identification of TF-miRNA association network reveals the interconnection between TF genes and miRNAs, which may be effective to reveal the other influenced disease that occurs for SARS-CoV-2 to CF. The enrichment of pathways reveals SARS-CoV-2-associated CF mostly engaged with the type of innate immune system, Toll-like receptor signaling pathway, pantothenate and CoA biosynthesis, allograft rejection, graft-versus-host disease, intestinal immune network for IgA production, mineral absorption, autoimmune thyroid disease, legionellosis, viral myocarditis, inflammatory bowel disease (IBD), etc. The drug compound identification demonstrates that the drug targets of IMIQUIMOD and raloxifene are the most significant with the significant hub DEGs.


Subject(s)
COVID-19 , Cystic Fibrosis , COVID-19/genetics , COVID-19/physiopathology , Cystic Fibrosis/genetics , Cystic Fibrosis/physiopathology , Gene Expression Profiling , Gene Ontology , Humans , MicroRNAs/genetics , SARS-CoV-2 , Transcription Factors/genetics
16.
Neuropharmacology ; 209: 109023, 2022 05 15.
Article in English | MEDLINE | ID: covidwho-1821424

ABSTRACT

Acute neurological alterations have been associated with SARS-CoV-2 infection. Additionally, it is becoming clear that coronavirus disease 2019 (COVID-19) survivors may experience long-term neurological abnormalities, including cognitive deficits and mood alterations. The mechanisms underlying acute and long-term impacts of COVID-19 in the brain are being actively investigated. Due to the heterogeneous manifestations of neurological outcomes, it is possible that different mechanisms operate following SARS-CoV-2 infection, which may include direct brain infection by SARS-CoV-2, mechanisms resulting from hyperinflammatory systemic disease, or a combination of both. Inflammation is a core feature of COVID-19, and both central and systemic inflammation are known to lead to acute and persistent neurological alterations in other diseases. Here, we review evidence indicating that COVID-19 is associated with neuroinflammation, along with blood-brain barrier dysfunction. Similar neuroinflammatory signatures have been associated with Alzheimer's disease and major depressive disorder. Current evidence demonstrates that patients with pre-existing cognitive and neuropsychiatric deficits show worse outcomes upon infection by SARS-CoV-2 and, conversely, COVID-19 survivors may be at increased risk of developing dementia and mood disorders. Considering the high prevalence of COVID-19 patients that recovered from infection in the world and the alarming projections for the prevalence of dementia and depression, investigation of possible molecular similarities between those diseases may shed light on mechanisms leading to long-term neurological abnormalities in COVID-19 survivors.


Subject(s)
COVID-19/complications , Cognitive Dysfunction/etiology , Depression/etiology , Neuroinflammatory Diseases/physiopathology , Affect/physiology , Blood-Brain Barrier/metabolism , COVID-19/physiopathology , Cognitive Dysfunction/physiopathology , Depression/physiopathology , Humans , Inflammation/physiopathology , SARS-CoV-2 , Virus Diseases/complications
17.
Nature ; 606(7914): 585-593, 2022 06.
Article in English | MEDLINE | ID: covidwho-1815563

ABSTRACT

Severe COVID-19 is characterized by persistent lung inflammation, inflammatory cytokine production, viral RNA and a sustained interferon (IFN) response, all of which are recapitulated and required for pathology in the SARS-CoV-2-infected MISTRG6-hACE2 humanized mouse model of COVID-19, which has a human immune system1-20. Blocking either viral replication with remdesivir21-23 or the downstream IFN-stimulated cascade with anti-IFNAR2 antibodies in vivo in the chronic stages of disease attenuates the overactive immune inflammatory response, especially inflammatory macrophages. Here we show that SARS-CoV-2 infection and replication in lung-resident human macrophages is a critical driver of disease. In response to infection mediated by CD16 and ACE2 receptors, human macrophages activate inflammasomes, release interleukin 1 (IL-1) and IL-18, and undergo pyroptosis, thereby contributing to the hyperinflammatory state of the lungs. Inflammasome activation and the accompanying inflammatory response are necessary for lung inflammation, as inhibition of the NLRP3 inflammasome pathway reverses chronic lung pathology. Notably, this blockade of inflammasome activation leads to the release of infectious virus by the infected macrophages. Thus, inflammasomes oppose host infection by SARS-CoV-2 through the production of inflammatory cytokines and suicide by pyroptosis to prevent a productive viral cycle.


Subject(s)
COVID-19 , Inflammasomes , Macrophages , SARS-CoV-2 , Angiotensin-Converting Enzyme 2 , Animals , COVID-19/pathology , COVID-19/physiopathology , COVID-19/virology , Humans , Inflammasomes/metabolism , Interleukin-1 , Interleukin-18 , Lung/pathology , Lung/virology , Macrophages/metabolism , Macrophages/pathology , Macrophages/virology , Mice , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Pneumonia/metabolism , Pneumonia/virology , Pyroptosis , Receptors, IgG , SARS-CoV-2/metabolism , SARS-CoV-2/pathogenicity
18.
Clin Dermatol ; 39(6): 934-965, 2021.
Article in English | MEDLINE | ID: covidwho-1797058

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiologic agent of coronavirus disease 2019 (COVID-19), is a single-stranded RNA virus whose sequence is known. COVID-19 is associated with a heterogeneous clinical phenotype ranging from asymptomatic to fatal disease. It appears that access to nasopharyngeal respiratory epithelia expressing angiotensin-converting enzyme (ACE) 2, the receptor for SARS-CoV-2, is followed by viral replication in the pulmonary alveolar septal capillary bed. We have demonstrated in earlier studies that incomplete viral particles, termed pseudovirions, dock to deep subcutaneous and other vascular beds, potentially contributing to the prothrombotic state and systemic complement activation that characterizes severe and critical COVID-19. A variety of skin eruptions have been described in the setting of SARS-CoV-2 infection and more recently, after COVID-19 vaccination. The vaccines deliver a laboratory-synthesized mRNA that encodes a protein that is identical to the spike glycoprotein of SARS-CoV-2, allowing the production of immunogenic spike glycoprotein that will then elicit T cell and B cell adaptive immune responses. In this contribution, we review an array of cutaneous manifestations of COVID-19 that provide an opportunity to study critical pathophysiologic mechanisms that underlie all clinical facets of COVID-19, ranging from asymptomatic/mild to severe and critical COVID-19. We classify cutaneous COVID-19 according to underlying pathophysiologic principles. In this regard we propose three main pathways: (1) complement mediated thrombotic vascular injury syndromes deploying the alternative and mannan binding lectin pathways and resulting in the elaboration of cytokines like interleukin 6 from endothelium in the setting of severe and critical COVID-19 and (2) the robust T cell and type I interferon-driven inflammatory and (3) humoral-driven immune complex mediated vasculitic cutaneous reactions observed with mild and moderate COVID-19. Presented are novel data on cutaneous vaccine reactions that manifest a clinical and morphologic parallel with similar eruptions observed in patients with mild and moderate COVID-19 and in some cases represent systemic eczematoid hypersensitivity reactions to a putative vaccine-based antigen versus unmasking subclinical hypersensitivity due to immune enhancing effects of the vaccine. Finally, we demonstrate for the first time the localization of human synthesized spike glycoprotein after the COVID-19 vaccine to the cutaneous and subcutaneous vasculature confirming the ability of SARS-CoV-2 spike glycoprotein to bind endothelium in the absence of intact virus.


Subject(s)
COVID-19 , Skin Diseases/virology , COVID-19/immunology , COVID-19/physiopathology , COVID-19 Vaccines , Cytokines , Humans , Skin Diseases/immunology , Spike Glycoprotein, Coronavirus
19.
J Pain ; 23(7): 1234-1244, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-1796448

ABSTRACT

Recent studies suggest that the COVID-19 pandemic can serve as a unique psychosocial stressor that can negatively impact individuals with chronic pain. Using a large online sample in the U.S., the present study sought to investigate the impact of the pandemic on the trajectories of pain severity and interference, emotional distress (ie, anxiety and depressive symptoms), and opioid misuse behaviors across one year. Potential moderating effects of socio-demographic factors and individual differences in pain catastrophizing, pain acceptance, and sleep disturbance on outcome trajectories were also examined. Adults with chronic pain were surveyed three times across 1 year (April/May 2020 [N = 1,453]; June/July 2020 [N = 878], and May 2021 [N = 813]) via Amazon's Mechanical Turk online crowdsourcing platform. Mixed-effects growth models revealed that pain severity and interference, emotional distress, and opioid misuse behaviors did not significantly deteriorate across one year during the pandemic. None of the socio-demographic factors, pain catastrophizing, or sleep disturbance moderated outcome trajectories. However, individuals with higher pain acceptance reported greater improvement in pain severity (P< .008, 95% CI: -.0002, -.00004) and depressive symptoms (P< .001, 95% CI: -.001, -.0004) over time. Our findings suggest that the negative impact of the pandemic on pain, emotional distress, and opioid misuse behaviors is quite small overall. The outcome trajectories were also stable across different socio-demographic factors, as well as individual differences in pain catastrophizing and sleep disturbance. Nevertheless, interventions that target improvement of pain acceptance may help individuals with chronic pain be resilient during the pandemic. PERSPECTIVE: Individuals with chronic pain overall did not experience significant exacerbation of pain, emotional distress, and opioid misuse across one year during the COVID-19 pandemic. Individuals with higher pain acceptance showed greater improvement in pain severity and depressive symptoms over time during the pandemic.


Subject(s)
Analgesics, Opioid , COVID-19 , Chronic Pain , Opioid-Related Disorders , Adult , Analgesics, Opioid/therapeutic use , COVID-19/physiopathology , COVID-19/psychology , Chronic Pain/complications , Chronic Pain/drug therapy , Humans , Longitudinal Studies , Opioid-Related Disorders/etiology , Psychological Distress
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