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1.
Ren Fail ; 46(1): 2338484, 2024 Dec.
Article En | MEDLINE | ID: mdl-38832469

Critically ill COVID-19 patients may exhibit various clinical symptoms of renal dysfunction including severe Acute Kidney Injury (AKI). Currently, there is a lack of bibliometric analyses on COVID-19-related AKI. The aim of this study is to provide an overview of the current research status and hot topics regarding COVID-19 AKI. The literature was retrieved from the Web of Science Core Collection (WoSCC) database. Subsequently, we utilized Microsoft Excel, VOSviewer, Citespace, and Pajek software to revealed the current research status, emerging topics, and developmental trends pertaining to COVID-19 AKI. This study encompassed a total of 1507 studies on COVID-19 AKI. The United States, China, and Italy emerged as the leading three countries in terms of publication numbers, contributing 498 (33.05%), 229 (15.20%), and 140 (9.29%) studies, respectively. The three most active and influential institutions include Huazhong University of Science and Technology, Wuhan University and Harvard Medical School. Ronco C from Italy, holds the record for the highest number of publications, with a total of 15 papers authored. Cheng YC's work from China has garnered the highest number of citations, totaling 470 citations. The co-occurrence analysis of author keywords reveals that 'mortality', 'intensive care units', 'chronic kidney disease', 'nephrology', 'renal transplantation', 'acute respiratory distress syndrome', and 'risk factors' emerge as the primary areas of focus within the realm of COVID-19 AKI. In summary, this study analyzes the research trends in the field of COVID-19 AKI, providing a reference for further exploration and research on COVID-19 AKI mechanisms and treatment.


Acute Kidney Injury , Bibliometrics , COVID-19 , Pandemics , SARS-CoV-2 , Humans , COVID-19/complications , COVID-19/epidemiology , Acute Kidney Injury/epidemiology , Acute Kidney Injury/etiology , Coronavirus Infections/epidemiology , Coronavirus Infections/complications , Pneumonia, Viral/epidemiology , Pneumonia, Viral/complications , Italy/epidemiology , Betacoronavirus , China/epidemiology , Global Health
2.
PLoS One ; 19(6): e0298254, 2024.
Article En | MEDLINE | ID: mdl-38843201

BACKGROUND: In randomized controlled trials, Nirmatrelvir/ritonavir (NMV/r) and Molnupiravir (MPV) reduced the risk of severe/fatal COVID-19 disease. Real-world data are limited, particularly studies directly comparing the two agents. METHODS: Using the VA National COVID-19 database, we identified previously uninfected, non-hospitalized individuals with COVID-19 with ≥1 risk factor for disease progression who were prescribed either NMV/r or MPV within 3 days of a positive test. We used inverse probability of treatment weights (IPTW) to account for providers' preferences for a specific treatment. Absolute risk difference (ARD) with 95% confidence intervals were determined for those treated with NMV/r vs. MPV. The primary outcome was hospitalization or death within 30 days of treatment prescription using the IPTW approach. Analyses were repeated using propensity-score matched groups. RESULTS: Between January 1 and November 30, 2022, 9,180 individuals were eligible for inclusion (6,592 prescribed NMV/r; 2,454 prescribed MPV). The ARD for hospitalization/death for NMV/r vs MPV was -0.25 (95% CI -0.79 to 0.28). There was no statistically significant difference in ARD among strata by age, race, comorbidities, or symptoms at baseline. Kaplan-Meier curves did not demonstrate a difference between the two groups (p-value = 0.6). Analysis of the propensity-score matched cohort yielded similar results (ARD for NMV/r vs. MPV -0.9, 95% CI -2.02 to 0.23). Additional analyses showed no difference for development of severe/critical/fatal disease by treatment group. CONCLUSION: We found no significant difference in short term risk of hospitalization or death among at-risk individuals with COVID-19 treated with either NMV/r or MPV.


Antiviral Agents , COVID-19 Drug Treatment , COVID-19 , Cytidine , Disease Progression , Hospitalization , Hydroxylamines , Leucine , Ritonavir , SARS-CoV-2 , Humans , Male , Female , Ritonavir/therapeutic use , Middle Aged , Hydroxylamines/therapeutic use , Cytidine/analogs & derivatives , Cytidine/therapeutic use , COVID-19/mortality , COVID-19/epidemiology , Antiviral Agents/therapeutic use , Leucine/analogs & derivatives , Leucine/therapeutic use , Aged , SARS-CoV-2/isolation & purification , Proline/analogs & derivatives , Proline/therapeutic use , Indoles/therapeutic use , Adult , Pandemics , Risk Factors , Coronavirus Infections/drug therapy , Coronavirus Infections/mortality , Pneumonia, Viral/drug therapy , Pneumonia, Viral/mortality , Pneumonia, Viral/virology , Betacoronavirus , Lactams , Nitriles
3.
Virol J ; 21(1): 131, 2024 Jun 05.
Article En | MEDLINE | ID: mdl-38840200

Neonatal pulmonary hemorrhage is a late manifestation of various diseases. Premature delivery and low body weight are frequently observed as high-risk factors, characterized by acute onset, rapid progression, and high mortality rates. Pulmonary hemorrhage caused by cytomegalovirus infection in newborns with normal immune function is a rare occurrence. This case report focuses on a term neonate with normal birth weight who presented solely with nasal obstruction shortly after birth. However, 4 days after birth, the newborn experienced a sudden onset of blood gushing from both the mouth and nasal cavity. The patient was diagnosed with gastrointestinal bleeding, neonatal pneumonia and neonatal lung consolidation. And he was discharged after ten days of symptomatic treatment. However, upon returning home, the patient experienced a sudden onset of bleeding from the mouth and nose, leading to his untimely demise. Subsequent autopsy revealed the presence of pulmonary hemorrhage in newborn, which presented as interstitial pneumonia. The cause of pulmonary hemorrhage is cytomegalovirus infection. This case emphasizes the importance of pediatricians enhancing their skills in differentiating pulmonary hemorrhage, especially from cytomegalovirus pneumonia.


Cytomegalovirus Infections , Hemorrhage , Humans , Cytomegalovirus Infections/complications , Cytomegalovirus Infections/diagnosis , Infant, Newborn , Male , Fatal Outcome , Hemorrhage/etiology , Cytomegalovirus , Lung/pathology , Lung/diagnostic imaging , Lung/virology , Pneumonia, Viral/complications , Pneumonia, Viral/diagnosis , Pneumonia, Viral/virology , Autopsy , Lung Diseases/virology , Lung Diseases/etiology
4.
Medicine (Baltimore) ; 103(19): e37817, 2024 May 10.
Article En | MEDLINE | ID: mdl-38728486

This study aimed to investigate the expression and significance of serum procalcitonin (PCT), leukotriene B4 (LTB4), Serum amyloid A (SAA), and C-reactive protein (CRP) in children with different types of pneumonia caused by different pathogenic infections. One hundred and one children with pneumonia admitted to The Fifth People Hospital of Zhuhai from July 2019 to June 2020 were enrolled and divided into 38 cases in the bacterial group, 30 cases in the mycoplasma group, and 33 cases in the virus group according to the different types of pathogens. The patients were divided into 42 cases in the noncritical group, 33 cases in the critical group, and 26 cases in the very critical group according to the pediatric clinical illness score (PCIS), and 30 healthy children were selected as the control group during the same period. Comparison of serum PCT, SAA: bacterial group > mycoplasma group > viral group > control group with significant differences (P < .05). Receiver operator characteristic (ROC) analysis showed that the area under the curves (AUCs) of serum PCT, LTB4, SAA, and CRP for the diagnosis of bacterial pneumonia were 1.000, 0.531, 0.969, and 0.833, respectively, and the AUCs for the diagnosis of mycoplasma pneumonia were 0.653, 0.609, 0.547, and 0.652, respectively, and the AUCs for the diagnosis of viral pneumonia were 0.888, 0.570, 0.955, and 1.000, respectively. Comparison of serum PCT, LTB4, SAA: very critical group > critical group > noncritical group > control group, with significant differences (P < .05). Serum PCT, LTB4, and SAA were negatively correlated with PCIS score by Pearson analysis (P < .05). Serum PCT and SAA showed diagnostic value for bacterial pneumonia, and serum SAA and CRP showed diagnostic value for viral pneumonia; serum PCT, LTB4, and SAA correlate with severity of disease and show higher expression with worsening of the condition.


Biomarkers , C-Reactive Protein , Leukotriene B4 , Pneumonia, Bacterial , Procalcitonin , Serum Amyloid A Protein , Humans , C-Reactive Protein/analysis , Serum Amyloid A Protein/analysis , Serum Amyloid A Protein/metabolism , Male , Female , Procalcitonin/blood , Child, Preschool , Pneumonia, Bacterial/blood , Pneumonia, Bacterial/diagnosis , Child , Leukotriene B4/blood , Biomarkers/blood , ROC Curve , Pneumonia, Mycoplasma/blood , Pneumonia, Mycoplasma/diagnosis , Infant , Pneumonia, Viral/blood , Pneumonia, Viral/diagnosis , Pneumonia/blood , Pneumonia/diagnosis
5.
Biol Pharm Bull ; 47(5): 930-940, 2024.
Article En | MEDLINE | ID: mdl-38692871

The coronavirus disease 2019 (COVID-19) is caused by the etiological agent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19, with the recurrent epidemics of new variants of SARS-CoV-2, remains a global public health problem, and new antivirals are still required. Some cholesterol derivatives, such as 25-hydroxycholesterol, are known to have antiviral activity against a wide range of enveloped and non-enveloped viruses, including SARS-CoV-2. At the entry step of SARS-CoV-2 infection, the viral envelope fuses with the host membrane dependent of viral spike (S) glycoproteins. From the screening of cholesterol derivatives, we found a new compound 26,27-dinorcholest-5-en-24-yne-3ß,20-diol (Nat-20(S)-yne) that inhibited the SARS-CoV-2 S protein-dependent membrane fusion in a syncytium formation assay. Nat-20(S)-yne exhibited the inhibitory activities of SARS-CoV-2 pseudovirus entry and intact SARS-CoV-2 infection in a dose-dependent manner. Among the variants of SARS-CoV-2, inhibition of infection by Nat-20(S)-yne was stronger in delta and Wuhan strains, which predominantly invade into cells via fusion at the plasma membrane, than in omicron strains. The interaction between receptor-binding domain of S proteins and host receptor ACE2 was not affected by Nat-20(S)-yne. Unlike 25-hydroxycholesterol, which regulates various steps of cholesterol metabolism, Nat-20(S)-yne inhibited only de novo cholesterol biosynthesis. As a result, plasma membrane cholesterol content was substantially decreased in Nat-20(S)-yne-treated cells, leading to inhibition of SARS-CoV-2 infection. Nat-20(S)-yne having a new mechanism of action may be a potential therapeutic candidate for COVID-19.


Antiviral Agents , COVID-19 , Cholesterol , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , SARS-CoV-2/drug effects , Antiviral Agents/pharmacology , Humans , COVID-19/virology , Cholesterol/metabolism , Vero Cells , Chlorocebus aethiops , Spike Glycoprotein, Coronavirus/metabolism , Animals , Virus Internalization/drug effects , Betacoronavirus/drug effects , Pandemics , COVID-19 Drug Treatment , Coronavirus Infections/drug therapy , Coronavirus Infections/virology , Angiotensin-Converting Enzyme 2/metabolism , Pneumonia, Viral/drug therapy , Pneumonia, Viral/virology
6.
Front Immunol ; 15: 1382655, 2024.
Article En | MEDLINE | ID: mdl-38803494

Introduction: Global microplastic (MP) pollution is now well recognized, with humans and animals consuming and inhaling MPs on a daily basis, with a growing body of concern surrounding the potential impacts on human health. Methods: Using a mouse model of mild COVID-19, we describe herein the effects of azide-free 1 µm polystyrene MP beads, co-delivered into lungs with a SARS-CoV-2 omicron BA.5 inoculum. The effect of MPs on the host response to SARS-CoV-2 infection was analysed using histopathology and RNA-Seq at 2 and 6 days post-infection (dpi). Results: Although infection reduced clearance of MPs from the lung, virus titres and viral RNA levels were not significantly affected by MPs, and overt MP-associated clinical or histopathological changes were not observed. However, RNA-Seq of infected lungs revealed that MP exposure suppressed innate immune responses at 2 dpi and increased pro-inflammatory signatures at 6 dpi. The cytokine profile at 6 dpi showed a significant correlation with the 'cytokine release syndrome' signature observed in some COVID-19 patients. Discussion: The findings are consistent with the recent finding that MPs can inhibit phagocytosis of apoptotic cells via binding of Tim4. They also add to a growing body of literature suggesting that MPs can dysregulate inflammatory processes in specific disease settings.


COVID-19 , Disease Models, Animal , Immunity, Innate , Lung , Microplastics , SARS-CoV-2 , Animals , COVID-19/immunology , COVID-19/virology , Immunity, Innate/drug effects , SARS-CoV-2/immunology , SARS-CoV-2/physiology , Mice , Lung/immunology , Lung/virology , Lung/pathology , Cytokines/metabolism , Humans , Pneumonia, Viral/immunology , Pneumonia, Viral/virology , Female , Cytokine Release Syndrome/immunology , Coronavirus Infections/immunology , Coronavirus Infections/virology , Betacoronavirus/immunology , Pandemics
7.
BMC Psychol ; 12(1): 313, 2024 May 29.
Article En | MEDLINE | ID: mdl-38811983

BACKGROUND: Sexual and marital satisfaction is considered one of the important factors in happiness and life satisfaction of couples. COVID-19 pandemic results in psychological effects, such as increased anxiety levels which can affect sexual and marital satisfaction. This study aimed to investigate the impact of positive psychology on women's sexual and marital satisfaction. METHODS: A randomized controlled trial was conducted on 72 married women of reproductive age in Tabriz, Iran between February 2021 and May 2022. The participants were randomly divided into the intervention and control groups. There was no significant difference between the control and intervention groups in terms of the socio-demographic characteristics (p < 0.05). The mean age of the participants in the intervention and control groups was 31.8 ± 6.92 and 30.97 ± 5.09 years, respectively. The intervention group attended seven 60-90 min counseling sessions at weekly intervals. The Spielberger anxiety, sexual satisfaction and marital satisfaction questionnaires were completed before and four weeks after the intervention. RESULTS: The results of this study indicated that after counseling, the average overall score of marital satisfaction [MD: 15.46, 95% CI: 7.47 to 23.41, p = 0.034] and sexual satisfaction [MD: 7.83, 95% CI: 6.25 to 9.41, p = 0.001] significantly increased in the intervention group compared to the control group. Also, the mean score of state anxiety [MD: -2.50, 95% CI: -4.19 to -0.80, p = 0.001] and trait anxiety [MD: -1.03, 95% CI: -2.46 to -0.09, p = 0.032] significantly decreased after counseling in the intervention group compared to the control group. CONCLUSIONS: Using counseling based on a positive psychology approach can improve anxiety, sexual and marital satisfaction, and anxiety of women of reproductive age during the COVID-19 pandemic. However, further randomized clinical trials are needed before making a definitive conclusion. TRIAL REGISTRATION: Iranian Registry of Clinical Trials (IRCT): IRCT20171007036615N8. Date of registration: 11/28/21. Date of first registration: 11/28/21. URL: https://www.irct.ir/user/trial/58680/view ; Date of recruitment start date: 12/01/21.


Anxiety , COVID-19 , Counseling , Marriage , Pandemics , Personal Satisfaction , Humans , COVID-19/psychology , Female , Adult , Anxiety/psychology , Iran , Counseling/methods , Marriage/psychology , Psychology, Positive/methods , Sexual Behavior/psychology , SARS-CoV-2 , Coronavirus Infections/psychology , Pneumonia, Viral/psychology , Surveys and Questionnaires , Young Adult
8.
Adv Exp Med Biol ; 1451: 183-204, 2024.
Article En | MEDLINE | ID: mdl-38801579

Poxviridae family includes several viruses that infecting humans usually causes skin lesions only, but in some cases their clinical course is complicated by viral pneumonia (with or without bacterial superinfections). Historically variola virus has been the poxviridae most frequently associated with the development of pneumonia with many large outbreaks worldwide before its eradication in 1980. It is still considered a biological threat for its potential in biological warfare and bioterrorism. Smallpox pneumonia can be severe with the onset of acute respiratory distress syndrome (ARDS) and death. Vaccinia virus, used for vaccination against smallpox exceptionally, in immunocompromised patients, can induce generalized (with also lung involvement) severe disease after vaccination. MPXV virus occasionally can cause pneumonia particularly in immunocompromised patients. The pathophysiology of poxviridae pneumonia is still an area of active research; however, in animal models these viruses can cause both direct damage to the lower airways epithelium and a hyperinflammatory syndrome, like a cytokine storm. Multiple mechanisms of immune evasion have also been described. The treatment of poxviridae pneumonia is mainly based on careful supportive care. Despite the absence of randomized clinical trials in patients with poxviridae pneumonia there are antiviral drugs, such as tecovirimat, cidofovir and brincidofovir, FDA-approved for use in smallpox and also available under an expanded access protocol for treatment of MPXV. There are 2 (replication-deficient modified vaccinia Ankara and replication-competent vaccinia virus) smallpox vaccines FDA-approved with the first one also approved for prevention of MPXV in adults that are at high risk of infection.


Antiviral Agents , Poxviridae Infections , Humans , Animals , Poxviridae Infections/drug therapy , Poxviridae Infections/virology , Poxviridae Infections/immunology , Antiviral Agents/therapeutic use , Pneumonia, Viral/virology , Pneumonia, Viral/drug therapy , Pneumonia, Viral/complications , Poxviridae/pathogenicity , Poxviridae/physiology , Poxviridae/genetics , Vaccinia virus/pathogenicity , Vaccinia virus/physiology , Smallpox/virology , Smallpox/prevention & control , Variola virus/pathogenicity , Variola virus/genetics
9.
Neurosciences (Riyadh) ; 29(2): 133-138, 2024 May.
Article En | MEDLINE | ID: mdl-38740405

Bilateral femoral neuropathy is rare, especially that caused by bilateral compressive iliopsoas, psoas, or iliacus muscle hematomas. We present a case of bilateral femoral neuropathy due to spontaneous psoas hematomas developed during COVID-19 critical illness. A 41-year-old patient developed COVID-19 pneumonia, and his condition deteriorated rapidly. A decrease in the hemoglobin level prompted imaging studies during his intensive care unit (ICU) stay. Bilateral psoas hematomas were identified as the source of bleeding. Thereafter, the patient complained of weakness in both upper and lower limbs and numbness in the lower limb. He was considered to have critical illness neuropathy and was referred to rehabilitation. Electrodiagnostic testing suggested bilateral femoral neuropathy because of compression due to hematomas developed during the course of his ICU stay. The consequences of iliopsoas hematomas occurring in the critically ill can be catastrophic, ranging from hemorrhagic shock to severe weakness, highlighting the importance of recognizing this entity.


COVID-19 , Femoral Neuropathy , Hematoma , Psoas Muscles , SARS-CoV-2 , Humans , COVID-19/complications , Hematoma/diagnostic imaging , Hematoma/etiology , Hematoma/complications , Male , Adult , Femoral Neuropathy/etiology , Psoas Muscles/diagnostic imaging , Critical Illness , Pneumonia, Viral/complications , Pneumonia, Viral/diagnostic imaging , Coronavirus Infections/complications , Coronavirus Infections/diagnostic imaging , Pandemics , Betacoronavirus
10.
Virol J ; 21(1): 110, 2024 May 14.
Article En | MEDLINE | ID: mdl-38745209

BACKGROUND: Severe pneumonia is one of the most important causes of mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Adenovirus (ADV) is a significant cause of severe viral pneumonia after allo-HSCT, and we aimed to identify the clinical manifestations, prognostic factors, and outcomes of ADV pneumonia after allo-HSCT. METHODS: Twenty-nine patients who underwent allo-HSCT at the Peking University Institute of Hematology and who experienced ADV pneumonia after allo-HSCT were enrolled in this study. The Kaplan-Meier method was used to estimate the probability of overall survival (OS). Potential prognostic factors for 100-day OS after ADV pneumonia were evaluated through univariate and multivariate Cox regression analyses. RESULTS: The incidence rate of ADV pneumonia after allo-HSCT was approximately 0.71%. The median time from allo-HSCT to the occurrence of ADV pneumonia was 99 days (range 17-609 days). The most common clinical manifestations were fever (86.2%), cough (34.5%) and dyspnea (31.0%). The 100-day probabilities of ADV-related mortality and OS were 40.4% (95% CI 21.1%-59.7%) and 40.5% (95% CI 25.2%-64.9%), respectively. Patients with low-level ADV DNAemia had lower ADV-related mortality and better OS than did those with high-level (≥ 106 copies/ml in plasma) ADV DNAemia. According to the multivariate analysis, high-level ADV DNAemia was the only risk factor for intensive care unit admission, invasive mechanical ventilation, ADV-related mortality, and OS after ADV pneumonia. CONCLUSIONS: We first reported the prognostic factors and confirmed the poor outcomes of patients with ADV pneumonia after allo-HSCT. Patients with high-level ADV DNAemia should receive immediate and intensive therapy.


Hematopoietic Stem Cell Transplantation , Pneumonia, Viral , Transplantation, Homologous , Humans , Hematopoietic Stem Cell Transplantation/adverse effects , Male , Female , Adult , Middle Aged , Prognosis , Pneumonia, Viral/mortality , Pneumonia, Viral/virology , Young Adult , Adolescent , Transplantation, Homologous/adverse effects , Adenoviridae Infections/mortality , Risk Factors , Retrospective Studies , Adenoviridae , Treatment Outcome , Incidence , Adenovirus Infections, Human/mortality , Adenovirus Infections, Human/virology
11.
Medicine (Baltimore) ; 103(20): e38185, 2024 May 17.
Article En | MEDLINE | ID: mdl-38758910

This study aims to evaluate chest computed tomography (CT) findings in hospital patients with primary varicella pneumonia (PVP). We retrospectively analyzed CT images of 77 PVP patients using 3D Slicer, an open-source software, to model lesions and lungs. This retrospective cohort study was approved by the Institutional Review Board (Ethical Committee, Renmin Hospital, Hubei University of Medicine, Shiyan, China) and waived the requirement for written informed consent. The left lung was more frequently and severely affected in PVP, with significant differences between the 2 groups in CT involvement percentage of each lung region, except for total lung inflation. Group A showed higher median percentages of lung collapse compared to Group B. The extent of left lung involvement is a critical predictor of emphysema in PVP patients, highlighting the importance of also monitoring the right lung for more severe cases. Lower emphysema levels correspond to more collapsed and infiltrated lung segments, suggesting a more severe clinical presentation.


Pulmonary Emphysema , Tomography, X-Ray Computed , Humans , Retrospective Studies , Male , Tomography, X-Ray Computed/methods , Female , Pulmonary Emphysema/diagnostic imaging , Child , Adolescent , Chickenpox/diagnostic imaging , Chickenpox/complications , Lung/diagnostic imaging , Pneumonia, Viral/diagnostic imaging , Pneumonia, Viral/complications , Adult , China/epidemiology , Young Adult , Child, Preschool
12.
Zhonghua Yi Xue Za Zhi ; 104(20): 1812-1824, 2024 May 28.
Article Zh | MEDLINE | ID: mdl-38782749

Although COVID-19 no longer constitutes a "public health emergency of international concern", which still has being spreading around the world at a low level. Small molecule drugs are the main antiviral treatment for novel coronavirus recommended in China. Although a variety of small-molecule antiviral drugs against COVID-19 have been listed in China, there is no specific drug recommendation for special populations. Society of Bacterial Infection and Resistance of Chinese Medical Association, together with the National Clinical Research Center for Respiratory Disease, and the National Center for Respiratory Medicine, organized domestic experts in various fields such as respiratory, virology, infection, critical care, emergency medicine and pharmacy to release Expert Consensus on the Clinical Application of Oral Small-Molecule Antiviral Drugs against COVID-19. The main content of this consensus includes the introduction of seven small-molecule antiviral drugs against COVID-19, focusing on the drug recommendations for 14 special groups such as the elderly, patients with complicated chronic diseases, tumor patients, pregnant women, and children, and providing suggestions for clinicians to standardize drug use.


Antiviral Agents , COVID-19 , Pandemics , SARS-CoV-2 , Antiviral Agents/therapeutic use , Humans , Pneumonia, Viral/drug therapy , COVID-19 Drug Treatment , Coronavirus Infections/drug therapy , Consensus , Betacoronavirus , Administration, Oral , China , Pregnancy
13.
Cells ; 13(10)2024 May 17.
Article En | MEDLINE | ID: mdl-38786077

Patients with COVID-19 have coagulation and platelet disorders, with platelet alterations and thrombocytopenia representing negative prognostic parameters associated with severe forms of the disease and increased lethality. METHODS: The aim of this study was to study the expression of platelet glycoprotein IIIa (CD61), playing a critical role in platelet aggregation, together with TRL-2 as a marker of innate immune activation. RESULTS: A total of 25 patients were investigated, with the majority (24/25, 96%) having co-morbidities and dying from a fatal form of SARS-CoV-2(+) infection (COVID-19+), with 13 men and 12 females ranging in age from 45 to 80 years. When compared to a control group of SARS-CoV-2 (-) negative lungs (COVID-19-), TLR-2 expression was up-regulated in a subset of patients with deadly COVID-19 fatal lung illness. The proportion of Spike-1 (+) patients found by PCR and ISH correlates to the proportion of Spike-S1-positive cases as detected by digital pathology examination. Furthermore, CD61 expression was considerably higher in the lungs of deceased patients. In conclusion, we demonstrate that innate immune prolonged hyperactivation is related to platelet/megakaryocyte over-expression in the lung. CONCLUSIONS: Microthrombosis in deadly COVID-19+ lung disease is associated with an increase in the number of CD61+ platelets and megakaryocytes in the pulmonary interstitium, as well as their functional activation; this phenomenon is associated with increased expression of innate immunity TLR2+ cells, which binds the SARS-CoV-2 E protein, and significantly with the persistence of the Spike-S1 viral sequence.


COVID-19 , Lung , Megakaryocytes , SARS-CoV-2 , Thrombosis , Toll-Like Receptor 2 , Up-Regulation , Humans , COVID-19/pathology , COVID-19/immunology , COVID-19/metabolism , Male , Female , Toll-Like Receptor 2/metabolism , Toll-Like Receptor 2/genetics , Megakaryocytes/metabolism , Megakaryocytes/pathology , Megakaryocytes/virology , Aged , Middle Aged , Aged, 80 and over , Lung/pathology , Lung/virology , Lung/metabolism , Up-Regulation/genetics , Thrombosis/pathology , Integrin beta3/metabolism , Integrin beta3/genetics , Spike Glycoprotein, Coronavirus/metabolism , Spike Glycoprotein, Coronavirus/genetics , Pneumonia, Viral/pathology , Pneumonia, Viral/immunology , Pneumonia, Viral/mortality , Pneumonia, Viral/virology , Pneumonia, Viral/metabolism , Immunity, Innate , Pandemics
14.
J Sep Sci ; 47(11): e2400090, 2024 Jun.
Article En | MEDLINE | ID: mdl-38819782

Ephedra herb (EH), an important medicine prescribed in herbal formulas by Traditional Chinese Medicine practitioners, has been widely used in the treatment of viral pneumonia in China. However, the molecular basis of EH in viral pneumonia remains unclear. In this study, a ternary correlation multi-symptom network strategy was established based on in vivo chemical profile identification and metabolomics to explore the molecular basis of EH against viral pneumonia. Results showed that 143 compounds of EH and 70 prototype components were identified in vivo. EH could reduce alveolar-capillary barrier disruption in rats with viral pneumonia and significantly downregulate the expression of inflammatory factors and bronchoalveolar lavage fluid. Plasma metabolomics revealed that EH may be involved in the regulation of arachidonic acid, tryptophan, tyrosine, nicotinate, and nicotinamide metabolism. The multi-symptom network showed that 12 compounds have an integral function in the treatment of viral pneumonia by intervening in many pathways related to viruses, immunity and inflammation, and lung injury. Further verification demonstrated that sinapic acid and frambinone can regulate the expression of related genes. It has been shown to be a promising representative of the pharmacological constituents of ephedra.


Drugs, Chinese Herbal , Ephedra , Metabolomics , Rats, Sprague-Dawley , Animals , Rats , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/chemistry , Ephedra/chemistry , Male , Pneumonia, Viral/drug therapy , Pneumonia, Viral/metabolism , Pneumonia, Viral/virology
15.
Med Sci (Basel) ; 12(2)2024 May 22.
Article En | MEDLINE | ID: mdl-38804384

mRNA vaccines have emerged as an optimistic technological platform for vaccine innovation in this new scientific era. mRNA vaccines have dramatically altered the domain of vaccinology by offering a versatile and rapid approach to combating infectious diseases and virus-induced cancers. Clinical trials have demonstrated efficacy rates of 94-95% in preventing COVID-19, and mRNA vaccines have been increasingly recognized as a powerful vaccine platform. Although mRNA vaccines have played an essential role in the COVID-19 pandemic, they still have several limitations; their instability and degradation affect their storage, delivery, and over-all efficiency. mRNA is typically enclosed in a transport mechanism to facilitate its entry into the target cell because it is an unstable and negatively charged molecule. For instance, mRNA that is given using lipid-nanoparticle-based vaccine delivery systems (LNPs) solely enters cells through endocytosis, establishing an endosome without damaging the cell membrane. The COVID-19 pandemic has accelerated the development of mRNA vaccine platforms used to treat and prevent several infectious diseases. This technology has the potential to change the future course of the disease by providing a safe and effective way to combat infectious diseases and cancer. A single-stranded genetic sequence found in mRNA vaccines instructs host cells to produce proteins inside ribosomes to elicit immunological responses and prepare the immune system to fight infections or cancer cells. The potential applications of mRNA vaccine technology are vast and can lead to the development of a preferred vaccine pattern. As a result, a new generation of vaccinations has gradually gained popularity and access to the general population. To adapt the design of an antigen, and even combine sequences from different variations in response to new changes in the viral genome, mRNA vaccines may be used. Current mRNA vaccines provide adequate safety and protection, but the duration of that protection can only be determined if further clinical research is conducted.


COVID-19 , SARS-CoV-2 , mRNA Vaccines , Humans , COVID-19/prevention & control , SARS-CoV-2/immunology , Pandemics/prevention & control , Oncogenic Viruses , Vaccines, Synthetic , Vaccine Development , COVID-19 Vaccines/immunology , Pneumonia, Viral/prevention & control , Coronavirus Infections/prevention & control , Betacoronavirus , Viral Vaccines/immunology , RNA, Messenger , Neoplasms
16.
Sao Paulo Med J ; 142(6): e2022608, 2024.
Article En | MEDLINE | ID: mdl-38808794

BACKGROUND: The cause of oropharyngeal dysphagia in patients with coronavirus disease (COVID-19) can be multifactorial and may underly limitations in swallowing rehabilitation. OBJECTIVE: Analyze the factors related to dysphagia in patients with COVID-19 immediately after orotracheal extubation and the factors that influence swallowing rehabilitation. DESIGN AND SETTING: A retrospective study. METHODS: The presence of dysphagia was evaluated using the American Speech-Language Hearing Association National Outcome Measurement System (ASHA NOMS) scale and variables that influenced swallowing rehabilitation in 140 adult patients who required invasive mechanical ventilation for >48 h. RESULTS: In total, 46.43% of the patients scored 1 or 2 on the ASHA NOMS (severe dysphagia) and 39.29% scored 4 (single consistency delivered orally) or 5 (exclusive oral diet with adaptations). Both the length of mechanical ventilation and the presence of neurological disorders were associated with lower ASHA NOMS scores (odds ratio [OR]: 0.80, 95% confidence interval [CI]: 0.74-0.87 P < 0.05; and OR: 0.13, 95% CI: 0.61-0.29; P < 0.05, respectively). Age and the presence of tracheostomy were negatively associated with speech rehabilitation (OR: 0.92; 95% CI: 0.87--0.96; OR: 0.24; 95% CI: 0.80--0.75), and acute post-COVID-19 kidney injury requiring dialysis and lower scores on the ASHA NOMS were associated with longer time for speech therapy outcomes (ß: 1.62, 95% CI, 0.70-3.17, P < 0.001; ß: -1.24, 95% CI: -1.55--0.92; P < 0.001). CONCLUSION: Prolonged orotracheal intubation and post-COVID-19 neurological alterations increase the probability of dysphagia immediately after extubation. Increased age and tracheostomy limited rehabilitation.


COVID-19 , Deglutition Disorders , Intubation, Intratracheal , Respiration, Artificial , SARS-CoV-2 , Humans , COVID-19/complications , Deglutition Disorders/etiology , Deglutition Disorders/rehabilitation , Retrospective Studies , Male , Female , Middle Aged , Aged , Airway Extubation/adverse effects , Adult , Pandemics , Coronavirus Infections/complications , Coronavirus Infections/rehabilitation , Pneumonia, Viral/complications , Pneumonia, Viral/rehabilitation , Betacoronavirus , Risk Factors , Aged, 80 and over
17.
An Acad Bras Cienc ; 96(2): e20231160, 2024.
Article En | MEDLINE | ID: mdl-38808879

This study investigated the association between the IFITM3 rs12252 polymorphism and the severity and mortality of COVID-19 in hospitalized Brazilian patients. A total of 102 COVID-19 patients were included, and the outcomes of interest were defined as death and the need for mechanical ventilation. Genotypes were assessed using Taqman probes. No significant associations were found between the rs12252 polymorphism and COVID-19 outcomes in the original sample, both for death and the need for mechanical ventilation. A meta-analysis, incorporating previous studies that used death as a severity indicator, revealed no association in the allelic and C-recessive models. However, due to the rarity of the T allele and its absence in the sample, further replication studies in larger and more diverse populations are needed to clarify the role of rs12252 in COVID-19 prognosis.


COVID-19 , Membrane Proteins , Polymorphism, Single Nucleotide , RNA-Binding Proteins , SARS-CoV-2 , Severity of Illness Index , Humans , COVID-19/genetics , COVID-19/mortality , Brazil/epidemiology , Membrane Proteins/genetics , SARS-CoV-2/genetics , Male , Female , RNA-Binding Proteins/genetics , Polymorphism, Single Nucleotide/genetics , Middle Aged , Pandemics , Betacoronavirus/genetics , Pneumonia, Viral/genetics , Pneumonia, Viral/mortality , Genotype , Aged , Genetic Predisposition to Disease/genetics , Respiration, Artificial , Adult
18.
Can J Rural Med ; 29(2): 71-79, 2024 Apr 01.
Article En, Fr | MEDLINE | ID: mdl-38709017

INTRODUCTION: The COVID-19 pandemic presented an unprecedented challenge for rural family physicians. The lessons learned over the course of 2 years have potential to help guide responses to future ecosystem disruption. This qualitative study aims to explore the leadership experiences of rural Canadian family physicians during the COVID-19 pandemic as both local care providers and community health leaders and to identify potential supports and barriers to physician leadership. METHODS: Semi-structured, virtual, qualitative interviews were completed with participants from rural communities in Canada from December 2021 to February 2022 inclusive. Participant recruitment involved identifying seed contacts and conducting snowball sampling. Participants were asked about their experiences during the COVID-19 pandemic, including the role of physician leadership in building community resilience. Data collection was completed on theoretical saturation. Data were thematically analysed using NVivo 12. RESULTS: Sixty-four participants took part from 22 rural communities in 4 provinces. Four key factors were identified that supported physician leadership towards rural resilience during ecosystem disruption: (1) continuity of care, (2) team-based care models, (3) physician well-being and (4) openness to innovative care models. CONCLUSION: Healthcare policy and practice transformation should prioritise developing opportunities to strengthen physician leadership, particularly in rural areas that will be adversely affected by ecosystem disruption. INTRODUCTION: La pandémie de COVID-19 a représenté un défi sans précédent pour les médecins de famille en milieu rural. Les leçons tirées au cours des deux années écoulées peuvent aider à orienter les réponses aux futures perturbations de l'écosystème. Cette étude qualitative vise à explorer les expériences de leadership des médecins de famille ruraux canadiens pendant la pandémie de COVID-19, en tant que prestataires de soins locaux et chefs de file de la santé communautaire, et à identifier les soutiens et les obstacles potentiels au leadership des médecins. MTHODES: Des entretiens qualitatifs virtuels semi-structurés ont été réalisés avec des participants issus de communautés rurales du Canada entre décembre 2021 et février 2022 inclus. Le recrutement des participants a consisté à identifier des contacts de base et à procéder à un échantillonnage boule de neige. Les participants ont été interrogés sur leurs expériences durant la pandémie de COVID-19, notamment sur le rôle du leadership des médecins dans le renforcement de la résilience des communautés. La collecte des données s'est achevée après saturation théorique. Les données ont été analysées thématiquement à l'aide de NVivo 12. RSULTATS: Soixante-quatre participants provenant de 22 communautés rurales de quatre provinces ont pris part à l'étude. Quatre facteurs clés ont été identifiés pour soutenir le leadership des médecins en faveur de la résilience rurale en cas de perturbation de l'écosystème: (1) la continuité des soins, (2) les modèles de soins en équipe, (3) le bien-être des médecins et (4) l'ouverture à des modèles de soins novateurs. CONCLUSION: La politique de santé et la transformation des pratiques devraient donner la priorité au développement d'opportunités pour renforcer le leadership des médecins, en particulier dans les zones rurales qui seront négativement affectées par la perturbation de l'écosystème.


COVID-19 , Leadership , Pandemics , Qualitative Research , Rural Health Services , SARS-CoV-2 , Humans , COVID-19/epidemiology , Canada , Rural Health Services/organization & administration , Pneumonia, Viral/epidemiology , Physicians, Family , Female , Coronavirus Infections/epidemiology , Betacoronavirus , Ecosystem , Male , Rural Population
19.
Anal Chem ; 96(19): 7360-7366, 2024 May 14.
Article En | MEDLINE | ID: mdl-38697955

During the coronavirus disease 2019 (COVID-19) pandemic, which has witnessed over 772 million confirmed cases and over 6 million deaths globally, the outbreak of COVID-19 has emerged as a significant medical challenge affecting both affluent and impoverished nations. Therefore, there is an urgent need to explore the disease mechanism and to implement rapid detection methods. To address this, we employed the desorption separation ionization (DSI) device in conjunction with a mass spectrometer for the efficient detection and screening of COVID-19 urine samples. The study encompassed patients with COVID-19, healthy controls (HC), and patients with other types of pneumonia (OP) to evaluate their urine metabolomic profiles. Subsequently, we identified the differentially expressed metabolites in the COVID-19 patients and recognized amino acid metabolism as the predominant metabolic pathway involved. Furthermore, multiple established machine learning algorithms validated the exceptional performance of the metabolites in discriminating the COVID-19 group from healthy subjects, with an area under the curve of 0.932 in the blind test set. This study collectively suggests that the small-molecule metabolites detected from urine using the DSI device allow for rapid screening of COVID-19, taking just three minutes per sample. This approach has the potential to expand our understanding of the pathophysiological mechanisms of COVID-19 and offers a way to rapidly screen patients with COVID-19 through the utilization of machine learning algorithms.


COVID-19 , SARS-CoV-2 , Humans , COVID-19/diagnosis , COVID-19/urine , COVID-19/virology , SARS-CoV-2/isolation & purification , Pandemics , Male , Pneumonia, Viral/diagnosis , Pneumonia, Viral/urine , Pneumonia, Viral/virology , Middle Aged , Coronavirus Infections/diagnosis , Coronavirus Infections/urine , Female , Betacoronavirus/isolation & purification , Mass Spectrometry/methods , Adult , Metabolomics/methods , Aged , Machine Learning
20.
J Med Virol ; 96(5): e29643, 2024 May.
Article En | MEDLINE | ID: mdl-38695269

Severe pneumonia caused by respiratory viruses has become a major threat to humans, especially with the SARS-CoV-2 outbreak and epidemic. The aim of this study was to investigate the universal molecular mechanism of severe pneumonia induced by multiple respiratory viruses and to search for therapeutic strategies targeting this universal molecular mechanism. The common differential genes of four respiratory viruses, including respiratory syncytial virus (RSV), rhinovirus, influenza, and SARS-CoV-2, were screened by GEO database, and the hub gene was obtained by Sytohubba in Cytoscape. Then, the effect of hub genes on inflammasome and pyrodeath was investigated in the model of RSV infection in vitro and in vivo. Finally, through virtual screening, drugs targeting the hub gene were obtained, which could alleviate severe viral pneumonia in vitro and in vivo. The results showed that CMPK2 is one of the hub genes after infection by four respiratory viruses. CMPK2 activates the inflammasome by activating NLRP3, and promotes the releases of inflammatory factors interleukin (IL)-1ß and IL-18 to induce severe viral pneumonia. Z25 and Z08 can reduce the expression level of CMPK2 mRNA and protein, thereby inhibiting NLRP3 and alleviating the development of severe viral pneumonia. In conclusion, the inflammatory response mediated by CMPK2 is the common molecular mechanism of severe pneumonia induced by viral infection, and Z25 and Z08 can effectively alleviate viral infection and severe pneumonia through this mechanism.


Inflammasomes , Pyroptosis , Pyroptosis/drug effects , Humans , Animals , Inflammasomes/metabolism , Mice , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/genetics , Interleukin-1beta/genetics , Interleukin-1beta/metabolism , Pneumonia, Viral/drug therapy , Pneumonia, Viral/virology , Interleukin-18/metabolism , Interleukin-18/genetics , SARS-CoV-2 , Respiratory Syncytial Virus Infections/drug therapy , Respiratory Syncytial Virus Infections/virology
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