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1.
Chem Biol Interact ; 358: 109898, 2022 May 01.
Article in English | MEDLINE | ID: covidwho-1838609

ABSTRACT

Coronavirus disease (COVID-19), a coronavirus-induced illness attributed to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission, is thought to have first emerged on November 17, 2019. According to World Health Organization (WHO). COVID-19 has been linked to 379,223,560 documented occurrences and 5,693,245 fatalities globally as of 1st Feb 2022. Influenza A virus that has also been discovered diarrhea and gastrointestinal discomfort was found in the infected person, highlighting the need of monitoring them for gastro intestinal tract (GIT) symptoms regardless of whether the sickness is respiration related. The majority of the microbiome in the intestines is Firmicutes and Bacteroidetes, while Bacteroidetes, Proteobacteria, and Firmicutes are found in the lungs. Although most people overcome SARS-CoV-2 infections, many people continue to have symptoms months after the original sickness, called Long-COVID or Post COVID. The term "post-COVID-19 symptoms" refers to those that occur with or after COVID-19 and last for more than 12 weeks (long-COVID-19). The possible understanding of biological components such as inflammatory, immunological, metabolic activity biomarkers in peripheral blood is needed to evaluate the study. Therefore, this article aims to review the informative data that supports the idea underlying the disruption mechanisms of the microbiome of the gastrointestinal tract in the acute COVID-19 or post-COVID-mediated elevation of severity biomarkers.


Subject(s)
COVID-19 , Gastrointestinal Diseases , Gastrointestinal Microbiome , Biomarkers , COVID-19/complications , Humans , SARS-CoV-2
2.
Natl Acad Sci Lett ; : 1-7, 2022 May 04.
Article in English | MEDLINE | ID: covidwho-1821033

ABSTRACT

Aim: To characterize Th1/Th2/Th17 cytokine profile (IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ, and IL-17A) among different stages of COVID-19 infection. Methods: This was a cross-sectional study which included six healthy individuals and 68 patients who were admitted with COVID-19 in the Department of Medicine, at All India Institute of Medical Sciences, New Delhi, from July 2020 to September 2020. Patients were categorized into mild, moderate, and severe COVID-19 groups, and serum samples were drawn for the measurement of Th1/Th2/Th17 cytokines (IL-4, IL-6, IL-10, TNF-α, IFN-γ, and IL-17A) which was done by BD™ Cytometric Bead Array. Results: All the cytokines showed dynamic expression in the COVID-19 group, of which only IL-6 was statistically significant. Among the three severity groups of COVID-19, increased severity did not transform into increased cytokine level, with the exception for IL-6, which was statistically significant. Conclusions: In our small sample study, six cytokines expressions were evaluated however most of them were elevated in COVID-19 patients but were not statistically significant except IL-6.

3.
Cell Signal ; 95: 110334, 2022 Apr 21.
Article in English | MEDLINE | ID: covidwho-1800158

ABSTRACT

Exosome trans-membrane signals provide cellular communication between the cells through transport and/or receiving the signal by molecule, change the functional metabolism, and stimulate and/or inhibit receptor signal complexes. COVID19 genetic transformations are varied in different geographic positions, and single nucleotide polymorphic lineages were reported in the second waves due to the fast mutational rate and adaptation. Several vaccines were developed and in treatment practice, but effective control has yet to reach in cent presence. It was initially a narrow immune-modulating protein target. Controlling these diverse viral strains may inhibit their transuding mechanisms primarily to target RNA genes responsible for COVID19 transcription. Exosomal miRNAs are the main sources of transmembrane signals, and trans-located miRNAs can directly target COVID19 mRNA transcription. This review discussed targeted viral transcription by delivering the artificial miRNA (amiRNA) mediated exosomes in the infected cells and significant resources of exosome and their efficacy.

4.
Interv Neuroradiol ; : 15910199221093896, 2022 Apr 11.
Article in English | MEDLINE | ID: covidwho-1785091

ABSTRACT

BACKGROUND: The neutrophil-lymphocyte ratio (NLR) is emerging as an important biomarker of acute physiologic stress in a myriad of medical conditions, and is a confirmed poor prognostic indicator in COVID-19. OBJECTIVE: We sought to describe the role of NLR in predicting poor outcome in COVID-19 patients undergoing mechanical thrombectomy for acute ischemic stroke. METHODS: We analyzed NLR in COVID-19 patients with large vessel occlusion (LVO) strokes enrolled into an international 12-center retrospective study of laboratory-confirmed COVID-19, consecutively admitted between March 1, 2020 and May 1, 2020. Increased NLR was defined as ≥7.2. Logistic regression models were generated. RESULTS: Incidence of LVO stroke was 38/6698 (.57%). Mean age of patients was 62 years (range 27-87), and mortality rate was 30%. Age, sex, and ethnicity were not predictive of mortality. Elevated NLR and poor vessel recanalization (Thrombolysis in Cerebral Infarction (TICI) score of 1 or 2a) synergistically predicted poor outcome (likelihood ratio 11.65, p = .003). Patients with NLR > 7.2 were 6.8 times more likely to die (OR 6.8, CI95% 1.2-38.6, p = .03) and almost 8 times more likely to require prolonged invasive mechanical ventilation (OR 7.8, CI95% 1.2-52.4, p = .03). In a multivariate analysis, NLR > 7.2 predicted poor outcome even when controlling for the effect of low TICI score on poor outcome (NLR p = .043, TICI p = .070). CONCLUSIONS: We show elevated NLR in LVO patients with COVID-19 portends significantly worse outcomes and increased mortality regardless of recanalization status. Severe neuro-inflammatory stress response related to COVID-19 may negate the potential benefits of successful thrombectomy.

5.
Br J Clin Pharmacol ; 2022 Mar 30.
Article in English | MEDLINE | ID: covidwho-1764882

ABSTRACT

COVID-19 has spread globally, affecting almost 160 million individuals. Elderly and pre-existing patients (such as diabetes, heart disease and asthma) seem more susceptible to severe illness with COVID-19. Roflumilast was licensed for usage in the European Union in July 2010 as a phosphodiesterase-4 (PDE4) inhibitor. Under preclinical studies, roflumilast has been shown to decrease bleomycin-induced lung fibrosis, lung hydroxyproline and right heart thickening. The current study reviewed existing data that the PDE-4 inhibitor, a roflumilast, protects renal tissues and other major organ systems after COVID-19 infection by decreasing immune cell infiltration. These immune-balancing effects of roflumilast were related to a decrease in oxidative and inflammatory burden, caspase-3 suppression and increased protein kinase A (PKA)/cyclic A.M.P. (cAMP) levels in renal and other organ tissue.

6.
Chemico-biological interactions ; 2022.
Article in English | EuropePMC | ID: covidwho-1749246

ABSTRACT

Coronavirus disease (COVID-19), a coronavirus-induced illness attributed to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission, is thought to have first emerged on November 17, 2019. According to World Health Organization (WHO). COVID-19 has been linked to 379,223,560 documented occurrences and 5,693,245 fatalities globally as of 1st Feb 2022. Influenza A virus that has also been discovered diarrhea and gastrointestinal discomfort was found in the infected person, highlighting the need of monitoring them for gastro intestinal tract (GIT) symptoms regardless of whether the sickness is respiration related. The majority of the microbiome in the intestines is Firmicutes and Bacteroidetes, while Bacteroidetes, Proteobacteria, and Firmicutes are found in the lungs. Although most people overcome SARS-CoV-2 infections, many people continue to have symptoms months after the original sickness, called Long-COVID or Post COVID. The term “post-COVID-19 symptoms” refers to those that occur with or after COVID-19 and last for more than 12 weeks (long-COVID-19). The possible understanding of biological components such as inflammatory, immunological, metabolic activity biomarkers in peripheral blood is needed to evaluate the study. Therefore, this article aims to review the informative data that supports the idea underlying the disruption mechanisms of the microbiome of the gastrointestinal tract in the acute COVID-19 or post-COVID-mediated elevation of severity biomarkers.

8.
Res Pract Thromb Haemost ; 6(1): e12645, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1626487

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) causes abnormalities in the hemostatic system, collectively known as COVID-associated coagulopathy. The dynamics of clot formation are best discerned by whole-blood viscoelastic tests, such as thromboelastography (TEG). We aimed to assess the various abnormalities seen on TEG and explored the predictors of outcomes in these patients. METHODS: Thromboelastography was performed for 28 patients with COVID-19 using an automated thromboelastogram. The hemostatic condition was categorized as hypercoagulable in 17 (63%), hypocoagulable in 2 (7%), and normal in 8 (30%) based on TEG variables, such as reaction time , time until clot reaches a fixed strength, alpha angle, maximum amplitude, and clotting index. Laboratory parameters and clinical outcomes were compared between hypercoagulable and normal groups. RESULTS: Twenty-seven patients with a median age of 50 years (interquartile range, 40-60 years), male-to-female ratio of 0.9:1, median C-reactive protein of 25.7 (10.9-108.8) mg/L, serum ferritin of 693 (317-1031) µg/L, and albumin 2.9 (2.6-3.3) g/dL were included. The median prothrombin time/international normalized ratio and activated partial thromboplastin time were within normal range in the hypercoagulable and normal groups. The severity of COVID-19 was mild in 6 (22.2%), moderate in 2 (7.4%), and severe in 19 (70.4%) patients. Twenty-eight-day mortality among patients with hypocoagulable and hypercoagulable states was higher than normal coagulation status. (log-rank test, P = .002). CONCLUSIONS: Hypercoagulable state, together with a severe inflammatory state, is common in patients with COVID-19, despite thromboprophylaxis. TEG assesses coagulation status better than conventional coagulation tests. Coagulation abnormalities are associated with poor outcomes.

10.
Cureus ; 13(12): e20072, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1579878

ABSTRACT

Introduction During the coronavirus disease 2019 (COVID-19) pandemic in India, several characteristics of hospitalized COVID-19 patients, based on demographics, mortality predictors, and presence of comorbidities, were found to be associated with poor outcomes. The objective of this study was to identify such epidemiological and clinical characteristics among the patients admitted at a tertiary-care center in India that may have predisposed them to COVID-19-related mortality. Methods This retrospective observational study conducted at the Department of Medicine, All India Institute of Medical Sciences, New Delhi, in May 2021 included 141 COVID-19 confirmed patients. The medical history, demographic characteristics, comorbidities, clinical findings, and laboratory data of each patient were obtained. The data were analyzed to identify significant clinical and laboratory parameters that led to the adverse final outcomes. Results Hypertension was the most common comorbidity and the presence of diabetes with hypertension led to poorer final outcomes. Lower oxygen saturation and requirement of oxygen supplementation at admission along with worse prognostic scores during admission led to poorer outcomes. Twenty-seven patients needed non-invasive ventilation (NIV) during the hospital course, and all ultimately landed up among the 56 patients who were managed on invasive mechanical ventilation (IMV). Multivariate logistic regression analysis performed identified COVID-19 severity at admission, co-existence of hypertension and diabetes mellitus, systolic blood pressure less than 90 mm Hg, and serum creatinine greater than 1.2 mg/dL to be associated with higher COVID-19 mortality. Conclusion COVID-19 patients having the co-existence of diabetes and hypertension constitute a high-risk group and may be targeted by prompt vaccination strategies. The presence of severe disease along with a need for oxygen therapy and other intensive care interventions ultimately led to unfavorable outcomes.

11.
Clin Med (Lond) ; 21(6): e615-e619, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1551858

ABSTRACT

BACKGROUND: There are limited data regarding the incidence of pneumothorax in COVID-19 patients as well as the impact of the same on patient outcomes. METHODS: A retrospective review of the medical records at three large tertiary care hospitals in Mumbai was performed to identify patients hospitalised with COVID-19 from March 2020 to October 2020. The presence of pneumothorax and/or pneumomediastinum was noted when chest radiographs or CT scans were performed. Demographic and clinical characteristics of patients who developed air leak were recorded. RESULTS: 4,906 patients with COVID-19 were admitted, with 1,324 (27%) having severe COVID-19 disease. The overall incidence of pneumothorax and/or pneumomediastinum in patients with severe disease was 3.2% (42/1,324). Eighteen patients had pneumothorax, 16 had pneumomediastinum and 8 patients had both. Fourteen patients (33.3%) developed this complication breathing spontaneously, 28 patients (66.6%) developed it during mechanical ventilation. Overall mortality in this cohort was 74%, compared with 17% in the COVID-19 patients without pneumothorax (p<0.001). CONCLUSIONS: Our study demonstrates that air leaks occur with a higher frequency in patients with COVID-19 than in other ICU patients. When present, such air leaks contributed to poor outcomes with almost 74% mortality rates in these patients.


Subject(s)
COVID-19 , Mediastinal Emphysema , Pneumothorax , Humans , Intensive Care Units , Mediastinal Emphysema/diagnostic imaging , Mediastinal Emphysema/epidemiology , Pneumothorax/diagnostic imaging , Pneumothorax/epidemiology , Retrospective Studies , SARS-CoV-2
12.
Diabetes Metab Syndr ; 15(6): 102308, 2021.
Article in English | MEDLINE | ID: covidwho-1517128

ABSTRACT

BACKGROUND AND AIMS: This meta-analysis aims to highlight the impact of cardio-metabolic comorbidities on COVID-19 severity and mortality. METHODS: A thorough search on major online databases was done for studies describing the clinical outcomes of COVID-19 patients. We used random-effects model to compute pooled estimates for critical or fatal disease. RESULTS: A total of 20,475 patients from 33 eligible studies were included. Maximum risk of development of critical or fatal COVID-19 disease was seen in patients with underlying cardiovascular disease [OR: 3.44, 95% CI: 2.65-4.48] followed by chronic lung disease, hypertension and diabetes mellitus. Of the total cases, 64% had one of the four comorbidities with the most prevalent being hypertension with a pooled prevalence of 27%. CONCLUSIONS: Presence of comorbidities like cardiovascular disease, chronic lung disease, hypertension and diabetes mellitus led to a higher risk of development of critical or fatal COVID-19 disease, with maximum risk seen with underlying cardiovascular disease.


Subject(s)
COVID-19/mortality , Cardiovascular Diseases/physiopathology , Diabetes Mellitus/physiopathology , Hypertension/physiopathology , Lung Diseases/physiopathology , SARS-CoV-2/isolation & purification , COVID-19/epidemiology , COVID-19/pathology , COVID-19/virology , Humans
13.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-292431

ABSTRACT

COVID-19 has spread globally, affecting almost 160 million individuals. Elderly and pre-existing patients (such as diabetes, heart disease and asthma), seems more susceptible to serious illness with COVID-19. Roflumilast was licensed for usage in the European Union in July 2010 as a phosphodiesterase-4 (PDE4) inhibitor. Roflumilast has been shown to decrease bleomycin-induced lung fibrosis, lung hydroxyproline, right heart thickning in animal prophylactic. The current study reviewed existing data that the PDE-4 inhibitor protects not just renal tissues but also other major organ systems after COVID-19 infection by decreasing immune cell infiltration. These immune-balancing effects of roflumilast were related with a decrease in oxidative and inflammatory burden, caspase-3 suppression, and increased PKA/cAMP levels in renal and other organ tissue.

14.
Cureus ; 13(10): e19080, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1513117

ABSTRACT

Introduction A cytokine storm is an important cause of morbidity and mortality in patients with coronavirus disease 2019 (COVID-19). The objective of the study was to determine the prognostic significance of pro-inflammatory cytokines with the overall final outcome of patients with COVID-19. Methods We conducted a retrospective study of 142 patients admitted with COVID-19 in the Department of Medicine at All India Institute of Medical Sciences, New Delhi, from May 2021 to June 2021. We obtained their demographic, clinical, and biochemical characteristics at baseline and 48-72 hours prior to the terminal event (survival/death). The data were analyzed to determine the prognostic significance of these markers on the final outcome. Results Higher levels of inflammatory markers were associated with a worse final outcome (ferritin p-value <0.001, c-reactive protein (CRP) p-value <0.001, interleukin 6 (IL-6) p-value 0.007, procalcitonin p-value 0.005, and lactic acid p-value 0.004). Optimal probability cut-offs for these markers for predicting mortality were: ferritin: 963 ng/mL (sensitivity - 67.35%, specificity - 67.50%), CRP: 66.3 mg/L (sensitivity - 78.43%, specificity - 74.12%), IL-6: 46.2 pg/mL (sensitivity - 59.26%, specificity - 59.57%), procalcitonin: 0.3ng/mL (sensitivity - 65.38 %, specificity - 66.67%), lactic acid: 1.5 mg/dL (sensitivity - 59.26%, specificity - 58.57%). Multivariate logistic regression analysis was done, which showed that pre-terminal event CRP was associated with a statistically significant higher risk of mortality (Unadjusted OR 18.89, Adjusted OR 1.008, p=0.002, 95% CI 6.815 - 47.541). Conclusion Inflammatory markers have a prognostic significance in patients with COVID-19, with higher levels being associated with worse outcomes.

15.
Chem Biol Interact ; 351: 109706, 2022 Jan 05.
Article in English | MEDLINE | ID: covidwho-1464614

ABSTRACT

The challenges and difficulties associated with conventional drug delivery systems have led to the emergence of novel, advanced targeted drug delivery systems. Therapeutic drug delivery of proteins and peptides to the lungs is complicated owing to the large size and polar characteristics of the latter. Nevertheless, the pulmonary route has attracted great interest today among formulation scientists, as it has evolved into one of the important targeted drug delivery platforms for the delivery of peptides, and related compounds effectively to the lungs, primarily for the management and treatment of chronic lung diseases. In this review, we have discussed and summarized the current scenario and recent developments in targeted delivery of proteins and peptide-based drugs to the lungs. Moreover, we have also highlighted the advantages of pulmonary drug delivery over conventional drug delivery approaches for peptide-based drugs, in terms of efficacy, retention time and other important pharmacokinetic parameters. The review also highlights the future perspectives and the impact of targeted drug delivery on peptide-based drugs in the coming decade.


Subject(s)
Drug Carriers/chemistry , Lung/metabolism , Peptides/administration & dosage , Proteins/administration & dosage , Administration, Inhalation , Animals , Drug Carriers/administration & dosage , Humans , Lung/drug effects , Lung Diseases/drug therapy , Nanoparticles/administration & dosage , Nanoparticles/chemistry , Peptides/therapeutic use , Proteins/therapeutic use
16.
Biotechnol Bioeng ; 119(1): 48-58, 2022 01.
Article in English | MEDLINE | ID: covidwho-1441944

ABSTRACT

Manufacturing has been the key factor limiting rollout of vaccination during the COVID-19 pandemic, requiring rapid development and large-scale implementation of novel manufacturing technologies. ChAdOx1 nCoV-19 (AZD1222, Vaxzevria) is an efficacious vaccine against SARS-CoV-2, based upon an adenovirus vector. We describe the development of a process for the production of this vaccine and others based upon the same platform, including novel features to facilitate very large-scale production. We discuss the process economics and the "distributed manufacturing" approach we have taken to provide the vaccine at globally-relevant scale and with international security of supply. Together, these approaches have enabled the largest viral vector manufacturing campaign to date, providing a substantial proportion of global COVID-19 vaccine supply at low cost.


Subject(s)
COVID-19 Vaccines , COVID-19/prevention & control , Drug Industry/methods , Animals , Escherichia coli , Geography , HEK293 Cells , Humans , Pan troglodytes , SARS-CoV-2 , Technology, Pharmaceutical , Vaccination/instrumentation
18.
Journal of Clinical Apheresis ; n/a(n/a), 2021.
Article in English | Wiley | ID: covidwho-1409862

ABSTRACT

Abstract Since vaccination for SARS-CoV-2 coronavirus started, the trajectory of patient numbers infected with the virus has improved once;however, variants of SARS-CoV-2 have emerged and more people have been infected;therefore, pandemic status is still far from resolution. Government and social efforts to prevent coronavirus infection continue in most states in the US and globally even after the Centers for Disease Control and Prevention declared some restriction relief for fully vaccinated people in March 2021. Healthcare institutions and various professional organizations have developed guidelines or policies to prevent the spread of these coronaviruses in the setting of apheresis. In this report, the issues that apheresis services may encounter under the current COVID-19 (SARS-CoV-2 coronavirus disease) pandemic will be discussed with potential strategies that can be adapted for efficient and optimum use of apheresis resources.

19.
Drug Dev Res ; 82(8): 1075-1078, 2021 12.
Article in English | MEDLINE | ID: covidwho-1380379

ABSTRACT

One of the most remarkable results in 2019 is the reduced prevalence and death of children from coronavirus infection (COVID-19). In 2019, a worldwide pandemic impacted around 0.1 billion individuals, with over 3.5 million mortality reported in the literature. There is minimal knowledge on SARS-CoV-2 infection immunological responses in kids. Studies have been focused mostly on adults and children since the course of pediatric sickness is often short. In adults, severe COVID-19 is related to an excessive inflammatory reaction. Macrophages and monocytes are well known to contribute to this systemic response, although numerous lines are indicative of the importance of neutrophils. An increased number of neutrophils and neutrophil to lymphocyte ratios are early signs of SARS-CoV-2 and a worse prognosis. In this study that it is crucial to monitor PAR2 and PAR4 expression and function (since nursing children have elevated levels) and the inhibiting the normal physiology through the use of anticoagulants may exacerbate the problem in adults. Thus, in COVID-19 infection, we propose the use of antiplatelet (thromboxane A2 inhibitors), if required rather than anticoagulants (FXa and thrombin Inhibitors).


Subject(s)
COVID-19/metabolism , Receptor, PAR-2/metabolism , Receptors, Thrombin/metabolism , Adult , Age Factors , Anticoagulants/pharmacology , Anticoagulants/therapeutic use , COVID-19/drug therapy , COVID-19/immunology , Child , Humans , Lymphocyte Count , Neutrophils/immunology , Platelet Aggregation Inhibitors/pharmacology , Platelet Aggregation Inhibitors/therapeutic use
20.
Transplantology ; 2(3):291-293, 2021.
Article in English | MDPI | ID: covidwho-1360820

ABSTRACT

Information regarding Coronavirus disease 2019 in the transplant population is lacking. Recently it has been suggested that cycle threshold values obtained on polymerase chain reaction tests may serve as a marker of disease severity with lower values (i.e., higher viral load) being associated with higher mortality. This study was done to assess the impact of remdesivir use on the time to a negative COVID-19 PCR as well as the degree of change between two Ct’s based on treatment. A total of 30 kidney transplant patients with a new diagnosis of COVID-19 were assessed. Serial PCR results were followed from the time of diagnosis then every 2–4 weeks until negative. In patients who received remdesivir immediately after COVID-19 confirmation compared to no remdesivir, time to negative PCR was not statistically different with a median duration of 57 days in both groups (p = 0.369). The change in the Ct between the first and the second PCR test was also not statistically different between groups with a median change of 18.4 cycles in the remdesivir group and 15.7 cycles without remdesivir (p = 0.516). The results of this small single-center analysis suggest that remdesivir may not be beneficial in shortening time to a negative COVID-19 PCR.

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