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Annals of Medicine Dec 2023This study evaluated the clinical efficacy and safety of interleukin-1 (IL-1) blockade for patients with COVID-19. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
This study evaluated the clinical efficacy and safety of interleukin-1 (IL-1) blockade for patients with COVID-19.
METHODS
The PubMed, Web of Science, Ovid Medline, Embase and Cochrane Library databases were searched for relevant articles from their inception to 25 September 2022. Only randomized clinical trials (RCTs) that assessed the clinical efficacy and safety of IL-1 blockade in the treatment of patients with COVID-19 were included.
RESULTS
This meta-analysis included seven RCTs. No significant difference in the all-cause mortality rate of patients with COVID-19 was observed between the IL-1 blockade and control groups (7.7 vs. 10.5%, odds ratio [OR] = 0.83, 95% confidence interval [CI] 0.57-1.22; = 18%). However, the study group was at significantly lower risk of requiring mechanical ventilation (MV) compared with the control group (OR = 0.53, 95% CI 0.32-0.86; = 24%). Finally, the risk of adverse events was similar between the two groups.
CONCLUSIONS
IL-1 blockade does not provide increased survival benefits in hospitalized patients with COVID-19, but it may reduce the need for MV. Furthermore, it is a safe agent for use in the treatment of COVID-19.>.
Topics: Humans; COVID-19; Interleukin-1; Randomized Controlled Trials as Topic; Treatment Outcome; COVID-19 Drug Treatment
PubMed: 37199379
DOI: 10.1080/07853890.2023.2208872 -
Daru : Journal of Faculty of Pharmacy,... Dec 2020A recent survey has shown that the COVID-19 pandemic has culminated in dramatical and critical treatment particularly in acute infected patients. In fact, this... (Meta-Analysis)
Meta-Analysis
PURPOSE
A recent survey has shown that the COVID-19 pandemic has culminated in dramatical and critical treatment particularly in acute infected patients. In fact, this systematic review-meta-analysis was directly pertained to estimation at the efficient value of some clinical managements to confront the COVID-19 infection.
METHODS
Pubmed, Embase, Scopus, Cochrane, and Scholar databases were searched from inception to July 1, 2020, to identify studies reporting the current treatment process and medications (e.g. hydroxychloroquine, antiviral therapy, convalescent plasma, and immunomodulatory agents) for COVID-19. A random-effects model meta-analysis was performed to calculate the relative risk (RR) with 95% confidence intervals (CI). The outcomes of this study were the frequency of negative conversion cases, clinical improvements, mechanical ventilation demand, intensive care unit (ICU) entry, and mortality. The standard treatment refers to the published guidelines and specialist experience which varies in different articles, and the proposed treatment refers to the kind of interest suggested in the included studies.
RESULTS
A number of 45 articles met the eligibility criteria (out of 6793 articles). Among them, 26 articles involving 3263 patients were included in quantitative analysis. Anti-COVID-19 interventions could significantly increase clinical improvement (RR 1.17, 95% CI 1.08-1.27; I = 49.8%) and reduce the mortality rate (RR 0.58, 95% CI 0.35-0.95; I = 74.8%). Although in terms of negative conversion, ICU entry, and mechanical ventilation demand, clinical intervention had no beneficial effect. The clinical effect of immunomodulatory agents (especially tocilizumab and anakinra) was noticeable compared to other medications with RR of 0.22 (95% CI 0.09-0.53; I = 40.9%) for mortality and 1.25 (95% CI 1.07-1.46; I = 45.4%) for clinical improvement. Moreover, Antivirals (RR 1.13, 95% CI 1.01-1.26; I = 47.0%) and convalescent plasma therapy (RR 1.41, 95% CI 1.01-1.98; I = 66.6%) had significant beneficial effects on clinical improvement.
CONCLUSION
Based on our findings, all the included interventions significantly declined the mortality and enhanced clinical improvements with no effect on negative conversion and mechanical ventilation demand. Especially, immunomodulators and plasma therapy showed favorable outcomes. An evaluation on the efficacy of proposed treatment against COVID-19.
Topics: Antiviral Agents; COVID-19; Humans; Immunization, Passive; Immunologic Factors; Intensive Care Units; Respiration, Artificial; COVID-19 Serotherapy
PubMed: 32812187
DOI: 10.1007/s40199-020-00367-4 -
Rheumatology International Dec 2020Children with Coronavirus disease 2019 (COVID-19) are being reported to have manifestations of hyperinflammatory states and/or Kawasaki-like disease. In this study, we...
Children with Coronavirus disease 2019 (COVID-19) are being reported to have manifestations of hyperinflammatory states and/or Kawasaki-like disease. In this study, we investigated children with typical and atypical Kawasaki disease (KD) likely to be associated with COVID-19. We have reported four children with Kawasaki-like disease probably associated with COVID-19. The clinical features were consistent with incomplete KD in three patients. SARS-CoV-2 RT-PCR was positive in one and the serology was positive in one patient with negative RT-PCR. Corticosteroids, anakinra, intravenous immunoglobulin (IVIG), and acetylsalicylic acid were used in the treatment. Three patients recovered after the treatment while one patient died. The literature review revealed 36 articles describing 320 children with Kawasaki-like disease associated with COVID-19. SARS-CoV-2 RT-PCR was negative in 120 (65.5%) of 183 patients while the serology was positive in 130 (83.8%) of 155 patients. The therapeutic options have included IVIG, acetylsalicylic acid, tocilizumab, anakinra, enoxaparin, and methylprednisolone. Pediatric COVID-19 cases may present with atypical/incomplete Kawasaki-like disease. Thus, pediatricians need to be aware of such atypical presentations resembling KD for early diagnosis of COVID-19.
Topics: Betacoronavirus; COVID-19; Child; Child, Preschool; Coronavirus Infections; Fatal Outcome; Female; Humans; Infant; Male; Mucocutaneous Lymph Node Syndrome; Pandemics; Pneumonia, Viral; SARS-CoV-2
PubMed: 32936318
DOI: 10.1007/s00296-020-04701-6 -
Clinical Rheumatology Oct 2023Rheumatoid arthritis (RA) increases the risk of cardiovascular disease (CVD), with inflammation playing a key role. Biologic and targeted synthetic drugs used to treat... (Review)
Review
BACKGROUND
Rheumatoid arthritis (RA) increases the risk of cardiovascular disease (CVD), with inflammation playing a key role. Biologic and targeted synthetic drugs used to treat RA can induce systemic immunomodulation and may have pleiotropic effects on vascular function, making it crucial to investigate their impact on CVD risk in RA patients.
METHODS
A systematic review of the literature was conducted to investigate the impact of biologic and targeted synthetic treatments approved for RA on various cardiovascular markers, including endothelial function, arterial stiffness, and subclinical atherosclerosis. Our analysis included a search of the MedLine (via PubMed) and Web of Science databases using a pre-determined search strategy. We conducted a narrative synthesis of the included studies due to heterogeneity in study design and outcome measures.
RESULTS
From an initial pool of 647 records, we excluded 327 studies based on their titles and abstracts, and we selected 182 studies for final examination. Ultimately, 58 articles met our inclusion criteria and were included in our systematic review. Our analysis of these studies revealed a positive effect of biologic and targeted synthetic therapies on vascular dysfunction associated with RA. However, the impact of these treatments on subclinical atherosclerosis was inconsistent.
CONCLUSION
Overall, our systematic review provides important insights into the potential cardiovascular benefits of biologic and targeted synthetic treatments for RA by a still unknown mechanism. These findings can inform clinical practice and contribute to our understanding of their possible effects on early vascular pathology. Key Points • Great heterogeneity of methods are used to evaluate the endothelial function and arterial stiffness in patients with RA on biologic and targeted synthetic antirheumatic drugs. • Most studies have shown a considerable improvement in endothelial function and arterial stiffness with TNFi, despite some studies reporting only transient or no improvement. • Anakinra and tocilizumab may have a beneficial effect on vascular function and endothelial injury, as indicated by increased FMD, coronary flow reserve, and reduced levels of biomarkers of endothelial function, while the overall impact of JAKi and rituximab remains inconclusive based on the reviewed studies. • To fully comprehend the distinctions between biologic therapies, more long-term, well-designed clinical trials are necessary using a homogeneous methodology.
Topics: Humans; Antirheumatic Agents; Arthritis, Rheumatoid; Rituximab; Biological Products; Cardiovascular Diseases
PubMed: 36991244
DOI: 10.1007/s10067-023-06587-8 -
Psychopharmacology Feb 2021Management of anxiety, delirium, and agitation cannot be neglected in coronavirus disease (COVID-19). Antipsychotics are usually used for the pharmacological management...
RATIONALE
Management of anxiety, delirium, and agitation cannot be neglected in coronavirus disease (COVID-19). Antipsychotics are usually used for the pharmacological management of delirium, and confusion and behavioral disturbances. The concurrent use of treatments for COVID-19 and antipsychotics should consider eventual drug-drug interactions OBJECTIVE: To systematically review evidence-based available on drug-drug interactions between COVID-19 treatments and antipsychotics.
EVIDENCE REVIEW
Three databases were consulted: Lexicomp® Drug Interactions, Micromedex® Solutions Drugs Interactions, and Liverpool© Drug Interaction Group for COVID-19 therapies. To acquire more information on QT prolongation and Torsade de Pointes (TdP), the CredibleMeds® QTDrugs List was searched. The authors made a recommendation agreed to by consensus. Additionally, a systematic review of drug-drug interactions between antipsychotics and COVID-19 treatment was conducted.
RESULTS
The main interactions between COVID-19 drugs and antipsychotics are the risk of QT-prolongation and TdP, and cytochromes P450 interactions. Remdesivir, baricinitib, and anakinra can be used concomitantly with antipsychotics without risk of drug-drug interaction (except for hematological risk with clozapine and baricinitib). Favipiravir only needs caution with chlorpromazine and quetiapine. Tocilizumab is rather safe to use in combination with antipsychotics. The most demanding COVID-19 treatments for coadministration with antipsychotics are chloroquine, hydroxychloroquine, azithromycin, and lopinavir/ritonavir because of the risk of QT prolongation and TdP and cytochromes interactions. The systematic review provides highly probable drug interaction between lopinavir/ritonavir plus quetiapine and ritonavir/indinavir plus risperidone.
CONCLUSIONS
Clinicians prescribing antipsychotics should be aware of the likely risk of drug-drug interaction with COVID-19 medication and may benefit from taking into account present recommendations of use to preserve patient safety.
Topics: Antipsychotic Agents; Antiviral Agents; Cytochrome P-450 Enzyme System; Drug Interactions; Humans; Long QT Syndrome; SARS-CoV-2; Torsades de Pointes; COVID-19 Drug Treatment
PubMed: 33410987
DOI: 10.1007/s00213-020-05716-4 -
Clinical Reviews in Allergy & Immunology Feb 2023Abnormal immunological indicators associated with disease severity and mortality in patients with COVID-19 have been reported in several observational studies. However,... (Meta-Analysis)
Meta-Analysis Review
Abnormal immunological indicators associated with disease severity and mortality in patients with COVID-19 have been reported in several observational studies. However, there are marked heterogeneities in patient characteristics and research methodologies in these studies. We aimed to provide an updated synthesis of the association between immune-related indicators and COVID-19 prognosis. We conducted an electronic search of PubMed, Scopus, Ovid, Willey, Web of Science, Cochrane library, and CNKI for studies reporting immunological and/or immune-related parameters, including hematological, inflammatory, coagulation, and biochemical variables, tested on hospital admission of COVID-19 patients with different severities and outcomes. A total of 145 studies were included in the current meta-analysis, with 26 immunological, 11 hematological, 5 inflammatory, 4 coagulation, and 10 biochemical variables reported. Of them, levels of cytokines, including IL-1β, IL-1Ra, IL-2R, IL-4, IL-6, IL-8, IL-10, IL-18, TNF-α, IFN-γ, IgA, IgG, and CD4 T/CD8 T cell ratio, WBC, neutrophil, platelet, ESR, CRP, ferritin, SAA, D-dimer, FIB, and LDH were significantly increased in severely ill patients or non-survivors. Moreover, non-severely ill patients or survivors presented significantly higher counts of lymphocytes, monocytes, lymphocyte/monocyte ratio, eosinophils, CD3 T,CD4T and CD8T cells, B cells, and NK cells. The currently updated meta-analysis primarily identified a hypercytokinemia profile with the severity and mortality of COVID-19 containing IL-1β, IL-1Ra, IL-2R, IL-4, IL-6, IL-8, IL-10, IL-18, TNF-α, and IFN-γ. Impaired innate and adaptive immune responses, reflected by decreased eosinophils, lymphocytes, monocytes, B cells, NK cells, T cells, and their subtype CD4 and CD8 T cells, and augmented inflammation, coagulation dysfunction, and nonpulmonary organ injury, were marked features of patients with poor prognosis. Therefore, parameters of immune response dysfunction combined with inflammatory, coagulated, or nonpulmonary organ injury indicators may be more sensitive to predict severe patients and those non-survivors.
Topics: Humans; COVID-19; Interleukin-10; Interleukin 1 Receptor Antagonist Protein; Interleukin-18; CD8-Positive T-Lymphocytes; Interleukin-6; SARS-CoV-2; Tumor Necrosis Factor-alpha; Interleukin-4; Interleukin-8; Cytokines; Killer Cells, Natural
PubMed: 35040086
DOI: 10.1007/s12016-021-08908-8 -
Frontiers in Pharmacology 2021Sepsis is a syndrome with high mortality, which seriously threatens human health. During the pandemic of coronavirus disease 2019 (COVID-19), some severe and critically... (Review)
Review
UNLABELLED
Sepsis is a syndrome with high mortality, which seriously threatens human health. During the pandemic of coronavirus disease 2019 (COVID-19), some severe and critically ill COVID-19 patients with multiple organ dysfunction developed characteristics typical of sepsis and met the diagnostic criteria for sepsis. Timely detection of cytokine storm and appropriate regulation of inflammatory response may be significant in the prevention and treatment of sepsis. This study evaluated the efficacy and safety of specific interleukin (IL)-1 inhibitors, specific IL-6 inhibitors, and GM-CSF blockades in the treatment of COVID-19 (at the edge of sepsis) patients through systematic review and meta-analysis.
METHODOLOGY
A literature search was conducted on PubMed, EMBASE, Clinical Key, Cochrane Library, CNKI, and Wanfang Database using proper keywords such as "SARS-CoV-2," "Corona Virus Disease 2019," "COVID-19," "anakinra," "tocilizumab," "siltuximab," "sarilumab," "mavrilimumab," "lenzilumab," and related words for publications released until August 22, 2021. Other available resources were also used to identify relevant articles. The present systematic review was performed based on PRISMA protocol.
RESULTS
Based on the inclusion and exclusion criteria, 43 articles were included in the final review. The meta-analysis results showed that tocilizumab could reduce the mortality of patients with COVID-19 (at the edge of sepsis) [randomized controlled trials, RCTs: odds ratio (OR) 0.71, 95%CI: 0.52-0.97, low-certainty evidence; non-RCTs: risk ratio (RR) 0.68, 95%CI: 0.55-0.84, very low-certainty evidence) as was anakinra (non-RCTs: RR 0.47, 95%CI: 0.34-0.66, very low-certainty evidence). Sarilumab might reduce the mortality of patients with COVID-19 (at the edge of sepsis), but there was no statistical significance (OR 0.65, 95%CI: 0.36-1.2, low-certainty evidence). For safety outcomes, whether tocilizumab had an impact on serious adverse events (SAEs) was very uncertain (RCTs: OR 0.87, 95%CI: 0.38-2.0, low-certainty evidence; non-RCTs 1.18, 95%CI: 0.83-1.68, very low-certainty evidence) as was on secondary infections (RCTs: OR 0.71, 95%CI: 0.06-8.75, low-certainty evidence; non-RCTs: RR 1.15, 95%CI: 0.89-1.49, very low-certainty evidence).
CONCLUSIONS
This systematic review showed that tocilizumab, sarilumab, and anakinra could reduce the mortality of people with COVID-19 (at the edge of sepsis), and tocilizumab did not significantly affect SAEs and secondary infections. The current evidence of the studies on patients treated with siltuximab, mavrilimumab, and lenzilumab is insufficient. In order to establish evidence with stronger quality, high-quality studies are needed. : PROSPERO (https://www.crd.york.ac.uk/prospero/), identifier CRD42020226545.
PubMed: 35126138
DOI: 10.3389/fphar.2021.804250 -
Vaccines Oct 2023A comprehensive, up-to-date systematic review (SR) of the new-onset rheumatic immune-mediated inflammatory diseases (R-IMIDs) following COVID-19 vaccinations is lacking.... (Review)
Review
A comprehensive, up-to-date systematic review (SR) of the new-onset rheumatic immune-mediated inflammatory diseases (R-IMIDs) following COVID-19 vaccinations is lacking. Therefore, we investigated the demographics, management, and prognosis of new R-IMIDs in adults following SARS-CoV-2 vaccinations. A systematic literature search of Medline, Embase, Google Scholar, LitCovid, and Cochrane was conducted. We included any English-language study that reported new-onset R-IMID in adults following the post-COVID-19 vaccination. A total of 271 cases were reported from 39 countries between January 2021 and May 2023. The mean age of patients was 56 (range 18-90), and most were females (170, 62.5%). Most (153, 56.5%) received the Pfizer BioNTech COVID-19 vaccine. Nearly 50% of patients developed R-IMID after the second dose of the vaccine. Vasculitis was the most prevalent clinical presentation (86, 31.7%), followed by connective tissue disease (66, 24.3%). The mean duration between the vaccine's 'trigger' dose and R-IMID was 11 days. Most (220, 81.2%) received corticosteroids; however, 42% (115) received DMARDs such as methotrexate, cyclophosphamide, tocilizumab, anakinra, IV immunoglobulins, plasma exchange, or rituximab. Complete remission was achieved in 75 patients (27.7%), and 137 (50.6%) improved following the treatment. Two patients died due to myositis. This SR highlights that SARS-CoV-2 vaccines may trigger R-IMID; however, further epidemiology studies are required.
PubMed: 37896974
DOI: 10.3390/vaccines11101571 -
Otology & Neurotology : Official... Jan 2023To answer the following question: In patients with primary autoimmune inner ear disease (AIED), (population) what impact do disease-modifying antirheumatic agents... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To answer the following question: In patients with primary autoimmune inner ear disease (AIED), (population) what impact do disease-modifying antirheumatic agents (DMARDs) (intervention) when compared with no treatment or corticosteroids (comparison) have on auditory and vestibular outcomes (outcome)?
STUDY DESIGN
Systematic review and meta-analysis.
DATA SOURCES
According to PRISMA guidelines, PubMed, Scopus, CINAHL, and Cochrane Library databases were searched from inception to March 10, 2022.
STUDY SELECTION
Studies of patients receiving DMARDs for the treatment of AIED were selected for review. Case reports, phase I/II trials, studies of patients with secondary AIED, and studies of AIED patients receiving solely corticosteroids were excluded.
DATA EXTRACTION
Primary outcomes were pure-tone audiometry and speech discrimination scores at baseline and after DMARD treatment. Secondary outcomes were rates of subjective audiovestibular complaints and rates of adverse reactions. No objective vestibular outcomes underwent meta-analysis.
DATA SYNTHESIS
Mean differences were calculated using RevMan 5.4. Heterogeneity was assessed with the Q test and I2 statistic. Pooled prevalence rates of audiovestibular symptoms were expressed as a percentage with 95% confidence intervals.
RESULTS
Ten studies with a total of 187 patients were included. Treatments included methotrexate, etanercept, azathioprine, anakinra, cyclophosphamide, rituximab, and infliximab. Mean treatment duration was 10.8 ± 22.2 months and mean follow-up was 13.7 ± 8.1 months. The pure-tone audiometry and speech discrimination scores mean differences between baseline and post-DMARD were -2.1 [-4.1, -0.1] dB and 13.9 [8.5, 19.4] %, respectively. Seven studies reported 38 adverse events, four of which were classified as serious.
CONCLUSION
DMARDs showed statistically significant improvement in auditory outcomes, as well as subjective symptoms, with relatively low rates of adverse events. They warrant further exploration to better compare with corticosteroids.
Topics: Humans; Antirheumatic Agents; Methotrexate; Etanercept; Rituximab; Autoimmune Diseases; Labyrinth Diseases
PubMed: 36509432
DOI: 10.1097/MAO.0000000000003743 -
BMJ Paediatrics Open 2021In this review, we discuss some important aspects of paediatric inflammatory multisystem syndrome temporally associated with COVID-19 (PIMS-TS), a new syndrome that is... (Review)
Review
Paediatric inflammatory multisystem syndrome temporally associated with COVID-19 (PIMS-TS): a narrative review and the viewpoint of the Latin American Society of Pediatric Intensive Care (SLACIP) Sepsis Committee.
BACKGROUND
In this review, we discuss some important aspects of paediatric inflammatory multisystem syndrome temporally associated with COVID-19 (PIMS-TS), a new syndrome that is temporally related to previous exposure to SARS-CoV-2 infection. This virus has a broad spectrum of presentation that may overlap with Kawasaki disease in terms of presenting symptoms and laboratory and cardiac findings. Our objective was to review and summarise published evidence regarding the most important aspects of PIMS-TS, with special emphasis on the treatment strategies suggested for middle-income and low-income countries.
METHODS
A systematic review of the literature was performed in the principal medical databases including PubMed, Embase (OVID) and Google Scholar between December 2019 and August 2020.
RESULTS
A total of 69 articles were identified in the described databases. Altogether, 13 articles met the inclusion criteria and were eligible. The most frequently described symptoms of PIMS-TS include fever (82%), shock (67%) and gastrointestinal (87%), skin (71%) and cardiac disorders (75%). In most series, it has been observed between 4 and 6 weeks after the pandemic appears in the general population. Multisystem inflammatory syndrome in children is presented as a great systemic inflammatory response syndrome, which sometimes presents as shock requiring fluid resuscitation and vasoactive drug support (26%). Several treatment strategies have been used, including immunoglobulin, steroids, aspirin, anakinra and anticoagulation among others. These general and specific interventions should be guided by an interdisciplinary and multidisciplinary team, especially in settings with limited resources.
CONCLUSIONS
PIMS-TS COVID-19 is a new type of presentation of SARS-CoV-2 infection, with an exaggerated inflammatory response and frequent--digestive and myocardial involvement. It is important to describe the clinical course and outcomes in countries with limited resources as well as establish the role of biomarkers for early diagnosis, effective therapeutic strategies and outpatient follow-up schemes.
Topics: COVID-19; Child; Critical Care; Humans; Latin America; SARS-CoV-2; Sepsis; Systemic Inflammatory Response Syndrome
PubMed: 34192188
DOI: 10.1136/bmjpo-2020-000894