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2.
Med.lab ; 26(4): 383-389, 2022. Tabs, ilus
Article in Spanish | WHO COVID, LILACS (Americas) | ID: covidwho-20242196

ABSTRACT

La enfermedad por coronavirus SARS-CoV-2 que surgió en el año 2019 (COVID-19), ha obligado al rápido desarrollo de vacunas para prevenir su propagación e intentar controlar la pandemia. Dentro de las vacunas desarrolladas, las primeras en ser aprobadas con una tecnología nueva en el campo de la vacunación, fueron las vacunas basadas en ARNm (ácido ribonucleico mensajero), que lograron tasas de efectividad cercanas al 95 % para la prevención de la enfermedad COVID-19 grave. Los eventos adversos comunes son reacciones locales leves, pero ha habido varios informes de pacientes que desarrollaron tiroiditis subaguda y disfunción tiroidea después de recibir la vacuna contra SARS-CoV-2. Este artículo presenta dos casos de tiroiditis subaguda poco después de recibir la vacuna contra COVID-19


The SARS-CoV-2 coronavirus disease which emerged in 2019 (COVID-19), has forced the rapid development of vaccines to prevent the spread of infection and attempt to control the pandemic. Among the vaccines developed, one of the first to be approved with a new technology in the field of vaccination, was the mRNA (messenger ribonucleic acid) vaccine, with rates of effectiveness close to 95% for the prevention of severe COVID-19 disease. Common adverse events are mild local reactions, but there have been some reports of patients developing sub-acute thyroiditis and thyroid dysfunction after receiving the SARS-CoV-2 vaccine. This article presents two case reports of subacute thyroiditis shortly after receiving the COVID-19 vaccine


Subject(s)
Humans , Male , Female , Adult , Aged , Thyroiditis, Subacute/chemically induced , Thyrotoxicosis/chemically induced , BNT162 Vaccine/adverse effects , ChAdOx1 nCoV-19/adverse effects , Thyroiditis, Subacute/diagnosis , Thyroiditis, Subacute/drug therapy , Thyrotoxicosis/diagnosis , Thyrotoxicosis/drug therapy , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Goiter/chemically induced
4.
Pediatr Endocrinol Diabetes Metab ; 27(2): 134-140, 2021.
Article in English | MEDLINE | ID: covidwho-20234510

ABSTRACT

Metformin is a widely used biguanide drug recommended as a first-line antidiabetic for type 2 diabetes. Currently, metformin is used not only in the treatment of diabetes but also in other diseases. Some studies have shown that metformin causes weight loss in insulin-sensitive and insulin-resistant overweight and obese patients. Metformin is an effective and safe option for women with gestational diabetes and type 2 diabetes in pregnancy, and it may also increase the ovulation rate in patients with polycystic ovary syndrome (PCOS). Longer survival times have been observed in cancer patients using metformin. Metformin has been shown to significantly correlate with lower mortality in obese or type 2 diabetic women hospitalized for COVID-19. It also has a protective effect on the development and progression of many types of cancer. The mechanisms of action of metformin are complex and still not fully understood. Metformin has been shown to act through both AMP-activated protein kinase (AMPK)-dependent mechanisms and AMPK-independent mechanisms. This paper presents the benefits of using metformin in the treatment of various diseases.


Subject(s)
COVID-19 , Diabetes Mellitus, Type 2 , Metformin , Diabetes Mellitus, Type 2/drug therapy , Female , Humans , Hypoglycemic Agents/therapeutic use , Metformin/therapeutic use , Pregnancy , SARS-CoV-2
5.
Blood Coagul Fibrinolysis ; 32(7): 427-433, 2021 Oct 01.
Article in English | MEDLINE | ID: covidwho-20233854

ABSTRACT

Immune thrombocytopenia is a haematological, autoimmune disorder characterized by elevated platelet demolition due to the presence of antiplatelet autoantibodies derived from B cells and to an irregular, deficient process of platelets production in bone marrow. In this review, after a brief presentation of 'old' strategies used nowadays yet, we focused on new drugs used in the treatment of immune thrombocytopenia and their mechanism of action and posology, basing on the last scientific literature. The observation that CoViD-19 can be associated with immune thrombocytopenia is also put in evidence. Particular attention will be dedicated on the concept that the ideal treatment should represent a solution not only for the failure of normal processes of production and survival of platelets, but also it should improve quality of life of patients, with minimum adverse events. Anyway, despite enormous advances of the last years, further investigations are necessary in order to define scrupulously long-term efficacy of new molecules proposed.


Subject(s)
Purpura, Thrombocytopenic, Idiopathic/drug therapy , Aminopyridines/therapeutic use , Antibodies, Monoclonal, Humanized/therapeutic use , COVID-19/complications , COVID-19/immunology , Histocompatibility Antigens Class I , Humans , Immunosuppressive Agents/therapeutic use , Morpholines/therapeutic use , Protein Kinase Inhibitors/therapeutic use , Purpura, Thrombocytopenic, Idiopathic/etiology , Purpura, Thrombocytopenic, Idiopathic/immunology , Pyrimidines/therapeutic use , Receptors, Fc/antagonists & inhibitors , Receptors, Thrombopoietin/agonists , SARS-CoV-2/immunology , Syk Kinase/antagonists & inhibitors , Thiazoles/therapeutic use , Thiophenes/therapeutic use
10.
Biomed Pharmacother ; 164: 114997, 2023 Aug.
Article in English | MEDLINE | ID: covidwho-20241696

ABSTRACT

The SARS-CoV-2 pandemic made evident that there are only a few drugs against coronavirus. Here we aimed to identify a cost-effective antiviral with broad spectrum activity and high safety profile. Starting from a list of 116 drug candidates, we used molecular modelling tools to rank the 44 most promising inhibitors. Next, we tested their efficacy as antivirals against α and ß coronaviruses, such as the HCoV-229E and SARS-CoV-2 variants. Four drugs, OSW-1, U18666A, hydroxypropyl-ß-cyclodextrin (HßCD) and phytol, showed in vitro antiviral activity against HCoV-229E and SARS-CoV-2. The mechanism of action of these compounds was studied by transmission electron microscopy and by fusion assays measuring SARS-CoV-2 pseudoviral entry into target cells. Entry was inhibited by HßCD and U18666A, yet only HßCD inhibited SARS-CoV-2 replication in the pulmonary Calu-3 cells. Compared to the other cyclodextrins, ß-cyclodextrins were the most potent inhibitors, which interfered with viral fusion via cholesterol depletion. ß-cyclodextrins also prevented infection in a human nasal epithelium model ex vivo and had a prophylactic effect in the nasal epithelium of hamsters in vivo. All accumulated data point to ß-cyclodextrins as promising broad-spectrum antivirals against different SARS-CoV-2 variants and distant alphacoronaviruses. Given the wide use of ß-cyclodextrins for drug encapsulation and their high safety profile in humans, our results support their clinical testing as prophylactic antivirals.


Subject(s)
COVID-19 , Dermatologic Agents , beta-Cyclodextrins , Humans , SARS-CoV-2 , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , beta-Cyclodextrins/pharmacology , beta-Cyclodextrins/therapeutic use
11.
J Prev Med Public Health ; 56(3): 221-230, 2023 May.
Article in English | MEDLINE | ID: covidwho-20241661

ABSTRACT

OBJECTIVES: The second wave of coronavirus disease 2019 (COVID-19) cases in Indonesia, during which the Delta variant predominated, took place after a vaccination program had been initiated in the country. This study was conducted to assess the impact of COVID-19 vaccination on unfavorable clinical outcomes including hospitalization, severe COVID-19, intensive care unit (ICU) admission, and death using a real-world model. METHODS: This single-center retrospective cohort study involved patients with COVID-19 aged ≥18 years who presented to the COVID-19 emergency room at a secondary referral teaching hospital between June 1, 2021 and August 31, 2021. We used a binary logistic regression model to assess the effect of COVID-19 vaccination on unfavorable clinical outcomes, with age, sex, and comorbidities as confounding variables. RESULTS: A total of 716 patients were included, 32.1% of whom were vaccinated. The elderly participants (≥65 years) had the lowest vaccine coverage among age groups. Vaccination had an effectiveness of 50% (95% confidence interval [CI], 25 to 66) for preventing hospitalization, 97% (95% CI, 77 to 99) for preventing severe COVID-19, 95% (95% CI, 56 to 99) for preventing ICU admission, and 90% (95% CI, 22 to 99) for preventing death. Interestingly, patients with type 2 diabetes had a 2-fold to 4-fold elevated risk of unfavorable outcomes. CONCLUSIONS: Among adults, COVID-19 vaccination has a moderate preventive impact on hospitalization but a high preventive impact on severe COVID-19, ICU admission, and death. The authors suggest that relevant parties increase COVID-19 vaccination coverage, especially in the elderly population.


Subject(s)
COVID-19 , Diabetes Mellitus, Type 2 , Adult , Humans , Aged , Adolescent , Indonesia/epidemiology , COVID-19 Vaccines/therapeutic use , Retrospective Studies , Secondary Care Centers , COVID-19/epidemiology , COVID-19/prevention & control , SARS-CoV-2 , Vaccination , Hospitalization
12.
Nat Commun ; 14(1): 3334, 2023 06 07.
Article in English | MEDLINE | ID: covidwho-20241659

ABSTRACT

COVID-19 patients at risk of severe disease may be treated with neutralising monoclonal antibodies (mAbs). To minimise virus escape from neutralisation these are administered as combinations e.g. casirivimab+imdevimab or, for antibodies targeting relatively conserved regions, individually e.g. sotrovimab. Unprecedented genomic surveillance of SARS-CoV-2 in the UK has enabled a genome-first approach to detect emerging drug resistance in Delta and Omicron cases treated with casirivimab+imdevimab and sotrovimab respectively. Mutations occur within the antibody epitopes and for casirivimab+imdevimab multiple mutations are present on contiguous raw reads, simultaneously affecting both components. Using surface plasmon resonance and pseudoviral neutralisation assays we demonstrate these mutations reduce or completely abrogate antibody affinity and neutralising activity, suggesting they are driven by immune evasion. In addition, we show that some mutations also reduce the neutralising activity of vaccine-induced serum.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , SARS-CoV-2/genetics , Antibodies, Monoclonal/therapeutic use , Immunotherapy , Mutation , Antibodies, Neutralizing , Antibodies, Viral
13.
Int J Mol Sci ; 24(10)2023 May 18.
Article in English | MEDLINE | ID: covidwho-20241658

ABSTRACT

Since the first description of COVID-19 infection, among clinical manifestations of the disease, including fever, dyspnea, cough, and fatigue, it was observed a high incidence of thromboembolic events potentially evolving towards acute respiratory distress syndrome (ARDS) and COVID-19-associated-coagulopathy (CAC). The hypercoagulation state is based on an interaction between thrombosis and inflammation. The so-called CAC represents a key aspect in the genesis of organ damage from SARS-CoV-2. The prothrombotic status of COVID-19 can be explained by the increase in coagulation levels of D-dimer, lymphocytes, fibrinogen, interleukin 6 (IL-6), and prothrombin time. Several mechanisms have been hypothesized to explain this hypercoagulable process such as inflammatory cytokine storm, platelet activation, endothelial dysfunction, and stasis for a long time. The purpose of this narrative review is to provide an overview of the current knowledge on the pathogenic mechanisms of coagulopathy that may characterize COVID-19 infection and inform on new areas of research. New vascular therapeutic strategies are also reviewed.


Subject(s)
Blood Coagulation Disorders , COVID-19 , Thrombophilia , Thrombosis , Humans , COVID-19/complications , SARS-CoV-2 , Blood Coagulation Disorders/complications , Blood Coagulation Disorders/drug therapy , Inflammation/drug therapy , Thrombosis/etiology , Thrombophilia/complications , Anticoagulants/therapeutic use
14.
Prim Care Companion CNS Disord ; 25(3)2023 May 23.
Article in English | MEDLINE | ID: covidwho-20241579

ABSTRACT

Objective: To synthesize the neurobiological basis of brain-resetting effects of psilocybin and identify neuroimaging correlates of psilocybin response in depressed patients.Data Sources: MEDLINE(R), Embase, APA PsycINFO, Cochrane, and CINAHL were systematically searched on June 3, 2022, with no date restrictions using the following string: (psilocybin) AND (psychedelics) AND (MRI) OR (fMRI)) OR (PET)) OR (SPECT)) OR (imaging)) OR (neuroimaging)).Study Selection: After duplicates were removed from 946 studies, 391 studies remained, of which 8 qualified for full-text analysis, but only 5 fulfilled the eligibility criteria of randomized, double-blind, or open-label neuroimaging study with psilocybin treatment in depressed patients.Data Extraction: The Covidence platform was used for deduplication and bias assessment. The a priori data points included concomitant psychological intervention, modality of neuroimaging technique, changes in depression scores, brain functional changes, and association between functional and psilocybin response. Assessment bias was assessed with the standard risk of bias tool for randomized controlled trials and the tool for risk of bias in nonrandomized studies of interventions.Results: Four studies were open-label, and one was a combined open-label and randomized controlled trial using functional magnetic resonance imaging. Psilocybin-assisted psychotherapy was administered in 3 studies, 1 in refractory and 2 in nonrefractory patients. The remaining 2 studies were in refractory patients. The transient increase in psilocybin-induced global connectivity in major neural tracts and specific areas of brain activation was associated with antidepressant response.Conclusions: Transient functional brain changes with psilocybin therapy resemble the "brain reset" phenomenon and may serve as the putative predictors of psilocybin antidepressant response.


Subject(s)
Depression , Psilocybin , Humans , Antidepressive Agents/pharmacology , Brain/diagnostic imaging , Depression/drug therapy , Psilocybin/pharmacology , Psilocybin/therapeutic use , Psychotherapy/methods , Randomized Controlled Trials as Topic
15.
N Engl J Med ; 388(21): 1931-1941, 2023 May 25.
Article in English | MEDLINE | ID: covidwho-20241324

ABSTRACT

BACKGROUND: Whether the antiinflammatory and immunomodulatory effects of glucocorticoids may decrease mortality among patients with severe community-acquired pneumonia is unclear. METHODS: In this phase 3, multicenter, double-blind, randomized, controlled trial, we assigned adults who had been admitted to the intensive care unit (ICU) for severe community-acquired pneumonia to receive intravenous hydrocortisone (200 mg daily for either 4 or 7 days as determined by clinical improvement, followed by tapering for a total of 8 or 14 days) or to receive placebo. All the patients received standard therapy, including antibiotics and supportive care. The primary outcome was death at 28 days. RESULTS: A total of 800 patients had undergone randomization when the trial was stopped after the second planned interim analysis. Data from 795 patients were analyzed. By day 28, death had occurred in 25 of 400 patients (6.2%; 95% confidence interval [CI], 3.9 to 8.6) in the hydrocortisone group and in 47 of 395 patients (11.9%; 95% CI, 8.7 to 15.1) in the placebo group (absolute difference, -5.6 percentage points; 95% CI, -9.6 to -1.7; P = 0.006). Among the patients who were not undergoing mechanical ventilation at baseline, endotracheal intubation was performed in 40 of 222 (18.0%) in the hydrocortisone group and in 65 of 220 (29.5%) in the placebo group (hazard ratio, 0.59; 95% CI, 0.40 to 0.86). Among the patients who were not receiving vasopressors at baseline, such therapy was initiated by day 28 in 55 of 359 (15.3%) of the hydrocortisone group and in 86 of 344 (25.0%) in the placebo group (hazard ratio, 0.59; 95% CI, 0.43 to 0.82). The frequencies of hospital-acquired infections and gastrointestinal bleeding were similar in the two groups; patients in the hydrocortisone group received higher daily doses of insulin during the first week of treatment. CONCLUSIONS: Among patients with severe community-acquired pneumonia being treated in the ICU, those who received hydrocortisone had a lower risk of death by day 28 than those who received placebo. (Funded by the French Ministry of Health; CAPE COD ClinicalTrials.gov number, NCT02517489.).


Subject(s)
Anti-Inflammatory Agents , Community-Acquired Infections , Hydrocortisone , Pneumonia , Adult , Humans , Anti-Inflammatory Agents/adverse effects , Anti-Inflammatory Agents/therapeutic use , Community-Acquired Infections/drug therapy , Community-Acquired Infections/mortality , Double-Blind Method , Hydrocortisone/adverse effects , Hydrocortisone/therapeutic use , Pneumonia/drug therapy , Pneumonia/mortality , Respiration, Artificial , Treatment Outcome
16.
BMJ Open ; 13(6): e070489, 2023 Jun 09.
Article in English | MEDLINE | ID: covidwho-20241289

ABSTRACT

OBJECTIVES: This study investigated remdesivir's clinical use to provide direct evidence of effectiveness for a low-middle income Asian setting. DESIGN: A one-to-one propensity score matching retrospective cohort study. SETTING: A tertiary hospital with COVID-19 treatment facilities in Vietnam. PARTICIPANTS: A total of 310 patients in standard of care (SoC) group were matched with 310 patients in SoC+remdesivir (SoC+R) group. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was time to critical progression, defined as all-cause mortality or critical illness. The secondary outcomes were length of oxygen therapy/ventilation and need for invasive mechanical ventilation. Outcome reports were presented as HR, OR or effect difference with 95% CI. RESULTS: Patients receiving remdesivir had a lower risk for mortality or critical illness (HR=0.68, 95% CI 0.47 to 0.96, p=0.030). Remdesivir was not associated with a shorter length of oxygen therapy/ventilation (effect difference -0.17 days, 95% CI -1.29 to 0.96, p=0.774). The need for invasive mechanical ventilation was lower in SoC+R group (OR=0.57, 95% CI 0.38 to 0.86, p=0.007). CONCLUSIONS: This study's results showing remdesivir's benefits in non-critical patients with COVID-19 may be extrapolated to other similar low-middle income countries, allowing more regimens for limited resource areas and reducing poor outcomes and equity gap worldwide.


Subject(s)
COVID-19 , Humans , SARS-CoV-2 , COVID-19 Drug Treatment , Critical Illness , Retrospective Studies , Oxygen , Antiviral Agents/therapeutic use
17.
Lancet Infect Dis ; 23(6): 706-718, 2023 06.
Article in English | MEDLINE | ID: covidwho-20241103

ABSTRACT

BACKGROUND: Understanding strategic commitments and policy responses to overcome antimicrobial resistance at the national, regional, and global levels is required to evaluate current progress and direct future planning. National action plans (NAPs) are the primary mechanism for guiding national strategy and action for antimicrobial resistance governance. Although several NAPs have been developed, no comprehensive content analysis of these plans exists. Using a governance framework, we aimed to assess all publicly available NAPs on antimicrobial resistance. METHODS: We systematically reviewed the contents of NAPs on antimicrobial resistance from 114 countries, applying a governance framework containing 18 domains and 54 indicators in three integral areas: policy design, implementation tools, and monitoring and evaluation. As well as manually searching NAPs and doing online and literature searches that were relevant to specific indicators from repository inception to June 1, 2022, several data sources were used to generate scores, including the Tripartite Antimicrobial Resistance Country Self-Assessment Survey, the Global Antimicrobial Resistance and Use Surveillance System, the Global Antimicrobial Resistance Research and Development Hub, and various WHO datasets. NAPs were included if the country had also submitted the NAP to the Tripartite Antimicrobial Resistance Country Self-Assessment Survey 2020-21, if the NAP was retrievable through a publicly accessible database or website, and if the NAP was either published in English or eligible for machine translation. Three researchers independently reviewed each NAP and were initially blinded to the evaluations of other researchers. They generated a score using a quantification system for each of 54 indicators. The Cochrane protocol for ensuring reliability was followed. The three researchers were then unblinded and met to resolve any disagreements in scoring to reach a consensus agreement. In each case of discrepancy, consensus was reached between the researchers. We developed criteria to standardise the process of quantifying each indicator. We also weighted and collated relevant national data from various sources to generate composite scores concordant with the key governance areas. We transformed these data to a scale of 0 (worst) to 100 (best), ranked countries on the basis of their mean scores, and used descriptive statistics to analyse global and regional trends. FINDINGS: 306 NAPs were identified and 114 were eligible for analysis. Between 2020 and 2021, the mean antimicrobial resistance governance score was 51 (SD 14). Norway had the highest governance score (mean 85 [SD 32]), and the Federated States of Micronesia had the lowest governance score (28 [37]). The highest scoring domain was participation (83 [16]), and the lowest scoring domains were accountability (30 [18]) and feedback mechanism (30 [25]). Domains relating to policy design (55 [13]) and implementation tools (54 [17]) scored similarly, whereas monitoring and evaluation (38 [20]) efforts were lower. INTERPRETATION: International efforts to control antimicrobial resistance varied considerably between countries. Monitoring and evaluation efforts need improving for continuous understanding of national and international progress. International response might not be commensurate with the scale and severity of antimicrobial resistance. FUNDING: None.


Subject(s)
Anti-Bacterial Agents , Drug Resistance, Bacterial , Humans , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Reproducibility of Results , Micronesia , Norway
19.
J Neonatal Perinatal Med ; 16(2): 235-237, 2023.
Article in English | MEDLINE | ID: covidwho-20240921

ABSTRACT

INTRODUCTION: The coronavirus disease (COVID-19) has created a serious health problem in pregnant people. We aimed to address whether vaccination can prevent development of placental disease in SARS-CoV-2 infected mothers. METHODS: We reported the pathology findings obtained from routine histopathological examination of placentas of overall 38 cases. RESULTS: We found low prevalence of placental pathology in vaccinated pregnant people with active SARS-CoV-2 infection in comparison to those unvaccinated cases. CONCLUSION: Based on our findings, SARS-CoV-2 vaccination can prevent development of placental pathological lesions and may lower the risk of serious illness in pregnant people.


Subject(s)
COVID-19 , Pregnancy Complications, Infectious , Pregnancy , Humans , Female , Placenta , SARS-CoV-2 , COVID-19/prevention & control , COVID-19 Vaccines/therapeutic use , Vaccination , Pregnancy Complications, Infectious/prevention & control , Infectious Disease Transmission, Vertical/prevention & control
20.
BMC Health Serv Res ; 23(1): 553, 2023 May 26.
Article in English | MEDLINE | ID: covidwho-20240897

ABSTRACT

BACKGROUND: To support public health measures during the COVID-19 pandemic, oral opioid agonist treatment (OAT) take-home doses were expanded in Western countries with positive results. Injectable OAT (iOAT) take-home doses were previously not an eligible option, and were made available for the first time in several sites to align with public health measures. Building upon these temporary risk-mitigating guidelines, a clinic in Vancouver, BC continued to offer two of a possible three daily doses of take-home injectable medications to eligible clients. The present study explores the processes through which take-home iOAT doses impacted clients' quality of life and continuity of care in real-life settings. METHODS: Three rounds of semi-structured qualitative interviews were conducted over a period of seventeen months beginning in July 2021 with eleven participants receiving iOAT take-home doses at a community clinic in Vancouver, British Columbia. Interviews followed a topic guide that evolved iteratively in response to emerging lines of inquiry. Interviews were recorded, transcribed, and then coded using NVivo 1.6 using an interpretive description approach. RESULTS: Participants reported that take-home doses granted them the freedom away from the clinic to have daily routines, form plans, and enjoy unstructured time. Participants appreciated the greater privacy, accessibility, and ability to engage in paid work. Furthermore, participants enjoyed greater autonomy to manage their medication and level of engagement with the clinic. These factors contributed to greater quality of life and continuity of care. Participants shared that their dose was too essential to divert and that they felt safe transporting and administering their medication off-site. In the future, all participants would like more accessible treatment such as access longer take-home prescriptions (e.g., one week), the ability to pick-up at different and convenient locations (e.g., community pharmacies), and a medication delivery service. CONCLUSIONS: Reducing the number of daily onsite injections from two or three to only one revealed the diversity of rich and nuanced needs that added flexibility and accessibility in iOAT can meet. Actions such as licencing diverse opioid medications/formulations, medication pick-up at community pharmacies, and a community of practice that supports clinical decisions are necessary to increase take-home iOAT accessibility.


Subject(s)
COVID-19 , Opioid-Related Disorders , Humans , Analgesics, Opioid/therapeutic use , Pandemics , Quality of Life , COVID-19/epidemiology , British Columbia , Opioid-Related Disorders/drug therapy , Opioid-Related Disorders/prevention & control
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