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1.
N Engl J Med ; 388(21): 1931-1941, 2023 May 25.
Artículo en Inglés | MEDLINE | ID: covidwho-20241324

RESUMEN

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.).


Asunto(s)
Antiinflamatorios , Infecciones Comunitarias Adquiridas , Hidrocortisona , Neumonía , Adulto , Humanos , Antiinflamatorios/efectos adversos , Antiinflamatorios/uso terapéutico , Infecciones Comunitarias Adquiridas/tratamiento farmacológico , Infecciones Comunitarias Adquiridas/mortalidad , Método Doble Ciego , Hidrocortisona/efectos adversos , Hidrocortisona/uso terapéutico , Neumonía/tratamiento farmacológico , Neumonía/mortalidad , Respiración Artificial , Resultado del Tratamiento
2.
Pharmacol Res ; 191: 106702, 2023 05.
Artículo en Inglés | MEDLINE | ID: covidwho-2245841

RESUMEN

We have recently demonstrated in a double-blind randomized trial the beneficial effects of L-Arginine in patients hospitalized for COVID-19. We hypothesize that one of the mechanisms underlying the favorable effects of L-Arginine is its action on inflammatory cytokines. To verify our hypothesis, we measured longitudinal plasma levels of pro-inflammatory and anti-inflammatory cytokines implied in the pathophysiology of COVID-19 in patients randomized to receive oral L-Arginine or placebo. The study was successfully completed by 169 patients. Patients in the L-Arginine arm had a reduced respiratory support evaluated at 10 and 20 days; moreover, the time to hospital discharge was significantly shorter in the L-Arginine group. The assessment of circulating cytokines revealed that L-Arginine significantly reduced the circulating levels of pro-inflammatory IL-2, IL-6, and IFN-γ and increased the levels of the anti-inflammatory IL-10. Taken together, these findings indicate that adding L-Arginine to standard therapy in COVID-19 patients markedly reduces the need of respiratory support and the duration of in-hospital stay; moreover, L-Arginine significantly regulates circulating levels of pro-inflammatory and anti-inflammatory cytokines.


Asunto(s)
COVID-19 , Humanos , SARS-CoV-2 , Citocinas , Arginina/uso terapéutico , Antiinflamatorios/efectos adversos
3.
J Physiol Pharmacol ; 73(4)2022 Aug.
Artículo en Inglés | MEDLINE | ID: covidwho-2218017

RESUMEN

Systemic hyperinflammation is a hallmark of severe coronavirus disease-2019 (COVID-19). Tocilizumab (TCZ) (an interleukin-6 receptor blocker) therapy is currently used as an anti-inflammatory intervention alongside corticosteroids to modulate the hyperinflammatory response (cytokine storm) in hospitalized patients with severe COVID-19 to prevent mortality. There is, however, a wide uncertainty about its pros and cons in patients with COVID-19, particularly, its possible immunosuppressive effect is of serious concern for the clinicians. The present study aimed to report response of a cohort of severely-ill hospitalized COVID-19 pneumonia patients who were treated with tocilizumab after the initial corticosteroids therapy failed to improve the patients' clinical condition. This was a single-arm retrospective study of 100 severely-ill COVID-19 pneumonia patients who were admitted to the specialized COVID-19 units of Mayo Hospital, Lahore, Pakistan from March 12, 2020, to May 25, 2021. These COVID-19 patients had progressed to cytokine storm with persistent hypoxia, associated with pneumonia, and markedly elevated serum levels of inflammatory biomarkers including C-reactive protein (CRP), D-dimer, and ferritin. All the patients had received two separate doses of intravenous 400 mg (4 mg/kg) tocilizumab with an 8-hour interval alongside standard COVID-19 care which includes corticosteroid, antibiotics, and anticoagulants. Following tocilizumab intervention, 75 (75.0%) patients showed clinical improvement, continued to recover, and were safely discharged from the hospital, while in 25 (25.0%) patients, TCZ failed to prevent clinical deterioration, and patients eventually died in the hospital. Amongst the 25 (25.0%) deaths, 8 (32.0%) patients had a single comorbidity, while 9 (36.0%) had two or more comorbidities. The median IQR age for survivors was 57.0 (50.0, 60.0) years, and non-survivors was 60.0 (55.0, 70.0) years; and the period of hospitalization was 25 (20, 40) days and 20 (14, 34) days, respectively. Tocilizumab treatment improved serum inflammatory biomarker levels including CRP, D-dimer, and ferritin, by almost a similar magnitude in both survivors and non-survivors. Development of secondary infections were reported in 25 (25.0%) patients, including 21% patients with bacterial (Pseudomonas, Klebsiella, Acinetobacter) and 4% with fungal (Aspergillus) infection. The emergence of secondary infection was higher in patients who died (72.0%) as compared to those who survived (28.0%). In conclusion: in low- and middle-income countries in the presence of limited therapeutic options, a timely intervention of TCZ alongside corticosteroids may be a suitable anti-inflammatory therapy for severely-ill hospitalized COVID-19 pneumonia patients to prevent mortality. However, patients must be closely monitored for secondary bacterial/fungal infections. Early diagnosis and management of secondary infection can reduce morbidity and mortality.


Asunto(s)
COVID-19 , Coinfección , Humanos , Estudios Retrospectivos , SARS-CoV-2 , Síndrome de Liberación de Citoquinas/tratamiento farmacológico , Síndrome de Liberación de Citoquinas/inducido químicamente , Coinfección/inducido químicamente , Tratamiento Farmacológico de COVID-19 , Antiinflamatorios/efectos adversos , Proteína C-Reactiva , Biomarcadores , Ferritinas , Resultado del Tratamiento
4.
Pharmacol Res ; 185: 106511, 2022 11.
Artículo en Inglés | MEDLINE | ID: covidwho-2132084

RESUMEN

Coronavirus Disease 19 (COVID-19) is associated with high morbidity and mortality rates globally, representing the greatest health and economic challenge today. Several drugs are currently approved for the treatment of COVID-19. Among these, glucocorticoids (GCs) have received particular attention due to their anti-inflammatory and immunosuppressive effects. In fact, GC are widely used in current clinical practice to treat inflammatory, allergic and autoimmune diseases. Major mechanisms of GC action include inhibition of innate and adaptive immune activity. In particular, an important role is played by the inhibition of pro-inflammatory cytokines and chemokines, and the induction of proteins with anti-inflammatory activity. Overall, as indicated by various national and international regulatory agencies, GCs are recommended for the treatment of COVID-19 in patients requiring oxygen therapy, with or without mechanical ventilation. Regarding the use of GCs for the COVID-19 treatment of non-hospitalized patients at an early stage of the disease, many controversial studies have been reported and regulatory agencies have not recommended their use. The decision to start GC therapy should be based not only on the severity of COVID-19 disease, but also on careful considerations of the benefit/risk profile in individual patients, including monitoring of adverse events. In this review we summarize the effects of GCs on the major cellular and molecular components of the inflammatory/immune system, the benefits and the adverse common reactions in the treatment of inflammatory/autoimmune diseases, as well as in the management of COVID-19.


Asunto(s)
Enfermedades Autoinmunes , Tratamiento Farmacológico de COVID-19 , Humanos , Glucocorticoides/uso terapéutico , Glucocorticoides/farmacología , Antiinflamatorios/efectos adversos , Enfermedades Autoinmunes/tratamiento farmacológico
5.
Ter Arkh ; 94(7): 872-875, 2022 Aug 12.
Artículo en Ruso | MEDLINE | ID: covidwho-2026363

RESUMEN

The specific feature of new coronavirus infection (COVID-19) is high risk of hyperinflammatory response or cytokine storm development, which underly the pathogenesis of several life-threatening conditions and determine the disease outcomes. Pathophysiological features of COVID-19 justify the search of effective drugs capable to control the hyperinflammatory response. AIM: To evaluate the efficacy and safety of Aterixen (1-[2-(1-Мethylimidazol-4-yl)-ethyl]perhydroazin-2,6-dion) for achieving clinical improvement in adult patients hospitalized with moderate and severe COVID-19. MATERIALS AND METHODS: Multicenter, adaptive, randomized, double-blind, placebo-controlled, phase III study to evaluate the efficacy and safety of Aterixen , tablets, 100 mg, in patients with COVID-19. The study analysis included 116 patients who, by randomization, were divided into 2 groups: 57 patients were included in the Aterixen drug group and 59 patients were in the placebo group. RESULTS AND CONCLUSION: Obtained results have shown high efficacy and statistically significant superiority of Aterixen over placebo. Thus, it allows us to consider it as viable medication for COVID-19 pathogenetic therapy.


Asunto(s)
Antiinflamatorios , Tratamiento Farmacológico de COVID-19 , Adulto , Humanos , Antiinflamatorios/efectos adversos , Método Doble Ciego , Hospitalización , SARS-CoV-2 , Resultado del Tratamiento
6.
Molecules ; 27(9)2022 May 02.
Artículo en Inglés | MEDLINE | ID: covidwho-1875712

RESUMEN

Hydroxylated polyphenols, also called flavonoids, are richly present in vegetables, fruits, cereals, nuts, herbs, seeds, stems, and flowers of numerous plants. They possess numerous medicinal properties such as antioxidant, anti-cancer, anti-microbial, neuroprotective, and anti-inflammation. Studies show that flavonoids activate antioxidant pathways that render an anti-inflammatory effect. They inhibit the secretions of enzymes such as lysozymes and ß-glucuronidase and inhibit the secretion of arachidonic acid, which reduces inflammatory reactions. Flavonoids such as quercetin, genistein, apigenin, kaempferol, and epigallocatechin 3-gallate modulate the expression and activation of a cytokine such as interleukin-1beta (IL-1ß), Tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-8 (IL-8); regulate the gene expression of many pro-inflammatory molecules such s nuclear factor kappa-light chain enhancer of activated B cells (NF-κB), activator protein-1 (AP-1), intercellular adhesion molecule-1 (ICAM), vascular cell adhesion molecule-1 (VCAM), and E-selectins; and also inhibits inducible nitric oxide (NO) synthase, cyclooxygenase-2, and lipoxygenase, which are pro-inflammatory enzymes. Understanding the anti-inflammatory action of flavonoids provides better treatment options, including coronavirus disease 2019 (COVID-19)-induced inflammation, inflammatory bowel disease, obstructive pulmonary disorder, arthritis, Alzheimer's disease, cardiovascular disease, atherosclerosis, and cancer. This review highlights the sources, biochemical activities, and role of flavonoids in enhancing human health.


Asunto(s)
COVID-19 , Flavonoides , Antiinflamatorios/efectos adversos , Antioxidantes/efectos adversos , Flavonoides/química , Flavonoides/farmacología , Flavonoides/uso terapéutico , Humanos , Inflamación/tratamiento farmacológico , FN-kappa B/metabolismo , Factor de Necrosis Tumoral alfa/farmacología
7.
J Med Virol ; 94(4): 1745-1747, 2022 04.
Artículo en Inglés | MEDLINE | ID: covidwho-1718409

RESUMEN

Methylprednisolone (MP) is usually used to reduce inflammation reaction and tissue damage, which may have a beneficial treatment effect on coronavirus disease 2019 (COVID-19). However, we present the case of a child who manifests significant bradycardia with the use of just low dose MP on the premise of the long-term use of arbidol. Arbidol can affect the activity of CYP3A4, which is also a key metabolic enzyme of MP by competitive inhibition, and which is easy to aggravate the side effects of MP. Therefore, more attention should be paid to bradycardia occurrence in the patient with COVID-19 when MP is considered in COVID-19.


Asunto(s)
Antiinflamatorios/efectos adversos , Bradicardia/inducido químicamente , Tratamiento Farmacológico de COVID-19 , Metilprednisolona/efectos adversos , Antivirales/efectos adversos , COVID-19/diagnóstico , Niño , Quimioterapia Combinada/efectos adversos , Humanos , Indoles/efectos adversos , Masculino , SARS-CoV-2/efectos de los fármacos , SARS-CoV-2/aislamiento & purificación , Sulfuros/efectos adversos
8.
JAMA Netw Open ; 4(12): e2141328, 2021 12 01.
Artículo en Inglés | MEDLINE | ID: covidwho-1592856

RESUMEN

Importance: Hospitalized patients with COVID-19 pneumonia have high rates of morbidity and mortality. Objective: To assess the efficacy of colchicine in hospitalized patients with COVID-19 pneumonia. Design, Setting, and Participants: The Estudios Clínicos Latino América (ECLA) Population Health Research Institute (PHRI) COLCOVID trial was a multicenter, open-label, randomized clinical trial performed from April 17, 2020, to March 28, 2021, in adults with confirmed or suspected SARS-CoV-2 infection followed for up to 28 days. Participants received colchicine vs usual care if they were hospitalized with COVID-19 symptoms and had severe acute respiratory syndrome or oxygen desaturation. The main exclusion criteria were clear indications or contraindications for colchicine, chronic kidney disease, and negative results on a reverse transcription-polymerase chain reaction test for SARS-CoV-2 before randomization. Data were analyzed from June 20 to July 25, 2021. Interventions: Patients were assigned in a 1:1 ratio to usual care or usual care plus colchicine. Colchicine was administered orally in a loading dose of 1.5 mg immediately after randomization, followed by 0.5 mg orally within 2 hours of the initial dose and 0.5 mg orally twice a day for 14 days or discharge, whichever occurred first. Main Outcomes and Measures: The first coprimary outcome was the composite of a new requirement for mechanical ventilation or death evaluated at 28 days. The second coprimary outcome was death at 28 days. Results: A total of 1279 hospitalized patients (mean [SD] age, 61.8 [14.6] years; 449 [35.1%] women and 830 [64.9%] men) were randomized, including 639 patients in the usual care group and 640 patients in the colchicine group. Corticosteroids were used in 1171 patients (91.5%). The coprimary outcome of mechanical ventilation or 28-day death occurred in 160 patients (25.0%) in the colchicine group and 184 patients (28.8%) in the usual care group (hazard ratio [HR], 0.83; 95% CI, 0.67-1.02; P = .08). The second coprimary outcome, 28-day death, occurred in 131 patients (20.5%) in the colchicine group and 142 patients (22.2%) in the usual care group (HR, 0.88; 95% CI, 0.70-1.12). Diarrhea was the most frequent adverse effect of colchicine, reported in 68 patients (11.3%). Conclusions and Relevance: This randomized clinical trial found that compared with usual care, colchicine did not significantly reduce mechanical ventilation or 28-day mortality in patients hospitalized with COVID-19 pneumonia. Trial Registration: ClinicalTrials.gov Identifier: NCT04328480.


Asunto(s)
Antiinflamatorios/uso terapéutico , COVID-19/terapia , Colchicina/uso terapéutico , Hospitalización , Intubación Intratraqueal , Respiración Artificial , Corticoesteroides/uso terapéutico , Adulto , Anciano , Antiinflamatorios/efectos adversos , COVID-19/mortalidad , COVID-19/patología , Colchicina/efectos adversos , Femenino , Humanos , Inflamación/tratamiento farmacológico , Inflamación/etiología , Masculino , Persona de Mediana Edad , SARS-CoV-2 , Nivel de Atención
9.
Pharmacol Rep ; 74(1): 229-240, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: covidwho-1536392

RESUMEN

BACKGROUND AND OBJECTIVES: Corticosteroids are commonly used in the treatment of hospitalized patients with COVID-19. The goals of the present study were to compare the efficacy and safety of different doses of dexamethasone in the treatment of patients with a diagnosis of moderate to severe COVID-19. METHODS: Hospitalized patients with a diagnosis of moderate to severe COVID-19 were assigned to intravenous low-dose (8 mg once daily), intermediate-dose (8 mg twice daily) or high-dose (8 mg thrice daily) dexamethasone for up to 10 days or until hospital discharge. Clinical response, 60-day survival and adverse effects were the main outcomes of the study. RESULTS: In the competing risk survival analysis, patients in the low-dose group had a higher clinical response than the high-dose group when considering death as a competing risk (HR = 2.03, 95% CI: 1.23-3.33, p = 0.03). Also, the survival was significantly longer in the low-dose group than the high-dose group (HR = 0.36, 95% CI = 0.15-0.83, p = 0.02). Leukocytosis and hyperglycemia were the most common side effects of dexamethasone. Although the incidence was not significantly different between the groups, some adverse effects were numerically higher in the intermediate-dose and high-dose groups than in the low-dose group. CONCLUSIONS: Higher doses of dexamethasone not only failed to improve efficacy but also resulted in an increase in the number of adverse events and worsen survival in hospitalized patients with moderate to severe COVID-19 compared to the low-dose dexamethasone. (IRCT20100228003449N31).


Asunto(s)
Antiinflamatorios/administración & dosificación , Antiinflamatorios/uso terapéutico , Tratamiento Farmacológico de COVID-19 , Dexametasona/administración & dosificación , Dexametasona/uso terapéutico , Adulto , Anciano , Antiinflamatorios/efectos adversos , Dexametasona/efectos adversos , Relación Dosis-Respuesta a Droga , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Femenino , Humanos , Hiperglucemia/inducido químicamente , Incidencia , Leucocitosis/inducido químicamente , Masculino , Persona de Mediana Edad , Análisis de Supervivencia , Resultado del Tratamiento
10.
Immunopharmacol Immunotoxicol ; 43(6): 633-643, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: covidwho-1467231

RESUMEN

The coronavirus disease-19 (COVID-19), at first, was reported in Wuhan, China, and then rapidly became pandemic throughout the world. Cytokine storm syndrome (CSS) in COVID-19 patients is associated with high levels of cytokines and chemokines that cause multiple organ failure, systemic inflammation, and hemodynamic instabilities. Acute respiratory distress syndrome (ARDS), a common complication of COVID-19, is a consequence of cytokine storm. In this regard, several drugs have been being investigated to suppress this inflammatory condition. Purinergic signaling receptors comprising of P1 adenosine and P2 purinoceptors play a critical role in inflammation. Therefore, activation or inhibition of some subtypes of these kinds of receptors is most likely to be beneficial to attenuate cytokine storm. This article summarizes suggested therapeutic drugs with potential anti-inflammatory effects through purinergic receptors.


Asunto(s)
Antiinflamatorios/uso terapéutico , Tratamiento Farmacológico de COVID-19 , Síndrome de Liberación de Citoquinas/prevención & control , Citocinas/sangre , Antagonistas Purinérgicos/uso terapéutico , Receptores Purinérgicos/efectos de los fármacos , SARS-CoV-2/efectos de los fármacos , Animales , Antiinflamatorios/efectos adversos , Biomarcadores/sangre , COVID-19/sangre , COVID-19/inmunología , COVID-19/virología , Síndrome de Liberación de Citoquinas/sangre , Síndrome de Liberación de Citoquinas/inmunología , Síndrome de Liberación de Citoquinas/virología , Interacciones Huésped-Patógeno , Humanos , Ligandos , Terapia Molecular Dirigida , Insuficiencia Multiorgánica/inmunología , Insuficiencia Multiorgánica/prevención & control , Insuficiencia Multiorgánica/virología , Antagonistas Purinérgicos/efectos adversos , Receptores Purinérgicos/metabolismo , SARS-CoV-2/inmunología , SARS-CoV-2/patogenicidad , Transducción de Señal
12.
Biosci Trends ; 15(4): 201-204, 2021 Sep 22.
Artículo en Inglés | MEDLINE | ID: covidwho-1436244

RESUMEN

Traditional Chinese medicine (TCM) is a valuable form of medicine with a long history in China. It has played a significant role in the control and prevention of infectious diseases including SARS and H7N9 flu. After the outbreak of COVID-19, China's National Health Commission included TCM in the Diagnosis and Treatment Protocol for COVID-19. During the COVID-19 pandemic, three traditional Chinese medicines (Jinhua Qinggan granules, Lianhua Qingwen medicine, and a Xuebijing Injection) and three TCM preparations (a Qingfei Paidu decoction, a Huashi Baidu decoction, and a Xuanfei Baidu decoction) have been screened for their efficacy against COVID-19. More than 150 trials involving TCMs are registered in the Chinese Clinical Trial Registry (ChiCTR), and those trials cover prevention, treatment, recovery, and illnesses diagnosed in accordance with TCM principles. TCM can effectively alleviate the symptoms of patients with COVID-19, delay the disease's progression from mild to severe or critical, and reduce severe and critical all-cause mortality. The underlying mechanisms of TCM mainly involve action against SARS-CoV-2, anti-inflammatory and immunomodulatory action, and organ protection. The current work provides a brief description of the current status of and issues with TCM to treat this novel infectious disease. The hope is that TCM can help considerably to control this global epidemic.


Asunto(s)
Tratamiento Farmacológico de COVID-19 , Medicamentos Herbarios Chinos/uso terapéutico , Antiinflamatorios/efectos adversos , Antiinflamatorios/uso terapéutico , Antivirales/efectos adversos , Antivirales/uso terapéutico , China , Ensayos Clínicos como Asunto , Medicamentos Herbarios Chinos/efectos adversos , Humanos , Medicina Tradicional China
13.
Lancet Respir Med ; 9(8): 924-932, 2021 08.
Artículo en Inglés | MEDLINE | ID: covidwho-1413874

RESUMEN

BACKGROUND: Evidence suggests a role for excessive inflammation in COVID-19 complications. Colchicine is an oral anti-inflammatory medication beneficial in gout, pericarditis, and coronary disease. We aimed to investigate the effect of colchicine on the composite of COVID-19-related death or hospital admission. METHODS: The present study is a phase 3, randomised, double-blind, adaptive, placebo-controlled, multicentre trial. The study was done in Brazil, Canada, Greece, South Africa, Spain, and the USA, and was led by the Montreal Heart Institute. Patients with COVID-19 diagnosed by PCR testing or clinical criteria who were not being treated in hospital were eligible if they were at least 40 years old and had at least one high-risk characteristic. The randomisation list was computer-generated by an unmasked biostatistician, and masked randomisation was centralised and done electronically through an automated interactive web-response system. The allocation sequence was unstratified and used a 1:1 ratio with a blocking schema and block sizes of six. Patients were randomly assigned to receive orally administered colchicine (0·5 mg twice per day for 3 days and then once per day for 27 days thereafter) or matching placebo. The primary efficacy endpoint was the composite of death or hospital admission for COVID-19. Vital status at the end of the study was available for 97·9% of patients. The analyses were done according to the intention-to-treat principle. The COLCORONA trial is registered with ClinicalTrials.gov (NCT04322682) and is now closed to new participants. FINDINGS: Trial enrolment began in March 23, 2020, and was completed in Dec 22, 2020. A total of 4488 patients (53·9% women; median age 54·0 years, IQR 47·0-61·0) were enrolled and 2235 patients were randomly assigned to colchicine and 2253 to placebo. The primary endpoint occurred in 104 (4·7%) of 2235 patients in the colchicine group and 131 (5·8%) of 2253 patients in the placebo group (odds ratio [OR] 0·79, 95·1% CI 0·61-1·03; p=0·081). Among the 4159 patients with PCR-confirmed COVID-19, the primary endpoint occurred in 96 (4·6%) of 2075 patients in the colchicine group and 126 (6·0%) of 2084 patients in the placebo group (OR 0·75, 0·57-0·99; p=0·042). Serious adverse events were reported in 108 (4·9%) of 2195 patients in the colchicine group and 139 (6·3%) of 2217 patients in the placebo group (p=0·051); pneumonia occurred in 63 (2·9%) of 2195 patients in the colchicine group and 92 (4·1%) of 2217 patients in the placebo group (p=0·021). Diarrhoea was reported in 300 (13·7%) of 2195 patients in the colchicine group and 161 (7·3%) of 2217 patients in the placebo group (p<0·0001). INTERPRETATION: In community-treated patients including those without a mandatory diagnostic test, the effect of colchicine on COVID-19-related clinical events was not statistically significant. Among patients with PCR-confirmed COVID-19, colchicine led to a lower rate of the composite of death or hospital admission than placebo. Given the absence of orally administered therapies to prevent COVID-19 complications in community-treated patients and the benefit of colchicine in patients with PCR-proven COVID-19, this safe and inexpensive anti-inflammatory agent could be considered for use in those at risk of complications. Notwithstanding these considerations, replication in other studies of PCR-positive community-treated patients is recommended. FUNDING: The Government of Quebec, the Bill & Melinda Gates Foundation, the National Heart, Lung, and Blood Institute of the US National Institutes of Health, the Montreal Heart Institute Foundation, the NYU Grossman School of Medicine, the Rudin Family Foundation, and philanthropist Sophie Desmarais.


Asunto(s)
Tratamiento Farmacológico de COVID-19 , COVID-19 , Colchicina , Administración Oral , Atención Ambulatoria/métodos , Atención Ambulatoria/estadística & datos numéricos , Antiinflamatorios/administración & dosificación , Antiinflamatorios/efectos adversos , COVID-19/diagnóstico , COVID-19/epidemiología , Colchicina/administración & dosificación , Colchicina/efectos adversos , Método Doble Ciego , Monitoreo de Drogas/métodos , Femenino , Hospitalización/estadística & datos numéricos , Humanos , Análisis de Intención de Tratar , Masculino , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud , Medición de Riesgo , SARS-CoV-2/aislamiento & purificación
14.
Clin Exp Nephrol ; 26(1): 75-85, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: covidwho-1372798

RESUMEN

BACKGROUND: Critical coronavirus disease 2019 (COVID-19) has a high fatality rate, especially in hemodialysis (HD) patients, with this poor prognosis being caused by systemic hyperinflammation; cytokine storms. Steroid pulse therapy or tocilizumab (TCZ) have insufficient inhibitory effects against cytokine storms in critical cases. This study evaluated the clinical effects and safety of combining steroid pulse therapy and TCZ. METHODS: From September 2020 to May 2021, 201 patients with COVID-19 were admitted to our hospital. Before February 2021, patients with an oxygen demand exceeding 8 L/min were intubated and treated with standard therapy (dexamethasone and antiviral therapy). After February 2021, patients underwent high-flow nasal cannula oxygen therapy and were treated with TCZ (8 mg/kg) and methylprednisolone (mPSL) (500 mg/day [≤ 75 kg], 1000 mg/day [> 75 kg]) for 3 days. We compared background characteristics, laboratory findings, and prognosis between non-HD and HD patients and between patients who received and did not receive TCZ and mPSL pulse therapy. RESULTS: Among non-HD patients, the TCZ + mPSL pulse group had significantly higher survival rates and lower secondary infection rates (p < 0.05), than the standard therapy group. All HD patients in the standard therapy group with oxygen demand exceeding 8 L/min died. Contrastingly, all patients in the TCZ + mPSL pulse group survived, with their oxygen demand decreasing to 0-1 L/min within 3 weeks post-administration. CONCLUSION: TCZ combined with mPSL pulse therapy improved the survival rate without significant adverse events in critical HD and non-HD patients with COVID-19 by strongly suppressing systemic hyperinflammation.


Asunto(s)
Antiinflamatorios/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Tratamiento Farmacológico de COVID-19 , Síndrome de Liberación de Citoquinas/prevención & control , Glucocorticoides/administración & dosificación , Enfermedades Renales/terapia , Metilprednisolona/administración & dosificación , Diálisis Renal , Adulto , Anciano , Anciano de 80 o más Años , Antiinflamatorios/efectos adversos , Anticuerpos Monoclonales Humanizados/efectos adversos , COVID-19/diagnóstico , COVID-19/inmunología , COVID-19/mortalidad , Síndrome de Liberación de Citoquinas/diagnóstico , Síndrome de Liberación de Citoquinas/inmunología , Síndrome de Liberación de Citoquinas/mortalidad , Quimioterapia Combinada , Femenino , Glucocorticoides/efectos adversos , Humanos , Enfermedades Renales/diagnóstico , Enfermedades Renales/inmunología , Enfermedades Renales/mortalidad , Masculino , Metilprednisolona/efectos adversos , Persona de Mediana Edad , Quimioterapia por Pulso , Diálisis Renal/efectos adversos , Diálisis Renal/mortalidad , Estudios Retrospectivos , Factores de Tiempo , Resultado del Tratamiento
16.
Pharmacol Res ; 157: 104849, 2020 07.
Artículo en Inglés | MEDLINE | ID: covidwho-1318926

RESUMEN

Taking anti-inflammatory drugs, including non-steroidal (NSAIDs), during Covid-19 infection, how much is risky? The French Minister of Health, who has raised an alarm on a possible risk deriving from the use of ibuprofen for the control of fever and other symptoms during the disease, opened the debate a few days ago. In this paper we examine available evidence from preclinical and clinical studies that had analysed the role of COX in the inflammatory process and the effects of NSAIDs in patients with infections. Most of the published studies that suggested not protective effects of NSAIDs were mainly performed in vitro or on animals. Therefore, their meaning in humans is to be considered with great caution. Based also on data suggesting protective effects of NSAIDs, we concluded that currently there is no evidence suggesting a correlation between NSAIDs and a worsening of infections. Further studies will be certainly needed to better define the role of NSAIDs and particularly COX2 inhibitors in patients with infections. In the meantime, we must wait for results of the revision started by the PRAC on May 2019 on the association ibuprofen/ketoprofen​​​​​​ and worsening of infections. Since nowadays no scientific evidence establishes a correlation between NSAIDS and worsening of COVID-19, patients should be advice against any NSAIDs self-medication when COVID-19 like symptoms are present.


Asunto(s)
Antiinflamatorios no Esteroideos/efectos adversos , Antiinflamatorios/efectos adversos , Infecciones por Coronavirus/tratamiento farmacológico , Neumonía Viral/tratamiento farmacológico , Virosis/tratamiento farmacológico , Animales , Antiinflamatorios/uso terapéutico , Antiinflamatorios no Esteroideos/uso terapéutico , Betacoronavirus/efectos de los fármacos , COVID-19 , Humanos , Pandemias , SARS-CoV-2
17.
Cardiovasc Toxicol ; 21(10): 781-789, 2021 10.
Artículo en Inglés | MEDLINE | ID: covidwho-1306730

RESUMEN

Since the onset of the global COVID-19 pandemic, there has been much discussion about the advantages and disadvantages of ongoing chronic drug therapies in SARS-CoV-2-positive patients. These discussions include also statins treatment. The statins are among the most widely used drugs in the global population. Statins aim to lower cholesterol, which is essential for many biological processes but can lead to heart disease if levels are too high; however, also the pleiotropic effects of statins are well known. So could the anti-inflammatory or the potential antiviral effects of statins be helpful in avoiding extreme inflammation and severity in COVID-19? To date, there are conflicting opinions on the effects of statins in the course of COVID-19 infection. The aim of this article is to describe the molecular and pharmacological basis of the pleiotropic effects of statins that could be more involved in the fight against COVID-19 infection and to investigate the current epidemiological evidence in the literature on the current and important topic.


Asunto(s)
Antiinflamatorios/uso terapéutico , Antivirales/uso terapéutico , Tratamiento Farmacológico de COVID-19 , Cardiopatías/tratamiento farmacológico , Corazón/efectos de los fármacos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , SARS-CoV-2/efectos de los fármacos , Animales , Antiinflamatorios/efectos adversos , Antivirales/efectos adversos , COVID-19/epidemiología , COVID-19/fisiopatología , COVID-19/virología , Corazón/fisiopatología , Corazón/virología , Cardiopatías/epidemiología , Cardiopatías/fisiopatología , Cardiopatías/virología , Interacciones Huésped-Patógeno , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/efectos adversos , SARS-CoV-2/patogenicidad , Resultado del Tratamiento
18.
Int J Immunopathol Pharmacol ; 35: 20587384211031763, 2021.
Artículo en Inglés | MEDLINE | ID: covidwho-1305554

RESUMEN

A recently discovered coronavirus, SARS-CoV-2, caused a global respiratory disease pandemic called COVID-19. Many studies have shown the excessive activation of the innate immune response that leads to the adverse outcomes of COVID-19, and anti-inflammatory drugs are very useful in the treatment and management of this infection. The activities of Colchicine, one of the anti-inflammatory drugs, target several pathways related to excessive inflammation of COVID-19. This study aimed to evaluate the efficacy of Colchicine in the treatment of COVID-19 using a meta-analysis approach. Scopus, Pubmed, Google scholars, Web of Science, and Science direct were used to search all the randomized controlled trials, case-control, and cross-sectional studies that have evaluated the efficacy of Colchicine as a treatment for COVID-19 (up to 28 May 2021). The overall effect of Colchicine versus the control group was determined using a random-effects model meta-analysis where we compared changes (i.e. mean differences-Colchicine group vs Control group) between the two conditions in test scores indicative of hospitalization time (day) and mortality rate. The results illustrated Colchicine therapy is associated with a decreased mortality rate in COVID-19 patients and associated with a decrease in hospitalization time (day) in COVID-19 patients. Present preliminary data shows that Colchicine has a beneficial effect on coronavirus disease care in 2019. Therefore, Colchicine can be a good suggestion in the management of COVID-19.


Asunto(s)
Antiinflamatorios/uso terapéutico , Tratamiento Farmacológico de COVID-19 , Colchicina/uso terapéutico , Antiinflamatorios/efectos adversos , COVID-19/diagnóstico , COVID-19/mortalidad , COVID-19/virología , Colchicina/efectos adversos , Mortalidad Hospitalaria , Humanos , Tiempo de Internación , Factores de Tiempo , Resultado del Tratamiento
19.
Medicine (Baltimore) ; 100(22): e25688, 2021 Jun 04.
Artículo en Inglés | MEDLINE | ID: covidwho-1257893

RESUMEN

RATIONALE: Hydroxychloroquine has excellent anti-inflammatory and immunomodulatory effects as one of the antimalarial drugs. In particular, hydroxychloroquine was once widely used as a treatment for the new coronavirus pneumonia epidemic in 2020. Retinopathy caused by hydroxychloroquine is normally irreversible, but little attention has been paid to it. PATIENT CONCERNS: A 38-year-old young Chinese woman was taking oral hydroxychloroquine 400 mg daily to control lupus disease activity for six years after the diagnosis of systemic lupus erythematosus (SLE). She did not have any history of eye disease and was admitted to the hospital with a sudden blurring of both eyes. DIAGNOSES: The diagnosis of retinal macular degeneration caused by hydroxychloroquine was made after excluding other interfering diseases based on the patient's long-term use of hydroxychloroquine and the results of the eye examination. INTERVENTIONS: The patient was discontinued from hydroxychloroquine. To control the recurrence of SLE, she was given intravenous methylprednisolone, oral tacrolimus and mycophenolate. Meanwhile, she was asked to take extra care of her eyes and to come to the hospital every three months to have her vision checked. OUTCOMES: The patient's blurred vision improved one week later. Three months later, her vision examination showed no further decline (0.4 in the right eye and 0.6 in the left eye). Meanwhile, the SLE disease activity index (SLEDAI) decreased from six points to five points currently. LESSONS: Retinopathy caused by hydroxychloroquine is irreversible and there is no particularly effective treatment. Discontinuation of hydroxychloroquine, better daily eye protection, and regular vision checks are the keys to preventing retinopathy. Although hydroxychloroquine causing retinal toxicity was mentioned several years ago, the rate and severity of retinal toxicity require further research. How to get more patients to take care of their eyes requires continuous and increased education by doctors.


Asunto(s)
Antiinflamatorios/efectos adversos , Hidroxicloroquina/efectos adversos , Lupus Eritematoso Sistémico/tratamiento farmacológico , Enfermedades de la Retina/inducido químicamente , Adulto , Antiinflamatorios/uso terapéutico , Femenino , Humanos , Hidroxicloroquina/uso terapéutico , Inmunosupresores/uso terapéutico , Agudeza Visual
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