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1.
J Med Virol ; 94(4): 1745-1747, 2022 04.
Article in English | MEDLINE | ID: covidwho-1718409

ABSTRACT

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.


Subject(s)
Anti-Inflammatory Agents/adverse effects , Bradycardia/chemically induced , COVID-19/drug therapy , Methylprednisolone/adverse effects , Antiviral Agents/adverse effects , COVID-19/diagnosis , Child , Drug Therapy, Combination/adverse effects , Humans , Indoles/adverse effects , Male , SARS-CoV-2/drug effects , SARS-CoV-2/isolation & purification , Sulfides/adverse effects
2.
JAMA Netw Open ; 4(12): e2141328, 2021 12 01.
Article in English | MEDLINE | ID: covidwho-1592856

ABSTRACT

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.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , COVID-19/therapy , Colchicine/therapeutic use , Hospitalization , Intubation, Intratracheal , Respiration, Artificial , Adrenal Cortex Hormones/therapeutic use , Adult , Aged , Anti-Inflammatory Agents/adverse effects , COVID-19/mortality , COVID-19/pathology , Colchicine/adverse effects , Female , Humans , Inflammation/drug therapy , Inflammation/etiology , Male , Middle Aged , SARS-CoV-2 , Standard of Care
3.
Pharmacol Rep ; 74(1): 229-240, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1536392

ABSTRACT

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).


Subject(s)
Anti-Inflammatory Agents/administration & dosage , Anti-Inflammatory Agents/therapeutic use , COVID-19/drug therapy , Dexamethasone/administration & dosage , Dexamethasone/therapeutic use , Adult , Aged , Anti-Inflammatory Agents/adverse effects , Dexamethasone/adverse effects , Dose-Response Relationship, Drug , Drug-Related Side Effects and Adverse Reactions/epidemiology , Female , Humans , Hyperglycemia/chemically induced , Incidence , Leukocytosis/chemically induced , Male , Middle Aged , Survival Analysis , Treatment Outcome
4.
Immunopharmacol Immunotoxicol ; 43(6): 633-643, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1467231

ABSTRACT

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.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , COVID-19/drug therapy , Cytokine Release Syndrome/prevention & control , Cytokines/blood , Purinergic Antagonists/therapeutic use , Receptors, Purinergic/drug effects , SARS-CoV-2/drug effects , Animals , Anti-Inflammatory Agents/adverse effects , Biomarkers/blood , COVID-19/blood , COVID-19/immunology , COVID-19/virology , Cytokine Release Syndrome/blood , Cytokine Release Syndrome/immunology , Cytokine Release Syndrome/virology , Host-Pathogen Interactions , Humans , Ligands , Molecular Targeted Therapy , Multiple Organ Failure/immunology , Multiple Organ Failure/prevention & control , Multiple Organ Failure/virology , Purinergic Antagonists/adverse effects , Receptors, Purinergic/metabolism , SARS-CoV-2/immunology , SARS-CoV-2/pathogenicity , Signal Transduction
6.
Biosci Trends ; 15(4): 201-204, 2021 Sep 22.
Article in English | MEDLINE | ID: covidwho-1436244

ABSTRACT

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.


Subject(s)
COVID-19/drug therapy , Drugs, Chinese Herbal/therapeutic use , Anti-Inflammatory Agents/adverse effects , Anti-Inflammatory Agents/therapeutic use , Antiviral Agents/adverse effects , Antiviral Agents/therapeutic use , China , Clinical Trials as Topic , Drugs, Chinese Herbal/adverse effects , Humans , Medicine, Chinese Traditional
7.
Lancet Respir Med ; 9(8): 924-932, 2021 08.
Article in English | MEDLINE | ID: covidwho-1413874

ABSTRACT

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.


Subject(s)
COVID-19 , Colchicine , Administration, Oral , Ambulatory Care/methods , Ambulatory Care/statistics & numerical data , Anti-Inflammatory Agents/administration & dosage , Anti-Inflammatory Agents/adverse effects , COVID-19/diagnosis , COVID-19/drug therapy , COVID-19/epidemiology , Colchicine/administration & dosage , Colchicine/adverse effects , Double-Blind Method , Drug Monitoring/methods , Female , Hospitalization/statistics & numerical data , Humans , Intention to Treat Analysis , Male , Middle Aged , Outcome Assessment, Health Care , Risk Assessment , SARS-CoV-2/isolation & purification
8.
Clin Exp Nephrol ; 26(1): 75-85, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1372798

ABSTRACT

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.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , Antibodies, Monoclonal, Humanized/therapeutic use , COVID-19/drug therapy , Cytokine Release Syndrome/prevention & control , Glucocorticoids/administration & dosage , Kidney Diseases/therapy , Methylprednisolone/administration & dosage , Renal Dialysis , Adult , Aged , Aged, 80 and over , Anti-Inflammatory Agents/adverse effects , Antibodies, Monoclonal, Humanized/adverse effects , COVID-19/diagnosis , COVID-19/immunology , COVID-19/mortality , Cytokine Release Syndrome/diagnosis , Cytokine Release Syndrome/immunology , Cytokine Release Syndrome/mortality , Drug Therapy, Combination , Female , Glucocorticoids/adverse effects , Humans , Kidney Diseases/diagnosis , Kidney Diseases/immunology , Kidney Diseases/mortality , Male , Methylprednisolone/adverse effects , Middle Aged , Pulse Therapy, Drug , Renal Dialysis/adverse effects , Renal Dialysis/mortality , Retrospective Studies , Time Factors , Treatment Outcome
10.
Pharmacol Res ; 157: 104849, 2020 07.
Article in English | MEDLINE | ID: covidwho-1318926

ABSTRACT

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.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Anti-Inflammatory Agents/adverse effects , Coronavirus Infections/drug therapy , Pneumonia, Viral/drug therapy , Virus Diseases/drug therapy , Animals , Anti-Inflammatory Agents/therapeutic use , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Betacoronavirus/drug effects , COVID-19 , Humans , Pandemics , SARS-CoV-2
11.
Cardiovasc Toxicol ; 21(10): 781-789, 2021 10.
Article in English | MEDLINE | ID: covidwho-1306730

ABSTRACT

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.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Heart Diseases/drug therapy , Heart/drug effects , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , SARS-CoV-2/drug effects , Animals , Anti-Inflammatory Agents/adverse effects , Antiviral Agents/adverse effects , COVID-19/epidemiology , COVID-19/physiopathology , COVID-19/virology , Heart/physiopathology , Heart/virology , Heart Diseases/epidemiology , Heart Diseases/physiopathology , Heart Diseases/virology , Host-Pathogen Interactions , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects , SARS-CoV-2/pathogenicity , Treatment Outcome
12.
Int J Immunopathol Pharmacol ; 35: 20587384211031763, 2021.
Article in English | MEDLINE | ID: covidwho-1305554

ABSTRACT

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.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , COVID-19/drug therapy , Colchicine/therapeutic use , Anti-Inflammatory Agents/adverse effects , COVID-19/diagnosis , COVID-19/mortality , COVID-19/virology , Colchicine/adverse effects , Hospital Mortality , Humans , Length of Stay , Time Factors , Treatment Outcome
13.
Medicine (Baltimore) ; 100(22): e25688, 2021 Jun 04.
Article in English | MEDLINE | ID: covidwho-1257893

ABSTRACT

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.


Subject(s)
Anti-Inflammatory Agents/adverse effects , Hydroxychloroquine/adverse effects , Lupus Erythematosus, Systemic/drug therapy , Retinal Diseases/chemically induced , Adult , Anti-Inflammatory Agents/therapeutic use , Female , Humans , Hydroxychloroquine/therapeutic use , Immunosuppressive Agents/therapeutic use , Visual Acuity
15.
Immunopharmacol Immunotoxicol ; 43(4): 395-409, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1246578

ABSTRACT

A global threat has emerged in 2019 due to the rapid spread of Coronavirus disease (COVID-19). As of January 2021, the number of cases worldwide reached 103 million cases and 2.22 million deaths which were confirmed as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This global pandemic galvanized the scientific community to study the causative virus (SARS-CoV2) pathogenesis, transmission, and clinical symptoms. Remarkably, the most common complication associated with this disease is the cytokine storm which is responsible for COVID-19 mortality. Thus, targeting the cytokine storm with new medications is needed to hamper COVID-19 complications where the most prominent strategy for the treatment is drug repurposing. Through this strategy, several steps are skipped especially those required for testing drug safety and thus may help in reducing the dissemination of this pandemic. Accordingly, the aim of this review is to outline the pathogenesis, clinical features, and immune complications of SARS-CoV2 in addition to suggesting several repurposed drugs with their plausible mechanism of action for possible management of severe COVID-19 cases.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , COVID-19/drug therapy , Cytokine Release Syndrome/drug therapy , Cytokines/antagonists & inhibitors , Drug Repositioning , SARS-CoV-2/pathogenicity , Animals , Anti-Inflammatory Agents/adverse effects , COVID-19/immunology , COVID-19/virology , Cytokine Release Syndrome/immunology , Cytokine Release Syndrome/virology , Cytokines/immunology , Host-Pathogen Interactions , Humans , SARS-CoV-2/immunology
16.
Epilepsy Res ; 174: 106675, 2021 08.
Article in English | MEDLINE | ID: covidwho-1233420

ABSTRACT

In regard to the global pandemic of COVID-19, it seems that persons with epilepsy (PWE) are not more vulnerable to get infected by SARS-CoV-2, nor are they more susceptible to a critical course of the disease. However, management of acute seizures in patients with COVID-19 as well as management of PWE and COVID-19 needs to consider potential drug-drug interactions between antiseizure drugs and candidate drugs currently assessed as therapeutic options for COVID-19. Repurposing of several licensed and investigational drugs is discussed for therapeutic management of COVID-19. While for none of these approaches, efficacy and tolerability has been confirmed yet in sufficiently powered and controlled clinical studies, testing is ongoing with multiple clinical trials worldwide. Here, we have summarized the possible mechanisms of action of drugs currently considered as potential therapeutic options for COVID-19 management along with possible and confirmed drug-drug interactions that should be considered for a combination of antiseizure drugs and COVID-19 candidate drugs. Our review suggests that potential drug-drug interactions should be taken into account with drugs such as chloroquine/hydroxychloroquine and lopinavir/ritonavir while remdesivir and tocilizumab may be less prone to clinically relevant interactions with ASMs.


Subject(s)
Anti-Inflammatory Agents/adverse effects , Anticonvulsants/adverse effects , Antiviral Agents/adverse effects , COVID-19/drug therapy , Enzyme Inhibitors/adverse effects , Epilepsy/drug therapy , Adenosine Monophosphate/adverse effects , Adenosine Monophosphate/analogs & derivatives , Alanine/adverse effects , Alanine/analogs & derivatives , Amides/adverse effects , Antibodies, Monoclonal, Humanized/adverse effects , COVID-19/complications , Chloroquine/adverse effects , Cytochrome P-450 CYP3A Inducers/adverse effects , Dexamethasone/adverse effects , Drug Combinations , Drug Interactions , Epilepsy/complications , Glucocorticoids/adverse effects , Humans , Hydroxychloroquine/adverse effects , Interleukin 1 Receptor Antagonist Protein/adverse effects , Ivermectin/adverse effects , Lopinavir , Pyrazines/adverse effects , Ritonavir , SARS-CoV-2
17.
Nat Rev Cardiol ; 18(9): 666-682, 2021 09.
Article in English | MEDLINE | ID: covidwho-1220034

ABSTRACT

Thrombosis is the most feared complication of cardiovascular diseases and a main cause of death worldwide, making it a major health-care challenge. Platelets and the coagulation cascade are effectively targeted by antithrombotic approaches, which carry an inherent risk of bleeding. Moreover, antithrombotics cannot completely prevent thrombotic events, implicating a therapeutic gap due to a third, not yet adequately addressed mechanism, namely inflammation. In this Review, we discuss how the synergy between inflammation and thrombosis drives thrombotic diseases. We focus on the huge potential of anti-inflammatory strategies to target cardiovascular pathologies. Findings in the past decade have uncovered a sophisticated connection between innate immunity, platelet activation and coagulation, termed immunothrombosis. Immunothrombosis is an important host defence mechanism to limit systemic spreading of pathogens through the bloodstream. However, the aberrant activation of immunothrombosis in cardiovascular diseases causes myocardial infarction, stroke and venous thromboembolism. The clinical relevance of aberrant immunothrombosis, referred to as thromboinflammation, is supported by the increased risk of cardiovascular events in patients with inflammatory diseases but also during infections, including in COVID-19. Clinical trials in the past 4 years have confirmed the anti-ischaemic effects of anti-inflammatory strategies, backing the concept of a prothrombotic function of inflammation. Targeting inflammation to prevent thrombosis leaves haemostasis mainly unaffected, circumventing the risk of bleeding associated with current approaches. Considering the growing number of anti-inflammatory therapies, it is crucial to appreciate their potential in covering therapeutic gaps in cardiovascular diseases.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , Blood Coagulation/drug effects , Fibrinolytic Agents/therapeutic use , Immune System/drug effects , Inflammation Mediators/antagonists & inhibitors , Inflammation/drug therapy , Thrombosis/prevention & control , Anti-Inflammatory Agents/adverse effects , COVID-19/blood , COVID-19/immunology , Fibrinolytic Agents/adverse effects , Humans , Immune System/immunology , Immune System/metabolism , Inflammation/blood , Inflammation/immunology , Inflammation Mediators/metabolism , Risk Assessment , Risk Factors , Signal Transduction , Thrombosis/blood , Thrombosis/immunology
18.
Expert Rev Clin Immunol ; 17(6): 601-618, 2021 06.
Article in English | MEDLINE | ID: covidwho-1193644

ABSTRACT

INTRODUCTION: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces a dysregulated hyperinflammatory response. AREAS COVERED: Authors review evidence on IL-6 and IL-6 blockade in coronavirus disease 2019 (COVID-19) and discuss the pathophysiological and prognostic roles of this cytokine and the clinical impact of pharmacological blockade of IL-6 . The material includes original articles and reviews published from March 2020 to March 2021 and searched on PubMed, medRxiv, and bioRxiv. EXPERT OPINION: IL-6 is one of the most prominent pro-inflammatory cytokines. Increased levels are recorded in COVID-19 patients, especially those with severe-to-critical disease. Evidence is accumulating on the relevance of IL-6 as a prognostic marker in COVID-19. Since IL-6 is a druggable target for several inflammatory diseases, pharmacological blockers of the IL-6 signaling pathway were repurposed to blunt the abnormal SARS-CoV-2-induced cytokine release. Data are limited to few randomized controlled trials that reported encouraging, though not conclusive, results, indicating the usefulness of IL-6 blockade early in the course of the disease in patients with hyperinflammation and no or limited organ damage. Further research is warranted to explore the role of IL-6 in different COVID-19 phenotypes and identify subgroups of patients who may mostly benefit from IL-6 pathway inhibition.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , COVID-19/drug therapy , Interleukin-6/antagonists & inhibitors , Receptors, Interleukin-6/antagonists & inhibitors , SARS-CoV-2/pathogenicity , Animals , Anti-Inflammatory Agents/adverse effects , COVID-19/immunology , COVID-19/virology , Host-Pathogen Interactions , Humans , Interleukin-6/metabolism , Receptors, Interleukin-6/metabolism , SARS-CoV-2/immunology , Signal Transduction , Treatment Outcome
20.
Drug Des Devel Ther ; 15: 1345-1356, 2021.
Article in English | MEDLINE | ID: covidwho-1171843

ABSTRACT

The coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), continues to spread around the world. While prophylactic vaccines against SARS-CoV-2 are making great progress, there is still a need to explore safe and effective therapies with biological products for COVID-19. Currently clinical trial efforts are planned and ongoing using different biological agents for anti-inflammatory therapies, immunomodulation, and therapeutic repair in COVID-19. Targeting inflammatory cytokines with antibodies or inhibitors may be an urgent therapeutic strategy for COVID-19. Importantly, it is critical for an in-depth understanding of these new clinical therapeutic agents in their conditions that are probably involved in both physiological and pathological host responses. In this article, we analyze the potential implications for the current clinical trials of therapeutic biologics and address issues for the development of the COVID-19-related biological therapies.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , Biological Products/therapeutic use , COVID-19/drug therapy , Cytokines/antagonists & inhibitors , Immunologic Factors/therapeutic use , SARS-CoV-2/immunology , Anti-Inflammatory Agents/adverse effects , Biological Products/adverse effects , COVID-19/diagnosis , COVID-19/immunology , COVID-19/virology , Clinical Trials as Topic , Cytokines/immunology , Host-Pathogen Interactions , Humans , Immunologic Factors/adverse effects , Molecular Targeted Therapy , SARS-CoV-2/pathogenicity , Treatment Outcome
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