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1.
Lancet Respir Med ; 9(5): 533-544, 2021 05.
Article in English | MEDLINE | ID: covidwho-1931217

ABSTRACT

Cough is one of the most common presenting symptoms of COVID-19, along with fever and loss of taste and smell. Cough can persist for weeks or months after SARS-CoV-2 infection, often accompanied by chronic fatigue, cognitive impairment, dyspnoea, or pain-a collection of long-term effects referred to as the post-COVID syndrome or long COVID. We hypothesise that the pathways of neurotropism, neuroinflammation, and neuroimmunomodulation through the vagal sensory nerves, which are implicated in SARS-CoV-2 infection, lead to a cough hypersensitivity state. The post-COVID syndrome might also result from neuroinflammatory events in the brain. We highlight gaps in understanding of the mechanisms of acute and chronic COVID-19-associated cough and post-COVID syndrome, consider potential ways to reduce the effect of COVID-19 by controlling cough, and suggest future directions for research and clinical practice. Although neuromodulators such as gabapentin or opioids might be considered for acute and chronic COVID-19 cough, we discuss the possible mechanisms of COVID-19-associated cough and the promise of new anti-inflammatories or neuromodulators that might successfully target both the cough of COVID-19 and the post-COVID syndrome.


Subject(s)
COVID-19/complications , COVID-19/physiopathology , Cough/etiology , Inflammation/etiology , Nervous System Diseases/etiology , Neuroimmunomodulation , Cough/physiopathology , Humans , Inflammation/physiopathology , Nervous System Diseases/physiopathology , SARS-CoV-2 , Syndrome
2.
Life Sci ; 284: 119201, 2021 Nov 01.
Article in English | MEDLINE | ID: covidwho-1574805

ABSTRACT

BACKGROUND: Cytokine storm is the exaggerated immune response often observed in viral infections. It is also intimately linked with the progression of COVID-19 disease as well as associated complications and mortality. Therefore, targeting the cytokine storm might help in reducing COVID-19-associated health complications. The number of COVID-19 associated deaths (as of January 15, 2021; https://www.worldometers.info/coronavirus/) in the USA is high (1199/million) as compared to countries like India (110/million). Although the reason behind this is not clear, spices may have some role in explaining this difference. Spices and herbs are used in different traditional medicines, especially in countries such as India to treat various chronic diseases due to their potent antioxidant and anti-inflammatory properties. AIM: To evaluate the literature available on the anti-inflammatory properties of spices which might prove beneficial in the prevention and treatment of COVID-19 associated cytokine storm. METHOD: A detailed literature search has been conducted on PubMed for collecting information pertaining to the COVID-19; the history, origin, key structural features, and mechanism of infection of SARS-CoV-2; the repurposed drugs in use for the management of COVID-19, and the anti-inflammatory role of spices to combat COVID-19 associated cytokine storm. KEY FINDINGS: The literature search resulted in numerous in vitro, in vivo and clinical trials that have reported the potency of spices to exert anti-inflammatory effects by regulating crucial molecular targets for inflammation. SIGNIFICANCE: As spices are derived from Mother Nature and are inexpensive, they are relatively safer to consume. Therefore, their anti-inflammatory property can be exploited to combat the cytokine storm in COVID-19 patients. This review thus focuses on the current knowledge on the role of spices for the treatment of COVID-19 through suppression of inflammation-linked cytokine storm.


Subject(s)
COVID-19/pathology , Cytokines/metabolism , Inflammation/pathology , Spices , COVID-19/epidemiology , COVID-19/virology , Cytokine Release Syndrome/pathology , Humans , SARS-CoV-2/physiology
3.
Mediterr J Rheumatol ; 31(Suppl 2): 295-297, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-1539055

ABSTRACT

Patients with various inflammatory diseases of the gastrointestinal tract, skin, liver, kidneys, and musculoskeletal system-connective tissues, often undergo different anti-inflammatory therapies to maintain remission and avoid serious and/or life-threatening complications. Available data so far show an increased rate of hospitalization in such patients during the COVID19 pandemic. The key points of our position statement are summarized below: Patients with inflammatory diseases who receive moderate or high-risk anti-inflammatory therapies might be considered as an increased risk group for severe COVID-19 and appropriate measures should be taken in order to protect them. Initiation of immuno-suppressive/modulatory therapies should be done with caution, taking into account the severity of the underlying inflammatory disease, the type of anti-inflammatory treatment, and the risk of exposure to the SARS-CoV-2 virus. Discontinuation of anti-inflammatory therapies in patients who have not been exposed to or infected with the SARS-CoV-2 virus is not recommended. In patients who become infected with SARS-CoV-2, anti-inflammatory therapies should be discontinued, except in special cases. Specialty physicians should actively participate in the Interdisciplinary Teams caring for patients with inflammatory diseases during COVID19 infection.

4.
Lancet Respir Med ; 9(5): 533-544, 2021 05.
Article in English | MEDLINE | ID: covidwho-1537202

ABSTRACT

Cough is one of the most common presenting symptoms of COVID-19, along with fever and loss of taste and smell. Cough can persist for weeks or months after SARS-CoV-2 infection, often accompanied by chronic fatigue, cognitive impairment, dyspnoea, or pain-a collection of long-term effects referred to as the post-COVID syndrome or long COVID. We hypothesise that the pathways of neurotropism, neuroinflammation, and neuroimmunomodulation through the vagal sensory nerves, which are implicated in SARS-CoV-2 infection, lead to a cough hypersensitivity state. The post-COVID syndrome might also result from neuroinflammatory events in the brain. We highlight gaps in understanding of the mechanisms of acute and chronic COVID-19-associated cough and post-COVID syndrome, consider potential ways to reduce the effect of COVID-19 by controlling cough, and suggest future directions for research and clinical practice. Although neuromodulators such as gabapentin or opioids might be considered for acute and chronic COVID-19 cough, we discuss the possible mechanisms of COVID-19-associated cough and the promise of new anti-inflammatories or neuromodulators that might successfully target both the cough of COVID-19 and the post-COVID syndrome.


Subject(s)
COVID-19/complications , COVID-19/physiopathology , Cough/etiology , Inflammation/etiology , Nervous System Diseases/etiology , Neuroimmunomodulation , Cough/physiopathology , Humans , Inflammation/physiopathology , Nervous System Diseases/physiopathology , SARS-CoV-2 , Syndrome
5.
Acta Anaesthesiol Scand ; 65(10): 1505-1513, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1455490

ABSTRACT

BACKGROUND: Multimodal analgesia is the leading principle for managing postoperative pain. Recent guidelines recommend combinations of paracetamol and a non-steroidal anti-inflammatory drug (NSAID) for most surgeries. Glucocorticoids have been used for decades due to their potent anti-inflammatory and antipyretic properties. Subsequently, glucocorticoids may improve postoperative analgesia. We will perform a systematic review to assess benefits and harms of adding glucocorticoids to paracetamol and NSAIDs. We expect to uncover pros and cons of the addition of glucocorticoid to the basic standard regimen of paracetamol and NSAIDs for postoperative analgesia. METHOD: This protocol for a systematic review was written according to the The Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidelines. We will search for trials in the following electronic databases: Medline, CENTRAL, CDSR and Embase. Two authors will independently screen trials for inclusion using Covidence, extract data and assess risk of bias using Cochrane's ROB 2 tool. We will analyse data using Review Manager and Trial Sequential Analysis. Meta-analysis will be performed according to the Cochrane guidelines and results will be validated according to the eight-step procedure suggested by Jakobsen et al We will present our primary findings in a 'summary of findings' table. We will evaluate the overall certainty of evidence using the GRADE approach. DISCUSSION: This review will aim to explore the combination of glucocorticoids together with paracetamol and NSAIDs for postoperative pain. We will attempt to provide reliable evidence regarding the role of glucocorticoids as part of a multimodal analgesic regimen in combination with paracetamol and NSAID.


Subject(s)
Acetaminophen , Pharmaceutical Preparations , Acetaminophen/therapeutic use , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Glucocorticoids , Humans , Meta-Analysis as Topic , Pain, Postoperative/drug therapy , Systematic Reviews as Topic
6.
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
7.
Br J Pharmacol ; 178(19): 3864-3868, 2021 10.
Article in English | MEDLINE | ID: covidwho-1402887

ABSTRACT

Sepsis induced by bacteria or viruses can result in multiorgan dysfunction, which is a major cause of death in intensive care units. Current treatments are only supportive, and there are no treatments that reverse the pathophysiological effects of sepsis. Vitamin C has antioxidant, anti-inflammatory, anticoagulant and immune modulatory actions, so it is a rational treatment for sepsis. Here, we summarise data that support the use of megadose vitamin C as a treatment for sepsis and COVID-19. Megadose intravenous sodium ascorbate (150 g per 40 kg over 7 h) dramatically improved the clinical state and cardiovascular, pulmonary, hepatic and renal function and decreased body temperature, in a clinically relevant ovine model of Gram-negative bacteria-induced sepsis. In a critically ill COVID-19 patient, intravenous sodium ascorbate (60 g) restored arterial pressure, improved renal function and increased arterial blood oxygen levels. These findings suggest that megadose vitamin C should be trialled as a treatment for sepsis and COVID-19.


Subject(s)
COVID-19 , Sepsis , Animals , Ascorbic Acid , Humans , Multiple Organ Failure/drug therapy , SARS-CoV-2 , Sepsis/drug therapy , Sheep
8.
Cureus ; 13(1): e12534, 2021 Jan 06.
Article in English | MEDLINE | ID: covidwho-1389784

ABSTRACT

SARS-CoV-2 infection presents with predominant respiratory illness. Cardiac injury has been reported in patients with SARS-CoV-2 infection. The spectrum of cardiac involvement ranges from pericarditis to myocarditis. Acute pericarditis attributed to SARS-CoV-2 is rare. A 68-year-old male with co-morbid condition of hypertension and arthritis presented with chest tightness, cough and exertional shortness of breath for five days. He was tachycardic at the time of presentation and cardiac auscultation was positive for pericardial rub. His room air oxygen saturation was 95%. Chest imaging studies revealed bilateral infiltrate. His electrocardiogram showed ST elevation with diffusely elevated J point in lead II, III, aVF and V4-V6. Echocardiogram was unrevealing for pericardial effusion and left ventricular ejection fraction was normal. Serial troponin level did not reveal a rising trend. The nasopharyngeal swab was positive for SARS-CoV-2 RNA. Nonsteroidal anti-inflammatory drugs (NSAIDs) use in SARS-CoV-2 positive patient is debatable. The patient had acute pericarditis due to SARS-CoV-2 and it was treated with high dose aspirin with colchicine. Acute pericarditis is a rare complication of SARS-CoV-2 infection and can be managed with aspirin and colchicine.

9.
Brief Bioinform ; 22(2): 1279-1290, 2021 03 22.
Article in English | MEDLINE | ID: covidwho-1343635

ABSTRACT

OBJECTIVES: Patients with colorectal cancer (CRC) may be susceptible to the coronavirus disease-2019 (COVID-19). However, anti-CRC/COVID-19 treatment options are currently unavailable. Since niacin is a vitamin with cytoprotective and anti-inflammatory functions, this study aimed to evaluate the possible functional roles and underlying mechanisms of action of niacin as an anti-COVID-19 and -CRC therapy. INTERVENTIONS: We used a series of network pharmacology-based and computational analyses to understand and characterize the binding capacity, biological functions, pharmacological targets and therapeutic mechanisms of niacin in CRC/COVID-19. MEASUREMENTS AND MAIN RESULTS: We revealed the clinical characteristics of CRC patients and COVID-19 patients, including predisposing genes, survival rate and prognosis. Moreover, the results of molecular docking analysis indicated that niacin exerted effective binding capacity in COVID-19. Further, we disclosed the targets, biological functions and signaling pathways of niacin in CRC/COVID-19. The analysis indicated that niacin could help in treating CRC/COVID-19 through cytoprotection, enhancement of immunologic functions, inhibition of inflammatory reactions and regulation of cellular microenvironment. Furthermore, five core pharmacological targets of niacin in CRC/COVID-19 were also identified, including BCL2L1, PTGS2, IL1B, IFNG and SERPINE1. CONCLUSIONS: This study, for the first time, revealed the niacin-associated molecular functions and pharmacological targets for treating CRC/COVID-19, as COVID-19 remains a serious pandemic. But the findings were not validated in actual CRC patients infected with COVID-19, so further investigation is needed to confirm the potential use of niacin for treating CRC/COVID-19.


Subject(s)
COVID-19/drug therapy , Computational Biology , Niacin/therapeutic use , SARS-CoV-2/drug effects , Aged , COVID-19/virology , Colorectal Neoplasms/genetics , Female , Humans , Male , Middle Aged , Molecular Docking Simulation , Niacin/pharmacology
10.
J Cardiovasc Med (Hagerstown) ; 22(9): 693-700, 2021 09 01.
Article in English | MEDLINE | ID: covidwho-1339455

ABSTRACT

AIMS: We performed a systematic review to summarize the clinical features, diagnostic methods, treatment, and outcomes of coronavirus disease 2019 (COVID-19) patients with pericarditis. METHODS: We searched electronic databases from inception to 17 December 2020. Studies that reported clinical data on patients with COVID-19 and pericarditis were included. Descriptive statistics were used for categorical and continuous variables [mean ±â€Šstandard deviation or median (interquartile range)]. As an exploratory analysis, differences between patients with acute pericarditis and myopericarditis were compared. RESULTS: A total of 33 studies (32 case reports and 1 case series) involving 34 patients were included. The mean age was 51.6 ±â€Š19.5 years and 62% of patients were men. Sixty-two percentage of patients were diagnosed with myopericarditis. The most frequent electrocardiographic pattern (56%) was diffuse ST-elevation and PR depression. Pericardial effusion and cardiac tamponade were reported in 76 and 35% of cases, respectively. The median values of C-reactive protein [77 mg/dl (12-177)] and white blood cells [12 335 cells/µl (5625-16 500)] were above the normal range. Thirty-eight percent and 53% of patients were treated with nonsteroidal anti-inflammatory drugs (NSAIDs) and colchicine, respectively. These drugs were more frequently used in patients with acute pericarditis compared with myopericarditis. The in-hospital mortality was 6% without a significant difference between both groups. CONCLUSION: Our review shows that COVID-19 patients with pericarditis had similar clinical features to other viral cardiotropic infections. However, NSAIDs and colchicine were used in half or less of the cases. Overall, the short-term prognosis was good across groups.


Subject(s)
COVID-19 , Patient Care Management , Pericarditis , COVID-19/complications , COVID-19/epidemiology , COVID-19/physiopathology , COVID-19/therapy , Case-Control Studies , Female , Humans , Male , Middle Aged , Patient Care Management/methods , Patient Care Management/statistics & numerical data , Pericarditis/diagnosis , Pericarditis/drug therapy , Pericarditis/etiology , Pericarditis/physiopathology , Prognosis , SARS-CoV-2/isolation & purification
11.
Pharmacol Res ; 158: 104939, 2020 08.
Article in English | MEDLINE | ID: covidwho-1318941

ABSTRACT

The Coronavirus Disease 2019 (COVID-19) has been declared as a global pandemic, but specific medicines and vaccines are still being developed. In China, interventional therapies with traditional Chinese medicine for COVID-19 have achieved significant clinical efficacies, but the underlying pharmacological mechanisms are still unclear. This article reviewed the etiology of COVID-19 and clinical efficacy. Both network pharmacological study and literature search were used to demonstrate the possible action mechanisms of Chinese medicines in treating COVID-19. We found that Chinese medicines played the role of antivirus, anti-inflammation and immunoregulation, and target organs protection in the management of COVID-19 by multiple components acting on multiple targets at multiple pathways. AEC2 and 3CL protein could be the direct targets for inhibiting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Quercetin, kaempferol, luteolin, isorhamnetin, baicalein, naringenin, and wogonin could be the main active ingredients of Chinese medicines for the management of COVID-19 by targeting on AEC2 and 3CL protein and inhibiting inflammatory mediators, regulating immunity, and eliminating free radicals through COX-2, CASP3, IL-6, MAPK1, MAPK14, MAPK8, and REAL in the signaling pathways of IL-17, arachidonic acid, HIF-1, NF-κB, Ras, and TNF. This study may provide meaningful and useful information on further research to investigate the action mechanisms of Chinese medicines against SARS-CoV-2 and also provide a basis for sharing the "China scheme" for COVID-19 treatment.


Subject(s)
Betacoronavirus/drug effects , Coronavirus Infections/drug therapy , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/therapeutic use , Phytotherapy , Pneumonia, Viral/drug therapy , COVID-19 , Humans , Models, Biological , Pandemics , SARS-CoV-2
12.
Pharmacol Res ; 158: 104904, 2020 08.
Article in English | MEDLINE | ID: covidwho-1318936

ABSTRACT

The anti-malarial drugs chloroquine (CQ) and primarily the less toxic hydroxychloroquine (HCQ) are currently used to treat autoimmune diseases for their immunomodulatory and anti-thrombotic properties. They have also been proposed for the treatment of several viral infections, due to their anti-viral effects in cell cultures and animal models, and, currently, for the treatment of coronavirus disease 2019 (COVID-19), the pandemic severe acute respiratory syndrome caused by coronavirus 2 (Sars-Cov-2) infection that is spreading all over the world. Although in some recent studies a clinical improvement in COVID-19 patients has been observed, the clinical efficacy of CQ and HCQ in COVID-19 has yet to be proven with randomized controlled studies, many of which are currently ongoing, also considering pharmacokinetics, optimal dosing regimen, therapeutic level and duration of treatment and taking into account patients with different severity degrees of disease. Here we review what is currently known on the mechanisms of action of CQ and HCQ as anti-viral, anti-inflammatory and anti-thrombotic drugs and discuss the up-to-date experimental evidence on the potential mechanisms of action of CQ/HCQ in Sars-Cov2 infection and the current clinical knowledge on their efficacy in the treatment of COVID-19 patients. Given the role of iron in several human viral infections, we also propose a different insight into a number of CQ and HCQ pharmacological effects, suggesting a potential involvement of iron homeostasis in Sars-Cov-2 infection and COVID-19 clinical course.


Subject(s)
Betacoronavirus/drug effects , Chloroquine/pharmacology , Chloroquine/therapeutic use , Coronavirus Infections/drug therapy , Homeostasis/drug effects , Hydroxychloroquine/pharmacology , Hydroxychloroquine/therapeutic use , Iron/metabolism , Pneumonia, Viral/drug therapy , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , COVID-19 , Coronavirus Infections/metabolism , Humans , Pandemics , Pneumonia, Viral/metabolism , SARS-CoV-2
13.
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
14.
Acta Neuropsychiatr ; 33(4): 165-177, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1297283

ABSTRACT

Neuropsychiatric sequalae to coronavirus disease 2019 (COVID-19) infection are beginning to emerge, like previous Spanish influenza and severe acute respiratory syndrome episodes. Streptococcal infection in paediatric patients causing obsessive compulsive disorder (PANDAS) is another recent example of an infection-based psychiatric disorder. Inflammation associated with neuropsychiatric disorders has been previously reported but there is no standard clinical management approach established. Part of the reason is that it is unclear what factors determine the specific neuronal vulnerability and the efficacy of anti-inflammatory treatment in neuroinflammation. The emerging COVID-19 data suggested that in the acute stage, widespread neuronal damage appears to be the result of abnormal and overactive immune responses and cytokine storm is associated with poor prognosis. It is still too early to know if there are long-term-specific neuronal or brain regional damages associated with COVID-19, resulting in distinct neuropsychiatric disorders. In several major psychiatric disorders where neuroinflammation is present, patients with abnormal inflammatory markers may also experience less than favourable response or treatment resistance when standard treatment is used alone. Evidence regarding the benefits of co-administered anti-inflammatory agents such as COX-2 inhibitor is encouraging in selected patients though may not benefit others. Disease-modifying therapies are increasingly being applied to neuropsychiatric diseases characterised by abnormal or hyperreactive immune responses. Adjunct anti-inflammatory treatment may benefit selected patients and is definitely an important component of clinical management in the presence of neuroinflammation.


Subject(s)
Autoimmune Diseases/psychology , COVID-19/psychology , Obsessive-Compulsive Disorder/psychology , Streptococcal Infections/psychology , Anti-Inflammatory Agents/therapeutic use , Autoimmune Diseases/epidemiology , Autoimmune Diseases/immunology , COVID-19/complications , COVID-19/diagnosis , COVID-19/epidemiology , Cyclooxygenase 2 Inhibitors/therapeutic use , Cytokine Release Syndrome/complications , Cytokine Release Syndrome/immunology , Cytokine Release Syndrome/mortality , Female , Humans , Inflammation/complications , Inflammation/immunology , Inflammation/psychology , Obsessive-Compulsive Disorder/epidemiology , Obsessive-Compulsive Disorder/etiology , Obsessive-Compulsive Disorder/immunology , SARS-CoV-2/genetics , Streptococcal Infections/complications , Streptococcal Infections/epidemiology , Streptococcal Infections/immunology
15.
Curr Pharm Biotechnol ; 22(10): 1315-1324, 2021.
Article in English | MEDLINE | ID: covidwho-1290817

ABSTRACT

BACKGROUND: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the causative agent of the current pandemic of Coronavirus Disease-2019 (COVID-19). The progression of COVID-19 is related to an excessive host inflammatory immune response to SARS-CoV-2 infection, which is considered a major cause of disease severity and death. Dysregulated immune response produces huge amounts of pro-inflammatory cytokines and chemokines called "cytokine storm". Moreover, the activation of microthrombi formation plays an important role in multiple organ failure. METHODS: Keeping into consideration the potent anti-inflammatory activity of black seed and its major constituent Thymoquinone (TQ), we hypothesize their potential implication in the treatment of COVID-19 patients. A literature search was performed in PubMed, ScienceDirect, Google Scholar and Scopus electronic databases using the terms, including black seed, N. sativa, thymoquinone, SARSCoV- 2, COVID-19 and inflammatory immune response. RESULTS: Various studies confirmed that Black seed and TQ reduced the thrombus formation, the expression of tissue factor and the immune activation. Furthermore, TQ demonstrated the broad-spectrum antimicrobial activity that may be effective in controlling the secondary infections in COVID-19 patients. CONCLUSION: Keeping into consideration the multi-targeting nature of the black seed and TQ, they may be used as a potential therapeutic formulation or as an adjunct therapy in the treatment of COVID-19 patients.


Subject(s)
COVID-19 , Benzoquinones , Cytokines , Humans , SARS-CoV-2 , Seeds
17.
JACC Case Rep ; 3(4): 550-554, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-1100718

ABSTRACT

A 4-year-old boy with multisystem inflammatory syndrome in children before widespread recognition of this disease developed complications, including coronary artery aneurysm, without anti-inflammatory treatment. With delayed treatment, all sequelae resolved. This case demonstrates a natural history supporting the role of anti-inflammatory treatment even with delayed or equivocal diagnosis. (Level of Difficulty: Intermediate.).

18.
Brief Bioinform ; 22(6)2021 11 05.
Article in English | MEDLINE | ID: covidwho-1266105

ABSTRACT

Recent studies have demonstrated that the excessive inflammatory response is an important factor of death in coronavirus disease 2019 (COVID-19) patients. In this study, we propose a deep representation on heterogeneous drug networks, termed DeepR2cov, to discover potential agents for treating the excessive inflammatory response in COVID-19 patients. This work explores the multi-hub characteristic of a heterogeneous drug network integrating eight unique networks. Inspired by the multi-hub characteristic, we design 3 billion special meta paths to train a deep representation model for learning low-dimensional vectors that integrate long-range structure dependency and complex semantic relation among network nodes. Based on the representation vectors and transcriptomics data, we predict 22 drugs that bind to tumor necrosis factor-α or interleukin-6, whose therapeutic associations with the inflammation storm in COVID-19 patients, and molecular binding model are further validated via data from PubMed publications, ongoing clinical trials and a docking program. In addition, the results on five biomedical applications suggest that DeepR2cov significantly outperforms five existing representation approaches. In summary, DeepR2cov is a powerful network representation approach and holds the potential to accelerate treatment of the inflammatory responses in COVID-19 patients. The source code and data can be downloaded from https://github.com/pengsl-lab/DeepR2cov.git.


Subject(s)
COVID-19/drug therapy , Drug Repositioning , Inflammation/drug therapy , SARS-CoV-2/drug effects , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/therapeutic use , COVID-19/complications , COVID-19/genetics , COVID-19/virology , Computational Biology , Deep Learning , Humans , Inflammation/complications , Inflammation/genetics , Inflammation/virology , Neural Networks, Computer , SARS-CoV-2/pathogenicity , Software , Transcriptome/drug effects , Transcriptome/genetics
19.
J Nanobiotechnology ; 19(1): 173, 2021 Jun 10.
Article in English | MEDLINE | ID: covidwho-1266489

ABSTRACT

BACKGROUND: The worldwide pandemic of COVID-19 remains a serious public health menace as the lack of efficacious treatments. Cytokine storm syndrome (CSS) characterized with elevated inflammation and multi-organs failure is closely correlated with the bad outcome of COVID-19. Hence, inhibit the process of CSS by controlling excessive inflammation is considered one of the most promising ways for COVID-19 treatment. RESULTS: Here, we developed a biomimetic nanocarrier based drug delivery system against COVID-19 via anti-inflammation and antiviral treatment simultaneously. Firstly, lopinavir (LPV) as model antiviral drug was loaded in the polymeric nanoparticles (PLGA-LPV NPs). Afterwards, macrophage membranes were coated on the PLGA-LPV NPs to constitute drugs loaded macrophage biomimetic nanocarriers (PLGA-LPV@M). In the study, PLGA-LPV@M could neutralize multiple proinflammatory cytokines and effectively suppress the activation of macrophages and neutrophils. Furthermore, the formation of NETs induced by COVID-19 patients serum could be reduced by PLGA-LPV@M as well. In a mouse model of coronavirus infection, PLGA-LPV@M exhibited significant targeted ability to inflammation sites, and superior therapeutic efficacy in inflammation alleviation and tissues viral loads reduction. CONCLUSION: Collectively, such macrophage biomimetic nanocarriers based drug delivery system showed favorable anti-inflammation and targeted antiviral effects, which may possess a comprehensive therapeutic value in COVID-19 treatment.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Antiviral Agents/pharmacology , Biomimetics , COVID-19/drug therapy , Cytokine Release Syndrome/prevention & control , Drug Carriers , Inflammation/prevention & control , Nanoparticles , SARS-CoV-2/drug effects , COVID-19/virology , Cytokine Release Syndrome/etiology , Humans , Inflammation/complications , SARS-CoV-2/isolation & purification
20.
Expert Rev Anti Infect Ther ; 20(1): 17-21, 2022 01.
Article in English | MEDLINE | ID: covidwho-1258702

ABSTRACT

INTRODUCTION: Mediators of immunity and inflammation are playing a crucial role in COVID-19 pathogenesis and complications as demonstrated by several genetic and clinical studies. Thus, repurposing of drugs that possess anti-inflammatory and/or immune-modulatory effects for COVID-19 is considered a rational approach. AREAS COVERED: We analyze selected studies that correlated COVID-19 with dysregulated interferon and inflammatory responses while reflecting on our academic and real-life experience using non-steroidal anti-inflammatory drugs, nitazoxanide and azithromycin for management of COVID-19. Moreover, we interpret the results that suggested a potential survival benefit of low-dose aspirin and colchicine when used for COVID-19. EXPERT OPINION: Nitazoxanide/azithromycin combination has been first hypothesized by the author and practiced by him and several researchers to benefit COVID-19 patients due to a potential ability to augment the natural interferon response as well as their positive immunomodulatory effects on several cytokines. Furthermore, NSAIDs, that are unfortunately currently at best of second choice after paracetamol, have been early postulated and clinically practiced by the author to prevent or ameliorate COVID-19 complications and mortality due to their anti-inflammatory and immunomodulatory properties. Finally, we repeat our previous call to adopt our observational study that used these drugs in sufficiently powered double blind randomized clinical trials.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Azithromycin/therapeutic use , COVID-19/drug therapy , COVID-19/immunology , Cytokine Release Syndrome/drug therapy , Drug Repositioning , Interleukin-6/antagonists & inhibitors , Nitro Compounds/therapeutic use , Thiazoles/therapeutic use , COVID-19/complications , Cytokine Release Syndrome/complications , Cytokine Release Syndrome/immunology , Humans , Interferons/immunology , Interleukin-6/immunology , Observational Studies as Topic , SARS-CoV-2/pathogenicity
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