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1.
Ter Arkh ; 94(5): 668-674, 2022 Jun 17.
Article in Russian | MEDLINE | ID: covidwho-2091500

ABSTRACT

AIM: To study the effect of levilimab or baricitinib in combination with standard therapy (ST) on the incidence of severe viral pneumonia associated with a new coronavirus infection COVID-19. MATERIALS AND METHODS: A multicenter, open-label observational study of the efficacy and safety of levilimab in combination with ST (group 1, n=100), baricitinib in combination with ST (group 2, n=139), or in comparison with ST (group 3, n=200) in outpatients with verified CT-1 pneumonia. RESULTS: According to the results of laboratory tests, patients treated with levilimab in combination with ST had the best dynamics of changes in CRP from reliably the highest level (mg/L) to the lowest in comparison with other groups. In the group of patients with ST, in contrast to the other groups, no dynamics of CRP was observed by day 5 of therapy. In group of hospitalized patients initially receiving levilimab in addition to ST, the rate of transfer to the intensive care unit (2 patients, 9.52%) and length of stay (4 days) was significantly lower compared to the values in patients in both the baricitinib group in combination with ST (7 patients, 15.56%; 5 days [interquartile range 36.5]) and in patients receiving ST alone (7 patients, 15.56%; 5 days [interquartile range 36.5]). Also in hospitalized patients we observed no statistically significant intergroup differences in the incidence of infectious complications and thromboembolic events, which confirms the safety of including levilimab or baricitinib in COVID-19 pathogenetic therapy regimens. Observational results support the hypothesis that the initial inclusion of levilimab or baricitinib in addition to ST is accompanied by a reduced risk of viral pneumonia progression. CONCLUSION: The addition of levilimab or baricitinib to the therapy regimen for coronavirus infection during the outpatient phase has demonstrated a preemptive anti-inflammatory effect and reduced the probability of lung tissue damage progression.


Subject(s)
COVID-19 , Pneumonia, Viral , Humans , COVID-19/drug therapy , Outpatients , SARS-CoV-2 , Pneumonia, Viral/complications , Pneumonia, Viral/drug therapy , Anti-Inflammatory Agents/therapeutic use , Treatment Outcome
2.
Ter Arkh ; 94(5): 636-641, 2022 Jun 17.
Article in Russian | MEDLINE | ID: covidwho-2091499

ABSTRACT

BACKGROUND: Currently, observations are accumulating indicating the negative effect of therapy with a number of biologic disease-modifying anti-rheumatic drugs (bDMARDs) drugs on the course of COVID-19. These facts determine the relevance of studying the factors of severe course and unfavorable outcome in immuno-inflammatory rheumatic diseases (IIRD) patients treated with bDMARDs in order to develop tactics for managing this category of patients in a pandemic. AIM: To evaluate the influence of clinical and demographic factors on the risk of development, severity of the course and clinical outcomes of a new coronavirus infection in patients suffering from IIRD and receiving therapy with genetically engineered biological drugs. MATERIALS AND METHODS: A retrospective analysis of the database of the register of patients with IIRD receiving bDMARDs in the Novosibirsk region was performed, which included 318 patients, 94 of whom had indications of having suffered viral infection/pneumonia for the period from 01.04.2020 to 31.12.2020. RESULTS: According to the data obtained, at the time of the analysis, 94 people out of 318 patients with IIRD had a new coronavirus infection. Most (53%) of the patients had a mild infection. At the same time, the nosological form, the use of anti-rheumatic drugs and glucocorticoids did not increase the risks of severe coronavirus infection. When using bDMARDs, only anti-B-cell therapy (rituximab) associated with statistically significant increase in the risk of severe/extremely severe COVID-19. The mortality rate according to the analysis of the register was 6,38%. CONCLUSION: Patients with IIRD have a high risk of severe coronavirus infection, while the severity of the disease is associated with the type of therapy performed.


Subject(s)
Antirheumatic Agents , Biological Products , COVID-19 , Pneumonia, Viral , Rheumatic Diseases , Humans , COVID-19/drug therapy , Rheumatic Diseases/drug therapy , Rheumatic Diseases/epidemiology , Retrospective Studies , Rituximab/therapeutic use , Pneumonia, Viral/chemically induced , Pneumonia, Viral/complications , Pneumonia, Viral/drug therapy , Antirheumatic Agents/adverse effects , Biological Products/adverse effects
3.
Curr Opin Rheumatol ; 32(6): 572-582, 2020 11.
Article in English | MEDLINE | ID: covidwho-2077899

ABSTRACT

PURPOSE OF REVIEW: The purpose of this review is highlighting the most recent evidence on the clinical efficacy and toxicity of antimalarials in systemic lupus erythematosus (SLE). RECENT FINDINGS: New data confirm the effects of antimalarials in preventing SLE activity, damage and infections and in decreasing mortality. An important reduction in use of health resources is related to continued antimalarial use. Hydroxychloroquine (HCQ) may prevent preeclampsia in pregnant women with SLE. HCQ ocular toxicity is infrequent and could be associated with blood levels. Gastrointestinal and skin toxicity are underrecognized and could influence adherence. Prolongation of QT interval is extremely unusual with HCQ. Doses of HCQ of 200 mg/day seem to offer a good efficacy/toxicity balance. HCQ protection against herpes zoster and Pneumocystis jirovecii infection has been shown. On the contrary, HCQ prescription by doctors and adherence by patients are both under recommended standards. The recent coronavirus disease 2019 pandemic has resulted in a significant shortage of HCQ in many countries with possible consequences in the correct treatment of lupus patients. SUMMARY: Recent evidence reinforces the central role of HCQ in SLE therapy. The reduction in activity, damage accrual and mortality is consistent across studies, countries and ethnical groups. On the contrary, and despite the well established beneficial effects of prolonged regular HCQ therapy, many SLE patients do never take this drug or it is eventually stopped in the setting of severe flares, pregnancy or presumed toxicity. Every effort must be made to assure the correct prescription of HCQ and not to withdraw the drug unless unequivocal signs of toxicity are present.


Subject(s)
Antimalarials/therapeutic use , Betacoronavirus , Coronavirus Infections/epidemiology , Lupus Erythematosus, Systemic/drug therapy , Pandemics , Pneumonia, Viral/epidemiology , COVID-19 , Comorbidity , Coronavirus Infections/drug therapy , Female , Humans , Lupus Erythematosus, Systemic/epidemiology , Pneumonia, Viral/drug therapy , SARS-CoV-2 , Treatment Outcome
5.
Lancet Infect Dis ; 20(11): e276-e288, 2020 11.
Article in English | MEDLINE | ID: covidwho-2062013

ABSTRACT

As severe acute respiratory syndrome coronavirus 2 continues to spread worldwide, there have been increasing reports from Europe, North America, Asia, and Latin America describing children and adolescents with COVID-19-associated multisystem inflammatory conditions. However, the association between multisystem inflammatory syndrome in children and COVID-19 is still unknown. We review the epidemiology, causes, clinical features, and current treatment protocols for multisystem inflammatory syndrome in children and adolescents associated with COVID-19. We also discuss the possible underlying pathophysiological mechanisms for COVID-19-induced inflammatory processes, which can lead to organ damage in paediatric patients who are severely ill. These insights provide evidence for the need to develop a clear case definition and treatment protocol for this new condition and also shed light on future therapeutic interventions and the potential for vaccine development. TRANSLATIONS: For the French, Chinese, Arabic, Spanish and Russian translations of the abstract see Supplementary Materials section.


Subject(s)
Betacoronavirus , Coronavirus Infections/epidemiology , Coronavirus Infections/immunology , Pneumonia, Viral/epidemiology , Pneumonia, Viral/immunology , Systemic Inflammatory Response Syndrome/epidemiology , Systemic Inflammatory Response Syndrome/immunology , Adolescent , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Antiviral Agents/therapeutic use , COVID-19 , Child , Child, Preschool , Coronavirus Infections/drug therapy , Coronavirus Infections/virology , Female , Humans , Immunoglobulins, Intravenous/therapeutic use , Infant , Infant, Newborn , Male , Mucocutaneous Lymph Node Syndrome/drug therapy , Mucocutaneous Lymph Node Syndrome/immunology , Pandemics , Pneumonia, Viral/drug therapy , Pneumonia, Viral/virology , Risk Factors , SARS-CoV-2 , Systemic Inflammatory Response Syndrome/drug therapy , Systemic Inflammatory Response Syndrome/virology , Young Adult
6.
Curr Opin Crit Care ; 28(5): 463-469, 2022 10 01.
Article in English | MEDLINE | ID: covidwho-2008657

ABSTRACT

PURPOSE OF REVIEW: Since the beginning of the severe acute respiratory syndrome coronavirus 2 pandemic, there has been a large increase in the consumption of antimicrobials, both as a form of treatment for viral pneumonia, which has been shown to be ineffective, and in the treatment of secondary infections that arise over the course of the severe presentation of coronavirus disease 2019 (COVID-19). This increase in consumption, often empirical, ends up causing an increase in the incidence of colonization and secondary infections by multi and pan-resistant germs. RECENT FINDINGS: The presence of a hyperinflammatory condition induced by the primary infection, associated with the structural damage caused by viral pneumonia and by the greater colonization by bacteria, generally multiresistant, are important risk factors for the acquisition of secondary infections in COVID-19. Consequently, there is an increased prevalence of secondary infections, associated with a higher consumption of antimicrobials and a significant increase in the incidence of infections by multi and pan-resistant bacteria. SUMMARY: Antimicrobial stewardship and improvement in diagnostic techniques, improving the accuracy of bacterial infection diagnosis, may impact the antibiotic consumption and the incidence of infections by resistant pathogens.


Subject(s)
Anti-Infective Agents , Bacterial Infections , COVID-19 , Coinfection , Pneumonia, Viral , Anti-Bacterial Agents/therapeutic use , Bacterial Infections/drug therapy , Bacterial Infections/epidemiology , COVID-19/epidemiology , Coinfection/drug therapy , Coinfection/epidemiology , Humans , Pneumonia, Viral/complications , Pneumonia, Viral/drug therapy , Pneumonia, Viral/epidemiology
7.
Crit Care ; 26(1): 236, 2022 Aug 03.
Article in English | MEDLINE | ID: covidwho-2002213

ABSTRACT

BACKGROUND: The COVID-19 pandemic presented major challenges for critical care facilities worldwide. Infections which develop alongside or subsequent to viral pneumonitis are a challenge under sporadic and pandemic conditions; however, data have suggested that patterns of these differ between COVID-19 and other viral pneumonitides. This secondary analysis aimed to explore patterns of co-infection and intensive care unit-acquired infections (ICU-AI) and the relationship to use of corticosteroids in a large, international cohort of critically ill COVID-19 patients. METHODS: This is a multicenter, international, observational study, including adult patients with PCR-confirmed COVID-19 diagnosis admitted to ICUs at the peak of wave one of COVID-19 (February 15th to May 15th, 2020). Data collected included investigator-assessed co-infection at ICU admission, infection acquired in ICU, infection with multi-drug resistant organisms (MDRO) and antibiotic use. Frequencies were compared by Pearson's Chi-squared and continuous variables by Mann-Whitney U test. Propensity score matching for variables associated with ICU-acquired infection was undertaken using R library MatchIT using the "full" matching method. RESULTS: Data were available from 4994 patients. Bacterial co-infection at admission was detected in 716 patients (14%), whilst 85% of patients received antibiotics at that stage. ICU-AI developed in 2715 (54%). The most common ICU-AI was bacterial pneumonia (44% of infections), whilst 9% of patients developed fungal pneumonia; 25% of infections involved MDRO. Patients developing infections in ICU had greater antimicrobial exposure than those without such infections. Incident density (ICU-AI per 1000 ICU days) was in considerable excess of reports from pre-pandemic surveillance. Corticosteroid use was heterogenous between ICUs. In univariate analysis, 58% of patients receiving corticosteroids and 43% of those not receiving steroids developed ICU-AI. Adjusting for potential confounders in the propensity-matched cohort, 71% of patients receiving corticosteroids developed ICU-AI vs 52% of those not receiving corticosteroids. Duration of corticosteroid therapy was also associated with development of ICU-AI and infection with an MDRO. CONCLUSIONS: In patients with severe COVID-19 in the first wave, co-infection at admission to ICU was relatively rare but antibiotic use was in substantial excess to that indication. ICU-AI were common and were significantly associated with use of corticosteroids. Trial registration ClinicalTrials.gov: NCT04836065 (retrospectively registered April 8th 2021).


Subject(s)
COVID-19 , Coinfection , Pneumonia, Bacterial , Pneumonia, Viral , Adrenal Cortex Hormones/therapeutic use , Adult , Anti-Bacterial Agents/therapeutic use , COVID-19/complications , COVID-19/epidemiology , COVID-19 Testing , Coinfection/drug therapy , Coinfection/epidemiology , Critical Illness , Humans , Intensive Care Units , Pandemics , Pneumonia, Bacterial/drug therapy , Pneumonia, Viral/complications , Pneumonia, Viral/drug therapy , Pneumonia, Viral/epidemiology
8.
Inflammopharmacology ; 30(5): 1927-1931, 2022 Oct.
Article in English | MEDLINE | ID: covidwho-1990702

ABSTRACT

The efforts of the scientific world directed to identifying new antiviral drugs and therapies effective against SARS-CoV-2 continue. New oral antivirals against SARS-CoV-2 such as paxlovid have recently authorized. Evidence shows that these antivirals have good efficacy in reducing the risk of hospitalization in COVID-19 positive patients. Remdesivir is an authorized antiviral for the treatment of SARS-CoV-2 infection. To date, there are still few data in the literature on the safety profile and the risk of generating antiviral-resistant SARS-CoV-2 drug variants. In this manuscript we describe the evidence in the literature on the monotherapy use of paxlovid and monotherapy use of remdesivir, and the scientific hypothesis of using nirmatrelvir and remdesivir in association with the aim of increasing treatment efficacy, reducing the risk of adverse reactions and generating antiviral drug-resistant variants.


Subject(s)
COVID-19 , Coronavirus Infections , Pneumonia, Viral , Adenosine Monophosphate/analogs & derivatives , Adult , Alanine/analogs & derivatives , Antiviral Agents/adverse effects , Betacoronavirus , COVID-19/drug therapy , Coronavirus Infections/drug therapy , Hospitalization , Humans , Pandemics , Pneumonia, Viral/drug therapy , SARS-CoV-2
11.
Cad Saude Publica ; 38(7): e00001022, 2022.
Article in English | MEDLINE | ID: covidwho-1963142

ABSTRACT

Off-label use of azithromycin, hydroxychloroquine, and ivermectin (the "COVID kit") has been suggested for COVID-19 treatment in Brazil without clinical or scientific evidence of efficacy. These drugs have known adverse drug reactions (ADR). This study aimed to analyze if the sales of drugs in the "COVID kit" are correlated to the reported number of ADR after the COVID-19 pandemic began. Data was obtained from the Brazilian Health Regulatory Agency (Anvisa) website on reported sales and ADRs for azithromycin, hydroxychloroquine, and ivermectin for all Brazilian states. The period from March 2019 to February 2020 (before the pandemic) was compared to that from March 2020 to February 2021 (during the pandemic). Trend adjustment was performed for time series data and cross-correlation analysis to investigate correlation between sales and ADR within the same month (lag 0) and in the following months (lag 1 and lag 2). Spearman's correlation coefficient was used to assess the magnitude of the correlations. After the pandemic onset, sales of all investigated drugs increased significantly (69.75% for azithromycin, 10,856,481.39% for hydroxychloroquine, and 12,291,129.32% for ivermectin). ADR levels of all medications but azithromycin were zero before the pandemic, but increased after its onset. Cross-correlation analysis was significant in lag 1 for all drugs nationwide. Spearman's correlation was moderate for azithromycin and hydroxychloroquine but absent for ivermectin. Data must be interpreted cautiously since no active search for ADR was performed. Our results show that the increased and indiscriminate use of "COVID kit" during the pandemic correlates to an increased occurrence of ADRs.


Subject(s)
COVID-19 , Coronavirus Infections , Drug-Related Side Effects and Adverse Reactions , Pneumonia, Viral , Azithromycin/adverse effects , Brazil/epidemiology , COVID-19/drug therapy , Coronavirus Infections/drug therapy , Coronavirus Infections/epidemiology , Drug-Related Side Effects and Adverse Reactions/epidemiology , Humans , Hydroxychloroquine/adverse effects , Ivermectin/adverse effects , Pandemics , Pneumonia, Viral/drug therapy , Pneumonia, Viral/epidemiology
12.
Ann Afr Med ; 21(2): 113-117, 2022.
Article in English | MEDLINE | ID: covidwho-1954253

ABSTRACT

Background: Coronavirus disease-2019 (COVID-19) pandemic has engulfed the whole world with millions getting infected and losing their lives. Health care professionals (HCPs) who are in the front line of fighting with COVID-19 are particularly vulnerable and it is crucial to protect them from COVID-19. In this regard, the Indian Council of Medical Research (ICMR) has recommended hydroxychloroquine (HCQS) chemoprophylaxis in HCPs. However, considering the lack of sufficient evidence the HCP are in a dilemma about this aspect. Moreover, there is a paucity of data on use of HCQS as a chemoprophylaxis among Indian HCP. Hence, this study was carried out to study the extent of use and also the perception of Indian HCP toward use of HCQS as a chemoprophylaxis for COVID-19. Materials and Methods: This was a cross-sectional study done on 205 HCPs working across India. The responses were collected electronically using a prevalidated semi-structured questionnaire. Results: 62.9% (129/205) respondents reported having taken HCQS chemo-prophylaxis for COVID-19 while 34.7% (76/205) did not take it. Among HCP, who did not take the prophylaxis, the main reasons cited were concern about adverse effects (61.5%) and lack of robust evidence (24%). Only 14% of respondents felt that there was sufficient evidence to justify use of HCQS for prophylaxis while an overwhelming majority (86%) felt otherwise or were uncertain. Conclusion: The majority of participants felt that despite a lack of proven efficacy, ICMR guidelines on HCQS prophylaxis in COVID-19 are justified considering the pandemic situation. Our study also found that HCQS is well tolerated by participants and there was no reported serious adverse effect and cardiac-related side effects among them.


Résumé Contexte: La pandémie de maladie à coronavirus-2019 (COVID-19) a englouti le monde entier avec des millions de personnes infectées et perdant leur des vies. Les professionnels de la santé (HCP) qui sont en première ligne dans la lutte contre le COVID-19 sont particulièrement vulnérables et il est essentiel de les protéger du COVID-19. À cet égard, le Conseil indien de la recherche médicale (ICMR) a recommandé l'hydroxychloroquine (HCQS) chimioprophylaxie chez les professionnels de la santé. Cependant, compte tenu du manque de preuves suffisantes, le professionnel de la santé est confronté à un dilemme à propos de cet aspect. En outre, il y a peu de données sur l'utilisation du HCQS comme chimioprophylaxie parmi les professionnels de la santé indiens. Par conséquent, cette étude a été menée pour étudier l'étendue de l'utilisation et aussi la perception des professionnels de la santé indiens à l'égard de l'utilisation du HCQS comme chimioprophylaxie pour le COVID-19. Matériel et Méthodes: c'était un étude transversale réalisée sur 205 professionnels de la santé travaillant en Inde. Les réponses ont été recueillies par voie électronique à l'aide d'un système semi-structuré prévalidé questionnaire. Résultats: 62,9% (129/205) des répondants ont déclaré avoir suivi une chimioprophylaxie HCQS pour le COVID-19, tandis que 34,7% (76/205) ne l'a pas pris. Parmi les professionnels de la santé qui n'ont pas pris de prophylaxie, les principales raisons invoquées étaient la préoccupation concernant les effets indésirables (61,5%) et le manque de preuves solides (24%). Seulement 14% des répondants estimaient qu'il y avait des preuves suffisantes pour justifier l'utilisation du HCQS à des fins prophylactiques alors qu'un une écrasante majorité (86%) pensait le contraire ou était incertaine. Conclusion: La majorité des participants ont estimé que malgré un manque de efficacité, les lignes directrices de l'ICMR sur la prophylaxie du HCQS dans le COVID-19 sont justifiées compte tenu de la situation pandémique. Notre étude a également révélé que Le HCQS est bien toléré par les participants et aucun effet indésirable grave ni effet secondaire cardiaque n'a été signalé parmi eux. Mots-clés: Chimioprophylaxie, COVID-19, hydroxychloroquine, Conseil indien de la recherche médicale.


Subject(s)
COVID-19 , Coronavirus Infections , Pneumonia, Viral , COVID-19/drug therapy , COVID-19/prevention & control , Coronavirus Infections/drug therapy , Coronavirus Infections/epidemiology , Coronavirus Infections/prevention & control , Cross-Sectional Studies , Health Personnel , Humans , Hydroxychloroquine/adverse effects , Pneumonia, Viral/drug therapy , Pneumonia, Viral/epidemiology , Pneumonia, Viral/prevention & control , Surveys and Questionnaires
13.
Adv Ther ; 39(7): 3061-3071, 2022 07.
Article in English | MEDLINE | ID: covidwho-1906545

ABSTRACT

The COVID-19 pandemic has drawn considerable attention to viral pneumonia from clinicians, public health authorities, and the general public. With dozens of viruses able to cause pneumonia in humans, differentiating viral from bacterial pneumonia can be very challenging in clinical practice using traditional diagnostic methods. Precision medicine is a medical model in which decisions, practices, interventions, and therapies are adapted to the individual patient on the basis of their predicted response or risk of disease. Precision medicine approaches hold promise as a way to improve outcomes for patients with viral pneumonia. This review describes the latest advances in the use of precision medicine for diagnosing and treating viral pneumonia in adults and discusses areas where further research is warranted.


Subject(s)
COVID-19 , Pneumonia, Bacterial , Pneumonia, Viral , Humans , Pandemics , Pneumonia, Bacterial/diagnosis , Pneumonia, Viral/drug therapy , Pneumonia, Viral/therapy , Precision Medicine/methods
14.
Clin Pharmacol Ther ; 112(4): 824-835, 2022 Oct.
Article in English | MEDLINE | ID: covidwho-1858580

ABSTRACT

Chloroquine and azithromycin were developed in combination for the preventive treatment of malaria in pregnancy, and more recently were proposed as coronavirus disease 2019 (COVID-19) treatment options. Billions of doses of chloroquine have been administered worldwide over the past 70 years but concerns regarding cardiotoxicity, notably the risk of torsades de pointes (TdP), remain. This investigation aimed to characterize the pharmacokinetics and electrocardiographic effects of chloroquine and azithromycin observed in a large previously conducted healthy volunteer study. Healthy adult volunteers (n = 119) were randomized into 5 arms: placebo, chloroquine alone (600 mg base), or chloroquine with either 500 mg, 1,000 mg, or 1,500 mg of azithromycin all given daily for 3 days. Chloroquine and azithromycin levels, measured using liquid-chromatography tandem mass spectrometry, and electrocardiograph intervals were recorded at frequent intervals. Time-matched changes in the PR, QRS, and heart rate-corrected JT, and QT intervals were calculated and the relationship with plasma concentrations was evaluated using linear and nonlinear mixed-effects modeling. Chloroquine and azithromycin pharmacokinetics were described satisfactorily by two- and three-compartment distribution models, respectively. No drug-drug interaction between chloroquine and azithromycin was observed. Chloroquine resulted in concentration-dependent prolongation of the PR, QRS, JTc and QTc intervals with a minimal additional effect of azithromycin. QRS widening contributed ~ 28% of the observed QT prolongation. Chloroquine causes significant concentration-dependent delays in both ventricular depolarization and repolarization. Co-administration of azithromycin did not significantly increase these effects. The arrhythmogenic risk of TdP associated with chloroquine may have been substantially overestimated in studies which did not separate electrocardiograph QRS and JT prolongation.


Subject(s)
Antimalarials , COVID-19 , Coronavirus Infections , Long QT Syndrome , Pneumonia, Viral , Torsades de Pointes , Adult , Azithromycin/adverse effects , COVID-19/drug therapy , Chloroquine , Coronavirus Infections/drug therapy , DNA-Binding Proteins/therapeutic use , Electrocardiography , Healthy Volunteers , Humans , Hydroxychloroquine , Long QT Syndrome/drug therapy , Pandemics , Pneumonia, Viral/drug therapy , Torsades de Pointes/drug therapy
15.
Inflammopharmacology ; 30(4): 1189-1205, 2022 Aug.
Article in English | MEDLINE | ID: covidwho-1844412

ABSTRACT

It has been reported that corticosteroid therapy was effective in the management of severe acute respiratory syndrome (SARS) and the Middle East Respiratory Syndrome (MERS), and recently in coronavirus disease 2019 (COVID-19). Corticosteroids are potent anti-inflammatory drugs that mitigate the risk of acute respiratory distress syndrome (ARDS) in COVID-19 and other viral pneumonia, despite a reduction of viral clearance; corticosteroids inhibit the development of cytokine storm and multi-organ damage. The risk-benefit ratio should be assessed for critical COVID-19 patients. In conclusion, corticosteroid therapy is an effective way in the management of COVID-19, it reduces the risk of complications primarily acute lung injury and the development of ARDS. Besides, corticosteroid therapy mainly dexamethasone and methylprednisolone are effective in reducing the severity of COVID-19 and associated comorbidities such as chronic obstructive pulmonary diseases (COPD), rheumatoid arthritis, and inflammatory bowel disease (IBD).


Subject(s)
COVID-19 , Pneumonia, Viral , Respiratory Distress Syndrome , Adrenal Cortex Hormones/adverse effects , COVID-19/drug therapy , Humans , Pneumonia, Viral/drug therapy , Respiratory Distress Syndrome/drug therapy , SARS-CoV-2
17.
Can J Anaesth ; 67(10): 1405-1416, 2020 10.
Article in English | MEDLINE | ID: covidwho-1777848

ABSTRACT

During the coronavirus disease (COVID-19) global pandemic, urgent strategies to alleviate shortages are required. Evaluation of the feasibility, practicality, and value of drug conservation strategies and therapeutic alternatives requires a collaborative approach at the provincial level. The Ontario COVID-19 ICU Drug Task Force was directed to create recommendations suggesting drug conservation strategies and therapeutic alternatives for essential drugs at risk of shortage in the intensive care unit during the COVID-19 pandemic. Recommendations were rapidly developed using a modified Delphi method and evaluated on their ease of implementation, feasibility, and supportive evidence. This article describes the recommendations for drug conservation strategies and therapeutic alternatives for drugs at risk of shortage that are commonly used in the care of critically ill patients. Recommendations are identified as preferred and secondary ones that might be less desirable. Although the impetus for generating this document was the COVID-19 pandemic, recommendations should also be applicable for mitigating drug shortages outside of a pandemic. Proposed provincial strategies for drug conservation and therapeutic alternatives may not all be appropriate for every institution. Local implementation will require consultation from end-users and hospital administrators. Competing equipment shortages and available resources should be considered when evaluating the appropriateness of each strategy.


RéSUMé: Pendant la pandémie mondiale du coronavirus (COVID-19), des stratégies urgentes pour réduire les pénuries sont nécessaires. L'évaluation de la faisabilité, de l'aspect pratique et du mérite des stratégies de préservation des médicaments et des alternatives thérapeutiques nécessite une approche collaborative au niveau provincial. Le Groupe de travail ontarien sur les médicaments à l'USI pendant la COVID-19 a reçu comme mandat d'élaborer des recommandations proposant des stratégies de préservation des médicaments et des alternatives thérapeutiques pour les médicaments essentiels utilisés dans les unités de soins intensifs courant un risque de pénurie pendant la pandémie de COVID-19. Des recommandations ont été rapidement élaborées en utilisant une méthode Delphi modifiée, puis évaluées selon leur facilité de mise en œuvre, leur faisabilité et les données probantes les préconisant. Cet article décrit les recommandations quant aux stratégies de préservation des médicaments et aux alternatives thérapeutiques aux médicaments possiblement à risque de pénurie fréquemment utilisés pour les soins des patients en état critique. Les recommandations sont identifiées comme 'à privilégier' ou 'secondaires' si moins souhaitables. Bien que la pandémie de la COVID-19 ait été l'impulsion incitant la création de ce document, ces recommandations devraient également être applicables pour réduire les pénuries de médicaments en contexte normal. Les stratégies provinciales proposées pour la préservation des médicaments et les alternatives thérapeutiques pourraient ne pas être adaptées pour toutes les institutions. La mise en œuvre locale nécessitera la consultation des utilisateurs et des administrateurs hospitaliers. Il faudrait tenir compte des pénuries de matériel concurrentes et des ressources disponibles lors de l'évaluation de la faisabilité de chaque stratégie.


Subject(s)
Coronavirus Infections/drug therapy , Intensive Care Units , Pharmaceutical Preparations/supply & distribution , Pneumonia, Viral/drug therapy , Advisory Committees , COVID-19 , Critical Illness , Humans , Ontario , Pandemics
18.
Proc Natl Acad Sci U S A ; 119(8)2022 02 22.
Article in English | MEDLINE | ID: covidwho-1758461

ABSTRACT

Viral causes of pneumonia pose constant threats to global public health, but there are no specific treatments currently available for the condition. Antivirals are ineffective when administered late after the onset of symptoms. Pneumonia is caused by an exaggerated inflammatory cytokine response to infection, but tissue necrosis and damage caused by virus also contribute to lung pathology. We hypothesized that viral pneumonia can be treated effectively if both virus and inflammation are simultaneously targeted. Combined treatment with the antiviral drug cidofovir and etanercept, which targets tumor necrosis factor (TNF), down-regulated nuclear factor kappa B-signaling and effectively reduced morbidity and mortality during respiratory ectromelia virus (ECTV) infection in mice even when treatment was initiated after onset of clinical signs. Treatment with cidofovir alone reduced viral load, but animals died from severe lung pathology. Treatment with etanercept had no effect on viral load but diminished levels of inflammatory cytokines and chemokines including TNF, IL-6, IL-1ß, IL-12p40, TGF-ß, and CCL5 and dampened activation of the STAT3 cytokine-signaling pathway, which transduces signals from multiple cytokines implicated in lung pathology. Consequently, combined treatment with a STAT3 inhibitor and cidofovir was effective in improving clinical disease and lung pathology in ECTV-infected mice. Thus, the simultaneous targeting of virus and a specific inflammatory cytokine or cytokine-signaling pathway is effective in the treatment of pneumonia. This approach might be applicable to pneumonia caused by emerging and re-emerging viruses, like seasonal and pandemic influenza A virus strains and severe acute respiratory syndrome coronavirus 2.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Antiviral Agents/therapeutic use , Cidofovir/therapeutic use , Etanercept/administration & dosage , Pneumonia, Viral/drug therapy , Animals , Antiviral Agents/pharmacology , Cell Line , Chlorocebus aethiops , Cidofovir/pharmacology , Cytokines/metabolism , Drug Evaluation, Preclinical , Drug Therapy, Combination , Ectromelia virus/drug effects , Female , Lung/drug effects , Lung/metabolism , Mice, Inbred C57BL , NF-kappa B/metabolism , Pneumonia, Viral/metabolism , STAT3 Transcription Factor/metabolism , Signal Transduction/drug effects , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Viral Load/drug effects
19.
J Pharm Pharm Sci ; 23(1): 75-85, 2020.
Article in English | MEDLINE | ID: covidwho-1727068

ABSTRACT

The presented work summarizes the results of studies underlining the crucial role of estrogen receptor (ER) signaling in both innate and adaptive immune responses as well as in tissue repairing processes during respiratory virus infection. Experimental studies justify that among respiratory virus infected mice, a weaker ER signaling leads to increased morbidity and mortality in both males and females. In animal experiments, estrogen treatment silences the inflammatory reactions and decreases virus titers leading to improved survival rate; it seems to be an ideal prevention and therapy against COVID-19. We should overcome the widespread reluctance to estrogen therapy as we have a unique estrogen formula; conjugated estrogens, or conjugated equine estrogens available under the brand name of Premarin deriving from natural sources. Premarin can exert similar ER upregulative and gene repairing power like endogenous estrogen without any risk for adverse reactions. Premarin is capable of stopping the COVID-19 pandemic.


Subject(s)
Coronavirus Infections/drug therapy , Estrogens/therapeutic use , Pneumonia, Viral/drug therapy , Receptors, Estrogen/physiology , Adaptive Immunity , Age Factors , Animals , Betacoronavirus , COVID-19 , Comorbidity , Coronavirus Infections/mortality , Estrogens, Conjugated (USP)/therapeutic use , Female , Humans , Immunity, Innate , Inflammation/drug therapy , Male , Mice , Pandemics , Pneumonia, Viral/mortality , SARS-CoV-2 , Sex Factors , Signal Transduction , Up-Regulation/drug effects
20.
Viruses ; 12(6)2020 06 10.
Article in English | MEDLINE | ID: covidwho-1726021

ABSTRACT

The ongoing Coronavirus Disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) signals an urgent need for an expansion in treatment options. In this study, we investigated the anti-SARS-CoV-2 activities of 22 antiviral agents with known broad-spectrum antiviral activities against coronaviruses and/or other viruses. They were first evaluated in our primary screening in VeroE6 cells and then the most potent anti-SARS-CoV-2 antiviral agents were further evaluated using viral antigen expression, viral load reduction, and plaque reduction assays. In addition to remdesivir, lopinavir, and chloroquine, our primary screening additionally identified types I and II recombinant interferons, 25-hydroxycholesterol, and AM580 as the most potent anti-SARS-CoV-2 agents among the 22 antiviral agents. Betaferon (interferon-ß1b) exhibited the most potent anti-SARS-CoV-2 activity in viral antigen expression, viral load reduction, and plaque reduction assays among the recombinant interferons. The lipogenesis modulators 25-hydroxycholesterol and AM580 exhibited EC50 at low micromolar levels and selectivity indices of >10.0. Combinational use of these host-based antiviral agents with virus-based antivirals to target different processes of the SARS-CoV-2 replication cycle should be evaluated in animal models and/or clinical trials.


Subject(s)
Antiviral Agents/pharmacology , Betacoronavirus/drug effects , Coronavirus Infections/drug therapy , Pneumonia, Viral/drug therapy , Animals , Antigens, Viral/immunology , Betacoronavirus/immunology , Betacoronavirus/metabolism , COVID-19 , Chlorocebus aethiops , Coronavirus Infections/virology , Humans , Interferons/metabolism , Lipogenesis/drug effects , Pandemics , Pneumonia, Viral/virology , SARS-CoV-2 , Signal Transduction/drug effects , Vero Cells , Viral Load/drug effects , Viral Plaque Assay , Virus Replication/drug effects
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