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1.
J Infect Dev Ctries ; 16(1): 63-72, 2022 01 31.
Article in English | MEDLINE | ID: covidwho-1702718

ABSTRACT

INTRODUCTION: Severe acute respiratory syndrome-related coronavirus (SARS-CoV-2) infection is characterised by a viral phase and a severe pro-inflammatory phase. The inhibition of the JAK/STAT pathway limits the pro-inflammatory state in moderate to severe COVID-19. METHODOLOGY: We analysed the data obtained by an observational cohort of patients with SARS-CoV-2 pneumonia treated with ruxolitinib in 22 hospitals of Mexico. The applied dose was determined based on physician's criteria. The benefit of ruxolitinib was evaluated using the 8-points ordinal scale developed by the NIH in the ACTT1 trial. Duration of hospital stay, changes in pro-inflammatory laboratory values, mortality, and toxicity were also measured. RESULTS: A total of 287 patients were reported at 22 sites in Mexico from March to June 2020; 80.8% received ruxolitinib 5 mg BID and 19.16% received ruxolitinib 10 mg BID plus standard of care. At beginning of treatment, 223 patients were on oxygen support and 59 on invasive ventilation. The percentage of patients on invasive ventilation was 53% in the 10 mg and 13% in the 5 mg cohort. A statistically significant improvement measured as a reduction by 2 points on the 8-point ordinal scale was described (baseline 5.39 ± 0.93, final 3.67± 2.98, p = 0.0001). There were 74 deaths. Serious adverse events were presented in 6.9% of the patients. CONCLUSIONS: Ruxolitinib appears to be safe in COVID-19 patients, with clinical benefits observed in terms of decrease in the 8-point ordinal scale and pro-inflammatory state. Further studies must be done to ensure efficacy against mortality.


Subject(s)
COVID-19 , Pyrazoles , Pyrimidines , COVID-19/drug therapy , Cohort Studies , Humans , Nitriles , Pyrazoles/therapeutic use , Pyrimidines/therapeutic use , SARS-CoV-2 , Treatment Outcome
2.
Biomed Pharmacother ; 147: 112614, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1682939

ABSTRACT

Post-Covid pulmonary fibrosis is evident following severe COVID-19. There is an urgent need to identify the cellular and pathophysiological characteristics of chronic lung squeals of Covid-19 for the development of future preventive and/or therapeutic interventions. Tissue-resident memory T (TRM) cells can mediate local immune protection against infections and cancer. Less beneficially, lung TRM cells cause chronic airway inflammation and fibrosis by stimulating pathologic inflammation. The effects of Janus kinase (JAK), an inducer pathway of cytokine storm, inhibition on acute Covid-19 cases have been previously evaluated. Here, we propose that Tofacitinib by targeting the CD8+ TRM cells could be a potential candidate for the treatment of chronic lung diseases induced by acute SARS-CoV-2 infection.


Subject(s)
CD8-Positive T-Lymphocytes/immunology , COVID-19/drug therapy , Janus Kinase Inhibitors/therapeutic use , Lung Injury/drug therapy , Piperidines/therapeutic use , Pyrimidines/therapeutic use , T-Lymphocyte Subsets/immunology , COVID-19/complications , COVID-19/immunology , Humans , Immunologic Memory/immunology , Lung/immunology , Lung Injury/etiology , Lung Injury/immunology , SARS-CoV-2 , T-Lymphocytes/immunology
3.
Nat Med ; 28(1): 39-50, 2022 01.
Article in English | MEDLINE | ID: covidwho-1641982

ABSTRACT

Immune dysregulation is an important component of the pathophysiology of COVID-19. A large body of literature has reported the effect of immune-based therapies in patients with COVID-19, with some remarkable successes such as the use of steroids or anti-cytokine therapies. However, challenges in clinical decision-making arise from the complexity of the disease phenotypes and patient heterogeneity, as well as the variable quality of evidence from immunotherapy studies. This Review aims to support clinical decision-making by providing an overview of the evidence generated by major clinical trials of host-directed therapy. We discuss patient stratification and propose an algorithm to guide the use of immunotherapy strategies in the clinic. This will not only help guide treatment decisions, but may also help to design future trials that investigate immunotherapy in other severe infections.


Subject(s)
Anticoagulants/therapeutic use , COVID-19/therapy , Complement Inactivating Agents/therapeutic use , Glucocorticoids/therapeutic use , Immunologic Factors/therapeutic use , Immunomodulation , Protein Kinase Inhibitors/therapeutic use , Antibodies, Monoclonal/therapeutic use , Antibodies, Monoclonal, Humanized/therapeutic use , Antibodies, Neutralizing/therapeutic use , Azetidines/therapeutic use , Bradykinin/analogs & derivatives , Bradykinin/therapeutic use , Bradykinin B2 Receptor Antagonists/therapeutic use , COVID-19/immunology , Dexamethasone/therapeutic use , Drug Combinations , Factor Xa Inhibitors/therapeutic use , Heparin/therapeutic use , Humans , Hydrocortisone/therapeutic use , Imatinib Mesylate/therapeutic use , Immunization, Passive , Interferon beta-1a/therapeutic use , Interferon beta-1b/therapeutic use , Interferon-gamma/therapeutic use , Interleukin 1 Receptor Antagonist Protein/therapeutic use , Kallikrein-Kinin System , Piperidines/therapeutic use , Purines/therapeutic use , Pyrazoles/therapeutic use , Pyrimidines/therapeutic use , SARS-CoV-2 , Sulfonamides/therapeutic use
4.
Am J Trop Med Hyg ; 105(6): 1472-1475, 2021 Oct 04.
Article in English | MEDLINE | ID: covidwho-1629955

ABSTRACT

Human lives and nations' economies have been adversely affected worldwide by the COVID-19 pandemic. The hyperinflammatory state associated with the disease may be related to mortality. Systemic glucocorticoid is the first-line therapy for cytokine storm. Various immunomodulatory drugs such as tocilizumab and baricitinib have been used in those not responding to glucocorticoid monotherapy. Amid the peak crisis of COVID-19 in India, there was an extreme paucity of medications, oxygen, and hospital beds. We describe three patients with COVID-19 who received low-dose tofacitinib (an oral Janus kinase inhibitor) in addition to moderate-dose glucocorticoid. These patients were treated at their homes, as the hospitals were short of beds. Rapid reduction in hypoxemia along with gradual resolution of other signs of the disease were observed. The results are reassuring regarding the feasibility of managing of severe COVID-19 outside the hospital setting when healthcare resources are overwhelmed by pandemic-related caseload.


Subject(s)
COVID-19/drug therapy , Piperidines/therapeutic use , Pyrimidines/therapeutic use , SARS-CoV-2 , Adult , Aged , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/therapeutic use , Anti-Inflammatory Agents/therapeutic use , Cytokine Release Syndrome/prevention & control , Cytokines/genetics , Cytokines/metabolism , Enoxaparin/administration & dosage , Enoxaparin/therapeutic use , Female , Gene Expression Regulation/drug effects , Humans , Methylprednisolone/administration & dosage , Methylprednisolone/therapeutic use , Middle Aged , Piperidines/administration & dosage , Prednisone/administration & dosage , Prednisone/therapeutic use , Pyrimidines/administration & dosage
5.
Ann Rheum Dis ; 81(1): 117-123, 2022 01.
Article in English | MEDLINE | ID: covidwho-1605885

ABSTRACT

OBJECTIVE: To compare the treatment efficacy and safety of tofacitinib (TOF) versus methotrexate (MTX) in Takayasu arteritis (TAK). METHODS: Fifty-three patients with active disease from an ongoing prospective TAK cohort in China were included in this study. Twenty-seven patients were treated with glucocorticoids (GCs) and TOF, and 26 patients were treated with GCs with MTX. The observation period was 12 months. Complete remission (CR), inflammatory parameter changes, GCs tapering and safety were assessed at the 6th, 9th and 12th month. Vascular lesions were evaluated at the 6th and 12th month, and relapse was analysed during 12 months. RESULTS: The CR rate was higher in the TOF group than in the MTX group (6 months: 85.19% vs 61.54%, p=0.07; 12 months: 88.46% vs 56.52%, p=0.02). During 12 months' treatment, patients in the TOF group achieved a relatively lower relapse rate (11.54% vs 34.78%, p=0.052) and a longer median relapse-free duration (11.65±0.98 vs 10.48±2.31 months, p=0.03). Average GCs dose at the 3rd, 6th and 12th month was lower in the TOF group than that in the MTX group (p<0.05). A difference was not observed in disease improvement or disease progression on imaging between the two groups (p>0.05). Prevalence of side effects was low in both groups (3.70% vs 15.38%, p=0.19). CONCLUSION: TOF was superior to MTX for CR induction, a tendency to prevent relapse and tapering of the GCs dose in TAK treatment. A good safety profile for TOF was also documented in patients with TAK.


Subject(s)
Antirheumatic Agents/therapeutic use , Janus Kinase Inhibitors/therapeutic use , Methotrexate/therapeutic use , Piperidines/therapeutic use , Pyrimidines/therapeutic use , Takayasu Arteritis/drug therapy , Adolescent , Adult , Antirheumatic Agents/adverse effects , Disease Progression , Drug Therapy, Combination , Female , Glucocorticoids/therapeutic use , Humans , Janus Kinase Inhibitors/adverse effects , Male , Methotrexate/adverse effects , Middle Aged , Piperidines/adverse effects , Prospective Studies , Pyrimidines/adverse effects , Recurrence , Time Factors , Treatment Outcome , Young Adult
6.
Biomed Pharmacother ; 146: 112592, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1588215

ABSTRACT

INTRODUCTION: The most grievous complication of the COVID-19 is the acute respiratory distress syndrome. A specific, rescue treatment for rapidly deteriorating patients should emerge to improve respiratory function and help patients to survive the most challenging period. Drugs used in targeted therapy of pulmonary arterial hypertension (PAH) appears to be suitable for this task and this article describes their potential for treatment of severe cases of COVID-19. METHODS: The authors reviewed the following databases for randomized controlled trials, reviews and meta-analyses published up to July 2020: Pubmed, Scopus, Google Scholar, Cochrane Database and ClinicalKey. The authors included every study contributory to the assessment of the potential of drugs used in targeted PAH therapy in treatment of COVID-19. RESULTS: Endothelin receptor antagonists, phosphodiesterase 5 inhibitors, riociguat and prostacyclin have proven ani-inflammatory effect and reduce pulmonary artery blood pressure, lung oedema and remodelling. Bosentan shows antiviral properties and sildenafil, as well as epoprostenol, inhibits apoptosis of lung epithelial cells. Among patients with lung lesions the decrease of pulmonary blood pressure can lead to increase of ventilation/perfusion mismatch and decrease of blood oxygenation. CONCLUSIONS: Among all assessed drugs bosentan, sildenafil and epoprostenol appear to be most promising and a combination of these drugs should be considered due to synergism. The targeted PAH therapy in treatment of COVID-19 associated ARDS could be a useful tool saving lives of patients with severe SARS-CoV-2 infection, however, its introduction should be investigated and monitored very carefully as it can lead to transient deterioration of patient condition.


Subject(s)
COVID-19/drug therapy , Pulmonary Artery/metabolism , Respiratory Distress Syndrome/drug therapy , Animals , COVID-19/complications , Endothelin Receptor Antagonists/therapeutic use , Humans , Phosphodiesterase Inhibitors/therapeutic use , Prostaglandins/therapeutic use , Pulmonary Artery/drug effects , Pyrazoles/therapeutic use , Pyrimidines/therapeutic use , Respiratory Distress Syndrome/complications
7.
Blood Coagul Fibrinolysis ; 32(7): 427-433, 2021 Oct 01.
Article in English | MEDLINE | ID: covidwho-1526210

ABSTRACT

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


Subject(s)
Purpura, Thrombocytopenic, Idiopathic/drug therapy , Aminopyridines/therapeutic use , Antibodies, Monoclonal, Humanized/therapeutic use , COVID-19/complications , COVID-19/immunology , Histocompatibility Antigens Class I , Humans , Immunosuppressive Agents/therapeutic use , Morpholines/therapeutic use , Protein Kinase Inhibitors/therapeutic use , Purpura, Thrombocytopenic, Idiopathic/etiology , Purpura, Thrombocytopenic, Idiopathic/immunology , Pyrimidines/therapeutic use , Receptors, Fc/antagonists & inhibitors , Receptors, Thrombopoietin/agonists , SARS-CoV-2/immunology , Syk Kinase/antagonists & inhibitors , Thiazoles/therapeutic use , Thiophenes/therapeutic use
8.
Ann Rheum Dis ; 81(1): 34-40, 2022 01.
Article in English | MEDLINE | ID: covidwho-1462913

ABSTRACT

OBJECTIVES: To update the EULAR points to consider (PtCs) on the use of immunomodulatory therapies in COVID-19. METHODS: According to the EULAR standardised operating procedures, a systematic literature review up to 14 July 2021 was conducted and followed by a consensus meeting of an international multidisciplinary task force. The new statements were consolidated by formal voting. RESULTS: We updated 2 overarching principles and 12 PtC. Evidence was only available in moderate to severe and critical patients. Glucocorticoids alone or in combination with tocilizumab are beneficial in COVID-19 cases requiring oxygen therapy and in critical COVID-19. Use of Janus kinase inhibitors (baricitinib and tofacitinib) is promising in the same populations of severe and critical COVID-19. Anti-SARS-CoV-2 monoclonal antibodies and convalescent plasma may find application in early phases of the disease and in selected subgroups of immunosuppressed patients. There was insufficient robust evidence for the efficacy of other immunomodulators with further work being needed in relation to biomarker-based stratification for IL-1 therapy CONCLUSIONS: Growing evidence supports incremental efficacy of glucocorticoids alone or combined with tocilizumab/Janus kinase inhibitors in moderate to severe and critical COVID-19. Ongoing studies may unmask the potential application of other therapeutic approaches. Involvement of rheumatologists, as systemic inflammatory diseases experts, should be encouraged in clinical trials of immunomodulatory therapy in COVID-19.


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , COVID-19/drug therapy , Glucocorticoids/therapeutic use , Janus Kinase Inhibitors/therapeutic use , Azetidines/therapeutic use , Consensus Development Conferences as Topic , Drug Therapy, Combination , Humans , Immunomodulation , Piperidines/therapeutic use , Purines/therapeutic use , Pyrazoles/therapeutic use , Pyrimidines/therapeutic use , SARS-CoV-2 , Sulfonamides/therapeutic use
9.
Am J Trop Med Hyg ; 105(6): 1472-1475, 2021 Oct 04.
Article in English | MEDLINE | ID: covidwho-1450911

ABSTRACT

Human lives and nations' economies have been adversely affected worldwide by the COVID-19 pandemic. The hyperinflammatory state associated with the disease may be related to mortality. Systemic glucocorticoid is the first-line therapy for cytokine storm. Various immunomodulatory drugs such as tocilizumab and baricitinib have been used in those not responding to glucocorticoid monotherapy. Amid the peak crisis of COVID-19 in India, there was an extreme paucity of medications, oxygen, and hospital beds. We describe three patients with COVID-19 who received low-dose tofacitinib (an oral Janus kinase inhibitor) in addition to moderate-dose glucocorticoid. These patients were treated at their homes, as the hospitals were short of beds. Rapid reduction in hypoxemia along with gradual resolution of other signs of the disease were observed. The results are reassuring regarding the feasibility of managing of severe COVID-19 outside the hospital setting when healthcare resources are overwhelmed by pandemic-related caseload.


Subject(s)
COVID-19/drug therapy , Piperidines/therapeutic use , Pyrimidines/therapeutic use , SARS-CoV-2 , Adult , Aged , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/therapeutic use , Anti-Inflammatory Agents/therapeutic use , Cytokine Release Syndrome/prevention & control , Cytokines/genetics , Cytokines/metabolism , Enoxaparin/administration & dosage , Enoxaparin/therapeutic use , Female , Gene Expression Regulation/drug effects , Humans , Methylprednisolone/administration & dosage , Methylprednisolone/therapeutic use , Middle Aged , Piperidines/administration & dosage , Prednisone/administration & dosage , Prednisone/therapeutic use , Pyrimidines/administration & dosage
12.
JNMA J Nepal Med Assoc ; 59(238): 593-596, 2021 Jul 01.
Article in English | MEDLINE | ID: covidwho-1310357

ABSTRACT

Severe coronavirus disease 2019 can be associated with progressive respiratory failure. In addition to respiratory support and other supportive care, use of corticosteroids has shown to improve outcome. Despite the use of steroids, a significant proportion of patients progressively worsen. Adjunct immunomodulators have been studied in addition to steroids in these patients. Here we present a successful use of tofacitinib, a Janus Kinase inhibitor, in conjunction with dexamethasone for a patient with rapid worsening of respiratory status and with high level of serum inflammatory biomarkers.


Subject(s)
COVID-19 , Humans , Immunologic Factors/therapeutic use , Piperidines , Pyrimidines/therapeutic use , Pyrroles/therapeutic use , SARS-CoV-2
14.
Int J Mol Sci ; 22(13)2021 Jun 30.
Article in English | MEDLINE | ID: covidwho-1288906

ABSTRACT

Coronavirus disease (COVID)-19 is the leading global health threat to date caused by a severe acute respiratory syndrome coronavirus (SARS-CoV-2). Recent clinical trials reported that the use of Bruton's tyrosine kinase (BTK) inhibitors to treat COVID-19 patients could reduce dyspnea and hypoxia, thromboinflammation, hypercoagulability and improve oxygenation. However, the mechanism of action remains unclear. Thus, this study employs structure-based virtual screening (SBVS) to repurpose BTK inhibitors acalabrutinib, dasatinib, evobrutinib, fostamatinib, ibrutinib, inositol 1,3,4,5-tetrakisphosphate, spebrutinib, XL418 and zanubrutinib against SARS-CoV-2. Molecular docking is conducted with BTK inhibitors against structural and nonstructural proteins of SARS-CoV-2 and host targets (ACE2, TMPRSS2 and BTK). Molecular mechanics-generalized Born surface area (MM/GBSA) calculations and molecular dynamics (MD) simulations are then carried out on the selected complexes with high binding energy. Ibrutinib and zanubrutinib are found to be the most potent of the drugs screened based on the results of computational studies. Results further show that ibrutinib and zanubrutinib could exploit different mechanisms at the viral entry and replication stage and could be repurposed as potential inhibitors of SARS-CoV-2 pathogenesis.


Subject(s)
Adenine/analogs & derivatives , Drug Repositioning , Molecular Dynamics Simulation , Piperidines/chemistry , Protein Kinase Inhibitors/chemistry , Pyrazoles/chemistry , Pyrimidines/chemistry , Adenine/chemistry , Adenine/metabolism , Adenine/therapeutic use , Agammaglobulinaemia Tyrosine Kinase/antagonists & inhibitors , Agammaglobulinaemia Tyrosine Kinase/metabolism , Angiotensin-Converting Enzyme 2/antagonists & inhibitors , Angiotensin-Converting Enzyme 2/metabolism , Binding Sites , COVID-19/drug therapy , COVID-19/pathology , COVID-19/virology , Humans , Molecular Docking Simulation , Piperidines/metabolism , Piperidines/therapeutic use , Protein Kinase Inhibitors/metabolism , Protein Kinase Inhibitors/therapeutic use , Pyrazoles/metabolism , Pyrazoles/therapeutic use , Pyrimidines/metabolism , Pyrimidines/therapeutic use , SARS-CoV-2/isolation & purification , SARS-CoV-2/metabolism , Serine Endopeptidases/chemistry , Serine Endopeptidases/metabolism , Thermodynamics , Viral Nonstructural Proteins/antagonists & inhibitors , Viral Nonstructural Proteins/metabolism
15.
Int J Biol Sci ; 17(9): 2348-2355, 2021.
Article in English | MEDLINE | ID: covidwho-1285527

ABSTRACT

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has led to more than 150 million infections and about 3.1 million deaths up to date. Currently, drugs screened are urgently aiming to block the infection of SARS-CoV-2. Here, we explored the interaction networks of kinase and COVID-19 crosstalk, and identified phosphoinositide 3-kinase (PI3K)/AKT pathway as the most important kinase signal pathway involving COVID-19. Further, we found a PI3K/AKT signal pathway inhibitor capivasertib restricted the entry of SARS-CoV-2 into cells under non-cytotoxic concentrations. Lastly, the signal axis PI3K/AKT/FYVE finger-containing phosphoinositide kinase (PIKfyve)/PtdIns(3,5)P2 was revealed to play a key role during the cellular entry of viruses including SARS-CoV-2, possibly providing potential antiviral targets. Altogether, our study suggests that the PI3K/AKT kinase inhibitor drugs may be a promising anti-SARS-CoV-2 strategy for clinical application, especially for managing cancer patients with COVID-19 in the pandemic era.


Subject(s)
COVID-19/drug therapy , Proto-Oncogene Proteins c-akt/antagonists & inhibitors , Pyrimidines/therapeutic use , Pyrroles/therapeutic use , SARS-CoV-2/drug effects , Virus Internalization/drug effects , Animals , COVID-19/enzymology , Chlorocebus aethiops , Computer Simulation , Humans , Neoplasms/enzymology , Neoplasms/mortality , Proto-Oncogene Proteins c-akt/metabolism , Pyrimidines/pharmacology , Pyrroles/pharmacology , Receptor Cross-Talk , Vero Cells
16.
N Engl J Med ; 385(5): 406-415, 2021 07 29.
Article in English | MEDLINE | ID: covidwho-1270703

ABSTRACT

BACKGROUND: The efficacy and safety of tofacitinib, a Janus kinase inhibitor, in patients who are hospitalized with coronavirus disease 2019 (Covid-19) pneumonia are unclear. METHODS: We randomly assigned, in a 1:1 ratio, hospitalized adults with Covid-19 pneumonia to receive either tofacitinib at a dose of 10 mg or placebo twice daily for up to 14 days or until hospital discharge. The primary outcome was the occurrence of death or respiratory failure through day 28 as assessed with the use of an eight-level ordinal scale (with scores ranging from 1 to 8 and higher scores indicating a worse condition). All-cause mortality and safety were also assessed. RESULTS: A total of 289 patients underwent randomization at 15 sites in Brazil. Overall, 89.3% of the patients received glucocorticoids during hospitalization. The cumulative incidence of death or respiratory failure through day 28 was 18.1% in the tofacitinib group and 29.0% in the placebo group (risk ratio, 0.63; 95% confidence interval [CI], 0.41 to 0.97; P = 0.04). Death from any cause through day 28 occurred in 2.8% of the patients in the tofacitinib group and in 5.5% of those in the placebo group (hazard ratio, 0.49; 95% CI, 0.15 to 1.63). The proportional odds of having a worse score on the eight-level ordinal scale with tofacitinib, as compared with placebo, was 0.60 (95% CI, 0.36 to 1.00) at day 14 and 0.54 (95% CI, 0.27 to 1.06) at day 28. Serious adverse events occurred in 20 patients (14.1%) in the tofacitinib group and in 17 (12.0%) in the placebo group. CONCLUSIONS: Among patients hospitalized with Covid-19 pneumonia, tofacitinib led to a lower risk of death or respiratory failure through day 28 than placebo. (Funded by Pfizer; STOP-COVID ClinicalTrials.gov number, NCT04469114.).


Subject(s)
COVID-19/drug therapy , Glucocorticoids/therapeutic use , Janus Kinase Inhibitors/therapeutic use , Piperidines/therapeutic use , Pyrimidines/therapeutic use , Adult , Aged , Antiviral Agents/therapeutic use , Brazil , COVID-19/complications , COVID-19/mortality , COVID-19/therapy , Double-Blind Method , Drug Therapy, Combination , Female , Hospitalization , Humans , Incidence , Janus Kinase 3/antagonists & inhibitors , Janus Kinase Inhibitors/adverse effects , Male , Middle Aged , Oxygen Inhalation Therapy , Piperidines/adverse effects , Pyrimidines/adverse effects , Respiratory Insufficiency/epidemiology , Respiratory Insufficiency/etiology
18.
Acta Haematol ; 144(6): 620-626, 2021.
Article in English | MEDLINE | ID: covidwho-1263968

ABSTRACT

INTRODUCTION: Currently, severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection is a major public health problem worldwide. Although most patients present a mild infection, effective strategies are required for patients who develop the severe disease. Anti-inflammatory treatment with JAK inhibitors has been considered in SARS-CoV-2. METHODS: In this study, we presented our experience in a group of severe SARS-CoV-2 Chilean patients. This prospective study was performed on consecutive patients presenting severe respiratory failure owing to COVID-19 or high-risk clinical condition associated with SARS-CoV-2, and who were treated with ruxolitinib for management of associated inflammation. Overall, 18 patients presenting SARS-CoV-2 viral-induced hyperinflammation were treated with ruxolitinib, with 16 patients previously treated with steroids, 4 with tocilizumab, and 3 with both treatments. RESULTS: Ten patients evolved with favorable response, including 7 patients admitted with severe respiratory failure (PaFi less than 200 mm Hg in high-flow nasal cannula), presenting complete regression of hyperinflammation, regression of the lung lesions, and subsequent discharge. In the remaining 8 patients, 25% showed reduced inflammation, but early discharge was not achieved owing to the slow evolution of respiratory failure. Unfortunately, 3 patients demonstrated a severe respiratory failure. The early initiation of ruxolitinib was found to be associated with better clinical evolution (p < 0.005). CONCLUSION: In this study, ruxolitinib resolved hyperinflammatory state in 55% of the patients, regardless of the previous steroid or tocilizumab therapy. Unfortunately, few patients demonstrated severe evolution despite ruxolitinib therapy. Notably, the treatment starting time appears to play an important role in achieving good outcomes. Further validation in randomized controlled trials is crucial.


Subject(s)
COVID-19/complications , Inflammation/drug therapy , Nitriles/therapeutic use , Protein Kinase Inhibitors/therapeutic use , Pyrazoles/therapeutic use , Pyrimidines/therapeutic use , Adult , Aged , Aged, 80 and over , Antibodies, Monoclonal, Humanized/therapeutic use , COVID-19/pathology , COVID-19/virology , Chile , Female , Humans , Inflammation/etiology , Male , Middle Aged , Nitriles/adverse effects , Prospective Studies , Protein Kinase Inhibitors/adverse effects , Pyrazoles/adverse effects , Pyrimidines/adverse effects , Respiratory Insufficiency/drug therapy , Respiratory Insufficiency/etiology , SARS-CoV-2/isolation & purification , Steroids/therapeutic use , Thrombocytopenia/etiology , Treatment Outcome
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