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2.
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
3.
J Allergy Clin Immunol ; 149(2): 569-578, 2022 02.
Article in English | MEDLINE | ID: covidwho-1587444

ABSTRACT

Our understanding of risk factors and interventions influencing outcomes from coronavirus disease 2019 (COVID-19) has continued to evolve, revealing advances emerging from hypotheses formed at the start of the pandemic. Epidemiologic studies have shown that asthma control, rather than a diagnosis of asthma, is a determinant of COVID-19 severity. Clinical outcomes in patients with primary immunodeficiencies, even in those with impaired cellular immunity, are variable. IL-6 has emerged as a reliable biomarker of COVID-19 severity, and large clinical trials have shown the potential for improving outcomes through inhibition of IL-6 signaling in some patients. Studies of genetic risk factors for severe COVID-19 have also revealed the importance of interferon homeostasis in the defense against severe acute respiratory syndrome coronavirus 2. Because COVID-19 vaccines constitute the primary tool for ending this pandemic, strategies have been developed to address potential allergic and immune-mediated reactions. Here, we discuss advances in our understanding of COVID-19 risk factors and outcomes within the context of allergic and immunologic mechanisms.


Subject(s)
Antiviral Agents/therapeutic use , Asthma/therapy , Biological Products/therapeutic use , COVID-19/therapy , Immunologic Deficiency Syndromes/therapy , SARS-CoV-2/drug effects , Antibodies, Monoclonal/therapeutic use , Asthma/immunology , Asthma/mortality , Asthma/virology , Azetidines/therapeutic use , Biomarkers/metabolism , COVID-19/immunology , COVID-19/mortality , COVID-19/virology , COVID-19 Vaccines/administration & dosage , Humans , Immunologic Deficiency Syndromes/immunology , Immunologic Deficiency Syndromes/mortality , Immunologic Deficiency Syndromes/virology , Interleukin 1 Receptor Antagonist Protein/therapeutic use , Interleukin-6/antagonists & inhibitors , Interleukin-6/genetics , Interleukin-6/immunology , Prognosis , Purines/therapeutic use , Pyrazoles/therapeutic use , Risk Factors , SARS-CoV-2/pathogenicity , Sulfonamides/therapeutic use , Survival Analysis , Treatment Outcome
4.
Lancet Respir Med ; 9(12): 1407-1418, 2021 12.
Article in English | MEDLINE | ID: covidwho-1545515

ABSTRACT

BACKGROUND: Baricitinib is an oral selective Janus kinase 1/2 inhibitor with known anti-inflammatory properties. This study evaluates the efficacy and safety of baricitinib in combination with standard of care for the treatment of hospitalised adults with COVID-19. METHODS: In this phase 3, double-blind, randomised, placebo-controlled trial, participants were enrolled from 101 centres across 12 countries in Asia, Europe, North America, and South America. Hospitalised adults with COVID-19 receiving standard of care were randomly assigned (1:1) to receive once-daily baricitinib (4 mg) or matched placebo for up to 14 days. Standard of care included systemic corticosteroids, such as dexamethasone, and antivirals, including remdesivir. The composite primary endpoint was the proportion who progressed to high-flow oxygen, non-invasive ventilation, invasive mechanical ventilation, or death by day 28, assessed in the intention-to-treat population. All-cause mortality by day 28 was a key secondary endpoint, and all-cause mortality by day 60 was an exploratory endpoint; both were assessed in the intention-to-treat population. Safety analyses were done in the safety population defined as all randomly allocated participants who received at least one dose of study drug and who were not lost to follow-up before the first post-baseline visit. This study is registered with ClinicalTrials.gov, NCT04421027. FINDINGS: Between June 11, 2020, and Jan 15, 2021, 1525 participants were randomly assigned to the baricitinib group (n=764) or the placebo group (n=761). 1204 (79·3%) of 1518 participants with available data were receiving systemic corticosteroids at baseline, of whom 1099 (91·3%) were on dexamethasone; 287 (18·9%) participants were receiving remdesivir. Overall, 27·8% of participants receiving baricitinib and 30·5% receiving placebo progressed to meet the primary endpoint (odds ratio 0·85 [95% CI 0·67 to 1·08], p=0·18), with an absolute risk difference of -2·7 percentage points (95% CI -7·3 to 1·9). The 28-day all-cause mortality was 8% (n=62) for baricitinib and 13% (n=100) for placebo (hazard ratio [HR] 0·57 [95% CI 0·41-0·78]; nominal p=0·0018), a 38·2% relative reduction in mortality; one additional death was prevented per 20 baricitinib-treated participants. The 60-day all-cause mortality was 10% (n=79) for baricitinib and 15% (n=116) for placebo (HR 0·62 [95% CI 0·47-0·83]; p=0·0050). The frequencies of serious adverse events (110 [15%] of 750 in the baricitinib group vs 135 [18%] of 752 in the placebo group), serious infections (64 [9%] vs 74 [10%]), and venous thromboembolic events (20 [3%] vs 19 [3%]) were similar between the two groups. INTERPRETATION: Although there was no significant reduction in the frequency of disease progression overall, treatment with baricitinib in addition to standard of care (including dexamethasone) had a similar safety profile to that of standard of care alone, and was associated with reduced mortality in hospitalised adults with COVID-19. FUNDING: Eli Lilly and Company. TRANSLATIONS: For the French, Japanese, Portuguese, Russian and Spanish translations of the abstract see Supplementary Materials section.


Subject(s)
Azetidines/therapeutic use , COVID-19 , Purines/therapeutic use , Pyrazoles/therapeutic use , Sulfonamides/therapeutic use , Adenosine Monophosphate/analogs & derivatives , Adrenal Cortex Hormones , Adult , Alanine/analogs & derivatives , Antiviral Agents , Asia , COVID-19/drug therapy , Dexamethasone , Double-Blind Method , Europe , Humans , North America , SARS-CoV-2 , South America , Treatment Outcome
5.
Pediatr Rheumatol Online J ; 19(1): 163, 2021 Nov 29.
Article in English | MEDLINE | ID: covidwho-1542116

ABSTRACT

BACKGROUND: Flares of juvenile idiopathic arthritis (JIA) have been described in the context of various infections. Flares of rheumatic diseases in adults have been described following infection with SARS-CoV-2 in several cohorts. So far, the effect of infection with SARS-CoV-2 on the course of JIA is unknown. METHODS: The database of the German Center for Pediatric and Adolescent Rheumatology was searched for patients with confirmed infection with SARS-CoV-2 and subsequent disease flare, admitted from July 2020 until June 2021. cJADAS-27, ESR and C-reactive protein, as well as uveitis activity, medication at the time of flare and treatment of flare was extracted. Patient cases were described individually. RESULTS: Out of 988 patients admitted, five patients with remission off medication (n = 2) or inactive disease on medication (n = 3) were identified, with flare symptoms up to four weeks after infection with SARS-CoV-2. CONCLUSIONS: Flares can occur after infection with SARS-CoV-2 in patients with JIA in remission or inactive disease on medication. Treating physicians need to be aware of this fact, especially when counseling patients with rheumatic diseases about the respective dangers of COVID-19 and vaccination against SARS-CoV-2.


Subject(s)
Arthritis, Juvenile/physiopathology , COVID-19/physiopathology , Symptom Flare Up , Adolescent , Antibodies, Monoclonal/therapeutic use , Antirheumatic Agents/therapeutic use , Arthritis, Juvenile/complications , Arthritis, Juvenile/drug therapy , Arthritis, Juvenile/metabolism , Azetidines/therapeutic use , Blood Sedimentation , C-Reactive Protein/metabolism , COVID-19/complications , Child , Etanercept/therapeutic use , Female , Humans , Male , Methotrexate/therapeutic use , Purines/therapeutic use , Pyrazoles/therapeutic use , Remission Induction , SARS-CoV-2 , Sulfonamides/therapeutic use , Uveitis/complications , Uveitis/physiopathology
6.
J Med Virol ; 94(4): 1523-1534, 2022 04.
Article in English | MEDLINE | ID: covidwho-1540137

ABSTRACT

The benefits of baricitinib in coronavirus disease-2019 are inadequately defined. We performed a systematic review and meta-analysis of studies of baricitinib to determine its clinical efficacy and adverse events in patients with COVID-19. Databases were searched from their inception to September 5, 2021. The primary outcome was the coefficient of mortality. We also compared secondary indicators and adverse events between baricitinib treatment and placebo or other treatments. Twelve studies of 3564 patients were included and assessed qualitatively (modified Jadad and Newcastle-Ottawa Scale scores). Baricitinib effectively improved the mortality rate (relative risk of mortality = 0.56; 95% confidence interval: 0.46-0.69; p < 0.001; I2 = 2%), and this result was unchanged by subgroup analysis. Baricitinib improved intensive care unit admission, the requirement for invasive mechanical ventilation, and improved the oxygenation index. Data from these studies also showed that baricitinib slightly reduced the risk of adverse events. Regarding the choice of the drug dosage of baricitinib, the high-dose group appeared to have additional benefits for clinical efficacy. Our study shows that baricitinib may be a promising, safe, and effective anti-severe acute respiratory syndrome-coronavirus-2 drug candidate, with the advantages of low cost, easy production, and convenient storage.


Subject(s)
Azetidines/therapeutic use , COVID-19/drug therapy , Purines/therapeutic use , Pyrazoles/therapeutic use , Sulfonamides/therapeutic use , Azetidines/administration & dosage , COVID-19/mortality , Dose-Response Relationship, Drug , Humans , Purines/administration & dosage , Pyrazoles/administration & dosage , SARS-CoV-2 , Sulfonamides/administration & dosage , Treatment Outcome
7.
Dtsch Med Wochenschr ; 146(23): 1538-1542, 2021 Nov.
Article in German | MEDLINE | ID: covidwho-1537357

ABSTRACT

The pathophysiological course of COVID-19 can be distinguished in a phase of viral replication and an inflammatory phase. Hyperinflammatory processes promote the development of severe COVID-19. Therefore, immunomodulating agents came into focus. Dexamethasone has already become standard of care for treatment of severe COVID-19. Two large randomized trials and a meta-analysis of collectively nine randomized trials showed a reduced mortality in patients with severe COVID-19 if Tocilizumab - an IL-6-rezeptor antagonist - was added to standard of care. Treatment with Baricitinib - a JAK 1/2 inhibitor - may also be beneficial for patients without or on low oxygen supplementation. National and international guidelines recommend Tocilizumab for treatment of severe COVID-19. Treatment with JAK inhibitors is an option for hospitalized patients with moderate COVID-19. It should be emphasized that comedication of JAK inhibitors and Tocilizumab is not recommended. Further high quality research is required for the widespread use of immunomodulating agents in COVID-19.


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , COVID-19/drug therapy , /therapeutic use , Azetidines/therapeutic use , Humans , Purines/therapeutic use , Pyrazoles/therapeutic use , Sulfonamides/therapeutic use
8.
Mol Biol Rep ; 49(1): 827-831, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1536338

ABSTRACT

BACKGROUND: The global COVID-19 pandemic is currently underway. A massive worldwide vaccination campaign is still underway, representing the most promising weapon available to stop the pandemic. METHODS AND RESULTS: However, research continues to investigate the most effective drug treatments to reduce and avoid the most serious complications caused by COVID-19 infection. Recently, new evidence of good therapeutic efficacy against COVID-19 has emerged for the antiviral Remdesivir and the immunomodulatory Baricitinib, also in combination. The first one showed SARS-CoV-2 antireplicative activity, the second one useful to reduce the hyperinflammatory state caused by cytokine storm in the most severe phases of the infection. CONCLUSIONS: In this short communication we describe the molecular pharmacological mechanisms and the latest evidence for the use of these therapeutic agents in the treatment of COVID-19 infection.


Subject(s)
Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Azetidines/therapeutic use , COVID-19/drug therapy , Purines/therapeutic use , Pyrazoles/therapeutic use , Sulfonamides/therapeutic use , Adenosine Monophosphate/therapeutic use , Adult , Alanine/therapeutic use , Antiviral Agents/therapeutic use , Cytokine Release Syndrome/drug therapy , Drug Combinations , Humans , Immunologic Factors/therapeutic use , Pandemics
9.
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
10.
Aging (Albany NY) ; 13(18): 21866-21902, 2021 09 16.
Article in English | MEDLINE | ID: covidwho-1417381

ABSTRACT

BACKGROUND: Many recent studies have investigated the role of drug interventions for coronavirus disease 2019 (COVID-19) infection. However, an important question has been raised about how to select the effective and secure medications for COVID-19 patients. The aim of this analysis was to assess the efficacy and safety of the various medications available for severe and non-severe COVID-19 patients based on randomized placebo-controlled trials (RPCTs). METHODS: We did an updated network meta-analysis. We searched the databases from inception until July 31, 2021, with no language restrictions. We included RPCTs comparing 49 medications and placebo in the treatment of severe and non-severe patients (aged 18 years or older) with COVID-19 infection. We extracted data on the trial and patient characteristics, and the following primary outcomes: all-cause mortality, the ratios of virological cure, and treatment-emergent adverse events. Odds ratio (OR) and their 95% confidence interval (CI) were used as effect estimates. RESULTS: From 3,869 publications, we included 61 articles related to 73 RPCTs (57 in non-severe COVID-19 patients and 16 in severe COVID-19 patients), comprising 20,680 patients. The mean sample size was 160 (interquartile range 96-393) in this study. The median duration of follow-up drugs intervention was 28 days (interquartile range 21-30). For increase in virological cure, we only found that proxalutamide (OR 9.16, 95% CI 3.15-18.30), ivermectin (OR 6.33, 95% CI 1.22-32.86), and low dosage bamlanivimab (OR 5.29, 95% CI 1.12-24.99) seemed to be associated with non-severe COVID-19 patients when compared with placebo, in which proxalutamide seemed to be better than low dosage bamlanivimab (OR 5.69, 95% CI 2.43-17.65). For decrease in all-cause mortality, we found that proxalutamide (OR 0.13, 95% CI 0.09-0.19), imatinib (OR 0.49, 95% CI 0.25-0.96), and baricitinib (OR 0.58, 95% CI 0.42-0.82) seemed to be associated with non-severe COVID-19 patients; however, we only found that immunoglobulin gamma (OR 0.27, 95% CI 0.08-0.89) was related to severe COVID-19 patients when compared with placebo. For change in treatment-emergent adverse events, we only found that sotrovimab (OR 0.21, 95% CI 0.13-0.34) was associated with non-severe COVID-19 patients; however, we did not find any medications that presented a statistical difference when compared with placebo among severe COVID-19 patients. CONCLUSION: We conclude that marked variations exist in the efficacy and safety of medications between severe and non-severe patients with COVID-19. It seems that monoclonal antibodies (e.g., low dosage bamlanivimab, baricitinib, imatinib, and sotrovimab) are a better choice for treating severe or non-severe COVID-19 patients. Clinical decisions to use preferentially medications should carefully consider the risk-benefit profile based on efficacy and safety of all active interventions in patients with COVID-19 at different levels of infection.


Subject(s)
Antibodies, Monoclonal/therapeutic use , COVID-19/drug therapy , Immunologic Factors/therapeutic use , Antibodies, Monoclonal, Humanized/therapeutic use , Azetidines/therapeutic use , COVID-19/mortality , Humans , Imatinib Mesylate/therapeutic use , Network Meta-Analysis , Oxazoles/therapeutic use , Purines/therapeutic use , Pyrazoles/therapeutic use , SARS-CoV-2 , Severity of Illness Index , Sulfonamides/therapeutic use , Thiohydantoins/therapeutic use , Treatment Outcome
11.
Front Immunol ; 12: 694300, 2021.
Article in English | MEDLINE | ID: covidwho-1389186

ABSTRACT

We are currently experiencing a deadly novel viral pandemic with no efficacious, readily available anti-viral therapies to SARS-CoV-2. Viruses will hijack host cellular machinery, including metabolic processes. Here, I provide theory and evidence for targeting the host de novo purine synthetic pathway for broad spectrum anti-viral drug development as well as the pursuit of basic science to mitigate the risks of future novel viral outbreaks.


Subject(s)
Antiviral Agents/therapeutic use , COVID-19/drug therapy , Purines/therapeutic use , SARS-CoV-2/physiology , Animals , Drug Development , Humans , Immunity , Pandemics , Purines/chemical synthesis , Virus Replication
12.
Rheumatology (Oxford) ; 60(1): 399-407, 2021 01 05.
Article in English | MEDLINE | ID: covidwho-1388014

ABSTRACT

OBJECTIVES: The Janus kinase (JAK) inhibitor baricitinib may block viral entry into pneumocytes and prevent cytokine storm in patients with SARS-CoV-2 pneumonia. We aimed to assess whether baricitinib improved pulmonary function in patients treated with high-dose corticosteroids for moderate to severe SARS-CoV-2 pneumonia. METHODS: This observational study enrolled patients with moderate to severe SARS-CoV-2 pneumonia [arterial oxygen partial pressure (PaO2)/fraction of inspired oxygen (FiO2) <200 mmHg] who received lopinavir/ritonavir and HCQ plus either corticosteroids (CS group, n = 50) or corticosteroids and baricitinib (BCT-CS group, n = 62). The primary end point was the change in oxygen saturation as measured by pulse oximetry (SpO2)/FiO2 from hospitalization to discharge. Secondary end points included the proportion of patients requiring supplemental oxygen at discharge and 1 month later. Statistics were adjusted by the inverse propensity score weighting (IPSW). RESULTS: A greater improvement in SpO2/FiO2 from hospitalization to discharge was observed in the BCT-CS vs CS group (mean differences adjusted for IPSW, 49; 95% CI: 22, 77; P < 0.001). A higher proportion of patients required supplemental oxygen both at discharge (62.0% vs 25.8%; reduction of the risk by 82%, OR adjusted for IPSW, 0.18; 95% CI: 0.08, 0.43; P < 0.001) and 1 month later (28.0% vs 12.9%, reduction of the risk by 69%, OR adjusted for IPSW, 0.31; 95% CI: 0.11, 0.86; P = 0.024) in the CS vs BCT-CS group. CONCLUSIONS: . In patients with moderate to severe SARS-CoV-2 pneumonia a combination of baricitinib with corticosteroids was associated with greater improvement in pulmonary function when compared with corticosteroids alone. TRIAL REGISTRATION: European Network of Centres for Pharmacoepidemiology and Pharmacovigilance, ENCEPP (EUPAS34966, http://www.encepp.eu/encepp/viewResource.htm? id = 34967).


Subject(s)
Azetidines/therapeutic use , COVID-19/drug therapy , Glucocorticoids/therapeutic use , Hypoxia/therapy , Janus Kinase Inhibitors/therapeutic use , Methylprednisolone/therapeutic use , Oxygen Inhalation Therapy/statistics & numerical data , Purines/therapeutic use , Pyrazoles/therapeutic use , Sulfonamides/therapeutic use , Aged , Antiviral Agents/therapeutic use , COVID-19/metabolism , COVID-19/physiopathology , Cohort Studies , Drug Combinations , Drug Therapy, Combination , Endothelium, Vascular , Enzyme Inhibitors/therapeutic use , Female , Fibrin Fibrinogen Degradation Products/metabolism , Humans , Hydroxychloroquine/therapeutic use , Immunoglobulins, Intravenous/therapeutic use , Immunologic Factors/therapeutic use , Interferon beta-1b/therapeutic use , Lopinavir/therapeutic use , Lung/blood supply , Male , Middle Aged , Oximetry , Prospective Studies , Ritonavir/therapeutic use , SARS-CoV-2 , Severity of Illness Index
13.
Blood Rev ; 51: 100888, 2022 01.
Article in English | MEDLINE | ID: covidwho-1385128

ABSTRACT

Hairy cell leukemia (HCL) is an indolent B-cell malignancy, usually driven by the BRAF V600E mutation. For 30 years, untreated and relapsed HCL was successfully treated with purine analogs, but minimal residual disease (MRD) remained in most patients, eventually causing relapse. Repeated purine analogs achieve decreasing efficacy and increasing toxicity, particularly to normal T-cells. MRD-free complete remissions (CRs) are more common using rituximab with purine analogs in both 1st-line and relapsed settings. BRAF inhibitors and Ibrutinib can achieve remission, but due to persistence of MRD, must be used chronically to prevent relapse. BRAF inhibition combined with Rituximab can achieve high MRD-free CR rates. Anti-CD22 recombinant immunotoxin moxetumomab pasudotox is FDA-approved in the relapsed setting and is unique in achieving high MRD-free CR rates as a single-agent. Avoiding chemotherapy and rituximab may be important in ensuring both recovery from COVID-19 and successful COVID-19 vaccination, an area of continued investigation.


Subject(s)
COVID-19 , Leukemia, Hairy Cell/diagnosis , Leukemia, Hairy Cell/therapy , Pandemics , Antineoplastic Agents/therapeutic use , COVID-19/epidemiology , Humans , Leukemia, Hairy Cell/epidemiology , Neoplasm, Residual/diagnosis , Proto-Oncogene Proteins B-raf/antagonists & inhibitors , Purines/therapeutic use , Recurrence , Rituximab/therapeutic use
15.
Respir Investig ; 59(6): 799-803, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1347805

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) has spread worldwide and is also an important disease in Japan. Thus, the optimal treatment strategy for severe COVID-19 should be established urgently. The effects of combination treatment with baricitinib-a Janus kinase inhibitor, remdesivir, and dexamethasone (BRD) are unknown. METHODS: Patients who received combination therapy with BRD at the Japanese Red Cross Medical Center were enrolled in the study. All patients received baricitinib (≤14 d), remdesivir (≤10 d), and dexamethasone (≤10 d). The efficacy and adverse events were evaluated. RESULTS: In total, 44 patients with severe COVID-19 were enrolled in this study. The 28-d mortality rate was low at 2.3% (1/44 patients). The need for invasive mechanical ventilation was avoided in most patients (90%, 17/19 patients). Patients who received BRD therapy had a median hospitalization duration of 11 d, time to recovery of 9 d, duration of intensive care unit stay of 6 d, duration of invasive mechanical ventilation of 5 d, and duration of supplemental oxygen therapy of 5 d. Adverse events occurred in 15 patients (34%). Liver dysfunction, thrombosis, iliopsoas hematoma, renal dysfunction, ventilator-associated pneumonia, infective endocarditis, and herpes zoster occurred in 11%, 11%, 2%, 2%, 2%, 2%, and 2% of patients, respectively. CONCLUSIONS: Combination therapy with BRD was effective in treating severe COVID-19, and the incidence rate of adverse events was low. The results of the present study are encouraging; however, further randomized clinical studies are needed.


Subject(s)
Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Azetidines/therapeutic use , Dexamethasone/therapeutic use , Purines/therapeutic use , Pyrazoles/therapeutic use , Sulfonamides/therapeutic use , Adenosine Monophosphate/adverse effects , Adenosine Monophosphate/therapeutic use , Aged , Alanine/adverse effects , Alanine/therapeutic use , Azetidines/adverse effects , COVID-19/diagnosis , COVID-19/drug therapy , Dexamethasone/adverse effects , Drug Therapy, Combination , Female , Humans , Male , Middle Aged , Purines/adverse effects , Pyrazoles/adverse effects , Respiration, Artificial , SARS-CoV-2 , Sulfonamides/adverse effects , Treatment Outcome
18.
J Microbiol Immunol Infect ; 54(5): 787-793, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1293986

ABSTRACT

OBJECTIVE: We aimed to analyze clinical outcomes from patients with severe COVID-19 pneumonia that received either baricitinib plus dexamethasone or dexamethasone monotherapy. METHODOLOGY: We performed a retrospective comparative study. Data from hospitalized patients with severe COVID-19 pneumonia (saturation <93%, bilateral pulmonary infiltrates) that were treated with baricitinib plus dexamethasone or dexamethasone were collected. Our primary objective was to compare overall mortality and secondly to compare progression to mechanical ventilation and over infection rates. RESULTS: A total of 793 patients were assessed for inclusion criteria, 596 were excluded and 197 were analyzed for primary outcome: 123 in the baricitinib plus dexamethasone group and 74 in the dexamethasone monotherapy group. The mean age was 59.9 years (SD ± 14.5) and 62.1% (123/197) were male. 42.9% (85/197) of the cases required ICU admission and 25.8% (51/197) underwent invasive mechanical ventilation (IMV). Overall thirty-day mortality was 27.9% (55/197); Mortality was significantly lower in the baricitinib plus dexamethasone group compared to the dexamethasone monotherapy group (20.3% vs 40.5%, P = <.05). There was no difference in hospital acquired infections between both groups. CONCLUSION: Thirty-day mortality was significantly lower in patients with COVID-19 pneumonia treated with baricitinib plus dexamethasone versus dexamethasone monotherapy. No difference was observed in progression to invasive mechanical ventilation and hospital acquired infections.


Subject(s)
Azetidines/therapeutic use , COVID-19/drug therapy , Dexamethasone/therapeutic use , Purines/therapeutic use , Pyrazoles/therapeutic use , Sulfonamides/therapeutic use , Aged , Drug Therapy, Combination , Female , Humans , Male , Middle Aged , Retrospective Studies , SARS-CoV-2/drug effects
20.
Leukemia ; 35(9): 2616-2620, 2021 09.
Article in English | MEDLINE | ID: covidwho-1228235

ABSTRACT

We analyzed reports on safety and efficacy of JAK-inhibitors in patients with coronavirus infectious disease-2019 (COVID-19) published between January 1st and March 6th 2021 using the Newcastle-Ottawa and Jadad scales for quality assessment. We used disease severity as a proxy for time when JAK-inhibitor therapy was started. We identified 6 cohort studies and 5 clinical trials involving 2367 subjects treated with ruxolitinib (N = 3) or baricitinib 45 (N = 8). Use of JAK-inhibitors decreased use of invasive mechanical ventilation (RR = 0.63; [95% Confidence Interval (CI), 0.47, 0.84]; P = 0.002) and had borderline impact on rates of intensive care unit (ICU) admission (RR = 0.24 [0.06, 1.02]; P = 0.05) and acute respiratory distress syndrome (ARDS; RR = 0.50 [0.19, 1.33]; P = 0.16). JAK-inhibitors did not decrease length of hospitalization (mean difference (MD) -0.18 [-4.54, 4.18]; P = 0.94). Relative risks of death for both drugs were 0.42 [0.30, 0.59] (P < 0.001), for ruxolitinib, RR = 0.33 (0.13, 0.88; P = 0.03) and for baricitinib RR = 0.44 (0.31, 0.63; P < 0.001). Timing of JAK-inhibitor treatment during the course of COVID-19 treatment may be important in determining impact on outcome. However, these data are not consistently reported.


Subject(s)
Azetidines/therapeutic use , COVID-19/drug therapy , Janus Kinase Inhibitors/therapeutic use , Purines/therapeutic use , Pyrazoles/therapeutic use , SARS-CoV-2/drug effects , Sulfonamides/therapeutic use , COVID-19/pathology , COVID-19/virology , Clinical Trials as Topic , Humans , Nitriles , Patient Safety , Pyrimidines , SARS-CoV-2/isolation & purification , Treatment Outcome
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