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1.
Trials ; 22(1): 9, 2021 Jan 06.
Article in English | MEDLINE | ID: covidwho-1011237

ABSTRACT

OBJECTIVES: 1. To assess the efficacy of Mesenchymal Stromal Cells (MSC) versus a control arm as described in the primary endpoint. 2. To evaluate the effects of MSC on the secondary efficacy endpoints. 3. To evaluate the safety and tolerability profiles of MSC. 4. To study soluble and cellular biomarkers that might be involved in the course of the disease and the response to the investigational product. TRIAL DESIGN: A double-blind, randomized, controlled, trial to evaluate the efficacy and safety of MSC intravenous administration in patients with COVID-induced Acute Respiratory Distress Syndrome (ARDS) compared to a control arm. PARTICIPANTS: The trial is being conducted at a third level hospital, Hospital Universitario Puerta de Hierro, in Majadahonda, Madrid (Spain). Inclusion criteria 1. Informed consent prior to performing study procedures (witnessed oral consent with written consent by representatives will be accepted to avoid paper handling). Written consent by patient or representatives will be obtained whenever possible. 2. Adult patients ≥18 years of age at the time of enrolment. 3. Laboratory-confirmed SARS-CoV-2 infection as determined by Polymerase Chain Reaction (PCR), in oropharyngeal swabs or any other relevant specimen obtained during the course of the disease. Alternative tests (e.g., rapid antigen tests) are also acceptable as laboratory confirmation if their specificity has been accepted by the Sponsor. 4. Moderate to severe ARDS (PaO2/FiO2 ratio equal or less than 200 mmHg) for less than 96 hours at the time of randomization. 5. Patients requiring invasive ventilation are eligible within 72 hours from intubation. 6. Eligible for ICU admission, according to the clinical team. Exclusion criteria 1. Imminent and unavoidable progression to death within 24 hours, irrespective of the provision of treatments (in the opinion of the clinical team). 2. "Do Not Attempt Resuscitation" order in place. 3. Any end-stage organ disease or condition, which in the investigator's opinion, makes the patient an unsuitable candidate for treatment. 4. History of a moderate/severe lung disorder requiring home-based oxygen therapy. 5. Patient requiring Extracorporeal Membrane Oxygenation (ECMO), haemodialysis or hemofiltration at the time of treatment administration. 6. Current diagnosis of pulmonary embolism. 7. Active neoplasm, except carcinoma in situ or basalioma. 8. Known allergy to the products involved in the allogeneic MSC production process. 9. Current pregnancy or lactation (women with childbearing potential should have a negative pregnancy test result at the time of study enrolment). 10. Current participation in a clinical trial with an experimental treatment for COVID-19 (the use of any off-label medicine according to local treatment protocols is not an exclusion criteria). 11. Any circumstances that in the investigator's opinion compromises the patient's ability to participate in the clinical trial. INTERVENTION AND COMPARATOR: - Experimental treatment arm: Allogeneic MSC (approximately 1 x 106 cells/kg). - Control arm: placebo solution (same composition as the experimental treatment, without the MSC). One single intravenous dose of the assigned treatment will be administered on Day 0 of the study. All trial participants will receive standard of care (SOC). In the context of the current worldwide pandemic, SOC can include medicines that are being used in clinical practice (e.g. lopinavir/ritonavir; hydroxy/chloroquine, tocilizumab, etc.), as well as those authorised for COVID (e.g., remdesivir). MAIN OUTCOMES: Primary endpoint: Change in the PaO2/FiO2 ratio from baseline to day 7 of treatment administration, or to the last available PaO2/FiO2 ratio if death occurs before day 7. Secondary endpoints: - All-cause mortality on days 7, 14, and 28 after treatment. - PaO2/FiO2 ratio at baseline and days 2, 4, 7, 14 and 28 after treatment. - Oxygen saturation (by standardized measurement) at baseline, daily until day 14, and on day 28 after treatment. - Time to PaO2/FiO2 ratio greater than 200 mmHg. - Subjects' clinical status on the WHO 7-point ordinal scale at baseline, daily until day 14, and on day 28 after treatment. - Time to an improvement of one category from admission on the WHO 7-point ordinal scale. - Percentage of patients that worsen at least one category on the WHO 7-point ordinal scale. - Percentage of patients that improve at least one category (maintained 48h) on the WHO 7-point ordinal scale. - Sequential Organ Failure Assessment (SOFA) scale at baseline and days 2, 4, 7, 14 and 28 after treatment. - Duration of hospitalization (days). - Duration of ICU stay (days). - Oxygen therapy-free days in the first 28 days after treatment. - Duration of supplemental oxygen. - Incidence of and duration of non-invasive and invasive mechanical ventilation in the first 28 days after treatment. - Mechanical ventilation-free days in the first 28 days after treatment. - Ventilation parameters. - Incidence of new onset pulmonary fibrosis at 3 and 12 months after treatment, based on CT scan and pulmonary function tests. - Survival at 3 and 12 months. - Cumulative incidence of Serious Adverse events (SAEs) and Grade 3 and 4 Adverse Events (AEs). - Cumulative incidence of Adverse Drug Reactions (ADR) in the experimental treatment arm. - Cumulative incidence of AEs of special interest. - Levels of analytical markers (C-Reactive Protein, lymphocyte and neutrophil counts, lymphocyte subpopulations, LDH, ferritin, D-dimer, coagulation tests and cytokines...) at baseline and days 2, 4, 7, 14 and 28 after treatment. - Other soluble and cellular biomarkers that might be involved in the course of the disease and the response to MSC. RANDOMISATION: The assignment to treatment will be carried out randomly and blinded, with a 1:1 allocation. Randomization will be done through a centralized system embedded in the electronic Case Report Form (CRF). BLINDING (MASKING): To ensure blinding, treatments will be prepared for administration at the Cell Production Unit and the administration of the treatment will be masked, not allowing the identification of the Investigational Medicinal Product (IMP). NUMBERS TO BE RANDOMISED (SAMPLE SIZE): A total of 20 participants are planned to be randomized, 10 to each treatment group. TRIAL STATUS: Protocol version: 1.2, dated October 14th, 2020 Start of recruitment: 01/10/2020 End of recruitment (estimated): December 2020. TRIAL REGISTRATION: EudraCT Number: 2020-002193-27 , registered on July 14th, 2020. NCT number: NCT04615429 , registered on November 4th, 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.


Subject(s)
Antiviral Agents/administration & dosage , Mesenchymal Stem Cell Transplantation/methods , /therapy , Administration, Intravenous , Adult , Biomarkers/blood , /diagnosis , Clinical Trials, Phase II as Topic , Combined Modality Therapy/adverse effects , Combined Modality Therapy/methods , Double-Blind Method , Female , Humans , Male , Mesenchymal Stem Cell Transplantation/adverse effects , Randomized Controlled Trials as Topic , Respiration, Artificial , /diagnosis , /isolation & purification , Severity of Illness Index , Spain , Standard of Care , Transplantation, Homologous/adverse effects , Transplantation, Homologous/methods
2.
Nutrients ; 12(12)2020 Dec 07.
Article in English | MEDLINE | ID: covidwho-967092

ABSTRACT

There are limited proven therapies for COVID-19. Vitamin C's antioxidant, anti-inflammatory and immunomodulating effects make it a potential therapeutic candidate, both for the prevention and amelioration of COVID-19 infection, and as an adjunctive therapy in the critical care of COVID-19. This literature review focuses on vitamin C deficiency in respiratory infections, including COVID-19, and the mechanisms of action in infectious disease, including support of the stress response, its role in preventing and treating colds and pneumonia, and its role in treating sepsis and COVID-19. The evidence to date indicates that oral vitamin C (2-8 g/day) may reduce the incidence and duration of respiratory infections and intravenous vitamin C (6-24 g/day) has been shown to reduce mortality, intensive care unit (ICU) and hospital stays, and time on mechanical ventilation for severe respiratory infections. Further trials are urgently warranted. Given the favourable safety profile and low cost of vitamin C, and the frequency of vitamin C deficiency in respiratory infections, it may be worthwhile testing patients' vitamin C status and treating them accordingly with intravenous administration within ICUs and oral administration in hospitalised persons with COVID-19.


Subject(s)
Ascorbic Acid Deficiency/drug therapy , Ascorbic Acid/therapeutic use , Respiratory Tract Infections/drug therapy , Sepsis/drug therapy , Vitamins/therapeutic use , Administration, Intravenous , Administration, Oral , Anti-Inflammatory Agents/therapeutic use , Ascorbic Acid Deficiency/complications , /virology , Chemotherapy, Adjuvant , Critical Care , Hospitalization , Humans , Immunologic Factors/therapeutic use , Intensive Care Units , Nutritional Status , Pandemics , Respiration, Artificial , Respiratory Tract Infections/etiology , Respiratory Tract Infections/virology , Sepsis/etiology , Sepsis/virology
3.
BMJ Open ; 10(12): e040580, 2020 Dec 02.
Article in English | MEDLINE | ID: covidwho-955465

ABSTRACT

INTRODUCTION: SARS-CoV-2 (COVID-19) has caused an international pandemic of respiratory illness, resulting in significant healthcare and economic turmoil. To date, no robust vaccine or treatment has been identified. Elemental zinc has previously been demonstrated to have beneficial effects on coronaviruses and other viral respiratory infections due to its effect on RNA polymerase. Additionally, zinc has well-demonstrated protective effects against hypoxic injury-a clear mechanism of end-organ injury in respiratory distress syndrome. We aimed to assess the effect of high-dose intravenous zinc (HDIVZn) on SARS-CoV-2 infection. The end of study analyses will evaluate the reduction of impact of oxygen saturations or requirement of oxygen supplementation. METHODS AND ANALYSIS: We designed a double-blind randomised controlled trial of daily HDIVZn (0.5 mg/kg) versus placebo. Primary outcome measures are lowest oxygen saturation (or greatest level of supplemental oxygenation) for non-ventilated patients and worst PaO2/FiO2 for ventilated patients. Following power calculations, 60 hospitalised patients and 100 ventilated patients will be recruited to demonstrate a 20% difference. The duration of follow-up is up to the point of discharge. ETHICS AND DISSEMINATION: Ethical approval was obtained through the independent Human Research Ethics Committee. Participant recruitment will commence in May 2020. Results will be published in peer-reviewed medical journals. TRIAL REGISTRATION NUMBER: ACTRN126200000454976.


Subject(s)
/drug therapy , Zinc/administration & dosage , Administration, Intravenous , Adult , Clinical Trials, Phase II as Topic , Double-Blind Method , Female , Humans , Hypoxia/prevention & control , Male , Oxygen/blood , Pandemics , Randomized Controlled Trials as Topic , Zinc/adverse effects
4.
Lancet ; 396(10266): 1895-1904, 2020 12 12.
Article in English | MEDLINE | ID: covidwho-922171

ABSTRACT

BACKGROUND: Intravenous ferric carboxymaltose has been shown to improve symptoms and quality of life in patients with chronic heart failure and iron deficiency. We aimed to evaluate the effect of ferric carboxymaltose, compared with placebo, on outcomes in patients who were stabilised after an episode of acute heart failure. METHODS: AFFIRM-AHF was a multicentre, double-blind, randomised trial done at 121 sites in Europe, South America, and Singapore. Eligible patients were aged 18 years or older, were hospitalised for acute heart failure with concomitant iron deficiency (defined as ferritin <100 µg/L, or 100-299 µg/L with transferrin saturation <20%), and had a left ventricular ejection fraction of less than 50%. Before hospital discharge, participants were randomly assigned (1:1) to receive intravenous ferric carboxymaltose or placebo for up to 24 weeks, dosed according to the extent of iron deficiency. To maintain masking of patients and study personnel, treatments were administered in black syringes by personnel not involved in any study assessments. The primary outcome was a composite of total hospitalisations for heart failure and cardiovascular death up to 52 weeks after randomisation, analysed in all patients who received at least one dose of study treatment and had at least one post-randomisation data point. Secondary outcomes were the composite of total cardiovascular hospitalisations and cardiovascular death; cardiovascular death; total heart failure hospitalisations; time to first heart failure hospitalisation or cardiovascular death; and days lost due to heart failure hospitalisations or cardiovascular death, all evaluated up to 52 weeks after randomisation. Safety was assessed in all patients for whom study treatment was started. A pre-COVID-19 sensitivity analysis on the primary and secondary outcomes was prespecified. This study is registered with ClinicalTrials.gov, NCT02937454, and has now been completed. FINDINGS: Between March 21, 2017, and July 30, 2019, 1525 patients were screened, of whom 1132 patients were randomly assigned to study groups. Study treatment was started in 1110 patients, and 1108 (558 in the carboxymaltose group and 550 in the placebo group) had at least one post-randomisation value. 293 primary events (57·2 per 100 patient-years) occurred in the ferric carboxymaltose group and 372 (72·5 per 100 patient-years) occurred in the placebo group (rate ratio [RR] 0·79, 95% CI 0·62-1·01, p=0·059). 370 total cardiovascular hospitalisations and cardiovascular deaths occurred in the ferric carboxymaltose group and 451 occurred in the placebo group (RR 0·80, 95% CI 0·64-1·00, p=0·050). There was no difference in cardiovascular death between the two groups (77 [14%] of 558 in the ferric carboxymaltose group vs 78 [14%] in the placebo group; hazard ratio [HR] 0·96, 95% CI 0·70-1·32, p=0·81). 217 total heart failure hospitalisations occurred in the ferric carboxymaltose group and 294 occurred in the placebo group (RR 0·74; 95% CI 0·58-0·94, p=0·013). The composite of first heart failure hospitalisation or cardiovascular death occurred in 181 (32%) patients in the ferric carboxymaltose group and 209 (38%) in the placebo group (HR 0·80, 95% CI 0·66-0·98, p=0·030). Fewer days were lost due to heart failure hospitalisations and cardiovascular death for patients assigned to ferric carboxymaltose compared with placebo (369 days per 100 patient-years vs 548 days per 100 patient-years; RR 0·67, 95% CI 0·47-0·97, p=0·035). Serious adverse events occurred in 250 (45%) of 559 patients in the ferric carboxymaltose group and 282 (51%) of 551 patients in the placebo group. INTERPRETATION: In patients with iron deficiency, a left ventricular ejection fraction of less than 50%, and who were stabilised after an episode of acute heart failure, treatment with ferric carboxymaltose was safe and reduced the risk of heart failure hospitalisations, with no apparent effect on the risk of cardiovascular death. FUNDING: Vifor Pharma.


Subject(s)
Anemia, Iron-Deficiency/drug therapy , Ferric Compounds/therapeutic use , Heart Failure/drug therapy , Maltose/analogs & derivatives , Administration, Intravenous , Aged , Aged, 80 and over , Double-Blind Method , Female , Ferric Compounds/administration & dosage , Heart Failure/complications , Heart Failure/mortality , Hospitalization/statistics & numerical data , Humans , Male , Maltose/administration & dosage , Maltose/therapeutic use , Middle Aged , Patient Discharge , Treatment Outcome , Ventricular Function, Left
5.
N Engl J Med ; 383(20): 1907-1919, 2020 11 12.
Article in English | MEDLINE | ID: covidwho-920642

ABSTRACT

BACKGROUND: Antibiotic therapy has been proposed as an alternative to surgery for the treatment of appendicitis. METHODS: We conducted a pragmatic, nonblinded, noninferiority, randomized trial comparing antibiotic therapy (10-day course) with appendectomy in patients with appendicitis at 25 U.S. centers. The primary outcome was 30-day health status, as assessed with the European Quality of Life-5 Dimensions (EQ-5D) questionnaire (scores range from 0 to 1, with higher scores indicating better health status; noninferiority margin, 0.05 points). Secondary outcomes included appendectomy in the antibiotics group and complications through 90 days; analyses were prespecified in subgroups defined according to the presence or absence of an appendicolith. RESULTS: In total, 1552 adults (414 with an appendicolith) underwent randomization; 776 were assigned to receive antibiotics (47% of whom were not hospitalized for the index treatment) and 776 to undergo appendectomy (96% of whom underwent a laparoscopic procedure). Antibiotics were noninferior to appendectomy on the basis of 30-day EQ-5D scores (mean difference, 0.01 points; 95% confidence interval [CI], -0.001 to 0.03). In the antibiotics group, 29% had undergone appendectomy by 90 days, including 41% of those with an appendicolith and 25% of those without an appendicolith. Complications were more common in the antibiotics group than in the appendectomy group (8.1 vs. 3.5 per 100 participants; rate ratio, 2.28; 95% CI, 1.30 to 3.98); the higher rate in the antibiotics group could be attributed to those with an appendicolith (20.2 vs. 3.6 per 100 participants; rate ratio, 5.69; 95% CI, 2.11 to 15.38) and not to those without an appendicolith (3.7 vs. 3.5 per 100 participants; rate ratio, 1.05; 95% CI, 0.45 to 2.43). The rate of serious adverse events was 4.0 per 100 participants in the antibiotics group and 3.0 per 100 participants in the appendectomy group (rate ratio, 1.29; 95% CI, 0.67 to 2.50). CONCLUSIONS: For the treatment of appendicitis, antibiotics were noninferior to appendectomy on the basis of results of a standard health-status measure. In the antibiotics group, nearly 3 in 10 participants had undergone appendectomy by 90 days. Participants with an appendicolith were at a higher risk for appendectomy and for complications than those without an appendicolith. (Funded by the Patient-Centered Outcomes Research Institute; CODA ClinicalTrials.gov number, NCT02800785.).


Subject(s)
Anti-Bacterial Agents/therapeutic use , Appendectomy , Appendicitis/drug therapy , Appendicitis/surgery , Appendix/surgery , Absenteeism , Administration, Intravenous , Adult , Anti-Bacterial Agents/adverse effects , Appendectomy/statistics & numerical data , Appendicitis/complications , Appendix/pathology , Fecal Impaction , Female , Health Status , Hospitalization/statistics & numerical data , Humans , Laparoscopy , Male , Middle Aged , Postoperative Complications/epidemiology , Quality of Life , Surveys and Questionnaires , Treatment Outcome
6.
Int J Infect Dis ; 101: 59-64, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-905663

ABSTRACT

BACKGROUND: The release of pro-inflammatory cytokines, resulting in cytokine storm syndrome, contributes to the morbidity and mortality associated with COVID-19 disease. This study aimed to compare the effects of intravenous (IV) and subcutaneous (SC) tocilizumab, an IL-6 receptor antagonist, on respiratory parameters and clinical outcome in patients with COVID 19. METHODS: We performed a retrospective cohort study of hospitalized patients with COVID-19 treated with either IV or SC tocilizumab from March 26, 2020, to May 18, 2020. Respiratory parameters seven days after receiving tocilizumab therapy were compared to baseline measurements. All patients were assessed until discharged from the hospital. RESULTS: Tocilizumab was administered to 125 patients: 65 received IV, and 60 received SC therapy. At day seven, 52% of the IV group patients demonstrated improvement in respiratory parameters, compared to 28% in the SC group (P = 0.01). Mortality rates at days seven and 28 were 15% and 37%, respectively, in the IV group and 17% and 50%, respectively, in the SC group (PNS). The in-hospital mortality rate was 38% for the IV group versus 57% for the SC group (P = 0.04). More than 90% of patients in each group received corticosteroids; however, significantly more patients received convalescent plasma in the IV group. CONCLUSIONS: At the doses used in this study, IV tocilizumab is preferred over SC therapy to treat cytokine storm syndrome due to COVID-19.


Subject(s)
Antibodies, Monoclonal, Humanized/administration & dosage , /drug therapy , Administration, Intravenous , Adult , Aged , Cytokine Release Syndrome/drug therapy , Female , Hospital Mortality , Humans , Injections, Subcutaneous , Male , Middle Aged , Retrospective Studies
7.
N Engl J Med ; 383(19): 1813-1826, 2020 11 05.
Article in English | MEDLINE | ID: covidwho-884844

ABSTRACT

BACKGROUND: Although several therapeutic agents have been evaluated for the treatment of coronavirus disease 2019 (Covid-19), no antiviral agents have yet been shown to be efficacious. METHODS: We conducted a double-blind, randomized, placebo-controlled trial of intravenous remdesivir in adults who were hospitalized with Covid-19 and had evidence of lower respiratory tract infection. Patients were randomly assigned to receive either remdesivir (200 mg loading dose on day 1, followed by 100 mg daily for up to 9 additional days) or placebo for up to 10 days. The primary outcome was the time to recovery, defined by either discharge from the hospital or hospitalization for infection-control purposes only. RESULTS: A total of 1062 patients underwent randomization (with 541 assigned to remdesivir and 521 to placebo). Those who received remdesivir had a median recovery time of 10 days (95% confidence interval [CI], 9 to 11), as compared with 15 days (95% CI, 13 to 18) among those who received placebo (rate ratio for recovery, 1.29; 95% CI, 1.12 to 1.49; P<0.001, by a log-rank test). In an analysis that used a proportional-odds model with an eight-category ordinal scale, the patients who received remdesivir were found to be more likely than those who received placebo to have clinical improvement at day 15 (odds ratio, 1.5; 95% CI, 1.2 to 1.9, after adjustment for actual disease severity). The Kaplan-Meier estimates of mortality were 6.7% with remdesivir and 11.9% with placebo by day 15 and 11.4% with remdesivir and 15.2% with placebo by day 29 (hazard ratio, 0.73; 95% CI, 0.52 to 1.03). Serious adverse events were reported in 131 of the 532 patients who received remdesivir (24.6%) and in 163 of the 516 patients who received placebo (31.6%). CONCLUSIONS: Our data show that remdesivir was superior to placebo in shortening the time to recovery in adults who were hospitalized with Covid-19 and had evidence of lower respiratory tract infection. (Funded by the National Institute of Allergy and Infectious Diseases and others; ACTT-1 ClinicalTrials.gov number, NCT04280705.).


Subject(s)
Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Antiviral Agents/therapeutic use , Coronavirus Infections/drug therapy , Pneumonia, Viral/drug therapy , Adenosine Monophosphate/administration & dosage , Adenosine Monophosphate/adverse effects , Adenosine Monophosphate/therapeutic use , Administration, Intravenous , Adult , Aged , Alanine/administration & dosage , Alanine/adverse effects , Alanine/therapeutic use , Antiviral Agents/administration & dosage , Antiviral Agents/adverse effects , Betacoronavirus , Coronavirus Infections/mortality , Coronavirus Infections/therapy , Double-Blind Method , Extracorporeal Membrane Oxygenation , Female , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Oxygen Inhalation Therapy , Pandemics , Pneumonia, Viral/mortality , Pneumonia, Viral/therapy , Respiration, Artificial , Time Factors , Young Adult
8.
J Med Virol ; 92(11): 2852-2856, 2020 11.
Article in English | MEDLINE | ID: covidwho-866098

ABSTRACT

INTRODUCTION: The most serious COVID-19 deriving from severe acute respiratory syndrome coronavirus 2 causes a cytokine release storm and it is associated with worse outcomes. In COVID-19 patients, interleukin-6 (IL-6) levels are significantly elevated. Blocking IL-6 preliminarily resulted in the improvement of this hyperinflammatory state. It is unknown which patients could require higher doses of tocilizumab to get out of the cytokine storm. MATERIALS AND METHODS: Twenty-four patients affected by COVID-19 pneumonia were included. All the patients underwent tocilizumab 8 mg/kg intravenously and were tested for serum IL-6 24 to 48 hours before and 12 to 48 hours after tocilizumab infusion. Comparisons between survivors and nonsurvivors were performed. RESULTS: Eighteen patients were discharged, while six patients died, with no clinical or laboratory differences between the two groups at baseline. IL-6 was not different at baseline (P = .41), while 24 to 48 hours post-tocilizumab IL-6 serum levels were significantly higher in nonsurvivors than in survivors (2398.5 [430.5-9372] vs 290.5 [58.5-1305.5] pg/mL, P = .022). Serum IL-6 post-tocilizumab showed a good predictive ability to discriminate survivors from nonsurvivors (area under the curve, 0.815; 95% confidence interval, 0.63-0.99, P = .02). CONCLUSION: Repeated measurement of the serum level of IL-6 early after tocilizumab may distinguish nonsurvivors from survivors and support the choice of deeper targeting IL-6 in COVID-19 pneumonia.


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Interleukin-6/blood , Survivors/statistics & numerical data , Administration, Intravenous , Aged , Biomarkers/blood , Cytokine Release Syndrome/drug therapy , Cytokine Release Syndrome/virology , Female , Humans , Male , Middle Aged , Retrospective Studies , Severity of Illness Index
9.
Contemp Clin Trials ; 98: 106165, 2020 11.
Article in English | MEDLINE | ID: covidwho-816323

ABSTRACT

BACKGROUND: Pneumonia is the most frequent complication of COVID-19, due to an aberrant host immune response that is associated with an acute respiratory distress syndrome, and, in most critical patients, with a "cytokine storm". IL-6 might play a key role in the cytokine storm and might be a potential target to treat severe and critical COVID-19. Tocilizumab is a recombinant humanized monoclonal antibody, directed against IL-6 receptor. METHODS: This multicentre study project includes a single-arm phase 2 study and a further parallel cohort, enrolling hospitalized patients with COVID-19 pneumonia and oxygen saturation at rest in ambient air ≤93% or requiring respiratory support. Patients receive tocilizumab 8 mg/kg (up to 800 mg) as one intravenous administration. A second administration (same dose) after 12 h is optional. Two-week and one-month lethality rates are the co-primary endpoints. Sample size planned for the phase 2 study is 330 patients. The parallel cohort will include patients who cannot enter the phase 2 study because being intubated from more than 24 h, or having already received tocilizumab, or the phase 2 study has reached sample size. Primary analysis will include patients enrolled in the phase 2 study. Results of the primary analysis will be validated in the prospective cohort of patients consecutively registered after phase 2 closure from March 20 to March 24, who were potentially eligible for the phase 2 study. CONCLUSION: This trial aims to verify the safety and efficacy of tocilizumab in the Italian population with COVID-19 pneumonia and respiratory impairment. EudraCT Number: 2020-001110-38; Clinicaltrials.gov ID NCT04317092.


Subject(s)
Antibodies, Monoclonal, Humanized , Cytokine Release Syndrome , Pneumonia, Viral , Receptors, Interleukin-6/antagonists & inhibitors , Administration, Intravenous , Adult , Antibodies, Monoclonal, Humanized/administration & dosage , Antibodies, Monoclonal, Humanized/adverse effects , /immunology , /therapy , Clinical Trials, Phase II as Topic , Cytokine Release Syndrome/drug therapy , Cytokine Release Syndrome/etiology , Cytokine Release Syndrome/immunology , Drug Administration Schedule , Drug Monitoring , Female , Humans , Immunologic Factors/administration & dosage , Immunologic Factors/adverse effects , Male , Multicenter Studies as Topic , Pneumonia, Viral/drug therapy , Pneumonia, Viral/etiology , Treatment Outcome
10.
JAMA ; 324(11): 1048-1057, 2020 09 15.
Article in English | MEDLINE | ID: covidwho-762932

ABSTRACT

Importance: Remdesivir demonstrated clinical benefit in a placebo-controlled trial in patients with severe coronavirus disease 2019 (COVID-19), but its effect in patients with moderate disease is unknown. Objective: To determine the efficacy of 5 or 10 days of remdesivir treatment compared with standard care on clinical status on day 11 after initiation of treatment. Design, Setting, and Participants: Randomized, open-label trial of hospitalized patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and moderate COVID-19 pneumonia (pulmonary infiltrates and room-air oxygen saturation >94%) enrolled from March 15 through April 18, 2020, at 105 hospitals in the United States, Europe, and Asia. The date of final follow-up was May 20, 2020. Interventions: Patients were randomized in a 1:1:1 ratio to receive a 10-day course of remdesivir (n = 197), a 5-day course of remdesivir (n = 199), or standard care (n = 200). Remdesivir was dosed intravenously at 200 mg on day 1 followed by 100 mg/d. Main Outcomes and Measures: The primary end point was clinical status on day 11 on a 7-point ordinal scale ranging from death (category 1) to discharged (category 7). Differences between remdesivir treatment groups and standard care were calculated using proportional odds models and expressed as odds ratios. An odds ratio greater than 1 indicates difference in clinical status distribution toward category 7 for the remdesivir group vs the standard care group. Results: Among 596 patients who were randomized, 584 began the study and received remdesivir or continued standard care (median age, 57 [interquartile range, 46-66] years; 227 [39%] women; 56% had cardiovascular disease, 42% hypertension, and 40% diabetes), and 533 (91%) completed the trial. Median length of treatment was 5 days for patients in the 5-day remdesivir group and 6 days for patients in the 10-day remdesivir group. On day 11, patients in the 5-day remdesivir group had statistically significantly higher odds of a better clinical status distribution than those receiving standard care (odds ratio, 1.65; 95% CI, 1.09-2.48; P = .02). The clinical status distribution on day 11 between the 10-day remdesivir and standard care groups was not significantly different (P = .18 by Wilcoxon rank sum test). By day 28, 9 patients had died: 2 (1%) in the 5-day remdesivir group, 3 (2%) in the 10-day remdesivir group, and 4 (2%) in the standard care group. Nausea (10% vs 3%), hypokalemia (6% vs 2%), and headache (5% vs 3%) were more frequent among remdesivir-treated patients compared with standard care. Conclusions and Relevance: Among patients with moderate COVID-19, those randomized to a 10-day course of remdesivir did not have a statistically significant difference in clinical status compared with standard care at 11 days after initiation of treatment. Patients randomized to a 5-day course of remdesivir had a statistically significant difference in clinical status compared with standard care, but the difference was of uncertain clinical importance. Trial Registration: ClinicalTrials.gov Identifier: NCT04292730.


Subject(s)
Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Antiviral Agents/therapeutic use , Betacoronavirus , Coronavirus Infections/drug therapy , Pneumonia, Viral/drug therapy , Adenosine Monophosphate/administration & dosage , Adenosine Monophosphate/adverse effects , Adenosine Monophosphate/therapeutic use , Administration, Intravenous , Aged , Alanine/administration & dosage , Alanine/adverse effects , Alanine/therapeutic use , Antiviral Agents/administration & dosage , Antiviral Agents/adverse effects , Coronavirus Infections/mortality , Drug Administration Schedule , Female , Hospitalization/statistics & numerical data , Humans , Male , Middle Aged , Odds Ratio , Pandemics , Patient Acuity , Pneumonia, Viral/mortality , Treatment Outcome
11.
JAMA ; 324(13): 1307-1316, 2020 10 06.
Article in English | MEDLINE | ID: covidwho-739602

ABSTRACT

Importance: Acute respiratory distress syndrome (ARDS) due to coronavirus disease 2019 (COVID-19) is associated with substantial mortality and use of health care resources. Dexamethasone use might attenuate lung injury in these patients. Objective: To determine whether intravenous dexamethasone increases the number of ventilator-free days among patients with COVID-19-associated ARDS. Design, Setting, and Participants: Multicenter, randomized, open-label, clinical trial conducted in 41 intensive care units (ICUs) in Brazil. Patients with COVID-19 and moderate to severe ARDS, according to the Berlin definition, were enrolled from April 17 to June 23, 2020. Final follow-up was completed on July 21, 2020. The trial was stopped early following publication of a related study before reaching the planned sample size of 350 patients. Interventions: Twenty mg of dexamethasone intravenously daily for 5 days, 10 mg of dexamethasone daily for 5 days or until ICU discharge, plus standard care (n =151) or standard care alone (n = 148). Main Outcomes and Measures: The primary outcome was ventilator-free days during the first 28 days, defined as being alive and free from mechanical ventilation. Secondary outcomes were all-cause mortality at 28 days, clinical status of patients at day 15 using a 6-point ordinal scale (ranging from 1, not hospitalized to 6, death), ICU-free days during the first 28 days, mechanical ventilation duration at 28 days, and Sequential Organ Failure Assessment (SOFA) scores (range, 0-24, with higher scores indicating greater organ dysfunction) at 48 hours, 72 hours, and 7 days. Results: A total of 299 patients (mean [SD] age, 61 [14] years; 37% women) were enrolled and all completed follow-up. Patients randomized to the dexamethasone group had a mean 6.6 ventilator-free days (95% CI, 5.0-8.2) during the first 28 days vs 4.0 ventilator-free days (95% CI, 2.9-5.4) in the standard care group (difference, 2.26; 95% CI, 0.2-4.38; P = .04). At 7 days, patients in the dexamethasone group had a mean SOFA score of 6.1 (95% CI, 5.5-6.7) vs 7.5 (95% CI, 6.9-8.1) in the standard care group (difference, -1.16; 95% CI, -1.94 to -0.38; P = .004). There was no significant difference in the prespecified secondary outcomes of all-cause mortality at 28 days, ICU-free days during the first 28 days, mechanical ventilation duration at 28 days, or the 6-point ordinal scale at 15 days. Thirty-three patients (21.9%) in the dexamethasone group vs 43 (29.1%) in the standard care group experienced secondary infections, 47 (31.1%) vs 42 (28.3%) needed insulin for glucose control, and 5 (3.3%) vs 9 (6.1%) experienced other serious adverse events. Conclusions and Relevance: Among patients with COVID-19 and moderate or severe ARDS, use of intravenous dexamethasone plus standard care compared with standard care alone resulted in a statistically significant increase in the number of ventilator-free days (days alive and free of mechanical ventilation) over 28 days. Trial Registration: ClinicalTrials.gov Identifier: NCT04327401.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , Coronavirus Infections/drug therapy , Dexamethasone/therapeutic use , Pneumonia, Viral/drug therapy , Respiration, Artificial/statistics & numerical data , /drug therapy , Administration, Intravenous , Aged , Anti-Inflammatory Agents/adverse effects , Betacoronavirus , Brazil , Catheter-Related Infections/epidemiology , Coronavirus Infections/complications , Coronavirus Infections/mortality , Coronavirus Infections/therapy , Dexamethasone/adverse effects , Early Termination of Clinical Trials , Female , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/complications , Pneumonia, Viral/mortality , Pneumonia, Viral/therapy , /etiology
12.
Clin Med (Lond) ; 20(6): e215-e217, 2020 11.
Article in English | MEDLINE | ID: covidwho-736877

ABSTRACT

The emergence of the novel beta coronavirus SARS-CoV-2 and the ensuing COVID-19 pandemic has generated a rapidly evolving research landscape in the search for new therapeutic agents. The intravenous antiviral drug remdesivir has in vitro activity against SARS-CoV-2 and now studies have reported its clinical efficacy, demonstrating shorter time to recovery in hospitalised patients with severe COVID-19. Adverse event rates were low and remdesivir has now received conditional marketing authorisation from the European Medicines Agency. An interim clinical commissioning policy is in place in the UK. These studies make remdesivir the first antiviral drug able to alter the natural history of severe COVID-19, and a benchmark for the comparison of new therapies in the future. Ongoing studies are investigating its use in early mild/moderate COVID-19, alternative formulations, and the combination of remdesivir with immunomodulatory agents.


Subject(s)
Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Antiviral Agents , Coronavirus Infections/drug therapy , Pneumonia, Viral/drug therapy , Adenosine Monophosphate/administration & dosage , Adenosine Monophosphate/adverse effects , Adenosine Monophosphate/therapeutic use , Administration, Intravenous , Alanine/administration & dosage , Alanine/adverse effects , Alanine/therapeutic use , Antiviral Agents/administration & dosage , Antiviral Agents/adverse effects , Antiviral Agents/therapeutic use , Betacoronavirus , Female , Humans , Male , Middle Aged , Pandemics , Randomized Controlled Trials as Topic
13.
Trials ; 21(1): 699, 2020 Aug 05.
Article in English | MEDLINE | ID: covidwho-696582

ABSTRACT

OBJECTIVES: • Primary objective: to evaluate the effect of intravenous melatonin (IVM) on mortality in adult patients admitted to the intensive care unit (ICU) with COVID-19. • Secondary objectives: ◦ To evaluate the effect of IVM on ICU length of stay. ◦ To evaluate the effect of IVM on the length of mechanical ventilation (MV). ◦ To evaluate if the use of IVM is associated with an increase in the number of ventilator-free days. ◦ To evaluate if the use of IVM is associated with a reduced number of failing organs as determined by the sequential organ failure assessment (SOFA) scale. ◦ To evaluate if the use of IVM is associated with a reduction of the frequency and severity of COVID-19-associated thromboembolic phenomena. ◦ To evaluate if the use of IVM is associated with a decreased systemic inflammatory response assessed by plasma levels of ferritin, D-dimer, C-reactive protein, procalcitonin and interleukin-6. ◦ To evaluate if the use of IVM is associated with an improvement in hematologic parameters. ◦ To evaluate if the use of IVM is associated with an improvement in biochemical parameters. ◦ To evaluate if the use of IVM is associated with an improvement in blood gas analysis parameters. ◦ To evaluate adverse events during the 28 day study period. TRIAL DESIGN: Phase II, single center, double-blind, placebo-controlled randomized trial with a two-arm parallel group design and 2:1 allocation ratio. PARTICIPANTS: Only critically ill adult patients that fulfill all of the inclusion criteria and none of the exclusion criteria will be included. The study will be conducted in a mixed ICU of a publicly funded tertiary referral center in Madrid, Spain with a 30-bed capacity and 1100 admissions per year. • Inclusion criteria: ◦ Patient, family member or legal guardian has provided written Informed Consent. ◦ Age ε 18 years. ◦ Confirmed SARS-CoV-2 infection with compatible symptoms AND a positive RT-PCR. ◦ Admission to the ICU with acute hypoxemic respiratory failure attributed to SARS-CoV-2 infection. ◦ ICU length of stay of less than 7 days prior to randomization with or without MV and without signs of improvement in respiratory failure (MURRAY score at randomization greater or equal to the MURRAY score at ICU admission). • Exclusion criteria: ◦ Participant in a different COVID-19 study in which the study drug is under clinical development and hasn't been previously authorized for commercialization. ◦ Liver enzymes > 5 times the upper normal range. ◦ Chronic kidney disease with GFR < 30 mL/min/1.73 m2 (stage 4 or greater) or need for hemodialysis. ◦ Pregnancy. A pregnancy test will be performed on every woman younger than 55 years of age prior to inclusion. ◦ Terminal surgical or medical illness. ◦ Autoimmune disease. ◦ Any patient condition that can prevent the study procedures to be carried out at the treating physician's judgement. INTERVENTION AND COMPARATOR: All patients will receive standard-of-care treatment according to the current institutional protocols. In addition, patients will be randomized in a 2:1 ratio to receive: • Experimental group (12 patients): 7 days of 5 mg per Kg of actual body weight per day of intravenous melatonin every 6 hours. Maximum daily dose 500 mg per day. • Control group (6 patients): 7 days of 5 mg per Kg of actual body weight per day of intravenous identically-looking placebo every 6 hours. After 3 days of treatment, 3 intensive care physicians will evaluate the participant and decide whether or not to complete the treatment based on their clinical assessment: • If objective or subjective signs of improvement or no worsening of the general clinical condition, respiratory failure, inflammatory state or multi-organ failure are observed, the participant will continue the treatment until completion. • If an adverse effect or clinical impairment is observed that is objectively or subjectively attributable to the study drug the treatment will be stopped. MAIN OUTCOME: Mortality in each study group represented in frequency and time-to-event at day 28 after randomization RANDOMIZATION: The randomization sequence was created using SAS version 9.4 statistical software (programmed and validated macros) with a 2:1 allocation. No randomization seed was pre-specified. The randomization seed was generated using the time on the computer where the program was executed. BLINDING (MASKING): Participants, caregivers and study groups will be blinded to arm allocation. NUMBERS TO BE RANDOMIZED (SAMPLE SIZE): A total of 18 patients will be randomized in this trial: 12 to the experimental arm and 6 to the control arm. TRIAL STATUS: Protocol version 2.0, June 5th 2020. Trial status: recruitment not started. The first patient is expected to be recruited in October 2020. The last patient is anticipated to be recruited in August 2021. TRIAL REGISTRATION: EU Clinical Trials Register. Date of trial registration: 10 July 2020. URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2020-001808-42/ES FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.


Subject(s)
Betacoronavirus , Coronavirus Infections/drug therapy , Melatonin/administration & dosage , Pneumonia, Viral/drug therapy , Randomized Controlled Trials as Topic , Administration, Intravenous , Double-Blind Method , Humans , Intensive Care Units , Length of Stay , Melatonin/adverse effects , Pandemics
14.
Expert Rev Anti Infect Ther ; 18(12): 1259-1261, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-692086

ABSTRACT

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has affected almost 2.5 million people worldwide with almost 170,000 deaths reported to date. So far, there is scarce evidence for the current treatment options available for COVID-19. Vitamin C has previously been used for treatment of severe sepsis and septic shock. We reviewed the feasibility of using vitamin C in the setting of COVID-19 in a series of patients. METHODS: We sequentially identified a series of patients who were requiring at least 30% of FiO2 or more who received IV vitamin C as part of the COVID-19 treatment and analyzed their demographic and clinical characteristics. We compared inflammatory markers pre and post treatment including D-dimer and ferritin. RESULTS: We identified a total of 17 patients who received IV vitamin C for COVID-19. The inpatient mortality rate in this series was 12% with 17.6% rates of intubation and mechanical ventilation. We noted a significant decrease in inflammatory markers, including ferritin and D-dimer, and a trend to decreasing FiO2 requirements, after vitamin C administration. CONCLUSION: The use of IV vitamin C in patients with moderate to severe COVID-19 disease may be feasible.


Subject(s)
Ascorbic Acid/therapeutic use , Vitamins/therapeutic use , Administration, Intravenous , Aged , Anti-Inflammatory Agents/therapeutic use , Antibodies, Monoclonal, Humanized/therapeutic use , Antiviral Agents/therapeutic use , /physiopathology , Drug Therapy, Combination , Feasibility Studies , Female , Ferritins/blood , Fibrin Fibrinogen Degradation Products/metabolism , Hospital Mortality , Humans , Hydroxychloroquine/therapeutic use , Hypoxia/physiopathology , Intubation, Intratracheal/statistics & numerical data , Male , Methylprednisolone/therapeutic use , Middle Aged , Respiration, Artificial/statistics & numerical data , Retrospective Studies , Severity of Illness Index
15.
Euro Surveill ; 25(30)2020 07.
Article in English | MEDLINE | ID: covidwho-690936

ABSTRACT

We report a case of Legionella pneumonia in a dishwasher of a restaurant in Rome, Italy, just after the end of the lockdown that was in place to control the SARS-CoV-2 epidemic. The case highlights the importance of strict monitoring of water and air systems immediately before reopening business or public sector buildings, and the need to consider Legionella infections among the differential diagnosis of respiratory infections after lockdown due to the ongoing COVID-19 pandemic.


Subject(s)
Antigens, Bacterial/urine , Legionella pneumophila/isolation & purification , Legionella/isolation & purification , Legionnaires' Disease/diagnosis , Levofloxacin/therapeutic use , Pneumonia/diagnosis , Administration, Intravenous , Adult , Anti-Infective Agents, Urinary/therapeutic use , Cough/etiology , Fever/etiology , Headache/etiology , Humans , Legionnaires' Disease/drug therapy , Legionnaires' Disease/urine , Male , Pneumonia/drug therapy , Pneumonia/urine , Treatment Outcome
16.
West J Emerg Med ; 21(4): 737-741, 2020 May 20.
Article in English | MEDLINE | ID: covidwho-690883

ABSTRACT

In March 2020, the World Health Organization declared the spread of SARS-CoV-2 a global pandemic. To date, coronavirus disease-2019 (COVID-19) has spread to over 200 countries, leading to over 1.6 million cases and over 99,000 deaths. Given that there is neither a vaccine nor proven treatment for COVID-19, there is currently an urgent need for effective pharmacotherapy. To address the need for an effective treatment of SARS-CoV-2 during the worldwide pandemic, this systematic review of intravenous (IV) remdesivir was performed. Remdesivir, an anti-viral prodrug originally developed to treat Ebola virus disease, has shown broad spectrum activity against the Coronavirus family. A recent case report reported improvement of clinical symptoms with remdesivir in a patient with COVID-19. After conducting a systematic search of 18 clinical trial registries and three large scientific databases, we identified 86 potentially eligible items. Following removal of duplicates (n = 21), eligible studies were reviewed independently by two authors. After the first round of screening, inter-rater agreement was 98.5% (κ = 0.925). After the second round of full-text screening, inter-rater agreement was 100%. A total of seven ongoing and recruiting clinical trials of remdesivir (100-200 milligrams, intravenous [IV]) were included. We identified the following primary outcomes: patients discharged (n = 2); time to clinical status improvement (n = 2); improved O2 saturation (n = 2); body temperature normalization (n = 2); and clinical status (n = 1). Secondary outcomes in all identified studies included documentation of adverse events. Phase 3 trials are expected to be completed between April 2020-2023. Therefore, despite supportive data from in vitro and in vivo studies, the clinical effectiveness of IV remdesivir for treatment of COVID-19 and potential side effects remain incompletely defined in the human population.


Subject(s)
Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Antiviral Agents/therapeutic use , Betacoronavirus/drug effects , Coronavirus Infections/drug therapy , Pneumonia, Viral/drug therapy , Adenosine Monophosphate/administration & dosage , Adenosine Monophosphate/therapeutic use , Administration, Intravenous , Alanine/administration & dosage , Alanine/therapeutic use , Antiviral Agents/administration & dosage , Clinical Trials as Topic , Humans , Pandemics , Treatment Outcome
17.
Medicina (Kaunas) ; 56(8)2020 Jul 27.
Article in English | MEDLINE | ID: covidwho-680490

ABSTRACT

Treatment of acute respiratory distress syndrome (ARDS) due to COVID-19 pneumonia (CARDS) represents a clinical challenge, requiring often invasive mechanical ventilation (IMV). Since the pathogenesis of CARDS it probably involves a direct viral attack to pulmonary and endothelium cells, and immune-mediated inflammation with dysfunctional coagulation, it was suggested to interfere with interleukin-6 (IL-6) activity by using the IL-6 receptor monoclonal antibody tocilizumab (TCZ). We reported the case of a 54-year-old 100 kg male COVID-19 patient (BMI 29) with severe respiratory insufficiency featuring dyspnea and hypoxia (SpO2 89% on room; PaO2 53 mmHg). Despite treatment with antiviral and non-invasive ventilation (NIV), after 24 h there was a progressive worsening of clinical conditions with higher fever (40 °C), increased dyspnea, and hypoxia (PaO2/FiO2 or P/F ratio of 150). The patient was at the limit to be sedated and intubated for IMV. He was treated with tocilizumab (8 mg/Kg i.v., single shot 800 mg) and NIV in the prone positioning. After only 96 h, the clinical, laboratory, and imaging findings showed incredible improvement. There was an important gain in oxygenation (P/F 300), a decrease of C-reactive protein values, and a decrease of the fever. Both the neutrophil-to-lymphocyte ratio (NLR) and the derived NLR ratio dropped down to 44%. Chest imaging confirmed the favorable response. This case suggested that for CARDS management efforts are needed for reducing its underlying inflammatory processes. Through a multiprofessional approach, the combination of IL-6-targeting therapies with calibrated ventilatory strategies may represent a winning strategy for improving outcomes.


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Coronavirus Infections/complications , Pneumonia, Viral/complications , /etiology , Administration, Intravenous , Antibodies, Monoclonal, Humanized/administration & dosage , Antiviral Agents/therapeutic use , Betacoronavirus/isolation & purification , Combined Modality Therapy , Dyspnea/diagnosis , Humans , Hypoxia/diagnosis , Male , Middle Aged , Noninvasive Ventilation/methods , Pandemics , /therapy , Tomography, X-Ray Computed/methods , Treatment Outcome
19.
J Stroke Cerebrovasc Dis ; 29(11): 105201, 2020 Nov.
Article in English | MEDLINE | ID: covidwho-675953

ABSTRACT

BACKGROUND/PURPOSE: Coronavirus disease 2019 (COVID-19) is associated with increased risk of acute ischemic stroke (AIS), however, there is a paucity of data regarding outcomes after administration of intravenous tissue plasminogen activator (IV tPA) for stroke in patients with COVID-19. METHODS: We present a multicenter case series from 9 centers in the United States of patients with acute neurological deficits consistent with AIS and COVID-19 who were treated with IV tPA. RESULTS: We identified 13 patients (mean age 62 (±9.8) years, 9 (69.2%) male). All received IV tPA and 3 cases also underwent mechanical thrombectomy. All patients had systemic symptoms consistent with COVID-19 at the time of admission: fever (5 patients), cough (7 patients), and dyspnea (8 patients). The median admission NIH stroke scale (NIHSS) score was 14.5 (range 3-26) and most patients (61.5%) improved at follow up (median NIHSS score 7.5, range 0-25). No systemic or symptomatic intracranial hemorrhages were seen. Stroke mechanisms included cardioembolic (3 patients), large artery atherosclerosis (2 patients), small vessel disease (1 patient), embolic stroke of undetermined source (3 patients), and cryptogenic with incomplete investigation (1 patient). Three patients were determined to have transient ischemic attacks or aborted strokes. Two out of 12 (16.6%) patients had elevated fibrinogen levels on admission (mean 262.2 ± 87.5 mg/dl), and 7 out of 11 (63.6%) patients had an elevated D-dimer level (mean 4284.6 ±3368.9 ng/ml). CONCLUSIONS: IV tPA may be safe and efficacious in COVID-19, but larger studies are needed to validate these results.


Subject(s)
Brain Ischemia/drug therapy , Coronavirus Infections/therapy , Fibrinolytic Agents/administration & dosage , Pneumonia, Viral/therapy , Stroke/drug therapy , Thrombolytic Therapy , Tissue Plasminogen Activator/administration & dosage , Administration, Intravenous , Aged , Aged, 80 and over , Brain Ischemia/diagnosis , Brain Ischemia/epidemiology , Coronavirus Infections/diagnosis , Coronavirus Infections/epidemiology , Female , Fibrinolytic Agents/adverse effects , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/diagnosis , Pneumonia, Viral/epidemiology , Risk Factors , Stroke/diagnosis , Stroke/epidemiology , Thrombectomy , Thrombolytic Therapy/adverse effects , Time Factors , Tissue Plasminogen Activator/adverse effects , Treatment Outcome , United States/epidemiology , Young Adult
20.
Clin Rheumatol ; 39(9): 2817-2821, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-671236

ABSTRACT

COVID-19 has significantly affected healthcare systems around the world. To prepare for this unprecedented emergency, elective patient care was put on hold across the National Health Service (NHS). Rheumatology service had to be reorganised with a cancellation of elective clinics and clinical reconfiguration to continue to deliver care to patients, support frontline, and prevent viral transmission. The rheumatology community's responsibility of providing a continuity of care for patients had to be balanced with measures to reduce the risk of viral transmission and also protection of both the patients and staff. We describe our experience of delivering rheumatology service as recommended by the National Institute for Health and Care Excellence (NICE NG167) guidelines at a district general hospital during the current pandemic. Key Points • Prepare to deliver a rapid mass communication; ensure email and mobile phones registered in patients' records; enable access to text and video messaging. • To ensure wider access to innovative digital technology in clinical practice; implement telephone and video consultations where appropriate. • To consider setting up community OP clinics, for example, mobile and satellite clinics.


Subject(s)
Coronavirus Infections/epidemiology , Delivery of Health Care/methods , Pneumonia, Viral/epidemiology , Rheumatic Diseases/therapy , Rheumatology/methods , Telemedicine , Administration, Intravenous , Ambulatory Care , Antirheumatic Agents/therapeutic use , Betacoronavirus , Continuity of Patient Care , Coronavirus Infections/prevention & control , Coronavirus Infections/transmission , Drug Substitution , Hospitals, District , Hospitals, General , Humans , Infusions, Subcutaneous , Nurses , Pandemics/prevention & control , Personnel Staffing and Scheduling , Pneumonia, Viral/prevention & control , Pneumonia, Viral/transmission , Rheumatologists , Risk Assessment , State Medicine , United Kingdom
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