The Lancet Respiratory Medicine

BackgroundColchicine has been proposed as a treatment for COVID-19 on the basis of its anti-inflammatory actions. MethodsIn this randomised, controlled, open-label trial, several possible treatments were compared with usual care in patients hospitalised with COVID-19. Eligible and consenting adults were randomly allocated in a 1:1 ratio to either usual standard of care alone or usual standard of care plus colchicine twice daily for 10 days or until discharge (or one of the other treatment arms)...

BackgroundEmpagliflozin has been proposed as a treatment for COVID-19 on the basis of its anti-inflammatory, metabolic and haemodynamic effects. MethodsIn this randomised, controlled, open-label trial, several possible treatments are compared with usual care in patients hospitalised with COVID-19. Eligible and consenting adults were randomly allocated in a 1:1 ratio to either usual standard of care alone or usual standard of care plus empagliflozin 10mg once daily for 28 days or until discharge...

BackgroundHydroxychloroquine has recently received Emergency Use Authorization by the FDA and is currently prescribed in combination with azithromycin for COVID-19 pneumonia. We studied the safety of hydroxychloroquine, alone and in combination with azithromycin. MethodsNew user cohort studies were conducted including 16 severe adverse events (SAEs). Rheumatoid arthritis patients aged 18+ and initiating hydroxychloroquine were compared to those initiating sulfasalazine and followed up over 30 d...

BACKGROUNDInhaled budesonide has shown efficacy for treating COVID-19 in the community but has not yet been tested in effectiveness trials. METHODSWe performed a multicenter, open-label, multi-arm, adaptive platform randomized controlled trial involving people aged [≥]65 years, or [≥]50 years with comorbidities, and unwell [≤]14 days with suspected COVID-19 in the community (PRINCIPLE). Participants were randomized to usual care, usual care plus inhaled budesonide (800{micro}g twice da...

BackgroundLow-dose corticosteroids (e.g. 6 mg dexamethasone) have been shown to reduce mortality for hypoxic COVID-19 patients. We have previously reported that higher dose corticosteroids cause harm in patients with hypoxia but not receiving ventilatory support (non-invasive mechanical ventilation, invasive mechanical ventilation or extra-corporeal membrane oxygenation), but the balance of efficacy and safety in patients receiving ventilatory support is uncertain. MethodsThis randomised, contr...

BackgroundThe oral, selective Janus kinase (JAK)1/JAK2 inhibitor baricitinib demonstrated efficacy in hospitalised adults with COVID-19. This study evaluates the efficacy and safety of baricitinib in critically ill adults with COVID-19 requiring invasive mechanical ventilation (IMV) or extracorporeal membrane oxygenation (ECMO). MethodsCOV-BARRIER was a global, phase 3, randomised, double-blind, placebo-controlled trial in patients with confirmed SARS-CoV-2 infection (ClinicalTrials.gov NCT0442...

BackgroundConcerns over the safety of non-steroidal anti-inflammatory drug (NSAID) use during SARS-CoV-2 infection have been raised. ObjectivesTo study whether use of NSAIDs is associated with adverse outcomes and mortality during SARS-CoV-2 infection. DesignPopulation based cohort study SettingDanish administrative and health registries. Participants Individuals tested positive for SARS-CoV-2 during Feb 27, 2020 to Apr 29, 2020. Treated individuals (defined as a filled NSAID prescription up...

We report the short- and long-term results of the SOLIDARITY Finland on mortality and other patient-important outcomes in patients hospitalised for COVID-19. Between 08/2021 and 03/2023, we randomised 156 patients in 15 hospitals. In the imatinib group, 7.2% of patients had died at 30 days and 13.3% at 1 year and in the standard of care group 4.1% and 8.3% (adjusted HR at 30 days 1.09, 95% CI 0.23-5.07). In a meta-analysis of randomised trials of imatinib versus standard of care (n=732), allocat...

BackgroundAzithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatory actions. We evaluated the efficacy and safety of azithromycin in hospitalised patients with COVID-19. MethodsIn this randomised, controlled, open-label, adaptive platform trial, several possible treatments were compared with usual care in patients hospitalised with COVID-19 in the UK. Eligible and consenting patients were randomly allocated to either usual standard of care alone or usual st...

BackgroundWe evaluated the use of baricitinib, a Janus kinase (JAK) 1/2 inhibitor, for the treatment of patients admitted to hospital because of COVID-19. MethodsThis randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple possible treatments in patients hospitalised for COVID-19. Eligible and consenting patients were randomly allocated (1:1) to either usual standard of care alone (usual care group) or usual care plus baric...

BackgroundTreatment of COVID-19 patients with plasma containing anti-SARS-CoV-2 antibodies may have a beneficial effect on clinical outcomes. We aimed to evaluate the safety and efficacy of convalescent plasma in patients admitted to hospital with COVID-19. MethodsIn this randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]) several possible treatments are being compared with usual care in patients hospitalised with COVID-19 in the UK. Eligibl...

BackgroundThe success of early dexamethasone therapy for hospitalised COVID-19 cases in treatment of Sars-CoV-2 infection may predominantly reflect its anti-inflammatory action against a hyperinflammation (HI) response. It is likely that there is substantial heterogeneity in HI responses in COVID-19. MethodsBlood CRP, ferritin, neutrophil, lymphocyte and platelet counts were scored to assess HI (HI5) and combined with a validated measure of generalised medical deterioration (NEWS2) before day 2...

BackgroundCoronavirus disease 2019 (COVID-19) is associated with diffuse lung damage. Corticosteroids may modulate immune-mediated lung injury and reducing progression to respiratory failure and death. MethodsThe Randomised Evaluation of COVID-19 therapy (RECOVERY) trial is a randomized, controlled, open-label, adaptive, platform trial comparing a range of possible treatments with usual care in patients hospitalized with COVID-19. We report the preliminary results for the comparison of dexameth...

JustificationStimulation of early innate anti-viral responses during the early phase of SARS-COV-2 infection oxygen may improve evolution of illness and late pulmonary complications. This may be possible using a TLR agonist such as a probiotic bacterium possessing desirable immunomodulatory properties. MethodWe performed a non-contact, open-label, prospective randomized clinical trial comparing intranasally applied Lactococcus lactis W136 with saline irrigation alone in patients within 96 hours...

BackgroundLong-term outcomes after critical COVID-19 have not been sufficiently studied. This study aimed to describe changes in functional outcome and health-related quality of life (HRQoL) assessed at 3 and 12 months in a cohort of critically ill COVID-19 survivors. A secondary aim was to investigate factors associated with good functional outcome and HRQoL at 12 months. MethodsThis prospective multicentre cohort study included critically ill COVID-19 patients admitted to six intensive care u...

BackgroundProton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2RAs) predominate as stress ulcer prophylaxis (SUP) agents in intensive care units (ICUs). Prescribing patterns may change over time as randomized controlled trials evaluate SUP in critically ill patients. ObjectiveThis study aims to compare site-specific, self-reported SUP prescribing practices before and after the REVISE trial in participating ICUs. MethodsThis is a pre-planned study as part of the REVISE trial (N...

BackgroundColchicine, an anti-inflammatory drug, was used early in the COVID-19 pandemic for its ability to modulate the inflammatory response. However, its clinical efficacy in hospitalized patients, particularly when used alongside corticosteroids, remains unclear. This systematic review and meta-analysis assessed colchicines efficacy in hospitalized COVID-19 patients. MethodsWe searched PubMed, Web of Science, and EMBASE databases for randomized controlled trials (RCTs) evaluating colchicine...

ObjectiveTo study whether COVID-19 infection may be associated with increased hospitalization and mortality from other diseases. DesignCohort study. SettingThe UK Biobank. ParticipantsAll subjects in the UK Biobank with available hospitalization records and alive as of 31-Jan-2020 (N= 412,096; age 50-87). Main outcome measuresWe investigated associations of COVID-19 with hospitalization and mortality due to different diseases post-infection. We conducted a comprehensive survey on disorders f...

BackgroundThe role of thromboprophylaxis in the post-acute phase of COVID-19 is uncertain due to conflicting results from randomised controlled trials and observational studies. We aimed to determine the effectiveness of post-hospital apixaban in reducing the rate of death and hospital readmission of hospitalised adults with COVID-19. MethodsHEAL COVID is an adaptive randomised open label multicentre platform trial recruiting participants from National Health Service Hospitals in the United Kin...

BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectivity is mediated by the androgen-promoted protease, transmembrane protease, serine 2 (TMPRSS2). Previously, we have shown that treatment with proxalutamide, a non-steroidal androgen receptor antagonist, accelerates viral clearance and clinical remission in outpatients with coronavirus disease 2019 (COVID-19) compared to placebo. The effects in hospitalized COVID-19 patients were unknown. MethodsMen and women hospitali...