COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Administration of taurolidine-citrate lock solution for prevention of central venous catheter infection in adult neutropenic haematological patients: a randomised, double-blinded, placebo-controlled trial (TAURCAT)

Abstract Background Catheter-related bloodstream infection (CRBSI) is one of the most frequent complications in patients with cancer who have central venous catheters (CVCs) implanted and is associated with substantial morbidity and mortality. Taurolidine is a non-antibiotic agent with broad-spectrum antimicrobial activity, which has been used as a lock solution to prevent CRBSI in some settings. However, little is known about its usefulness in high-risk adult neutropenic patients with cancer. This prospective randomised clinical trial aims to test the hypothesis that taurolidine-citrate lock solution is more effective than placebo for preventing catheter infection in neutropenic haematological patients. Methods This study is a prospective, multicentre, randomised, double-blinded, parallel, superiority, placebo-controlled trial. Patients with haematological cancer who are expected to develop prolonged neutropenia (> 7 days) and who have a non-tunnelled CVC implanted will be randomised to receive prophylactic taurolidine-citrate-heparin solution using a lock technique (study group) or heparin alone (placebo group). The primary endpoint will be bacterial colonisation of the CVC hubs. The secondary endpoints will be the incidence of CRBSI, CVC removal, adverse events, and 30-day case-fatality rate. Discussion The lock technique is a preventive strategy that inhibits bacterial colonisation in the catheter hubs, which is the initial step of endoluminal catheter colonisation and the development of infection. Taurolidine is a nontoxic agent that does not develop antibiotic resistance because it acts as an antiseptic rather than an antibiotic. Taurolidine has shown controversial results in the few trials conducted in cancer patients. These studies have important limitations due to the lack of data on adult and/or high-risk neutropenic patients, the type of catheters studied (tunnelled or ports), and the lack of information regarding the intervention (e.g. dwelling of the solution, time, and periodicity of the lock technique). If our hypothesis is proven, the study could provide important solid evidence on the potential usefulness of this preventive procedure in a population at high risk of CRBSI, in whom this complication may significantly impair patient outcome. Trial registration ISRCTN, ISRCTN47102251. Registered on 9 September 2015

Additional file 1: of Administration of taurolidine-citrate lock solution for prevention of central venous catheter infection in adult neutropenic haematological patients: a randomised, double-blinded, placebo-controlled trial (TAURCAT)

SPIRIT 2013 Checklist: recommended items to address in a clinical trial protocol and related documents*. (DOCX 36 kb

Efficacy and safety of an early oral switch in low-risk Staphylococcus aureus bloodstream infection (SABATO): an international, open-label, parallel-group, randomised, controlled, non-inferiority trial

International audienceBACKGROUND: Staphylococcus aureus bloodstream infection is treated with at least 14 days of intravenous antimicrobials. We assessed the efficacy and safety of an early switch to oral therapy in patients at low risk for complications related to S aureus bloodstream infection. METHODS: In this international, open-label, randomised, controlled, non-inferiority trial done in 31 tertiary care hospitals in Germany, France, the Netherlands, and Spain, adult patients with low-risk S aureus bloodstream infection were randomly assigned after 5-7 days of intravenous antimicrobial therapy to oral antimicrobial therapy or to continue intravenous standard therapy. Randomisation was done via a central web-based system, using permuted blocks of varying length, and stratified by study centre. The main exclusion criteria were signs and symptoms of complicated S aureus bloodstream infection, non-removable foreign devices, and severe comorbidity. The composite primary endpoint was the occurrence of any complication related to S aureus bloodstream infection (relapsing S aureus bloodstream infection, deep-seated infection, and mortality attributable to infection) within 90 days, assessed in the intention-to-treat population by clinical assessors who were masked to treatment assignment. Adverse events were assessed in all participants who received at least one dose of study medication (safety population). Due to slow recruitment, the scientific advisory committee decided on Jan 15, 2018, to stop the trial after 215 participants were randomly assigned (planned sample size was 430 participants) and to convert the planned interim analysis into the final analysis. The decision was taken without knowledge of outcome data, at a time when 126 participants were enrolled. The new sample size accommodated a non-inferiority margin of 10%; to claim non-inferiority, the upper bound of the 95% CI for the treatment difference (stratified by centre) had to be below 10 percentage points. The trial is closed to recruitment and is registered with ClinicalTrials.gov (NCT01792804), the German Clinical trials register (DRKS00004741), and EudraCT (2013-000577-77). FINDINGS: Of 5063 patients with S aureus bloodstream infection assessed for eligibility, 213 were randomly assigned to switch to oral therapy (n=108) or to continue intravenous therapy (n=105). Mean age was 63·5 (SD 17·2) years and 148 (69%) participants were male and 65 (31%) were female. In the oral switch group, 14 (13%) participants met the primary endpoint versus 13 (12%) in the intravenous group, with a treatment difference of 0·7 percentage points (95% CI -7·8 to 9·1; p=0·013). In the oral switch group, 36 (34%) of 107 participants in the safety population had at least one serious adverse event compared with 27 (26%) of 103 participants in the intravenous group (p=0·29). INTERPRETATION: Oral switch antimicrobial therapy was non-inferior to intravenous standard therapy in participants with low-risk S aureus bloodstream infection. However, it is necessary to carefully assess patients for signs and symptoms of complicated S aureus bloodstream infection at the time of presentation and thereafter before considering early oral switch therapy. FUNDING: Deutsche Forschungsgemeinschaft. TRANSLATIONS: For the German, Spanish, French and Dutch translations of the abstract see Supplementary Materials section