Variant of Concern-Matched COVID-19 Convalescent Plasma Usage in Seronegative Hospitalized Patients.

COVID-19 convalescent plasma (CCP) has been the only specific anti-viral therapy against SARS-CoV-2 available for more than one year. Following the negative results from most randomized controlled trials on its efficacy in COVID-19 hospitalized patients and the availability of anti-spike monoclonal antibodies (mAbs), the use of CCP has subsequently rapidly faded. However, the continuous appearance of new variants of concern (VOCs), most of which escape mAbs and vaccine-elicited neutralizing antibodies (nAbs), has renewed the interest towards CCP, at least in seronegative immunocompetent patients, and in immunocompromised patients not able to mount a protective immune response. We report here the experience of a single Italian hospital in collecting and transfusing CCP in immunocompromised patients hospitalized for severe COVID-19 between October 2021 and March 2022. During this 6-month period, we collected CCP from 32 vaccinated and convalescent regular blood donors, and infused high nAb-titer CCP units (titered against the specific VOC affecting the recipient) to 21 hospitalized patients with severe COVID-19, all of them seronegative at the time of CCP transfusion. Patients' median age was 66 years (IQR 50-74 years) and approximately half of them (47.6%, 10/21) were immunocompromised. Two patients were rescued after previous failure of mAbs. No adverse reactions following CCP transfusion were recorded. A 28-day mortality rate of 14.3 percent (3/21) was reported, with age, advanced disease stage and late CCP transfusion associated with a worse outcome. This real-life experience also supports the use of CCP in seronegative hospitalized COVID-19 patients during the Delta and Omicron waves.

Regular versus as-needed budesonide and formoterol combination treatment for moderate asthma: a non-inferiority, randomised, double-blind clinical trial.

BACKGROUND: Treatment guidelines for patients with moderate persistent asthma recommend regular therapy with a combination of an inhaled corticosteroid and a longacting ß2 agonist plus as-needed rapid-acting bronchodilators. We investigated whether symptom-driven budesonide and formoterol combination therapy administered as needed would be as effective as regular treatment with this combination plus as-needed symptom-driven terbutaline for patients with moderate asthma. METHODS: In this non-inferiority randomised clinical trial, we recruited adult patients (18-65 years of age) with stable moderate persistent asthma, according to 2006 Global Initiative for Asthma guidelines. Patients were recruited from outpatient clinics of secondary and tertiary referral hospitals and university centres. After a 6-week run-in period of inhaled regular budesonide and formoterol plus as-needed terbutaline, the patients were randomly assigned in a 1:1 ratio to receive placebo twice daily plus as-needed treatment with inhaled 160 µg budesonide and 4·5 µg formoterol (as-needed budesonide and formoterol therapy) or twice-daily 160 µg budesonide and 4·5 µg formoterol combination plus symptom-driven 500 µg terbutaline (regular budesonide/formoterol therapy) for 1 year. Randomisation was done according to a list prepared with the use of a random number generator and a balanced-block design stratified by centre. Patients and investigators were masked to treatment assignment. The primary outcome was time to first treatment failure measured after 1 year of treatment using Kaplan-Meier estimates, and the power of the study was calculated based on the rate of treatment failure. Analyses were done on the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT00849095. FINDINGS: Between April 20, 2009, and March 31, 2012, we screened 1010 patients with moderate asthma and randomly assigned 866 eligible patients to the two treatment groups (424 to as-needed budesonide and formoterol therapy and 442 to regular budenoside and formoterol therapy). Compared with regular budesonide and formoterol therapy, as-needed budesonide and formoterol treatment was associated with a lower probability of patients having no treatment failure at 1 year (Kaplan-Meier estimates 53·6% for as-needed treatment vs 64·0% for regular treatment; difference 10·3% [95% CI 3·2-17·4], at a predefined non-inferiority limit of 9%). Patients in the as-needed budesonide and formoterol group had shorter time to first treatment failure than those in the regular therapy group (11·86 weeks vs 28·00 weeks for the first quartile [ie, the time until the first 25% of patients experienced treatment failure]). The difference in treatment failures was largely attributable to nocturnal awakenings (82 patients in the as-needed treatment group vs 44 in the regular treatment group). Both treatment regimens were well tolerated. INTERPRETATION: In patients with moderate stable asthma, as-needed budesonide and formoterol therapy is less effective than is the guideline-recommended regular budesonide and formoterol treatment, even though the differences are small. FUNDING: Italian Medicines Agency.

Erdosteine enhances airway response to salbutamol in patients with mild-to-moderate COPD.

BACKGROUND: Oxidative stress is presumed to impair beta-adenoceptor function and airway patency. Erdosteine (E), a mucomodulatory compound, has shown important antioxidant properties. METHODS: The objective was to assess the effect of antioxidant interventions on short-term airway response to salbutamol in non-reversible mild-to-moderate COPD patients. Thirty COPD patients (GOLD class 1-2), current smoker (>or=10 pack/year), randomly received E 300 mg, N-acetylcysteine (NAC) 600 mg, or placebo, twice daily for ten days. Reversibility to salbutamol 200 microg was tested in baseline, after four and ten days of each treatment. ROS and 8-isoprostane blood levels were measured on the same days. Between-treatment comparison was performed by ANOVA and t-test or Wilcoxon test, and p<0.05 assumed. E enhanced FEV1 reversibility after four and ten days significantly (+5.1% and +5.0%; both p<0.01 vs. placebo), while NAC only showed a transient effect at day 4 (+3.0%, p<0.05), but not at day 10 (+1.3%, p = ns). RESULTS: E and NAC caused significant drops in ROS blood levels after four and ten days (p<0.001 and p<0.0001 vs. placebo). In contrast to NAC, E lowered 8-isoprostane levels substantially for ten days (p = 0.017 and p = 0.0004 vs. placebo, respectively). Only E restored significantly short-term reversibility in COPD patients previously unresponsive to beta(2)-adrenergics. CONCLUSIONS: This effect seems more related to the peculiar protection against lipid peroxidation rather than to the scavenging activity, which proves equal to that of NAC. E provides a sort of indirect bronchodilation through 're-sensitisation' of beta( 2)-adrenoceptors. Once confirmed in further controlled studies, it may be useful in long-term treatment of COPD.