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Vaccination and immunity against omicron variant of COVID-19: limited benefit if vaccination more than 6 months ago
The protection conferred by natural immunity, vaccination and both against symptomatic SARS-CoV-2 infection with the BA.1 or BA.2 sublineages of the omicron variant is unclear. Altarawneh et al (N Engl J Med 2022;387:21) conducted an observational, matched, test-negative case–control national study in Qatar, with a data collection period of 2 months to assess the effectiveness against symptomatic infection of different immunity situations (previous infection alone, two doses vaccination, three doses vaccination and two doses vaccination plus previous infection; termed hybrid immunity) using BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna) vaccines. In case of BA.1 infection,the effectiveness of vaccination with two doses of BNT162b2 and no previous infection was negligible (-4.9%; 95% CI -16.4 to 5.4), but nearly all had received their second dose more than 6 months earlier while with three doses, and no previous infection effectiveness was 59.6% (95% CI 52.9 to 65.3). In case of previous infection and no vaccination, the effectiveness was 50.2% (95% CI 38.1 to 59.9). The effectiveness of hybrid immunity was 51.7% (95% CI 43.5 to 58.7), which was similar to effectiveness of previous infection alone. The strongest protection was found in the cases of previous infection and three dose vaccination (74.4%; 95% CI 63.4 to 82.2). Similar results were found with mRNA-1273 and between BA.1 and BA.2. Previous infection, two doses, three doses and hybrid immunity all provided strong protection against severe COVID-19 infection, although with wide margins of error given the low pathogenicity (0.3% infections progressed to severe, critical or fatal COVID-19 infection in the study). These results show that vaccination enhanced protection among individuals who had a previous infection. But that a person without a previous infection must be vaccinated with at least three doses to have significant protection against symptomatic infection.
Myopericarditis after vaccination: no more likely after COVID-19 than non-COVID-19 vaccinations
Myopericarditis is a rare complication of vaccination previously linked to smallpox vaccination. There have been increasing case reports following COVID-19 vaccination but with limited data comparing the incidence to other vaccinations. Ruiyang et al (Lancet Respir Med 2022;10:679) performed a systematic review and metanalysis, searching through four international databases from 1 January 1947 to 31 December 2021. The primary outcome was the incidence of myopericarditis after any vaccination allowing for comparison with the incidence following COVID-19 vaccination. The overall incidence of myopericarditis was 33.3 cases per million vaccine doses (95% CI 15.3 to 72.6) without significant difference between non-COVID-19 and COVID-19 vaccines. Compared with COVID-19 vaccinations, myopericarditis was significantly higher following smallpox vaccinations (132.1 case per million vaccinations: 95% CI 81.3 to 214.6). Among people who received COVID-19 vaccines and between all the subgroups, people younger than 30 years and men had a higher incidence of myopericarditis, as did those receiving mRNA vaccines and after the second dose (compared with first or third doses). Reassuringly, these findings show that overall incidence of myopericarditis following COVID-19 is low, similar to the incidence after influenza vaccination and lower than after smallpox vaccination. It must be highlighted that the risks of such infrequent complication are outweighed by the benefits of vaccination, which include lower risk of infection, hospitalisation, severe disease and death from COVID-19 and other diseases with available vaccines.
Nebulised gentamicin in children with bronchiectasis: clinical trials are hard to recruit, and treatment adherence limited
The effectiveness of inhaled antibiotics in children with bronchiectasis unrelated to cystic fibrosis (CF) is unknown. Considering that inhaled antibiotics have some effectiveness in adults with bronchiectasis and children and adults with CF, Twiss et al (J Paediatr Child Health 2022;;58: 1039) completed a randomised, double-blind, placebo-controlled, cross-over trial to investigate the efficacy of 12 weeks of nebulised gentamicin in children with non-CF bronchiectasis. The primary outcome was change in forced expiratory volume in the first second (FEV1) and hospitalisation days. Participants were children (5–15 years) with bronchiectasis, chronic infection (any pathogen) and able to perform spirometry. The enrolment was from the hospital bronchiectasis clinic between June 2003 and December 2005. Participants received 12 weeks treatment with nebulised saline (placebo), followed by 6 weeks washout and 12 weeks treatment with nebulised gentamicin or the reverse. The study identified 42 potential participants of whom only 15 children commenced treatment (sample size target n=35). There were no differences between gentamicin and placebo in FEV1 % predicted on hospital admissions for respiratory exacerbations (p=0.123). However, some secondary outcomes such as sputum inflammatory markers’ reduction and H. influenzae sputum clearance reached statistical significance (p<0.001) during gentamicin compared with placebo period with an associated improvement in symptom severity score. Treatment adherence defined by achieving 50% of the required nebuliser minutes to deliver therapy indicated low overall adherence (34%; range 0–72%) and was lower in the gentamicin (28%) compared with placebo (41%) periods. Unfortunately, the poor recruitment means that the trial is underpowered to make a meaningful statement on efficacy of nebulised antibiotics in children with bronchiectasis but highlights some microbiological and inflammatory impact and the clear challenges in delivering this intervention in this patient population that may limit impact of any real-world intervention.
High flow therapy in COPD: further evidence of impact on exacerbations
The long-term effects of high-flow therapy (HFT) for chronic hypercapnic respiratory failure due to chronic obstructive pulmonary disease remain unclear. Nagata et al (Am.J. Respir. Crit. Care Med; 2022. doi:10.1164/rccm.202201-0199OC) report results of a multicentre clinical trial in which 104 patients with chronic hypercapnic respiratory failure and a history of exacerbations of COPD were randomised to receive long-term oxygen therapy (LTOT) and domiciliary nocturnal HFT or LTOT alone for 1 year. Patients who required non-invasive ventilation (NIV) within the past 1 year and with a history of obstructive sleep apnoea syndrome were excluded. The primary endpoint was the rate of moderate/severe exacerbations. Secondary endpoints included the time to the first COPD exacerbation, changes in physiological parameters and quality of life. The adjusted mean rate of moderate/severe exacerbations in HFT/LTOT was lower than that in LTOT alone (2.85, 95% CI 1.48 to 5.47, p=0.002). The median time to first moderate/severe COPD exacerbation in LTOT group was 25 weeks (95% CI 14.1 to 47.4) but was not reached in the HFT/LTOT group. There were only transient improvements in physiological and quality of life measures. Given the high rating given to exacerbation prevention by patients with COPD, HFT should be further explored as a therapeutic option in these high-risk patients. However, more work is needed on the optimum patient group who benefit from treatment and to optimum treatment delivery.
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Footnotes
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Provenance and peer review Commissioned; internally peer reviewed.