Rebound in asthma exacerbations following relaxation of COVID-19 restrictions: a longitudinal population-based study (COVIDENCE UK)

BackgroundThe imposition of restrictions on social mixing early in the COVID-19 pandemic was followed by a reduction in asthma exacerbations in multiple settings internationally. Temporal trends in social mixing, incident acute respiratory infections (ARI) and asthma exacerbations following relaxation of COVID-19 restrictions have not yet been described. MethodsWe conducted a population-based longitudinal study in 2,312 UK adults with asthma between November 2020 and April 2022. Details of face covering use, social mixing, incident ARI and moderate/severe asthma exacerbations were collected via monthly on-line questionnaires. Temporal changes in these parameters were visualised using Poisson generalised additive models. Multilevel logistic regression was used to test for associations between incident ARI and risk of asthma exacerbations, adjusting for potential confounders. ResultsRelaxation of COVID-19 restrictions from April 2021 coincided with reduced face covering use (p<0.001), increased frequency of indoor visits to public places and other households (p<0.001) and rising incidence of COVID-19 (p<0.001), non-COVID-19 ARI (p<0.001) and moderate/severe asthma exacerbations (p=0.007). Incident non-COVID-19 ARI associated independently with increased risk of asthma exacerbation (adjusted odds ratio 5.75, 95% CI 4.75 to 6.97) as did incident COVID-19, both prior to emergence of the omicron variant of SARS-CoV-2 (5.89, 3.45 to 10.04) and subsequently (5.69, 3.89 to 8.31). ConclusionsRelaxation of COVID-19 restrictions coincided with decreased face covering use, increased social mixing and a rebound in ARI and asthma exacerbations. Associations between incident ARI and risk of moderate/severe asthma exacerbation were similar for non-COVID-19 ARI and COVID-19, both before and after emergence of the SARS-CoV-2 omicron variant. FundingBarts Charity, UKRI

Vitamin D supplementation to prevent acute respiratory infections: systematic review and meta-analysis of aggregate data from randomised controlled trials

ObjectivesTo assess the overall effect of vitamin D supplementation on risk of acute respiratory infection (ARI), and to identify factors modifying this effect. DesignWe conducted a systematic review and meta-analysis of data from randomised controlled trials (RCTs) of vitamin D for ARI prevention using a random effects model. Pre-specified sub-group analyses were done to determine whether effects of vitamin D on risk of ARI varied according to baseline 25-hydroxyvitamin D (25[OH]D) concentration or dosing regimen. Data SourcesMEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, ClinicalTrials.gov and the International Standard RCT Number (ISRCTN) registry from inception to May 2020. Eligibility Criteria for Selecting StudiesDouble-blind RCTs of supplementation with vitamin D or calcidiol, of any duration, were eligible if they were approved by a Research Ethics Committee and if ARI incidence was collected prospectively and pre-specified as an efficacy outcome. ResultsWe identified 40 eligible RCTs (total 30,956 participants, aged 0 to 95 years). Data were obtained for 29,841 (96.5%) of 30,909 participants in 39 studies. For the primary comparison of vitamin D supplementation vs. placebo, the intervention reduced risk of ARI overall (Odds Ratio [OR] 0.89, 95% CI 0.81 to 0.98; P for heterogeneity 0.009). No statistically significant effect of vitamin D was seen for any of the sub-groups defined by baseline 25(OH)D concentration. However, protective effects were seen for trials in which vitamin D was given using a daily dosing regimen (OR 0.75, 95% CI 0.61 to 0.93); at daily dose equivalents of 400-1000 IU (OR 0.70, 95% CI 0.55 to 0.89); and for a duration of [≤]12 months (OR 0.82, 95% CI 0.72 to 0.94). Vitamin D did not influence the proportion of participants experiencing at least one serious adverse event (OR 0.94, 95% CI 0.81 to 1.08). Risk of bias within individual studies was assessed as being low for all but two trials. A funnel plot showed asymmetry, suggesting that small trials showing non-protective effects of vitamin D may have been omitted from the meta-analysis. ConclusionsVitamin D supplementation was safe and reduced risk of ARI, despite evidence of significant heterogeneity across trials. The overall effect size may have been over-estimated due to publication bias. Protection was associated with administration of daily doses of 400-1000 IU vitamin D for up to 12 months. The relevance of these findings to COVID-19 is not known and requires investigation. Systematic Review RegistrationCRD42020190633 O_TEXTBOXSummary Box What is already known on this subject?O_LIA previous individual participant data meta-analysis from 10,933 participants in 25 randomised controlled trials (RCTs) of vitamin D supplementation for the prevention of acute respiratory infection (ARI) demonstrated an overall protective effect (number needed to treat to prevent one ARI [NNT]=33).Sub-group analysis revealed most benefit in those with the lowest vitamin D status at baseline and not receiving bolus doses. C_LI What this study addsO_LIWe updated this meta-analysis with trial-level data from an additional 14 placebo-controlled RCTs published since December 2015 (i.e. new total of 39 studies with 29,841 participants). C_LIO_LIAn overall protective effect of vitamin D supplementation against ARI was seen (NNT=36). C_LIO_LIA funnel plot revealed evidence of publication bias, which could have led to an over-estimate of the protective effect. C_LIO_LINo statistically significant effect of vitamin D was seen for any of the sub-groups defined by baseline 25(OH)D concentration. C_LIO_LIStrongest protective effects were associated with administration of daily doses of 400-1000 IU vitamin D for [≤]12 months (NNT=8). C_LI C_TEXTBOX

RT-PCR testing to detect a COVID-19 outbreak in Austria: rapid, accurate and early diagnosis in primary care (The REAP study)

BackgroundDelay in COVID-19 detection has led to a major pandemic. We report rapid early detection of SARS-CoV-2 by reverse transcriptase-polymerase chain reaction (RT-PCR), comparing it to the serostatus of convalescent infection, at an Austrian National Sentinel Surveillance Practice in an isolated ski-resort serving a population of 22,829 people. MethodsRetrospective dataset of all 73 patients presenting with mild to moderate flu-like symptoms to a sentinel practice in the ski-resort of Schladming-Dachstein, Austria, between 24 February and 03 April, 2020. We split the outbreak in two halves, by dividing the period from the first to the last case by two, to characterise the following three cohorts of patients with confirmed infection: people with reactive RT-PCR presenting during the first half (early acute infection) vs. those presenting in the second half (late acute), and people with non-reactive RT-PCR (late convalescent). For each cohort we report the number of cases detected, the accuracy of RT-PCR and the duration of symptoms. We also report multivariate regression of 15 clinical symptoms as covariates, comparing all people with convalescent infection to those with acute infection. FindingsAll 73 patients had SARS-CoV-2 RT-PCR testing. 22 patients were diagnosed with COVID-19, comprising: 8 patients presenting early acute, and 7 presenting late acute and 7 late convalescent respectively; 44 patients tested SARS-COV-2 negative, and 7 were excluded. RT-PCR sensitivity was high (100%) among acute presenters, but dropped to 50% in the second half of the outbreak; specificity was 100%. The mean duration of symptoms was 2 days (range 1-4) among early acute presenters, and 4.4 days (1-7) among late acute and 8 days (2-12) among late convalescent presenters respectively. Convalescent infection was only associated with loss of taste (ORs=6.02;p=0.047). Acute infection was associated with loss of taste (OR=571.72;p=0.029), nausea and vomiting (OR=370.11;p=0.018), breathlessness (OR=134.46;p=0.049), and myalgia (OR=121.82;p=0.032); but not loss of smell, fever or cough. InterpretationRT-PCR rapidly and reliably detects early COVID-19 among people presenting with viral illness and multiple symptoms in primary care, particularly during the early phase of an outbreak. RT-PCR testing in primary care should be prioritised for effective COVID-19 prevention and control. Research in ContextO_ST_ABSEvidence before this studyC_ST_ABSA comprehensive and effective test-trace-isolate (TTI) strategy is necessary to keep track of current and future COVID-19 infection in the UK and avoid a secondary wave later this year, as society reopens. As part of a wider TTI strategy, it is important to assess the feasibility of COVID-19 testing in primary care. We searched PubMed for implementation of SARS-CoV-2 testing in primary care using the following search terms: ("SARS-CoV-2" OR "COVID-19") AND "testing" AND ("primary care" OR "general practice"). We did not find any studies that met these criteria. Added value of this studyTo our knowledge, our study provides first evidence that extension of a National Influenza Surveillance Programme to include SARS-CoV-2 RT-PCR testing in primary care leads to viral detection among patients presenting with mild to moderate flu-like illness during a local outbreak of COVID-19. We show that the sensitivity of reverse transcriptase-polymerase chain reaction (RT-PCR), the technique to detect viral RNA, is high (100%) in the initial phase of the outbreak and among patients who were acutely unwell. Acute infection was associated with multiply symptoms: loss of taste, nausea and vomiting, breathlessness, myalgia and sore throat; but not loss of smell, fever or cough. We also show high correlation between reactive RT-PCR and seropositivity. Implications of all available evidenceOur findings suggest that RT-PCR can rapidly and reliably detect early COVID-19 among people presenting with viral illness and multiple symptoms in primary care, particularly during the early phase of an outbreak. Furthermore RT-PCR testing in primary care can effectively detect new COVID-19 clusters in the community and should be included in any strategy for prevention and control of the disease.

Patient reported outcomes for preschool children with recurrent wheeze.

Children with preschool wheeze regularly attend UK emergency departments. There is no international consensus on any specific personalised management approach. This paper describes the first attempt to co-design patient-centred outcomes with families. Preschool wheezers' parents participated in semi-structured interviews and focus-group discussions to air their concerns and identify potential additional support. Fifty-seven families participated in these interviews. From these, themes were defined through qualitative content analysis. Parental experience was mapped to the patient pathway and seven important personalised outcomes were described. These can be used to inform a tool which following further validation could potentially support management of children with preschool wheeze and provide an additional patient focused clinical outcome measure in audit and research.