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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
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OBJECTIVESTo determine whether population-level implementation of a test-and- treat approach to correction of sub-optimal vitamin D status (25-hydroxyvitamin D [25(OH)D] <75 nmol/L) influences risk of all-cause acute respiratory infection (ARI) or coronavirus disease 2019 (COVID-19). DESIGNPhase 3 open-label randomised controlled trial (CORONAVIT) utilising trials-within-cohorts (TwiCs) methodology. SETTINGUnited Kingdom. PARTICIPANTS6200 adults aged 16 years or older, who were not already taking vitamin D supplements at baseline. INTERVENTIONSOffer of a postal finger-prick test of blood 25(OH)D concentration with provision of a 6-month supply of higher-dose vitamin D (3200 IU/day, n=1550) or lower-dose vitamin D (800 IU/day, n=1550) to those with blood 25(OH)D concentration <75 nmol/L, vs. no offer of testing or supplementation (n=3100). Follow-up was from 17th December 2020 to 16th June 2021. MAIN OUTCOME MEASURESThe primary outcome was the proportion of participants experiencing at least one doctor- or swab test-confirmed ARI of any cause. Secondary outcomes included the proportion of participants developing swab test-confirmed COVID-19. Logistic regression was used to calculate odds ratios and associated 95% confidence intervals. RESULTSOf 3100 participants offered 25(OH)D testing, 2958 (95.4%) accepted, and 2690 (86.8%) had 25(OH)D <75 nmol/L and were sent vitamin D supplements (1356 higher-dose, 1334 lower-dose). 76 (5.0%) vs. 87 (5.7%) vs. 136 (4.6%) participants in higher-dose vs. lower-dose vs. no offer groups experienced at least one ARI of any cause (odds ratio [OR] for higher-dose vs. no offer 1.09, 95% CI 0.82-1.46; lower-dose vs. no offer 1.26, 0.96-1.66). 45 (3.0%) vs. 55 (3.6%) vs. 78 (2.6%) participants in higher-dose vs. lower-dose vs. no offer groups developed COVID-19 (OR for higher-dose vs. no offer 1.13, 0.78-1.63; lower-dose vs. no offer 1.39, 0.98-1.97). CONCLUSIONSAmong adults with a high baseline prevalence of sub-optimal vitamin D status, implementation of a population-level test-and-treat approach to vitamin D replacement did not reduce risk of all-cause ARI or COVID-19. TRIAL REGISTRATIONClinicalTrials.gov no. NCT04579640 SUMMARY BOXO_ST_ABSWhat is already known on this topic?C_ST_ABSVitamin D metabolites support innate immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and other respiratory pathogens. Sub-optimal vitamin D status (25-hydroxyvitamin D <75 nmol/L) associates with increased susceptibility to all-cause acute respiratory infections (ARI) and coronavirus disease 2019 (COVID-19). Phase 3 randomised controlled trials of vitamin D to prevent COVID-19 have not yet reported. What this study addsThis phase 3 randomised controlled trial, including 6200 participants, shows that implementation of a population-level test-and-treat approach to oral vitamin D replacement at a dose of 800 IU or 3200 IU per day did not reduce risk of all-cause ARI or COVID-19 among adults with a high baseline prevalence of sub-optimal vitamin D status.