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ObjectivesTo investigate the association of severe COVID-19 in those with inflammatory rheumatic diseases (IRD) treated with immunosuppressive drugs. MethodsA list of 4633 patients on biologics and targeted synthetic (ts) DMARDs in March 2020 was linked to a case-control study that includes all cases of COVID-19 in Scotland. ResultsBy 22 November 2021 433 of the 4633 patients treated with biologics and tsDMARDs had been diagnosed with COVID-19, of whom 58 had been hospitalised. With all those in the population not on DMARDs as reference category, the rate ratio for hospitalised COVID-19 associated with DMARD treatment was 2.14 (95% CI 2.02 to 2.26) in those on conventional synthetic (cs) DMARDs, 2.01 (95% CI 1.38 to 2.91) in those on TNF inhibitors as the only biologic agent, and 3.83 (95% CI 2.65 to 5.56) in those on other biologic agents. Among those on csDMARDs, rate ratios for hospitalised COVID-19 were lowest at 1.66 (95% CI 1.51 to 1.82) in those on methotrexate and highest at 5.4 (95% CI 4.4 to 6.7) in those on glucocorticoids at average dose >10 mg/day prednisolone equivalent. ConclusionThe risk of hospitalised COVID-19 is elevated in IRD patients treated with immunosuppressive drugs. Of these drugs, methotrexate, hydroxychloroquine, and TNF inhibitors carry the lowest risk, JAK inhibitors and B-cell depleting agents a higher risk and prednisolone the highest risk. A larger study is needed to estimate reliably the risks associated with each class of biologic agent. Key messagesO_LIRisk of hospitalised COVID-19 is about twofold higher in IRD patients treated with immunosuppressive therapies - csDMARDS or biologics - than in the general population. C_LIO_LIRisk is lowest in those treated with methotrexate, hydroxychoroquine and TNF inhibitors. Of the other biologic drugs, treatment with B cell depleters and JAK inhibitors is associated with higher risk but the numbers are too small for risk associated with each drug class to be estimated reliably. C_LIO_LIThe risk of severe COVID-19 with glucocorticoids at a dose greater than 10 mg/day prednisolone equivalent is higher than that of any other drug class studied. C_LI
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BackgroundStudies using claims databases have reported that SARS-CoV-2 infection >30 days earlier increased the incidence of type 1 diabetes (T1DM). Using exact dates of type 1 diabetes diagnosis from the national register in Scotland linked to virology laboratory data we sought to replicate this finding. MethodsA cohort of 1849411 individuals aged <35 years without diabetes, including all those in Scotland who subsequently tested positive for SARS-CoV-2, was followed from 1 March 2020 to 22 November 2021. Incident T1DM was identified by linkage to the national registry. Cox regression was used to test the association of time-updated infection with incident T1DM. Trends in incidence of T1DM in the total population from 2015-2021 were estimated in a generalized additive model. FindingsThere were 365080 in the cohort with at least one detected SARS-CoV-2 infection during follow-up and 1074 who developed T1DM. The rate ratio for incident T1DM associated with first positive test for SARS-CoV-2 (with no previous infection as reference category) was 0.88 (95% CI 0.63 to 1.23) for infection more than 30 days earlier and 2.62 (95% CI 1.81 to 3.79) for infection in the previous 30 days. However negative and positive SARS-CoV-2 tests were more frequent in the days surrounding T1DM presentation. In those aged 0-14 years incidence of T1DM during 2020-2021 was 20% higher than the 7-year average. InterpretationT1DM incidence in children increased during the pandemic. However the cohort analysis does not support a causal effect of SARS-CoV-2 infection itself on T1DM incidence. FundingNone
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ObjectivesTo investigate the association of primary acute cerebral venous thrombosis (CVT) with COVID-19 vaccination through complete ascertainment of all diagnosed CVT in the population of Scotland. DesignCase-crossover study comparing recent (1-14 days after vaccination) with less recent exposure to vaccination among cases of CVT. SettingNational data for Scotland from 1 December 2020, with diagnosed CVT case ascertainment through neuroimaging studies up to 17 May 2021 and diagnostic coding of hospital discharges up to 28 April 2021 and with linkage to vaccination records. Main outcome measurePrimary acute cerebral venous thrombosis ResultsOf 50 primary acute CVT cases, 29 were ascertained only from neuroimaging studies, 2 were ascertained only from hospital discharges, and 19 were ascertained from both sources. Of these 50 cases, 14 had received the Astra-Zeneca ChAdOx1 vaccine and 3 the Pfizer BNT162b2 vaccine. The incidence of CVT per million doses in the first 14 days after vaccination was 2.2 (95% credible interval 0.9 to 4.1) for ChAdOx1 and 1 (95% credible interval 0.1 to 2.9) for BNT162b2. The rate ratio for CVT associated with exposure to ChAdOx1 in the first 14 days compared with exposure 15-84 days after vaccination was 3.2 (95% credible interval 1.1 to 9.5). The 95% credible interval for the rate ratio associated with recent versus less recent exposure to BNT162b2 (0.6 to 95.8) was too wide for useful inference. ConclusionsThese findings support a causal association between CVT and the AstraZeneca vaccine. The absolute risk of post-vaccination CVT in this population-wide study in Scotland was lower than has been reported for populations in Scandinavia and Germany; the explanation for this is not clear. What is already known on this topicThe risk of cerebral venous thrombosis (CVT) within 28 days of receiving the AstraZeneca ChAdOx1 vaccine has been estimated as 18 to 25 per million doses in Germany and Scandinavia, but only 5 per million doses in the UK based on the Yellow Card reporting scheme. Risk estimates based on adverse event reporting systems are subject to under-ascertainment and other biases. What this study addsAll diagnosed cases of CVT in Scotland were ascertained by searching neuroimaging studies from December 2020 to May 2021 and linked to national vaccination records. The risk of CVT within 28 days of vaccination with ChAdOx1 was estimated as 3.5 per million doses with an upper bound of 6 per million doses, against a background incidence of about 12 per million adults per year. This indicates that the Yellow Card system has not seriously underestimated the risk in the UK; the explanation for higher risk in other European countries is not clear.
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ObjectiveTo determine the risk of hospitalisation with COVID-19 and severe COVID-19 among teachers and their household members, overall and compared to healthcare workers and the general working-age population. DesignPopulation-based nested case-control study. SettingsScotland, March 2020 to January 2021. Before and after schools re-opened in early August 2020. ParticipantsAll cases of COVID-19 in Scotland in adults ages 21 to 65 (n = 83,817) and a random sample of controls matched on age, sex and general practice (n = 841,708). ExposureIndividuals identified as actively teaching in a Scottish school by the General Teaching Council for Scotland, and household members of such individuals identified via the Unique Property Reference Number. ComparatorIndividuals identified as healthcare workers in Scotland, their household members, and the remaining "general population" of working-age adults. Main outcomesThe primary outcome was hospitalisation with COVID-19 defined in anyone testing positive with COVID-19 in hospital, admitted to hospital within 28 days of a positive test, and/or diagnosed with COVID-19 on discharge from hospital. Severe COVID-19 was defined as individuals admitted to intensive care or dying within 28 days of a positive test or assigned COVID-19 as a cause of death. ResultsMost teachers were young (mean age 42), female (80%) and had no underlying conditions (84%). The cumulative incidence (risk) of hospitalisation with COVID-19 was below 1% for all of the working age adults. In the period after school re-opening, compared to the general population, in conditional logistic regression models adjusting for age, sex, general practice, deprivation, underlying conditions and number of adults in the household, the relative risk in teachers (among 18,479 cases and controls) for hospitalisation was rate ratio (RR) 0.97 (95%CI 0.72-1.29) and for severe COVID-19 was RR 0.27 (95%CI 0.09-0.77). Equivalent rate ratios for household members of teachers were 0.97 (95%CI 0.74-1.27) and 0.67 (95%CI 0.36-1.24), and for healthcare workers were 1.82 (95%CI 1.55-2.14) and 1.76 (95%CI 1.22-2.56), respectively. ConclusionCompared to working-age adults who are otherwise similar, teachers and their household members are not at increased risk of hospitalisation with COVID-19 and are at lower risk of severe COVID-19. These findings are broadly reassuring for adults engaged in face to face teaching.