SARS-CoV-2 incidence among teaching staff in primary and secondary schools-Wales, 2020-2021.

BACKGROUND: During the COVID-19 pandemic, face-to-face delivery of education in schools across Wales was disrupted with repeated school closures to limit risk of infection. Evidence describing the incidence of infection amongst school staff during times when schools were open is limited. A previous research study found infection rates were higher in English primary school settings when compared with secondary. An Italian study suggested teachers weren't at greater risk of infection in comparison to the general population. The aim of this study was to identify whether educational staff had higher incidence rates than their counterparts in the general population in Wales, and secondly whether incidence rates amongst staff differed between primary and secondary school settings and by teacher age. METHODS: We performed a retrospective observational cohort study using the national case detection and contact tracing system implemented during the COVID pandemic. Age stratified person-day COVID-19 incidence rates amongst teaching staff linked to primary or secondary schools in Wales were calculated for the autumn and summer terms during 2020-2021. RESULTS: The observed pooled COVID-19 incidence rates for staff across both terms was 23.30 per 100,000 person days (95% CI: 22.31-24.33). By comparison, the rate in the general population aged 19-65, was 21.68 per 100,000 person days (95%: CI 21.53-21.84). Incidence among teaching staff was highest in the two youngest age groups (< 25 years and 25-29 years). When compared to the age matched general population, incidence was higher in the autumn term amongst primary school teachers aged ≤ 39 years, and in the summer term higher only in the primary school teachers aged < 25 years. CONCLUSION: The data were consistent with an elevated risk of COVID-19 amongst younger teaching staff in primary schools when compared to the general population, however differences in case ascertainment couldn't be excluded as a possible reason for this. Rate differences by age group in teaching staff mirrored those in the general population. The risk in older teachers (≥ 50 years) in both settings was the same or lower than in the general population. Amongst all age groups of teachers maintaining the key risk mitigations within periods of COVID transmission remain important.

Immunology of pregnancy and reproductive health in autoimmune rheumatic diseases. Update from the 11th International Conference on Reproduction, Pregnancy and Rheumatic Diseases.

Autoimmune rheumatic diseases (ARD) can affect women and men during fertile age, therefore reproductive health is a priority issue in rheumatology. Many topics need to be considered during preconception counselling: fertility, the impact of disease-related factors on pregnancy outcomes, the influence of pregnancy on disease activity, the compatibility of medications with pregnancy and breastfeeding. Risk stratification and individualized treatment approach elaborated by a multidisciplinary team minimize the risk of adverse pregnancy outcomes (APO). Research has been focused on identifying biomarkers that can be predictive of APO. Specifically, preeclampsia and hypertensive disorders of pregnancy tend to develop more frequently in women with ARD. Placental insufficiency can lead to intrauterine growth restriction and small-for-gestational age newborns. Such APO have been shown to be associated with maternal disease activity in different ARD. Therefore, a key message to be addressed to the woman wishing for a pregnancy and to her family is that treatment with compatible drugs is the best way to ensure maternal and fetal wellbeing. An increasing number of medications have entered the management of ARD, but data about their use in pregnancy and lactation are scarce. More information is needed for most biologic drugs and their biosimilars, and for the so-called small molecules, while there is sufficient evidence to recommend the use of TNF inhibitors if needed for keeping maternal disease under control. Other issues related to the reproductive journey have emerged as "unmet needs", such as sexual dysfunction, contraception, medically assisted reproduction techniques, long-term outcome of children, and they will be addressed in this review paper. Collaborative research has been instrumental to reach current knowledge and the future will bring novel insights thanks to pregnancy registries and prospective studies that have been established in several Countries and to their joint efforts in merging data.

IMPACT Study: Preliminary results of a trial with a biologic to prevent preeclampsia in women with antiphospholipid syndrome

BackgroundPregnant women with antiphospholipid antibodies and/or lupus have higher rates of adverse pregnancy outcomes (APOs), such as fetal loss and preterm birth due to severe preeclampsia (PE) or placental insufficiency (PI). The presence of lupus anticoagulant (LAC) is the strongest predictor of an APO. At present, there is no effective treatment for women with these high-risk pregnancies, but in an animal model that mimics this human condition we found that TNF-α was a critical downstream effector of abnormal placental development and fetal damage, and that TNF-α blockade normalized placentation and spiral artery remodeling, and rescued pregnancies. We sought to determine whether TNF-α blockade during pregnancy, added to a regimen of heparin and low dose aspirin, reduces the rate of APOs in women with clinical APS and LAC.MethodsThe IMPACT Study (IMProve Pregnancy in APS with Certolizumab Therapy) is an open label single-stage Phase II trial to evaluate the effect of certolizumab, a TNF-α inhibitor that does not cross the placenta and has been shown to be well tolerated in pregnancy, to reduce the risk of adverse outcomes in this population. Patients with APS and LAC are referred to IMPACT by their physicians, consented and screened remotely by a study investigator, and medication is sent to the patient. They are treated with certolizumab from gestational week 8 through 28. Investigators contact patients every 2 weeks and receive medical reports and research blood samples monthly. The primary outcome is a composite of two APOs associated with poor placentation: fetal death >10 WG or severe preeclampsia/placental insufficiency requiring delivery prior to 34 weeks gestation. The target sample size is 45 evaluable subjects. We hypothesize that the rate of the primary outcome in these pregnancies will be reduced from ~40% based on historical data to 20% with certolizumab.ResultsSince May 2017 and despite the COVID-19 pandemic, we have enrolled 41 patients from ten states and 1 Canadian province. Characteristics: 56% previous PE or PI <34 weeks requiring delivery, 83% previous fetal death >10 weeks;61% thrombosis and/or stroke and 24% SLE in addition to APS. During the trial, no new clinical manifestations of SLE have been observed in participants who did not carry the SLE diagnosis. There were no instances of new anti-DNA antibodies or increases in autoantibody titres in those patients who were anti-DNA antibody positive. ACL or anti-β2GPI antibody titres did not change during the trial. There have been no serious adverse events attributable to the study medication.ConclusionWe are successfully using a "rare disease study” approach to conduct the first trial of a biologic therapy to prevent pregnancy complications in women with APS and LAC. Certolizumab appears to be safe in this small trial. Certolizumab appears to be safe so far in this small trial. IMPACT must be completed before we can draw any conclusions about efficacy, and its results must be confirmed in a future study.AcknowledgementsNIAMS, Lupus Research institute, Lupus Foundation of AmericaClinicalTrials. gov Identifier: NCT03152058Lay SummaryPregnancies in patients with antiphospholipid syndrome who have a lupus anticoagulant in their blood have a high likelihood of ending in fetal death or very premature delivery because of poor placental development and preeclampsia. At present, there is no effective treatment for women with these high-risk pregnancies, but our work in an animal model that mimics this human condition shows that blockade of TNF-α, a pivotal mediator of inflammation, prevents adverse outcomes. Our study will determine whether treatment during pregnancy with certolizumab, a TNF-α inhibitor that does not cross the placenta, reduces the rate of poor pregnancy outcomes in women with clinical antiphospholipid syndrome;and, if successful, it will provide a new approach to protecting pregnancies in women with antiphospholipid syndrome and a rationale for trials of TNF-α blockade in women with other conditions, like SLE, who are a risk for preeclampsia or placental insufficiency.

Comparative risk of cerebral venous sinus thrombosis (CVST) following COVID-19 vaccination or infection: A national cohort study using linked electronic health records.

To inform the public and policy makers, we investigated and compared the risk of cerebral venous sinus thrombosis (CVST) after SARS-Cov-2 vaccination or infection using a national cohort of 2,643,699 individuals aged 17 y and above, alive, and resident in Wales on 1 January 2020 followed up through multiple linked data sources until 28 March 2021. Exposures were first dose of Oxford-ChAdOx1 or Pfizer-BioNTech vaccine or polymerase chain reaction (PCR)-confirmed SARS-Cov-2 infection. The outcome was an incident record of CVST. Hazard ratios (HR) were calculated using multivariable Cox regression, adjusted for confounders. HR from SARS-Cov-2 infection was compared with that for SARS-Cov-2 vaccination. We identified 910,556 (34.4%) records of first SARS-Cov-2 vaccination and 165,862 (6.3%) of SARS-Cov-2 infection. A total of 1,372 CVST events were recorded during the study period, of which 52 (3.8%) and 48 (3.5%) occurred within 28 d after vaccination and infection, respectively. We observed slight non-significant risk of CVST within 28 d of vaccination [aHR: 1.34, 95% CI: 0.95-1.90], which remained after stratifying by vaccine [BNT162b2, aHR: 1.18 (95% CI: 0.63-2.21); ChAdOx1, aHR: 1.40 (95% CI: 0.95-2.05)]. Three times the number of CVST events is observed within 28 d of a positive SARS-Cov-2 test [aHR: 3.02 (95% CI: 2.17-4.21)]. The risk of CVST following SARS-Cov-2 infection is 2.3 times that following SARS-Cov-2 vaccine. This is important information both for those designing COVID-19 vaccination programs and for individuals making their own informed decisions on the risk-benefit of vaccination. This record-linkage approach will be useful in monitoring the safety of future vaccine programs.

COVID-19 vaccine uptake and effectiveness in adults aged 50 years and older in Wales UK: a 1.2m population data-linkage cohort approach.

Vaccination programs against COVID-19 vary globally with estimates of vaccine effectiveness (VE) affected by vaccine type, schedule, strain, outcome, and recipient characteristics. This study assessed VE of BNT162b2 and ChAdOx1 vaccines against PCR positive SARS-CoV-2 infection, hospital admission, and death among adults aged 50 years and older in Wales, UK during the period 7 December 2020 to 18 July 2021, when Alpha, followed by Delta, were the predominant variants. We used individual-level linked routinely collected data within the Secure Anonymized Information Linkage (SAIL) Databank. Data were available for 1,262,689 adults aged 50 years and over; coverage of one dose of any COVID-19 vaccine in this population was 92.6%, with coverage of two doses 90.4%. VE against PCR positive infection at 28-days or more post first dose of any COVID-19 vaccine was 16.0% (95%CI 9.6-22.0), and 42.0% (95%CI 36.5-47.1) seven or more days after a second dose. VE against hospital admission was higher at 72.9% (95%CI 63.6-79.8) 28 days or more post vaccination with one dose of any vaccine type, and 84.9% (95%CI 78.2-89.5) at 7 or more days post two doses. VE for one dose against death was estimated to be 80.9% (95%CI 72.1-86.9). VE against PCR positive infection and hospital admission was higher for BNT162b2 compared to ChAdOx1. In conclusion, vaccine uptake has been high among adults in Wales and VE estimates are encouraging, with two doses providing considerable protection against severe outcomes. Continued roll-out of the vaccination programme within Wales, and globally, is crucial in our fight against COVID-19.

COVID-19 and antiphospholipid antibodies: A position statement and management guidance from AntiPhospholipid Syndrome Alliance for Clinical Trials and InternatiOnal Networking (APS ACTION).

Coronavirus disease 2019 (COVID-19) is associated with a high rate of thrombosis. Prolonged activated partial thromboplastin times (aPTT) and antiphospholipid antibodies (aPL) are reported in COVID-19 patients. The majority of publications have not reported whether patients develop clinically relevant persistent aPL, and the clinical significance of new aPL-positivity in COVID-19 is currently unknown. However, the reports of aPL-positivity in COVID-19 raised the question whether common mechanisms exist in the pathogenesis of COVID-19 and antiphospholipid syndrome (APS). In both conditions, thrombotic microangiopathy resulting in microvascular injury and thrombosis is hypothesized to occur through multiple pathways, including endothelial damage, complement activation, and release of neutrophil extracellular traps (NETosis). APS-ACTION, an international APS research network, created a COVID-19 working group that reviewed common mechanisms, positive aPL tests in COVID-19 patients, and implications of COVID-19 infection for patients with known aPL positivity or APS, with the goals of proposing guidance for clinical management and monitoring of aPL-positive COVID-19 patients. This guidance also serves as a call and focus for clinical and basic scientific research.

Impact of the first wave of the COVID-19 pandemic on systemic lupus erythematosus patients: Results from a multi-center prospective cohort.

OBJECTIVE: The aim of this study was to evaluate the initial impact of the COVID-19 pandemic on individuals with systemic lupus erythematosus (SLE). METHODS: Patients with SLE participating in a multi-center longitudinal cohort study in New York and Boston were invited to complete a supplemental web-based questionnaire in the summer of 2020. Participants completed standardized patient-reported outcome (PRO) measures and a combination of Likert scale and open-ended questions exploring the impact of the COVID-19 pandemic on their health and access to health care. Changes in PROs were evaluated with paired t-tests and frequencies of worsened symptoms were calculated. A thematic qualitative analysis was conducted on free text responses. RESULTS: Of 97 patients invited, 63 (65%) completed a supplemental questionnaire. Nearly 50% of respondents exhibited increases in anxiety (47.5%) and depression (48.3%) and over 40% scored worse in measures of pain interference, fatigue, and cognitive abilities. Respondents with pre-existing diagnoses of anxiety did not differ from other participants in PRO scores, but were more than three times as likely to report worsened health status. Patients denied difficulties accessing medications (85%) or medical care (84%) and over 50% participated in telehealth visits. Anxiety and increased health risks due to immunosuppression were recurring themes in free text responses. CONCLUSIONS: SLE patients experienced a significant physical and emotional toll in the initial months of the COVID-19 pandemic. Comprehensive patient-centered care, including monitoring and addressing anxiety and health-related quality of life, is critical to improving health outcomes in this population during the ongoing health crisis.

Risk factors for outbreaks of COVID-19 in care homes following hospital discharge: A national cohort analysis.

BACKGROUND: The population of adult residential care homes has been shown to have high morbidity and mortality in relation to COVID-19. METHODS: We examined 3115 hospital discharges to a national cohort of 1068 adult care homes and subsequent outbreaks of COVID-19 occurring between 22 February and 27 June 2020. A Cox proportional hazards regression model was used to assess the impact of time-dependent exposure to hospital discharge on incidence of the first known outbreak, over a window of 7-21 days after discharge, and adjusted for care home characteristics, including size and type of provision. RESULTS: A total of 330 homes experienced an outbreak, and 544 homes received a discharge over the study period. Exposure to hospital discharge was not associated with a significant increase in the risk of a new outbreak (hazard ratio 1.15, 95% CI 0.89, 1.47, P = .29) after adjusting for care home characteristics. Care home size was the most significant predictor. Hazard ratios (95% CI) in comparison with homes of <10 residents were as follows: 3.40 (1.99, 5.80) for 10-24 residents; 8.25 (4.93, 13.81) for 25-49 residents; and 17.35 (9.65, 31.19) for 50+ residents. When stratified for care home size, the outbreak rates were similar for periods when homes were exposed to a hospital discharge, in comparison with periods when homes were unexposed. CONCLUSION: Our analyses showed that large homes were at considerably greater risk of outbreaks throughout the epidemic, and after adjusting for care home size, a discharge from hospital was not associated with a significant increase in risk.

Pregnancy and Rheumatic Disease: Experience at a Single Center in New York City During the COVID-19 Pandemic.

OBJECTIVE: The present study was undertaken to evaluate the pregnancy experiences of women receiving care in the division of rheumatology at a major academic center in New York City during the COVID-19 pandemic. METHODS: A web-based COVID-19 survey was emailed to 26,045 patients who were followed in the division of rheumatology at a single center in New York City. Women ages 18-50 years were asked about their pregnancy. We compared the COVID-19 experience between pregnant and nonpregnant women and also explored the impact of the pandemic on prenatal care and perinatal outcomes. RESULTS: Among 7,094 of the 26,045 respondents, 1,547 were women ages 18-50 years, with 61 (4%) reporting being pregnant during the pandemic. The prevalence of self-reported COVID-19 was similar in pregnant and nonpregnant women (8% versus 9%, respectively; P = 0.76). Among women with COVID-19, pregnant women had a shorter duration of symptoms (P < 0.01) and were more likely to experience loss of smell or taste (P = 0.02) than nonpregnant women. Approximately three-fourths of women had a systemic rheumatic disease, with no differences when stratified by pregnancy or COVID-19 status. In all, 67% of pregnant women noted changes to prenatal care during the pandemic, and 23% of postpartum women stated that the pandemic affected delivery. CONCLUSION: Among women followed in the division of rheumatology at a major center in New York City, pregnancy was not associated with increased self-reported COVID-19. Pregnancy was associated with a shorter duration of COVID-19 symptoms and a higher prevalence of loss of smell or taste. The COVID-19 pandemic impacted prenatal care for the majority of pregnant patients.

Hydroxychloroquine and Chloroquine in COVID-19: A Survey of Prescription Patterns Among Rheumatologists.

OBJECTIVE: With hydroxychloroquine (HCQ) and chloroquine (CQ) emerging as potential therapies for coronavirus disease 2019 (COVID-19), shortages have been reported. We aimed to understand how rheumatologists, one of the most common prescribers of HCQ/CQ, prescribed these medications to manage COVID-19 and to understand if their patients are affected by shortages. METHODS: Between April 8 and April 27, 2020, an online survey was distributed to a convenience sample of rheumatologists who practice medicine in a diverse range of settings globally, resulting in 506 responses. Adjusted Poisson regression models were calculated. RESULTS: Only 6% of respondents prescribed HCQ/CQ for COVID-19 prophylaxis, and only 12% for outpatient treatment of COVID-19. Compared to the United States, the likelihood of prescribing HCQ/CQ for prophylaxis was higher in India (adjusted risk ratio [aRR], 6.7; 95% confidence interval [CI], 2.7-16.8; p < 0.001). Further, compared to the United States and those with 1 to 5 years of experience, rheumatologists in Europe (aRR, 2.9; 95% CI, 1.6-5.3; p < 0.001) and those with 10+ years of experience (11-20 years: aRR, 2.5; 95% CI, 1.2-5.3; p = 0.015; 21+ years: aRR = 3.3; 95% CI, 1.4-7.4; p = 0.004) had a higher likelihood of prescribing HCQ/CQ for outpatient treatment. Of note, 71% of all rheumatologists reported that their patients were directly affected by HCQ/CQ shortages. CONCLUSION: The results suggest that only a small percentage of rheumatologists are prescribing HCQ/CQ for prophylaxis or outpatient treatment of COVID-19. Medication shortages experienced by large numbers of autoimmune disease patients are concerning and should play a role in decisions, especially given poor efficacy data for HCQ/CQ in COVID-19.