Changes in symptomatology, reinfection, and transmissibility associated with the SARS-CoV-2 variant B.1.1.7: an ecological study

Background The SARS-CoV-2 variant B.1.1.7 was first identified in December, 2020, in England. We aimed to investigate whether increases in the proportion of infections with this variant are associated with differences in symptoms or disease course, reinfection rates, or transmissibility. Methods We did an ecological study to examine the association between the regional proportion of infections with the SARS-CoV-2 B.1.1.7 variant and reported symptoms, disease course, rates of reinfection, and transmissibility. Data on types and duration of symptoms were obtained from longitudinal reports from users of the COVID Symptom Study app who reported a positive test for COVID-19 between Sept 28 and Dec 27, 2020 (during which the prevalence of B.1.1.7 increased most notably in parts of the UK). From this dataset, we also estimated the frequency of possible reinfection, defined as the presence of two reported positive tests separated by more than 90 days with a period of reporting no symptoms for more than 7 days before the second positive test. The proportion of SARS-CoV-2 infections with the B.1.1.7 variant across the UK was estimated with use of genomic data from the COVID-19 Genomics UK Consortium and data from Public Health England on spike-gene target failure (a non-specific indicator of the B.1.1.7 variant) in community cases in England. We used linear regression to examine the association between reported symptoms and proportion of B.1.1.7. We assessed the Spearman correlation between the proportion of B.1.1.7 cases and number of reinfections over time, and between the number of positive tests and reinfections. We estimated incidence for B.1.1.7 and previous variants, and compared the effective reproduction number, Rt, for the two incidence estimates. Findings From Sept 28 to Dec 27, 2020, positive COVID-19 tests were reported by 36 920 COVID Symptom Study app users whose region was known and who reported as healthy on app sign-up. We found no changes in reported symptoms or disease duration associated with B.1.1.7. For the same period, possible reinfections were identified in 249 (0·7% [95% CI 0·6–0·8]) of 36 509 app users who reported a positive swab test before Oct 1, 2020, but there was no evidence that the frequency of reinfections was higher for the B.1.1.7 variant than for pre-existing variants. Reinfection occurrences were more positively correlated with the overall regional rise in cases (Spearman correlation 0·56–0·69 for South East, London, and East of England) than with the regional increase in the proportion of infections with the B.1.1.7 variant (Spearman correlation 0·38–0·56 in the same regions), suggesting B.1.1.7 does not substantially alter the risk of reinfection. We found a multiplicative increase in the Rt of B.1.1.7 by a factor of 1·35 (95% CI 1·02–1·69) relative to pre-existing variants. However, Rt fell below 1 during regional and national lockdowns, even in regions with high proportions of infections with the B.1.1.7 variant. Interpretation The lack of change in symptoms identified in this study indicates that existing testing and surveillance infrastructure do not need to change specifically for the B.1.1.7 variant. In addition, given that there was no apparent increase in the reinfection rate, vaccines are likely to remain effective against the B.1.1.7 variant. Funding Zoe Global, Department of Health (UK), Wellcome Trust, Engineering and Physical Sciences Research Council (UK), National Institute for Health Research (UK), Medical Research Council (UK), Alzheimer's Society

Effects of continuous feedback on households’ electricity consumption: Potentials and barriers

Two field experiments were carried out to study (a) the effects on energy savings of continuous visual feedback via in-home displays, and (b) the motives for responding or not. In study 1, 40 participants living in separate or semi-detached houses in two different towns participated. All participants received a questionnaire and a list of possible energy saving measures. Households were then randomly assigned to an experimental condition (display) or a control condition (no display). In study 2, 32 households in rented apartments participated. No significant differences between the conditions were found for either of the studies. In study 2, semi-structured interviews were conducted among nine of the households. Through an analysis of interview transcripts barriers were identified explaining why the feedback intervention was not sufficient to change behaviour and reduce consumption. The barriers experienced indicate that there is a risk of overconfidence in IHDs. For the development of energy policies and more wide-scale implementation, it is important to be aware of the potential obstacles to success

Early integration of the user’s perspective in the renovation process: Experiences from an “In-depth Dialogue Process with Residents” in rental flats from the 1950s

An “In-depth dialogue with residents” has been applied in the pre-study of a renovation of a housing area from 1950s with about 500 rental flats. The paper presents the result from this dialogue process and discusses the potential of the methodology to achieve a more integrated, sustainable renovation. The process was carried out by a transdisciplinary team with representatives from the housing manager, an architect firm with competences in sociology, the tenant organization, and researchers from architecture and environmental psychology. The dialogue process comprised four main activities: design of process and selection of tools, data collection, compilation of material and feedback to residents and housing company, and a following-up. Data about the residents view were collected by intercept interviews, a questionnaire survey, a walking tour, and a focus group interview. The dialogue process identified values appreciated by the residents and had impact on alternative renovation option for the flats

Early integration of the user’s perspective in the renovation process: Experiences from an “In-depth Dialogue Process with Residents” in rental flats from the 1950s

An “In-depth dialogue with residents” has been applied in the pre-study of a renovation of a housing area from 1950s with about 500 rental flats. The paper presents the result from this dialogue process and discusses the potential of the methodology to achieve a more integrated, sustainable renovation. The process was carried out by a transdisciplinary team with representatives from the housing manager, an architect firm with competences in sociology, the tenant organization, and researchers from architecture and environmental psychology. The dialogue process comprised four main activities: design of process and selection of tools, data collection, compilation of material and feedback to residents and housing company, and a following-up. Data about the residents view were collected by intercept interviews, a questionnaire survey, a walking tour, and a focus group interview. The dialogue process identified values appreciated by the residents and had impact on alternative renovation option for the flats

Fitusiran prophylaxis in people with severe haemophilia A or haemophilia B without inhibitors (ATLAS-A/B): a multicentre, open-label, randomised, phase 3 trial

Background: fitusiran, a subcutaneous investigational siRNA therapeutic, targets antithrombin with the goal of rebalancing haemostasis in people with haemophilia A or haemophilia B, regardless of inhibitor status. We aimed to evaluate the efficacy and safety of fitusiran prophylaxis in people with severe haemophilia without inhibitors.Methods: this multicentre, open-label, randomised phase 3 study was conducted at 45 sites in 17 countries. Male participants aged at least 12 years with severe haemophilia A or B without inhibitors, who had previously been treated on-demand with clotting factor concentrates, were randomly assigned in a 2:1 ratio to receive 80 mg subcutaneous fitusiran prophylaxis once per month or to continue on-demand clotting factor concentrates for a total of 9 months. Randomisation was stratified by the number of bleeding events in the 6 months before screening (≤10 bleeds and >10 bleeds) and by haemophilia type (haemophilia A or B). The primary endpoint was annualised bleeding rate, analysed in the intention-to-treat analysis set. Safety and tolerability were assessed in the safety analysis set. This trial is registered with ClinicalTrials.gov, NCT03417245, and is complete.Findings: between March 1, 2018, and July 14, 2021, 177 male participants were screened for eligibility and 120 were randomly assigned to receive fitusiran prophylaxis (n=80) or on-demand clotting factor concentrates (n=40). Median follow-up was 7·8 months (IQR 7·8–7·8) in the fitusiran group and 7·8 months (7·8–7·8) in the on-demand clotting factor concentrates group. The median annualised bleeding rate was 0·0 (0·0–3·4) in the fitusiran group and 21·8 (8·4–41·0) in the on-demand clotting factor concentrates group. The estimated mean annualised bleeding rate was significantly lower in the fitusiran prophylaxis group (3·1 [95% CI 2·3–4·3]) than in the on-demand clotting factor concentrates group (31·0 [21·1–45·5]; rate ratio 0·101 [95% CI 0·064–0·159]; p<0·0001). In the fitusiran group, 40 (51%) of 79 treated participants had no treated bleeds compared with two (5%) of 40 participants in the on-demand clotting factor concentrates group. Increased alanine aminotransferase concentration (18 [23%] of 79 participants in the safety analysis set) was the most common treatment-emergent adverse event in the fitusiran group and hypertension (four (10%) of 40 participants) was the most common in the on-demand clotting factor concentrates group. Treatment-emergent serious adverse events were reported in five (6%) participants in the fitusiran group (cholelithiasis [n=2, 3%], cholecystitis [n=1, 1%], lower respiratory tract infection [n=1, 1%], and asthma [n=1, 1%]) and five (13%) participants in the on-demand clotting factor concentrates group (gastroenteritis, pneumonia, suicidal ideation, diplopia, osteoarthritis, epidural haemorrhage, humerus fracture, subdural haemorrhage, and tibia fracture [all n=1, 3%]). No treatment-related thrombosis or deaths were reported.Interpretation: in participants with haemophilia A or B without inhibitors, fitusiran prophylaxis resulted in significant reductions in annualised bleeding rate compared with on-demand clotting factor concentrates and no bleeding events in approximately half of participants. Fitusiran prophylaxis shows haemostatic efficacy in both haemophilia A and haemophilia B, and therefore has the potential to be transformative in the management of all people with haemophilia