In the US, states enacted nonpharmaceutical interventions, including school closure, to reduce the spread of coronavirus disease 2019 (COVID-19). All 50 states closed schools in March 2020 despite uncertainty if school closure would be effective. OBJECTIVE To determine if school closure and its timing were associated with decreased COVID-19 incidence and mortality. DESIGN, SETTING, AND PARTICIPANTS US population-based observational study conducted between March 9, 2020, and May 7, 2020, using interrupted time series analyses incorporating a lag period to allow for potential policy-associated changes to occur. To isolate the association of school closure with outcomes, state-level nonpharmaceutical interventions and attributes were included in negative binomial regression models. States were examined in quartiles based on state-level COVID-19 cumulative incidence per 100 000 residents at the time of school closure. Models were used to derive the estimated absolute differences between schools that closed and schools that remained open as well as the number of cases and deaths if states had closed schools when the cumulative incidence of COVID-19 was in the lowest quartile compared with the highest quartile. EXPOSURES Closure of primary and secondary schools. MAIN OUTCOMES AND MEASURES COVID-19 daily incidence and mortality per 100 000 residents. RESULTS COVID-19 cumulative incidence in states at the time of school closure ranged from 0 to 14.75 cases per 100 000 population. School closure was associated with a significant decline in the incidence of COVID-19 (adjusted relative change per week, −62% [95% CI, −71% to −49%]) and mortality (adjusted relative change per week, −58% [95% CI, −68% to −46%]). Both of these associations were largest in states with low cumulative incidence of COVID-19 at the time of school closure. For example, states with the lowest incidence of COVID-19 had a −72% (95% CI, −79% to −62%) relative change in incidence compared with −49% (95% CI, −62% to −33%) for those states with the highest cumulative incidence. In a model derived from this analysis, it was estimated that closing schools when the cumulative incidence of COVID-19 was in the lowest quartile compared with the highest quartile was associated with 128.7 fewer cases per 100 000 population over 26 days and with 1.5 fewer deaths per 100 000 population over 16 days. CONCLUSIONS AND RELEVANCE Between March 9, 2020, and May 7, 2020, school closure in the US was temporally associated with decreased COVID-19 incidence and mortality; states that closed schools earlier, when cumulative incidence of COVID-19 was low, had the largest relative reduction in incidence and mortality. However, it remains possible that some of the reduction may have been related to other concurrent nonpharmaceutical interventions.

Extensive global sampling and sequencing of the pandemic virus SARS-CoV-2 have enabled researchers to monitor its spread, and to identify concerning new variants. Two important determinants of variant spread are how frequently they arise within individuals, and how likely they are to be transmitted. To characterize within-host diversity and transmission we deep-sequenced 1313 clinical samples from the UK. SARS-CoV-2 infections are characterized by low levels of within-host diversity when viral loads are high, and a narrow bottleneck at transmission. Most variants are either lost, or occasionally fixed, at the point of transmission, with minimal persistence of shared diversity - patterns which are readily observable on the phylogenetic tree. Our results suggest that transmission-enhancing and/or immune-escape variants are likely to arise infrequently, but could spread rapidly if successfully transmitted.

Plain English summaryThere is some evidence that there is a mismatch between what patients and health professionals want to see researched and the research that is actually done. The James Lind Alliance (JLA) research Priority Setting Partnerships (PSPs) were created to address this mismatch. Between 2007 and 2014, JLA partnerships of patients, carers and health professionals agreed on important treatment research questions (priorities) in a range of health conditions, such as Type 1 diabetes, eczema and stroke. We were interested in how much these JLA PSP priorities were similar to treatments undergoing evaluation and research over the same time span. We identified the treatments described in all the JLA PSP research priority lists and compared these to the treatments described in a group of research studies (randomly selected) registered publically. The priorities identified by JLA PSPs emphasised the importance of non-drug treatment research, compared to the research actually being done over the same time period, which mostly involved evaluations of drugs. These findings suggest that the research community should make greater efforts to address issues of importance to users of research, such as patients and healthcare professionals.Abstract Background Comparisons of treatment research priorities identified by patients and clinicians with research actually being done by researchers are very rare. One of the best known of these comparisons (Tallon et al. Relation between agendas of the research community and the research consumer 355:2037–40, 2000) revealed important mismatches in priorities in the assessment of treatments for osteoarthritis of the knee: researchers preferenced drug trials, patients and clinicians prioritised non-drug treatments. These findings were an important stimulus in creating the James Lind Alliance (JLA). The JLA supports research Priority Setting Partnerships (PSPs) of patients, carers and clinicians, who are actively involved in all aspects of the process, to develop shared treatment research priorities. We have compared the types of treatments (interventions) prioritised for evaluation by JLA PSPs with those being studied in samples of clinical trials being done over the same period. Objective We used treatment research priorities generated by JLA PSPs to assess whether, on average, treatments prioritised by patients and clinicians differ importantly from those being studied by researchers. Methods We identified treatments mentioned in prioritised research questions generated by the first 14 JLA PSPs. We compared these treatments with those assessed in random samples of commercial and non-commercial clinical trials recruiting in the UK over the same period, which we identified using WHO’s International Clinical Trials Registry Platform. Results We found marked differences between the proportions of different types of treatments proposed by patients, carers and clinicians and those currently being evaluated by researchers. In JLA PSPs, drugs accounted for only 18 % (23/126) of the trea...

The SARS-CoV-2 Delta variant has spread rapidly worldwide. To provide data on its virological profile, we here report the first local transmission of Delta in mainland China. All 167 infections could be traced back to the first index case. Daily sequential PCR testing of quarantined individuals indicated that the viral loads of Delta infections, when they first become PCR-positive, were on average ~1000 times greater compared to lineage A/B infections during the first epidemic wave in China in early 2020, suggesting potentially faster viral replication and greater infectiousness of Delta during early infection. The estimated transmission bottleneck size of the Delta variant was generally narrow, with 1-3 virions in 29 donor-recipient transmission pairs. However, the transmission of minor iSNVs resulted in at least 3 of the 34 substitutions that were identified in the outbreak, highlighting the contribution of intra-host variants to population-level viral diversity during rapid spread.