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Cases of SARS-CoV-2 infection in Manaus, Brazil, resurged in late 2020, despite previously high levels of infection. Genome sequencing of viruses sampled in Manaus between November 2020 and January 2021 revealed the emergence and circulation of a novel SARS-CoV-2 variant of concern. Lineage P.1, acquired 17 mutations, including a trio in the spike protein (K417T, E484K and N501Y) associated with increased binding to the human ACE2 receptor. Molecular clock analysis shows that P.1 emergence occurred around mid-November 2020 and was preceded by a period of faster molecular evolution. Using a two-category dynamical model that integrates genomic and mortality data, we estimate that P.1 may be 1.7–2.4-fold more transmissible, and that previous (non-P.1) infection provides 54–79% of the protection against infection with P.1 that it provides against non-P.1 lineages. Enhanced global genomic surveillance of variants of concern, which may exhibit increased transmissibility and/or immune evasion, is critical to accelerate pandemic responsiveness.

The SARS-CoV-2 lineage B.1.1.7, designated variant of concern (VOC) 202012/01 by Public Health England 1 , was first identified in the UK in late summer to early autumn 2020 2 . Whole-genome SARS-CoV-2 sequence data collected from community-based diagnostic testing for COVID-19 show an extremely rapid expansion of the B.1.1.7 lineage during autumn 2020, suggesting that it has a selective advantage. Here we show that changes in VOC frequency inferred from genetic data correspond closely to changes inferred by S gene target failures (SGTF) in community-based diagnostic PCR testing. Analysis of trends in SGTF and non-SGTF case numbers in local areas across England shows that B.1.1.7 has higher transmissibility than non-VOC lineages, even if it has a different latent period or generation time. The SGTF data indicate a transient shift in the age composition of reported cases, with cases of B.1.1.7 including a larger share of under 20-year-olds than non-VOC cases. We estimated time-varying reproduction numbers for B.1.1.7 and co-circulating lineages using SGTF and genomic data. The best-supported models did not indicate a substantial difference in VOC transmissibility among different age groups, but all analyses agreed that B.1.1.7 has a substantial transmission advantage over other lineages, with a 50% to 100% higher reproduction number.Phylogenetic studies carried out by the UK COVID-19 Genomics Consortium (COG-UK) (https://www.cogconsortium.uk) 8 provided the first indication that B.1.1.7 has an unusual accumulation of substitutions and was growing at a higer rate than other circulating lineages. We investigated time trends in the frequency of sampling VOC genomes and the proportion of PCR tests exhibiting SGTF across the UK, which we calibrated as a biomarker of VOC infection. Using multiple approaches and both genetic and SGTF data, we conclude that B.1.1.7 is associated with a higher reproduction number (R) than previous non-VOC lineages.We examined whole-genome SARS-CoV-2 sequences from randomly sampled residual materials obtained from community-based COVID-19 testing in England, collected between 1 October 2020 and 16 January 2021. These data included 31,390 B.1.1.7 sequences for which the time and location of sample collection were known. Over the same period, 52,795 non-VOC genomes were collected. VOC sequences were initially concentrated in London (n = 9,134), the South East (n = 5,609), and the East of England (n = 4,413), but is now widely distributed across England.

The ongoing COVID-19 pandemic poses a severe threat to public health worldwide. We combine data on demography, contact patterns, disease severity, and health care capacity and quality to understand its impact and inform strategies for its control. Younger populations in lower income countries may reduce overall risk but limited health system capacity coupled with closer inter-generational contact largely negates this benefit. Mitigation strategies that slow but do not interrupt transmission will still lead to COVID-19 epidemics rapidly overwhelming health systems, with substantial excess deaths in lower income countries due to the poorer health care available. Of countries that have undertaken suppression to date, lower income countries have acted earlier. However, this will need to be maintained or triggered more frequently in these settings to keep below available health capacity, with associated detrimental consequences for the wider health, well-being and economies of these countries.

The SARS-CoV-2 B.1.617.2 (Delta) variant was first identified in the state of Maharashtra in late 2020 and spread throughout India, outcompeting pre-existing lineages including B.1.617.1 (Kappa) and B.1.1.7 (Alpha) 1 . In vitro, B.1.617.2 is 6-fold less sensitive to serum neutralising antibodies from recovered individuals, and 8-fold less sensitive to vaccine-elicited antibodies as compared to wild type (WT) Wuhan-1 bearing D614G. Serum neutralising titres against B.1.617.2 were lower in ChAdOx-1 versus BNT162b2 vaccinees. B.1.617.2 spike pseudotyped viruses exhibited compromised sensitivity to monoclonal antibodies against the receptor binding domain (RBD) and N-terminal domain (NTD). B.1.617.2 demonstrated higher replication efficiency in both airway organoid and human airway epithelial systems compared to B.1.1.7, associated with B.1.617.2 spike in a predominantly cleaved state compared to B.1.1.7. The B.1.617.2 spike protein was able to mediate highly efficient syncytium formation that was less sensitive to inhibition by neutralising antibody as compared to WT spike. Additionally we observed that B.1.617.2 had higher replication and spike mediated entry as compared to B.1.617.1, potentially explaining B.1.617.2 dominance. In an analysis of over 130 SARS-CoV-2 infected healthcare workers across three centres in India during a period of mixed lineage circulation, we observed reduced ChAdOx-1 vaccine effectiveness against B.1.617.2 relative to non-B.1.617.2, with the caveat of possible residual confounding. Compromised vaccine efficacy against the highly fit and immune evasive B.1.617.2 Delta variant warrants continued infection control measures in the post-vaccination era. India's first wave of SARS-CoV-2 infections in mid-2020 was relatively mild and was controlled by a nationwide lockdown. Since easing of restrictions, India has seen expansion in cases of COVID-19 since March

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Summary Background COVID-19 has the potential to cause substantial disruptions to health services, due to cases overburdening the health system or response measures limiting usual programmatic activities. We aimed to quantify the extent to which disruptions to services for HIV, tuberculosis, and malaria in low-income and middle-income countries with high burdens of these diseases could lead to additional loss of life over the next 5 years. Methods Assuming a basic reproduction number of 3·0, we constructed four scenarios for possible responses to the COVID-19 pandemic: no action, mitigation for 6 months, suppression for 2 months, or suppression for 1 year. We used established transmission models of HIV, tuberculosis, and malaria to estimate the additional impact on health that could be caused in selected settings, either due to COVID-19 interventions limiting activities, or due to the high demand on the health system due to the COVID-19 pandemic. Findings In high-burden settings, deaths due to HIV, tuberculosis, and malaria over 5 years could increase by up to 10%, 20%, and 36%, respectively, compared with if there was no COVID-19 pandemic. The greatest impact on HIV was estimated to be from interruption to antiretroviral therapy, which could occur during a period of high health system demand. For tuberculosis, the greatest impact would be from reductions in timely diagnosis and treatment of new cases, which could result from any prolonged period of COVID-19 suppression interventions. The greatest impact on malaria burden could be as a result of interruption of planned net campaigns. These disruptions could lead to a loss of life-years over 5 years that is of the same order of magnitude as the direct impact from COVID-19 in places with a high burden of malaria and large HIV and tuberculosis epidemics. Interpretation Maintaining the most critical prevention activities and health-care services for HIV, tuberculosis, and malaria could substantially reduce the overall impact of the COVID-19 pandemic. Funding Bill & Melinda Gates Foundation, Wellcome Trust, UK Department for International Development, and Medical Research Council.

Brazil currently has one of the fastest growing SARS-CoV-2 epidemics in the world. Owing to limited available data, assessments of the impact of non-pharmaceutical interventions (NPIs) on virus spread remain challenging. Using a mobility-driven transmission model, we show that NPIs reduced the reproduction number from >3 to 1–1.6 in São Paulo and Rio de Janeiro. Sequencing of 427 new genomes and analysis of a geographically representative genomic dataset identified >100 international virus introductions in Brazil. We estimate that most (76%) of the Brazilian strains fell in three clades that were introduced from Europe between 22 February11 March 2020. During the early epidemic phase, we found that SARS-CoV-2 spread mostly locally and within-state borders. After this period, despite sharp decreases in air travel, we estimated multiple exportations from large urban centers that coincided with a 25% increase in average travelled distances in national flights. This study sheds new light on the epidemic transmission and evolutionary trajectories of SARS-CoV-2 lineages in Brazil, and provide evidence that current interventions remain insufficient to keep virus transmission under control in the country.