Genomics and epidemiology of a novel SARS-CoV-2 lineage in Manaus, Brazil

Cases of SARS-CoV-2 infection in Manaus, Brazil, resurged in late 2020, despite high levels of previous infection there. Through genome sequencing of viruses sampled in Manaus between November 2020 and January 2021, we identified the emergence and circulation of a novel SARS-CoV-2 variant of concern, lineage P.1, that 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 early 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 1.4-2.2 times more transmissible and 25-61% more likely to evade protective immunity elicited by previous infection with 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. One-Sentence SummaryWe report the evolution and emergence of a SARS-CoV-2 lineage of concern associated with rapid transmission in Manaus.

Social and racial inequalities in COVID-19 risk of hospitalisation and death across Sao Paulo state, Brazil

BackgroundLittle evidence exists on the differential health effects of COVID-19 on disadvantaged population groups. Here we characterise the differential risk of hospitalisation and death in Sao Paulo state, Brazil and show how vulnerability to COVID-19 is shaped by socioeconomic inequalities. MethodsWe conducted a cross-sectional study using hospitalised severe acute respiratory infections (SARI) notified from March to August 2020, in the Sistema de Monitoramento Inteligente de Sao Paulo (SIMI-SP) database. We examined the risk of hospitalisation and death by race and socioeconomic status using multiple datasets for individual-level and spatio-temporal analyses. We explained these inequalities according to differences in daily mobility from mobile phone data, teleworking behaviour, and comorbidities. FindingsThroughout the study period, patients living in the 40% poorest areas were more likely to die when compared to patients living in the 5% wealthiest areas (OR: 1{middle dot}60, 95% CI: 1{middle dot}48 - 1{middle dot}74) and were more likely to be hospitalised between April and July, 2020 (OR: 1{middle dot}08, 95% CI: 1{middle dot}04 - 1{middle dot}12). Black and Pardo individuals were more likely to be hospitalised when compared to White individuals (OR: 1{middle dot}37, 95% CI: 1{middle dot}32 - 1{middle dot}41; OR: 1{middle dot}23, 95% CI: 1{middle dot}21 - 1{middle dot}25, respectively), and were more likely to die (OR: 1{middle dot}14, 95% CI: 1{middle dot}07 - 1{middle dot}21; 1{middle dot}09, 95% CI: 1{middle dot}05 - 1{middle dot}13, respectively). InterpretationLow-income and Black and Pardo communities are more likely to die with COVID-19. This is associated with differential access to healthcare, adherence to social distancing, and the higher prevalence of comorbidities. FundingThis project was supported by a Medical Research Council-Sao Paulo Research Foundation (FAPESP) CADDE partnership award (MR/S0195/1 and FAPESP 18/14389-0) (http://caddecentre.org/). This work received funding from the U.K. Medical Research Council under a concordat with the U.K. Department for International Development.

Evolution and epidemic spread of SARS-CoV-2 in Brazil

Brazil currently has one of the fastest growing SARS-CoV-2 epidemics in the world. Due to limited available data, assessments of the impact of non-pharmaceutical interventions (NPIs) on virus transmission and epidemic spread remain challenging. We investigate the impact of NPIs in Brazil using epidemiological, mobility and genomic data. Mobility-driven transmission models for Sao Paulo and Rio de Janeiro cities show that the reproduction number (Rt) reached below 1 following NPIs but slowly increased to values between 1 to 1.3 (1.0-1.6). Genome sequencing of 427 new genomes and analysis of a geographically representative genomic dataset from 21 of the 27 Brazilian states identified >100 international introductions of SARS-CoV-2 in Brazil. We estimate that three clades introduced from Europe emerged between 22 and 27 February 2020, and were already well-established before the implementation of NPIs and travel bans. During this first phase of the epidemic establishment of SARS-CoV-2 in Brazil, we find that the virus spread mostly locally and within-state borders. Despite sharp decreases in national air travel during this period, we detected a 25% increase in the average distance travelled by air passengers during this time period. This coincided with the spread of SARS-CoV-2 from large urban centers to the rest of the country. In conclusion, our results shed light on the role of large and highly connected populated centres in the rapid ignition and establishment of SARS-CoV-2, and provide evidence that current interventions remain insufficient to keep virus transmission under control in Brazil. One Sentence SummaryJoint analysis of genomic, mobility and epidemiological novel data provide unique insight into the spread and transmission of the rapidly evolving epidemic of SARS-CoV-2 in Brazil.

Epidemiological and clinical characteristics of the early phase of the COVID-19 epidemic in Brazil

BackgroundThe first case of COVID-19 was detected in Brazil on February 25, 2020. We report the epidemiological, demographic, and clinical findings for confirmed COVID-19 cases during the first month of the epidemic in Brazil. MethodsIndividual-level and aggregated COVID-19 data were analysed to investigate demographic profiles, socioeconomic drivers and age-sex structure of COVID-19 tested cases. Basic reproduction numbers (R0) were investigated for Sao Paulo and Rio de Janeiro. Multivariate logistic regression analyses were used to identify symptoms associated with confirmed cases and risk factors associated with hospitalization. Laboratory diagnosis for eight respiratory viruses were obtained for 2,429 cases. FindingsBy March 25, 1,468 confirmed cases were notified in Brazil, of whom 10% (147 of 1,468) were hospitalised. Of the cases acquired locally (77{middle dot}8%), two thirds (66{middle dot}9% of 5,746) were confirmed in private laboratories. Overall, positive association between higher per capita income and COVID-19 diagnosis was identified. The median age of detected cases was 39 years (IQR 30-53). The median R0 was 2{middle dot}9 for Sao Paulo and Rio de Janeiro. Cardiovascular disease/hypertension were associated with hospitalization. Co-circulation of six respiratory viruses, including influenza A and B and human rhinovirus was detected in low levels. InterpretationSocioeconomic disparity determines access to SARS-CoV-2 testing in Brazil. The lower median age of infection and hospitalization compared to other countries is expected due to a younger population structure. Enhanced surveillance of respiratory pathogens across socioeconomic statuses is essential to better understand and halt SARS-CoV-2 transmission. FundingSao Paulo Research Foundation, Medical Research Council, Wellcome Trust and Royal Society.

Risk of COVID-19 is associated with long-term exposure to air pollution

People with chronic obstructive pulmonary disease, cardiovascular disease or hypertension have a high risk of severe coronavirus disease 2019 (COVID-19). Long-term exposure to air pollution, especially PM2.5, has also been associated with COVID-19 mortality. We collated individual-level data of confirmed COVID-19 cases during the first wave of the epidemic in mainland China. We fitted a generalized linear model using city-level COVID-19 cases and severe cases as the outcome, and long-term average levels of air pollutants as the exposure. Our analysis was adjusted using several variables, including a mobile phone dataset, covering human movement from Wuhan before the travel ban and movements within each city during the time of emergency response. Other variables included census, smoking prevalence, climate, and socio-economic data from 324 cities in China. We adjusted for human mobility and socio-economic factors, and found that an increase in long-term NO2 or PM2.5 may correspond to an increase in the number of COVID-19 cases and severe infections. However, the linkage might also be affected by the confounding factor of population size because of the predefined correlation between population size and air pollution. The results are derived from a large, newly compiled and geocoded repository of population and epidemiological data relevant to COVID-19. The findings of this paper (and other previous studies that have given ambiguous results) indicate that a more definitive analysis is needed of the link between COVID-19 and air pollution.

The effect of human mobility and control measures on the COVID-19 epidemic in China

The ongoing COVID-19 outbreak has expanded rapidly throughout China. Major behavioral, clinical, and state interventions are underway currently to mitigate the epidemic and prevent the persistence of the virus in human populations in China and worldwide. It remains unclear how these unprecedented interventions, including travel restrictions, have affected COVID-19 spread in China. We use real-time mobility data from Wuhan and detailed case data including travel history to elucidate the role of case importation on transmission in cities across China and ascertain the impact of control measures. Early on, the spatial distribution of COVID-19 cases in China was well explained by human mobility data. Following the implementation of control measures, this correlation dropped and growth rates became negative in most locations, although shifts in the demographics of reported cases are still indicative of local chains of transmission outside Wuhan. This study shows that the drastic control measures implemented in China have substantially mitigated the spread of COVID-19.

Early evaluation of the Wuhan City travel restrictions in response to the 2019 novel coronavirus outbreak

Respiratory illness caused by a novel coronavirus (COVID-19) appeared in China during December 2019. Attempting to contain infection, China banned travel to and from Wuhan city on 23 January and implemented a national emergency response. Here we evaluate the spread and control of the epidemic based on a unique synthesis of data including case reports, human movement and public health interventions. The Wuhan shutdown slowed the dispersal of infection to other cities by an estimated 2.91 days (95%CI: 2.54-3.29), delaying epidemic growth elsewhere in China. Other cities that implemented control measures pre-emptively reported 33.3% (11.1-44.4%) fewer cases in the first week of their outbreaks (13.0; 7.1-18.8) compared with cities that started control later (20.6; 14.5-26.8). Among interventions investigated here, the most effective were suspending intra-city public transport, closing entertainment venues and banning public gatherings. The national emergency response delayed the growth and limited the size of the COVID-19 epidemic and, by 19 February (day 50), had averted hundreds of thousands of cases across China. One sentence summaryTravel restrictions and the national emergency response delayed the growth and limited the size of the COVID-19 epidemic in China.

Effects of active and negative mutants of Ras on rat arterial neointima formation.

BACKGROUND: Ras protein is a key signal transducer in the cause of cell proliferation. We studied the effects of active and negative mutants of the Ras gene on arterial neointimal formation in rats, with the aim of elucidating the molecular mechanisms regulating restenosis following percutaneous transluminal coronary angioplasty. MATERIALS AND METHODS: AdRasV12 and AdRasN17, the recombinant adenoviruses containing a constitutively active mutant and a dominant negative mutant of Ras, respectively, were used to determine whether Ras is necessary and sufficient to modulate the smooth muscle cell proliferation and neointima formation. Following balloon injury, rat common carotid arteries were treated in their distal half with AdRasV12, AdRasN17, or AdLacZ, with the proximal half used as uninfected control. RESULTS: In rat arteries subjected to balloon injury, either uninfected or treated with AdLacZ, there were pronounced SMC proliferation and neointima formation. These changes were markedly augmented by AdRasV12 and reduced by AdRasN17. CONCLUSION: Ras is necessary and sufficient for SMC proliferation and neointima formation and may play a critical role in restenosis following balloon angioplasty.