SARS-CoV-2 lineage-specific disease symptoms and disease severity in Sao Caetano do Sul city, Brazil (preprint)

Background: The city of Sao Caetano do Sul, Brazil, established a web-based platform to provide primary care to suspected COVID-19 patients, integrating clinical and demographic data and sample metadata. Here we describe lineage-specific spatiotemporal dynamics of infections, clinical symptoms, and disease severity during the first year of the epidemic. Methods: We selected and sequenced 879 PCR+ swab samples (8% of all reported cases), obtaining a spatially and temporally representative set of sequences. Daily lineage-specific prevalence was estimating using a moving-window approach, allowing inference of cumulative cases and symptom probability stratified by lineage using integrated data from the platform. Results: Most infections were caused by B.1.1.28 (41.3%), followed by Gamma (31.7%), Zeta (9.6%) and B1.1.33 (9.0%). Gamma and Zeta were associated with larger prevalence of dyspnoea (respectively 81.3% and 78.5%) and persistent fever (84.7% and 61.1%) compared to B.1.1.28 and B.1.1.33. Ageusia, anosmia, and coryza were respectively 18.9%, 20.3% and 17.8% less commonly caused by Gamma, while altered mental status was 108.9% more common in Zeta. Case incidence was spatially heterogeneous and larger in poorer and younger districts. Discussion: Our study demonstrates that Gamma was associated with more severe disease, emphasising the role of its increased disease severity in the heightened mortality levels in Brazil.

The Brazilian COVID-19 vaccination campaign: A modelling analysis of socio-demographic factors on uptake (preprint)

The COVID-19 pandemic has caused over half a million deaths in Brazil, and public healthcare nearly collapsed. Vaccination differs between states and demographics. Dose shortages delayed access. In this cross-sectional study, data were retrieved from the Brazilian Ministry of Health databases published since 17 January 2021, respectively. We developed a campaign optimality index to characterise inequality in vaccination access caused by age due to premature vaccination towards younger populations before older and vulnerable populations were fully vaccinated. We assessed geographical inequalities in full vaccination coverage and dose by age, sex, race, and socioeconomic status. Generalised linear regression was used to investigate the risk of death and hospitalisation by age group, socioeconomic status, and vaccination coverage. Vaccination coverage is higher in the wealthier South and Southeast. Men, people of colour, and low-income groups were more likely to be only partially vaccinated due to missing or delaying a second dose. Vaccination started prematurely for age groups under 50 years and may have hindered uptake of older age groups. Vaccination coverage was associated with a lower risk of death, especially in older age groups (OR: 10.5-34.8, 95% CI: (10.2, 35.9)). Risk of hospitalisation was greater in areas with higher vaccination rates due to higher access to care and reporting. Vaccination inequality persists between states, age and demographic groups despite increasing uptake. The association between hospitalisation rates and vaccination is attributed to preferential delivery to areas of greater transmission and access to healthcare.

Reinfection by the SARS-CoV-2 P.1 variant in blood donors in Manaus, Brazil (preprint)

The city of Manaus, north Brazil, was stricken by a severe epidemic of SARS-Cov-2 in March 2020, reaching a seroprevalence of 76% by October 2020. Nevertheless, in late November an abrupt increase in hospitalizations and deaths hit Manaus, causing higher number of deaths compared to the first epidemic wave. It has been hypothesized that virus lineages circulating in the second wave, namely the P.1 variant of concern first detected in early December in Manaus, could be better at evading immunity generated in response to previous infection with other lineages. In order to estimate the reinfection rate during the resurgence of SARS-CoV-2 in Manaus, we tested serial samples from 238 unvaccinated repeat blood donors using a SARS-CoV-2 anti-N IgG chemiluminescence microparticle assay. Blood donors were divided into six groups that reflected the inferred sequence of infection and reinfection with non-P.1 and P.1 variants. We assumed that reinfections induce a recrudescence (or boosting) of plasma anti-N IgG antibody levels, yielding a V-shaped time series of antibody reactivity levels. We infer that 16.9% (95% CI [9.48%, 28.5%]) of all presumed P.1 infections that were observed in 2021 were reinfections. If we also include cases of probable or possible reinfections (defined by considering the time period when the antibody levels are expected to grow after recovery and the range of half-lives for antibody waning after seroconversion), these percentages increase respectively to 25.8% (95% CI [16.7%, 37.4%]), and 31.0% (95% CI [21.4%, 42.5%]). Our data suggest that reinfection due to P.1 is common and more frequent than what has been detected by traditional epidemiologic, molecular and genomic surveillance of clinical cases.

Tracking the emergence of disparities in the subnational spread of COVID-19 in Brazil using an online application for real-time data visualisation. (preprint)

Brazil is one of the countries worst affected by the COVID-19 pandemic. We have developed CLIC-Brazil an online application for the real-time visualisation of COVID-19 data in Brazil at the municipality level. In the app, case and death data are standardised to allow comparisons to be made between places and over time. Estimates of Rt , a measure of the rate of propagation of the epidemic, over time are also made. Using data from the app, regression analyses identified factors associated with; the rate of initial spread, early epidemic intensity and predictions of the likelihood of occurrence of new incidence maxima. Municipalities with higher metrics of social development experienced earlier onset and faster growing epidemics, although space and time were the predominant predictive factors. Differences in the initial epidemic intensity (mean Rt ) were largely driven by geographic location and the date of local onset. This study demonstrates that by monitoring, standardising and analysing the development of an epidemic at a local level, insights can be gained into spatial and temporal heterogeneities.

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

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.

Serial Interval Distribution of SARS-CoV-2 Infection in Brazil (preprint)

Using 65 transmission pairs of SARS-CoV-2 reported to the Brazilian Ministry of Health we estimate the mean and standard deviation for the serial interval to be 2.97 and 3.29 days respectively. We also present a model for the serial interval probability distribution using only two parameters.

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

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.