'REBRACOVID' - multicentre cohort study of the natural history and immunology of COVID-19 in Brazil
Lead Research Organisation:
Imperial College London
Department Name: Immunology and Inflammation
Abstract
COVID-19 disease cohorts have been recruited and studied in many parts of the world in recent months, but there is still much to learn. There is a specific and urgent need to better understand this disease in Brazil: WHO data places Brazil 2nd in the world for
COVID-19 cases and deaths, and the country faces challenges of urban crowding (including favelas), socioeconomic disparities, and a healthcare system stretched by disease burden including the mosquito-borne infections. Our aim here is to collect and
analyse disease parameters in a large disease cohort of hospitalised and community cases, from 9 centres across the country. In doing so, we benefit also from building a consortium that bolts-on to our established consortium studies, REPLICK (Brazil) and
SPIICA (Anglo-Brazil, MRC-Newton), designed to conduct analogous cohort studies in relation to the immunopathology and chronic disease phenotype in infection by Chikungunya virus - a mosquito-borne infection that can also lead to chronic disease
symptoms. We aim to recruit a cohort of 20,000 total infected patients, as well as household contacts and at-risk healthcare workers. Our data will allow us to define impacts of age, gender, occupation, ethnicity, other health conditions, socio-economic
factors, blood markers and importantly, measures of protective immunity and its durability. Our intention is to better understand susceptibility and mechanisms underlying this disease, drawing on specific insights from the serious situation in Brazil to impact local
management of the response.
COVID-19 cases and deaths, and the country faces challenges of urban crowding (including favelas), socioeconomic disparities, and a healthcare system stretched by disease burden including the mosquito-borne infections. Our aim here is to collect and
analyse disease parameters in a large disease cohort of hospitalised and community cases, from 9 centres across the country. In doing so, we benefit also from building a consortium that bolts-on to our established consortium studies, REPLICK (Brazil) and
SPIICA (Anglo-Brazil, MRC-Newton), designed to conduct analogous cohort studies in relation to the immunopathology and chronic disease phenotype in infection by Chikungunya virus - a mosquito-borne infection that can also lead to chronic disease
symptoms. We aim to recruit a cohort of 20,000 total infected patients, as well as household contacts and at-risk healthcare workers. Our data will allow us to define impacts of age, gender, occupation, ethnicity, other health conditions, socio-economic
factors, blood markers and importantly, measures of protective immunity and its durability. Our intention is to better understand susceptibility and mechanisms underlying this disease, drawing on specific insights from the serious situation in Brazil to impact local
management of the response.
Technical Summary
While a number of COVID-19 cohort disease demographic and mechanism studies are in progress, many unknowns remain, and each setting has offered distinctive insights. The clinical imperative to better understand the specific challenges in Brazil is strong: WHO data places Brazil 2nd in the world for COVID-19 cases and deaths. Furthermore, this huge country poses challenges of urban crowding and socioeconomic disparities and a healthcare system stretched by disease burden. On a COVID-19 disease trajectory lagging about 1-month behind Europe, there is potential to establish a large cohort during acute disease, taking into account mechanistic insights already gained. In doing so, we benefit also from building a consortium that bolts-on to our established consortium, international,collaborative studies, REPLICK (Brazil) and SPIICA (Anglo-Brazil, MRCNewton ref MR/S019553/1), designed to conduct analogous cohort studies in relation to the immunopathology and chronic disease phenotype in Chikungunya virus infection. We aim to recruit a cohort of 20,000 total infected, PCR+ COVID-19 cases from 9 centres across Brazil, as well as household contacts and healthcare workers. We will characterise basic demographics of those affected, including impacts of age, gender, occupation, ethnicity, co-morbidities, socio-economic factors, blood biochemistry, antibody and T cell immunity (and durability), CT findings, as well as defining chronic sequelae. We will also
investigate treatment modalities and co-infections in relation to disease outcome. Communication of findings from this cohort study will be valuable to inform management of the pandemic in Brazil and elsewhere
investigate treatment modalities and co-infections in relation to disease outcome. Communication of findings from this cohort study will be valuable to inform management of the pandemic in Brazil and elsewhere
Publications
Da Silva Duarte G
(2023)
Multicenter study of the natural history and therapeutic responses of patients with chikungunya, focusing on acute and chronic musculoskeletal manifestations - a study protocol from the clinical and applied research in Chikungunya (REPLICK network)
in BMC Infectious Diseases
Altmann DM
(2021)
Children and the return to school: how much should we worry about covid-19 and long covid?
in BMJ (Clinical research ed.)
Altmann DM
(2021)
Decoding the unknowns in long covid.
in BMJ (Clinical research ed.)
Doykov I
(2022)
Quantitative, multiplexed, targeted proteomics for ascertaining variant specific SARS-CoV-2 antibody response.
in Cell reports methods
Chandran A
(2022)
Rapid synchronous type 1 IFN and virus-specific T cell responses characterize first wave non-severe SARS-CoV-2 infections.
in Cell reports. Medicine
Altmann DM
(2021)
SARS-CoV-2 variants: Subversion of antibody response and predicted impact on T cell recognition.
in Cell reports. Medicine
Captur G
(2022)
Plasma proteomic signature predicts who will get persistent symptoms following SARS-CoV-2 infection.
in EBioMedicine
Astbury S
(2022)
HLA-DR polymorphism in SARS-CoV-2 infection and susceptibility to symptomatic COVID-19.
in Immunology
Milighetti M
(2023)
Large clones of pre-existing T cells drive early immunity against SARS-COV-2 and LCMV infection.
in iScience
Boyton RJ
(2021)
Risk of SARS-CoV-2 reinfection after natural infection.
in Lancet (London, England)
Manisty C
(2021)
Antibody response to first BNT162b2 dose in previously SARS-CoV-2-infected individuals.
in Lancet (London, England)
Swadling L
(2022)
Pre-existing polymerase-specific T cells expand in abortive seronegative SARS-CoV-2.
in Nature
Altmann DM
(2023)
Persistent symptoms after COVID-19 are not associated with differential SARS-CoV-2 antibody or T cell immunity.
in Nature communications
Boyton RJ
(2021)
The immunology of asymptomatic SARS-CoV-2 infection: what are the key questions?
in Nature reviews. Immunology
Altmann DM
(2023)
The immunology of long COVID.
in Nature reviews. Immunology
McDonald I
(2021)
Comparative systematic review and meta-analysis of reactogenicity, immunogenicity and efficacy of vaccines against SARS-CoV-2.
in NPJ vaccines
Altmann DM
(2020)
Adaptive immunity to SARS-CoV-2.
in Oxford open immunology
Altmann DM
(2021)
Immunity to SARS-CoV-2 variants of concern.
in Science (New York, N.Y.)
Reynolds CJ
(2022)
Heterologous infection and vaccination shapes immunity against SARS-CoV-2 variants.
in Science (New York, N.Y.)
Reynolds CJ
(2021)
Prior SARS-CoV-2 infection rescues B and T cell responses to variants after first vaccine dose.
in Science (New York, N.Y.)
| Description | Four years into the pandemic, there is a large, detailed narrative being built, from which there is much to be learnt. The global pandemic has played out slightly differently in different regions, depending on mitigation policies, healthcare, prevalent variants, and vaccination strategy. We have been in the unique situation of being able to recruit a large Brazilian study cohort across multiple regional centres, spanning across the Gamma variant wave through to Delta and Omicron. Our large dataset and biobank is allowing us to address novel questions about acute COVID-19, vaccine responses, and Long Covid in the Brazilian setting |
| Exploitation Route | We anticipate that it may inform vaccination and boosting policy |
| Sectors | Healthcare |
| Description | Concepts derived through this work, especially that of differential immune imprinting, are feeding into debate on future policy |
| First Year Of Impact | 2022 |
| Impact Types | Policy & public services |
| Description | Prof Andre Siquiera policy engagement meetings with FAPESP |
| Geographic Reach | South America |
| Policy Influence Type | Participation in a guidance/advisory committee |
| Description | New Chikungunya collaboration with Dr Moacyr JESUS BARRETO DE MELO REGO |
| Organisation | UFPE |
| Country | Brazil |
| Sector | Academic/University |
| PI Contribution | We have built a strong ongoing collaboration with Dr Moacyr JESUS BARRETO DE MELO REGO in Recife, a region that has suffered high prevalence of COVID-19 and Chikungunya. We are working together closely on recruitment and analysis. |
| Collaborator Contribution | Cohort recruitment, biobanking, data analysis |
| Impact | Manuscripts and a follow-on grants submission are in progress |
| Start Year | 2021 |
| Description | New collaboration and publications with Prof Pritesh Lalwani |
| Organisation | Oswaldo Cruz Foundation (Fiocruz) |
| Country | Brazil |
| Sector | Public |
| PI Contribution | During the early phase of the COVID-19 pandemic there was alarm about the very high SARS-CoV-2 seroprevalence in Manaus in the Amazonas. A valuable research collaboration was established with Prof Lalwani there. We jointly analysed immune status in his locally recruited cohort. |
| Collaborator Contribution | We jointly analysed immune status in his locally recruited cohort. |
| Impact | Salgado BB, Barbosa ARC, Arcanjo AR, de Castro DB, Ramos TCA, Naveca F, Altmann DM, Boyton RJ, Lalwani JDB, Lalwani P. Hybrid Immunity Results in Enhanced and More Sustained Antibody Responses after the Second Sinovac- CoronaVac Dose in a Brazilian Cohort: DETECTCoV-19 Cohort. Viruses. 2023 Sep 23;15(10):1987. doi: 10.3390/v15101987. PMID: 37896766; PMCID: PMC10610994. |
| Start Year | 2020 |