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SARS-CoV-2 intra-host diversity, antibody response, and disease severity after reinfection by the variant of concern Gamma in Brazil.

ABSTRACT: The rapid spread of the SARS-CoV-2 Variant of Concern (VOC) Gamma in Amazonas during early 2021 fueled a second large COVID-19 epidemic wave and raised concern about the potential role of reinfections. Very few cases of reinfection associated with the VOC Gamma have been reported to date, and their potential impact on clinical, immunological, and virological parameters remains largely unexplored. Here we describe 25 cases of SARS-CoV-2 reinfection in Brazil. SARS-CoV-2 genomic analysis confirmed that individuals were primo-infected with distinct viral lineages between March and December 2020 (B.1.1, B.1.1.28, B.1.1.33, B.1.195, and P.2) and reinfected with the VOC Gamma between 3 to 12 months after primo-infection. We found a similar mean cycle threshold (Ct) value and limited intra-host viral diversity in both primo-infection and reinfection samples. Sera of 14 patients tested 10-75 days after reinfection displayed detectable neutralizing antibodies (NAb) titers against SARS-CoV-2 variants that circulated before (B.1.*), during (Gamma), and after (Delta and Omicron) the second epidemic wave in Brazil. All individuals had milder or no symptoms after reinfection, and none required hospitalization. These findings demonstrate that individuals reinfected with the VOC Gamma may display relatively high RNA viral loads at the upper respiratory tract after reinfection, thus contributing to onward viral transmissions. Despite this, our study points to a low overall risk of severe Gamma reinfections, supporting that the abrupt increase in hospital admissions and deaths observed in Amazonas and other Brazilian states during the Gamma wave was mostly driven by primary infections. Our findings also indicate that most individuals analyzed developed a high anti-SARS-CoV-2 NAb response after reinfection that may provide some protection against reinfection or disease by different SARS-CoV-2 variants.

SUBMITTER: Naveca FG

PROVIDER: S-EPMC10160723 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature

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SARS-CoV-2 intra-host diversity, antibody response, and disease severity after reinfection by the variant of concern Gamma in Brazil.

Naveca Felipe Gomes FG Nascimento Valdinete Alves VA Nascimento Fernanda F Ogrzewalska Maria M Pauvolid-Corrêa Alex A Araújo Mia Ferreira MF Arantes Ighor I Batista Érika Rocha ÉR Magalhães Alessandro Álvares AÁ Vinhal Fernando F Mattos Tirza Peixoto TP Riediger Irina I Debur Maria do Carmo MDC Grinsztejn Beatriz B Veloso Valdiléa G VG Brasil Patrícia P Rodrigues Rodrigo Ribeiro RR Rovaris Darcita Buerger DB Fernandes Sandra Bianchini SB Fernandes Cristiano C Santos João Hugo Abdalla JHA Abdalla Lígia Fernandes LF Costa-Filho Rubens R Silva Marineide M Souza Victor V Costa Ágatha Araújo ÁA Mejía Matilde M Brandão Maria Júlia MJ Gonçalves Luciana Fé LF Silva George Allan GA de Jesus Michele Silva MS Pessoa Karina K Corado André de Lima Guerra ALG Duarte Debora Camila Gomes DCG Machado Ana Beatriz AB Zukeram Ketiuce de Azevedo KA Valente Natalia N Lopes Renata Serrano RS Pereira Elisa Cavalcante EC Appolinario Luciana Reis LR Rocha Alice Sampaio AS Tort Luis Fernando Lopez LFL Sekizuka Tsuyoshi T Itokawa Kentaro K Hashino Masanori M Kuroda Makoto M Dezordi Filipe Zimmer FZ Wallau Gabriel Luz GL Delatorre Edson E Gräf Tiago T Siqueira Marilda Mendonça MM Bello Gonzalo G Resende Paola Cristina PC

Scientific reports 20230505 1

The rapid spread of the SARS-CoV-2 Variant of Concern (VOC) Gamma in Amazonas during early 2021 fueled a second large COVID-19 epidemic wave and raised concern about the potential role of reinfections. Very few cases of reinfection associated with the VOC Gamma have been reported to date, and their potential impact on clinical, immunological, and virological parameters remains largely unexplored. Here we describe 25 cases of SARS-CoV-2 reinfection in Brazil. SARS-CoV-2 genomic analysis confirmed ...[more]

PMID: 37147348

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Project description:BackgroundThe city of Manaus, north Brazil, was stricken by a second epidemic wave of SARS-CoV-2 despite high seroprevalence estimates, coinciding with the emergence of the Gamma (P.1) variant. Reinfections were postulated as a partial explanation for the second surge. However, accurate calculation of reinfection rates is difficult when stringent criteria as two time-separated RT-PCR tests and/or genome sequencing are required. To estimate the proportion of reinfections caused by Gamma during the second wave in Manaus and the protection conferred by previous infection, we identified anti-SARS-CoV-2 antibody boosting in repeat blood donors as a mean to infer reinfection.MethodsWe tested serial blood samples from unvaccinated repeat blood donors in Manaus for the presence of anti-SARS-CoV-2 IgG antibodies using two assays that display waning in early convalescence, enabling the detection of reinfection-induced boosting. Donors were required to have three or more donations, being at least one during each epidemic wave. We propose a strict serological definition of reinfection (reactivity boosting following waning like a V-shaped curve in both assays or three spaced boostings), probable (two separate boosting events) and possible (reinfection detected by only one assay) reinfections. The serial samples were used to divide donors into six groups defined based on the inferred sequence of infection and reinfection with non-Gamma and Gamma variants.ResultsFrom 3655 repeat blood donors, 238 met all inclusion criteria, and 223 had enough residual sample volume to perform both serological assays. We found 13.6% (95% CI 7.0-24.5%) of all presumed Gamma infections that were observed in 2021 were reinfections. If we also include cases of probable or possible reinfections, these percentages increase respectively to 22.7% (95% CI 14.3-34.2%) and 39.3% (95% CI 29.5-50.0%). Previous infection conferred a protection against reinfection of 85.3% (95% CI 71.3-92.7%), decreasing to respectively 72.5% (95% CI 54.7-83.6%) and 39.5% (95% CI 14.1-57.8%) if probable and possible reinfections are included.ConclusionsReinfection by Gamma is common and may play a significant role in epidemics where Gamma is prevalent, highlighting the continued threat variants of concern pose even to settings previously hit by substantial epidemics.

Project description:BackgroundP.1 lineage (Gamma) was first described in the State of Amazonas, northern Brazil, in the end of 2020, and has emerged as a very important variant of concern (VOC) of SARS-CoV-2 worldwide. P.1 has been linked to increased infectivity, higher mortality, and immune evasion, leading to reinfections and potentially reduced efficacy of vaccines and neutralizing antibodies.MethodsThe samples of 276 patients from the State of Amazonas were sent to a central referral laboratory for sequencing by gold standard techniques, through Illumina MiSeq platform. Both global and regional phylogenetic analyses of the successfully sequenced genomes were conducted through maximum likelihood method. Multiple alignments were obtained including previously obtained unique human SARS-CoV-2 sequences. The evolutionary histories of spike and non-structural proteins from ORF1a of northern genomes were described and their molecular evolution was analyzed for detection of positive (FUBAR, FEL, and MEME) and negative (FEL and SLAC) selective pressures. To further evaluate the possible pathways of evolution leading to the emergence of P.1, we performed specific analysis for copy-choice recombination events. A global phylogenomic analysis with subsampled P.1 and B.1.1.28 genomes was applied to evaluate the relationship among samples.ResultsForty-four samples from the State of Amazonas were successfully sequenced and confirmed as P.1 (Gamma) lineage. In addition to previously described P.1 characteristic mutations, we find evidence of continuous diversification of SARS-CoV-2, as rare and previously unseen P.1 mutations were detected in spike and non-structural protein from ORF1a. No evidence of recombination was found. Several sites were demonstrated to be under positive and negative selection, with various mutations identified mostly in P.1 lineage. According to the Pango assignment, phylogenomic analyses indicate all samples as belonging to the P.1 lineage.ConclusionP.1 has shown continuous evolution after its emergence. The lack of clear evidence for recombination and the positive selection demonstrated for several sites suggest that this lineage emergence resulted mainly from strong evolutionary forces and progressive accumulation of a favorable signature set of mutations.

Project description:The SARS-CoV-2 P.1 lineage emerged in Amazonas (AM), North Brazil and its evolution has been dynamically reported associated with increased transmissibility and/or immune evasion. Here, we evaluated the lineages circulating in 29 cities in Rio Grande do Sul (RS), Southern Brazil between March 2020 and May 2021 and investigated the genetic events associated with the emergence of the P.1. A total of 202 oro/nasopharyngeal SARS-CoV-2 specimens from patients during routine hospital care were submitted to whole-genome sequencing. Phylogenetic and Bayesian Evolutionary Analyses of the P.1 lineage were carried out to determine the relationship between sequences from RS and AM and dated their common ancestor and origin. One hundred six (53%) sequences were assigned as P.1 and most carried the 22 lineage-defining mutations. All the P.1 sequences included other important mutations, such as P314L and R203K/G204R, and revealed a high genetic diversity in the phylogenetic tree. The time-scaled inference suggests that the oldest P.1 sequences from different Brazilian states share a ancestor with those from AM, but the origin of some sequences from RS is unknown. Further, the common ancestor of sequences from RS is dated to mid-June/July 2020, earlier than those previously reported from AM. Our results demonstrate that there is a high degree of genetic diversity among P.1 sequences, which suggests a continuous evolution and community spread of the virus. Although the first P.1 outbreak was reported in AM, the lineage was associated with multiple introductory events and had already been circulating in Southern Brazil prior to November 2020. IMPORTANCE The SARS-CoV-2 P.1 lineage is associated with increased transmissibility and/or immune evasion and presents a dynamic evolution in Brazil. The significance of our research relies in the fact that we evaluated the SARS-CoV-2 lineages circulating in Southern Brazil between March 2020 and May 2021. This evaluation allowed us to detect the genetic events associated with the emergence of the P.1 and its sublineages. This study is important because we were able to establish that the common ancestor of P.1 sequences from Rio Grande do Sul, Southern Brazil, is dated of mid-June/July 2020, earlier than the P.1 sequences previously reported from Amazonas (AM) state. Noteworthy, the high degree of genetic diversity among P.1 sequences found in this study suggests a continuous evolution and community spread of the virus. Moreover, the oldest P.1 sequences from different Brazilian states share a ancestor with those from AM.

Dataset Information

SARS-CoV-2 intra-host diversity, antibody response, and disease severity after reinfection by the variant of concern Gamma in Brazil.

Publications

SARS-CoV-2 intra-host diversity, antibody response, and disease severity after reinfection by the variant of concern Gamma in Brazil.

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