A case series of SARS-CoV-2 reinfections caused by the variant of concern Gamma in Brazil
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Abstract
The rapid spread of the SARS-CoV-2 Variant of Concern (VOC) Gamma during late 2020 and early 2021 in Brazilian settings with high seroprevalence raised some concern about the potential role of reinfections in driving the epidemic. Very few cases of reinfection associated with the VOC Gamma, however, have been reported. Here we describe 25 cases of SARS-CoV-2 reinfection confirmed by real-time RT-PCR twice within months apart in Brazil. SARS-CoV-2 genomic analysis confirmed that individuals were primo-infected between March and December 2020 with distinct viral lineages, including B.1.1, B.1.1.28, B.1.1.33, B.1.195 and P.2, and then reinfected with the VOC Gamma between 3 to 12 months after primo-infection. The overall mean cycle threshold (Ct) value of the first (25.7) and second (24.5) episodes were roughly similar for the whole group and 14 individuals displayed mean Ct values < 25.0 at reinfection. Sera of 14 patients tested by plaque reduction neutralization test after reinfection displayed detectable neutralizing antibodies against Gamma and other SARS-CoV-2 variants (B.1.33, B.1.1.28 and Delta). All individuals have milder or no symptoms after reinfection and none required hospitalization. The present study demonstrates that the VOC Gamma was associated with reinfections during the second Brazilian epidemic wave in 2021 and raised concern about the potential infectiousness of reinfected subjects. Although individuals here analyzed failed to mount a long-term sterilizing immunity, they developed a high anti-Gamma neutralizing antibody response after reinfection that may provide some protection against severe disease.
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SciScore for 10.1101/2021.11.29.21266109: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IRB: This study was approved by the Ethics Committee of the Amazonas State University (CAAE: 25430719.6.0000.5016) and by the Ethics Committee of the FIOCRUZ (CAAE: 68118417.6.0000.5248). Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Table 2: Resources
Antibodies Sentences Resources Serological analyses: A total of 14 serum samples collected from 12 to 70 days after the second episode of COVID-19 were tested for SARS-CoV-2-specific neutralizing antibodies (NAb) by plaque reduction neutralization test (PRNT90). SARS-CoV-2-specific neutralizing antibodiessuggested: NonePRNT90suggested: NoneSoftware and Algorithms Sentences Resources SciScore for 10.1101/2021.11.29.21266109: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IRB: This study was approved by the Ethics Committee of the Amazonas State University (CAAE: 25430719.6.0000.5016) and by the Ethics Committee of the FIOCRUZ (CAAE: 68118417.6.0000.5248). Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Table 2: Resources
Antibodies Sentences Resources Serological analyses: A total of 14 serum samples collected from 12 to 70 days after the second episode of COVID-19 were tested for SARS-CoV-2-specific neutralizing antibodies (NAb) by plaque reduction neutralization test (PRNT90). SARS-CoV-2-specific neutralizing antibodiessuggested: NonePRNT90suggested: NoneSoftware and Algorithms Sentences Resources The FASTQ reads were obtained following the Illumina pipeline on BaseSpace, imported into Geneious v10.2.6, trimmed (BBDuk 37.25) or into CLC Genomic Workbench (Qiagen), and mapped (BBMap 37.25) against the reference sequence EPI_ISL_402124 available in EpiCoV database from GISAID Illuminasuggested: (Illumina, RRID:SCR_010233)Geneioussuggested: (Geneious, RRID:SCR_010519)BBMapsuggested: (BBmap, RRID:SCR_016965)The final dataset of each variant to which primoinfection and reinfection sequences were previously assigned were obtained by clusterization of their GISAID complete datasets using CD-HIT v.4.8.131. CD-HITsuggested: (CD-HIT, RRID:SCR_007105)The resulting dataset was aligned by MAFFT v7.46732 and subjected to a maximum likelihood (ML) phylogenetic analysis with IQ-TREE v2.1.233 under the best nucleotide substitution model selected by the ModelFinder application34. MAFFTsuggested: (MAFFT, RRID:SCR_011811)IQ-TREEsuggested: (IQ-TREE, RRID:SCR_017254)ModelFindersuggested: NoneGraphics and statistical analyses were performed using GraphPad v9.02 GraphPadsuggested: (GraphPad Prism, RRID:SCR_002798)Results from OddPub: Thank you for sharing your data.
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:Our study has several limitations. First, although Ct values could be used as a surrogate of infectivity, we have no contact-tracing information to demonstrate that reinfected subjects were able to transmit the virus to susceptible individuals. Second, our study was limited by the absence of longitudinal data of anti-SARS-CoV-2 NAb, particularly between the first and the second COVID-19 episodes. Thus, we could not confirm if primo-infections effectively induce a transient neutralization response, we could not measure the level of NAb immediately before reinfections and no definitive conclusions could be drawn about the precise impact of reinfections on NAb titers. In summary, these findings confirm that natural infection by SARS-CoV-2 do not necessarily prevent subsequent infections and further demonstrate that reinfection with the VOC Gamma in people who had a first symptomatic infection between 3 to 12 months earlier was not a rare phenomenon in Brazil. Although, reinfections cases were observed in individuals without comorbidities and with mild disease, no significant decrease in viral load, represented by Ct values, during reinfection was observed when compared with primo-infection. Further studies are necessary to determine whether reinfection with Gamma and other VOCs is a widespread phenomenon and to understand to what extent reinfection will contribute to the onward endemic transmission of SARS-CoV-2. Further work is also needed to understand how primary infections i...
Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
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Results from scite Reference Check: We found no unreliable references.
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