Viral Genetic Evidence and Host Immune Response of a Small Cluster of Individuals with Two Episodes of SARS-CoV-2 Infection

33 Pages Posted: 15 Jan 2021

See all articles by Natalia Fintelman-Rodrigues

Natalia Fintelman-Rodrigues

Oswaldo Cruz Foundation (FIOCRUZ)

Aline de Paula Dias Da Silva

Oswaldo Cruz Foundation (FIOCRUZ)

Monique Cristina dos Santos

Oswaldo Cruz Foundation (FIOCRUZ)

Felipe Saraiva

Oswaldo Cruz Foundation (FIOCRUZ)

Marcelo Alves Ferreira

Oswaldo Cruz Foundation (FIOCRUZ)

João Gesto

Oswaldo Cruz Foundation (FIOCRUZ)

Danielle A.S. Rodrigues

Biology Institute, Genetics Department, Molecular Virology Lab, Federal University of Rio de Janeiro -UFRJ

Andre M. Vale

Universidade Federal do Rio de Janeiro (UFRJ) - Program in Immunobiology

Isaclaudia Gomes de Azevedo

Oswaldo Cruz Foundation (FIOCRUZ)

Vinícius Cardoso Soares

Oswaldo Cruz Foundation (FIOCRUZ)

Hui Jiang

MGI Tech Co., Ltd

Hongdong Tan

MGI Tech Co., Ltd

Diogo Tschoeke

Universidade Federal do Rio de Janeiro (UFRJ)

Carolina Sacramento

Oswaldo Cruz Foundation (FIOCRUZ)

Fernando A. Bozza

FIOCRUZ - Laboratório de Medicina Intensiva

Carlos Morel

Oswaldo Cruz Foundation (FIOCRUZ)

Patricia Bozza

Oswaldo Cruz Foundation (FIOCRUZ); Oswaldo Cruz Foundation (FIOCRUZ)

Thiago Souza

Oswaldo Cruz Foundation (FIOCRUZ)

Date Written: December 16, 2020

Abstract

Background: The dynamics underlying severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reinfection remains poorly understood. We added to the registered case reports of reinfection in USA, Belgium/Netherlands, Ecuador and Hong Kong, a small cluster of individuals with two episodes of 2019 coronavirus disease (COVID-19). Virus genomic analysis and the host immune response were used to characterize this group.

Methods: Four individuals from Rio de Janeiro, Brazil, with clinical manifestations of COVID-19 on March and again in late May of 2020 were studied. Nasopharyngeal swabs were collected for RT-PCR and viral genome sequencing (BGI-MGI-2000). Plasma samples from the acute and convalescent phases of both infection episodes were accessed to document innate and humoral responses.

Findings: After approximately 60 days of the first diagnostic episode of SARS-CoV-2 infection, the four individuals presented new clinical and molecular evidence of COVID-19. Complete SARS-CoV-2 genome sequence provided genetic evidence of reinfection. The individuals presented an enhanced innate response compared to healthy SARS-CoV-2 negative controls. Patients did not develop a neutralizing humoral immunity, possibly remaining susceptible to another episode of COVID-19. The second episode, associated with higher viral loads and clinical symptoms, likely boosted their anti-SARS-CoV-2 humoral response.

Interpretation: SARS-CoV-2 reinfection was fully documented by identification of genetically distinct virus sequences in the first and second episodes for two individuals. The quantity of SARS-CoV-2-associated genetic reads and coverage of virus genome ruled out that the initial RT-PCR results were false positive. The identification that some individuals with mild COVID-19 may have controlled SARS-CoV-2 replication without developing detectable humoral immunity, opens the possibility that reinfection may be more frequent than supposed – but weakly documented.

Note: Funding: This work was supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ). This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Brasil (CAPES) - Finance Code 001. Funding was also provided by CNPq, CAPES and FAPERJ through the National Institutes of Science and Technology Program (INCT) to Carlos Morel (INCT-IDPN).

Declaration of Interests: Authors declare no conflict of interest.

Ethics Approval Statement: The National Review Board of Brazil approved the study protocol (Comissão Nacional de Ética em Pesquisa [CONEP] 30650420.4.1001.0008), and informed consent was obtained from all participants or patients’ representatives.

Keywords: SARS-COV-2, reinfection, Brazil, next generation sequencing, immune response

Suggested Citation

Fintelman-Rodrigues, Natalia and Dias Da Silva, Aline de Paula and dos Santos, Monique Cristina and Saraiva, Felipe and Alves Ferreira, Marcelo and Gesto, João and Rodrigues, Danielle A.S. and Vale, Andre M. and Gomes de Azevedo, Isaclaudia and Cardoso Soares, Vinícius and Jiang, Hui and Tan, Hongdong and Tschoeke, Diogo and Sacramento, Carolina and Bozza, Fernando A. and Morel, Carlos and Bozza, Patricia and Souza, Thiago, Viral Genetic Evidence and Host Immune Response of a Small Cluster of Individuals with Two Episodes of SARS-CoV-2 Infection (December 16, 2020). Available at SSRN: https://ssrn.com/abstract=3750109 or http://dx.doi.org/10.2139/ssrn.3750109

Natalia Fintelman-Rodrigues

Oswaldo Cruz Foundation (FIOCRUZ) ( email )

Rio de Janeiro
Brazil

Aline de Paula Dias Da Silva

Oswaldo Cruz Foundation (FIOCRUZ) ( email )

Rio de Janeiro
Brazil

Monique Cristina Dos Santos

Oswaldo Cruz Foundation (FIOCRUZ) ( email )

Rio de Janeiro
Brazil

Felipe Saraiva

Oswaldo Cruz Foundation (FIOCRUZ) ( email )

Rio de Janeiro
Brazil

Marcelo Alves Ferreira

Oswaldo Cruz Foundation (FIOCRUZ) ( email )

Rio de Janeiro
Brazil

João Gesto

Oswaldo Cruz Foundation (FIOCRUZ) ( email )

Rio de Janeiro
Brazil

Danielle A.S. Rodrigues

Biology Institute, Genetics Department, Molecular Virology Lab, Federal University of Rio de Janeiro -UFRJ ( email )

Andre M. Vale

Universidade Federal do Rio de Janeiro (UFRJ) - Program in Immunobiology ( email )

Rio de Janiero
Brazil

Isaclaudia Gomes de Azevedo

Oswaldo Cruz Foundation (FIOCRUZ) ( email )

Rio de Janeiro
Brazil

Vinícius Cardoso Soares

Oswaldo Cruz Foundation (FIOCRUZ) ( email )

Rio de Janeiro
Brazil

Hui Jiang

MGI Tech Co., Ltd ( email )

Building No.11, Beishan Industrial Zone, Yantian D
Shenzhen, 518083
China

Hongdong Tan

MGI Tech Co., Ltd ( email )

Building No.11, Beishan Industrial Zone, Yantian D
Shenzhen, 518083
China

Diogo Tschoeke

Universidade Federal do Rio de Janeiro (UFRJ) ( email )

Av; Pasteur, 250
terreo - Bairro Maracana
Rio de Janeiro, Rio de Janeiro 23890000
Brazil

Carolina Sacramento

Oswaldo Cruz Foundation (FIOCRUZ) ( email )

Rio de Janeiro
Brazil

Fernando A. Bozza

FIOCRUZ - Laboratório de Medicina Intensiva ( email )

Carlos Morel

Oswaldo Cruz Foundation (FIOCRUZ) ( email )

Rio de Janeiro
Brazil

Patricia Bozza

Oswaldo Cruz Foundation (FIOCRUZ) ( email )

Rio de Janeiro
Brazil

Oswaldo Cruz Foundation (FIOCRUZ) ( email )

Rio de Janeiro
Brazil

Thiago Souza (Contact Author)

Oswaldo Cruz Foundation (FIOCRUZ) ( email )

Rio de Janeiro
Brazil

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