SARS-CoV-2 intra-host diversity, antibody response, and disease severity after reinfection by the variant of concern Gamma in Brazil
Authors: Naveca Felipe Gomes , Nascimento Valdinete Alves , Nascimento Fernanda , Ogrzewalska Maria , Pauvolid-Corrêa Alex , Araújo Mia Ferreira , Arantes Ighor , Batista Érika Rocha , Magalhães Alessandro Álvares , Vinhal Fernando , Mattos Tirza Peixoto , Riediger Irina , Debur Maria do Carmo , Grinsztejn Beatriz , Veloso Valdiléa G. , Brasil Patrícia , Rodrigues Rodrigo Ribeiro , Rovaris Darcita Buerger , Fernandes Sandra Bianchini , Fernandes Cristiano , Santos João Hugo Abdalla , Abdalla Lígia Fernandes , Costa-Filho Rubens , Silva Marineide , Souza Victor , Costa Ágatha Araújo , Mejía Matilde , Brandão Maria Júlia , Gonçalves Luciana Fé , Silva George Allan , de Jesus Michele Silva , Pessoa Karina , Corado André de Lima Guerra , Duarte Debora Camila Gomes , Machado Ana Beatriz , Zukeram Ketiuce de Azevedo , Valente Natalia , Lopes Renata Serrano , Pereira Elisa Cavalcante , Appolinario Luciana Reis , Rocha Alice Sampaio , Tort Luis Fernando Lopez , Sekizuka Tsuyoshi , Itokawa Kentaro , Hashino Masanori , Kuroda Makoto , Dezordi Filipe Zimmer , Wallau Gabriel Luz , Delatorre Edson , Gräf Tiago , Siqueira Marilda Mendonça , Bello Gonzalo , Resende Paola Cristina 
Published: May 2023

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.