Oligosymptomatic long-term carriers of SARS-CoV-2 display impaired innate resistance but increased high-affinity anti-spike antibodies

Elena Montes-Cobos; Victoria C Bastos; Clarice Monteiro; João C R de Freitas; Heiny D P Fernandes; Clarice S Constancio; Danielle A S Rodrigues; Andreza M D S Gama; Vinicius M Vidal; Leticia S Alves; Laura Zalcberg-Renault; Guilherme S de Lira; Victor A Ota; Carolina Caloba; Luciana Conde; Isabela C Leitão; Amilcar Tanuri; Orlando D C Ferreira; Renata M Pereira; André M Vale; Terezinha M Castiñeiras; Dominique Kaiserlian; Juliana Echevarria-Lima; Marcelo T Bozza

doi:10.1016/j.isci.2023.107219

Oligosymptomatic long-term carriers of SARS-CoV-2 display impaired innate resistance but increased high-affinity anti-spike antibodies

iScience. 2023 Jun 28;26(7):107219. doi: 10.1016/j.isci.2023.107219. eCollection 2023 Jul 21.

Authors

Elena Montes-Cobos¹, Victoria C Bastos^{1

2}, Clarice Monteiro¹, João C R de Freitas¹, Heiny D P Fernandes¹, Clarice S Constancio³, Danielle A S Rodrigues⁴, Andreza M D S Gama¹, Vinicius M Vidal¹, Leticia S Alves¹, Laura Zalcberg-Renault^{1

2}, Guilherme S de Lira^{1

2}, Victor A Ota^{1

2}, Carolina Caloba⁵, Luciana Conde⁴, Isabela C Leitão², Amilcar Tanuri⁶, Orlando D C Ferreira⁶, Renata M Pereira⁵, André M Vale⁴, Terezinha M Castiñeiras², Dominique Kaiserlian⁷, Juliana Echevarria-Lima³, Marcelo T Bozza¹

Affiliations

¹ Laboratório de Inflamação e Imunidade, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
² Departamento de Doenças Infecciosas e Parasitárias, Faculdade de Medicina, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
³ Laboratório de Imunologia Básica e Aplicada, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
⁴ Laboratório de Biologia de Linfócitos, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
⁵ Laboratório de Imunologia Molecular, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
⁶ Laboratório de Virologia Molecular, Instituto de Biologia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
⁷ INSERM U1060, Université Claude Bernard Lyon 1, Centre hospitalier Lyon-Sud, Pierre-Benite, France.

Abstract

The vast spectrum of clinical features of COVID-19 keeps challenging scientists and clinicians. Low resistance to infection might result in long-term viral persistence, but the underlying mechanisms remain unclear. Here, we studied the immune response of immunocompetent COVID-19 patients with prolonged SARS-CoV-2 infection by immunophenotyping, cytokine and serological analysis. Despite viral loads and symptoms comparable to regular mildly symptomatic patients, long-term carriers displayed weaker systemic IFN-I responses and fewer circulating pDCs and NK cells at disease onset. Type 1 cytokines remained low, while type-3 cytokines were in turn enhanced. Of interest, we observed no defects in antigen-specific cytotoxic T cell responses, and circulating antibodies displayed higher affinity against different variants of SARS-CoV-2 Spike protein in these patients. The identification of distinct immune responses in long-term carriers adds up to our understanding of essential host protective mechanisms to ensure tissue damage control despite prolonged viral infection.

Keywords: Health sciences; Immunology; Virology.