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

• Published in: iScience Vol. 26; no. 7; p. 107219
• Main Authors: Montes-Cobos, Elena, Bastos, Victoria C., Monteiro, Clarice, de Freitas, João C.R., Fernandes, Heiny D.P., Constancio, Clarice S., Rodrigues, Danielle A.S., Gama, Andreza M.D.S., Vidal, Vinicius M., Alves, Leticia S., Zalcberg-Renault, Laura, de Lira, Guilherme S., Ota, Victor A., Caloba, Carolina, Conde, Luciana, Leitão, Isabela C., Tanuri, Amilcar, Ferreira, Orlando D.C., Pereira, Renata M., Vale, André M., Castiñeiras, Terezinha M., Kaiserlian, Dominique, Echevarria-Lima, Juliana, Bozza, Marcelo T.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 21.07.2023; The Author(s); Elsevier
• Subjects: Health sciences; Immunology; Virology; Health sciences; Immunology; Virology
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2023.107219

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. [Display omitted] •Immunocompetent oligosymptomatic COVID-19 patients may have persistent infection•Long-term COVID-19 patients show low antiviral immunity, with fewer NK cells/pDCs•A systemic type 3 immune profile characterizes persistent SARS-CoV-2 infection•Long-term carriers develop anti-spike antibodies with enhanced binding capacity Health sciences; Immunology; Virology