Protective role of anti-SARS-CoV-2 antibody responses against vital organ related long COVID symptoms, 2025, Yukari Magawa et al.

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Protective role of anti-SARS-CoV-2 antibody responses against vital organ related long COVID symptoms
Yukari Magawa, Jhosiene; Jacintho, Lucas Cauê; Alves Ferreira, Marcelo; Ramos Oliveira, Jamille; Rahal Guaragna Machado, Rafael; Kuramoto Takara, Andreia; Moreno Lima de Oliveira, Renata; Cesario Lima, Ariane; Sasahara, Greyce Luri; Lopes Adami, Flávia; Xavier Medeiros, Giuliana; de Souza Apostolico, Juliana; Ruz Fernandes, Edgar; Bruna Leal de Oliveira, Danielle; Durigon, Edison Luiz; Giavina Bianchi, Pedro; Boscardin, Silvia Beatriz; Santoro Rosa, Daniela; Cunha-Neto, Edecio; Kalil, Jorge; Coelho, Verônica; Souza Santos, Keity

COVID-19 pandemic continues to challenge the world with a major public health problem, long COVID (LC), which is estimated to affect over 400 million people worldwide. Many unknowns remain regarding the mechanisms involved in LC.

We investigated the impact of anti-SARS-CoV-2 antibody and IFN-γ responses on the development of LC and its various phenotypes. We studied a cohort of 137 convalescents following predominantly mild COVID-19 during the first pandemic wave (2020) and up to one-year post-infection.

We found 45% of LC cases that were associated with a greater number and duration of acute-phase symptoms. Cardiovascular and/or gastrointestinal symptoms in the acute phase were associated to protection against LC development, while pulmonary, otorhinolaryngological, musculoskeletal and other symptoms were associated with increased risk of LC development. Regarding LC phenotypes, we observed risk associations and potentially deleterious effects of anti-SARS-CoV-2 antibodies for LC symptoms classified as general or other. In contrast, for vital organ-related LC symptoms, we found only protective associations, particularly for cardiovascular symptoms, which indeed had a low prevalence in LC (16%).

Collectively, our data suggest that anti-SARS-CoV-2 antibodies play a protective role against vital organ-related LC symptoms, especially cardiovascular symptoms, but are insufficient in preventing or limiting other highly prevalent LC symptoms, such as neurological, psychiatric and pulmonary.

Link | PDF | Nature Scientific Reports [Open Access]

 

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Although our data reveal intriguing associations between anti-SARS-CoV-2 antibody profiles and LC phenotypes, we emphasize these findings are observational and mechanistic interpretations remain speculative. While antibodies may show dual roles, protective via viral clearance versus harmful via inflammation, the identified signatures—particularly IgA/IgG anti-NP links to cardiovascular protection—offer testable hypotheses.

Further underscoring the complexity of LC, several systemic immune profile perturbations may persist even six months following COVID-19, even in asymptomatic individuals recovered from severe COVID-19, indicating that homeostasis has not been reestablished. This disturbed immunological profile supports the idea of some sort of silent long COVID, that may eventually manifest as critical clinical events, such as acute myocardial infarction or cerebral vascular accidents. These clinically silent biological perturbations may, at least in part, account for the excess number of deaths reported worldwide following the COVID-19 pandemic.