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Divergent systemic and airway mucosal adaptive immunity to SARS-CoV-2 in African adults

Year: 2026

Type: preprint

Abstract: Systemic antibody responses are more strongly associated with protection against severe COVID-19 in the lung than with protection against SARS-CoV-2 infection in the upper airway. To define the immunological basis of this divergence, we performed contemporaneous sampling of blood, nasal lining fluid (NLF), and bronchoalveolar lavage (BAL) fluid in HIV-uninfected adults and antiretroviral therapy (ART)-treated people with HIV (PWH). Serum spike-specific IgG antibodies correlated more strongly with BAL than with NLF across multiple variants of concern and were not confounded by HIV status. In contrast, IgA drove ACE2–spike inhibition activity in NLF, and this was not predicted by systemic or LRT antibodies. SARS-CoV-2–specific CD4⁺ and CD8⁺ T cells were enriched in BAL, exhibited tissue-resident phenotypes, and did not correlate with circulating T cells, even in ART-treated PWH. Together, these findings could provide an immunological basis for why systemic antibody responses reliably correlate with protection against lung disease but poorly predict nasal immunity.

Source: Research Square

DOI: 10.21203/rs.3.rs-10997315/v1

Authors: Gloria Kapira, Joseph Phiri, Robert Nyirenda, Memory Mvula, Edwin Lisimba, Austine Kumwenda, Dorothy Kazembe, Alice Kusakala, Anstead Kankwatira, Rose Malamba, Lucy Cooper, Mariana Diniz, Elena Mitsi, Mala Maini, Daniela Ferreira, Rhona Mijumbi, Henry Mwandumba, Kondwani Jambo

Institutions: Malawi-Liverpool-Wellcome Trust Clinical Research Programme, University College London, University of Oxford, Wellcome Trust, Liverpool School of Tropical Medicine

Language: English

Topic: SARS-CoV-2 and COVID-19 Research

Subfield: Infectious Diseases

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: green

OpenAlex ID: W7214643282

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