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Background: Mucosal IgA is key in preventing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Several mucosal vaccines are in development, and consistent methodologies assessing mucosal IgA are crucial for evaluation across clinical trials.

Methods: We compared SARS-CoV-2 ancestral spike-specific IgA and secretory IgA (SIgA) in nasal secretions and saliva from 20 adults enrolled at Danderyd Hospital, Stockholm, Sweden, and 23 adults enrolled at the Icahn School of Medicine at Mount Sinai, New York, USA. Nasal secretions were collected by Nasosorption® and nasal swabs, and saliva by passive drooling, Salivette®, and saliva swabs. Antibody levels were measured in all samples using an electrochemiluminescence assay (ECL) and two enzyme-linked immunosorbent assays (ELISAs).

Findings: Spike-specific IgA and SIgA levels measured by ECL correlated well with those measured by ELISA across nasal and saliva samples (range 0.42–0.94, p < 0.01), except for saliva collected by saliva swabs yielding lower IgA concentrations and weaker correlations (range − 0.21-0.27). Spike-specific IgA levels also correlated well across collection methods (range 0.7–0.9, p < 0.0001), with a weaker correlation between saliva collected by passive drooling and saliva swab (r = 0.55, p < 0.001). Although antibody levels correlated well between nasal secretions and saliva collected by passive drooling or Salivette® (range 0.64–0.86, p < 0.01), the overall levels were > 3-fold higher in nasal secretions compared to saliva (p < 0.01).

Interpretation: This multi-center study demonstrates an overall good comparability between spike-specific IgA and SIgA across assays and collection methods, except for saliva swabs. Our findings suggest that nasal secretions may be preferable due to higher spike-specific IgA levels compared to in saliva.