Early, Robust Mucosal Secretory Immunoglobulin A but not Immunoglobulin G Response to Severe Acute Respiratory Syndrome Coronavirus 2 Spike in Oral Fluid Is Associated With Faster Viral Clearance and Coronavirus Disease 2019 Symptom Resolution
Nora Pisanic, Annukka A.R. Antar, Marissa K. Hetrich, Zoe O Demko, Xueyan Zhang, Kristoffer Spicer, Kate Kruczynski, Barbara Detrick, William Clarke, Maria Deloria Knoll, David L. Thomas, Fatimah S. Dawood, Vic Veguilla, Ruth A. Karron, Yukari C. Manabe, Christopher D. Heaney
Abstract
BACKGROUND: Efforts are underway to support the development of novel mucosal coronavirus disease 2019 (COVID-19) vaccines. However, there is limited consensus about the complementary role of mucosal immunity in disease progression and how to evaluate immunogenicity of mucosal vaccines. This study investigated the role of oral mucosal antibody responses in viral clearance and COVID-19 symptom duration. METHODS: Participants with polymerase chain reaction (PCR)-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection provided oral fluid for testing with SARS-CoV-2 antibody multiplex assays, nasal swabs for reverse-transcription PCR, and symptom information at up to 8 follow-ups from April 2020 to February 2022. RESULTS: High and moderate oral fluid anti-spike (S) secretory IgA (SIgA) postinfection was associated with significantly faster viral clearance and symptom resolution across age groups with effect sizes equivalent to prior COVID-19 vaccine immunity at the time of infection. Those with high and moderate anti-S SIgA cleared the virus 14 (95% confidence interval [CI], 10-18) days and recovered 9-10 (95% CI, 6-14) days earlier. Delayed and higher anti-S IgG was associated with significantly longer time to clearance and recovery. Experiencing symptoms >4 weeks was associated with lower anti-receptor-binding domain SIgA 15-30 days after infection onset (P < .001). CONCLUSIONS: Robust mucosal SIgA early postinfection appears to support faster clearance of SARS-CoV-2 and recovery from COVID-19 symptoms. This research underscores the importance of harmonizing mucosal immune response assays to evaluate new mucosal vaccines.