Background
We assessed associations between antibody concentrations within 7 days of symptom onset and testing positive for influenza virus infection among outpatients enrolled in a test-negative study.

Methods
From November 2018─May 2019, study sites in five states obtained serum and respiratory specimens from outpatients aged ≥18 years presenting with acute respiratory illness. Respiratory specimens were tested for influenza virus, and viral clades were identified by genomic sequencing. We measured influenza antibody titers against vaccine and circulating viruses by hemagglutination inhibition (HI), microneutralization (MN) and neuraminidase inhibition (NAI) assays. Reduction in odds of influenza-associated illness at increasing HI, MN and NAI antibody titers was estimated using logistic regression adjusting for influenza vaccination status and time since beginning of influenza season.

Results
Among 175 patients with confirmed influenza virus infection, including 112 with influenza A(H1N1)pdm09 and 63 with A(H3N2) (44 clade 3C.3a), and 130 test-negative control patients, higher HI, MN and NAI antibody titers against circulating influenza viruses were associated with lower odds of confirmed influenza. Odds of A(H1N1)pdm09 infection were 44% and 54% lower for each two-fold increase in A(H1N1)pdm09 HI or NAI titer, respectively. Odds of A(H3N2) infection were 49% and 28% lower, respectively, for each two-fold increase in MN or NAI titer against circulating A(H3N2) virus clade. NAI titers were independently associated with lower odds of influenza A(H1N1)pdm09 and A(H3N2) after controlling for HI titer.

Conclusion
Higher influenza antibody titers against circulating viruses were associated with lower likelihood of influenza virus infection among adult patients with acute respiratory illness.