Salivary autoantibodies to type I IFNs: Mirror plasma levels, predispose to severe COVID-19, and enhance feasibility for clinical screening.

BACKGROUND

Autoantibodies have been demonstrated to dampen the interferon (IFN) response in viral infections. Elevated levels of these preexisting autoantibodies (aAbs) decrease basal interferon levels, increasing susceptibility to severe infections.

OBJECTIVES

This study aimed to evaluate the prevalence of type I IFN aAbs in both plasma and saliva from COVID-19 patients, analyze their neutralizing activity, and examine their associations with clinical outcomes, including the need for mechanical ventilation and in-hospital mortality.

METHODS

Prospective analyses of patients admitted to intensive care units in three UAE hospitals from June 2020 to March 2021 were performed to measure aAbs using enzyme-linked immunosorbent assay (ELISA), assess aAbs activity via neutralization assays, and correlate aAbs with clinical outcomes.

RESULTS

Type I IFN aAbs (α2 and/or ω) were measured in plasma samples from 213 ICU patients, and positive results were obtained for 20 % (n = 42) of the patients, with half exhibiting neutralizing activity. Saliva samples from a subgroup of 24 patients reflected plasma levels. In multivariate regression analyses, presence of type I IFN aAbs was associated with a higher need for mechanical ventilation (OR 2.58; 95 % CI 1.07-6.22) and greater in-hospital mortality (OR 2.40; 95 % CI 1.13 - 5.07; P = 0.022). Similarly, positive neutralizing aAbs (naAbs) were associated with a greater need for mechanical ventilation (OR 4.96; 95 % CI 1.12-22.07; P = 0.035) and greater odds of in-hospital mortality (OR 2.87; 95 % CI 1.05-7.89; P = 0.041).

CONCLUSIONS

Type I IFN autoantibodies can be detected in noninvasive saliva samples, alongside conventional plasma samples, from COVID-19 patients and are associated with worse outcomes, such as greater mechanical ventilation needs and in-hospital mortality.