Altered auditory brainstem responses are post-acute sequela of SARS-CoV-2 (PASC)

Abstract

The Post-acute Sequela of SARS-CoV-2 (PASC) syndrome, also known as Long-COVID, often presents with subjective symptoms such as brain fog and cognitive fatigue. Increased tinnitus, and decreased hearing in noise ability also occur with PASC, yet whether auditory manifestations of PASC are linked with the cognitive symptoms is not known. Electrophysiology, specifically the Auditory Brainstem Response (ABR), provides objective measures of auditory processing. We hypothesized that ABR findings would be linked to PASC and with subjective feelings of cognitive fatigue. Eighty-two individuals, 37 with PASC (mean age: 47.5, Female: 83%) and 45 healthy controls (mean age: 38.5, Female: 76%), were studied with an auditory test battery that included audiometry and ABR measures. Peripheral hearing thresholds did not differ between groups. The PASC group had a higher prevalence of tinnitus, anxiety, depression, and hearing handicap in addition to increased subjective cognitive fatigue. ABR latency findings showed a significantly greater increase in the wave V latency for PASC subjects when a fast (61.1 clicks/sec) compared to a slow click (21.1 clicks/sec) was used. The increase in latency correlated with cognitive fatigue scores and predicted PASC status. The ABR V/I amplitude ratio was examined as a measure of central gain. Although these ratios were not significantly elevated in the full PASC group, to minimize the cofounding effect of age, the cohort was median split on age. Elevated V/I amplitude ratios were significant predictors of both predicted PASC group classification and cognitive fatigue scores in the younger PASC subjects compared to age-matched controls providing evidence of elevated central gain in younger individuals with PASC. More frequent tinnitus also significantly predicted higher subjective cognitive fatigue scores. Our findings suggest that PASC may alter the central auditory pathway and lead to slower conduction and elevated auditory neurophysiology responses at the midbrain, a pattern associated with the typical aging process. This study marks a significant stride toward establishing an objective measure of subjective cognitive fatigue through assessment of the central auditory system.

Fig. 1

ABR Grand Mean Waveforms for PASC and Control Subjects – The top panel shows the averaged grand mean waveforms for both PASC and control subjects. Control subjects are plotted with a black line while PASC patients are plotted in red. The bottom two panels show the slow click rate (right – 21.1 per second) and fast click rate (left – 61.1 per second). Shading represents +1 standard deviation. Waves I and V are outlined with dashed rectangles.

Fig. 2

Age vs. ABR V/I Ratio. The solid black line is a second order polynomial fit using least absolute residuals to control subjects (blue dots). Dotted lines above and below the line of best fit represent the upper and lower bounds of the polynomial fit. PASC subjects (red dots) were then overlayed.

Fig. 3

ABR Grand Mean Waveforms for Younger and Older Subgroups—The left panel shows the averaged grand mean waveforms (averaged across click rate) for younger PASC and control subjects and the left panel shows the older subjects. Control subjects are plotted with a black line while PASC patients are plotted in red. Shading represents +1 standard deviation. Waves I and V are outlined with dashed rectangles.

Fig. 4

Amplitude of Waves I and V for Entire Cohort and Age Subgroups. The top panel shows amplitude of wave I (top left panel) and wave V (top right panel) for PASC (red) and Controls (blue). A linear fit is also plot for both groups. The size of the individual datapoints represents the perceived tinnitus of the subject. Larger dots equate to more frequently perceived tinnitus. The bottom four panels show waves I and V for the younger and older group respectively.