Recombinant spike proteins of the SARS-Cov-2 virus induce damage to the murine cochlea.

Introduction The long COVID – a sequel of COVID-19 – is associated with hearing pathologies in 15% of patients. Interestingly, recent studies indicated the continuous presence of spike proteins in the plasma of long COVID patients. Hence, we investigated the impact of recombinant SARS-Cov-2 spikes proteins (S1 and S2) on the murine cochlea.

Methods Explanted cochleae from p3-p5 C57BL/6 mice were used as a model. The cochlear morphology was determined using fluorescent staining; the concentration of TNF-alpha was determined with a commercial ELISA kit. Neutralizing antibody against TNF-alpha was used to assess its impact on the effects induced by spikes proteins on cochlear morphology.

Results The number of intact inner and outer hair cells decreased significantly after 24h exposure to S1 or S2 spike proteins (Mann–Whitney test, p<0.001). At the same time, a significant increase in TNF-alpha concentration was observed in the supernatant from cochlear cultures exposed to S1 and S2. We identified the source of TNF-alpha as cochlear F4/80-positive macrophages; however, other F4/80-negative cells also produced TNF-alpha. The addition of neutralizing anti-TNF-alpha antibody to the S1 or S2-exposed cochlear cultures protected the hair cells from damage.

Discussion The recombinant spike proteins of the SARS-Cov-2 virus damage the cochlear hair cells. This effect could be attributed to TNF-alpha released from the cochlear F4/80-positive resident macrophages in response to S1 or S2 spikes proteins. It remains to be determined if the effect is direct or indirect. Our research provides a plausible explanation of some auditory pathologies seen in long COVID patients.

Charité intramural funding

Conflict of Interest

The authors declare that they have no conflict of interest.

Publication History

Article published online:
12 May 2023