Vaccines and treatments for COVID-19

The following is an edited excerpt from Cherchi (Cherchi 2022).

For patients

Several vaccines are used to stop a person from getting COVID‑19. Other drugs are used to treat a person already infected with COVID‑19. It is unclear whether symptoms of disequilibrium and ear symptoms are really due to COVID‑19 vaccines and treatments.

For practitioners

Overview

Auditory and vestibular symptoms are also being reported in association with the vaccines and treatments for COVID‑19. While causality has not yet been proven, this relationship warrants further scrutiny. However, in view of the evidence of “long-haul” COVID‑19 symptoms (mentioned earlier), and the absence (so far) of evidence for similarly lasting symptoms from vaccines and treatments for COVID‑19, our current impression is that the overall the risk of harm from the vaccines and treatments seems significantly lower than the risks of SARS‑CoV‑2 infection itself.

Auditory and Vestibular Symptoms Associated with Vaccination for SARS‑CoV‑2 and Treatment for COVID‑19

Concerted research and pharmaceutical efforts have been directed at developing vaccines for SARS‑CoV‑2 and treatments for COVID‑19. As these interventions have come to market, new questions have been raised regarding potential adverse effects, including auditory and vestibular symptoms. Here we review several studies and reports regarding the vaccines and antiviral agents. Other interventions, such as interleukin modulators (anakinra, tocilizumab, and sarilumab) and other immunomodulators being used on an experimental basis in patients who are in (or who are at risk of entering) intensive care units, are covered elsewhere (Skarzynska et al. 2022).

Vaccines for COVID‑19

As of this writing, several vaccines have received FDA approval for use (Baden et al. 2021; Polack et al. 2020; Sadoff et al. 2021). A broader review of possible adverse effects associated with the vaccines can be found elsewhere in this volume (Ajmera 2022). We have received questions from patients regarding whether the vaccines themselves can cause otovestibular symptoms or exacerbate pre‑existing otovestibular diseases. There are still insufficient data to answer these questions confidently. Our general experience so far has been that (1) apparent adverse effects from the vaccines have been transient, lasting days to weeks; (2) although symptoms from COVID‑19 infection itself can be very mild, they can also be devastating (if a patient survives) or lethal. On the whole, the potential protection conferred by receiving the vaccines appears greatly to outweigh the risk of the vaccines.

Vaccines for COVID‑19 and Dizziness

The literature regarding potential adverse effects from the Pfizer vaccine (BNT162b2 mRNA) is somewhat difficult to interpret as it pertains to vestibular symptoms. The original trial (Polack et al. 2020) included 43,548 participants (of whom 21,720 received the intervention and 21,828 received a placebo). The report, and its supplementary material, do not list dizziness/vertigo as an adverse event. However, a much smaller study (Kadali, Janagama et al. 2021) of 1245 recipients of the vaccine (no placebo arm), documented that out of 803 patients with “generalized” or “neurological” symptoms, 67 (8.34%) reported “dizziness,” and 20 (2.49%) reported “vertigo.” There has additionally been a case report of postural orthostatic tachycardia occurring following receipt of this vaccine (Reddy et al. 2021). There is a case report (Jeong 2021) of a patient who received the Pfizer vaccine and subsequently developed vestibular neuritis (supposedly corroborated on video head impulse testing), but whether this relationship was causal or associative is not known.

It is also difficult to interpret the literature about the Moderna vaccine’s (mRNA-1273) association with vestibular symptoms. The original trial (Baden et al. 2021) studied 30,420 participants (of whom 15,210 received the vaccine and 15,210 received a placebo). Symptoms of “dizziness and “vertigo” were reported as adverse effects of zero patients in the trial’s supplementary material. In contrast, a much smaller study of 432 vaccine recipients (Kadali et al. 2021) reported “vertigo like symptoms” in 15 (3.47%) patients and “dizziness” in 63 (14.58%) patients.

It is similarly difficult to interpret the literature about the Johnson & Johnson’s Janssen vaccine (Ad26.COV2.S). The original trial (Sadoff et al. 2021) included 39,260 participants (of whom 19,630 received the vaccine and 19,630 received placebo). The supplementary material from the trial reported that no vaccine recipients endorsed symptoms of “dizziness” or “vertigo.” Yet, the product monograph (https://covid-vaccine.canada.ca/info/pdf/janssen-covid-19-vaccine-pm-en.pdf, accessed June 26, 2022) that reviewed data from 43,783 participants (of whom 21,895 received the vaccine and 21,888 received placebo) stated 13 patients in the treatment group and 7 patients in the placebo group endorsed the symptom of “vertigo.”

Vaccines for COVID‑19 and Hearing Loss

The Centers for Disease Control’s Vaccine Adverse Effects Reporting System (CDC VAERS) provides publicly available data regarding the two mRNA vaccines (Pfizer and Moderna). Analysis of these data revealed 40 cases of unilateral sensorineural hearing loss (confirmed on audiometric testing) thought “most likely” to be attributable to the vaccines themselves (Formeister et al. 2021). The report indicated that the unilateral hearing loss occurred within 3 weeks (mean 4 days) of having received the vaccines. The calculated incidence was 0.3 cases per 100,000 individuals (i.e., 3 per million).

Vaccines for COVID‑19 and Tinnitus

Tinnitus has been less studied as a potential adverse effect of COVID‑19 vaccines, but emerging literature is beginning to discuss this (Ahmed et al. 2022; Parrino et al. 2021).

Anti-Viral Therapies for COVID‑19

For an individual already infected with COVID‑19 the vaccines play no role in acute management, but treatments aiming at the virus itself are being investigated. These have recently been reviewed elsewhere (Coffin et al. 2021). Some of these agents are already known to be ototoxic, such as chloroquine, hydroxychloroquine, and ivermectin.

As of this writing there was considerable interest in the combination antiviral agent Paxlovid, which contains ritonavir (an agent already used in the treatment of HIV) and nirmatrelvir (an investigational agent); unfortunately, there is almost no literature about the potential ototoxicity of these agents; ritonavir is also one component of the combination antiviral drug, Kaletra (which also contains lopinavir), which has been reported to cause reversible bilateral hearing loss (Williams 2001), but whether that property is due to ritonavir or lopinavir remains unclear.

Bamlanivimab (LY‑CoV555 by Lilly) is a neutralizing IgG1 antibody for SARS‑CoV‑2 ([No authors] 2021). In a randomized phase 3 trial of 1035 patients (Dougan et al. 2021), of whom 518 individuals received bamlanivimab in combination with another antiviral agent (etesevimab), and 517 individuals received a placebo, the symptom of “dizziness” was reported in four patients (0.8%) from the treatment group and three patients (0.6%) from the control group. The comparable rate of this symptom in both groups and the fact that the intervention group received a combination agent (bamlanivimab + etesevimab) makes it unclear what risk of vestibular symptoms bamlanivimab actually incurs.

Molnupiravir (MK‑4882/EIDD‑2801 by Merck) is a nucleotide analogue that inhibits SARS‑CoV‑2 replication. In a randomized phase 3 trial completed by 1411 patients (Jayk Bernal et al. 2022), of whom 710 individuals received molnupiravir and 701 individuals received placebo, the symptom of “dizziness” was reported in 1% of the treatment group and 0.7% of the placebo group. The comparable rate of this symptom in both groups makes it unclear what risk of vestibular symptoms molnupiravir actually incurs.

References

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