Long COVID, audiovestibular symptoms and persistent chemosensory dysfunction: a systematic review of the current evidence.

Objective: The persistence of auditory, vestibular, olfactory, and gustatory dysfunction for an extended time after COVID-19 has been documented, which represents an emerging challenge of which ENT specialists must be aware. This systematic review aims to evaluate the prevalence of persistent audiovestibolar and olfactory/gustatory symptoms in patients with "long-COVID". Methods: The literature was systematically reviewed according to PRISMA guidelines; PubMed, Scopus and Google Scholar were screened by searching articles on audiovestibular symptoms and olfactory/gustatory dysfunction after SARS-CoV-2 infection. The keywords used were hearing loss, tinnitus, vertigo, smell disorders, parosmia, anosmia, hyposmia, dysgeusia combined with COVID-19 or SARS-CoV-2. Results: 1100 articles were identified. After removal of duplicates (382), 702 articles were excluded, and 16 were included in the systematic review. All articles included identified an association between SARS-CoV-2 infection and persistent hearing or chemosensory impairment. The studies were published over a period of 2 years, between 2019 and 2021. Conclusions: The likelihood of patients with persistent audiovestibular symptoms related to COVID-19 was different among the articles; however, olfactory and gustatory disturbances were more consistently reported. Studies with longer follow-up are required to fully evaluate the long-term impact of these conditions.

The effect of coronavirus disease 2019 on the hearing system.

OBJECTIVE: This study aimed to evaluate different auditory regions with audiological tests, based on the presumption that there may be damage to the structures in the hearing system after coronavirus disease 2019. METHODS: Twenty individuals with no history of coronavirus disease 2019 and 27 individuals diagnosed with coronavirus disease 2019 were compared. Pure tone, speech and extended high-frequency audiometry, acoustic immitansmetry, transient evoked and distortion product otoacoustic emissions testing, and auditory brainstem response testing were conducted. RESULTS: The pure tone audiometry and extended high-frequency mean threshold values were higher in the coronavirus disease 2019 group. The transient evoked otoacoustic emissions signal-to-noise ratios were bilaterally lower at 4 kHz in individuals with a coronavirus disease 2019 history. In the auditory brainstem response test, only the interpeak latencies of waves III-V were significantly different between groups. CONCLUSION: Coronavirus disease 2019 may cause damage to the hearing system. Patients should be followed up in the long term with advanced audiological evaluation methods in order to determine the extent and level of damage.

Hearing screening outcomes in neonates of SARS-CoV-2 positive pregnant women.

OBJECTIVE: The current study aimed to investigate possible association of maternal SARS-CoV-2 with newborn hearing loss. We compared hearing screening outcomes in neonates born to women with positive SARS-CoV-2 PCR test results during pregnancy with healthy controls. METHODS: Neonates born between April and December 2020 in our hospital to mothers with positive SARS-CoV-2 PCR test results during pregnancy were included in this study. Neonates with risk factors for universal newborn hearing screening (NHS) were excluded. Neonates born to mothers with positive SARS-CoV-2 PCR test results during pregnancy were compared with healthy controls in terms of newborn hearing screening results and independent variables. RESULTS: Neonates in the COVID-19 group were more likely to have a "refer" result in auditory brainstem responses (ABR) compared with the control group (53/118 and 28/118, respectively; p = 0.001). The second ABR test results did not differ significantly between the groups (p = 0.618). Logistic regression revealed that birth week and type of birth were not associated with the "refer" result. PCR positivity in the second trimester was more likely to produce the "refer" result in the first ABR test (p = 0.014). CONCLUSION: SARS-CoV-2 PCR positivity in pregnancy is significantly associated with an increased risk of abnormal NHS results. Also, the timing of PCR positivity in pregnancy (trimester) may be related to abnormal NHS results.

Does coronavirus affect the audio-vestibular system? A rapid systematic review.

Objective: This rapid systematic review investigated audio-vestibular symptoms associated with coronavirus.Design: The protocol for the rapid review was registered in the International Prospective Register of Systematic Reviews and the review methods were developed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Risk of bias was assessed using the National Institute of Heath quality assessment tools.Study sample: After rejecting more than 2300 records, there were five case reports and two cross-sectional studies that met the inclusion criteria.Results: No records of audio-vestibular symptoms were reported with the earlier types of coronavirus (i.e. severe acute respiratory syndrome [SARS] and Middle East respiratory syndrome [MERS]). Reports of hearing loss, tinnitus, and vertigo have rarely been reported in individuals who tested positive for the SARS-CoV-2.Conclusion: Reports of audio-vestibular symptoms in confirmed COVID-19 cases are few, with mostly minor symptoms, and the studies are of poor quality. Emphasis over time is likely to shift from life-threatening concerns to longer-term health-related consequences such as audio-vestibular dysfunction. High-quality studies are needed to investigate the acute effects of COVID-19, as well as for understanding long-term risks, on the audio-vestibular system. Review registration: Prospective Register of Systematic Reviews (PROSPERO; registration number CRD42020184932).

Association of Adverse Hearing, Growth, and Discharge Age Outcomes With Postnatal Cytomegalovirus Infection in Infants With Very Low Birth Weight.

Importance: Studies suggest that postnatal cytomegalovirus (CMV) infection can lead to long-term morbidity in infants with very low birth weight (VLBW; <1500 g), including bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC), and neurodevelopmental impairment. However, to date, the association of postnatal CMV with hearing, growth, and length of stay among VLBW infants is unknown. Objectives: To determine the risk for failed hearing screen, increased postnatal age at discharge, or decreased growth at discharge in VLBW infants with postnatal CMV infection compared with CMV-uninfected infants and to compare the risk for other major outcomes of prematurity, including BPD and NEC, in infants with and without postnatal CMV infection. Participants: This multicenter retrospective cohort study included VLBW infants from 302 neonatal intensive care units managed by the Pediatrix Medical Group from January 1, 2002, through December 31, 2016. Infants hospitalized on postnatal day 21 with a diagnosis of postnatal CMV and hearing screen results after a postmenstrual age of 34 weeks were included in the study population. Data were analyzed from December 11, 2017, to June 14, 2019. Main Outcomes and Measures: Infants with and without postnatal CMV infection were matched using propensity scores. Poisson and linear regression were used to examine the association between postnatal CMV and the risk of failed hearing screen, postnatal age at discharge, growth, BPD, and NEC. Results: A total of 304 infants with postnatal CMV were identified, and 273 of these infants (89.8%; 155 boys [56.8%]) were matched with 273 infants without postnatal CMV (148 boys [54.2%]). Hearing screen failure occurred in 45 of 273 infants (16.5%) with postnatal CMV compared with 25 of 273 infants (9.2%) without postnatal CMV (risk ratio [RR], 1.80; 95% CI, 1.14 to 2.85; P = .01). Postnatal CMV was also associated with an increased postnatal age at discharge of 11.89 days (95% CI, 6.72 to 17.06 days; P < .001) and lower weight-for-age z score (-0.23; 95% CI, -0.39 to -0.07; P = .005). Analysis confirmed an increased risk of BPD (RR, 1.30; 95% CI, 1.17 to 1.44; P < .001), previously reported on infants from this cohort from 1997 to 2012, but not an increased risk of NEC after postnatal day 21 (RR, 2.00; 95% CI, 0.18 to 22.06; P = .57). Conclusions and Relevance: These data suggest that postnatal CMV infection is associated with lasting sequelae in the hearing and growth status of VLBW infants and with prolonged hospitalization. Prospective studies are needed to determine the full effects of postnatal CMV infection and whether antiviral treatment reduces the associated morbidity.

Congenital Cytomegalovirus Infection Alters Olfaction Before Hearing Deterioration In Mice.

In developed countries, cytomegalovirus (CMV)-infected newborns are at high risk of developing sensorineural handicaps such as hearing loss, requiring extensive follow-up. However, early prognostic tools for auditory damage in children are not yet available. In the fetus, CMV infection leads to early olfactory bulb (OB) damage, suggesting that olfaction might represent a valuable prognosis for neurological outcome of this viral infection. Here, we demonstrate that in utero CMV inoculation causes fetal infection and growth retardation in mice of both sexes. It disrupts OB normal development, leading to disproportionate OB cell layers and rapid major olfactory deficits. Olfaction is impaired as early as day 6 after birth in both sexes, long before the emergence of auditory deficits. Olfactometry in males reveals a long-lasting alteration in olfactory perception and discrimination, particularly in binary mixtures of monomolecular odorants. Although sensory inputs to the OB remain unchanged, hallmarks of autophagy are increased in the OB of 3-postnatal week-old mice, leading to local neuroinflammation and loss of neurons expressing tyrosine hydroxylase and calbindin. At the cellular level, we found CMV-infected cells and an increased number of apoptotic cells scattered throughout the OB layers, whereas cell proliferation in the neurogenic subventricular zone was decreased. These cellular observations were long-lasting, persisting up to 16 weeks after birth in both males and females and thus providing a mechanism supporting olfactory loss. Despite obvious differences in neurogenesis between human and mouse, these findings offer new strategies aimed at early detection of neurological dysfunctions caused by congenital infections.SIGNIFICANCE STATEMENT In developed countries, congenital cytomegalovirus (CMV)-infected newborns are at high risk of developing sensory handicaps such as hearing loss, thus requiring prolonged follow-up. In this study, we describe for the first time the functional impact of congenital CMV infection on the olfactory system and its associated sense of smell. We demonstrate that a mouse model of congenital CMV infection shows defects in olfactory bulb (OB) normal development and pronounced olfactory deficits affecting acuity and discrimination of odorants. These major olfactory deficits occur long before the emergence of auditory deficits through the upregulation of OB autophagy inducing local neuroinflammation and altered neuron content. Our findings provide new opportunities for designing olfactory means to monitor the possible neurological outcome during congenital CMV infection.

Systematic review of vestibular disorders related to human immunodeficiency virus and acquired immunodeficiency syndrome.

INTRODUCTION: Disorders of the auditory and vestibular system are often associated with human immunodeficiency virus infection and acquired immunodeficiency syndrome. However, the extent and nature of these vestibular manifestations are unclear. OBJECTIVE: To systematically review the current peer-reviewed literature on vestibular manifestations and pathology related to human immunodeficiency virus and acquired immunodeficiency syndrome. METHOD: Systematic review of peer-reviewed articles related to vestibular findings in individuals with human immunodeficiency virus infection and acquired immunodeficiency syndrome. Several electronic databases were searched. RESULTS: We identified 442 records, reduced to 210 after excluding duplicates and reviews. These were reviewed for relevance to the scope of the study. DISCUSSION: We identified only 13 reports investigating vestibular functioning and pathology in individuals affected by human immunodeficiency virus and acquired immunodeficiency syndrome. This condition can affect both the peripheral and central vestibular system, irrespective of age and viral disease stage. Peripheral vestibular involvement may affect up to 50 per cent of patients, and central vestibular involvement may be even more prevalent. Post-mortem studies suggest direct involvement of the entire vestibular system, while opportunistic infections such as oto- and neurosyphilis and encephalitis cause secondary vestibular dysfunction resulting in vertigo, dizziness and imbalance. CONCLUSION: Patients with human immunodeficiency virus and acquired immunodeficiency syndrome should routinely be monitored for vestibular involvement, to minimise functional limitations of quality of life.

Audiovestibular sequelae of congenital cytomegalovirus infection in 3 children presumably representing 3 symptomatically different types of delayed endolymphatic hydrops.

Three cases of congenital cytomegalovirus (CMV) infection with long-term audiovestibular sequelae are presented. Case 1 had no hearing in one ear and severe progressive hearing loss in the other ear; he showed vestibular symptoms at the age of 4.5 years. Case 2 had severe but stationary hearing loss in one ear and showed hearing impairment symptoms in the other ear at 9-13 years of age. Case 3 did not have hearing impairment symptoms, or vestibular symptoms, but was found to have severe progressive hearing loss from the age of 15 months onwards, which led to profound deafness at the age of 2 years and vestibular areflexia at or before the age of 4 years. These cases may represent 3 symptomatically different types of delayed endolabyrinthine hydrops. Type 1 (ipsilateral hydrops) incorporates vestibular symptoms only because of a lack of hearing in the offending labyrinth. Type 2 (contralateral hydrops) incorporates hearing impairment symptoms only because of a lack of vestibular function on both sides and type 3 does not incorporate hearing impairment symptoms or vestibular symptoms (other than those relating to a complete lack of function). Given the present findings, those described by Weiss and Ronis (Trans. Pa. Acad. Opthalmol. Otolaryngol., 30 (1977) 52-54) in one case and other reported findings relating to histopathological or imaging methods in somewhat similar cases, it seems appropriate to include congenital CMV infection in the differential diagnosis of delayed endolymphatic hydrops.

Late sequelae of cochlear infection.

Inflammatory reactions within the inner ear are deleterious to cochlear function and can result in server hearing loss that does not recover. This study investigated a guinea pig model of long-term cytomegalovirus infection. At high doses active inflammation was still present after 35 days. At lower doses some ears showed partial resolution while others were still inflamed. Hearing was totally lost in all cases of persistent inflammation. There was some residual hearing in the cases that had resolved. Cochlear structures including the organ of Corti, stria vascularis, and spiral ganglion were partially degenerated. Fibrotic matrix within scala tympani was ossified in many cases. These changes are consistent with those described for human cochleas following putative viral infections.