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Le Infezioni in Medicina, n. 1, 117-122, 2021 CASE REPORTS 117

A case series of vestibular symptoms in positive or suspected COVID-19 patients

Srikrishna Varun Malayala1, Gisha Mohan2, Deepa Vasireddy3, Paavani Atluri4 1Temple University Health System, Philadelphia, Pennsylvania, USA; 2Physicians for American Healthcare Access, Philadelphia, Pennsylvania, USA; 3Pediatric Group of Acadiana, Lafayette, Louisiana, USA; 4Bay Area Hospital, Coos Bay, Oregon, USA

SUMMARY Respiratory symptoms are the most common presen- The pathophysiology of vestibular neuritis induced tation of an acute COVID-19 infection, but thrombo- by COVID-19 is similar to any other viral infection. embolic phenomena, encephalopathy and other neu- Whether in the inpatient or outpatient settings, CO- rological symptoms have been reported. VID-19 should be considered in the differential diag- With these case series, we present multiple presentations nosis for patients presenting with these symptoms, of COVID-19 induced vestibular symptoms namely diz- irrespective of the presence of respiratory symptoms ziness, and nystagmus. The patients reported in or hypoxia. this case series are from different parts of the world, be- long to different age groups and had manifested these Keywords: COVID-19, vestibular neuritis, vertigo, diz- symptoms in different periods of the pandemic. ziness.

n INTRODUCTION quiring imaging to be supported with exclusion of other similar disorders [3]. he Covid-19 pandemic outbreak still remains The accumulating evidence from Wuhan pub- Ta major global challenge for physicians and lished case series confirmed 8% of COVID-19 patients. The spectrum of the disease and organ patients reported . Another study from involvement is still not fully known and evolving. Wuhan reports 16.8% confirmed cases of COV- The symptoms vary between asymptomatic to se- ID-19 causing vestibular symptoms [2, 4]. Though vere multiorgan complications [1]. the mechanism by which COVID-19 causes ves- Vestibular neuritis is an inner ear disorder as- tibular neuritis is unclear, it could be due to its sociated with symptoms such as sudden, severe effect on individual similar to its vertigo, dizziness, balance problems, and pathogenesis in causing , optic neuritis or . It is a result of 8th cranial nerve disorder a result of vasculitis or vasculopathy. following a viral infection leading to inflamma- We compiled a case series of six patients who had tory changes of the nerve [2]. It is a benign con- distinct symptoms of different severities diag- dition and usually self-limiting but the recovery nosed eventually with vestibular neuritis. Some time can vary from days to months. Diagnosis of the neurological manifestations that have al- is usually based on symptomatology seldom re- ready been identified are , anosmia, headache, corticospinal tract signs, dizziness, , encephalopathy, encephalitis but as de- Corresponding author scribed in our case series vestibular neuritis can Srikrishna Varun Malayala also be their initial presentation [5-7]. The partici- E-mail: [email protected] pant in case 2 was admitted and treated by the 118 S.V. Malayala, G. Mohan, D. Vasireddy, et al.

primary author in Delaware, United States. The She described it as “persistent” vertigo in every participant in case 4 is an American female but position, though she was not able to explain the on an extended trip to Europe (country was kept direction in which movement made it worse. anonymous per her request). Rest of the partici- She seemed to be in severe distress from her nau- pants are from Iran, Brazil, Canada and Switzer- sea, non-bilious non bloody vomiting, and severe land and they volunteered to discuss their clinical vertigo. Nystagmus, positioning maneuvers like presentation through a telephone interview. Dix Hallpike, gait could not be attempted because of her distress. The cranial nerve exam did not Case 1 show defects. A 31-year-old Persian female, resident of Iran Her urine toxicology and rest of the laboratory presented with runny nose, sweating, and parameters were completely within normal lim- lethargy. She did not report shortness of breath, its. Computed Tomography (CT) scan of the head loss of or loss of smell. She had a known showed no acute pathology. A CT chest/abdo- exposure to a COVID-19 contact. Diagnosis of men and pelvis without contrast showed multifo- COVID-19 infection was confirmed with PCR of cal, bilateral, peripheral, ill-defined, ground-glass nasal swab. She received symptomatic treatment opacifications, features consistent with acute CO- and was advised home quarantine. VID-19 pneumonia. Acute cerebrovascular attack About thirteen days after the initial infection, she was also considered a differential but the MRI of developed dizziness and vertigo that worsened the did not show any acute findings. on any head movement and would get better on She was admitted to the hospital with acute ves- lying still. The symptoms were associated with tibular neuritis as the admission diagnosis and lack of appetite and fatigue. She denied earache, she was offered symptomatic management with tinnitus, loss or unsteady gait. She denied anti-emetics and meclizine as needed. When she any other history of similar illness, recent upper was found to be positive for COVID-19 infec- respiratory tract infection or recent trauma. tion through a nasal Polymerase Chain Reaction She seeked medical attention due to worsening (PCR), she was started on oral hydroxychloro- symptoms. On examination her vital signs were quine and azithromycin (which was the standard within normal limits, systemic examination and of treatment for acute COVID-19 infection). The neurological examination by her physician did acute phase reactants, coagulation parameters not reveal any abnormalities. Audiometric exami- and other inflammatory markers were within nation and Magnetic Resonance Imaging (MRI) normal limits. scan of the brain did not reveal any underlying With no improvement in the symptoms, she was pathology. A diagnosis of COVID-19 induced ves- subsequently treated with intravenous steroids. tibular neuritis was made after excluding other She also required vestibular rehabilitation from diagnoses. She was prescribed dimenhydrinate physical and occupational therapy while she but her symptoms still persisted despite conser- remained inpatient. The symptoms were quite vative measures. Subsequently she was given 60 persistent and refractory to this treatment and it mg prednisone that was tapered over the next ten took almost a week for her to recover and become days. With this therapy, her symptoms improved asymptomatic. She was eventually discharged and gradually resolved over the next six weeks. home after a prolonged eight-day stay in the hos- pital. Case 2 A 29-year-old Hispanic female residing in Dela- Case 3 ware, USA, presented to the emergency room in A 63-year-old Caucasian female with a known April 2020 with sudden onset of severe vertigo, medical history of aplastic , mitral valve nausea and vomiting two days prior to arrival. prolapse with regurgitation, celiac disease, and She was working at a chicken plant in the local ru- , presented with a runny nose ral community, which had a huge cluster of CO- and would feel out of breath with activity. She did VID-19 infections. She denied tinnitus, hearing not report fever, chills, cough, wheezing or chest loss or unsteady gait. She described the vertigo at . Given the past history of aplastic anemia, rest and it worsened with any type of movement. she took over-the-counter iron pills for shortness Vestibular symptoms in COVID-19 patients 119

of breath with no improvement. She is a resident a slight improvement in her vision post cessation of the United States but in Europe on a trip when of steroids. the symptoms developed. The symptoms devel- Several weeks later, she developed a high-grade oped in March 2020 when there were no reported fever, pain and swelling of her joints and a non- COVID-19 cases. itchy erythematous rash all over her chest and Due to lack of improvement despite a few days abdomen eight hours following the intake of 2 of symptomatic management, the PCR on nasal g amoxicillin/clavulanic acid for a dental proce- swab for the SARS-CoV-2 test was performed in dure. Tmax was 102F, not associated with chills an ambulatory setting. It was positive for COV- and rigors. She did not report lymphadenopathy ID-19 and she was advised home quarantine. or pedal edema. Symptoms self-resolved after About four weeks after the initial episode, she de- 48hrs. Five months after her positive COVID-19 veloped twitching of her left eye and left cheek, test, she was tested for COVID-19 immunoglobu- non-bloody , generalized weakness, pal- lin G (IgG) antibodies and was found to be nega- pitations, sleep disturbances, decreased appetite, tive. skin rash, anosmia, and . The twitch- ing was involuntary, initially involving the left Case 4 eye which then progressed to the left side of the A previously healthy 35-year-old Canadian fe- face. No pain, loss of sensation or numbness were male presented to the hospital with a 4-day his- reported. There were 8 to 10 painful, red skin le- tory of dizziness, and loss of bal- sions around 3 mm in size over perioral area. She ance describing it as a “drunk like feeling”. She was clinically diagnosed with herpes labialis. She works as a television producer and reportedly also developed purple discoloration at the base of worked with people on a cruise ship during the her fingers and whitish discoloration at her fin- COVID-19 outbreak in March 2020. She started gertips with temperature changes. She continued noticing the symptoms a week after that. Her conservative management with ample hydration, symptoms were aggravated with caffeine intake antipyretics, and over-the-counter aspirin, multi- and staring at laptop screens and alleviated by ly- vitamins, and calcium supplements. She gradual- ing down. These symptoms were associated with ly had some clinical improvement over a 4-week fatigue, nausea, crackling sound like period. She was tested for COVID-19 every week with loud voices in the right ear. She denied fever, until she was negative on the 58th day. headache, vomiting, diarrhea and earache. No ab- A week post being tested negative for COVID-19, normalities in facial sensations were reported. she suddenly developed chills and vomiting. She She sought medical attention due to worsening woke up in the middle of the night with dizziness, of symptoms. On examination her vitals were a of the room spinning and an unsteady within normal limits, systemic examination and gait. She did not have tinnitus or hearing loss. neurological examination did not reveal any ab- She immediately sought medical attention and normalities. No abnormalities were revealed on the physical examination showed a strong nys- routine tests. However, she was never test- tagmus to the right. Dix-Hallpike maneuver was ed for COVID-19 infection as she did not meet the performed, and she was confirmed to have ver- “testing criteria” around that time, as she was not tigo and was diagnosed with post-viral vestibular hospitalized. She was treated with betahistine and neuritis. She was treated initially with meclizine, vestibular therapy but her symptoms persisted antiemetics, and Cawthorne vestibular rehabili- even after that for a while. Her symptoms gradu- tation exercises. Due to lack of symptomatic im- ally improved over the next 10 weeks. She was provement she was subsequently given 60 mg tested for COVID-19 antibodies (IgG and IgM) in prednisone with a gradual taper over the next 10 September which turned out to be negative. days. On the 10th day of prednisone, the patient noticed a sudden onset of flashes and floaters in Case 5 the left eye. A slit-lamp examination diagnosed A 71-year-old Brazilian female with a history of Posterior Vitreous Detachment (PVD) of the left obesity developed sudden onset lightheadedness, eye. PVD was attributed to an increase in intraoc- a sense of loss of balance between May 24th 2020 ular pressure with the use of steroids. There was and May 31st 2020. The severity of symptoms had 120 S.V. Malayala, G. Mohan, D. Vasireddy, et al.

progressively worsened and the episodes would and negative inflammatory markers excluded last her about 15 to 20 minutes. She also devel- other differential diagnoses [9]. The history, pre- oped nausea and could perceive a white noise senting clinical , exposure to resembling sound. On 1st June she was evalu- or confirmation of Covid-19 confirmed the pre- ated by her primary care physician who advised sumptive diagnosis of vestibular neuritis second- admission to the hospital for further testing. On ary to COVID-19. June 2nd 2020 she tested negative for COVID-19 An antigen test on an upper respiratory specimen via nasal PCR. She was kept admitted over the obtained by nasopharyngeal or oropharyngeal next 4 days for monitoring of symptoms. A repeat swab is preferred for initial diagnostic testing. nasal PCR swab was obtained on June 4th 2020 Nucleic Acid Amplification Tests (NAAT) such as which was resulted 2 days later as being posi- RT-PCR that detect Viral Ribonucleic Acid (RNA) tive for COVID-19. She did not have any further are considered as the gold standard test at pres- episodes during her hospital stay and was dis- ent [10]. There are several factors that can lead charged on the day of the positive test result to to a false negative RT-PCR result in a COVID-19 quarantine at home. About 6 days post hospital infected patient. Multiple regions of the viral ge- discharge, the patient redeveloped the symptoms nome should be targeted to avoid target region of nausea, vomiting, “buzzing noise” sensation and primer mismatches. Precision in sample col- and dizziness and had intermittent episodes of it lection affects the obtained sample. The exposure over a duration of a month. time to the virus and the viral load in the patient are also pertinent factors [11-13]. Antibody tests Case 6 should not be utilized in diagnosing an acute CO- A 57-year-old female residing in Switzerland had VID-19 infection as antibody development may an exposure to COVID-19 at her workplace. 5-day take upto 2 weeks [14-18]. Total antibody testing post exposure she had tested negative to COVID-19 could be more sensitive than IgM or IgG alone for via nasal PCR. 7 days post exposure she developed early detection [14]. sudden onset dizziness. The episodes were inter- The severity of COVID-19 disease symptoms is mittent and recurred. She also developed accom- attributed to the marked inflammatory response panying nystagmus 3 days later. During the course following the virus entry into the host cell. The of her illness as her symptoms progressively wors- effects of SARS-CoV-2 on the neuronal tissue ened in intensity, she also developed nausea and could be due to a direct infection of the central non-bloody non bilious vomiting. or related to a vascular damage She was evaluated by an Ear, Nose and Throat caused by vasculitis or vasculopathy, similarly (ENT) physician and was diagnosed with ves- to the mechanism described for Varicella Zoster tibular neuritis. She was prescribed meclizine, Virus (VZV) and Human Immunodeficiency Vi- ondansetron, and . Due to minimal im- rus (HIV). The other members of the coronavirus provement of symptoms her physician prescribed family have a history of invading the neurologi- her a five-day course of steroid which brought cal system resulting in optic neuritis, encephalitis, about symptomatic relief. encephalomyelitis [19, 20]. The invasion of SARS- COV2 within CNS is through binding to the An- giotensin Converting Enzyme (ACE) receptors n DISCUSSION once the viruses have gained entry into the CNS, These cases confirm the diagnosis of vestibular they appear advancing by axonal transport [20]. neuritis by excluding other possible differential Evidence about the virus shows that COVID-19 diagnoses. Our cases had either known or sus- can affect the central nervous system resulting in pected exposure to or confirmation of COVID-19. neurological symptoms similar to other members They lacked other neurologic signs and symp- in the coronavirus family [21]. The neurological toms (dysarthria, dysphagia, weakness, sensory symptoms of COVID-19 vary from dizziness, loss, or facial droop). There were no abnormalities headache, and impaired consciousness to severe in imaging studies thus excluding the possibility symptoms like encephalopathy, encephalomyeli- of an acute vascular event in the central nervous tis, ischemic stroke and intracerebral hemorrhage, system [8]. Lack of abnormalities in blood tests anosmia, dysgeusia and neuromuscular diseases. Vestibular symptoms in COVID-19 patients 121

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