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. 2022 Oct 28;5(6):e887. doi: 10.1002/hsr2.887

Facial palsy as a manifestation of COVID‐19: A systematic review of cases

Aiman Khurshid 1, Maman Khurshid 2, Aruba Sohail 2, Imran Mansoor Raza 2, Muhammad Khubab Ahsan 3, Mir Umer Farooq Alam Shah 4, Anab Rehan Taseer 5, Abdulqadir J Nashwan 6,✉, Irfan Ullah 7
PMCID: PMC9616168  PMID: 36320650

Abstract

Background and Aims

Facial palsy is a rare complication of the COVID‐19 infection. Herein, we conducted a systematic review of all published cases of facial palsy post‐COVID‐19 infection in an attempt to educate the general population and medical practitioners regarding the likely occurrence of facial palsy in COVID‐19 patients, its detection, effective treatment plan, and prognosis of the condition.

Methods

We searched PubMed, Google Scholar, and Directory of Open Access Journals (DOAJ) from December 1, 2019 to September 21, 2021.

Results

We included 49 studies bearing accounts of 75 cases who had facial palsy. The mean age of patients was 42.9 ± 19.59 years, with a male‐to‐female ratio of 8:7. The majority of the cases were reported from Brazil (n = 14), USA (n = 9), Turkey (n = 9), and Spain (n = 9). Noticeably, 30.14% of COVID‐19 patients were diagnosed with Guillain‐Barré syndrome. In total, 22.97% of patients complained of bilateral facial paralysis (n = 17), whereas ipsilateral paralysis was observed in 77.03% (n = 57). These were common complaints of Lagophthalmos, otalgia, facial drooping, dysarthria, and compromised forehead wrinkling. The treatment regimen mainly included the use of corticosteroids (n = 51) (69.86%), antivirals (n = 23) (31.51%), IVIG (n = 18) (24.66%), antibiotics (n = 13) (17.81%), antiretroviral (n = 9) (12.33%), and antimalarial (n = 8) (10.96%) medications. In all, 35.62% of patients (n = 26) adhered to a combination of antiviral and corticosteroid‐based therapy. Positive treatment outcomes were observed in 83.58% (n = 56) of cases. In contrast, 10 patients (14.93%) showed nonsignificant recovery, out of which 3 (4.48%) died from the disease.

Conclusion

The association of facial palsy with COVID‐19 is controversial and therefore requires further investigation and published work to confirm a causal relationship. However, physicians should not overlook the likelihood of facial palsy post‐COVID‐19 infection and treat it accordingly.

Keywords: COVID‐19, facial palsy, neurological symptoms, SARS‐CoV‐2, systematic review

1. INTRODUCTION

On December 31, 2019, a novel coronavirus was first identified in Wuhan, China, after reports of multiple cases of pneumonia among its people. 1 This was the start of an outbreak that took the shape of a pandemic over a few months, owing to its rapid transmission through respiratory droplets. As of May 10, 2022, 6.53% of the world population (n = 515,748,861) has confirmed infection with COVID‐19, while 1.21% of these have lost their lives to the complications of COVID‐19. 2

COVID‐19 patients commonly complain of fever, fatigue, nasal congestion, myalgia, anosmia, dry cough, ageusia, hemoptysis, dyspnea, and so forth. 3 Under more serious circumstances, COVID‐19 can result in severe pneumonia, acute respiratory distress syndrome, sepsis, septic shock, multiple organ failure, and so forth. 4 While these are some of the most widely reported complications of COVID‐19 infection, other less common ones have also surfaced, for example, hemophagocytic lymphohistiocytosis (HLH), vasculitis, central retinal vein occlusion, and so forth. 5 , 6 , 7 Similarly, facial palsy has emerged as an unusual yet interesting complication of COVID‐19, whose pathophysiology is yet to be known.

Numerous case reports and series documenting facial palsy as a complication of COVID‐19 have been published. In addition, some systematic reviews have discussed the association of facial palsy with COVID‐19. However, none of these reviews collectively assessed all the cases of facial palsy secondary to COVID‐19. For instance, Gupta et al. 8 included only those cases in which facial palsy was an isolated neurological finding. Therefore, in our systematic review, we aim to develop a stronger evidence base by including all the cases of facial palsy secondary to COVID‐19 that have been published to date. Moreover, we generated patient‐level data by including case reports to thoroughly evaluate the patient characteristics and clinical course of facial palsy secondary to COVID‐19. This will not only bridge the gap in literature but will also aid physicians in reaching a timely diagnosis and in devising treatment regimens that cater to the patients' individual needs.

2. METHODOLOGY

2.1. Literature review

Our work aligns with the Preferred Reporting Items for Systematic Reviews and Meta‐Analysis (PRISMA) checklist (Supporting Information: File S1). 9 We searched PubMed, Google Scholar, and Directory of Open Access Journals (DOAJ) from December 1, 2019 to September 21, 2021 for published accounts of cases of facial palsy as a symptom of COVID‐19. Search terms were combined using appropriate Boolean operators. Our search strategy included keywords/subject headings pertaining to COVID‐19 (e.g., SARS‐CoV‐2 OR Coronavirus Disease 2019 OR COVID‐19 OR severe acute respiratory syndrome coronavirus 2 OR coronavirus infection) and facial palsy (e.g., facial palsy OR facial weakness OR facial paresis OR bell's palsy). The Reference section of included studies was also checked for completeness' sake. Please refer to our Supporting Information: File S1 for a detailed search strategy. Furthermore, this study is registered in the International prospective register of systematic reviews (PROSPERO) and holds the unique identifying number (UIN); CRD42022324693. 10

2.2. Inclusion and exclusion criteria

Our search criteria included all case reports, case series, editorials, correspondence, and retrospective cohorts on the topic of facial palsy following COVID‐19 infection. Only work published in English and containing comprehensive detail of clinical presentation and progression of the condition in each patient was included in our systematic review. Studies bearing aggregate level data, language barriers, and incomplete detail of the condition were excluded from our study. The title, abstract, and full‐text screening were completed in duplicate and independently by two reviewers (M.K. and A.S.). Disagreements regarding the inclusion of studies for data extraction were resolved by the senior author (A.K.).

2.3. Data extraction

Duplicate work was removed after a final version of included literature was entered on excel sheets. We gathered available data on the origin of the reported case (country), date of publication, study type, relevant case within every included study, patient characteristics, age, sex, the status of Guillain‐Barré syndrome (present or absent), affected side of the face, the onset of facial palsy, the test used for detection of COVID‐19, features related to facial palsy, results of cerebrospinal fluid (CSF) analysis, COVID‐19 related symptoms, other signs/symptoms, imaging results, treatment regimen and outcome of treatment. Due to a lack of uniformity in the assessment of facial symptoms between included studies, the percentage‐wise prevalence of symptoms could not be calculated. Additionally, since follow‐up time varied between studies, treatment follow‐up results are not comparable. The terms “complete recovery,” “partial recovery,” “progressive improvement,” and “significant improvement” were regarded as positive treatment outcomes by the author of this review.

2.4. Quality assessment

The quality of included cases was assessed using Joanna Briggs institute's critical appraisal tools. 11 Selected studies were examined for inclusion criteria, sample size, description of study participants, and setting. Two reviewers independently assessed the methodological quality of each paper. Quality assessments were done with different tools based on different study designs. Each tool was modified to provide a numeric score. Tools had 8 items for case reports and 10 for case series. Included case reports (n = 39) had a mean score of 6.385 ± 1.41 with scores ranging from 2 to 8 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 10 case series had a mean score of 5.60 ± 2.01, and scores ranged from 3 to 9. 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 The detailed results of the quality assessment are provided in Supporting Information: File S1. The quality of our systematic review was assessed using AMSTAR 2 criteria. 60 The level of compliance with AMSTAR 2 came out to be “low.” We could not conduct a meta‐analysis because only case reports and case series were included in the analyses without quantitative data.

2.5. Statistical analysis

This systematic review reported descriptive information using individual‐level data of 75 cases from a total of 49 studies reported on facial palsy as a manifestation of COVID‐19. The data focused on the date and country of publication, patient's characteristics, detailed symptoms of facial palsy and COVID‐19, the status of Guillain‐Barré syndrome (present or absent), results of imaging and Cerebrospinal Fluid (CSF) analysis, treatment plan and its outcome. In addition, the continuous variable's mean, median, and SD were calculated where possible.

3. RESULTS

Our initial search provided 1408 results. After removing duplicate studies (N = 1006), 347 studies were screened individually by the two reviewers (M.K. and A.S.). Two hundred and sixteen studies were rejected after going through their titles and abstracts, while full‐text versions of the remaining articles (N = 131) were opened to ascertain their relevance to the topic. Out of these, 82 were excluded for reporting aggregate‐level data (N = 35), not being of the desired study type (N = 12), not being in English (N = 19), or for reporting insufficient data on medical manifestation (N = 16). Finally, 49 studies met our inclusion criteria and were, thus, included for systematic analysis (Figure 1).

Figure 1.

Figure 1

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Flow chart of selected studies

3.1. Patient characteristics

A total of 75 patients gathered from 49 studies who developed facial palsy due to COVID‐19 [Table 1]. The mean age of patients was 42.91 ± 19.59 years, ranging from 15 months to 88 years. In addition, 40 out of 75 patients were males. At the same time, 35 were females, giving a slightly higher ratio of male to female sufferers (8:7). Highest number of cases were reported from Brazil (n = 14), followed by the USA (n = 9), Turkey (n = 9), and Spain (n = 7). Iran and Italy reported six cases each, whereas Singapore, Morocco, and France published accounts of three people each suffering from the condition. India, Egypt, and Japan reported two cases each. At the same time, Canada, Nepal, UK, Belgium, Qatar, Germany, Sweden, Norway, and Portugal each had one published account of a patient complaining of facial palsy due to COVID‐19. It is noteworthy that 13 out of 62 patients had hypertension (20.97%), 9 had diabetes mellitus (14.52%), and 3 of the women were pregnant (4.84%). Twenty‐seven patients had no comorbid condition (43.55%), while no information was shared for 13 patients (17.33%).

Table 1.

Patient characteristics

Author Country Study type No of cases Patient No. Patient characteristics Age/Sex GB present Affected side of face Facial palsy as first sign or not Features related to facial palsy CSF results COVID‐19 related symptoms Other signs/symptoms Imaging Treatment Treatment outcome
Lima et al. Brazil Case series 8 1 None 43/F No Right Yes Moderate (HB Grade 3) NS Mild symptoms Ipsilateral abducent nerve palsy CT Scan normal Oral corticosteroids PR
2 None 25/F No Right Yes Mild (HB Grade 2) NS Mild None Brain MRI normal Oral corticosteroids +  acyclovir CR.
3 None 33/F No Right Yes Moderate (HB Grade 3) NS Mild None NA Oral corticosteroids + acyclovir PR
4 None 26/F No Left No (after 2–10 days for all Nos) Mild (HB Grade 2) NS Mild None MRI: left CN7 enhancement Oral corticosteroids CR
5 None 50/F No Left No Moderate (HB Grade 3) Protein: mildly elevated; WBC: normal; SARS‐COV: negative Mild None CT scan: normal Oral corticosteroids PR
6 None 38/F No Left No Mild (HB Grade 2) NS Mild None Brain MRI: normal Supportive (eye lubricant) CR
7 None 39/F No Right No Mild (HB Grade 2) NS Mild None Brain MRI: normal Oral corticosteroids CR
8 None 34/M No Left No Mild (HB Grade 2) NS Mild None Brain MRI: normal IV corticosteroids CR
Homma et al. Japan Case report 1 1 Smoker 35/F No Right Yes NA NS Cough, malaise, sore throat, nausea, fever, right‐sided aguesia of tongue and anosmia None CT scan: multiple bilateral ground‐glass opacities Acetaminophen, Maoto, favipiravir, and inhaled Ciclesonide (corticosteroid) CR
Goh et al. Singapore Case report 1 1 NA 27/M No Left No (after 6 days) Left‐sided otalgia NS Myalgia, cough, fever, dysguesia, left‐sided throbbing headache, and conjunctival infection None Chest X‐ray: unremarkable; brain MRI; left CN7 enhancement Oral corticosteroid, valacyclovir and Lopinavir/ritonavir No significant improvement.
Figueiredo et al. Portugal Case report 1 1 Pregnant 35/F No Left Yes Involuntary drooling, left‐side labial commissure deviation and ipsilateral lagophthalmos NA None None NA Corticosteroid therapy and eye hydration therapy No significant improvement.
Caamaño et al. Spain Case report 1 1 None 61/M Yes Bilateral No (after 10 days) Involuntary drooling on his right facial commissure, unresponsive blink reflex on both eyes Protein: mildly elevated; WBC: normal; SARS‐COV: negative Fever, cough, and pneumonia None Brain MRI: unremarkable; Chest X‐ray: bilateral frosted glass pneumonia Oral corticosteroid, antimalarial and lopinavir/Ritonavir No significant improvement.
Muras et al. Spain Case report 1 1 None 20/M No Bilateral No (after a week) NA Protein: elevated; WBC: elevated; SARS‐COV: negative Fever, significant asthenia, headache, myalgia, nausea, headache, odynophagia and vomiting EBV coinfection Brain MRI: confirmed bilateral facial neuritis Levofloxacin and oral corticosteroid CR
Manganotti et al. Italy Case series 3 1 NA 72/M Yes Right No (after 18 days) Mild right sided lower face weakness Protein: elevated; WBC: normal; SARS‐COV: negative Fever, dyspnea, hyposmia, ageusia Flaccid tetraparesis, hypesthesia of extremities, dysuria, dysphasia, sinus arrythmia NA IVIG cycle, antimalarial, oseltamivir, darunavir, IV corticosteroid, and tocilizumab NA
2 NA 49/F Yes Right No (after 14 days) Right‐sided hypoesthesia of the face Protein: elevated; WBC: normal; SARS‐COV: negative Fever, cough, dyspnea, hyposmia, and ageusia Ophthalmoplegia with diplopia in the vertical and lateral gaze, and limb ataxia Brain MRI: normal IVIG cycle, antimalarial, lopinavir–ritonavir, IV corticosteroid Progressive improvement
3 NA 76/M Yes Left No (after 22 days) Mild left‐sided lower facial deficit Protein: elevated; WBC: normal; SARS‐COV: negative Fever, cough, hyposmia, ageusia Mild transient diplopia, tetraparesis and dysuria NA IVIG cycle, oseltamivir, darunavir, IV corticosteroid, Progressive improvement
Tocilizumab,
meropenem, linezolid
clarithromycin,
doxycycline and fluconazole
Khaja et al. USA Case report 1 1 HTN and asthma 44/M Yes Bilateral No (after 3 days) Severe (HB Grade 5) Protein: elevated; WBC: normal; glucose: normal Ageusia None Chest X‐ray: clear; MRI brain: unremarkable IVIG CR
Sancho‐Saldaña et al. Spain Case report 1 1 None 56/F Yes Bilateral No (after 20 days) NA Protein: elevated; WBC: normal; SARS‐COV: negative Fever, dry cough, and dyspnea Tetraparesis, lumbar pain, pararesthesia in both hands and oropharyngeal weakness Chest X‐ray: lobar consolidation Antimalarial, azithromycin and IVIG PR
Theophanous et al. USA Case report 1 1 Prematurely born, multiple congenital abnormalities, asthma, and gastrostomy tube feeding 6/M No Right Yes Moderate severe (HB Grade 4) NA None Tachycardiac NA IV acyclovir, IVIG infusion, lubricating eye drops and IV corticosteroids Significant improvement
Dahl et al. Norway Case report 1 1 Acute MI 37/M No Right No (after 18 days) NA Protein: elevated; IgG: normal; WBC: elevated Fever, headache, dyspnea Oliguria, hypotension, tachycardiac, tachypneic and unilateral painful neck swelling X‐ray thorax: bibasal consolidations IV furosemide and intermittently required low‐dose norepinephrine CR
Egilmez et al. Turkey Retrospective cohort 8 1 HTN, CHF 90/M No Left Yes Moderate severe (HB Grade 4) NA Pneumonia None Thorax CT: Intense pneumonia with ground glass opacities IV moxifloxacin and corticosteroids (dexamethasone and prednisolone) PR
2 None 4/F No Left No (after 7 days) Moderate severe (HB Grade 4) NA Cough and fever None Thorax CT: normal Oral corticosteroid CR
3 None 17/F No Right Yes Moderate (HB Grade 3) NA Cough, ageusia and anosmia None Thorax CT: normal Favipravir and oral corticosteroid CR
4 HTN, DM 71/F No Right Yes Moderate severe (HB Grade 4) NA Fever, ageusia and anosmia None Thorax CT: normal Favipravir and IV corticosteroid CR
5 None 63/F No Left Yes Moderate severe (HB Grade 4) NA Fever, myalgia, ageusia and anosmia None Thorax CT: Mild pneumonia with ground glass appearance Favipravir and oral corticosteroid PR
6 None 60/F No Left No (after 12 days) Moderate severe (HB Grade 4) NA Fever, ageusia and anosmia None Thorax CT: normal Favipravir and oral corticosteroid PR
7 HTN 65/F No Left Yes Moderate (HB Grade 3) NA Ageusia and anosmia None Thorax CT: Mild pneumonia with ground glass opacities IV corticosteroids PR
8 HTN, OSA 30/M No Left No (after 9 days) Moderate (HB Grade 3) NA ageusia and anosmia None Thorax CT: Mild pneumonia with ground glass appearance; brain MRI: normal Favipravir and oral corticosteroid (methylprednisolone and dexamethasone) No improvement
Engström et al. Sweden Case report 1 1 None 46/F No Left No (after 26 days) Tongue deviation to left, inability to wrinkle forehead and left lagophthalmos, drooping left corner of mouth, vocal cord paresis, left‐sided paresis NA High fever, cough, dyspnea, dysphagia, and severe headaches None CT thorax: bilateral ground glass appearance. MRI brain: some edema in the parotid gland High‐flow oxygen therapy, dalteparin, IV cefotaxime, oral and IV corticosteroids, and tear substitutes with watch bandages Significant improvement
Corrêa et al. Brazil Case series 4 1 None 25/F No Right No (after 2 weeks) Right‐sided facial muscle weakness and right lagophthalmos NA Vertigo, mild dyspnea, and fever Strabismus in the right eye after right CN6 palsy Brain MRI: restricted diffusion (right CN6 nucleus) and an asymmetrical enhancement (right CN7) Oral corticosteroids CR
2 None 30/F No Right No (after 10 days) NA NA Mild fever and sore throat None Brain MRI: enhancement in right CN7 Oral corticosteroids CR
3 OA, AF 65/M Yes Bilateral No (after 2 weeks) NA Protein: elevated; WBC: normal; SARS‐COV: negative Headache, fever, and generalized myalgia Lower limbs weakness Brain MRI: bilateral enhancement in CN7 IVIg PR
4 None 33/M No Bilateral No (after 2 weeks) NA NA Fever NA Brain MRI: enhancement in CN7 Oral corticosteroids CR
Chan et al. Canada Case report 1 1 None 58/M Yes Bilateral Yes Dysarthria, bilateral lagophthalmos, inability to raise eyebrow, wrinkle forehead, smile, and close lips Protein: elevated; WBC: normal; SARS‐COV: negative None Hypertension, tachypnea, paresthesia in his feet, and tachycardia Chest X‐ray: bilateral infiltrates; CT: bilateral ground‐glass opacities in lung apices; Brain MRI: Bilateral CN7 enhancement Empiric ceftriaxone, azithromycin and IVIG PR
Decio et al. Italy Correspondence 1 1 NA 1.25/F No Right NA NA NA Mild respiratory symptoms, fever, anosmia, and ageusia None Brain MRI: right CN7 enhancement Oral corticosteroids CR
Ozer et al. Turkey Case report 1 1 NA 62/F No Left No (after 2 days) Total paralysis (HB Grade 6) NA Fatigue, chills, and myalgia Sensorineural hearing loss Brain MRI: CN7 and CN 8 enhancement Oral corticosteroids, famotidine, oral favipiravir and SQ enoxaparin sodium PR
Neo et al. Singapore Case series 2 1 NA 25/M No Left Yes Severe (HB Grade 5) NA None None All imaging were unremarkable Oral corticocorticosteroids, valaciclovir and given eye care advice CR
2 NA 34/M No Right Yes Moderate severe (HB Grade 4) NA None None All imaging were unremarkable Oral corticocorticosteroids, valaciclovir and given eye care advice PR
Mackenzie et al. USA Case report 1 1 HTN, T2DM 39/F Yes Bilateral No (after 20 days) NA NA Ageusia, anosmia, headache, myalgias, malaise, and cough Left arm paresthesia, generalized flaccid areflexia, and inability to walk NA Enoxaparin SC, losartan, meperidine IV, antimalarial drug, oral corticosteroids and plasmapheresis PR
Bastola et al. Nepal Case report 1 1 DM 48/M No Left No (after 4 days) Left‐sided facial droop with inability to wrinkle left forehead, raise left eyebrow and left laogphthalmus NA Mild dry cough and hyposmia None HRCT chest: ground‐glass opacity in the right lower lobe Regular insulin and other antidiabetic medications, tear plus drops for dry eyes, and IV corticosteroid Significant improvement with some residual weakness
Hookham et al. UK Case report 1 1 Childhood asthma and HTN 17/M No Right No (after 1.5 months) Right‐sided facial droop with right‐sided facial hypoesthesia NA Fever, diarrhea, vomiting, mild headache, intermittent right‐sided chest pain, myalgia and lethargy, diaphoretic and conjunctival injection (anterior uveitis) Pediatric inflammatory multisystem syndrome, tachycardiac, tachypnea, raised blood pressure, palpitations Brain MRI: minimal increased enhancement of a segment of right CN 7 IV fluids, broad spectrum antibiotics, oral corticosteroids, tocilizumab, amlodipine (for HTN), aspirin and eye drops NA
Khedr et al. Egypt Case report 2 1 None 49/F Yes Left No Right‐sided deviation of mouth and left lagophthalmos NA Fever, dysphagia, and vomiting Flaccid areflexic quadriplegia, hoarseness of voice, and an impaired cough reflex and stock and glove hypoesthesia CT chest: bilateral ground‐glass opacities Plasmapheresis and IVIg Progressive improvement
2 None 55/F Yes Bilateral No Bilateral inability to close eyes, with reduced blinking, inability to whistle, protrude the lips or expose the teeth. NA Fever, cough, and expectoration flaccid areflexic quadriplegia, stock and glove hypoesthesia CT chest: bilateral ground‐glass opacities IVIg CR
Kumar et al. India Case report 1 1 pregnant and PCOS 28/F No Right No Inability to wrinkle right forehead and close right eye, left‐sided deviation of mouth, numbness of the right side of the face and right‐sided drooling NA Fever, dysgeusia, and anosmia Persistently high blood pressure (160/110), generalized weakness NA Oral valacyclovir and oral corticosteroid, insulin (for steroid‐induced DM) with physiotherapy and eye protective measures CR
Aasfara et al. Morocco Case report 1 1 Pregnant 36/F Yes Bilateral Yes Moderate severe (HB Grade 4) protein: elevated; WBC: normal cell count; glucose: normal Vertigo, nausea, and vomiting asymmetric numbness in the lower limbs and left fingers, right sensorineural hearing loss, right vestibular areflexia and nystagmus NA IVIg and IV corticosteroids CR of facial palsy.
Paybast et al. Iran Case report 1 1 HTN 38/M Yes Bilateral Yes Bilateral facial droop, drooling, and slurred speech Glucose: normal; WBC: normal; protein: elevated Band‐like headache, dysphagia, and mild dizziness quadriparesthesia, decrease in all sensation modalities in four limbs affecting the distal parts up to ankle and elbow joints, tachycardia, blood pressure instability NA Plasmapharesis and labetalol (for HTN) No significant improvement
Bigaut et al. France Case report 2 1 None 43/M Yes Right No NA WBC: normal; protein: elevated Cough, anosmia, ageusia, and diarrhea Flaccid paraparesis, generalized areflexia, hypoesthesia, fore limb paresthesia, ataxia, myalgias in legs Chest CT: bilateral ground‐glass opacities; MRI: CN 3, 5, 6, 7, and 8 neuritis IVIg Progressive improvement
2 Obesity 70/M Yes Left No NA WBC: normal; protein: elevated anosmia, ageusia, diarrhea, dyspnea Flaccid tetraparesis, generalized areflexia, forelimb paresthesia Chest CT: bilateral moderate ground‐glass opacities IVIg and physiotherapy No significant improvement.
Ottaviani et al. Italy Case report 1 1 Mild HTN 66/F NA left Yes NA Protein: elevated; rest; normal Acute fatigue, mild fever, and cough Paraplegia, transient pruriginous dorsal rash, initial distal weakness in the upper limbs and diffuse areflexia Lung CT: bilateral ground‐glass opacities IVIg, lopinavir/ritonavir and antimalarial NA
Casas et al. Spain Case report 1 1 vWB 32/M No Left No Moderate severe (HB Grade 4) NA Malaise, fever, dry cough, and headache None Brain MRI: asymmetric contrast uptake in a segment of Left CN7 acetaminophen, metamizole, physiotherapy and ocular hydration CR.
Hutchins et al. USA Case report 1 1 HTN, prediabetes, Class I obesity 21/M Yes Bilateral No Dysarthria, hypogeusia, and facial numbness Protein: mildly elevated; WBC: normal; SARS‐COV: negative Fever, cough, dyspnea, diarrhea, nausea, headache, and sinonasal congestion, dizziness, hypogeusia Tachycardic, bilateral lower extremity weakness, bilateral upper extremity paranesthesia, Grade 4/5 weakness in the deltoids and hip flexors bilaterally, diffuse areflexia Chest X‐ray: increased bilateral air space opacities; brain MRI: abnormal bilateral enhancement of CN 6 and 7, alongside right CN 3 Plasmapheresis Nonsignificant improvement
Abolmaali et al. Iran Case series 3 1 HTN 88/F Yes Left Yes Left lagophthalmos and neck flexion weakness Protein: elevated; rest: normal Fatigue Quadriparesis, low back and thigh pain, impaired proprioception CT: pneumonia with a ground‐glass pattern Plasmapharesis, intubation, corticosteroids, antimalarial and lopinavir/ritonavir No significant improvement.
2 NA 47/M Yes Bilateral No Weakness of neck flexors and dysarthria Protein: elevated; rest: normal Fatigue, dyspnea, and cough Generalized hyporeflexia, urinary retention, quadriparesis, low back pain CT: ground‐glass opacities Plasmapharesis, intubation, corticosteroids, antimalarial and lopinavir/ritonavir Death
3 NA 58/M Yes NA No NA Protein: elevated; rest: normal Progressive dyspnea, dry cough, and dizziness Muscle weakness, gait disturbance and areflexia. CT: ground‐glass opacities Plasmapharesis, IVIg, remdesivir, antimalarial, favipiravir and lopinavir/ritonavir Death
Oke et al. USA Case report 1 1 history of nephrolithiasis 36/M No Right No Moderate severe (HB Grade 4) NA Fever and body aches NA Brain MRI: asymmetric enhancement of the right CN7 Oral valacyclovir, corticosteroid, eye patch and artificial tears Significant improvement
Derollez et al. France Case report 1 1 Overweight 57/F NA Left No NA NA Fatigue, myalgia, chills, and moderate cough NA Chest X‐ray: infiltrates Ocular protection CR
Hasibi et al. Iran Case report 1 1 Class 1 obesity 52/M No Right No Severe (HB Grade 5) NA Fever, malaise, dry cough, and anorexia NA CT: multiple bilateral peripheral ground glass opacities Oral and corticosteroid, favipiravir, remdesivir, arbidol and NSAID CR
Taouihar et al Morocco Case report 2 1 DM, CML 39/M No Right Yes Facial asymmetry, dysarthria, and difficulty chewing NA Dyspnea NA NA Azithromycin, zinc, vitamin C, oral corticosteroid, preventive anticoagulation CR of facial palsy
2 DM, HTN 57/M No Right Yes Dysarthria, facial asymmetry, swallowing disorder, and left‐sided deviation of mouth NA Dyspnea NA NA Azithromycin, zinc, vitamin C, oral corticosteroid, and preventive anticoagulation Significant improvement
Kaplan et al. USA Case report 1 1 DM 48/F No Left No Asymmetric forehead folds, dry eye, inability to raise the left eyebrow and left facial droop NA Fever, chills, headaches, fatigue, myalgia, and weakness NA CT: bilateral ground‐glass opacities Oral corticosteroids, valacyclovir, and doxycycline Significant improvement
Kerstens et al. Belgium Case report 1 1 NA 27/M No Bilateral Yes Severe (HB Grade 5) IgG: elevated; rest: normal Ageusia None MRI: bilateral CN7 contrast enhancement Valaciclovir, artificial tears and oral corticosteroids CR
Kakumoto et al. Japan Case report 1 1 NA 22/M Yes Bilateral No Dysarthria Protein: elevated; rest: normal Fever and dysphagia Tetraparesis, hypesthesia of extremities, dysuria, inability to defecate, dyschezia, sinus arrythmia. Head MRI: bilateral CN7 contrast enhancement IVIG, intubated and managed on a ventilator CR
Al‐Mashdali et al. Qatar Case report 1 1 Atrial septal defect 21/M No Right No NA NA Fever, cough, watery diarrhea, vomiting, conjunctivitis, and abdominal pain Acute myocarditis CT: Bilateral ground‐glass opacities and pleural effusion IV corticosteroids and ocular lubricant Significant improvement
Judge et al. USA Case report 1 1 NA 64/M No Bilateral No Dysarthria and subjective facial paresthesia WBC: elevated; protein: elevated; Glucose: normal Cough, fever, and chills None NA NA Progressive improvement
Tran et al. USA Case report 1 1 DM 42/M Yes Right Yes Right‐sided hypesthesia, dysarthria, diplopia, ptosis, and inability to raise eyebrows or smile protein: elevated; WBC: normal; glucose: elevated None Right lower extremity weakness Chest X‐ray: bibasilar infiltrates; CT: ground‐glass opacities IV corticosteroids, electrolyte replacement for hypokalemia, IVIg, physical, occupational, and speech therapy CR
Silveira et al. Brazil Case report 1 1 DM, HTN 65/M No Left Yes Facial asymmetry, otalgia, and ophthalmoplegia NA Fever, dry cough, and dyspnea Clear left eye proptosis and blindness, otorrhea and complete hearing loss on the left and partial hearing on the right Initial CT: erosion of the anterior wall of the left external ear conduct and left mandible condyle; brain MRI: compression of left CN 2, 3, 4 and 6 IV Meropenem, IV vancomycin, IV Ciprofloxacin, and mastoidectomy Death
Liberatore et al. Italy Case report 1 1 HTN and history of testicular seminoma 49/M Yes Left No NA Glucose: normal; protein: slight elevation; WBC: normal Fever, cough Symmetric weakness in the upper limbs with flaccid tone, reduced tendon reflexes, and respiratory insufficiency; gastroparesis, alternating episodes of tachy‐/bradyarrhythmia, and frequent hypertensive crises) Chest CT: multifocal ground‐glass opacities; Brain MRI: normal Antimalarial, lopinavir/ritonavir, and ceftriaxone NA
Shinde et al. India Case report 1 1 HTN 64/M No Right Yes Severe (HB Grade 5) NA None Macular erythematous rash along zygomatic arch, maxillary and mandibular division of trigeminal nerve Chest X‐ray: normal Eye care, acyclovir, corticosteroid, and methyl cobalamin PR
Ochoa‐Fernández et al. Spain Case report 1 1 None 6/F No Left Yes Moderate (HB Grade 3) NA None None NA Eye protection and oral corticosteroids CR
Zain et al. USA Case report 1 1 None 2/F No Right Yes Right lagophthalmos, ptosis, and drooping of corner of mouth, flattening of the nasiolabial fold, dryness of the eye and tearing Glucose: normal; protein: normal; WBC: normal None EBV coinfection and contact dermatitis Brain MRI: abnormal enhancement of the canalicular segment of right CN7 IV corticosteroids CR
Ribeiro et al. Brazil Case report 1 1 None 26/M No Right No (on 8th day from first onset of symptoms) Right facial weakness NA Cough and fever None Chest CT: multiple bilateral ground‐glass opacities and some superimposed intralobular septal thickening; Brain MRI: enhancement of the right CN7 NA NA
González‐Castro et al. Spain Case series 2 1 Obesity 40/F No Left No (after 2nd day of ward admission) Moderate (HB Grade 3) NA NA None MRI: poorly defined contrast uptake in the left hemifacial/malar subcutaneous region High‐flow oxygen therapy NA
2 DM, smoker and Parkinson's disease patient 65/M No Left No Moderate (HB Grade 3) NA NA None NA High‐flow oxygen therapy NA
Pelea et al. Germany Case report 1 1 HTN, hypothereosis 56/F yes Bilateral No Severe (HB Grade 5) Protein: elevated; glucose: normal; WBC: elevated; SARS‐COV: negative Dry cough, mild fever, and a general weakness Tingling sensation in all fingertips and toes, flaccid tetraparesis, arreflexia and tachycardia Chest CT: leaky infiltrates in the right lower lobe IVIG and Plasmapharesis PR
Karimi‐Galougahi Iran Letter to the editor 1 1 None 60/M No Right No Right‐sided facial nerve palsy, involving mouth, eye, and forehead NA Fever, cough, and dyspnea None Chest CT: ground‐glass opacitiesAbbr Remdesivir, corticosteroid, and oxygen therapy NA
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Abbreviations: CR, complete recovery; CT, computed tomography; IVIg, intravenous immunoglobulin; MRI, magnetic resonance imaging; NA, not applicable; PR, partial recovery. 

3.2. Symptom presentation

Noticeably, 30.14% of the patients were diagnosed with Guillain‐Barré Syndrome associated with COVID‐19. Facial palsy was observed as an initial symptom in 26/74 (35.14%) patients. In all, 22.97% of patients complained of bilateral facial paralysis, whereas ipsilateral paralysis was observed in 77.03%. Out of this 77.03% of patients, left (n = 29) and right (n = 28) sided involvement was observed in an almost equal number of patients. In all, 76.47% of bilateral facial paralysis patients also had GBS. Varying intensity of facial paralysis was seen among the 75 COVID‐19‐inflicted patients. While some experienced only mild facial deficit, weakness, or hypesthesia of the face, others complained of complete facial paralysis (n = 1). Most people complained of moderate‐severe facial dysfunction (n = 10) based on the House Brackmann scale. Among sufferers, Lagophthalmos, otalgia, facial drooping, dysarthria, and compromised forehead wrinkling were common complaints. Most patients witnessed mild to moderate COVID‐19‐specific symptoms. These included complaints of fever, fatigue, cough, ageusia, and headache.

3.3. Diagnostic results

Polymerase chain reaction (PCR), reverse transcriptase (RT)‐PCR, and serology were the most used tests to confirm COVID‐19 infection among 75 individuals. CSF analysis was performed in only half (48%) of the patients, 55.56% of whom had elevated CSF protein levels. CSF SARS‐CoV‐2 result was negative in all (100%), while approximately 1 in every 7 patients (13.5%) had elevated WBC levels on CSF report. Moreover, some patients underwent radiologic imaging to reach a diagnosis. Common findings on chest X‐ray, computer tomography (CT) thorax, and magnetic resonance imaging (MRI) brain included the presence of infiltrates/consolidations (50%), ground glass opacities (71.88%), and enhancement of CN 7 of the affected side (51.52%), respectively.

3.4. Treatment regimen and disease prognosis

Data on treatment plans were shared for 73 (97.33%) out of 75 patients. Although every individual had a treatment plan tailored according to his age, comorbidities, severity of the condition, availability of resources, and so forth, a handful of overlapping medications were prescribed too. Treatment regimen mainly included the use of corticosteroids (69.86%), antivirals (31.51%), IVIG (24.66%), antibiotics (17.81%), antiretroviral (12.33%), and antimalarial (10.96%) medications. Lopinavir/Ritonavir was the most readily prescribed antiretrovirals, whereas hydrochloroquine (100%) was the only antimalarial advised to patients. Three antivirals, namely, acyclovir, valacyclovir, and favipiravir, were predominantly administered to these patients. In total, 35.62% of patients (n = 26) adhered to a combination of antiviral‐corticosteroid‐based therapy. Furthermore, in some cases, eye care (19.18%) medications, for example, lubricants, artificial tears and watch bandages, and so forth, were also encouraged eye care. Physiotherapy (5.48%) and plasmapheresis (10.96%), though less common, were also a part of the treatment plan of some patients. The outcome of treatment was provided for 67 (89.33%) patients. Positive treatment outcomes were observed in 83.58% of cases. In contrast, 10 patients (14.93%) showed nonsignificant recovery, out of which 3 (4.48%) died from the disease.

4. DISCUSSION

Systematic reviews have been conducted in the past that discussed the association of facial palsy with COVID‐19. The reviews indirectly discussed facial palsy concerning COVID‐19 by establishing the correlation of COVID‐19 with GBS, while some only explored cases in which facial palsy was an isolated neurological finding. 8 , 61 , 62  However, none of them collectively assessed all the cases of facial palsy seconCarrillodary to COVID‐19. In our study, we could summate the vast amount of literature available by including all the cases of peripheral facial palsy secondary to COVID‐19 regardless of associated conditions. Thus, we were able to collate a stronger evidence base to support our findings concerning facial palsy and COVID‐19.

Cranial nerve involvement in GBS most commonly results in bilateral facial palsy, rarely unilateral involvement, and facial palsy mostly occurs in the early stage of the disease. 63 , 64 The findings of our study corroborate this observation. Of the 17 patients who demonstrated bilateral facial nerve palsy, 13 (76.5%) had accompanying GBS. Thus, cases of bilateral facial palsy are mostly attributed to GBS.

4.1. Pathophysiology

Pathomechanisms of nervous tissue involvement have been discussed in great detail in the literature. 65 , 66 , 67 , 68 , 69 , 70 , 71 Some of these mechanisms have been highlighted in Figure 2. In our study, unilateral facial palsy patients demonstrated right and left side involvement in almost equal proportions. This shows that SARS‐CoV‐2 has an equivalent predilection for right and left facial nerves.

Figure 2.

Figure 2

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Pathophysiology behind the onset of facial palsy in COVID‐19 patients

In clinical practice, various other viruses have been observed to be associated with facial palsy as well, which include echovirus, enterovirus, herpes simplex virus, Epstein‐Barr virus, cytomegalovirus, human herpesvirus 6, human immunodeficiency virus, mumps, rubella, poliomyelitis, and varicella zoster virus. 72 , 73 , 74 Thus, this further corroborates that a virus like SARS‐CoV‐2 could be behind the etiopathogenesis of facial palsy.

Classically, facial palsy is known to show a predominance in females, which is evident in the prevalence studies conducted. 66 , 75 Moreover, a systematic review involving studies in which Bell's palsy was the only major neurological manifestation in COVID‐19 patients also showed a female preponderance. 8 However, our study demonstrated a slightly high male preponderance. This is because our study included a significantly high number (30.14%) of patients with accompanying GBS, and previous reviews evaluating the relationship between COVID‐19 and GBS have demonstrated a high male preponderance. 61 , 62 , 76 In addition, approximately 21% of the patients had hypertension, and 14.5% demonstrated diabetes mellitus. This finding is corroborated by a study conducted in Korea which demonstrated that facial palsy was associated with age, gender, smoking status, alcohol drinking, history of hypertension, stroke, CVD, diabetes mellitus, total cholesterol level in the blood, and hearing loss through a univariable analysis. 75

Furthermore, Paolino and colleagues 77 , 78  reported a greater frequency of arterial hypertension and lipid disorders in patients with Bell's palsy than in controls. Moreover, a study showed that the risk of Bell's palsy was increased in diabetes. 79 Also, patients with underlying comorbidities such as DM, obesity, hypertension, respiratory distress, or advanced age are at higher risk of developing COVID‐19. 80 Thus, all these factors contribute to the findings of our study.

The treatment regimen mainly involved corticosteroids (69.86%), and 35.62% of patients adhered to a combination of antiviral‐corticosteroid‐based therapy. This finding corroborates a meta‐analysis demonstrating significant benefits of treating Bell's palsy with corticosteroids. 81 Moreover, a network meta‐analysis showed that combined therapy remains the best regimen for a good recovery outcome, supporting its use by a significant 35.62% of patients. 82 However, only two patients used antivirals without corticosteroids to treat facial palsy. A systematic review supports this finding by demonstrating that corticosteroids alone were superior to antivirals alone in treating facial palsy. There was no clear benefit from antivirals alone over placebo. 83 Our findings show that the successful regimens in treating facial palsy due to other etiologies are also effective in treating facial palsy secondary to COVID‐19.

Positive treatment outcomes were observed in 83.58% of patients. This corroborates the effectiveness of the treatment regimens used in the case reports to treat facial palsy secondary to COVID‐19. A favorable response to treatment has also been shown in other complications that arise secondary to COVID‐19, such as central retinal vein occlusion. 7 However, some complications, such as hypoxic encephalopathy, have also shown a poor prognosis. 84 Thus, this highlights that many distinct complications can arise due to COVID‐19 with differing pathogenesis and severity.

There were some limitations in our study. Due to lack of provision of pertinent analytical data, no meta‐analysis could be conducted on the topic to confirm the relationship between COVID‐19 and facial palsy. Our review only comprised of case reports/series in which a limited number of patients were assessed. Therefore, large‐scale studies with more patients and longer follow‐ups are warranted to reliably draw the correlation between COVID‐19 and facial palsy. Moreover, studies in languages other than English were excluded from the analyses. Lastly, adequate representation of most countries was not seen in our review, which implies that many cases went unreported there, so they could not be included in our analyses. Despite the limitations, we tried to include all relevant cases to date and demonstrated an in‐depth comparison of clinical, radiological, and diagnostic features of COVID‐19 and concomitant facial palsy in our patient‐level analyses.

5. CONCLUSION

To the best of our knowledge, this is the most updated review of facial palsy cases following COVID‐19 infection. Although our patient‐level systematic review successfully collated published accounts of facial palsy cases post COVID‐19 infection while theorizing the pathophysiology behind COVID‐19 and subsequent onset of facial palsy, the likelihood of the association being purely coincidental cannot be overlooked. Therefore, large‐scale studies are still warranted to thoroughly understand the association between COVID‐19 and concomitant facial palsy. Systematic reviews involving studies with large sample sizes, such as retrospective cohorts, should be conducted, generating a large patient pool for analyses. This would allow us to develop a clearer understanding of patient characteristics and devise more effective treatment regimens that cater to the needs of individual patients.

AUTHOR CONTRIBUTIONS

Aiman Khurshid: Conceptualization, methodology, writing – original draft preparation, writing – review & editing. Maman Khurshid, Aruba Sohail, Imran Mansoor Raza, Muhammad Khubab Ahsan, Mir Umer Farooq Alam Shah, Anab Rehan Taseer, Abdulqadir J. Nashwan, Irfan Ullah: Data curation, writing – review & editing. All authors read and approved the final manuscript.

CONFLICT OF INTEREST

Abdulqadir J. Nashwan is an Editorial Board member of Health Science Reports and co‐author of this article. He is excluded from editorial decision‐making related to the acceptance of this article for publication in the journal. The remaining authors declare no conflict of interest.

TRANSPARENCY STATEMENT

The lead author Abdulqadir J. Nashwan affirms that this manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.

Supporting information

Supporting information.

Click here for additional data file. (33.6KB, docx)

ACKNOWLEDGMENTS

Open Access funding was provided by the Qatar National Library.

Khurshid A, Khurshid M, Sohail A, et al. Facial palsy as a manifestation of COVID‐19: A systematic review of cases. Health Sci Rep. 2022;5:e887. 10.1002/hsr2.887

DATA AVAILABILITY STATEMENT

The authors confirm that the data supporting the findings of this study are available within the article and its Supporting Information.

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