ABSTRACT: Background/Objective: Coronavirus disease 2019 (COVID-19) has been associated with various neurological and atypical head/eyes/ears/nose/throat (HEENT) manifestations. We sought to review the evidence for these manifestations. Methods: In this systematic review and meta-analysis, we compiled studies published until March 31, 2021 that examined non-respiratory HEENT, central, and peripheral nervous system presentations in COVID-19 patients. We included 477 studies for qualitative synthesis and 59 studies for meta-analyses. Results: Anosmia, ageusia, and conjunctivitis may precede typical upper/lower respiratory symptoms. Central nervous system (CNS) manifestations include stroke and encephalopathy, potentially with brainstem or cranial nerve involvement. MRI studies support CNS para-/postinfectious etiologies, but direct neuroinvasion seems very rare, with few cases detecting Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in the CNS. Peripheral nervous system (PNS) manifestations include muscle damage, Guillain–Barre syndrome (GBS), and its variants. There was moderate-to-high study heterogeneity and risk of bias. In random-effects meta-analyses, anosmia/ageusia was estimated to occur in 56% of COVID-19 patients (95% CI: 0.41–0.71, I2:99.9%), more commonly than in patients without COVID-19 (OR: 14.28, 95% CI: 8.39–24.29, I2: 49.0%). Neurological symptoms were estimated to occur in 36% of hospitalized patients (95% CI: 0.31–0.42, I2: 99.8%); ischemic stroke in 3% (95% CI: 0.03–0.04, I2: 99.2%), and GBS in 0.04% (0.033%–0.047%), more commonly than in patients without COVID-19 (OR[stroke]: 2.53, 95% CI: 1.16–5.50, I2: 76.4%; OR[GBS]: 3.43,1.15–10.25, I2: 89.1%). Conclusions: Current evidence is mostly from retrospective cohorts or series, largely in hospitalized or critically ill patients, not representative of typical community-dwelling patients. There remains a paucity of systematically gathered prospective data on neurological manifestations. Nevertheless, these findings support a high index of suspicion to identify HEENT/neurological presentations in patients with known COVID-19, and to test for COVID-19 in patients with such presentations at risk of infection.
【저자키워드】 COVID-19, stroke, Sensory systems, Neurology – General, Guillain–Barre, Peripheral Neuropathy, 【초록키워드】 coronavirus disease, severe acute respiratory syndrome coronavirus 2, Meta-analysis, SARS-CoV-2, Coronavirus disease 2019, coronavirus, Hospitalized, systematic review, hospitalized patients, severe acute respiratory syndrome Coronavirus, coronavirus 2, variants, MRI, Anosmia, Critically ill, Ageusia, Ischemic Stroke, Risk of bias, Patient, nervous system, Manifestations, neurological manifestations, Encephalopathy, Central nervous system, Neurological symptoms, Brainstem, respiratory, CNS, conjunctivitis, patients, critically ill patients, COVID-19 patients, Guillain–Barrè syndrome, Evidence, meta-analyses, risk of infection, Atypical, Peripheral nervous system, neurological, COVID-19 patient, manifestation, respiratory symptoms, Cranial nerve, Support, 95% CI, acute respiratory syndrome coronavirus, random-effects meta-analyses, syndrome, suspicion, Anosmia/ageusia, study heterogeneity, retrospective cohort, HEENT, retrospective cohorts, Neurological symptom, current, etiologies, identify, examined, include, occur, hospitalized patient, COVID-19 in patient, cranial, patients without COVID-19, 【제목키워드】 review, manifestation,