Neurological and Head/Eyes/Ears/Nose/Throat Manifestations of COVID-19: A Systematic Review and Meta-Analysis.

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, I299.9%), 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.