With confirmed cases of the 2019 coronavirus disease (COVID-19) on the rise, neurological symptoms and syndromes have been reported by a significant proportion of patients in addition to the predominant respiratory symptoms.^1-3 A recent study from Italy further demonstrated that long-term neurologic manifestations were seen in more than a third of previously hospitalized COVID-19 patients who had no prior neurological disease.⁴ The study also noted that multiple neurological abnormalities, including mild cognitive impairment, are associated with the severity of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.⁴

Shortly after the first case was reported in Wuhan, China, COVID-19 has rapidly developed into pandemic.⁴ Clinical findings on previously hospitalized and non-hospitalized patients with COVID-19 reported the persistence of multiple symptoms, particularly fatigue and dyspnea.⁵ Accordingly, some authors have suggested the so-called, but not yet defined, “post-COVID-19 syndrome” based on the symptoms reported after three months of SARS-CoV-2 infection.⁶ Few follow-up studies, however, have investigated COVID-19 patients discharged from hospitals after recovery, but with no data published on the persistent neurological manifestations in such patients.⁴

Dr. Padovani and his colleagues, thus developed a longitudinal study to evaluate the neurological manifestations of SARS-CoV-2 after 6 months of follow-up and the potential relationship between pre-morbid conditions and the severity of SARS-CoV-2 infection.⁴ COVID-19 survivors without pre-morbid neurologic disease and discharged from the Azienda Socio Sanitaria Territoriale (ASST) Spedali Civili Hospital in Italy between February and April 2020 were recruited in a follow-up study which included a standardized neurologic symptoms checklist and a neurologic exam at 6 months.⁴ The neurological checklist included symptoms related to central, peripheral, myopathic and cognitive manifestations, whereas the neurological examination assessed cranial nerves, motor, sensory, cerebellar, basal ganglia-related function, deep tendon reflexes, pyramidal signs and global cognitive function using the Montreal Cognitive Assessment (MoCA).⁴ Premorbid conditions were recorded at hospital admission using the Cumulative Illness Rating Scale (CIRS).^4,7 Hospitalization data included the severity of the COVID-19 disease which was classified according to the Brescia COVID Respiratory Severity Scale (BCRSS).^4,8

At 6 months of follow-up, the most common symptoms reported were fatigue (34.0%), memory complaints (30.8%), sleep disorders (30.8%) and myalgias (29.6%), followed by depression or anxiety symptoms (26.0%), loss of dependency in instrumental activities of daily living (IADL), blurring or other visual disturbances (19.5%), numbness or tingling (18.3%) and hyposmia or hypogeusia (16.5%).⁴ Patients with higher BCRSS scores reported a higher number of symptoms at follow-up (p=0.004), memory complaints (p=0.015) and visual disturbances (p=0.006) after correction for age and CIRS.⁴

105 patients were further evaluated with a neurologic exam and cognitive screening. Among them, 42 patients were identified with neurologic abnormalities consisting of dysgeusia/hyposmia (n=19), enhanced physiological tremor (n=15), low-limb hypoesthesia (n=6), low-limb motor deficits (n=3) and cognitive deficits (n=17) according to the Italian validated version of MoCA.^4,9 Neurologic abnormalities at examination were associated with older age (p=0.005), higher premorbid comorbidity index (p=0.001), worse BCRSS (p=0.05), longer hospitalization duration (p=0.002), and higher number of neurologic symptoms reported (p=0.007).⁴ Length of hospitalization (p=0.02) and premorbid comorbidity index (p=0.03) were also predictors of neurologic abnormalities.⁴

In summary, findings from this study demonstrated that previously hospitalized COVID-19 patients reported a wide array of neurological symptoms at 6 months after SAR-CoV-2 infections which could be predicted by the combination of age, premorbid conditions and severity of COVID-19.⁴ These findings supported the observation of a high prevalence of post-COVID-19 clinical manifestations and the claim that long-term consequences of COVID-19 involve both central and peripheral nervous systems.⁴ Dr. Padovoni concluded, “[These results] suggest the importance of long-term follow-up programs to properly care for patients and to evaluate the real impact of SARS-CoV-2 infection on brain health status which is still uncertain.”⁴