The main demographic and clinical features of 344 consecutive patients evaluated are summarized in Table 3.
The mean age of the entire sample was 61.5 years: 4.7% of patients were ≤30-year-old, while 33.7% were ≥70-year-old. Male accounted for 59.3% of cases. The mean latency between the symptoms’ onset and the ER admittance was 6.1 days, ranging from 0 to 30 days; only two patients (0.6%) with mild symptoms (sore throat and sporadic cough) had a latency of 30 days, while 91.6% of patients were evaluated within 10 days from the onset, and 7.8% between 11 and 15 days. The most frequent symptom at COVID-19 onset was fever (74.1%; n = 255; isolated in 100 patients, associated with ≥1 other symptoms in 155 patients), followed by cough (44.8%; n = 154), dyspnea (13.7%; n = 47), and diarrhea (9.3%; n = 32). The majority of patients reported a monosymptomatic onset (52.0%; n = 179), while 36.3% (n = 125) presented with two symptoms, and 11.6% (n = 40) with three or more symptoms. Thirty-four percent of cases (n = 118) entered the ER with a severe form of infection.
Arterial hypertension was the most frequent comorbidity (45.9%), followed by neurological diseases (22.4%), neoplastic diseases (14.2%), diabetes (12.2%), chronic obstructive pulmonary disease (COPD) (11.9%), and renal failure (5.2%).
None of the patients were treated with specific antiviral drugs before admission; 9 of them (2.6%) were on hydroxychloroquine therapy (200 mg bid; therapy duration 5.2 ± 2.6 days, range 1–10).
Prevalence and type of neurological diseases
A total of 22.4% of patients (n = 77) showed a neurological comorbidity. Compared to patients not affected by neurological diseases (Table 4), they were disproportionately overrepresented among the severe COVID-19 (p < 0.001). They were older (mean difference 16.2 years; p < 0.001), had a shorter interval between symptoms onset and ER admittance (mean difference 1.9 days; p = 0.001), and were more frequently affected by hypertension, renal failure, and neoplastic diseases (p≤0.001); their CCI was higher (p < 0.001), and they presented a higher prevalence of institutionalization (p < 0.001). Pre-existing cerebrovascular diseases were the most common comorbidity, affecting 39.0% of patients (n = 30/77, including 7 patients with hemorrhagic and 23 with ischemic stroke), followed by cognitive impairment (32.5%, including 4 patients with Mild Cognitive Impairment, 10 with Alzheimer’s Disease or Alzheimer’s Disease-like dementia, and 11 with vascular dementia), migraine or chronic tension-type headache or trigeminal neuralgia (14.3%; n = 11), epilepsy (6.5%; n = 5), peripheral neuropathy (5.2%; n = 4), Parkinson disease (1.3%; n = 1), and multiple sclerosis (1.3%; n = 1).
A minority of patients (18.2%; n = 14) suffered only from neurological disease. The remaining 63 patients suffered also from one (32.5%; n = 25), two (37.7%; n = 29), or three or more (11.7%; n = 9) other comorbidities, with arterial hypertension representing the most frequent comorbidity (90.5% of cases), followed by neoplastic diseases (36.5% of cases).
Neurological diseases and infection severity
The univariate binary logistic regression analysis (Table 5) revealed that a more severe form of infection was significantly associated with the presence of neurological disease (OR 5.855; 95% CI 3.387–10.122; p = 0.001), together with male gender, arterial hypertension, diabetes, renal failure, COPD, neoplastic disease, institutionalization, older age, and higher CCI.
On the multivariate binary logistic regression analysis (Fig. 1a), the presence of neurological diseases remained independently associated with severe infection (OR 2.305; 95% CI 1.053–5.046; p = 0.012), as well as male gender (p = 0.001), older age (p = 0.001), neoplastic diseases (p = 0.039), and arterial hypertension (p = 0.045).
After the ER admittance, patients affected by neurological diseases showed a lower rate of discharge at home (15.6% vs. 42.7%; p < 0.001), a higher rate of non-invasive mechanical respiratory support (15.6% vs. 4.9%; p = 0.001) and intensive care indication (14.3% vs. 4.5%; p = 0.002). In contrast, they showed a similar rate of hospitalization without the need of mechanical respiratory support (54.5% vs. 47.9%; p = 0.307).
After dividing the sample in patients without any comorbidities, patients with neurological disease without other comorbidities, patients with other comorbidities without neurological diseases, and patients with neurological disease and other comorbidities, the latter group showed the strongest association with a severe COVID-19 (OR 7.394; 95% CI 1.840–29.704; p = 0.005), compared with patients with neurological (OR 2.332; 95% CI 1.202–6.858; p = 0.035) or non-neurological (OR 1.724; 95% CI 1.100–3.790; p = 0.041) comorbidity alone (Fig. 1b).
Comparison of infection severity among different neurological diseases
The association between neurological comorbidity and COVID-19 severity varied among the different neurological diseases (Table 6). Patients affected by cerebrovascular diseases and cognitive impairment showed a higher prevalence of severe infection, a lower rate of discharge at home and a higher rate of non-invasive mechanical ventilation or intensive care indication, significantly different from patients without neurological diseases (p < 0.001). Conversely, patients affected by headache/facial pain, epilepsy, and peripheral neuropathy did not show any significant differences.
Both patients affected by multiple sclerosis and Parkinson disease (not shown in Table 6) suffered from severe COVID-19 that required hospitalization, without the need of mechanical respiratory support.