COVID-19 and stroke: from the cases to the causes.

During COVID-19 pandemic, a wide variety of stroke typologies have been described in patients affected by SARS-CoV-2. Investigating the case reports of acute stroke in COVID-19 patients, published since the beginning of the pandemic, we tried to trace the pathogenic mechanisms of stroke during SARS-CoV-2 infection. We conducted a systematic review analyzing demographic data, cerebrovascular risk factors, NIHSS score, vascular territory involvement and laboratory findings of 168 patients described in 89 studies, from a pool of 1243 records. Based on our results, we have identified different stroke profiles: (1) cerebral large vessel disease (CLVD) profile with a low disability, simultaneous onset of COVID-19 and stroke symptoms, good outcome and low serum levels of D-dimer and CRP; (2) intracranial bleeding (IB) profile with high disability, poor outcome and low levels of serum markers of inflammation and coagulopathy; (3) CLVD profile with a short time-lapse between COVID-19 symptoms and stroke onset, high neurological disability and very high systemic inflammatory markers; (4) multiple thrombo-embolic disease (MTED) profile with older patients, many comorbidities, disabling stroke, poor outcome, evident alteration of coagulation tests and high serum levels of both D-dimer and CRP. We therefore summarized these different profiles in a spectrum similar to that of visible light, where the violet-blue band included IB and CSVD with low inflammation and prothrombotic activity, the green-yellow band included CLVD with high inflammation and moderate prothrombotic activity and the orange-red band for MTED with moderate-high levels of inflammation and very high prothrombotic activity.

COVID-19 Vaccination Is Associated with a Better Outcome in Acute Ischemic Stroke Patients: A Retrospective Observational Study.

Background: It is unclear whether and how COVID-19 vaccination may affect the outcome of patients with acute ischemic stroke (AIS). We investigated this potential association in a retrospective study by comparing previously vaccinated (VAX) versus unvaccinated (NoVAX) stroke patients. Methods: We collected clinical reports for all consecutive AIS patients admitted to our hospital and evaluated the outcome predictors in VAX and NoVAX groups. Adjustments were made for possible confounders in multivariable logistic regression analysis, and adjusted hazard ratios were calculated. Results: A total of 466 AIS patients (287 VAX and 179 NoVAX) were included in this study. The NIHSS score at discharge and mRS score at a 3-month follow-up visit were significantly lower in VAX patients compared to NoVAX patients (p < 0.001). Good outcomes (mRS 0−2) were significantly associated with COVID-19 vaccination before AIS (adjusted hazard ratio, 0.400 [95% CI = 0.216−0.741]). Conclusions: The observation that COVID-19 vaccination can influence the outcome of AIS provides support for further studies investigating the role of immunity in ischemic brain damage.

Autonomic Dysfunction during Acute SARS-CoV-2 Infection: A Systematic Review.

Although autonomic dysfunction (AD) after the recovery from Coronavirus disease 2019 (COVID-19) has been thoroughly described, few data are available regarding the involvement of the autonomic nervous system (ANS) during the acute phase of SARS-CoV-2 infection. The primary aim of this review was to summarize current knowledge regarding the AD occurring during acute COVID-19. Secondarily, we aimed to clarify the prognostic value of ANS involvement and the role of autonomic parameters in predicting SARS-CoV-2 infection. According to the PRISMA guidelines, we performed a systematic review across Scopus and PubMed databases, resulting in 1585 records. The records check and the analysis of included reports' references allowed us to include 22 articles. The studies were widely heterogeneous for study population, dysautonomia assessment, and COVID-19 severity. Heart rate variability was the tool most frequently chosen to analyze autonomic parameters, followed by automated pupillometry. Most studies found ANS involvement during acute COVID-19, and AD was often related to a worse outcome. Further studies are needed to clarify the role of autonomic parameters in predicting SARS-CoV-2 infection. The evidence emerging from this review suggests that a complex autonomic nervous system imbalance is a prominent feature of acute COVID-19, often leading to a poor prognosis.

Autonomic dysfunction in non-critically ill COVID-19 patients during the acute phase of disease: an observational, cross-sectional study.

INTRODUCTION: Evidence is emerging about an extra-pulmonary involvement of SARS-CoV-2, including the nervous system. Autonomic dysfunction in patients recovering from acute coronavirus disease 2019 (COVID-19) has been recently described. Dysautonomic symptoms have been reported in the acute phase of the disease, but clear evidence is lacking, especially in the non-critical forms of the infection. OBJECTIVE: The aim of this study is to assess the prevalence of dysautonomia in acute, non-critically ill COVID-19 patients. METHODS: In this observational, cross-sectional study, we compared 38 non-critically ill patients with acute COVID-19 (COVID + group) to 38 healthy volunteers (COVID - group) in order to assess the prevalence of signs and symptoms of dysautonomia through the administration of the composite autonomic symptom score 31 (COMPASS-31) and an active standing test. Comparisons between groups were performed by means of both univariate and multivariate analyses. RESULTS: The prevalence of orthostatic hypotension was significantly higher in the COVID + group. Higher total scores of COMPASS-31 were observed in the COVID + group than controls. Significant differences between groups emerged in the secretomotor, orthostatic intolerance, and gastrointestinal COMPASS-31 domains. All these results maintained the statistical significance after the adjustment for concomitant drugs with a known effect on the autonomic nervous system assumed by the study participants, except for the differences in the gastrointestinal domain of COMPASS-31. CONCLUSION: Our results suggest that an autonomic dysfunction could be an early manifestation of COVID-19, even in the contest of mild forms of the infection.

The Effects of COVID-19 Pandemic on Italian School-Aged Children: Sleep-Related Difficulties and Trauma Reactions.

PURPOSE: The COVID-19 pandemic has affected the mental and physical health of the world population. This study aims to investigate incidence of sleep-related difficulties and post-traumatic stress disorder in the school-aged children after 1 year of the pandemic. METHODS: A sample of Italian children (6-12 years) was queried about their sleep behaviors after 1 year of the pandemic, answering the Children's Sleep Habits Questionnaire (CSHQ). We also evaluated trauma symptoms with the Children's Impact of Event Scale (CRIES-8). RESULTS: Among 205 participants, 184 (89.8%) presented sleep-related difficulties. Out of all, 99 (48.3%) had a high risk to develop post-traumatic stress disorder. Ninety-five (51.6%) children with sleep-related difficulties also presented an abnormal CRIES-8 total score. A correlation was found between the CSHQ total score and the CRIES-8 total score (r = 0.354, P < .01). CONCLUSIONS: The sleep-related difficulties occurring during COVID-19 outbreak may compound to increase the risk to develop post-traumatic stress disorder among Italian children.

Delirium in hospitalized patients with COVID-19 pneumonia: a prospective, cross-sectional, cohort study.

Delirium is an acute confusional state characterized by altered level of consciousness and attention. Coronavirus Disease 2019 (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), can manifest itself with this neuropsychiatric disorder. The endpoints of our study were: the frequency of delirium in subjects with COVID-19 pneumonia; the risk factors that predispose to this condition; and the impact of delirium on mortality. Subjects were consecutively enrolled in a Geriatric Unit from January 5th to March 5th, 2021. Inclusion criteria were: diagnosis of SARS-CoV-2 infection, a radiologically documented pneumonia, and the ability of providing informed consent. Exclusion criteria were: absence of radiological evidence of pneumonia, sepsis, and the need of intensive care unit treatment. All subjects were evaluated by means of Richmond Agitation Sedation Scale (RASS) and Confusion Assessment Method-Intensive Care Unit (CAM-ICU) at least twice per day. In the study cohort (n = 71), twenty patients (28.2%) had delirium. Delirium was present on admission in 11.3%, and occurred during hospitalization in 19.0%. Compared to patients without delirium, patients who developed this neuropsychiatric disorder had a higher mortality rate (35% vs 5.9%) and an increased average hospital length of stay (21 days vs 17 days). In the multivariate analysis delirium was associated with frailty (OR = 2.81; CI = 1.4-5.8) and helmet ventilation (OR = 141.05; CI = 4.3-4663.9). Delirium was an independent predictor of mortality. Nearly a third of subjects (28.2%) had delirium during hospitalization for COVID-19. This finding supports the notion that delirium is a common complication of SARS-CoV2 infection. Since delirium is associated with longer hospital stay, and it is an independent marker of increased mortality, clinicians should assess and prevent it.

Instrumental Evaluation of COVID-19 Related Dysautonomia in Non-Critically-Ill Patients: An Observational, Cross-Sectional Study.

Coronavirus disease-19 (COVID-19) is a predominantly respiratory syndrome. Growing reports about a SARS-CoV-2 neurological involvement, including autonomic dysfunction (AD), have been reported, mostly in critically-ill patients, or in the long-COVID syndrome. In this observational, cross-sectional study, we investigated the prevalence of AD in 20 non-critically-ill COVID-19 patients (COVID+ group) in the acute phase of the disease through a composite instrumental evaluation consisting of Sudoscan, automated pupillometry, heart rate variability (HRV), and pulse transit time (PTT). All the parameters were compared to a control group of 20 healthy volunteers (COVID- group). COVID+ group presented higher values of pupillary dilatation velocities, and baseline pupil diameter than COVID- subjects. Moreover, COVID+ patients presented a higher incidence of feet sudomotor dysfunction than COVID- group. No significant differences emerged in HRV and PTT parameters between groups. In this study we observed the occurrence of autonomic dysfunction in the early stage of the disease.

Effect of lockdown on the management of ischemic stroke: an Italian experience from a COVID hospital.

OBJECTIVE: To evaluate the impact of the lockdown measures, consequent to the outbreak of COVID-19 pandemic, on the quality of pre-hospital and in-hospital care of patients with acute ischemic stroke. METHODS: This is an observational cohort study. Data sources were the clinical reports of patients admitted during the first month of lockdown and discharged with a confirmed diagnosis of stroke or TIA. Data were collected in the interval ranging from March 11th to April 11th 2020. As controls, we evaluated the clinical reports of patients with stroke or TIA admitted in the same period of 2019. RESULTS: The clinical reports of patients eligible for the study were 52 in 2020 (71.6 ± 12.2 years) and 41 in 2019 (73.7 ± 13.1 years). During the lockdown, we observed a significant increase in onset-to-door time (median = 387 vs 161 min, p = 0.001), a significant reduction of the total number of thrombolysis (7 vs 13, p = 0.033), a non-significant increase of thrombectomy (15 vs 9, p = 0.451), and a significant increase in door-to-groin time (median = 120 vs 93 min, p = 0.048). No relevant difference was observed between 2019 and 2020 in the total number of patients admitted. CONCLUSIONS: Due to the COVID-19 pandemic and lockdown measures, the stroke care pathway changed, involving both pre-hospital and in-hospital performances.

An Italian Neurology Outpatient Clinic Facing SARS-CoV-2 Pandemic: Data From 2,167 Patients.

Objective: Neurological sequelae of SARS-CoV-2 infection have already been reported, but there is insufficient data about the impact of the pandemic on the management of the patients with chronic neurological diseases. We aim to analyze the effect of COVID-19 pandemic and social restriction rules on these fragile patients. Methods: Patients with chronic neurologic diseases routinely followed at the outpatient clinic of Gemelli University Hospital, Rome, were assessed for symptoms suggestive of SARS-CoV-2 infection in the pandemic period, consequences of social restrictions, and neurological disease features, concomitant medical conditions, current medical and disease-specific treatments. Data source: a dedicated telephone survey designed to encompass questions on COVID-19 symptoms and on pandemic effects in chronic neurologic conditions. Results: Overall, 2,167 individuals were analyzed: 63 patients reported contact with COVID-19 positive cases, 41 performed the swab, and 2 symptomatic patients tested positive for COVID-19 (0.09%). One hundred fifty-eight individuals (7%) needed urgent neurological care, deferred due to the pandemic; 641 patients (30%) suspended hospital treatments, physiotherapy or other support interventions; 405 individuals (19%) reported a subjective worsening of neurological symptoms. Conclusions: In our population, the presence of neurological chronic diseases did not increase the prevalence of COVID-19 infection. Nevertheless, the burden of neurological disorders has been worsened by the lockdown.

Stroke and COVID19: Not only a large-vessel disease.

Recent evidence has underlined the association between large-vessel stroke and COVID-19, probably due to a proinflammatory and prothrombotic microenvironment induced by SARS-CoV-2. Here, we report the case of a young fit woman affected by COVID-19 without any flu-like symptom, who suffered from speech disorder and left hemiparesis. Brain magnetic resonance evidenced two small acute brain infarctions in right perirolandic cortex without signs of previous ischemic lesions and hemorrhagic infarction. Diagnostic workup excluded cardiac embolic sources, acquired and inherited thrombophilia or autoimmune diseases. Two positive nasopharyngeal swab tests and high titers of serum specific IgA/IgM confirmed COVID-19 diagnosis. In our case stroke seems to be the only manifestation of SARS-COV-2 infection. Therefore the hypothesis of an underlying viral infection, as COVID-19, should be investigated in all the cases of small vessel cryptogenic stroke.

Unprotected stroke management in an undiagnosed case of Severe Acute Respiratory Syndrome Coronavirus 2 infection.

Coronavirus disease 19 (COVID-19) is an emerging infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this scenario, managing acute medical conditions, such as stroke, requires a timely treatment together with proper strategies that minimize the risk of infection spreading to health care workers and other patients. We report the case of a 79-year-old woman, who was admitted for a wake-up stroke due to occlusion of the left middle cerebral artery. She was treated outside the COVID-19-dedicated track of the hospital because she had no concomitant signs or symptoms suggestive of SARS-CoV-2 infection nor recent contact with other infected individuals. Post-mortem nasal and pharyngeal swab was positive for SARS-CoV-2 infection. We propose that hyperacute stroke patients should be tested for SARS-CoV-2 infection at admission and then managed as having COVID-19 until cleared by a negative result. We are aware that such measure results in some delay of the acute treatment of stroke, which could be minimal using well-exercised containment protocols.