Prenatal maternal stress during the COVID-19 pandemic and infant regulatory capacity at 3 months: A longitudinal study.

The COVID-19 pandemic is a global traumatic experience for citizens, especially during sensitive time windows of heightened plasticity such as pregnancy and neonatal life. Pandemic-related stress experienced by mothers during pregnancy may act as an early risk factor for infants' regulatory capacity development by altering maternal psychosocial well-being (e.g., increased anxiety, reduced social support) and caregiving environment (e.g., greater parenting stress, impaired mother-infant bonding). The aim of the present longitudinal study was to assess the consequences of pandemic-related prenatal stress on infants' regulatory capacity. A sample of 163 mother-infant dyads was enrolled at eight maternity units in northern Italy. They provided complete data about prenatal stress, perceived social support, postnatal anxiety symptoms, parenting stress, mother-infant bonding, and infants' regulatory capacity at 3 months of age. Women who experienced emotional stress and received partial social support during pregnancy reported higher anxious symptoms. Moreover, maternal postnatal anxiety was indirectly linked to the infants' regulatory capacity at 3 months, mediated by parenting stress and mother-infant bonding. Dedicated preventive interventions should be delivered to mothers and should be focused on protecting the mother-infant dyad from the detrimental effects of pandemic-related stress during the COVID-19 healthcare emergency.

COVID-19-associated Guillain-Barré syndrome in the early pandemic experience in Lombardia (Italy).

OBJECTIVE: To estimate the incidence and describe clinical characteristics and outcome of GBS in COVID-19 patients (COVID19-GBS) in one of the most hit regions during the first pandemic wave, Lombardia. METHODS: Adult patients admitted to 20 Neurological Units between 1/3-30/4/2020 with COVID19-GBS were included as part of a multi-center study organized by the Italian society of Hospital Neuroscience (SNO). RESULTS: Thirty-eight COVID19-GBS patients had a mean age of 60.7 years and male frequency of 86.8%. CSF albuminocytological dissociation was detected in 71.4%, and PCR for SARS-CoV-2 was negative in 19 tested patients. Based on neurophysiology, 81.8% of patients had a diagnosis of AIDP, 12.1% of AMSAN, and 6.1% of AMAN. The course was favorable in 76.3% of patients, stable in 10.5%, while 13.2% worsened, of which 3 died. The estimated occurrence rate in Lombardia ranges from 0.5 to 0.05 GBS cases per 1000 COVID-19 infections depending on whether you consider positive cases or estimated seropositive cases. When we compared GBS cases with the pre-pandemic period, we found a reduction of cases from 165 to 135 cases in the 2-month study period in Lombardia. CONCLUSIONS: We detected an increased incidence of GBS in COVID-19 patients which can reflect a higher risk of GBS in COVID-19 patients and a reduction of GBS events during the pandemic period possibly due to a lower spread of more common respiratory infectious diseases determined by an increased use of preventive measures.

Failure of Therapeutic Anticoagulation in COVID-19 Patients With Acute Ischemic Stroke. A Retrospective Multicenter Study.

Background: Acute ischemic stroke (AIS) is a possible complication of coronavirus disease 2019 (COVID-19) infection. Although peculiar clinical features and underlying specific mechanisms of thrombogenesis have been suggested so far, there is no consensus on the appropriate vascular preventive drug regimen in patients with COVID-19. Aim and Methods: From a larger clinical series of consecutive acute ischemic strokes related to COVID-19 admitted to three cerebrovascular units in Northern Italy, herein, we describe the clinical features of a subgroup of patients in whom stroke occurred despite therapeutic anticoagulation. Results: A total of seventeen/80 AIS related to COVID-19 (21.2%) occurred in anticoagulated patients. Although no blood level was available for Direct Oral AntiCoagulant, the drug dosage was appropriate according to guidelines. Their National Institute of Health Stroke Scale (NIHSS) at admission was 12.0 (SD = 7.4) and 58.8% of them had evidence of large vessel occlusion. The case fatality rate was as high as 64.7%. Discussion and Conclusions: The occurrence of an anticoagulation failure seems to be increased in the setting of COVID-19 infection, with worse clinical outcomes if compared to non-COVID-19 related ischemic strokes. We discuss the diagnostic and therapeutic implications of such evidence, suggesting that some arterial thrombotic complications might be either resistant to or independent of the anticoagulation effect.

Imaging features and ultraearly hematoma growth in intracerebral hemorrhage associated with COVID-19.

PURPOSE: Intracerebral hemorrhage (ICH) is an uncommon but deadly event in patients with COVID-19 and its imaging features remain poorly characterized. We aimed to describe the clinical and imaging features of COVID-19-associated ICH. METHODS: Multicenter, retrospective, case-control analysis comparing ICH in COVID-19 patients (COV19 +) versus controls without COVID-19 (COV19 -). Clinical presentation, laboratory markers, and severity of COVID-19 disease were recorded. Non-contrast computed tomography (NCCT) markers (intrahematoma hypodensity, heterogeneous density, blend sign, irregular shape fluid level), ICH location, and hematoma volume (ABC/2 method) were analyzed. The outcome of interest was ultraearly hematoma growth (uHG) (defined as NCCT baseline ICH volume/onset-to-imaging time), whose predictors were explored with multivariable linear regression. RESULTS: A total of 33 COV19 + patients and 321 COV19 - controls with ICH were included. Demographic characteristics and vascular risk factors were similar in the two groups. Multifocal ICH and NCCT markers were significantly more common in the COV19 + population. uHG was significantly higher among COV19 + patients (median 6.2 mL/h vs 3.1 mL/h, p = 0.027), and this finding remained significant after adjustment for confounding factors (systolic blood pressure, antiplatelet and anticoagulant therapy), in linear regression (B(SE) = 0.31 (0.11), p = 0.005). This association remained consistent also after the exclusion of patients under anticoagulant treatment (B(SE) = 0.29 (0.13), p = 0.026). CONCLUSIONS: ICH in COV19 + patients has distinct NCCT imaging features and a higher speed of bleeding. This association is not mediated by antithrombotic therapy and deserves further research to characterize the underlying biological mechanisms.

Did the role of the neurologist in the emergency department change during the COVID-19 pandemic? Evidence from an Italian nationwide survey.

OBJECTIVE: This study aims to assess whether the role of neurologists in the emergency department changed during the coronavirus (COVID)-19 pandemic. METHODS: Data from an Italian national survey investigating the role of neurologists in the emergency room conducted in December 2020 were compared with those of the same survey of the previous year. These surveys involved a questionnaire being completed filled in for patients who received a neurological consultation following a visit to the emergency room. Information gathered included demographic characteristics, triage level according to both the emergency physician and neurologist, reason for the consultation, neurological evaluation, and discharge mode. RESULTS: In both years, approximately half of the patients were women, and the median age was 61 years. More patients in 2020 arrived by ambulance and had a greater need for assistance based on triage level than in 2019. During 2020, the proportion of consultancy requests judged by the neurologist was higher than that in 2019 (77% vs. 73%). Moreover, in 2020, fewer patients required consultation for headache, muscle pain, fever, and neurological signs, whereas coma was more prevalent. The diagnosis of ischemic stroke was the most prevalent in both years, followed by transient ischemic attack. In 2020, the status epilepticus increased and discopathy decreased. CONCLUSION: This study showed the significant role played by neurologists in emergency activities, especially during the COVID-19 pandemic, and highlighted the differences in patients admitted between the year of the epidemic and the year previous.

Vessel wall magnetic resonance imaging in COVID-19-associated cryptogenic ischemic stroke.

BACKGROUND AND PURPOSE: Acute ischemic stroke (AIS) is a common complication of coronavirus disease 2019 (COVID-19), but the underlying biological mechanisms remain unclear. We aimed to describe the prevalence of vessel wall alterations in patients with cryptogenic stroke through vessel wall magnetic resonance imaging (vwMRI). METHODS: All consecutive patients admitted for AIS and COVID-19 to a single neuro-COVID unit from 10 November to 31 December 2020 were prospectively evaluated and underwent a complete etiologic workup for AIS. In patients with cryptogenic stroke, the diagnostic workup was completed with vwMRI study. RESULTS: After the exclusion of four patients ineligible for MRI, a total of 10 patients were included (median age = 78 years, 50% males), of whom four (40%) had a cryptogenic stroke. vwMRI showed vascular changes consistent with inflammation of intracranial artery walls in three subjects (75%). Two patients had focal and one multifocal involvement. CONCLUSIONS: vwMRI detected signs of vascular inflammation in the majority of patients with cryptogenic AIS, leading to an etiologic definition with potential therapeutical implications. Our findings are best interpreted as hypothesis-generating, suggesting the possibility of expanding the diagnostic workup of cryptogenic stroke with vessel wall imaging.

Depression and Anxiety in Mothers Who Were Pregnant During the COVID-19 Outbreak in Northern Italy: The Role of Pandemic-Related Emotional Stress and Perceived Social Support.

The COVID-19 pandemic is a collective trauma that is threatening citizens' mental health resulting in increased emotional stress, reduced social support, and heightened risk for affective symptoms. The present study aimed to investigate the effects of antenatal pandemic-related emotional stress and perceived social support on the symptoms of depression and anxiety of mothers who were pregnant during the initial COVID-19 outbreak in northern Italy. A sample of 281 mothers was enrolled at eight maternity units in the first hotspot region of the COVID-19 outbreak in northern Italy. Participants filled out online questionnaires assessing the direct or indirect exposure to the SARS-CoV-2 virus, pandemic-related stress, perceived social support, as well as symptoms of depression and anxiety. Depressive and anxious symptomatology was above clinical concern, respectively, in 26 and 32% of the respondents. Mothers who reported no exposure to SARS-CoV-2 during pregnancy and those who reported at least one direct or indirect exposure did not differ in terms of affective symptoms. Continuous scores and risk for severe depression and anxiety were positively associated with prenatal pandemic-related emotional stress and negatively linked with perceived social support during pregnancy. Women who become mothers during the COVID-19 emergency may be at high risk for affective problems. Dedicated preventive programs are needed to provide adequate preventive support and care for maternal mental health during and after the COVID-19 pandemic.

SARS-CoV-2 infection and acute ischemic stroke in Lombardy, Italy.

OBJECTIVE: To characterize patients with acute ischemic stroke related to SARS-CoV-2 infection and assess the classification performance of clinical and laboratory parameters in predicting in-hospital outcome of these patients. METHODS: In the setting of the STROKOVID study including patients with acute ischemic stroke consecutively admitted to the ten hub hospitals in Lombardy, Italy, between March 8 and April 30, 2020, we compared clinical features of patients with confirmed infection and non-infected patients by logistic regression models and survival analysis. Then, we trained and tested a random forest (RF) binary classifier for the prediction of in-hospital death among patients with COVID-19. RESULTS: Among 1013 patients, 160 (15.8%) had SARS-CoV-2 infection. Male sex (OR 1.53; 95% CI 1.06-2.27) and atrial fibrillation (OR 1.60; 95% CI 1.05-2.43) were independently associated with COVID-19 status. Patients with COVID-19 had increased stroke severity at admission [median NIHSS score, 9 (25th to75th percentile, 13) vs 6 (25th to75th percentile, 9)] and increased risk of in-hospital death (38.1% deaths vs 7.2%; HR 3.30; 95% CI 2.17-5.02). The RF model based on six clinical and laboratory parameters exhibited high cross-validated classification accuracy (0.86) and precision (0.87), good recall (0.72) and F1-score (0.79) in predicting in-hospital death. CONCLUSIONS: Ischemic strokes in COVID-19 patients have distinctive risk factor profile and etiology, increased clinical severity and higher in-hospital mortality rate compared to non-COVID-19 patients. A simple model based on clinical and routine laboratory parameters may be useful in identifying ischemic stroke patients with SARS-CoV-2 infection who are unlikely to survive the acute phase.

Impact of SARS-CoV-2 infection on acute intracerebral haemorrhage in northern Italy.

INTRODUCTION: Growing evidence has been published as to the impact of SARS-CoV-2 (Severe acute respiratory syndrome coronavirus 2) on cerebrovascular events over the last few months, with considerable attention paid to ischemic strokes. Conversely, little is known about the clinical course of intracerebral haemorrhage (ICH) and simultaneous SARS-CoV-2 infection. METHOD: The Italian Society of Hospital Neurosciences (SNO) promoted a multicentre, retrospective, observational study (SNO-COVID-19), involving 20 Neurological Departments in Northern Italy. Clinical data on patients with acute cerebrovascular diseases, admitted from March 1st to April 30th, 2020, were collected. A comparison was made of the demographical and clinical features of both SARS-CoV-2 positive and negative patients with ICH. RESULTS: 949 patients were enrolled (average age 73.4 years; 52.7% males); 135 patients had haemorrhagic stroke and 127 (13.4%) had a primary ICH. Only 16 patients with ICH (12.6%) had laboratory confirmed SARS-CoV-2 infection, both symptomatic and asymptomatic. SARS-CoV-2 related pneumonia or respiratory distress (OR 5.4), lobar location (OR 5.0) and previous antiplatelet or anticoagulant treatment (OR 2.9) were the only factors significantly associated with increased mortality in ICH. SARS-CoV-2 infection, regardless of respiratory involvement, led to a non-significantly increased risk of in-hospital death (37.5% vs 23.4%, p = 0.2). DISCUSSION: ICH patients with COVID-19 did not experience an increase in mortality as striking as ischemic stroke. The inflammatory response and respiratory complications could justify the slight increase of death in ICH. Bleeding sites and previous antiplatelet or anticoagulant treatment were the only other predictors of a worse outcome.

Impact of SARS-CoV-2 on reperfusion therapies for acute ischemic stroke in Lombardy, Italy: the STROKOVID network.

Whether and how SARS-CoV-2 outbreak affected in-hospital acute stroke care system is still matter of debate. In the setting of the STROKOVID network, a collaborative project between the ten centers designed as hubs for the treatment of acute stroke during SARS-CoV-2 outbreak in Lombardy, Italy, we retrospectively compared clinical features and process measures of patients with confirmed infection (COVID-19) and non-infected patients (non-COVID-19) who underwent reperfusion therapies for acute ischemic stroke. Between March 8 and April 30, 2020, 296 consecutive patients [median age, 74 years (interquartile range (IQR), 62-80.75); males, 154 (52.0%); 34 (11.5%) COVID-19] qualified for the analysis. Time from symptoms onset to treatment was longer in the COVID-19 group [230 (IQR 200.5-270) minutes vs. 190 (IQR 150-245) minutes; p = 0.007], especially in the first half of the study period. Patients with COVID-19 who underwent endovascular thrombectomy had more frequently absent collaterals or collaterals filling ≤ 50% of the occluded territory (50.0% vs. 16.6%; OR 5.05; 95% CI 1.82-13.80) and a lower rate of good/complete recanalization of the primary arterial occlusive lesion (55.6% vs. 81.0%; OR 0.29; 95% CI 0.10-0.80). Post-procedural intracranial hemorrhages were more frequent (35.3% vs. 19.5%; OR 2.24; 95% CI 1.04-4.83) and outcome was worse among COVID-19 patients (in-hospital death, 38.2% vs. 8.8%; OR 6.43; 95% CI 2.85-14.50). Our findings showed longer delays in the intra-hospital management of acute ischemic stroke in COVID-19 patients, especially in the early phase of the outbreak, that likely impacted patients outcome and should be the target of future interventions.

Measuring the Outcomes of Maternal COVID-19-related Prenatal Exposure (MOM-COPE): study protocol for a multicentric longitudinal project.

INTRODUCTION: COVID-19 is a highly infectious respiratory disease that rapidly emerged as an unprecedented epidemic in Europe, with a primary hotspot in Northern Italy during the first months of 2020. Its high infection rate and rapid spread contribute to set the risk for relevant psychological stress in citizens. In this context, mother-infant health is at risk not only because of potential direct exposure to the virus but also due to high levels of stress experienced by mothers from conception to delivery. Prenatal stress exposure associates with less-than-optimal child developmental outcomes, and specific epigenetic mechanisms (eg, DNA methylation) may play a critical role in mediating this programming association. METHODS AND ANALYSIS: We present the methodological protocol for a longitudinal, multicentric study on the behavioural and epigenetic effects of COVID-19-related prenatal stress in a cohort of mother-infant dyads in Northern Italy. The dyads will be enrolled at 10 facilities in Northern Italy. Saliva samples will be collected at birth to assess the methylation status of specific genes linked with stress regulation in mothers and newborns. Mothers will provide retrospective data on COVID-19-related stress during pregnancy. At 3, 6 and 12 months, mothers will provide data on child behavioural and socioemotional outcomes, their own psychological status (stress, depressive and anxious symptoms) and coping strategies. At 12 months, infants and mothers will be videotaped during semistructured interaction to assess maternal sensitivity and infant's relational functioning. ETHICS AND DISSEMINATION: This study was approved by the Ethics Committee (Pavia). Results will be published in peer-reviewed journals and presented at national and international scientific conferences. TRIAL REGISTRATION NUMBER: NCT04540029; Pre-results.