Objective:To determine the prevalence and associated mortality of well-defined neurologic diagnoses among COVID-19 patients, we prospectively followed hospitalized SARS-Cov-2 positive patients and recorded new neurologic disorders and hospital outcomes.Methods:We conducted a prospective, multi-center, observational study of consecutive hospitalized adults in the NYC metropolitan area with laboratory-confirmed SARS-CoV-2 infection. The prevalence of new neurologic disorders (as diagnosed by a neurologist) was recorded and in-hospital mortality and discharge disposition were compared between COVID-19 patients with and without neurologic disorders.Results:Of 4,491 COVID-19 patients hospitalized during the study timeframe, 606 (13.5%) developed a new neurologic disorder in a median of 2 days from COVID-19 symptom onset. The most common diagnoses were: toxic/metabolic encephalopathy (6.8%), seizure (1.6%), stroke (1.9%), and hypoxic/ischemic injury (1.4%). No patient had meningitis/encephalitis, or myelopathy/myelitis referable to SARS-CoV-2 infection and 18/18 CSF specimens were RT-PCR negative for SARS-CoV-2. Patients with neurologic disorders were more often older, male, white, hypertensive, diabetic, intubated, and had higher sequential organ failure assessment (SOFA) scores (all P<0.05). After adjusting for age, sex, SOFA-scores, intubation, past history, medical complications, medications and comfort-care-status, COVID-19 patients with neurologic disorders had increased risk of in-hospital mortality (Hazard Ratio[HR] 1.38, 95% CI 1.17-1.62, P<0.001) and decreased likelihood of discharge home (HR 0.72, 95% CI 0.63-0.85, P<0.001).Conclusions:Neurologic disorders were detected in 13.5% of COVID-19 patients and were associated with increased risk of in-hospital mortality and decreased likelihood of discharge home. Many observed neurologic disorders may be sequelae of severe systemic illness.

Background and Purpose: Patients with the Coronavirus Disease of 2019 are at increased risk for thrombotic events and mortality. Various anticoagulation regimens are now being considered for these patients. Anticoagulation is known to increase the risk for adverse bleeding events, of which intracranial hemorrhage (ICH) is one of the most feared. We present a retrospective study of 33 patients positive for COVID-19 with neuroimaging-documented ICH and examine anticoagulation use in this population. Methods: Patients over the age of 18 with confirmed COVID-19 and radiographic evidence of ICH were included in this study. Evidence of hemorrhage was confirmed and categorized by a fellowship trained neuroradiologist. Electronic health records were analyzed for patient information including demographic data, medical history, hospital course, laboratory values, and medications. Results: We identified 33 COVID-19 positive patients with ICH, mean age 61.6 years (range 37À83 years), 21.2% of whom were female. Parenchymal hemorrhages with mass effect and herniation occurred in 5 (15.2%) patients, with a 100% mortality rate. Of the remaining 28 patients with ICH, 7 (25%) had punctate hemorrhages, 17 (60.7%) had small-moderate size hemorrhages, and 4 (14.3%) had a large single site of hemorrhage without evidence of herniation. Almost all patients received either therapeutic dose anticoagulation (in 22 [66.7%] patients) or prophylactic dose (in 3 [9.1] patients) prior to ICH discovery. Conclusions: Anticoagulation therapy may be considered in patients with COVID-19 though the risk of ICH should be taken into account when developing a treatment regimen.

Background and Purpose: We conducted this study to investigate the prevalence and distribution of cerebral microbleeds and leukoencephalopathy in hospitalized patients with coronavirus disease 2019 (COVID-19) and correlate with clinical, laboratory, and functional outcomes. Methods: We performed a retrospective chart review of 4131 COVID-19 positive adult patients who were admitted to 3 tertiary care hospitals of an academic medical center at the epicenter of the COVID-19 pandemic in New York City from March 1, 2020, to May 10, 2020, to identify patients who had magnetic resonance imaging (MRI) of the brain. We evaluated the MRIs in detail, and identified a subset of patients with leukoencephalopathy and/or cerebral microbleeds. We compared clinical, laboratory, and functional outcomes for these patients to patients who had a brain MRI that did not show these findings. Results: Of 115 patients who had an MRI of the brain performed, 35 (30.4%) patients had leukoencephalopathy and/or cerebral microbleeds. Patients with leukoencephalopathy and/or cerebral microbleeds had neuroimaging performed later during the hospitalization course (27 versus 10.6 days; P <0.001), were clinically sicker at the time of brain MRI (median GCS 6 versus 14; P <0.001), and had higher peak D-dimer levels (8018±6677 versus 3183±3482; P <0.001), lower nadir platelet count (116.9±62.2 versus 158.3±76.2; P =0.03), higher peak international normalized ratio (2.2 versus 1.57; P <0.001) values when compared with patients who had a brain MRI that did not show these findings. They required longer ventilator support (34.6 versus 9.1 days; P <0.001) and were more likely to have moderate and severe acute respiratory distress syndrome score (88.6% versus 23.8%, P <0.001). These patients had longer hospitalizations (42.1 versus 20.9 days; P <0.001), overall worse functional status on discharge (mRS 5 versus 4; P =0.001), and higher mortality (20% versus 9%; P =0.144). Conclusions: The presence of leukoencephalopathy and/or cerebral microbleeds is associated with a critical illness, increased mortality, and worse functional outcome in patients with COVID-19.

Background Little is known regarding long-term outcomes of patients hospitalized with COVID-19. Methods We conducted a prospective study of 6-month outcomes of hospitalized COVID-19 patients. Patients with new neurological complications during hospitalization who survived were propensity score-matched to COVID-19 survivors without neurological complications hospitalized during the same period. The primary 6-month outcome was multivariable ordinal analysis of the modified Rankin Scale(mRS) comparing patients with or without neurological complications. Secondary outcomes included: activities of daily living (ADLs;Barthel Index), telephone Montreal Cognitive Assessment and Neuro-QoL batteries for anxiety, depression, fatigue and sleep. Results Of 606 COVID-19 patients with neurological complications, 395 survived hospitalization and were matched to 395 controls; N = 196 neurological patients and N = 186 controls completed follow-up. Overall, 346/382 (91%) patients had at least one abnormal outcome: 56% had limited ADLs, 50% impaired cognition, 47% could not return to work and 62% scored worse than average on ≥1 Neuro-QoL scale (worse anxiety 46%, sleep 38%, fatigue 36%, and depression 25%). In multivariable analysis, patients with neurological complications had worse 6-month mRS (median 4 vs. 3 among controls, adjusted OR 1.98, 95%CI 1.23–3.48, P = 0.02), worse ADLs (aOR 0.38, 95%CI 0.29–0.74, P = 0.01) and were less likely to return to work than controls (41% versus 64%, P = 0.04). Cognitive and Neuro-QOL metrics were similar between groups. Conclusions Abnormalities in functional outcomes, ADLs, anxiety, depression and sleep occurred in over 90% of patients 6-months after hospitalization for COVID-19. In multivariable analysis, patients with neurological complications during index hospitalization had significantly worse 6-month functional outcomes than those without.

We sought to review the literature on cerebrospinal fluid (CSF) testing in patients with COVID-19 for evidence of viral neuroinvasion by SARS-CoV-2. Methods: We performed a systematic review of Medline and Embase between December 1, 2019 and November 18, 2020 to identify case reports or series of patients who had COVID-19 diagnosed based on positive SARS-CoV-2 polymerase chain reaction (PCR) or serologic testing and had CSF testing due to a neurologic symptom. Results: We identified 242 relevant documents which included 430 patients with COVID-19 who had acute neurological symptoms prompting CSF testing. Of those, 321 (75%) patients had symptoms that localized to the central nervous system (CNS). Of 304 patients whose CSF was tested for SARS-CoV-2 PCR, there were 17 (6%) whose test was positive, all of whom had symptoms that localized to the central nervous system (CNS). The majority (13/17, 76%) of these patients were admitted to the hospital because of neurological symptoms. Of 58 patients whose CSF was tested for SARS-CoV-2 antibody, 7 (12%) had positive antibodies with evidence of intrathecal synthesis, all of whom had symptoms that localized to the CNS. Of 132 patients who had oligoclonal bands evaluated, 3 (2%) had evidence of intrathecal antibody synthesis. Of 77 patients tested for autoimmune antibodies in the CSF, 4 (5%) had positive findings. Conclusion: Detection of SARS-CoV-2 in CSF via PCR or evaluation for intrathecal antibody synthesis appears to be rare. Most neurological complications associated with SARS-CoV-2 are unlikely to be related to direct viral neuroinvasion.

No abstract

Quantitative trait locus mapping of chemical/inflammatory pain in the mouse identified the Avpr1a gene, encoding the vasopressin-1A receptor (V1AR), as responsible for strain-dependent pain sensitivity to formalin and capsaicin. A genetic association study in humans revealed the influence of a single nucleotide polymorphism (rs10877969) within AVPR1A on capsaicin pain levels, but only in male subjects reporting stress at the time of testing. The analgesic efficacy of the vasopressin analog, desmopressin, revealed a similar interaction between the drug and acute stress, as desmopressin inhibition of capsaicin pain was seen only in non-stressed subjects. Additional experiments in mice confirmed the male-specific interaction of V1AR and stress, leading to the conclusion that vasopressin activates endogenous analgesia mechanisms unless they have already been activated by stress. These findings represent the first explicit demonstration of analgesic efficacy depending on the emotional state of the recipient, and illustrate the heuristic power of a bench-to-bedside-to-bench translational strategy.

There have been multiple descriptions of seizures during the acute infectious period in patients with COVID-19. However, there have been no reports of status epilepticus after recovery from COVID-19 infection. Herein, we discuss a patient with refractory status epilepticus 6 weeks after initial infection with COVID-19. Extensive workup demonstrated elevated inflammatory markers, recurrence of a positive nasopharyngeal SARS-CoV-2 polymerase chain reaction, and hippocampal atrophy. Postinfectious inflammation may have triggered refractory status epilepticus in a manner similar to the multisystemic inflammatory syndrome observed in children after COVID-19.