Patients with coronavirus disease 2019 (COVID-19) may have symptoms of anosmia or partial loss of the sense of smell, often accompanied by changes in taste. We report 5 cases (3 with anosmia) of adult patients with COVID-19 in whom injury to the olfactory bulbs was interpreted as microbleeding or abnormal enhancement on MR imaging. The patients had persistent headache (n ¼ 4) or motor deficits (n ¼ 1). This olfactory bulb injury may be the mechanism by which the Severe Acute Respiratory Syndrome coronavirus 2 causes olfactory dysfunction. ABBREVIATIONS: COVID-19 ¼ coronavirus disease 2019; SARS-CoV-2 ¼ Severe Acute Respiratory Syndrome coronavirus 2 C oronavirus has the human respiratory system as its main target but also has neuroinvasive capabilities and can spread from the respiratory tract to the CNS. 1-3 Therefore, patients with coronavirus disease 19 (COVID-19) may present with neurologic symptomatology with repercussions on imaging examinations, 4-18 and these have been described in association with ischemic infarct, 8,9 hemorrhage, 11 acute hemorrhagic necrotizing encephalopathy, 10 cerebral venous thrombosis, 13 and diffuse leukoencephalopathy with microhemorrhage. 15 Transmission from person to person occurs mainly by direct contact or droplets spread by coughing or sneezing by an infected individual with Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2). 5,19 Symptoms of COVID-19 usually appear after an incubation period of about 5 days. The most common symptoms are fever, cough, fatigue, headache, and dyspnea. 5,19,20 In the most severe cases, patients may develop pneumonia, acute respiratory failure, distress syndrome, and acute heart problems. 5,19,20 Anosmia or partial loss of the sense of smell, usually accompanied by changes in taste, is a frequent symptom that helps in the diagnosis of COVID-19. 21-28 It is often a transitory

Background The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men.

Different neurological manifestations of COVID-19 in adults and children and their impact have not been well characterized. We aimed to determine the prevalence of neurological manifestations and in-hospital complications among hospitalized COVID-19 patients and ascertain differences between adults and children. We conducted a prospective multicenter observational study using the International Severe Acute Respiratory and emerging Infection Consortium cohort across 1507 sites worldwide from January/30th/2020 to May/25th/2021. Analyses of neurological manifestations and neurological complications considered unadjusted prevalence estimates for predefined patient subgroups, and adjusted estimates as a function of patient age and time of hospitalization using generalized linear models. Overall, 161,239 patients (158,267 adults; 2,972 children) hospitalized with COVID-19 and assessed for neurological manifestations and complications were included. In adults and children, the most frequent neurological manifestations at admission were fatigue (adults: 37.4%; children: 20.4%), altered consciousness (20.9%; 6.8%), myalgia (16.9%; 7.6%), dysgeusia (7.4%; 1.9%), anosmia (6.0%; 2.2%), and seizure (1.1%; 5.2%). In adults, the most frequent in-hospital neurological complications were stroke (1.5%), seizure (1%), and central nervous system (CNS) infection (0.2%). Each occurred more frequently in ICU than in non-ICU patients. In children, seizure was the only neurological complication to occur more frequently in ICU vs. non-ICU (7.1% vs. 2.3%, P &lt; .001). Stroke prevalence increased with increasing age, while CNS infection and seizure steadily decreased with age. There was a dramatic decrease in stroke over time during the pandemic. Hypertension, chronic neurological disease, and the use of extracorporeal membrane oxygenation were associated with increased risk of stroke. Altered consciousness was associated with CNS infection, seizure, and stroke. All in-hospital neurological complications were associated with increased odds of death. The likelihood of death rose with increasing age, especially after 25 years of age. In conclusion, adults and children have different neurological manifestations and in-hospital complications associated with COVID-19. Stroke risk increased with increasing age, while CNS infection and seizure risk decreased with age.

Patients with COVID-19 can require radiological examination, with chest CT being more frequent than neuro-imaging. The objective is to identify epidemiological, clinical and radiological factors considered as predictors of neurological involvement in patients with COVID-19 assessed by neuroimaging and to describe the neuroimaging findings. This retrospective study was performed with 232 consecutive confirmed COVID-19 patients, from two radiological units, which were divided into two groups: (1) those who underwent a brain CT/MRI scan (n = 35) versus (2) those who did not undergo the brain CT/MRI scan, but underwent only chest CT (n = 197). There was a statistically significant difference with associations regarding the COVID-19 brain scan group for: admission to ICU, greater severity of lung injuries, the use of a mechanical ventilator and sepsis. Statistical tendency was found for chronic renal failure and systemic arterial hypertension. Forty-percent of COVID-19 patients from the brain scan group were abnormal on brain CT and/or brain MRI (22.9% of the cases with bleeding or microbleeding, 8.6% with restricted diffusion lesions). One ischemic stroke case was associated with irregularity at the M1 segment of the right middle cerebral artery. There was a case of left facial nerve palsy with enhancement of the left geniculate ganglia. An analysis of the olfactory bulbs was possible in 12 brain MRIs and 100% had enhancement and/or microbleeding. In conclusion, a more severe COVID-19 disease from ICU, a more severe form of lung disease, the use of mechanical ventilator and sepsis were associated to the COVID-19 patients with neurological involvement who had undergone brain scans. Microvascular phenomenon was a frequent finding in the brain and olfactory bulbs evaluated by neuroimaging.

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