Is the Frontal Lobe the Primary Target of SARS-CoV-2?

Toniolo, Sofia; Lorenzo, Francesco Di; Scarioni, Marta; Frederiksen, Kristian Steen; Nobili, Flavio

doi:10.3233/jad-210008

Cited by 53 publications

(52 citation statements)

References 36 publications

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“…Accordingly, isolated frontocingulate dysfunction among COVID-19 survivors may underlie deficits in executive function while other cognitive processes remain unscathed. Some postulate that frontal circuitry is preferentially targeted by SARS-CoV-2, contributing to executive dysfunction ( Toniolo et al, 2021 ). Direct links between frontal lobe abnormalities and cognitive impairment post-COVID-19 are lacking, but there is some evidence of frontal hypometabolism in severe cases ( Hosp et al, 2021 ; Matschke et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Post-acute sequelae of COVID-19: Evidence of mood & cognitive impairment

Lamontagne

Winters

Pizzagalli

et al. 2021

Brain, Behavior, & Immunity - Health

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Acute health consequences associated with coronavirus disease 2019 (COVID-19) infection have been thoroughly characterized; however, long-term impacts are not yet understood. Post-acute sequelae of COVID-19 (PASC), also known as Long COVID syndrome, is the persistence of COVID-19 symptoms long after viral infection. In addition to physical symptoms, those with PASC experience changes in mental health, but few studies have empirically examined these effects. The current study investigated mood and cognitive functioning in individuals who have recovered from COVID-19 infection. We recruited 100 male and female adults (M=30 years old) with no history of mood or cognitive impairment prior to the COVID-19 pandemic (Jan. 2020). Half of the subjects were healthy controls (i.e., no prior COVID-19 infection) and half had received a past COVID-19 diagnosis (ascertained by PCR or antibody test) but were no longer infectious. Participants completed self-reported measures of stress, depression, and anhedonia, as well as the Attention Network Test (ANT), a behavioural measure of attentional alerting, orienting and executive functioning. Relative to controls, depression and anhedonia were significantly higher in the past-COVID group. Selective impairment in attention was observed in the past-COVID group, marked by deficits in executive functioning while alerting and orienting abilities remained intact. Effects were most pronounced among individuals diagnosed 1-4 months prior to assessment. There were no group differences in pandemic-related experiences with respect to social interaction, social distancing, or isolation. The past-COVID group scored significantly higher on perceived stress; however, this did not moderate any effects observed on mood or cognition. These findings implicate a protracted reaction to the virus, possibly via prolonged inflammation, contributing to sustained mood dysregulation and cognitive impairment. Future research should examine the neural and physiological underpinnings of PASC, particularly mechanisms that promote psychiatric sequelae 1 to 4 months following diagnosis.

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Section: Discussionmentioning

confidence: 99%

Post-acute sequelae of COVID-19: Evidence of mood & cognitive impairment

Lamontagne

Winters

Pizzagalli

et al. 2021

Brain, Behavior, & Immunity - Health

View full text Add to dashboard Cite

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“…Five were diagnosed with mild COVID-19, and two had a moderate disease based primarily on the presence or absence of symptoms of mild pneumonia. Neurologic symptoms developed at a median of 16 (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33) days after initial COVID-19 manifestations. All patients had headache and altered behavior (reported as mild irritability 1 lists the laboratory test results.…”

Section: Resultsmentioning

confidence: 99%

“…Considering our patients' impairments in verbal fluency, poor constructional strategies, and behavior alterations, the dorsolateral prefrontal circuit, the anterior cingulate cortex, and the lateral orbitofrontal circuit are likely the most affected regions in SARS-CoV-2 encephalopathy. These circuits have been associated with different types of subcortical infectious dementia and hypothesized as affected in COVID-19 ( 32 , 33 ).…”

Section: Discussionmentioning

confidence: 99%

Subacute Cognitive Impairment in Individuals With Mild and Moderate COVID-19: A Case Series

et al. 2021

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Background: Previous reported neurologic sequelae associated with SARS-CoV-2 infection have mainly been confined to hospital-based patients in which viral detection was restricted to nasal/throat swabs or to IgM/IgG peripheral blood serology. Here we describe seven cases from Brazil of outpatients with previous mild or moderate COVID-19 who developed subacute cognitive disturbances.Methods: From June 1 to August 15, 2020, seven individuals 18 to 60 years old, with confirmed mild/moderate COVID-19 and findings consistent with encephalopathy who were observed >7 days after respiratory symptom initiation, were screened for cognitive dysfunction. Paired sera and CSF were tested for SARS-CoV-2 (IgA, IgG ELISA, and RT-PCR). Serum and intrathecal antibody dynamics were evaluated with oligoclonal bands and IgG index. Cognitive dysfunction was assessed by the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and the Clock Drawing Test (CDT).Results: All but one of our patients were female, and the mean age was 42.6 years. Neurologic symptoms were first reported a median of 16 days (IQR 15–33) after initial COVID-19 symptoms. All patients had headache and altered behavior. Cognitive dysfunction was observed mainly in phonemic verbal fluency (MoCA) with a median of six words/min (IQR 5.25–10.75) and altered visuospatial construction with a median of four points (IQR 4–9) (CDT). CSF pleocytosis was not detected, and only one patient was positive for SARS-CoConclusions: A subacute cognitive syndrome suggestive of SARS-CoV-2-initiated damage to cortico-subcortical associative pathways that could not be attributed solely to inflammation and hypoxia was present in seven individuals with mild/moderate COVID-19.

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“…Supporting the CSN tropism of the virus, several studies have indicated the SARS-CoV-2 presence in the brain of patients affected by epilepsy [ 11 ], cerebral edema [ 12 ], encephalitis [ 13 ], and multiple sclerosis [ 14 ]. Recent hypothesis suggest that the frontal lobes in particular could be a specific target of SARS-CoV-2 infection [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

Delirium in COVID-19 patients: a multicentric observational study in Italy

et al. 2021

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Introduction Although recent data show that SARS-CoV-2 infection seems to affect the central nervous system (CNS), little is known about the neuropsychiatric effects resulting from this condition. In addition to the well-known neurotrophism of coronaviruses, recent evidence shows also that the “cytokine storm” induced by the infection is at the basis of the neuroinflammation of the CNS. Furthermore, prolonged hospitalization, polypharmacotherapy, and isolation could be at the basis of the onset of delirium in hospitalized COVID patients. This multicentric observational study explores the incidence of the onset of delirium in an Italian cohort of SARS-CoV-2 positive inpatients. Methods Data were collected in the COVIDhospitals of Brescia, Bergamo, Chieti, and Genova. Different socio-demographic, medical, neurological, and pharmacological parameters were collected. As a rapid screening for delirium, the 4AT scale was used. Eighty COVID-19 inpatients (mean age 74.7 ± 14.5 years) met the inclusion criteria (confirmed positivity to the SARS-CoV-2 virus; the presence of delirium and/or psychomotor agitation and/or new onset of other neuropsychiatric symptoms during hospitalization). Results The majority of these patients (68.8%) had “hyperactive delirium” subtype. Polypharmacotherapy, current treatment with corticosteroids, and higher age were associated with delirium severity. Conclusion These data provide an insight into the onset of delirium among COVID-19 patients underlining the need for monitoring, especially in elderly patients, the neuropsychiatric symptoms, and the therapy in order to have shorter hospitalization times and better outcomes.

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Is the Frontal Lobe the Primary Target of SARS-CoV-2?

Cited by 53 publications

References 36 publications

Post-acute sequelae of COVID-19: Evidence of mood & cognitive impairment

Post-acute sequelae of COVID-19: Evidence of mood & cognitive impairment

Subacute Cognitive Impairment in Individuals With Mild and Moderate COVID-19: A Case Series

Delirium in COVID-19 patients: a multicentric observational study in Italy

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