J Clin Med Res

Journal of Clinical Medicine Research, ISSN 1918-3003 print, 1918-3011 online, Open Access

Article copyright, the authors; Journal compilation copyright, J Clin Med Res and Elmer Press Inc

Journal website https://www.jocmr.org

Review

Volume 13, Number 2, February 2021, pages 82-91

COVID-19-Associated Acute Brain Dysfunction Related to Sepsis

**Table 1.** The Definition and Diagnostic Evidence of COVID-19-Associated Acute Brain Dysfunction
Qualification	Definitions	Evidence of imagines	Evidence of CSF analysis	Evidence of qSOFA	Mechanisms
CSF: cerebrospinal fluid; MRI: magnetic resonance imaging; qSOFA: quick Sequential (sepsis-related) Organ Function Assessment (range, 0 - 3 points, with 1 point each for systolic hypotension (≤ 100 mm Hg), tachypnea (≥ 22/min), or altered mentation, if ≥ 2 points indicates sepsis); ELVO: emergent large vessel occlusion; CNS: central nervous system; COVID-19: coronavirus disease 2019; ICD-10: International Classification of Diseases, Tenth Revision; RT-PCR: reverse transcriptase-polymerase chain reaction; Ig: immunoglobulin; ACE2: angiotensin-converting enzyme 2; BBB: blood-brain barrier.
COVID-19-associated acute cerebrovascular disease (CVD)	COVID-19-indused acute CVD, including ICD-10 diagnosis code I61 and I60, such as cerebral infarction and intracranial hemorrhage [45]	Pneumonia: usual	Almost no testing	Most ≥ 2	Inflammatory storm
Hemorrhage: unusual
MRI: infarcts: usual	Coagulopathy
ELVO: usual	ACE2-induced endotheliitis
COVID-19-associated encephalopathy	Refers to COVID-19-due to inflammatory storm induced diffuse/multi-focal neural deficits (range from delirium to coma) without evidence of CNS infection [13].	Pneumonia: most	No cell, no protein/mildly elevated protein	Most ≥ 2	Inflammatory storm
MRI: diffuse edema, multiple ischemic lesion, perfusion abnormalities, or BBB damage and vasogenic edema
ACE2-induced endotheliitis
Cytokine: (+)
RT-PCR: (-)
Culture: (-)
IgG or IgM: (-)
COVID-19-associated CNS infections	Refers to COVID-19-direct into CNS leading to acute encephalitis/meningitis [22-33]	Pneumonia: with/without	Pleocytosis and elevated protein (+++)	Most ≥ 2	Virus direct into brain
MRI: multifocal lesion (temporal and hippocampus)
RT-PCR: (+)
Cytokine: (+)
IgG or IgM: (+)
COVID-19-associated other encephalitis	Including acute disseminated encephalomyelitis, immune-mediated encephalitis [36-39]	Pneumonia: with/without		More	Immune-mediated
MRI: non-specific
Unspecified COVID-19-associated acute brain dysfunction	Including COVID-19-induced altered mental status, delirium, seizure, and corticospinal tract signs [13]	Pneumonia: with/without	Less testing	More	Inflammatory storm
MRI: non-specific
	ACE2-induced endotheliitis
Sepsis	Sepsis-3 criteria [3]	Similar above	Similar above	All ≥ 2	All
Septic-metastatic encephalitis	Due to bacterial or fungal sepsis [44]	MIR: microabscesses	17 to 10,000 × 10⁶/L	All ≥ 2	Bacteria direct into brain
Elevated protein

Table 1. The Definition and Diagnostic Evidence of COVID-19-Associated Acute Brain Dysfunction

Qualification

Definitions

Evidence of imagines

Evidence of CSF analysis

Evidence of qSOFA

Mechanisms

CSF: cerebrospinal fluid; MRI: magnetic resonance imaging; qSOFA: quick Sequential (sepsis-related) Organ Function Assessment (range, 0 - 3 points, with 1 point each for systolic hypotension (≤ 100 mm Hg), tachypnea (≥ 22/min), or altered mentation, if ≥ 2 points indicates sepsis); ELVO: emergent large vessel occlusion; CNS: central nervous system; COVID-19: coronavirus disease 2019; ICD-10: International Classification of Diseases, Tenth Revision; RT-PCR: reverse transcriptase-polymerase chain reaction; Ig: immunoglobulin; ACE2: angiotensin-converting enzyme 2; BBB: blood-brain barrier.

COVID-19-associated acute cerebrovascular disease (CVD)

COVID-19-indused acute CVD, including ICD-10 diagnosis code I61 and I60, such as cerebral infarction and intracranial hemorrhage [45]

Pneumonia: usual

Almost no testing

Most ≥ 2

Inflammatory storm

Hemorrhage: unusual

MRI: infarcts: usual

Coagulopathy

ELVO: usual

ACE2-induced endotheliitis

COVID-19-associated encephalopathy

Refers to COVID-19-due to inflammatory storm induced diffuse/multi-focal neural deficits (range from delirium to coma) without evidence of CNS infection [13].

Pneumonia: most

No cell, no protein/mildly elevated protein

Most ≥ 2

Inflammatory storm

MRI: diffuse edema, multiple ischemic lesion, perfusion abnormalities, or BBB damage and vasogenic edema

ACE2-induced endotheliitis

Cytokine: (+)

RT-PCR: (-)

Culture: (-)

IgG or IgM: (-)

COVID-19-associated CNS infections

Refers to COVID-19-direct into CNS leading to acute encephalitis/meningitis [22-33]

Pneumonia: with/without

Pleocytosis and elevated protein (+++)

Most ≥ 2

Virus direct into brain

MRI: multifocal lesion (temporal and hippocampus)

RT-PCR: (+)

Cytokine: (+)

IgG or IgM: (+)

COVID-19-associated other encephalitis

Including acute disseminated encephalomyelitis, immune-mediated encephalitis [36-39]

Pneumonia: with/without

Immune-mediated

MRI: non-specific

Unspecified COVID-19-associated acute brain dysfunction

Including COVID-19-induced altered mental status, delirium, seizure, and corticospinal tract signs [13]

Pneumonia: with/without

Less testing

Inflammatory storm

MRI: non-specific

ACE2-induced endotheliitis

Sepsis

Sepsis-3 criteria [3]

Similar above

All ≥ 2

All

Septic-metastatic encephalitis

Due to bacterial or fungal sepsis [44]

MIR: microabscesses

17 to 10,000 × 10⁶/L

All ≥ 2

Bacteria direct into brain

Elevated protein